ML20198K638

Requests That Commission Action Be Implemented by Arranging for Publication of Encl Final Rule on Exempt Distribution & Use of Radioactive Drug Containing 1 Uci C-14 Urea as Set Out in SECY-97-232 in FRN

ML20198K638
Person / Time
Issue date:	11/17/1997
From:	Trottier C NRC OFFICE OF NUCLEAR REGULATORY RESEARCH (RES)
To:	Meyer D NRC OFFICE OF ADMINISTRATION (ADM)
Shared Package
ML20198K526	List: ML20198K525 ML20198K534 ML20198K567 ML20198K576 ML20198K638 ML20198L375 ML20198L385 ML20198L432 ML20198L463 ML20198L477 ML20198L495 ML20198L514 ML20198L521
References
FRN-62FR63634, RULE-PR-30, RULE-PR-32 AF70-2-005, AF70-2-5, SECY-97-232-C, NUDOCS 9801150061
Download: ML20198K638 (132)

Text

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November 17, 1997 i

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l MEMORANDUM TO: David L Meyer, Chief 'ppQ (

Rules and Directives Branch l y

Division of Administrative Services

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Office of Administration l t

FROM: Cheryl A. Trottier Chief 0:lfn 1@my j Radiation Protection and HeaRh Effects Branch j Division of Regulatory Applications i Office of Nuclear Regulatory Research l

SUBJECT:

FINAL RULE ON EXEMPT DISTRIBUTION AND USE OF A l j

RADIOACTIVE DRUG CONTAINING ONE MICROCURIE OF CARBON 14 UREA (PARTS 30 AND 32) j py memorandum dated November 5,1997, the Secretary of the Commission indice*ed that the

, Commission has approvedwa final rule on exempt distributiondan usef o a di ti vedrug ra oac L containing one microcurie of carbon 14 uros as ut out in SECY.g7 232, and recommended y that the final rule should be published in the Federal Register after making certain specified  ;

changes to the Federal Register notice (FRN), Environmental Assessment, Regulatory _ l j

Analysis, Public Announcement, and Congressional Letters. Marked-up copies of the FRl1 and l

i- other documents are attached. l 1

Please implement the Commission's action by arranging for publication of the attacher 1 final rule In the Faderal Begister. OMB approval for the rule was granted at the time the proposed rule l l

was issued.

Copies of the Federal Register notice are attached in both hard copies and diskette. Also l attached are a Congressional letter psckage and a Small Business Regulatory Enforcement l Fsimess Act letter package for transmittal to OCA. A public announcement on this rule was  !

prepared and will be issued at the time of publication of the Federal Register notiu. l Attachments:

1. FR Notice + 3 Copies & Diskette i

2. Marked-up Copy of FR Notice with SRM 1

' ' 3. Regulatory Analysis

4. Environmental Assessment

5. Cer.,:f-r.s4 Letter Package -

16. Small Business Regulatory Enforcement Faimess Act Letter Package j, t

7. Public Announcement M' Has RF -(ghWieyevc14.tr) :

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p. k UNITED STATES y } NUCLEAR REGULATORY COMMISSION

• WASHINGTON, 0.0. 30006 00M J

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MEMORANDUM TO: David L. Meyer, Chief Rules and Directives Branch Division of Administrative Services Office of Administration FROM: Cheryl A. Trottier, Chief Radiation Protection and Health Effects Branch Division of Regulatory Applications Omco of Nuclear Regulatory Research

SUBJECT:

FINAL RULE ON EXEMPT DISTRiBUllON AND USE OF A RADKr CTIVE DRUG CONTAINING ONE MICROCURIE OF CARBON 14 UREA (PARTS 30 AND 32)

By memorandum dated November 5,1997, the Secretary of the Commission indicated that the Commission has approved the final rule on exempt distribution and use of a radioactive drug containing one microcurie of carbon 14 urea as set out in SECY 97 232, and recommended that the final rule should be published in the Endatal Beglatat after making certain specified changes to the Federal Register notice (FRN), Environmental Assessment, Regulatory Analysis, Public Announcement, ed Congressional Letters. Marked-up copies of the FRN and other documents are attached.

Please implement the Commission's action by arranging for publication of the attached final rule in the Endstal Register. OMB approval for the rule was granted at the time the proposed rule was issued.

Copies of the Federal Register notice are attached in both hard copies and diskette. Also attached are a Congressional letter package and a Small Business Regulatory Enforcement Fairness Act letter package for transmittal to OCA. A public announcement on this rule was prepared and will be issued at the time of publication of the Federal Register notice.

Attachments:

1. FR Notice + 3 Copies & Diskette

2. Marked up Copy of FR Notice with SRM

3. Regulatory Analysis

4. Environinental Assessment

5. Congressional Letter Package

6. Small Business Regulatory Enforcement Falmess Act Letter Package

7. Public Announcement

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J ENCLOSURE 1 FEDERAL REGISTER NOTICE 1

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NUCLEAR REGULATORY COMMISSION I

10 CFR Parts 30 and 32 .;

t RIN: 3150-AF70 l J

Exempt Distribution of a Radioactive Drug i Containing One Microcurie of Carbon-14 Ursa l

AGENCY: Nuclear Regulatory Commission, j 4 ACTlON: Final rule.

SUMMARY

The Nuclear Regulatory Commission (NRC) is amending its regulations to permit NRC licensees to distribute a radioactive drug containing one microcurie of carbon 14 unna to I

any person for "in vivo" diagnostic use. The NRC has determined that the radioactive i aniasi n:Rcut  ;

component of suc'h a drug in capsule form presents red!Mion risk and, therefore, X  :

regulatory control of the drug for radiation safety is not necessary. This amendment makes the drug more widely available and reduces costs to patients, insurers, and the health care i

industry. This action grants a petition for rulemaking (PRM 35-12) from Tri-Med Specialties, inc. and completes action on the petition. .

EFFECTIVE DATE:- (30 days from date of publication in the Federal Register). f l

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and provides a comperside allemative to the C 14 tool The apparent aneumption undertying

- the omsonmentri aseeeement is that in the abeenos of the C-14 test, the only altemotive for l

the detection of H. pylori is immelve c %-#-:+:-w. I BeeDones' alocause the C-14 urea capsules are already available to authortrod user j physionens, the only regulatory issue in this rulemaking is whether the C-14 method should be made eveliebie to indhmals who em not authortred users. The purpose of the enviror. mental ]

assessment is to consider and document whether the subject rule is expected to have any 1 1

signincent impact to the erwironment. In this environment aseseement, the NRC has I l determined that the em&onmental impact is expooled to be insignifloont because of the )

extremely low radiologioni hazards ansceisted with the uos of capsules containing one l

< i microcurie C 14 ures. The presence of an additional non-invasive altemative procedu does not affect NP.C's determination of no significant environmental impact.  ;

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Comment 10: NRC's policy in the post has been not to exempt byproduct material that  ;

j is ingested. Any change in this policy would to e signi6 cont departure from existing NRC  :

1 4

regulations, i

Rannonas: % change is a departure from existing NRC regulations, in the statomont  ;

of consideration for the proposed rule, under the heading ' Current NRC Regulations on ,

Exemptions From Llooneing,' the NRC stated that, although two broad material exemptions ,

2 i

($ 30.14,

• Exempt concentrations,' and $ 30.18, *Ezempt quantitles") exclude the transfer of

byproduct meterial contained in any product designed t< ingestion or Inhalation by a human  !

2 being, the C 14 capsules manufactured or prepared as a radioactive drug con be distributed to ,

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9ertons exempt florn licensing for *in vivo

• diagnostic use because the agouies present an c ,1 W onh @ to '

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ca>sules may be disposed of by users as ordinary trash Paragraph (a)(o) of 9 32.21 requires that applicants submit copies of prototype labels and brochures for NRC approval. The NRC will ensure that the labels meet the requirements of 9 32.21a before they are approved. Since paragraph (a) of 9 32.21a specifies that the label must be durable and legible, the use of an additional phrase such as ' conspicuously and prominently

• is unneassary. Promotional u u e n.4 t 4 e " 4*

brochures are for information only; CNag w,ll piovent manufacture hemTindi ingPon the X promotional brochures that C-14 is a radioactive material.

ill. Summary of the Final Amendments Final Amendment to 10 CFR Part 32 The regulations in 10 CFR Part 32 are amended to add new $$ 32.21 and 32.21a, to provide requirements for a specific license to manufacture, prepare, process, produce, package, repackage, or transfer for commercial distribution, capsules containing one microcurie of C-14 urea, as a radioactive drug, to be distributed to any person for "in vivo" diagnostic use.

These requirements are consistent with the existing requirements on other items under the heading " Exemptions" in 10 CFR Part 30. The amendment includes a reminder that li:ensees distributing the radioactive drug to persons exempt from licensing would not be relieved from other applicable Federal (e.g., FDA) or State requirements goveming the manufacture and distribution of drugs.

The amendment requires that the manufacture or preparation of coules containing one microcurie of C-14 urea be prepared by persons who meet the current NRC regulations to manufacture and commercially distribute radioactive drugs. The NRC believes regulatory 12

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controlis needed to provide high confidence that the drug contains one microcurit of C 14 uros and does not contain any other radioactive contaminants.

Final Amendment to 10 CFR Part 30 q An ihrigaEM X The NRC has determined that the drug in capsule form presents = i;;r.ir.?

anA X

- radiological safety [ environmental risk, and that it is not necessary to regulate the use of this drug for its radioactive component. Therefore, the NRC can not justify requiring physicians, or

- any other person, to meet NRC training and experience criteria directed at the safe use of radioactive drugs, or to become an " authorized user " Hence, the capsules can be distributed

to any person. However, other Federal or State agencies may limit the receipt and use of the capsules in accordance with their own requirements.

The regulations in 10 CFR Part 30 ore amended to add a new $ 30.21, to permit any person to receive, possess, use, transfer, own, or acquire for "in vivo" diagnostic use, capsules containing one microcurie of C-14 urea without a license: The final regulation includes a reminder that persons receiving the capsules would not be relieved from other Federal or Stato law govem'ng drugs. Further, in accordance with the NRC's provisio1s for research involving human subjects (10 CFR 35.6), the exemption permitting receipt and use of the capsules for "in vivo" diagnostic use does not extend to use of the capsules for research involving human

- subjects. Any person desiring to use the capsules for human research would still be required to submit an application for a specific license under Part 35. The phrase "in vivo diagnostic use" was selected to describe the activity authorized in $30.21 to differentiate it from the term

" medical use" because:

's 13.

e (1) Medical use"Irnits administration to authorized users; use of this drug would not be so limited; and (2)

• Medical use' includes the administration of the drug to a human research subject, i which would be pic,hibhd by tNtHu!cmakingr b 6H%e h r(- W% A spudu. 6,<, s c. pq gaat -4 bd h vo% % iJ e int.

Effects of the Final Amendments The final amendments make the drug available to any person, for "in vivo" diagnostic use, without need for an NRC or Agreement State license. Because the receipt and use of the drug are exempt from NRC licensing, Agreement States need to make appropriate provisions in their regulations to recognize the exempt distribution of the drug, for "in vivo" diagnostic use.

4 Thus, after the manufacture and distribution pf the dru e NRC and the Agreement States will not regulate the use of the drug as long as its use is for "in vivo" diagnostic use. This means that, under NRC and Agreement State regulations, primary-care physicians do not need to be 'authonzed users' in order to administer the drug, and do not need to refer their patients to nuclear medicine physicians. This should result in cost savings to patients. Other Federal and State organizt4tiora with responsibilities for regulating drugs will determile old regulate who can receive and use the drug for "in vivo" diagnostic use. NRC will continue to regulate the use of the drug for research involving human subjects under a specific Part 35 license.

14

distribution, capsules contair.ing one microcurie carbon 14 urea each for "in vivo" diagnostic use, to persons exempt from licensing.

Paracraoh (aif1)

This paragraph limits issuance of an " exempt distribution license" for distribution of the capsules to persons exempt from licensing to only those who possess either a NRC or Agreenient State " specific license" for possession and use of byproduct material.

Parmaraoh f aif2)

To assure that the capsules contain one microcurie of carbon 14 and present no other radiologica' risks, this paragraph requires that the persons manufacturing and/or commercially distributing the capsules for "in vivo" diagnostic use must also meet the requirements of 9 32.72(a)(2). Specifica!!y, these persons must be:

(1) Registered with or licensed by the FDA as a drug manufacturer, or (2) Registered with or licensed by a state agency as a drug manufacturer, or (3) Licensed as a pharmacy by a State Board of Pharmacy; or (4) Operating as a nuclear pharmacy within a Federal medical institution.

Paracraoh (31@

This paragraph requires applicants to provide evidence that each carbon 14 urea capsule contains one microcurie. The NRC's evaluation that the capsules would suit in x ir)significant radiation risks was basad on the r:apsules containing one microcurie of carbon-% g urea. Therefore, applicants must demonstrate that the activity of each caroon-14 capsule 16

i requirements for the manufacture anc commercial distribution of carbon 14 urea capsules to j pelsons exempt from licensing and establishes regulations to permit any person to receive the capsules without an NRC license. The Commission believes that the radioactive component of ,

un A.

X this drug presents significant radiation risk and, therefore, regulatory control of the in vivo"

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diagnostic use of the capsules for radiation safety is not necessary, it is expected that this final l rule wil! not cause any significant increase in radiation exposure to the public or radiation i

. rolesse to the environment beyond the exposures or releases resulting from the use of the carbon 14 capsuies under the current regulations. Also, it is expected that there will be no non-i radiological impacts. One public comme it on the draft environmental atsessment has been received (See Comment 9 under the heading ' Proposed Rule, Public Comments, and NRC Responses *).

The environmental assessment and finding of no significant imp,act on which this determination is based is available for inspection at the NRC Public Document Room,2120 L Street NW. (Lower Level), Washington, DC. Single copies of the environmental assessment and the finding of no significant impact are available from Dr. Anthony N. Tse, Office of Nuclear Regulatory Research, U.S. Nuclear Regulatory Commission, Washington, DC 20555-0001, telephone (301) 415-6233 or e-mail at ANT @nrc. gov.

Vll Paperwork Reduction Act Statement This final rule amends information collection requirements that cre subject to the Paperwork Reduction Act of 1995 (44 U.S.C. 3501 et seq.). These requirements were approved by the Office of Management and Budget, approval numbers 3150-0001,3150-0017, and 3150-0120.

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I~ 1A Pmnomad Rule and Public comments )

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,- . The proposed rule vnes published in the Fadaral Regentar (62 FR 32552, June 16,19g7) for a  !

t L 30<$ay public comment period. The NRC received seven public comment letters. Four commenters supported the. rule, one opposed the rule, and two provided comments without

explicitly stating whether they support or oppose the rule. A summary of public comments and i NRC's responses are presented in the preamble of the Federal Register notice. Except a minor  !

l change in wording, the final amendments are the same as the proposed amendments. No l comments related to the draft Regulatory Guide has been received, i

2. Qhingthip

i. The objective of the rulemaidng is to amend 10 CFR Part 32 to permit the manufacture and i

!. commercial distribution of "C-ures capsules to any person (including physicians who are not

' authorized users' under Part 35) and to amend 10 CFR Part 30 to permit any person, without i l

. en NRC license, to receive and use the capsules for in vivo diagnostic use for humans..

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j F Three altematives have boon considered in the regulatory analysis: deny the petition, i.e., j maintain the status quo, permit the distribution of the capsules to persons exempt from  ;

licensing, and permit the distribution of the aspsules to general licensees. j

, t l Under the first sitemative, only physicians who are authorized users under Part 35 would be i 4- allowed to possess and administer the "C-ures test. Any physician could apply to become an =

authorized user. However, the NRC expects few physicians would apply for a Part 35 license 1 for the soie purpose of using the capsules because of the requirement for training and l

experience and the naam costs of obtaining and maintaining a Part 35 license. l Altomatively, physicians who are not authorized users een continue to refer their patients to i physicians who are authorized users to undergo the diagnostic test. However this would not a l' relieve the current expense, inconvenience, and delay encountered in an otherwise straight-4 forward procedure.

Under the second attemative,10 CFR Parts 32 and 30 would be amended.10 CFR Part 32  !

would be amended to permit the manufacture and commercial distribution of "C-urea capsules

- to any person (including physicians who are not " authorized users" under Part 35); 10 CFR ,

Part 30 would be amended to permit the manufacture and commercial distribution of the ,

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capsules to any person, for in vivo diagnostic use for humgns. The NRC has determined that the radioactive component of this drug presents e - ' 'n rad J

- reguistory control of the capsules is not noosssary, h ,iation risk and, therefore,Q4

- Under the third alternative,10 CFR Part 35 would be amended to permit any physician to  ;

4 receive and use the capsules under a general license. The health and safety concems for this -l aitomotive are the same as the Altemative 2.' However, if this altomative were adopted, there

_ could be a burden to those Agreement States that normally require registration of general ,

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Scenario Maximum Exposed Routine Exposure Indiv! dual Worker administering "C- Full-time worker,8,000 Less than 0.7 mrem /yr urea bresth tests patients /yr Routine exposure of patients Patient tests negative 0.38 mrem / capsule from "C-urea breath tests Patient tests pesitive 0.18 mrem / capsule Release of 150 pCi of "CO, Member of public in the Less than 0.0002 mrem into administration administration area facility from fire Rupture of a capsu!c Skin (100 cm') exposed for 5.8 mrad skin dose, causing skin contamin- one hour prior to washing; 0.029 mrem (CEDE) ation of worker or patient 0.075 pCl skin absorption Furthermore, the NRC concluded that the impacts associated with any releases of "C to the surrounding environment are expected to be very small and the expected isks are minimal.

The earth's atmosphere contains an loventory of naturally occurring "C of about 3.0 m'.llion curies (equivalent to the activity in 3 8 trillion breath tests), which is in addition to the huge inventory of about 240 million curies in the world's oceans. The "C released into the atmosphere from the use of this test would mix with the global inventory and expose the public and other blotic components of the environment to "C intakes from Inhalation, drinking water, and all possible food pathways in the same manner as naturally occurring "C. The current world inventory of naturally occumr,) "C results in an average dose to the public of about 1.25 mrem / year, and the release of 0.6 curies of "C from the total of 600,000 tests assumed to 4

be administered annually would result in an additional average annual dose of 2 X 10 mrem.

This is far below the EPA reporting level of 1,m[em/ year required under the Clean Air Act for X

routine exposures to a member of the public, onthe 4 mrem / year EPA limit for public drinking water. In a tott! population of about 260 million people in the U.S., the collect!ve annual dosa from the breath tosts would be about 0.051 person-rem. In addition, the doses from normal use of breath tests, or from any accidental release of "C to the environment also are expected to be very small because the concentration of CO, released is very low and it would mix immediately with the atmosphere. 'Ti* mhb enoue Jr pwh wa nc+ r.+s d* ad den c k Ahk fit mL.. L J , co u n ha d ow r e sq % o. '"6a 4 le s k .

O The small doses from naturally occurring "C are of little significance to human health and the environment. Potentiallong term impacts from widespread releases of the long-lived "C (5,730 year radiological half-life) from breath tests were concluded to be insignificant.

Assuming that the testing in the U.S. would increase over a period of time to an average of a million tests per year for 50 years the collective annuaTdose to the U.S. population would be x about 5 person-rem over the 50 year $,This dose is very small when compared to the x annual collective dose to the U.S. populatioh from naturally occur-ing "C of over 300,000 person-rem, and about 78,000,000 person- 'em from all naturally occurring radiation. Clearly, an increase of a few person rem will not si ificantly change these exposures, and thus there is no expected impact from the v.idespread e of the breath test on the entire U.S. population.

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I As a result of this analys!s, the NRC concludes that Alternatives 2 and 3 are clearly preferable to the no action anomative. This is because either of the two altematives will result in significant cost savings with no measurable adverse effect on health and safety. Furthermore,  !

the NRC's recommended option is Ahemative 2 because it would avoid the unnecessary cost  !

bsrden to some Agreement States and their general licensees. j Therefore, by promulgating the final rule, the cost savings would be maximized without any ..

measurable adverse effect on public health and safety.  !

5. Decision Rationale Based on the above analysis, the NRC is amending its regulations to permit the manufacture ,

and commercial distribution of Cart >on 14 uros capsules to any person (including physicians - l 3

who are not " authorized users" under Part 35) and permit any person, without an NRC license, .

to receive and use the capsules for in vivo de nostic use for humans because the radiological l risk from such distribution would be nd the savings to patients could be significant.  !

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Environmental Assessment For Final Amendments to 10 CFR Parts 30 and 32 l "DiMribution of a Radioactive Drug Containing One Microcurie of Carbon 14 Urea as Exempt Material for "in Vivo" Diagnostic Testing"  !

S'aiament of the Final Action ,

The Nuclear Regulatory Commission (NRC) is amending its regulations to allow NRC l licensees to distribute a radioactive drug containing one microcurie of carbon 14 ures to any person for "in vivo" diagnostic usp'. The NRC has determined that the radiosctive com such capsules presents $ 'Ir'ad ation risk and, therefore, regulatory control of the drug for K radiation safety is not necessary. This amenoment makes the drug more widely available, thus rsducing costs to patients, insurers, and the health care industry. This action is being taken in response to a petition for rulemaking (PRM 3512) submitted by Tri-Med Specialties, Inc.

Need for the Amendments The amendments have been developed to grant the petition for rulemaking. The final rule permits manufacturers or commercial distributors to distribute carbon 14 urea capsules as exempt material to any person. The Commission is promulgating this rulemaking because it ns.y.h believes that the radiological risk from such distribution would be =JC:gtsand the savings N to patients could be significant. In addition, the Commission recognizes that other Federal and State agencies (e.g., Food and Drug Administration and the State Boards of Pharmacy) are responsible for the receipt and use of drugs that do not contain byproduct materials, and would provide necessary oversight for te safe use of these carbon 14 urea capsules as dmgs.

6Bamahyes Considered Three altematives have been considered regarding the petition: deny the petition, i.e.,

. maintain the status quo, permit the distribution of the capsules as exempt material, and permit

. the distribution of the capsules to general licensees.

Under the first attemative, ths current situation would continue; only physicians who are ,

authortred users under Part 35 would be allowed to possess and administer the C 14 ures test.

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i j Any physicien could apply to become an authertred user. However, the NMC enes few physicians would apply for a Part 35 license for the solo purpose of using such capsules i

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i because of the requirement for training and experience and the escociated costs of obtaining l j and maintaining a Part 36 license. Allematively, physicians who are not authorized users een l continue to refer their patiente to physionens who are authorized users to undergo the diagnostic

.: test. However this woud not relieve the cunent expense, inconvenience, and delay

encountered in an otherwise straight-forward procedure. l 1

4 Under the escond allemative,10 CFR Ports 32 and 30 would be amended. Part 32 l h would be amended to estatdish requirements for the manufacture and tjistribution of C 14 uros  !

capsules to persons exempt from lloonsing. i.e., any person (including physialens who are not - j

" authorized users" under Part 36); Part 30 would be amended to permit any person to receive,  !

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possess, use, transfer, own, or acquire the capsules for in vivo diagnostic use for humans j:

without a NRC has determined that the radiosotive component of this drug f

l _y presents +w redsstion risk and, therefore, regulatory control of the capsules is not l necessary,  ;

s i Under the third altemotive,10 CFR Part 35 would be amended to permit any physician to ,

I rece've and use the capsules under a general license. The health and asfoty conoems for this .

I altemative are the same as the Altemative 2. However, if this attemative were adopted, there i could be a burden to those Ay,uwnt States that normally require registration of general j 16 cones holders. An additional burden could also be imposed on generallicensees loosted in the Agreement State if the Stato charges a licones or registration fee. .

Based on the Draft Regulatory Analysis propered for this proposed rule, the Commiselon i 1

concludes that Allematives 2 and 3 are cieerty preferable to the no action altomotive. This is i because either of the two allematives will result in signifloent oost savings with no measurable b- advs.rse afloat on health and safety. Furthermore, the NRC's recommended option is [

, Allemative 2 because it avoids the unnecessary cost burden to some Agreement States and L . theirliconeses.

d imnad on the Puolle and the Envimnment .

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I The amendments are expected to have n(significant impact on the putdic and the K

environment. The NRC assumes that the same number of breath tests will be administered  ;

regenmees of the level of NRC regulatory control. This view is prediosted on the belief that 1 2 4

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v' each physician's prima *y motivation is to ,)tovide the best possible care to his or her patients, if the breath test is judged preferable to endoscopy, or other procedure, any physician not authorized to use the test will refer his or her patient to authorized users who could perform the test under existing NRC regulations. Under this assumption, this rulemaking action is expected to result in no change in radiation exposures to the workers and patients when compared with the t:stus quo. Similar1y, it is expected that there will be no change in impact to the environment because the Commission assumes that the same number of tests will be administered regardless of which attemative is adopted.

The earth's atmosphere contains an inventory of naturally occurring C-14 of about 3.8 million curies which is in addition to the huge inventory of about 240 millbn cudes in the world's oceans. The small amount of C 14 released into the atmosphere from the use of this test would mlx with the global inventory and would have no impact on public health. The current world inventory of naturally occurring C 14 results in an average dose to the public of about 1.25 mrem per year, and the release of 0.6 curies of C 14 from the total of 600,000 tes's assumed to be administered annually would result in an additional average annual dose of ,

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List of Aaencies and Persons Consulted and Identification of Sources Used Following the receipt of the petition for rulemaking, a Notice of receipt of petition for rulemakino" was published for public comment in the Federal Reaister on December 2,1994.

(59 FR 61831). A total of 315 public comment letters,313 supporting (mostly form letters) and 2 opposing letters, were re elved. This petition was discussed with NRC's Advisory Committee on the Medical Uses of Isotopes ACMUI) at the October 1995 meeting. Furthermore, the draft rulemaking plan was forwarded to 29 Agreement States for comments.

A proposed rule wun published in the Federal Reaister (62 FR 32552, June 16,1997) for a 30-day public comment period. The NRC received seven public comment letters. Four commenters supported the rule, one opposed the rule, and two provided comments without explicitly stating support of or opposition to the rule. A summary of public comments and NRC's responses are presented in the preamble of the Federal Register notice. Except a minor change in wording, the final amendments are the same as the proposed amendments.

One commenter addressed the draft environmental Assessment. The commenter stated that the environmental Assessment fails to consider the fact that another equally non-invasive, 3

4

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' i but norH.adiological, ^== ^ procedure (such as C 13 test) is available and provides a comparable altemotive to the C-14 test. The commenter apparerWy conduded that the assomption undottying the envronmental assessment is that in the absence of the C-14 test, the only altemotive for the detection of H. pylori is invasive gastroendoscopy.  !

The purpose of the erwitonmental assessment is to address and document the expected j impact to the environment of subject mio. As presented in the regulatory analysis prepared for -

this rule, the NRC has determined that the environmental impact is expected to be insignificant  ;

< because of the extremely low radiological hazards associated with thu use of capsules j containing one microcur6e C-14 ures. I If the environmentalimpact had been significant, then the existence of a non radioactive l attemotive would have been a factor in assessing the cost-benefit of this rulemaking. However, l 4

. the impact is not significant. Hence, the regulatory issue in this rulemaking is whether the C 14

! method should be made evallable to physicians who are not authortred users, and not whether j i

there exists a non-radioactive altemative.

.l l i

Finding of No Significant impacts j The Commission has determined under the National Environmental Policy Act of 1969,. j

as amended, and the Commission's regulations in Subpart A of 10 CFR Part 51, that the  !

amendments will not be a major Federal action significantly affecting the quality of the human environment, and therefore an environmental impact statement is not required. The final rule I

! s amends 10 CFR Part 32 to permit the manufacture and commercial distribution of C-14 uros 3

~-

. capsules to any person (including physicians who are not "authortrod users" under Part 35) and .

i to amend 10 CFR Part 30 to permit any person, without an NRC license, to receive and use the capsules for in vivo diagnostic use for.hu ,

m we n esk. The Commission believes that the radioact

% uomponent of this drug presents istion risk and, therefore, regulatory control of the capsules for "in vivo" diagnostic use is not necessary. It is expected that this final rule will -

not cause any significant incrosse in radiation exposure to the public or radiation release to the environmerit beyond the exposures or releases resulting from the use of the carbon-14 l capsules under the cunent regulations.

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[7590-01 P]

NUCLEAR REGULATORY COMMISSION I

10 CFR Parts 30 and 32 RIN: 3150-AF70 i

Exempt Distribution of a Radioactive Drug l J

Containing One Microcurie of Carbon 14 Uree

- AGENCY: Nuclear Regulatory Commission.

ACTION: Final rule. ,

SUMMARY

The Nuclear Regulatory Commission (NRC) is amending its regulations to permit NRC licensees to distribute a radioactive drug containing one microcurie of carbon-14 urea to any person for "in vivo" diagnostic use. The NRC has determined that the radioactive component cf such a drug in capsule form presents an insignificant radiation risk ar'd, therefore, regulatory control of the drug for radiation safety is not necessary. This amendment makes the drug more widely available and reduces costs to patients, insurers, and the health care industry. This action grants a petition foi rulemaking (: rtM 35-12) from Tri Med Specialties, Inc. and completes action on the petition.

EFFECTIVE DATE: -(30 days from da's of publication in the Federal Register). i 4

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ADDRESS: Copbs of the public record, including the final regulatory analysis and any public ,

1 comments received on the proposed rule, may be examined and copied for a fee in the o

Commission's Public Document Room at 2120 L Street, NW (Lower Level), Washington, DC. l 1

FOR FURTHER INFORMATION CONTACT: Dr. Anthony N. Tse, Office of Nuclear Regulatory Research, U.S. Nuclear Regulatory Commission, Washington, DC 20555-0001, telephone (301) 415-6233 or e mail at ANT @nrc. gov.

I T

. SUPPLEMENTARY INFORMATION: a

1. The Petition for Rulemaking.

t II. Proposed Rule, Public Comments, and NRC Responses.

111. Summary of the Final Amendments.

IV. Description of the Final Amendments.

V. Agreement State Compatibility.

VI. Finding of No Significant Environmentalimpact: Availability.

Vll. Paperwork Reduction Act Statement.

Vill. Regulatory Analysis.

IX. Regulatory Flexibi'ity Certification.

X. Small Business Regulatory Enforcement Fairness Act.

. XI, Backfit Analysis.

P a- XII. List of Subjects.

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l. The Petition for Rulemaking l

On October 6,1994, the Commission docketed a petition for rulemaking (Docket No.

PRM-3512) from Tri Med Specialties, Inc (Tri Med). In a letter dated August 23,1994, Tri Med  ;

petitioned the NRC to amend its regulations "to allow for the general licensing and/or exemption for the cornmercial distribution by licensed phartnaceutical manufacturers of a capsule I

containing one micro-Curie (pCl) of C-14-ures for in vivo diagnostic testing." The purpose of this diagnostic test is to detect the presence of the ba::terium Helicobacter pylori (H. pylori), a cause of peptic ulcers in humans.

Following the receipt of the petition, the NRC published for public comment a notice of receipt of petition for rulemaking in the Federal Register on December 2,1994 (59 FR 61831). ,

The comment period closed on February 15,1995. The NRC received 315 public comment letters, of which 313 supported the petition (they were mostly form letters) and 2 letters opposed the petition, ll, Proposed Rule, Public Comments, and NRC Responses A proposed rule was published on June 16,1997 (62 FR 32552) that would permit NRC licensees to distribute capsules containing one microcurie C-14 urea to any person fer *in vivo" diagnostic use. The public comment period closed on July 16,1997, in the preamble of the proposed rule, the NRC stated that, because the capsules

- present an insignificant radiological risk to the public and the environment, the NRC believes the capsules could be distributed for 'in vivo" diagnostic use to persons exempt from licensing.

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This change makes the drug more widely available and reduces costs to patiento, insurers, and f-t the health care industry.

i The NRC received seven public comment letters on the proposed rule: three from t

industry, three from State agencies, and one from a physicbn associated with a university j medical facility. Four commenters supported the rule, ona opposed the rule, and two provided crinments but did not explicitly state whether they supported or opposed the rule. Public comments and NRC's responses are presented below.  ;

I i

Comment 1: Under the proposed distribution, the NRC should not be forbidding research use of this drug by the same physicians who may use it clinically. Research use also should be permitted under this exemption because the radiological risk for using C 14 capsules  ;

is insignificant.

Rasponse: The NRC did not change the final rule in response to this comment. A F

common rule entitled ' Federal Policy for the Protection of Human Subjects; Notices and Rules" was promulgated by 16 Federal agencies on June 18,1991 (56 FR 28002) and was intended to ensure the protection of human research subjects. This rule was adopted to implement a i recom'endation of the President's Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research which was established on November 9,1978, by Public Law 95-622. The Federal Policy requires that Federal agencies that conduct, fund, support, or regulate research involving human subjects ensure adequate protection of the rights of the human subj9 cts. The Federal policy represents a societal determination that any research (inclu6ng research involving radioactive material) must provide for th6 following minimal protections for the human subjects: (1) that the research is approved by an Institutional Review Board (IRB) and (2) that the human subject gives informed consent to 4 l

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participate in the research. Further, these protections must be provided regardless of whether or not there is any risk of consequences (including radiological consequences). This view is supported by the fact that during the oublic comment period of the common rule, a commenter ,

suggested that all minimal risk research be exempt from the regulations; however, the final rule did not t dopt this comment. [

NRC did not participate in the promulgation of the common rule. Subsequently, the NRC adopted 10 CFR 35.6 that requires a licensee who conducts research involving human subjects using byproduct material to obtain informed consent from the human subjects and obtain prior approval by an IRB, Although the NRC did not adopt the common rule, the intention is to follow the essential requirements of the common rule. Because the common rule 4

does not provide an exemption for research involving minimal risk, the Commission has determined that such research use should not be exempt from 10 CFR 35.6.

Comment 2: Two commenters expressed concerns that the proposed rule language,

'not exceeding one microcurie,' appeared to indicate that the upper limit of the radioactivity in a capsule is exactly one microcurie of C-14. Both stated that it is not possible to make the capsules to exactly one microcurie because of statistical deviations during the manufacturing process. .

RanDQuse' The NRC agrees with the commenters. The proposed rule did not intend to limit the radioactivity of C-14 to exactly one microcurie. The final rule language has been mcdified to read "capsufes containing one microcurie C 14 urea (allowing for nominal variation that may occur during the manufacturing process).*

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CommenL3: one commenter stated that, when the total amount of energy released from complete decay of a radionuclide is considered, one microcurie of C 14 has the largest energy release, because of its long half-hfe, when compared to one microcerie of Tc-99m or 1 131. The commenter concluded that, given the insignificant radiation risk from the diagnostic use of C-14 urea, the radiation risk from the diagnostic use of Tc-99m or 1131 also would be insignificant.

Resoonse: In comparing the hazard significance of the one microcurie C.14 Urea diagnostic test to the extensive use of Tc-99m and 1 131, the NRC did not evaluate the dose to the patient because this dose would be justified for medical reasons. Justification for retalning some licensing control on the medical use of Tc 99m and 1 131 while exempting the one microcurie carbon 14 urea capsules relies on the relative occupational hazards to technicians and physicians administering the radiopharmaceuticals.  ;

Administering an encapsulated dosage of one microcurie C-14 involves virtually no occupational dose due to the low energy beta radiation and minimal possibility for contamination of personnel or facilities. On the other hand dosages of Tc 99m and 1131 entall extracting 10s to 100s of millicurie amounts, often in liquid form, from shielded sources of even higher activity. The possibility of direct exposure to gamma radiation and the possibility of contamination requires that radiation protection measures be in place to maintain exposure to staff as low as is reasonably achievable.

Tc-99m and 1 131, having relatively short half lives, present minimal environmental hazard C-14 as crea is excreted from the patient as carbondioxide (CO2) which diffuses into the atmosphere. Based on a calculation found in the regulatory analysis for this rule, the current world inventory of naturally occurring C-14 results in an average dose to members of the public of about 1.25 mremlyr. A release of 0.6 curies of C-14 from the 600,000 tests 6

expected to be adrninistered annually, would result in an additional average annual dose of 2X104 mrem. Comparing this estimate to the EPA Clean Air Act reporting level of 1 mrem / year,

. this new test is environmentally insignificant.

1 Comment /* Because of the small quantity of radioactive materialin C 14 capsules, this product may be disposed of in the general trash. To avoid unnecessary concem for health risks in the disposal of the product, labels should contain a statement that the product may be ,

disposed of in the general trash.

Response. In the final rule, the label requirements include a statement that the product may be disposed of in ordinary trash.

Comment 5: The Commenter agrees that the widespread use of this product will require ,

uniform regulations and that Agreement States will need to make appropriate regulatory provisions to enable persons to receive the drug for *in vivo

• diagnostic use. To avoid confusing licensees and users, these changes to NRC and Agreement State regulations should be made simu'taneously. The commenter urges that the NRC take action to expedite the Agreement State regulatory changes.

Responan: The NRC has urged the Agreement States to adopt compatible changes in their regulations expeditiously. However, under NRC's Adequacy and Compatibility Policy, Agreement States have up to three years to change their regulations for amendments or program requirements that are items of compatibility.

Comment 6: The NRC should address this rule in its ongoing effort to revise 10 CFR Part 35 in its entirety. The commenter believes that (1) this rule represents a piecemeal effort 7

4 to respond to a narrow issue and (2) the issue of reduced regulation for medical use of C 14 capsules is applecable to the same extent for virtually the entire range of diagnostic ,

redoisotopes.  ;

Besponse: If this rule is combined with the overall 10 CFR Part 35 revision, the C-14 capsules would only be available to authorized user physicians during the revision period.

Thus, the NRC decided to proceed with this rule now because the benefits of making this capsule available to anyone, including primary-care physicians, outweigh the benefits of

. addressing this issue in the overall revision of 10 CFR Part 35.

Comment 7: An appropriate function of the regulatory regime is to assure that personnel handling and administering radioactive drugs meet certain basic training and qualification requirements. The proposed exemption would impose no training or qualification requirements on users.

Bennante: The amount of radiation safety training needed fer personnel depends on the level of radiation risk associated with the radioactive drug, Because C 14 capsules present insignificant radiation risk, radiation safety training for personnel handling and administering the capeule is not necessary, and thus, not required.

CommenLS: If the NRC promulgates the proposed rule in its present form, the exemption will divest the Agreement States of any authority to regulate this product under a general or specific license, Had the NRC instead simply proposed a generallicense, Agreement State agencies would retain the authority to adopt the generallicense or continue to require specific licensing.

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Ramponne: In the draft rulemaking plan, the NRC suggested using the general license approach. The NRC received nine comment letters from Agreement States on the draft rulemaking plan; three suggested that an exemption approach would be more appropriate because it would be less costly to the Agreement States and their licensees than the general

license approach.

Based on these comments, the NRC chose the exemption approach in the final rule plan as more cost effective than a general license approach. The final rulemaking plan was revised accordingly and was provided to the Agreement States. No Agreement States expressed opposition to the NRC on the exemption approach.

Among the seven public comment letters received on the proposed rule, two were from Agreement St-stes and one from a non Agreement State. All three supported the proposed rule.

Comment 9 The environmental assessment fails to consider the fact that another equally noninvasive, but nonradiological, diagnostic procedure (such as C 13 test) is available and provides a comparable alternative to the C 14 test. The apparent assumption underlying the environmental assessment is that in the absence of the C-14 test, the only afternative for the detection of H. pylori is invasive gastroendoscopy.

Response: Because the C 14 urea capsules are already available to authorized user physicians, the only regulatory issue in this rulemaking is whether the C-;4 method should be made available to individuals who are not authorized users. The purpose of the environmental assessment is to consider and document whether the subject rule is expected to have any significant impact to the environment. - In this environment assessment, the NRC has determ:ned that the environmental impact is expected to be insignificant because of the extremely low radiological hazards associated with the use of capsules containing one 9

microcurie C 14 urea. The presence of ten additional non-invasive alternative procedure does not affect NRC's determination of no significant environmental impact.

Comment 10: NRC's policy in the past has been not to exempt byproduct material that is ingested. Any change in this policy would be a significant departure from existing NRC regulations.

Resoonse: This rhange is a departure from existing NRC regulations. In the statement of consideration for the proposed rule, under the heading ' Current NRC Regulations on Exemptions From Licensing," the NRC stated that, although two broad material exemptions (9 30.14,

• Exempt concentrations," and 9 30.18,

• Exempt quantities") exclude the transfer of byproduct material contained in any product designed for ir.gestion or inhalation by a human being, the C-14 capsules manufactured or prepared as a radioactive drug can be distributed to persons exempt frem licensing for *in vivo" diagnostic use becease the capsules present an insignmcant cediological risk to the public and the environment. This exemption only applies to the diagnostic use of capsules containing one microcurie C-14 manufactured or prepared as a radioactive drug to make a clear distinction between this radioactive drug that is intended for ingestion by humans and other uses of C-14 urea and byproduct material distributed under SS 30.14 and 30.18.

Comment 11: The ACMUI's (Advisory Committee on Medical Uses of Radioisotopes) conciusions that eith6r an exemption or generallicense is appropriate for the C-14 product do not address the fundamental aspects of nuclear safety, its judgment was based partially on the assumpticas: (1) the product may only be dispensed by prescription, (2) the product is 10

approved by the Food and Drug Administration, and (3) the office / facility using the product will be subject to Clinical Laboratory improvement Amendment (CLIA) regulation.

Resoonse: The transcript from the ACMUI meeting shows the Committee did include radiation safety ir. its considerations and did not consider it to be an issue. Further, as stated in the supplemental material supporting the proposed rule, there are no nuclear safety issues arsociated with t.1e use of the C-14 capsules for clinical diagnostic testing. Therefore, use of either an exemption or generallicense is appi priate.

Comment 12: The exemption approach does not provide the NRC with flexibility to impose a limitation on the amount of C-14 capsules any physician can possess in an office, in the event there is a recall of the product, or a large amount of product becomes unusable, the NRC will have no control over the disposal of the product.

flesponte: It is not necessary to impose a possession limit on the amount of C-14 capsules because the radiation risk is insignificant. The earth's atmosphere contains an inventory of naturally occurring C-14 of about 3.8 million curies which is in addition to the huge inventory of about 240 million curies in the world's oceans. The small arnount of C-14 released into the atmosphere from the use of this test would mix with the globalinventory and would have no impact on public health. The current world inventory of naturally occurring C-14 results in an average dose to the public of about 1.25 mrem per year, and the release of 0.6 curies of C-14 from the total of 600,000 tests assumed to be administered annually would result in an additional average annual dose of 2 X 104 mrem. In the event that a recallis necessary, the manufacturer may use the same process for recalling any other non-radioactive drugs. If C-14 urea capsules are retumed to the manufacturers, they will be disposed of in accordance with the manufacturer's possession license. A user, however, can dispose the C-14 urea capsules 11

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as ordinary trash, Medical users of the C 14 urea test would be unlikely to acquire significant j

-i quantities of capsules bedause they can be ordered within a few days iThus,' even under a >

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recall, the impact of disposing of C-14 urea capsules into landfills by the user would also be 1 ~

i insignificant! s l

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Comment 13' It is essential that end users be adequately informed of the product's

[ radioactive characteristics, so that some form of storage, use, and disposal precautions can be =

1 followed.= Th'us',2the labeling'must be conspicuously and prominently placed.' The commenter. 3

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suggested the following: (1) the phrase ." conspicuously.and prominently" in front of the t proposed labeling " bears the words Radioactive Material" should be added, and (2) the NRC  ;

'should require tb W the radioactive material legend, " Radioactive Material," be included on promotional brochures.-

Response' Becadse the' radiation risk from C-14 capsules is insignificant, regulatory control of the use, storspe, and disposal of the drug for purpose of radiation safety is not

necessary, in fact, the label accompanying C-14 capsules is required to indicate that the

' capsules may be disposed of by users as ordinary trash. Paragraph (a)(6) of 6 32.21 requires that applicants submit copies of prototype labels and brochures for NRC approval. The NRC ,

will ensure that the labels meet the requirements of 6 32.21a before they are approved, Since-paragraph (a) of 6 32.21a specifies that the label must be durable and legible, the use of an

. additional phrase such as " conspicuously and prominently" is unnecessary. Promotional brochures are for information.only; manufacturers are not required to indicate on the i promotional brochures that C .14 is a radioactive material.

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2 Ill.: Summary of the Final Amendments a

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' Final Amendment to 10 CFR Part 32

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[w _. The reguls.tions in 10 CFR Part 32 are' amended to add new $$ 32,21 and 32.21a, to .

. provide requirements for a specific license to manufacture, prepare, process, produce,- 1

, > package, repackage, or transfer for commercial distribution, capsules containing one microcurie l h.

F of C-.14 urea, as a radioactive' drug, to be distributed to any person for "in vivo" diagnostic use.

( a 1

L These requirements are consistent with tho' existing requirements on other items under the heading ." Exemptions" in 10 CFR Part 30. The amendment includes a reminder that licensees distributing the radioactive drug to persons exempt from licensing would not be relieved from other applicable Federal (e.g., FDA) or State requirements goveming the manufacture and distribution of drugs.

The amendment requires that the manufacture or preparation of capsules containing one microcurie of C-14 urea be prepared by persons who meet the current NRC regulations to manufacture and commercially distribute radioactive drugs. The NRC believes regulatory control is needed to provide high confidence that the drug contains one microcurie of C-14 urea and does not contain any other radioactive contaminants.

Final Amendment to 10 CFR Part 30 -

f The NRC has determined that the drug in . capsule form presents an insignificant radiological or en iror. mental risk, and that it is not _necessary to regulate the use of this -

13

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9

a

- drug for its radioactive component. Therefore,'the NRC can not justify requiring physicians, or any other person, to meet NRC training and experience criteria directed at the safe use of radioactive drugs, or to become an " authorized user." Hence, the capsules can be distributed to any person. 'However, other Federal or State agencies may limit the receipt and use of the ,

1 capsules in accordance with their own requirements.

I The regulations in 10 CFR Part 30 are amended to add a new $ 30.21, to permit any person to receive, possess, use, transfer, own, or acquire for "in vivo" diagnostic use, capsules  ;

(

' containing one microcurie of C-14 urea without a license. The final regulation includes a reminder that persons receiving the capsules would not be relieved from other Federal or State ,

law goveming druge. Fudher, in accordance with the NRC's provisions for research involving human subjects (10 CFR 35.6), the exemption permitting receipt and use of the capsules for "in vivo" diagnostic use does not extend to use of the capsules for research involving human

, subjects. Any person desiring to use the capsules for human research would still be required to submit an application for a specific license under Part 35.- The phrsse "in vivo diagnostic use" was selected to describe the activity authorized in 90.21 to differentiate it from the term

" medical use" because:

(1) " Medical use" limits administration to authorized users; use of this drug would not be so limited; and

. (2)

• Medical use" includes the administration o' the drug to a human research subject, which would continue to require a specific license pursuant to Part 35 under this rulemaking.

14

-,-. . L F.ffects of the Final Amendments Th final amendments make the drug available to any person, for "in vivo" diagnostic use, without need for an NRC or Agreement State license. Because the receipt and use of the drug are exempt from NRC licensing, Agreement States need to make appropriate provisions in-their regulations to recognize the exempt distribution of the drug, for "in vivo" diagnostic use.

Thus after the manufacture and distribution of the drug, the NRC and the Agreement States will not reculate the use of the drug as long as its use is for "in vivo" diagnostic use. This means that, under NRC and Agreement State regulations, primary-care physicians do not need to be

" authorized users' in order to administer the drug, and do not need to refer their patients to nuclear medicine physicians. This should result in cost savings to patients. Other Federal and '

State organizations with responsibilities for regulating drugs will determine and regulate who can receive and use the drug for "in vivo" diagnostic use. NRC will continue to regulate the use of the drug for research involving humu subjects under a specific' Part 35 license.

3 15

'\..

W, Description of the Final Amendments The final amendments are the sam'e as the proposed amendments xcept for two minor 4 changes. Public comments suggested that the phrase

• carbon-14 urea capsules not exceeding one microcurie" used in the proposed rule may be interpreted as an exact limit of one microcurie per capsule (See Comment 2 under the heading "Public Comment and NRC Responses). The final rule has been modified and the phrase " capsules containing one microcurie carbon-14 urea (allowing for nominal variation that may occur during the manufacturing process)" is used. Another public comment suggested that labels should contain a statement that the product may be disposed of in the general trash. In the final rule, the label requirements include such a statement.

Manufacturer and Distributors 4

A new section is added to 10 CFR Part 32 to permit the distribution of the capsules to persons who are exempt from licensing.

4 s 32.21 Radioactive drua: Manufacture,.rneoaration. or transfer,for commercial distribution of cnnsu!es containino one microcurie carbon-14 urea each for "in vivo" diaonostig use for humang to oersons exemot from licensino: Reauirements for a license Paracraoh (a)

This paragraph establishes the requirements for approval of a license application to manufacture, prepare, process, produce, package, repackage, or transfer for commercial 16 9

7 .

4 '.

-;.. 1 distribution, capsules containing one microcurie carbon-14 urea each for "in vivo" diagnostic ..

use, to' persons exempt from licensing. I

-1 1 Paraaraoh (a)(1)' 4 This paragraph limits issuance of an " exempt distribution license" for distribution of the capsuies to persons exempt from licensing to only those who possess either a NRC or.

' A0reement State " specific license" for possession and use of byproduct material '

- Paragraph (a)(2) ,

To assure that the capsules contain one microcurie of carbon 14 and present no other radiological risks, this paragraph requires that the persons manufacturing and/or commercially

-1 distnbuting the capsules for "in vivo" diagnostic use must also meet the requirements of

- $ 32,72(a)(2). Specifically, these persons must be:

(1) Registered with or licensed by the FDA as a drug manufacturer, or (2) Registered with or licensed by a state agency as a drug manufacturer, or (3) Licensed as a pharmacy by a State Board of Pharmacy; or (4) Operating as a nuclear pharmacy within a Federal medical institution.

Parmaraoh (a)(3)

This paragraph requires applicants to provide evidence that each carbon-14 urea capsule contains one microcurie. The NRC's evaluation that the capsules would result in insignificant radiation risks was based on the capsules containing one microcurie of carbon-14 urea. ' Therefore, applicants must derenstrate that the activity of each carbon-14 capsule

-17 e- r w -- 4

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f contains one microcurie, allowing for nominal variation that may occur during the manufacturing

-process.=

' Paraaraoh (a)(4)

This paragraph prohibits carbon-14 urea from being contained in any food, beverage,

. cosmetic, drug or other commodity designed for ingestion or inhalation by, or topical application to, a human being except for the capsules as described in this section, because exempt

- distribution of this drug has only been evaluated for "in vivo" diagnostic use in the form of a m

capsule containing one microcurie of carbon-14 urea. There is no prohibition against the -

capsule being combined'with food or beverage at the time of administration so that the capsule A

can be. ingested by the patient.

Paraaraoh (a)(S)

Because the exempt distribution of this drug has only been evaluated for "in vivo"

. diagnostic use in the form of a capsule containing one microcurie of carbon-14 urea, this paragraph prohibits incorporation of the capsules into any manufactured or assembled commodity, product, or device inonded for commercial distribution. Further, although the drug '

is being distributed to persons exempt from licensing, this paragraph requires the carbon-14

> urea to be identified as radioactive because the drug is being used for its radioactive content; therefore, the end user must be provided with information that the drug contains a radioactive

- materia!.

' 18 4

4

Parnaraoh fa)f6)

+

As with any proded approved for distribution to persons exempt from licensing, this paragraph requires persons who apply for a license to manufacture or commercially distribute these capsules to submit copies of prototype labels or brochures for NRC approval :This will allow the NRC to confirm that the labels or brochures meet the requirements of 9 32.21a(a) and (b);

Parnaranh (b)

This paragraph declares that the regulations do not relieve licensees or applicants from complying with applicable FDA, other Federal, and State requirements goveming the manufacture and distribution of drugs.

Section 32.21a Same: Conditions of licanse This section establishes the conditions required for a licensee to commercially distribute the capsules to persons exempt from licensing, s

Paraorech (a)

To inform the end user cf the identity of the radioisotope, the physical and chemical form, and the dosage of radioactivity, this paragraph establishes that the immediate container of each capsule or capsules must bear a durable, legible label that:

(1) Identifies the radioisotope, the physical and chemical form of the radioisotope, the quantity of radioactivity contained in each container at a specific date; and (2) . Bears the words " Radioactive Material "

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The date requirement is consistent with labeling requirements for other radioactive'  ;

drugs with a half life of greater thari 100 days.

& 7 Paragraoh (bF  !

I This paragraph establishes that, consistent with the intended use of the capsules, the label affixed to the immediate container, or an accompanying brochure, must:-

(1) State that the contents are exempt from NRC or Agreement State licensing t

. requirements; 4

(2) Bear the words " Radioactive Material. For "In Vivo" Diagnostic Use Only. This -

Material is Not To Be Used for Research involving Human Subjects, and Must Not Be Introduced into Foods, Beverages, Cosmetics, or Other Drugs or Medicinals, or into Products '

Manufactured for Commercial Distribution. This Product May Be Disposed of in Ordinary Trash."

The intent of the requirement set out in Paragraph (b)(2) is to make clear that the

- capsule must remain in the form of a capsule and is not to be combined with one of the listed items such as food or beverages whi ch would result in a radioactive product other than in the form of a capsule for commercial distribution. There is no prohibition against the capsule b(,ing combined with food or beverage at the time of administration so that the capsule can be

' ingested by the patien't. This label also informs the user that this product may be disposed of in

- ordinary trash.

"In vivo" dimanostic use by oersons exemot from licensing y . A new section is added to.10 CFR Part 30 to exempt any pers.on from NRC or the Agreement State regulations to receive the drug for "in vivo" diagnostic use for humans.

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This paragraph provides an exemption to any person from the requirements for a  ;

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4 . license to receive, possess, use, transfer, own, or acquire capsules containing one 'microcuriej

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, 3e of carbon-14 uros for "in vivo" diagnostic purposes. ' it should be noted that the ftransfer" in this '

paragraph'does not include " transfer for commercial distribution," which is covered in paragraph -

4 (c) of this section, m ,

'41 Paragraoh (*2) 4

> i This paragraph establishes that persons who desire to use the drug for,research 3 o

involving humans subjects must apply for and receive a specific Part 35 license. Such a license :

would ensure the protection of the rights of the human subjects by requiring that the research c ,

be approved by an'IRB and that the human subjects give their informed consent to participate ,

x I .-in the'research.  ;

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. This paragraph' specifies that a specific license is needed to manufacture, prepare,

. process, produce, package, repackage or transfer such capsules for commercial distribution.-

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i This paragraph declares that the regulations _do not miieve end users ffom complying - 'l 1

twith applicable FDA, other Federal,~ or State requirements goveming the receipt, administration l and use of drugs.

s 5

V.- Agreement S' tate Compatibility ~ _

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.I Under the Atomic Energy a.ct, certain regulatory functions are reserved to the NRC.

j  ? Among these are the distribution of products to persons exempt from licensing, as dir. cussed in e

'10 CFR Part 150,'. Hence, amendments related to the manufacture and commercial distribution i of the capsules (10 CFR Part 32) is a Division 4 item of compatibility (Category NRC under the new adequacy and compatibility policy), However, amendments related to possession and use (10 CFR Part 30) are a Division 1 item of compatibility (Category B under the new adequacy

. and compatibility policy) because of the need for nationwide consistency in the use of products which are widely distributed Therefore, the Agreement States will need to make appropriate

= provisions in their regulations to allow any person to receive capsules containing one microcurie c-of carbon-14 urea for "in vivo" diagnostic use in humans without need for a license.

J VI. Finding of No Significant EnvironmentalImpact: Availability The Commission has determined under the National Environmental Policy Act of 1969,

. as amended, and the Commission's regulations in Subpart A cf 10 CFR Part 51, that the final rule is'not a major Federal action significantly affecting the quality of the (~.iman environment; ,

1 therefore, an environmental impact statement is not required. The final rule establishes 22 f

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-._ requirements for the manufacture and commercial distribution of carbon-14 urea capsules to [

persons exempt from licensing and establishes regulations to permit any person to receivu the capsules without an NRC license." The Commission' believes that the radioactive comp. rent of : -

t

this drug presents an insignificant radiation risk and, therefore, regulatory control of the "in vivo" I diagnostic use of the capsules for radiation safety is not necessary.; it is expected that this final

~

rule will not cause any significant increase in radiation exposure to the public or radiation .  ;

^ . release to the environment.beyond the exposures or releases resulting from the use of the carbon-14 capsules under the current regulations. : Also, it is expected that there will be no non- ,

< radiological impacts. One public comment _on the draft environmental assessment hss been' f 1 ,

I 2 received (Ses Comment g under the heading " Proposed Rule, Public Comments, and NRC 1

_ Responses").

The environmental assessment and finding of no significant impact on' which this

- determination is based is available for inspection at the NRC Public Document Room, 2120 LD Street NW, (Lower Level), Washington, DC.- Single copies of the environmental assessment I

' and the finding of no significant impact are available from Dr. Anthony N..Tse, Office of Nuclear

[ Regulatory Research, U.S. Nuclear Regulatory Commission, Washington, DC 20555-0001, telephone (301) 415-6233 or e-mail at ANT @nrc. gov, i

E Vil; Paperwork Reduction Act Statement This final rule amends information collection requirements that are subject to the

! Paperwork Reduc; ion Act of 1995 (44 U.S.C. 3501 et seq.). These requirements were -

approved by tha Office of Management and Budget, approval numbers 3150-0001,3150-0017,

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and 3150-0120; .,

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l The public reporting burden for this collection of information is estimated to average 16 ?  ;

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X9 f hours por rg.onse, including the time for reviewing instructions, sea'rching existing data i

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sources, gathering and maintaining the data needed,1 and completing and reviewing the -

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• c611ection of information.JSend comments on any aspect of this collection of information,

includog suggestions for reducing the burden, to the information and Records Management -

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Branch (T 6 F33), U.S. Nuclear Regulatory Commission, Washington, DC 20555 0001, or byi  !

' intemet electronic mail at BJS10NRC. GOV; and to the Desk Officer, Office of Information and

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. Regulatory Affairs, NEOB-10202, (3150-0001, 3150-0017, and 3150-0120),' Office of

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$Management and Budget, Washington,~=DC 20503. '

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Public Protection Notification E .  ;

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.The NRC may not conduct or sponsor, and a person is not required to respond to, a i - collection of information unless it displays a currently valid OMB control number.

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Vill. Regulatory Analysis .

L; The NRC has prepared a regulatory analysis for the final rule. The analysis examines w.

- i the benefits and impacts considered by the NRC, No public comments on the draft regulatory - . _

i analysis have been received during the public comment period. -The regulatory analysis is

available for inspection at the NRC Public Document Room, 2120 L Street NW. (Lower Level),  ;

Washinston, DC.: Single copies of the regulatory analysis are available from Dr. Anthony N.-

3 r

m _ Tse, Offlee of Nuclear Regulatory Research, U.S Nuclear _ Regulatory Commission,

, _- Washmgton, DC 20555-0001i telephone (301) 415-6233 or e-mail at ANT @nrc. gov. .

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IX. Regulatory Flexibility Certification As r64uired by the Regulatory Flexibility Act of 1980, 5 U.S.C. 605(b), the Commission certifies that this rule does not have a significant economic impact upon a substantial number of small entities. The final rule permits physicians and other health care providers to use an additional diagnostic test without having to obtain an NRC license, thus, would provide cost

, savings to patients, insurers, and the health care industry. The final rule does not impose any additional obligations on entitles that may fall within the definition of 'small entities

• as set forth in Section 601(3) of the Regulatory Flexibility Act; or within the definition of 'small business' as found in Section 3 of the Small Business Act,15 U.S.C. 632; or within the size standards adopted by the NRC on April 11,1995 (60 FR 18344).

X. Small Business Regulatory Enforcement Fairness Act in accordance with the Small Business Regulatory Enforcement Falmess Act of 1996,

1. the NRC has determined that this action is not "a major" rule and has verified this determination with the Office of information and Regulatory Affairs, Office of Management and Budget.

XI. Backfit Analysis The NRC has determined that the backfit rule 10 CFR 50.109, does not apply to this nile, and therefore, a backfit analysis is not required because these amendments do not involve any provisions that would impose backfits as defined in 10 CFR 50.109(a)(1).

25

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. c Xil. List of Subjects 10 CFR Part 30 Byproduct material, Criminal penalties, Government contracts, Intergwemmental -

- relations, Isotopes, Nuclear materials, Radiation protection, Reporting and record keeping -

requirements.

10 CFR Pad 32 Byprc.Juct material, Criminal penalties, Labeling, Nuclear materials, Radiation

" protection, Reporting and recordkooping requirements.

For the reasons set o- , the preamble and under the authority of the Atomic energy ,

Act of 1954, as amended, the Energy Reorganization Act of 1974, as amended, and 5 U.S.C.

552 and 553, the NRC is adopting the following amendments to 10 CFR Parts 30 and 32.

PART 30--RULES OF GENERAL APPLICABILITY TO DOMESTIC LICENSING OF BYPRODUCT MATERIAL

1. The authority citation for Part 30 continues to read as follows:

AUTHORITY: Secs. 81i 82,161,182,183,186, 68 Stat. 935, 948, 953, 954, 955, as amended, sec. 234, 83 Stat. 444, as amended (42 U.S.C. 2111, 2112, 2201,2232, 2233,' 2236,

- 2282); secs. 201, as amended,202,206,88 Stat.1242, as amended, 1244,1246 (42 U.S.C.

5841, 5842,5846).

Section 30.7 also issued under Pub. L.95-601, sec.10,92 Stat. 2951 as amended by Pub. L 102-486, sec. 2902,106 Stat. 3123, (42 U.S.C. 5851). Section 30.34(b) also issued 26 t

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under sec."164,68 Stat. 954, as amended (42 U.S.Cl2234). Section 30.61 also issued underl _

sec; 187,68 Stat. 955 (4_2 U.S.C. 2237).

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l 2i in $ 30.8, paragraph (b) is revised to read as follows: j a

8 ML8 inform =E-7 J"--r -, r== *ernents: OMB anaroval. l 1

' (b) The approved information collection requirements contained in this part appear in ]

l v $$30.9, 30.11, 30.15, 30.18, 30,19, 30.20, 30.21, 30.32, 30.34, 30.35, 30.36, 30.37, 30.38, -  ;

1 l ;30A1,30.50,30.51,30.55, appendices A and C to this part.-  ;

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' 3. A new $ 30.21 is added under the undesignated center heading " Exemptions" to read as follows:

I-6 30.21 RNive drua: Omaantas containina carbon-14 urea for "in vivo" dimanostic use for

% humans,

~

(a) Except as provided in paragraphs (b) and (c) of this section, any person is exempt -

l ~ from the requirements for a license set forth in Section 81 of the Act and from the regulations in ,

this part and Part 35_of this chapter provided that such person receives, pussesser., uses, ,

transfers, owns, or acquires capsules containing 37 kBq (1y Cl) carbon-14 urea (allowing for _

]

T ' nominal varietion that may occur _ during the manufacturing process) each, for "in vivo" diagnostic use for humans.

a

'( b): Any person who desires to use the capsules for research involving human subjects -

f shall apply for and receive a specific license pursuant to Part 35 of this chapter.

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^ l (c) Any person who desires to manufacture, prepare, process, produce, package, -.

repackage, or transfer for commercial distribution such capsules shall' apply for and receive a specific license pursuant to 6 32.21 of this chapter, q (d) Nothing in this'section relieves persons from complying with applicable FDA, other - -j Federal, and State requirements goveming receipt, administration, and use of drugs.

E PART 32 -SPECIFIC DOMESTIC LICENSES TO MANUFACTURE OR TRANSFER CERTAIN . f ITEMS CONTAINING BYPRODUCT MATERIAli  !

i 2

= 4, The authonty citation for Part 32 continues to read as follows:

1 AUTHORITY:- Secs. 81,161,182,183, 68 Stat. 935, 948, 953, 954, as amended (42 - l

' U.S.C. 2111; 2201,2232,2233); sec. 20h 88 Stat.1242, as amended (42 U.S.C. 5841).

- 5. In 6 32.8, paragraph (b) is revised to read as follows: ,

6 32.8 information collection reouirements OMB accroval. -l

.. (b)' The approved information collection requirements contained in this part appear in L $$ 32.11, 32.12, 32.14, 32.15, 32.16, 32.17, 32.18, 32.19, 32.20, 32.21, 32.21 a, 32.22, 32.23, .

32.25, 32.26, 32.27, 32.29, 32.51, 32.51 a, 32.52, 32.53, 32.54, 32.55, 32.56,' 32.57, 32.58,:-

. ' 32.61,32.62,32.71,32.72,52.74, and 32.210; ,

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6h A now $ 32.21 is added to road as follows:

L322L.Badiss;tivs drun: unrma-an, : or-aar=+1an. or transfer for reer..r.e,ds: distribution of-:

capsulas containing carbon-14 urea each for "in vivo" di==v=Euse for humans to normons -

--amnt from lieannino: Raouirements for a firmose.' .3 (a)T An application for a specific license to manufacture, prepare, process, produce,1

- pid-ge, repackage or tran61er for commercial distribution capsules containing 37 kBq (1g Cl) f 9 2

carbon 14 uros (allowing for nominal variation that may occur during tht manufacturing procoes) each for "in vivo" diagnostic use, to persons exempt from licensing under $ 30.21 of -  ;

i -.

this chapter or the equivalent regulations of an Agreement State will be approved if: '

(1) The applicant satisfies the general requirements specified in 6 30,33 of this chapter,.

provided that the requirements of $ 30.33(a)(2) and (3) of this chapter do not apply to an

application for a license to transfer byproduct material manufactured, prepared, processed, p;duced, packaged, o, repackaged pursuant to a license issued by an Agreement State;

. (2) The apphcant meets the requirements under 6 32.72(a)(2) of this Part; (3) The apphcant provides evidence that each capsule contains 37 kBq (1u Cl) carbon-14 uros (allowing for nominal variation that may occur during the manufacturing

( ,

process);

i

' (4) The carbon-14 urea is not contained in any food, beverage, cosmetic, drug (except

' as described in this section) or other commodity designed for ingestion or inhalation by, or

- topical apphcation to, a human being; F

2 (5), The carbon-14 urea is in the form of a capsule, identified as radioactive, and to be used for its radioactive properties,;but is not incorporated into any manufactured or assembled

., ? . ,

. . commodity, produrit, or device intended for commercial distnbution; and t

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- (6) The appliennt submits copies of prototype labels and brochdres and tne NRC Ipproves these labels and brochures. j

-(b) Nhthir:3 in this section."elieves the licensee from complying with appkcable FDA,-

- other Federal, and State requirements governing druDs.

' 7. A new $ 32.21a is added to read as folic ws:

, < $ 32.21a Same: Conditions of license.

Each license issued under S 32.21 of this Part is subject to the following conditions:

(a) The immediate container of the capsule (s) must bear a durable, legible label which:

(1) Identifies the radioisotope, the physical and chemical form, the quantity of radioactivity of each capsule at a specific date; and .

(2) Bears the words " Radioactive Material."

- (b) In addition to the labeling information required by paragraph (a) of this section, the label affixed to the immediate container, or an accompanying brochure also must:

-(1) State that the contents are exempt from NRC or Agreement State licensing

- requirements; and J

30

(

(2) Bear the words " Radioactive Material, For "In Vivo" Diagnostic Use Only. This Material is Not To Be Used for Research involving Human Subjects and Must Not Be :

Introduced into Foods, Beverages, Cosmetics, or Other Drugs or Medicinals, or into Products - ,

Manufactured for Commercial Distribution This Material May Be Disposed of in Ordinary-Trash."

Dated at Rockville, Maryland this _ day of c1997.

For the Nuclear Regulatory Commission, John C. Hoyle,-

Secretary of the Commission.

b I 5

31 .

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ATTACHMENT 2 Marked-up Copy of FR Notice with SRM 1

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[7590-01-P]

' NUCLEAR PEGULATORY COMMISSION

-10 CFR Parts 30 and 32 -

RIN: 3150-AF70 Exempt Distribution of a Radioactive Drug

. Containing One Microcurie of Carbon-14 Urea AGENCY: Nuclear Regu!atory Commission.

ACTION: Final rule.

SUMMARY

The Nuclear Regulatory Commission (NRC) is amending its regulations to permit NRC licensees to distribute a radioactive drug containing one microcurie of carbon-14 urea to any person for "in vivo" diagnostic use. The NRC has determined,that the radioactive o.n $nifuad component of such a drug in capsule form presents e W ...g. radiation risk and, therefore, regulatory control of the drug for radiation safety is not neesssary. This amendment makes the drug more widely available and reduces costs to patients, insurers, and the health care industry. This action grants a petition for rulemaking (PRM-35-12) from Tri-Med Specialties, Inc. and completes action on the petition.

' EFFECTIVE DATE: (30 days from'date of publication in the Federal Register).

- . - - - . . . - ~ .-

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.+ , . ; .p ADDRESSi Copies of the public record, including the final regulatory analysis and any public 7 g

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comments received on the proposed rule, may be examined and copied for a fee _ in the f

, Commission's Public Document Room at 2120 t Street, NW.- (Lower L'evel),- Washington, DC. l

. r  ;

r FOR FURTHER INFORMATION CONTACT: Dr.' Anthony N. Tse,- Office of Nuclear Regulatoryi Research, U.Sc Nuclear Regulatory Commission, Washington, DC 20555-0000 telephone (301) l l

,eg

. 415-6233 or e-mail at ANT @nrc, gov. '

6 SOPPLEMENTARY INFORMATION:

. 1. ;The Petition for Rulemaking.  ;

- lll. Proposed Rule, Public Comments, and NRC Responses.

i 111. Summary of the Final Amendments.

IV. Description of the Final Amendments,

[; .V.: Agreement State Compatibility.-

4-Vi. Finding of No Significant Environmental Impact: Availability.

1. Vilc - Paperwork Reduction Act Statement.

Vill. Regulatory Analysisc

IX. Regulatory Flexibility Certification.

TX. Small Business Regulatory Enforcement Falmess Act. 't

, L XI. Backfit Analysis.-

~ Xil. Ust of Subjects.

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l. The Petition for Rulemaking l

On October 6,1994, the Commission docketed a petition for rulemaking (Docket No.

PRM 35-12) from Tri-Med Specialties, Inc (Tii-Med). In a letter dated August 23,1994, Tri-Med . j l

petitioned the NRC to amend its regulations "to allow for the general licensing and/or exemption for the commercial distribution by licensed pharmaceutical manufacturers of a capsule i containing one micro-Curie (pCl) of C-14-urea for in vivo diagnostic testing." The purpose of l

this diagnostic test is to detect the presence of the bacterium Helicobacter pylori (H. pylori), a cause of peptic ulcers in humans.

Following the receipt of the petition, the NRC published for public comment a notice of receipt of petition for rulemaking in the Federal Register on December 2,1994 (59 FR 61831).

The comment period closed on February 15,1995. The NRC received 315 public comment letters, of which 313 supported the petition (they were mostly form lettets) and 2 letters opposed the petition.

11. Proposed Rule, Public Comments, and NRC Responses A proposed rule was published on June 16,1997 (62 FR 32552) that would permit NRC

. licensees to distribute capsules containing one microcurie C-14 urea to any person for 'in vivo' diagnostic use. The public comment period closed on July 16,1997.

in the preamble of the proposed rule, the NRC stated that, because the capsules present an_ insignificant radiological risk to the public and the environment, the NRC ' believes the capsules could be distributed for "in vivo" diagnostic use to persons exempt from licensing.

3

, . , . - , ~ ,,

, 4 This change makes the drug more widely available and reduces costs to patients, insurers, and the health care industry.

The NRC received seven public comment letters on the proposed rule: three from industry, three from State agencies, ar.d one from a physician associated with a university medical facility. Four commenters supported the rule, one opposed the rule, and two provided comments but did not explicitly state whether they supported or opposed the rule, Public comments and NRC's responses are presented below.

Comment 1: Under the proposed distribution, the NRC should not be forbidding research use of this drug by the same physicians w',io may use it clinically Research use also should be permitted under this exemption because the radiological risk for using C-1/ capsules is insignificant.

flesponse The NRC did not change the final rule in response to this comment. A common rule entitled " Federal Policy for the Protection of Human Subjects; Notices and Rules' was promulgated by 16 Federal agencies on June 18,1991 (56 FR 28002) and was intended to ensure the protection of human research subjects. This rule was adopted to implement a recommendation of the President's Commission for the Study of Ethical Problems in Medicir,e and Biomedical and Behavioral Research which was establish 1d on November 9,1978, by Public Law 95-622. The Federal Policy requires that Federal agencies that conduct, fund, support, or regulate research involving human subjects ensure adequate protection of the rights of the human subjects. The Federal policy represents a societal determination that any research (including research involving radioactive material) must provide for the fol'owing minimal protections for the human subjects: (1) that the research is approved by an Institutional Review Board (IRB) and (2) that the human subject gives informed consent to 4

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$ or not there is any risk of consequences (including radiological consequences).' This view is '

Laupported by the fact that during the public comment period of the' common rule, a commenter -

suggested that all min;mel risk research be exempt from tne regulations; however, the final rule .

L

--did not adopt this comment. 1

. NRC did not participate in the promulgation of the common rule. : Subsequently, thh NRC adopted 10 CFR 35.6 that requires a licensee who conducts research involving human. .

" subjects using byproduct material to obtain informed consent from the human subjects'and

obtain prior approval by an IRB,- Although the NRC did not adopt the common rule, the - ,

I intention is to follow the essential requirements of the common rule. Because the common rule

does not provide an exemption for research involving minimal risk, the Com.nission has e

determined that such research use should not be exempt from 10 CFR 35.6.

p Comment 2: Two commenters expressed concerns that the proposed rule language,

• not exceeding one microcurie," appeared to indicate that the upper limit of the radioactivity in a capsule is exactly one microcurie of C-14. Both stated that it is not possible to make the capsules to exactly one microcurie because of statistical deviations during the manufacturing process.

- Responae' The NRC agrees with the commenters. The proposed rule did not intend to limit the radiodivity of C-14 to exactly one micrecurie. The final rule language has been

> modified to read " capsules containing one microcurie C-14 urea (allowing for nominal variation

- that may occur duri_ng the manufacturing process),"

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COREDenL3: one commenter stated that, when the total amount of energy released from complete decay of a radionuclide is considered, one microcurie of C 14 has the largest energy release, because of its long half life, when compared to one microcurie of Tc 99m or l-131. The commenter concluded that, given the insignificant radiation risk from the diagnostic use of C 14 urea, the radiation risk from the diagnostic use of Tc 99m or 1 131 also would be insignificant.

Sgtsponse: In comparing the hazard significance of the in Cl C 14 Urea diagnostic test to the extensive use of Tc-99m and 1 131, the NRC did not evaluate the dose to the patient i because this dose would be justified for medical reasons. Justification for retaining some licensing control on the medical use of Tc-99m and 1 131 while exempting the in Cl C 14 ulcer test relies on the relative occupational hazards to technicians and physicians administering the K radiopharmaceuticals. p Administering an encapsulated dosage of in Cl C 14 involves virtually no occupational dose due to the low energy beta radiation and minimal possibility for contamination of personnel or facilities. On the other hand dosages of Tc 99m and 1 131 entail extracting 10s to 100s of millieurie amounts of ligeld, often in liquid form, from shielded sources of even higher activity.  !

1 The possibility of direct upesure to gamma radiation and the possibility of contamination  !

requires that indiation protection measures be in place to maintain exposure to staff ALARA.

Tc-99m and 1 13), having relatively short half-lives, present minimal environmental hazard. C-14 as urea is excre'ed from the patient as carbondioxide (CO2) which diffuses into

. the atmosphere. Based on a calculatien found in the regulatory analysis for this rule, the current wnrld inventory of naturally occurdng C-14 results in an average dose to members of the public c: about 1.25 mrem /yr. A release of 0.6 curies of C-14 from the 600,000 tests expected to be administered annually, would result in an adoitional average annual dose of 6

e .

4 2X10' mrem. Comparing this estimate to the EPA Clean Air Act reporting level of 1 mrem / year, ,

l we see that this new test is environmentally insignificant.

Comment 4: Because of the small quantity of radioactive materialin C-14 capsules, this product may be disoosed of in the general trash. To avoid unnecessary concern for health risks in the disposal of the product, labels should contain a statement that the product may be disposed of in the general trash.

Responna: In the final rule, the label requirements include a statement that the product may be disposed of in ordinary trash.

CommenL5' The Commenter 80rees that the widespread use of this product will require uniform regulations and that Agreement States will need to make appropriate regulatory provisions to enable persons to receive the drug for 'in vivo" diagnostic use. To avoid confusing licensees and users, these changes to NRC and Agreement State regulations should be made simultaneously The commenter urges that the NRC take action to expedite the Agreement State :eguiatory changes.

Easponan: The NRC has wged the Agreement States to adopt compatible changes in their regulations expeditiously. However, under NRC's Adequacy and Compatibility Policy, Agreement States have up to three ) ears to change their regulations for amendments or program requirements that are items of compatibility, Comment 6: The NRC should address this rule in its ongoing effort to revise 10 CFR Part 35 in its entirety, The commenter believes that (1) this rule represents a piecemeal effort to respond to a narrow issue and (2) tha issue of reduced regulation for medical use of C-14 7

capsules is applicable to the same extent for virtually the entire range of diagnostic radioisotopes.

Resoonse: If this rule is combined with the overall 10 CFR Part 35 revision, the C-14 capsules would only be available to authorized user physicians during the revision period.

Thus, the NRC decided to proceed with this rule now because the benefits of making this capsule available to anyone, including primary-care physicians, outweigh the benefits of

>- addressing this is, sue in the overall revision of 10 CFR Part 35.

COnsment 7: An appropriate function of the reguletory regime is to assure that personnel handling and administering radioactive drugs meet certain basic training and qualification requirements. The proposed exemption would impose no training or quahfication requirements on users.

Besponse: The amount of radiation safety training needed for personnel depends on the level of radiation risk associated with the radioactive drug. Because C-14 capsules present insignificant radiation risk, radiation safety training for personnel handling and administering the capsule is not necessary, and thus, not required.

Gqmment 8: If the NRC promulgates the proposed rule in its present form, the exemption will divest the Agreement States of any authority to regulate this product under a general or specific license. Had the NRC instead simply proposed a generallicense, Agreement State agencies would retain the authority to adopt the generallicense or continue to require specific licensing.

Etaponse: In the draft rulemaking plan, the NRC suggested usin0 the generallicense approach. The NRC received nine comment letters from Agreement States on the draft 8

M

rulemaking plan; three suggested that an exemption approach would be more appropriate because it would be less costly to the Agreement States and their licensees than the general  ;

license approach.

Based on these comments, the NRC chose the exemption approach in the final rule plan as more cost-effective than a generallicense approach. The final rulemaking plan was revised accordingly and was provided to the Agreement States. No Agreement States expressed opposition to the NRC on the exemption approach.

Among the seven public comment letters received on the proposed rule, two were from Agreement States and one from a non Agreement State. All three supported the proposed rule.

CommenL9: The environmental assessment fails to consider the fact that ant,ther equally noninvasive, but nonradiological, diagnostic procedure (such as C 13 test) is available and provides a comparable alternative to the C-14 test. The apparent assumption underlying the environmental assessment is that in the absence of the C 14 test, the only attemative for the detection of H. pylorlis invasive gastroendoscopy.

BURQDH: Because the C-14 urea capsules are already available to authorized user physicians, the only regulatory issue in this rulemaking is whether the C-14 method should be made available to individuals who are not authorized users. The purpose of the environmental assessment is to consider and document whether the subject rule is expected to have any significant impact to the environment, in this environment assessment, the NRC has determined that the environmental impact is expected to be insignificant because of the extremely low radiological hazards associated with the use of capsules containing one microcurie C 14 urea. The presence of an additional non-invasive attemative procedures does not affect NRC's determination of no significant environinentalimpact.

9

Comment 10: NRC's policy in the past has been not to exempt byproduct material that is ingested. Any change in this policy would be a significant departure from existing NRC regulations.

Resoonse: This change is a departure from existing NRC regulations. In the statement of consideration for the proposed rule, under the heading *Cunent NRC Regulations on Exemptions From Licensing," the NRC stated that, although two broad material exemptions (9 30.14, ' Exempt concentrations,' and 9 30.18, ' Exempt quantities") exclude the transfer of byproduct material contained in any product designed for ingestion or inhalation by a human being, the C-14 capsules manufactured or prepared as a radioactive drug can be distributed to ps. sons exempt from licensing for "in vivo" diagnostic use because the capsules present an insignificant radiological risk to the public and the environment. This exemption only applies to the diagnostic use of capsules containing one microcurie C-14 manufactured or prepared as a radioactive drug to make a clear distinction between this radioactive drug that is intended for ingestion by humans and other uses of C 14 urea and byproduct material distributed under SS 30.14 and 30.18, Comment 11: The ACMUl's (Advisory Committee on Medical Uses of Radioisotopes) conclusions that either an exemption or general license is appropriate for the C-14 product do not address the fundamental aspects of nuclear safety. Its judgment was based partially on the assumptions: (1) the product may only be dispensed by prescription, (2) the product is approved by the Food and Drug Administration, and (3) the office / facility using the product will be subject to Clinical Laboratory improvement Amendment (CLIA) regulation.

Response, The transcript from the ACMUI meeting shows the Committee did include radiation safety in its considerations and did not consider it to be an issue. Further, as stated in 10

.i s

. m

- the suppiamental material supportwg the proposed rule, there em no nuclear safety is6ues associated with the use of the C 14 capsules for clinical diagnostic testing. Therefore, use of

, either an exemption or general license is appropriate.

-t Comment 12: The exemption approach does not provide the NRC with flexibility to -

impose a limitation on the amount of C-14 capsules any physician can possess in an office in ,

t the event there is a recall of the product, or a large amount of product becomes unusable, the .j NRC will have no control over the disposal of the product.-

Raaponas: N is not necessary to impose a possession limit on the amount of C 14 f capsules l'ecause the radiation risk is insignificant. The earth's atmosphere contains an -

h. q

- inventory of naturally occurring C 14 of about 3.8 million curies which is in addition to the huge j

inventhry of about 240 million curies in the world's oceans. The small amount of C-14 released into the atmosphere from the use of this test would mix with the global inventory and would have no impact on public health. The current world inventory of naturally occurring C-14 results in an average dose to the public of about 1.25 mrom por year, and the release of 0.6 curies of ,

- C 14 from the total of 600,000 tests assumed to be administered annually would result in an {

c additional average annual dose of 2 X 104 mrom, in the event that a recallis necessary, the I manuf$cturer may use the same process for recalling any other non-radioactive drugs If C 14 -

}

urea capsules are retumed to the manufacturers, they will be disposed of in accordance with

the manufacturer's possession license. A user, however, can dispose the C 14 uros capsules i

as ordinary trash. Medical users of the C-14 uros test would be unlikely to acquire significant ,

quantities of capsules because they can be ordered within a few days. Thus, even under a j recall, the impact of disposing of C-14 urea capsules into landfills by the user would also be  ;

insignificantJ i

11 i

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l Comment 13: It is essential that and users be adequately informed of the product's radioactive characteristics, so that some form of storage, use, and disposal precautions can be l followed Thus, the labeling must be conspicuously and promirently placed. The commenter j suggested the following: (1) the phrase ' conspicuously and prominently" in front of the proposed la' eling ' bears the words Radioactive Material'should be added, and (2) the NRC l should require that the radioactive material legend,

• Radioactive Material," be included on promotional brochures.

BeS90Daa: Because the radiation risk from C-14 capsules is insignificant, regulatory control of the use, storage, and disposal of the drug for purpose of radiation safety is not necessary, in fact, the label accompanying C 14 capsules is required to indicate that the capsules may be disposed of by users as ordinary trash. Paragraph (a)(6) of 9 32.21 requires that applicants submit copies of prototype labels and brochures for NRC approval. The NRC will ensure that the labels meet the requirements of 9 32.21a before they are approved. Since .

paragraph (a) of 9 32.21a specifies that the label must le durable and legible, the use of an additional phrase such as ' conspicuously and prominently" is unnecessary. *Promotional are norp y,r e d Vs M brochures are for information only; e% "'! p': :M manufacturerg'em hi Gas, on the promotional brochures that C 14 is a radioactive material.

111. Summary of the Final Amendments Final Amendment to 10 CFR Part 32 The regulations in 10 CFR Part 32 are amended to add new $$ 32.21 and 32.21a, to provide requirements for a specific iicense to manufacture, prepare, process, produce, package, repackage, or transfer for commercial distribution, capsules containing one microcurie 12 c- m , ., r , .,n ~ , , c

of C-14 urea, as a radioactive drug, to be distributed to any person for "in vivo" diagnostic use.

These requirements are consistent with the existing requirements on other items under the heading " Exemptions"in 10 CFR Part 30. The amendment includes a reminder that licensees distributing the radioactive drug to persons exempt from licensing would not be relieved from other applicable Federal (e g., FDA) or State requirements goveming the manufacture and distribution of drugs.

The amendment requires that the manufacture or preparation of capsules containing one microcurie of C 14 utea be prepared by persons who meet the current NRC regulations to manufacture and commercially distribute radioactive drugs. The NRC believen regulatory controlis needed to provide high confidence that the drug contains one microcurie of C-14 urea and does not contain any other radioactive contaminants.

Final Amendment to 10 CFR Part 30 m kn)diCU The NRC has determined that the drug in capsule form presentsyc !!g9cW, I

radiological safety or environmental risk, and that it is not necessary to regulate the use of this drug for its radioactive component. Therefore, the NRC can not justify requiring physicians, or any other person, to meet NRC training and experience criteria directed at the safe use of radioactive drugs, or to become an " authorized user " Hence, the capsutes can be distributed to any person. However, other Federal or State agencies may limit the receipt and use of the capsules in accordance with their own requirements.

The regulations in 10 CFR Part 30 are aniended to add a new S 30.21, to permis <y person to receive, possess, use, transfer, own, os acquire for "in vivo" diagnostic use, capsules containing one microcurie of C-14 urea without a license. The final regulation includes a 13 l

reminder that persons receiving the capsules would not be relieved from other Federal or State law governing drugs. Further, in accordance with the NRC's provisions for research involving human subjects (10 CFR 35.6), the exemptioh permitting recefpt and use of the capsules for "in vivo" diagnostic use does not extend to use of the capsules for research involving human subjects. Any person desiring to use the capsules for human research would still be required to submit an application for a specific license under Part 35. The phrase "in vivo diagr ostic use" was selected to describe the activity authorized in $30.21 to differentiate it from the term

" medical use" because:

(1) " Medical use" limits administration to authorized users; use of this drug would not be so limited; and ,

(2) ' Medical use" includes the administration f t e drug to a human research subject, y^ ,'

h ~

1. 4M pht.y Agh_

which woulgh F2.Ltd b, t rulemaking.

Effects of the Final Amendments The final amendments make the drug available to any person, for "in vivo" diagnostic use, without need for an NRC or Agr6ement State license. Because the receipt and use of the drug are exempt from NRC licensing, Agreement States need in make appropriate provisions in their regulations to recognize the exempt distribution of the drug, for "in vivo" diagnostic use, after the manufacture and distribution of the drug, the NRC and the Agreement States will not regulate the use of the drug as long as its use is for "in vivo" diagnostic use. This means that, under NRC and Agreement State regulations, primary care physicians do not need to be " authorized users' in order to administer the drug, and do not need to refer their patients to nuclear medicine physicians. This should result in cost savings to patients. Other Federal 14

i

. c7

1. '4 .

- and State organizations with responeMities for regulating drugs will determine and regulate j 4

who can receive and use the drug for *in vivo" diagnostic use. NRC will continue to regulate the i,

- use of the ~ drug for research involving human subjects under a specific Part 35 license. .

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IV. Description of the Final Amendments The final amendments are the same as the proposed amendments except for t vo minor  ;

changes. Public comments suggested that the phrase " carbon 14 urea capsules not exceeding i

one microcurie" used in the proposed rule may be interpreted as an exact limit of one i

microcurie per capsule (See Comment 2 under the heading 'Public Comment and NRC

Responses). The final rule has been modified and the phrase ' capsules containing one t

microcurie carbon 14 urea (allowing for nominal variation that may occur during the i

i manufacturing process)" is used. Another public comment suggested that labels should contain a statement that the product may be disposed of in the general trash, in the final rule, the label t

requirements include such a statement. b d

Manufacturer and Distributors A new section is added to 10 CFR Pert 32 to permit the distribution of the capsules to r

, persons who are exempt from licensing.

9 32 21 Radioactive druaWanufacture. orecaration. or transfer for commercial distribution of capsules _containina one microcurie carbon-14 urea each for "in vivo" diagnostic use for humans to persons exemot from licensina: Reauirements for a license l

Paragrach f a)

This paragraph establishes the requirements for approval of a license applicationi to

' manufacture, prepare, process, produce, package, repackage, or transfer for commercial 16 4

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distribution, capsules containing one microcurie carbon-14 urea each for "in vivo" diagnostic use, to persons exempt from licensing.

PEastpoh (a)f1)

This paragraph limits issuance of an " exempt distribution license" for distribution of the capsules to persons exempt from licensing to only those who possess either a NRC or ADreement Stata " specific license" for possession and use of byproduct material.

PEagraoh (a)(2)

To acsure that the capsules contain one microcurie of carbon 14 and present no other radiological risks, this paragraph requires that the persons manufacturing and/or commercially distributing the capsules for "in vivo" diagnostic use must also meet the requirements of S 32.72(a)(2). Specifically, these persons must be:

(1) Registered with or licensed by the FDA as a drug manufacturer; or (2) Registered with or licensed by a state agency as a drug manufacturer; or (3) Licensed as a pharmacy by a State Board of Pharmacy; or (4) Operating as a nuclear pharmacy within a Federal medicalinstitution.

Paraaraoh (a)Q)

This paragraph requires applicants to provide evidence that each carbon-14 urea ute contains one microcurie. The NRC's evaluation that the capsules would esult in in signincant radiation risks was based on the capsules containing one microcurie of carbon-14 ur a. Therefore, applicants must demonstrate that the activity of each carbon-14 capsule 17

t, cordains one microcurie, allowing for nominal variation that may occur during the manufacturing i

process.

3

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Parmaraoh (aif4)

This paragraph prohibits carbon 14 ures from being contained in any food, beverage, cosmetic, drug or other commodity designed for ingestion or Inhalation by, or topical application to, a human being except for the capsules as described in this section, because exempt distilbution of this drug has only been evaluated for in vivo" diagnostic use in the form of a capsule containing one microcurie of carbon-14 uroa. There is no prohibition against the ,

t capsule being combined with food or beverage at the time of administration so that the capsule l can be Ingested by the patient.  :

Parmaraoh (a)(5)

Because the exempt distribution of this drug has only been evaluated for "in vivo"

' diagnostic use in the form of a capsule containing one microcurie of carbon 14 urea, this paragraph prohibits incorporation of the capsules into any manufactured or assembled commodity, product, or device intended for commercial dir,tribution. Further, although the drug is being distributed to persons exempt from licensing, this paragraph requires the carbon-14 ure: to be identified :: redie:ctive becau:e the dmg !s baln; pwi for its radioactiva content; therefore, the end user must be provided with information that the drug contains a radioactive material, p

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., 1 Paragraoh fa)f6) j As with any product approved for distribution to persons exempt from licensing, this paragraph requires persons who apply for a license to manufacture or commercially distribute these capsules to submit copies of prototype labels or brochures for NRC approval. This will allow the NRC to confirm that the labels or brochures meet the requirements of 9 32.21a(a) and (b).  !

P_aragraohlti)

This paragraph declares that the regulations do not relieve licensees or applicants from  ;

e complying with applicable FDA other Federal, and State requirements governing the manufacture and distribution of drugs.

Section 32.21a Same: Conditions of license ,

This section establishes the conditions required for a licensee to commercially distribute the capsules to persons exempt from licensing.

Paraoraoh (a)

To inform the end user of the identity of the radioisotope, the physical and chemical form, cr.d the dosage of radioactivdy, W,s paragraph establishet init ihd imiiisdiili c66tilhsi of each capsule or capsules must bear a durable, legible label that:

(1) Identifies the radio'sotope, the physical and chemical form of the radioisotope, the quantity of radioactivity contained in each container at a specific date; and (2) Bears the words

• Radioactive Material."

19

t

• ,p The date requirement is consistent with labeling requirements for other radioactive >

i drugs with a haN iife of greater than 100 days. [

?

Parmaraoh (b) j This paragraph establishes that, consistent with the intended use of the capsules, the j label affixed to the immediate container, or an accompanying brochure, must:

(1) Ste's that the contents are exempt from NRC or Agreement State licensing requirements, 1 (2) Bear the words " Radioactive Material. For "In Vivo" Diagnostic Use Only. This

~ Material is Not To Be Used for Research involving Human Subjects, and N, st Not Be l Introduced into Foods, Beverages, Cosmetics, or Other Drugs or Medicinals, or into Products Manufactured for Commercial Distribution. This Product May Be Disposed of in Ordinary Trash."

The intent of the requirement set out in Paragraph (b)(2) is to make clear that the capsule must remain in the form of a capsule and is not to be combined with one of the listed items such as food or beverages which would result in a radioactive product other than in the form of a capsule for commercial distribution. There is no prohibition against the capsule being combined with food or beverage at the time of administration so that the capsule can be  ;

ingested by the patient. This label also informs the user that this product may be disposed of in ordinary trash.

"In vivo" dimanaatic une by oarsons exemot from licensing A new section is added to 10 CFR Part 30 to exempt any person from NRC or the ,

Agreement State regulations to receive the drug for "in vivo" diagnostic use for humans.

20 x

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= i Jnr 'in vivo" diagnantic upp for humans

- i Paragraph fa) .

This paragraph provides en exemption to any person from the requirements for a a i t lloonse to receive, possess, use, transfer, own, or acquire capsules containing one, microcurie -

.a

- of certion.14 uros for "in vivo" diagnostic purposes, it should be noted that the tronsfer" in this -- [

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i paragraph does not include " transfer for commercial distribution," which is covered in paragraph - ..

. . .(c) of this section. -i a

Paragranh (b) t This paragraph establishes that persons who desire to use the drug for research .l involving humans subjects must apply for and receive a specific Port 35 license. Such a license

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would ensure the protection of the rights of the human subjects by requiring that the research f be approved by an IRB and that the human subjects give their informed consent to participate _

in the research, ,

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This paragraph specifies _that a specific license is needed to manufacture, prepare, ~;

{ pn.c ass, produce, package, repackage or transfer such capsules for commercial distribution. -l i

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Paraoraoh (d)

This paragraph declares that the regulations do not relieve end users from complying with applicable FDA, other Federal, or State requirements governing the receipt, administration, and use of drugs.

V. Agreement State Compatibility Under the Atomic Energy Act, certain regulatory functions are reserved to the NRC.

Among these are the distribution of products to persons exempt from licensing, as discussed in 10 CFR Part 150. Hence, amendments related to the manufacture and commercial distribution of the capsules (10 CFR Part 32) is a Division 4 item of compatibility (Category NRC under the ,

new adequacy and compatibility policy). However, amendments related to possession and use (10 CFR Part 30) are a Division 1 item of compatibility (Category B under the new adequacy and compatibility policy) because of the need for nationwide consistency in the use of producte which are widely distributed. Therefore, the Agreement States will need to make appropriate provisions in their regulations to allow any person to receive capsules containing one microcurie of carbon 14 urea for "in vivo" diagnostic use in humans without need for a license, VI. Finding of No Significant EnvironmentalImpact: Avaliability The Commission has determined under the National Environmental Policy Act of 1969, as amended, and the Commission's regulations in Subpart A of 10 CFR Part 51, that the final rule is not a major Federal action significantly affecting the quality of the human environment; therefore, an environmentalimpact statement is not required. The final rute establishes 22

f:

requirements for the manufacture and commercial distribution of carbon 14 urea capsules to

. persons exempt from locansing and establishes regulations to permit any person to receive the -

capsulot without an NRC license. The Commission beleeves that the radioactive component of

= - in this drug presentsp/psignificant radiation risk and, therefore, rogulatory control of the "in vivo" diagnostic use of the capsules for radiation safety is not necessary. It is expected that this final rule will not cause any significant increase in radiation exposure to the public or radiation release to the environment beyond ths exposures or releases resulting from the use of the carbon-14 capoules under the current regulations. Also, it is expected that there will be no non-radiological impacts. . One public comment on the draft environmental assessment has been y .

received (See Comment 9 under the heading " Proposed Rule, Public Comments, and NRC -

Responses *).

The environmental assessment and finding of no significant impact on which this determination is based is available for inspection at the NRC Public Document Room, 2120 L Street NW. (Lower Level), Washington, DC. Single copies of the environmental assessment:

and the finding of no significant impact are available from Dr. Anthony N. Tse, Omco of Nuclear

' Regulatory Research, U.S. Nuclear Regulatory Commission, Washington, DC 20555-0001, telephone (301) 415 6233 or e-mail at ANT @nrc. gov.

Vll. Paperwork Reduction Act Statement This final rule amends information collection requirements that are subject to the Paperwork Reduction Act of 1995 (44 U.S.C. 3501 et seq,). -These requirements were

approved by the Office of Management and Budget, approval numbers 3150-0001,3150-0017, and 31500120.

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The public reporting burden for this collection of information is estimated to average 16  ;

hours per response, including the time for reviewing instructions, searching existing data i sources, gathedag and maintaining the data needed, and completing and revi6 wing the collection of information. Send comments on any aspect of this collection of information, including suggestions for reducing the burden, to the Information and Records Management Branch (T-6 F33), U.S. Nuclear Regulatory Commission, Washington, DC 20555-0001, or by Internet electronic mall at BJS1@NRC. GOV; and to the Desk O#icer, O# ice of information and Regulatory A#alts, NEOB 10202, (3150-0001, 3150-0017, and 3150-0120), O# ice of l Management and Budget, Washington, DC 20503. .

s Public Protection Notification The NRC may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB control number. ,

Vill. Regulatory Analysis The NRC has prepared a regulatory analysis for the final rule. The analysis examines the benefits and impacts considered by the NRC. No public comments on the draft regulatory analysis have been received during the public comment period. The regulatory analysis is

- availaole for inspection at the NRC Public Document Room,2120 L Street NW. (Lower Level),

Washington, DC. Single copies of the regulatory analysis are available from Dr. Anthony N.

Tse, Office of Nuclear Regulatory Research, U.S. Nuclear RegLlatory Commission,

. Washington; DC 20555-0001, telephone (301) 415-6233 or e-mail at ANT @rirc. gov.

24 1

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.IX. Regulatory Flexibility Certification i

As required by the Regulatory Flexibility Act of 1980,5 U.S.C. 605(b), the Commission f i

i certifies that this rule does not have a significant economic impact upon a substantial number of small entities. The final rule permits physicians and other health care providers to use an additional diagnostic test without having to obtain an NRC license, thus, would provide cost l savirgs to patients, insurers, and the health care Industry. The final rule does not impose any j add #tional obligations on entities tht! may fall within the def,nition of *small entities

• as set forth  ;

in Section 601(3) of the Regulatory Flexibility Act; or within the definition of 'small business' as

' found in Section 3 of the Small Businese Act,15 U.S.C. 632; or within the size standards adopted by the NRC on April 11,1995 (60 FR 18344).  :

I

~

X. Sma'l Business Regulatory Enforcement Faimess Act  ;

d in accordance with the Small Business Regelatory Enforcement Faimess Act of 1996, l the NRC has determined that this action is not "a major" rule and has verified this determination with the" Office of Information and Regulatory Affairs, Office of Management and Budget, XI. Backfit Analysis 4

i The NRC has determined that the backfit rule,10 CFR 50.109, does not apply to this i ..

rule, and therefore, a backfit analysis is not required because th.se amendments do not involve  !

any provisions that would impose backfits as defined in 10 CFR 50.109(a)(1). l 25 w y-, -

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Xil. List of Subjects 10 CFR Pad 30 Byproduct material, Criminal penalties, Govemment contracts, Intergovernmental relations, Isotopes, Nuclear materials, Radiation protection Reporting and record keeping requirements.

10 CFR Part 32 Byproduct material, Criminal penalties, Labeling, Nuclear materials, Radiation protortion, Repcrting and recordkeeping requirements.

For the reasons set out in the preamble and under the authority of the Atomic energy Act of 1954, as aroended, the Energy Reorganization Act of 1974, as amended, and 5 U.S.C.

552 and 553, the NRC is adopting the following amendments to 10 CFR Parts 30 and 32.

PART 30-RU'.ES OF GENERAL APPLICABILITY TO DOMESTIC LICENSING OF FYPRODUCT MATERIAL

1. The authority citation for Part 30 continues to read as follows:

AUTHORITY: Secs. 81,82,161,182,183,186,68 Stat. 935,948,953,954,955, as amended, sec. 234, 83 Stat. 444, as amended (42 U S.C. 2111, 2112, 2201, 2232, 2233, 2236, 22821. secs. 201, as amended,202,206,88 Stat.1242, as amended, 1244,1246 (42 U.S.C.

5841, 5842,SS46).

Section 30 7 also issued under Pub. L.95-601, sec.10,92 Stat. 2951 as amended by Pub. L.102 480, sec. 2002,106 Stat. 3123, (42 U.S.C. 5851). Section 30.34(b) also issuer' 26

under sec.164,68 Stat. 954, as amended (42 U.S C. 2234). Section 30.61 also issued under r

sec.187,68 Stat. 955 (42 U.S.C. 2237).

f

2. In 9 30.8, paragraph (b)is revised to read as follows:

$20JLJnfonnation collection requirements: OMB approyal (b) The approved information collection requirements contained in this part appear in

$$30.9, 30.11, 30.1!i, 30.18, 30.19, 30.20, 30.21, 30.32, 30.34, 30.35, 30.38, 30.37, 30.38, 30.41, 30.50,30.51, 30.55, appendices A and C to this part.

2 L

3. A new $ 30 21 is added under the undesignated conter heading " Exemptions" to read as follows:

$ 30.21 RadioacilinJtug: Caosufes_ coDiainina one mictogurie of carbon-14 urea for "in vivo" diagnoliiG uit.lothumana.

(a) Except as provided in paragraphs (b) and (c) of this section, any person is exempt from the requirements for a license set forth in Section 81 of the Act and from the regulations in this part and Part 35 of this chapter provided that such person receives, possesses, uses, transfers, owns, or acquires capsules containing one microcurie carbon 14 urea (allowing for nominal variation that may occur during the manufacturing process) each, for "in vivo" diagnostic use for humans.

(b) Any persen who desires to use the capsules for research involving human subjects shall apply for and receive a specific license pursuant to Part 35 of this chapter.

?.7

f (c) Any person who desires to manufacture, prepare, process, produce, package, ,

- repackage, or transfer for commercial distribution such capsules shall apply for and receive a specific license pursuant to $ 32.21 of this chapter.

(d) Nothing in this section relieves persons from complying with applicable FDA, other l

?

Federal, and State requirements goveming receipt, administration, and use of drugs. j PART 32-SPECIFIC DOMESTIC LICENSES TO MANUFACTURE OR TRANSFER CERTAIN ITEMS CONTAINING BYPRODUCT MATERIAL

- 4. The authority citation for Par 132 continues to read as follows:

AUTHORITY: Secs. 81,161,182,183,68 Stat. 935,948,953,954, as amended (42 ,

U.S.C. 2111,2201,2232,2233); sec. 201,88 Stat.1242, as amended (42 U.S.C. 5841). ,

s

5. In 6 32.8, paragraph (b) is revised to read as follows:

$ 32.8 information collection reouirements: OMB aooroval.

t (b) The approved information collection requirements contained in this part appear in 4

$$ 32.11, 32.12, 32.14, 32.15, 32.16, 32.17, 32.18, 32.19, 32.20, 32.21, 32.21 a, 32.22, 32.23, 32.25, 32.26, 32.27, 32.29, 32.51, 32.51 a, 32.52, 32. 53, 32.54, 32.55, 32.56, 32.57, 32.58, 32.61,32.62,32.71,32.72,32.74, and 32.210.

4 9 $ 9 9 r

28 4

.,_.e. - -,-p > v --,, .- -,---m-

I i

. . t

6. A new 9 32.21 is added ta read as follows:

Q2.21 Pa*weive drua: Manufacture. orecaration. or transfer for commercial distribution of 4

e=A= containina one micrneurie cart:on 14 urea each for "in vivo" diaanonbc use for humanst to. persons spamot from licensina: Raouirements for a license, (a) An application for a specific license to manufacture, prepare, process, produce, package, repackage, or transfer for commercial distribution capsules containing one microcurie carbon 14 uros (allowing for nominal variation that may occur during the manufacturing -

process) each for in vivo" diagnostic use, to persons exempt from licensing under 9 30.21 of this chapter or the equivalent regulations of an Agreement State will be approved if:

(1) The applicant satisfies the general requirements specified in 9 30.33 of this chapter, provided that the requirements of 9 30.33(a)(2) and (3) of this chapter do not apply to an )

application for a license to transfer byproduct material manufactured, prepared, processed, produced, packaged, or repackaged pursuant to a license issued by an Agreement State; (2) The applicant meets the requirements under 9 32.72(a)(2) of this Part; (3) The applicant provides evidence that each capsule contains one microcurie carbon-14 urea (allowing for nominal variation that may occur during the manufacturing process);

(4) The carbon 14 urea is not contained in any food, beverage, cosmetic, drug (except as described in this section) or other commodity designed for ingestion or inhalation by, or topical application to, a human being; (5) The carbon 14 urea is in the form of a capsule, identified as radioactive, and to be used for its radioactive properties, but is not incorporated into any manufactured or assernbied  ;

commodity, product, or device intended for commercial distribution; and (6) The applicant submits copies of prota+ype labels and brochures and the NRC ,

approves these labels and brochures, t

29 i

- - . . . . . _ - . , , - . , - ,-m... . _._

(b) Nothing in this section relieves the licensee from complying with applicable FDA,

, other Federal, and State requirements goveming drugs.

7 A new $ 32.21a is added to read as follows:

fjl21aSame: Conditions of license.

Each license issued under 9 32.21 of this Part is subject to the following conditions:

(a) The immediate container of the capsule (s) must bear a durable, legible label which:

(1) Identifies the radioisotope, the physical and chemical form, the quantity of

. radioactivity of each cipoule at a specific date; and (2) Bears the words " Radioactive Material." j (b) In addition to the labeling information required by paragraph (s) of this section, the  !

l label affixed to the immediate container, or an accompanying brochure also must:

(1) State that the contents are exempt from NRC or Agreement State licensing I

requirements; and (2) Bear the words " Radioactive Material. For "In Vivo" Diagnostic Use Only. Tnis l

Material is Not To Be Used for Research involving Human Subjects and Must Not Be Introduced into Foods, Beverages, Cosmetics, or Other Drugs or Medicinals, or into Productc Manufactured for Commercial Distribution. This Material May Be Disposed of in Ordinary Trash."

Dated at Rockville, Maryland this day of 1997, For the Nuclear Regulatory Commission. l John C. Hoyle, Secretary of the Commission.

30

O d SRM

ATTACHMENT 3 Regulatory Analysis

REGULATORY ANALYSIS FOR FINAL RULEMAKING

" EXEMPT DISTRIBUTION AND USE OF A RADIOACTIVE DRUG CONTAINING ONE MICROCURIE OF CARBON 14 UREA" 10 CFR PARTS 30 AND 32

1. Background 1.1 Statement of thef_mblem On October 6,1994, the Commission docketed a petition for rulemaking (Docket No. PRM ?L

12) from Tri-Med Specialties, Inc (Tri Med). In a letter dated August 23,1994, Tri Med petitioned the NRC to amend its regulations "to allow for the general licensing and/or exemption for the commercial distribution by licensed pharmaceutical manufacturers of a capsule containing one micro-Curie (pCl) of "C-ures for in vivo diagnostic testing." The purpose of this diagnostic test is to detect the presence of the bacterium Helicobacter py!ori (H. rylori), a cause of peptic ulcers.

" Peptic ulcer disease is a chronic inflamm.')ry condition of the stomach and duodenum that affects as many as ten percent of people in the United States at some time in their lives. The disease has relatively low mortality, but it results in substantial human suffering and nigh economic costs." (Source: Article included as an appendix to the petition, from JAMA, July 6, 1994 Vol 272, No.1,"H. pylori in Peptic Ulcer Disease-NIH Consensus Conference").

In the petition dated August 23,1994, the petitioner stated the fo!!owing:

Recent medical research has found that peptic ulcers are comnionly caused by a bacterium called H. pylori. This bacterium lives in the stomach of most ulcer sufferers. By treating ulcer patients with antibiotics, doctors can now cure most ulcer problems.

It is therefore necessary to detect the presence of H. py!ori bacteria in ulcer patients so that the new treatment can be given appropriately, in the past, this was done by a gastroenterologist who took biopsy samples of the stomach lining at endoscopy, a procedure which was uncomfortable and expensive ($1000).

With the new test, H. pylori can be detected noninvasively using a "C-urea tracer. "C-urea is broken down by H. pylori to form labeled CO, which is expired in the breath. To do the test, a doctor asks the p'eient to swallow the capsule with 30 mis of water. After 15 minutes the patient blows 2 liters of breath into a collection bag (a mylar balloon) which is mailed to a testing laboratory. If "C-CO, more than twice background is present in the breath sample, then the patient must be infected with H. pylori.

n. _ . ,

1 1.2 t Qurrent NRC Regulations

!, In 10 CFR Part'32, " Specific Domestic Licenses.To Manufacture or Transfer Certai,i items : ,

Comaining Byproduct Materials," $ 32? 1, " Manufacture, preparation, or transfer for commercial

= dis'ribution of rodeactive drugs containing byproduct material for medical use under Part 35,"

provides for commorcial distribution of radioactive drugs containing byproduct mat 6 rial for use L

g _

by persons authorized pursuant to Part 35J Thus, the regulations currently would permit : l{

1- Part 32 licensees to commercially distribute capsules contain!ng 1 pCi of "C-urea to persons -

g ~ authorized pursuant to Part 35.

c 4

In 10 CFR Part 35, " Medical Use of i

• product Material," sets forth radiation safety-requirements', including requirements for the training and experience of authorized user F physicians to assure the safe possession and use of radioactive drugs containing byproduct ' i

, material. -

Existing exemptions for use of byproduct material in 6 30.14 " Exemption concentrations" and

.$ 32.18, " Manufacture, distribution and transfer of exempt quantities of byproduct material:

- Requirements for license," do not permit the exempt transfer of byproduct material contained in any food, beverage,- cosmetic, drug, or any product designed for ingestion or inhalation by, or

- application to, a human being.

Therefore, under current regulations, the "C-urea capsules must ce used under a Part 35 4 license.:

1.3 Earher NRC Actions ,

l Following the receipt of the petition, a " Notice of receipt of petition for rulemaking" was published for public comment in the Federal Regiatet on December 2,1994 (59 FR 61831), A

total of 315 public comment letters were received. Of these,313 supported the petition (they were mostly form letters) and two letters opposed the petition. The two letters opposing the petition stated that (1) the product should not receive an exempt status because the uncontrolled distribution and application of this product could lead to significant risk to the MF; and (2) medical uses should be restricted to short lived isotopes because of disposal protpr*

. presented by long-lived isotopes.

g -_This petition was discussed with NRC's Advisory Committee on the Medical Uses of isotopes 7

. (ACMUI) at the October 1995 meeting. The ACMUI indicated that it endorsed the wide -

' availability of this diagnostic test and that the radios:tive drug could be used under a general license or an exemption, _whichever the NRC may t.etermine to be pro ~Jdurally easier.

A rulemaking On was prepared. After receiving comments from Agreement States on the i draft rulemakmg plan, the Commission approved a final rulemaking plan to develop a proposed  :

rule to amend 10 CFR Parts 30 and 32 allowing the distribution of the Carbon-14 capsules as

1. an exempt materialto any person l

1 1'

v 0

, -i -i Y i 1

1 A. Pmposed Rule and Pubhc Comments -

(The proposed rule was published in the Federal Register (62 FR 32552, June iti,1M7) for a ,

j 30-day public comtrent period.,The NRC received seven public comment letters. Four , _ j commenters supported the rule, one opposed the rule, and two provided comments without '

explicitly stating whether the y support or oppose the rule." A summary of public comments and - -'

t NRC's responses are neseniM in the preamtge of the Federal Register notice. Except a minor.-

change in wording, the final amand nents are the same as the proposed amendments._ No.

comments related to tM draft Regslatory Guide has been received, i

l* ' 2. - Ot$ active a , The objective of the ruireaking is to amend 10 CFR Part 32 to permit the manufacture and ,

t commercial aistribution of "C-urea capsules to any person (including physicians who are not

- "authorimod users' under Part 35) and to amend 10 CFR Part 30 to permit any person, without b an NRC license; to rece8ve and use the capsules foi !n vivo diagnostic use for humans. .

13. Allematives _;

LThree attematives have been con idered in the regulatory analysis: deny the petition, i e., .

maintain the status quo, permit the distribution of the capsules to persons exempt from ,

licensing, and permit the distribution of the capsules to general licensees; E Under the first attemative, only physicians who are authorized users under Part 35 would be allowed to possess and administer the "C-ures test.' Any physician could apply to become an authorized user. However, the NRC expects few physicians would apply for a Part 35 license for the sole purpose of using the capsules because of the requirement for training and -

4 experience and the sesociated costs of obtaining and maintaining a Part 35 license.

Altemative'y, physicians whc are not authorized useis can continue to refer their patients to

. physicians who are authorized users to undergo the diagnostic test.- However this would not rehove the current expense,- inconvenience, and delay encountered in an otherwise straight-forward procedure, Under the second altemative,10 CFR Parts 32 and 30 would be amended.10 CFR Part 32 ,

would be amended to permit the manufacture and commercial distribution of "C-urea capsules -

to any person (including physicians who are not " authorized users" under Part 35); 10 CFR Part 30 would be ameaded to permit the manufacture and commercial distribution of the -

capsules to any person, for in vivo diagnostic use for humans. The NRC has determined that

+ the radioactive component of this drug presents an insignificant radiation risk and, therefore, tsgulatory control of tho' capsules is not necessary.

Under the third altemative; 10 CFR Part 35 would be amendad to permit any physician to -

receive and use the capsules under a general license.1 The health and safety concems for this altemative are the same as the Attemative 2. However, if this attemative were adopted,' there could be' a burden to those Agreement States that normally require registration of general

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heense holdersJ An additional burden could also be imposed on general licensees located.in i L ~ the Agreement State if the State charges a license or registration fee.

i value-impact Analysis  ;

i

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~

11 The Petitioner's' Assessment lni the letters detec' t,ugwt 23,1994 and November 30,1994, the petitioner statad,- respectively:

If exempted, the C 14 breath test could be done by most doctors for less than $100 cost - -

1 to the patient.-- This is a considerable savings over endoscopy and biopsy ($1000);

m

... Tho' test is 95 percent accurate and quite inexpensive because of its simplicity. -The l i; i test would permit doctors to determine easily whether or not ulcer patients have been

cured of their infection. By providing the public with an inexpensive, easily accessible '

i; diagnostic test, more individuals would be accurately diagnosed and treated for their..

- H. pyloriinfection This would save the United States an estimated $500 million per -

annum ever conventional therapy,  ;

l The petitioner estimates annual bensfits to be on the order of $500 million/ year.= This assumes L approximately 600,000 "C-ures breath tests / year, at an average cost of $100, in lieu of -

d performitig endoscopy at an average cost of $1000/ test; it assumes that the lower coat and ,

greater availability of an unregulated b7ath test would result in a complete substitution for endoscopy. Tri-Med's benefit analysis provides a measure of the total benefits associated with the test and does not focus on the incremental benefits of administering the test pursuant to

- 10 CFR 35.100 regulation (status quo) versus releasing the test to all physicians (NRC licensed .

and non licensed alike). Implicit in Tri-Med's estimated annual benefits is the presumption that none of these "C tests and corresponding savings would accrue if the petition were denied. In l

- reality, under the status quo, the test would be available and administered by physicians or ,

c ~clinics holding a license under NRC's Part 35 or an equivalent Agreement State regulations.

Further, Tri-Med's estimate did not allow for the substitution of other non-invasive tests (e.g.,

' serological test for igg antibodies to H. pylori antigens) for both endoscopy and "C-ures tests.

[

4 = 4.2 The NRC's Assessment (a) Caat Savirss Aa=M ^-i with A.T,erdTerits to 10 CFR Part 30

) ?The value-impact analysis focuses on the incremental benefits of granting relief consistent with

. Altemative 2 or 3, as specified in Section 3 above. The analysis looks solely at changes relative to the base case or status c;uo, in this analysis, the comparison is between regulated and unregulated "C-ures breath tests, not unregulated "C-urea breath tests and endoscopies

- or other noninvasive tests. For the purposes of this regulatory analysis, the NRC assumes that the same number of breath tests (i.e.,600,000 tests) will be administered regardless of the level of NRC regulatory control. This view is predicated on the belief that each physician's

! primary mobvahon is to provide the best'possible care to his or her patients. If the breath test is

judged preferable to endoscopy, or other procedure, any physician not authorized to use the

_ test will refer his or her patient to authorized users who could perform the test undar existing l 4

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NRC regulations. This appears fully consistent with P' Aard medical practice, wherebyL  :

patients are referred routinely to laboratories and specialists for a wide array of tests and L l

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procedures.

i

~

The benefits of adopting the petition accrus as a result of reduced patient cost and reduced -

j health care cost resulting from the elimination of the need for referrals fromia physician who is i not an authorized user (e.g., gastrointestinal specialist). There would also be some regulatory; ,

'  : savings because the NRC would not have to expend resources _ reviewing new applications for,  :

specific medical use licenses However, these savings would be small because the NRC = j expects that few physicians who a o not authorized users would apply for a specific NRC

+

hoense for use of this one product. g The benefit ct.iculation is based on the ' assumption that as a result of this rulemaking action, a ; i

. significant portion of the 800,000 patients would receive the "C breath test from physicians who '

are not authorized users (e.g., gastrointestinal specialists). The actual savings would be l

. dependent on the number of tests ultimately administered by physicians who are not authorized L users; thereby eliminating the need for a referral to physicians who are authorized users (e.g., .

nuclear medicine specialists)c

. The annual savings could be as high as approximately $20 million if there were a complete shift i of the administration of the tests from physicians who are authorized users (i.e., base case) to

;

n physicians who are not authorized users.

, The basis for this estimate is as follows. ,

- Assuming aaption of the petition eliminates the need for up to 600,000 referrals, patient '

savings in averted travel expenses (transportation and personal time incurred with medical referral) would be:

Assuming round trip of 20 miles @ $0.25/ mile, and personal time of 0.5/ hours / trip valued I

at $25.00/ hour 600,000 trips / year x (20 miles / trip x $0.25/ mile + 0.5 hours5.787037e-5 days <br />0.00139 hours <br />8.267196e-6 weeks <br />1.9025e-6 months <br /> / trip x $25.00/ hour) =

$10.5 million/ year t

Health Care Savings in averted'adrainistrative expenses (administrative costs incurred with

( medical referral) would be:

600,000 patients / year x $19.00/ patient = $1154 million/ year

- Assuming $1g.00 (administrative cost / patient) as the differential between the cost of an office visit to a general family practi::e physician by an established patient ($45.90)i and

- the cost to a' new patient ($64.90 per visit) for completion of new patient paperwork, reviewing health history, maintaining medical records, etc. The patient who is referred to i

. an authorized user (e.g., nuclear medicne specialist) for the "C-urea breath test would -

most likely be a new patient for the twtho)ted user.

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, i 4-tTotal Savings: ,

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$10.5 million/ year + $11.4 million/ year = $.21.g million/ year 1 Allematively', if only 200,000 or 400,000 of the 600,000 tests were performed by a physician - j who is not an authonzed user, the annual cost savings wculd be approximately $7 million per - _

year and $15 million per year, respectively. -

- if Ahemative 3 were adopted, it would permit any physician to receive and use capsules

containing 1 pCl "C-ures for human use under a general license.-: The health and safety .

concems for this altamative are the same as Altemative 2, However, the adoption of -

' Altemative 3 could add unnecessary burden to those Agreement States and Agreement State j licensees in States that assess licensing or registration fees for general license holders.

Altemative 2 also imposes incremental cost burden for manufacturers or commercial l destributors of the capsules because they would need to obtain an exempt distribution license.

Each application is estimated to take up to 16 hours1.851852e-4 days <br />0.00444 hours <br />2.645503e-5 weeks <br />6.088e-6 months <br /> to prepare. Assuming 3 applicants per _ .

year, the total reporting burden would be _48 hours. For recordkeeping burden, assuming each ' '

of the 3 applicants in a year would need 2 hours2.314815e-5 days <br />5.555556e-4 hours <br />3.306878e-6 weeks <br />7.61e-7 months <br /> to reprogram its computer to print additional -

words on the label or brochure, the one-time total recordkeeping burden would be 6 hours6.944444e-5 days <br />0.00167 hours <br />9.920635e-6 weeks <br />2.283e-6 months <br />.

t Assuming a labor rate of $125 per hour, the total burden would be about $6,750 per year.

There would be costs for the Federal and State governments if Alternative 2 or 3 is adopted.

Under both Altematives 2 or 3, the NRC and some Agreement States would need to amend their regulations to permit the use of the capsules by persons other than physician who are

authorized users.-

, (b) . Health and Safety Effects o

Nthe purposes of this regulatory analysis, the NRC assumes that the same number of breath tests (i.e.', 600,000 tests) will be administered regardless of the level of NRC regulatory control. ,

This view is predicated on the belief that each physician's primary motivation is to provide the ,

best possible care to his or her patients. In addition, the routine and accidental exposures per carbon-14 urea breath test is not expected to be affected by the level of NRC regulatory control.

Thus, radiation exposures to thqworkers and members of the public would be the same

. regardless of which attemative is adopted.

4~ -

The NRC has concluded that the human use of these capsules results in insignificant exposures as depicted below:

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- Maximum Exposed zRoutine Exposurec  !

- Individual' - {

(Worker administering "C - Fdil-time worker,8,000 Less than 0.7 mrom/yr_ -

1. uros breath tests ~ ipatients/yr

Routine exposure of patients ; Patient tests negative . -

0.38 mrom/ capsule 1 from "C-ures breath tests ; Patient tests positive _0.18 mrom/ capsule l Release of 150 pCl of !'CO, Member of public in the - Less than 0.0002 mrom -

7 into administrationi ' administration area

facility from fire : .i

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Rupture of a capsule? Skin (100 cm') exposed for - 5.8 mrad skin dose, causing skin contamin- one hour prior to washing; 0.02g mrom (CEDE) -;

stion of worker or patient 0.075 pCl skin absorption , :l

~

iFurthermore, the NRC condluded that the impacts associated with_ any releases of "C to the h

surrounding environment are expected to be very small and the expected risks are minimal.

i, uThe earth's atmosphere contains.an inventory of naturally occurring "C of about 3.8 million  ;

. curies (equivalent to the activity in 3.8 trillion breath tests), which is in addition to the huge inventory of about 240 million curies in the world's oceans. The "C released into the E atmosphere from the use of this test would mix with the global inventory and expose the public l

and other biotic components of the environment to "C intakes from Inhalation, drinking water,

- and all poss#ble food pathways in the same manner as naturally occurring "C. The currenf ,

i world inventory of naturally occurring "C results in an average dose to the public of about l1.25 mrom/ year, and the release of 0.6 curies of "C from the total of 600,000 tests assumed to y be administered annually would ' result in an additional average annual dose of 2 X 104 mrom to ,

the public. This is far below the EPA reporting level of 1 mrom/ year required under the Clean -

=

0 i Air Act for routine exposures to a member cf the public, and the 4 mrem / year EPA limit for -

t

- public drinking water, In a total population of about 260 million people in the U.S., the collective

- annual dose to the public from the breath tests would be about 0.051 person-rem. In addition, the doses from normal use of breath tests, or from any accidental release of "C to the environ _ ment also are expected to be very small because the concentration of CO, released is .

.very low and it would mix immediately with the atmosphere. Exposure to patients was not cc.asidered when calculating the individual or collective desas resulting from the diagnostic-tests' O The small doses from naturally occurring "C are of little significance to human health and the ,

- ~ environment.. Potential long-term impacts from widespread releases of ths long-lived "C ,

.(5,730-year radiological half-life) from breath tests were concluded to be insignificant.' a

; Assuming that the testing in the U.S, would increase over a period of time to an average of a _ -

[ million tests por year for 50 years, the collective dose to the U.S. population would be a total of f about 5 person-rom over the 50 year period. This dose is very small when compared to the .

7

. - annual collective dose to the U.S; population from naturally occurring'dC of over 300,000

!: person-rem, and about 78,000,000 persorMem from all naturally occurring radiation. Clearly, 4 an increase of a few person-rem w _ ill not significantly change these exposures, and thus there is

no expected impact from the widespread use of the breath test on the entire U.S. population.  ;

i 7 f

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__ =. . ._

A . 4 As a result of this analysis. the NRC concludes that Altematives 2 and 3 are clearly preferable to the no action attemative. This is because either of the two alternatives will result in -

significant cost savings with no measurable adverse effect on health and safety. Furthermore, '

the NRC's recommended option is Altemative 2 because it would avoid the unnecessary cost burden to some Agreement States and their generallicensees.

Therefore, by promulgating the final rule, the cost savings would be maximized without any ,

measurable adverse effect on public health and safety.

5. Decision Rationale Based on the above analysis, the NRC is amending its regulations to permit the manufacture and commercial distribution of Carbon-14 urea capsules to any person (including physicians who are not " authorized users" under Part 35) and permit any person, without an NRC license, to receive and use the capsules for in vivo diagnostic use for humans because the radiological risk from such distribution would be insignificant and the savings to patients could be significant.

8

37.-

y. . i h

w , -

4 i - - - REGULATORY ANALYSIS . M U -

FOR FINAL RULEMAKINGi .

" EXEMPT DISTRIBUTION AND USE OF A RADIOACTIVE DRUG i CONTAINING ONE MICROCURIE OF CAABON 14 UREA" 110 CFR PARTS 30 AND 32- y r

a L Background ,

1,1 - r 9%nant of the Prahlam - ]

~

L _

On October 6,1994, the Commission docketed a petition for rulemaking (Docket No. PRM 35 -

~

12) from Tri-Med Specialties, Inc (Tri-Med). In a letter dated August 23,1994, Tri-Med L petitioned the NRC to amend its _ regulations "to allow for the general licensing and/or exemption

for the commercial distribution by licensed pharmaceutical manufacturers of a capeule containing one micro-Curie (pCl) of .*C-u os for in vivo diagnostic testing." The purpose of this

( diagnostic test is to detect the presence of the bacterium Helicobacter pylori (H. pylori)la cause of peptic ulcers. ,

" Peptic ulcer disease is a chronic inflammatory condition of the stomach and duodenum that ,

affects as many as ten percent of people in the United States at some time in their lives. The

- disease has relatively low mortality, but it results in substantial human suffering and high

- economic costs." (Source: Article included as an appendix to the petition, from JAMA, July 6, 1994-Vol 272, No.1, ."H. pylori in Peptic Ulcer Disease-NIH Consensus Conference").

E in the petition dated August 23, 1994, the petitioner stated the fcilowing:

- Recent medical research has found that peptic ulcers are commonly caused by a

- bacterium called H. pylori. This bacterium lives in the stomach of most ulcer -

sufferers. By treating ulcer patients with antibiotics, doctors can now cure most ulcer problems.

b It is therefore necessary to detect the presence of H. pylori bacteria in ulcer patients so that the new trestraent can be given appropriately. In the past, this was done by a gastroenterologist who took biopsy samples of the stomach lining at endoscopy, a procedure which was uncomfortable and expensive ($1000).

With the new test, H. pylori can be detected noninvasively using a "C-urea-tracer. "C-urea is bn. ken down by H. pylori to form labeled CO2 which is expired 1

in the breath.- To do the test, a doctor asks the patient to swallow the capsule :

with 30 mis of water. After 15 minutes the patient blows 2 liters of breath into a - ,

collection bag (a mylar balloon) which is mailed to a testing laboratory. if "C-i CO, more than twice background is present in the breath sample, then the patient must be infected with H. pylori.'

4.

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11.2: Current NRC Regulchons

In 10 CFR Part 32, " Specific Domestic Licenses To Manufactwo or Transfer Certain items : . 3

~ Containing Byproduct Materials," $ 32.72, " Manufacture, preparation, or transfer for commercial 1 distribution of radioactive drugs containing byproduct material for medical use under Part 35," -  :

provides for commercial distribution of radioactive drugs containing byproduct material for use

by persons authorized pursuant to Part 35. Thus, the regulations currently would permit Part 32 licensees to commercially distribute capsules containing 1 pCi of "C-ures to persons authorized pursuant to Part 35l a

in 10 CFR Part 35, " Medical Use of Byproduct Material," sets forth radiation safety -

requirements; including requirements for the training and experience of authorized user ";

physicians to assure the safe possession and use of radioactive drugs contMning bypmduct--

material.

~

Existing exemptions for use of byproduct material in g 30.14, " Exemption concentrations" and

f $ 32.18. " Manufacture, distribution and transfer of exempt quantities of byproduct material

- Requirements for license," do not permit the exempt transfer of byproduct material contained in i< ,y food, beverage, cosmetic, drug, or any product designed for ingestion or inhalation by, or ' '

s application to, a human being.--

Therefore, under current regulations, the "C-urea capsules must be used under a Part 35 license.

4 1.3 Earlier NRC Achons Following the receipt of the' petition, a " Notice of receipt of petition for rulemaking' was published for public comment in the Federal Register on December 2,1994 (59 FR 61831). A total of 315 public comment letters were received. Of these,313 supported the petition (they were mostly form letters) and two letters opposed the petition. The two letters opposing the petition stated that (1) the product should not receive an exempt status because the l

= unceubviled distribution and application of this product could lead to significant risk to the public L and (2) medical user, should be restricted to short lived isotopes because of disposal problems presented by long-lived isotopes.-

This petition was discussed with NRC's Advisory Committee on the Medical Uses of Isotopes (ACMUI) at the October 1995 meeting. The ACMUI indicated that it endorsed the wide  !

availability of this diagnostic test and that the radioactive drug could be used under a general license or an exemption, whichever the NRC may determine to be procedurally easier.

t-A rulemaking plan was prepared. After receiving comments from Agreement States on the

. draft rulemaking plan, the Commission approved a final rulemaking plan to develop a proposed J rule to amend 10 CFR Parts 30 and 32 allowing the distribution of the Carbon-14 capsules as an exempt material to any person .

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-1A: Pr= -i Re and PiMn Comments

- The pic-;-:::d rule was published in the Federal Register (62 FR 32552,- June 16,1997) for a ;

30-day public comment period. The NRC received seven public comment letters. Four,

.commenters supported the rule, one opposed the rule, and two provided comments without = l

'r explicitly stating whether they support or oppose the rule. A summary of public comments and NRC's responses are presented in the preamble of the Federal Register notice. _ Except a minor charge in wording, the final amendments are the same as the proposed amendments. No -

comments rc!sted to the draft Regulatory Guide has been received, f 2. Oyective _

iThe oyectNo of the rulemaking is to amend 10 CFR Part 32 to permit the manufacture and commercial distribution of "C-urea capsules to any person (including physicians who are not  ;

" authorized users' under Part 35) and to amend 10 CFR Part 30 to permit any person, without Jan NRC license, to receive and use the capsules for in vivo diagnostic use for humans.

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3. Altamatives 1

Three attematives have been considered in the regulatory analysis: deny the petition, i.e.,

-maintain the status quo,' permit the distribution of the capsules to persons exempt from licensing, and permit the distribution of the capsules to generallicensees.

Under the first altomative, only physicians who are authorized users under Part 35 would be allowed to possess and administer the "C-ures test. Any physician could apply to become an authorized user. However, the NRC expects few physicians would apply for a Part 35 license for the sole purpose of using the capsules because of the requirement for training and -

experience and the associated costs of obtaining and maintaining a Part 35 license.

Altematively, physicians who are not authorized users can continue to refer their patients to physicians who are authorized users to undergo the diagnostic test. However this would not relieve the current expense, inconvenience, and delay encountered in an otherwise straight-forward procedure.

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+ Under the second altemative,10 CFR Parts 32 and 30 id tn amended.10 CFR Part 32 would be amended to permit the manufacture and co mercial distribution of "C-urea capsules' to any person (including physicians who are not "a rized users" under Part 35); 10 CFR -

Part 30 would be amended to permit the manufa re and commercial distribution of the capsules to any person, for in vivo diagnostic u for humans. The NRC has determined that the radioactive component of this drug presents I radiation risk and, therefore, regulatory control of the capsules is not necessary.-

Under the third altemative,10 CFR Part 35 would be amended to permit any physician to

,  : receive and use the capsules under a generallicense. The health and safety concems for this altemative are the same as the Altemative 2. However, if this attemative were adopted, there could be a burden to those Ayre,ement States that normally require registration of general 3

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license holders. An additional burden could also be imposed on general licensees located in -j l

the A0reement State if the State charges a license or registration fee.~

74[.l Value-impact Analysis -

4.1 : The Petitione(s Assessment u

in the letters dated August 23,1994 and November 30,1994, the petitioner stated _, respectively:

if exempted, the C-14 bream test could be done by most doctors for less than $100 cost i '

b . to the patient. This is a considerable savings over endoscopy and biopsy ($1000).

[ ... The test is 95 percent accurate and quite inexpensive because of its simplicity. The test would permit doctors to determine oasily whether or not ulcer patients have been -

=- cured of their infection.1 By providing the public with an inexpensive, easily accessible  ;

e F diagnostic test, more individuals would.be accurately diagnosed and treated for theirL H. pylori infection. This would save the United States an estimated $500 million per--  ;

p

" + annum over conventional therapy,-

The petitioner estimates annual benefits to be on the order of $500 million/ year. This assumes

. approximately 600,000 "C ures breath tests / year, at an_ average cost of $100, in lieu of e

?: performing endoscopy at an average cost of $1000/ test. It assumes that the lower cost and

[ greater availability of an unregulated breath test would result in a complete substitution for endoscopy. Tri-Med's benefit analysis provides a measure of the total benefits associated with

' the test and does not focus on the incremental benefits of administering the test pursuet ic 10 CFR 35.100 regulation (status quo) versus releasing the test to all physicians (NRC licensed and non licensed alike). Implicit in Tri Med's estimated annual benefits is the presumption that 3 none of these "C tests and corresponding savings would accrue if the petition were denied. In C <

L  ; reality, under the status quo, the test would be available and administered by physicians or clinics holding a license under NRC's Part 35 or an equivalent Agreement State regulations.

Further Tri-Med's estimate did not allow for the substitution of other _non-invasive tests (e.g.,

serological test for_lgG antibodies to H, pylori antigens) for both endoscopy and "C-urea tests. ,

s 4.2' The NRC's Assessment' (a) Cost Savinas Asse64=d with Amendments to 10 CFR Part 30 ,

h ~ The value-impact analysis focuses on the incremental benefits of granting relief consistent with

Alternative 2 or 3, as specified in Section 3 above. The analysis looks solely at changes - ~

relative to the base case or status quo. In this analysis, the comparison is between regulated

and unregulated !*C-urea breath tests, not unregulated "C-ures breath tests and endoscopies 1 ~ or other noninvasive tests. For the purposes of this regulatory snalysis, the NRC assumes that

- the same number of breath tests (i.e.,600,000 tests) will be administered regardless of the

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level of NRC regulatory control. This view is predicated on the belief that each ' physician's primary motivation is'to provide the best possible care to his or her patients. 'If the breath test is judged preferable to' endoscopy, or other procedure, any physician not authorized to use the 2: -

L test will refer his or her patient to authorized users who could perform the test under existing j-4-

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NRC regulations. This appears fully consistent with standard medical practice, wherebv~ . '

patients are referred routinely.to laboratories and_ specialists for a wide array of tests and-;

- L procedures. .

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' The benefits of adopting the petition accrue as a result of feduced patient cost and reduced :

Lhealth-care cost resulting from the elimination of the need for referrals from a physician who is:

not an authorized user (e.gc, gastrointestinal specialist).< There would also be some regulatory  :

savings because the NRC would not have to expend resources reviewing new applications for--

, specific medical use licenses.- However, these savings would be small because the NRCl expects that few physicians who are not authorized users would apply for a specific NRC ~

license for use of this one product. g The benefit calculation is' based on the assumption that as a result of this rulemaking action, a 3

! significant portion of the 600,000 patients would receive the "C breath test from physicians who' _

are not authonzed users (e.g., gastrointestinal specialists). -The actual savings would be j

dependent on the number of tests ultimately administered by physicians who are not authorized '

L users, thereby. eliminating the'need for a referral to physicians who are authorized users (e.g.,-- ~

nuclear medicine specialists). -

The annual savings could be as high as approximately $20 million if there were a complete shift 1 of the administration of the tests from physicians who are authorized users (i.e., base case) to physicians who are not authorized' users.

' The basis for this estimate is as follows.

. Assuming adoption of the petition eliminates the need for up 'o 600,000 referrals, patient savings in averted travel expenses (transportation and personal time incurred with medical

, ' referral) would be:

r

Assuming round trip of 20 miles @ $0.25/ mile, and personal time of 0.5/ hours / trip valued at $25.00/ hour 600,000 trips / year x (20 miles / trip x $0.25/ mile + 0 'i hours / trip x $25.00/ hour) =

$10.5 million/ year -

Health Care Savings in averted administrative expenses (administrative costs incurred with

- medical referral) would be:

1 600,000 patients / year x $19.00/ patient = $11 A million/ year

- Assuming $19.00 (administrative cost / patient) as the differential between the cost of an office visit to a general family practice physician by an establie,hed patient ($45.90), and

• the cost to a new patient ($64.90 per visit) for completion of new patient paperwork, reviewing health history, maintaining medical records, etc. The patient who is referred to an authorized user (e.g., nuclear medicine specialist) for the "C-urea breath test would most likely be'a new patient for the authorized user.

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j T $10.5 minion / year + $11.4 million/ year = $ 21.g million/yearf

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ANomatrvely, if only 200,000 or 400,000 of the 600,000 tests were performed by a physician

who is not an authorized user, the annual cost savings would be approximately $7 m;llion per _

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year and $15 million per year, respectively.

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if Alternative 3 were adopted, it would permit any physician to receive and use_ capsules ~

F ' containing 1 pCi "C-ures for human use under a general licenser The health and safety _ ,

concems for this altemative are the same as Altemative 2. However, the adoption of '

Altomative 3 could add unnecessary burden to those Agrooment States and Agreement State licensees in States that assess licensing _or_ registration fees for general license holders, a F

Allemative 2 also imposes incremental cost burden for manufacturers or commercial; '

destributors of the capsules because_they would need to obtain an exempt distributio1 license, -

Each application is estimated to take up to 16 hours1.851852e-4 days <br />0.00444 hours <br />2.645503e-5 weeks <br />6.088e-6 months <br /> to prepare. Assuming 3 applicants por, .

e year, the total reporting burden would be 48 hours5.555556e-4 days <br />0.0133 hours <br />7.936508e-5 weeks <br />1.8264e-5 months <br />.~ For recordkeeping burden,- assuming each ->

of the 3 applicants in a year would need 2 hours2.314815e-5 days <br />5.555556e-4 hours <br />3.306878e-6 weeks <br />7.61e-7 months <br /> to reprogram its computer to print additional ~ *

' words on the label or brochure, the one-time total recordkeeping burden would be 6 hours6.944444e-5 days <br />0.00167 hours <br />9.920635e-6 weeks <br />2.283e-6 months <br />.'

Assuming a labor rate of $125 per hour, the total burden woulci be about $8,750 per year. i There would be casts for the Federal and State governments if Altemative 2 or 3 is adopted.  :

4

' Under both Altematives 2 or 3, the NRC and some Agreement States would need to amend their regulations to permit the use of the capsules by persons other than physician who are authorized users.

(b) Health and Safety Effects

)4 For the purposes of this regulatory analysis, the NRC assumes that the same number of breath tests (i.e.,600,000 tests) will be administered regardless of the level of NRC regu'atory control.

4 .This view is predicated on the belief that each physician's primary motivation is to provide the

! best possible care to his or her patients, in addition, the routine and accidental exposures per

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carbon-14 urea breath test is not expected to be affected by the lael of NRC regulatory control.

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- Thus, radiation exposures to the workers and members of the public would be the same regardless of which altemative is adopted.

The NRC has concluded that the human use of these capsules results in insignific9nt

,. exposures as depicted below! .

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Scenario Masimum Exposed Routine Exposure ilndividual^ j Worker administorireg "C- Full-time worker,8,000_ Less than 0.7 mrom/yr..

urea breath tests ! Lpatients/yr Routme exposure of patients Patient tests negative.  : 0.38 mrom/ capsule _ l from "C-ures teath tests ' Patient tests positive . 0.18 mrom/ capsule l

' Release'of 150 pCi of "CO, . Member of publicin the Less than 0.0002 mrom - ,

L L into administration administration area

- facliity from fire 7 3

- Ru'pture of al capsule - Skin (100 cm') exposed for- 5.8 mrad skin dose,-

' causing skin contamin- one hour prior to washing; 0.02g mrom (CEDE) ation of worker or pahent 0.075 pCI skin absorption l

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!  ; Furthermore,'the NRC concluded that the impacts associated with any releases of "C to the 1

. surrounding environment are expected to be very small and the expected risks are minimal.

- The earth's atmosphere contains an inventory of naturally occurring "C of about 3.8 million

curies (equivalent to the activity in 3.8 trillion breath tests), which is in addition to the huge -

inventory of about 240 million curies in the world's oceans. The "C released into the  ;

atmosphere from the use'of this test would mix with the globalinventory and expose the public - $

and other biotic components of the environment to "C intakes from innalation, drinking water, - #

l and all possible food pathways in the same manner as naturally occurring "C. The currect world I,tventory of naturally occurring "C results in an average dose to the public of 1.25 mrom/ year, and the release of 0.6 curies of "C from the total of 600,000 t assumed to t

' be administered annually would result in an additional ual 2 X 104 mrem to the public. This is far below the EPA reporting level o uired under the Clean Air Act for routine exposures to a member of the public, 4 mrem / year EPA limit for public drinking water.L in a total population of about 260 million people in the U.S., the collective annual dose to the public from the breath tests would be about 0.051 person-rem. In addition, the doses from r.ormal use of breath tests, or from any accidental release of "C to the environment also are expected to be very small because the concentration of CO, released is very low and it would mix immediately with the atmosphere. j P

The small doses from naturally occurring "C are of little sig i nce to human health and the environment, _ Potential long-term impacts from widespre r ases of the long-lived "C (5,730; year radiological half-life) from bresth te luded to be insignificant.

!1 Assuming that the testing in the U.S. would i rease a riod of time to an average of a L

! million tests per year for 50 years, t tive do to the U.S. population would be a ose is very smallwhen compared to

= total of about 5 person-rem over t nault the annual collective dose to the a r - __ ion om naturally occurring "C of over 300,000 poison-rom, and about 78,000,000 -rem from all naturally occurring radiation. Clearly, 1 an increase of a few perton- will not significantly change these exposures, and thus there is 30 ed impact widespread use of the breath test on the entire U.S. population.

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L As a result of this analysis, the NRC concludes that Alternatives 2 and 3 are clearly preferable  !

. to the no action altemative. This is because either of the two alternatives will result in

. significant cost savings with no measurable adverse effect on health and safety. Furthermore, '

the NRC's recommended option is Attemative 2 because it would avoid the unnecessary cost burden to some Agreement States and their general licensees.

Therefore, by promulgating the final rule, the cost savings would be maximized without any measurable adverse effect on public health and safety.

S. Decision Rationale Based on the above analysis, the NRC is amending its regulations to permit the manufacture and commercial distribution of Carbon-14 urea capsules to any person (including physicians -

who are not " authorized users" under Part 35) and permit any person, without an NRC license, to receive and use the capsules for in vivo diagnostic use for humans because the radiological-risk from such distribution would be#:;";S: and the savings to patients could be significant.

4 4

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8 W d

e ATTACHMENT 4 Environmental Assessment

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q 1 Environmental Assessment

> For Finai Amendments to 10 CFR Parts 30 and 32

" Distribution of a Radioactive Drug Containing One Microcurie of :  ;

Carbon 14 Ursa as Exempt Material for "In Vivo" Diagnostic Testing" 'l 4 --

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Statemord of the Final Action e The Nucieer Regulatory Commission (NRC) is amending its regulations to allow NRC E  ;

licensees to distribute a radioactive drug containing one microcurie of carbon-14 uros to any j

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person for "in vivo" diagnostic use. The NRC has determined that the radioactive component of -

i- ~~such capsules presents an insignificant radiation risk and, therefore, regulatory control of the 2 drug for radiation safety is not necessary. This amend ment makes the drug more widely ,

!  ! available, thus reducing costs to patients, insurers, and the health care industry. -This action is

- being taken in response to a petition for rulemaking (PRM-3512) submitted by Tri-Med i Specialties,' ln' c.

l Need for the Medmonts The amorch '** have been developed to grant the petition for rulemaking. The final rule permits manufacturers or commercial distributors to distribute carbon-14 urea capsules as '

exempt material to any person. The Commission is promulgating this rulemaking because it -

believes that the radiological risk from such distribution would be insignificant and the savings to patients could be significant, in addnion, the Commission recognizes that other Federal and ,

State agencies (e.g., Food and Drug Ac' ministration and the State Boards of Pharmacy) are -

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• responsible for the receipt and use of drugs that do not contain byproduct materials, and would

. provide necessary oversight for the safe use of these carbon-14 urea capsules as drugs. _

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[ 'd Mamdivas Considered j t Three allematives have been considered regarding the petition: deny the petition,' l.e., j 4

mainteen the status quo, permit the. distribution of the capsules as exempt material, and permit -- f the distribution of the capsules to general licensees.' ~_

~

Under the Arzt altemative, the current situation would continue: only physicians who are l

- authorized users under Part 35 would be allowed to possess and administer the C-14 uros test.-

L Any physician could epply to become an authorized user. Hr ever, the NRC expects. few - -

3

physicians would apply for a Part 35 license for the sole purpose of using such capsules -

' i because of the requi.ement for training and experience and the associated costs of obtaining and maintaining a Part 35 license. Altematively, physicians who are not authorized users can 4- continue to refer their patients to physicians who are authorized users to undergo the diagnostic test. However this would not relieve the current expense, inconvenience, and delay -  !

encountered in an otherwise' straight-forward procedure.

l - -

3 Under the second attemative,10 CFR Parts 32 and 30 would be amended. Part 32  :

t would be amended to establish requirements for the manufacture and distribution of C-14 urea capsules to persons exempt from licensing, i.eiany person (including physicians who are not

" authorized users" under Part 35); Part 30 would be amended to permit any person to receive, possess, use, transfer, own, or acquire the capsules for in vivo diagnostic use for humans without a license. The NRC has determined that the radioactive component of this drug presents an insignificant radiation risk and, therefore, regulatory control of the capsules is not necessary.

Under the third altomative,10 CFR Part 35 would be amended to permit any physician to )

receive and use the capsules under a general license. The (~,ealth and safety concems for this altemative are the same as the Altemative 2. However, if this altemative were adopted, there .

could be a burden to those Agreement States that nomisily require registration of general

- license holders. An additional burden could also be imposed on general licensees located in ,

the Agreement State if the State charges a license or registration fee.

Based on the Draft Regulatory Analysis prepared for this proposed rule, the Commission concludes that Altematives 2 and 3'are clearly preferable to_ the no action altemative. This is  :

because either of the two attematives will resu't in significant cost savings with no measurable adverse effect on health and safety. Furthermore, the NRC's recommended option is 2-

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A Alternative 2 because it avoids the unnecessary cost burden to some Agreement States and ]

, theirlicensees. ,

maari on the Pohlic and the Environment l

The amendments are expected to have an insignificant impact on the'publ'c and the environment.- The NRC assumes th'at the same number of breath tests will be administered regardless of the fevel of NRC regulatory control. This view is predicated on the belief that each physician's primary motivation is to provide the best possible care to his or her patients, if the breath test is judged preferable to endoscopy, or other procedure, any physician not . t authorized to use the test will refer his or her patient to authorized users who could pet form the i test under existing NRC regulations. Under this assumption, this rulemaking action is expected

-l

to result in no change in radiation exposures to the workers and patients when compared with the status quo. Similarly, it is expected that there will be no change in impact to the environment because the Commission assumes that the same number of tests will be

- administered regardless of which altunative is adopted.-

i; The earth's atmosphere contains an irsentory of naturally occurring C-14 of about 3.8 million o

curies which is in addition to the huge inventory of about 240 million curies in the world's oceans.- The small amount of C-14 released into the atmosphere from the use of this test m

would mix with the global inventory and would have no impact on public health. The current world inventory of naturally occurring C-14 results in an average dose to the public of about 1.25 mrem per year, and the release of 0.6 curies of C-14 from the total of 600,000 tests assumed to be administered annually would result in an additional average annual dose of 2 X 104mrom. This is far below the EPA reporting level of 1 mrem / year required under the

- Clean Air Act for routine exposures to a member of the public, and the 4 mrum/ year EPA limit

.for public drinking water.-

List of Aaencies and Persons Consulted and identification of Sources Used Following the receipt of the petition for rulemaking, a " Notice of receipt of petition for rulemaking" was published for public comment in the Egleral Reaister on December 2,1994, (5g FR 61831). A total of 315 public comment letters,313 supporting (mostly form letters) and 2 opposing letters, were received. This petition was discussed with NRC's Advlaory Committee 3

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4

4. , * ,

L  : on the Medical Uses of lootopes ACMUI) at the October 1995 meeting.; Furthermore, the draft : q

- rulemaking plan was forwarded to 29 Agreement States for comments.

A proposed rule.was ' published in the Federal Register (62 FR 32552, June 16,- 1997) for i

=

a 30-day public comment period.;The NRC received seven public comment letters.1 Four .

x: .. .

commenters supported the rule, one opposed the rule, and two provided comments without q explicitly. stating support of or opposition to the rule.- A summary'of public comments and NRC's l responses are presonted in the preamble of the Federal Register notice. Except a minora q j

change in wording, the final amendments are the same as the proposed amendments.

- One commenter addressed the draft environmental Assessment. The commenter stated

_ that the environmental Assessment fails to consider the fact that another equally non-invasive,

. but non-radiological, diagnostic procedure (such as C-13 test) is available and provides a ; _

toomparable allemative to the C-14 test. The commenter apparently concluded that the assumption underlying the environmental assessment is that in the absence of the C-14 test,

~t he only altomative for the detection of H. pylori is invasive gastroendoscopy.

- The purpose of the environmental assessment is to address and document the expected j impact to the environment of subject rule. As presented in the regulatory analysis prepared for j this rule, the NRC has determined that the environmental impact is expected to be insignificant -.

because of the extremely low radiological hazards associated with the use of capsules -

containing on: microcurie C-14 orea.

~

< if the environmentalimpact had been significant, then the existence of a non-radioactive -

attemative would have been a factor in assessing the cost - benefit of this rulemaking.

However, the impact is not significant. Hence, the regulatory issue in this rulemaking is .

whether the C-14 method should be made available to physicians who are not authorized users, and not whether there exists a non-radioactive attemative.

Findana of No Sionificant Imnacts The Commission has determined under the National Environmental Policy Act of 1969,-

as amended, and the Commission's regulations in Subpart A of 10 CFR Part 51, that the amendments will not be a major Federal action significantly affecting the quality of the human L environment, and therefore an environmental impact statement is not required. .The final rule amends _10 CF.R Part 32 to permit the manufacture and commercial distribution of C-14 urea capsules to any person (including physicians who are not " authorized users" under Part 35) and 4 <

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to amend 10 CFR Part 30 to permit any person, without an NRC license, to receive and use the': -i capsules for in vivo diagnoste use for humans.SThe Commission believes that the radioactive q

componert of this drug presents an inssnificant radiation risk and, therefore, regulatory control _

I of the capsules for "in vivo' diagnostic use is not necessary< lt is expected that this final rule 1 l

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. will not cause any significant increase in radiation exposure to the public or radiation release to j

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' the ' environment beyond the'sxposures or releases resulting from the use of the carbon-14 : t capsules under the current regulations.

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Environmental Assessment For Final Amendments to 10 CFR Parts 30 and 32

" Distribution of a Radioactive Drug Containing One Microcurie of Carbon-14 Urea as Exempt Material for "In Vivo" Diagnostic Testing" Pdament of the Final Action The Nuclear Regulatory Commi ion (NRC) is amending its regulations to allow NRC licensees to distribute a radioactive containing one microcurie of carbon-14 urea to any person for "in vivo" diagnostic use. NRC has determint,d that the radioactive component of such capsules presents rs diation risk and, therefore, regulatory control of the drug for radiation eafety is not necessary. This amendment makes the drug more widely available, thus reducing costs to patients, insurers, and the health care industry. This action is being taken in response to a petition for rulemaking (PRM-35-12) submitted by Tri-Med Specialties, Inc.

Need for the Amendments The amendments have been developed to grant the petition for rulemaking. The final rule permits manufacturers or commercial distributors to distribute carbon-14 urea capsulas as exempt material to any person. The Commission is promulga, ting thi[rulemaking because it believes that the radiological risk from such distribution woulE% 'and the savings to patients ceuld be significant. In addition, the Commicsion recognizes that other Federal and State agencies (e.g., Food and Drug Administration and the State Boards of Pharmacy) are responsible for the rece'pt and use of drugs that do not contain byproduct materialc, and would provide necessary oversight for the safe use of these carbon-14 urea capsules as drugs.

Afternatives Conaldered Three attematives have been considered regarding the petition: deny the petition, i.e.,

maintain the status quo, permit the distribution of the capsules as exempt material, and permit the distribution of the capsules to generallicensees.

Under the first attemative, the current situation would continue: only physicians who are l

authorized users under Part 35 would be allowed to possess and administer the C-14 urea test.

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L__ _ - _ _ _ _ _ - _ - -

l l

l Any physician could apply to become an authorized user. However, the NRC expects few physicians would apply for a Part 35 license for the sole purpose of using such capsules because of the requirement for training and experience and the associated costs of obtaining and maintelning a Part 35 license. Attemstively, physicians who are not authorized users can continue to refer their patients to physicians who are authorized users to undergo the diagnostic test. However this would not relieve the current expense, inconvenience, and delay encountered in an otherwise straQht-forward procedure.

Under the second attemative,10 CFR Parts 32 and 30 would be amended. Part 32 would be amended to establish requirements for the manufacture and distribution of C-14 urea capsules to persone 6empt licensing 1.e., any person (including physicians who are not

" authorized sersu/" under Part 35); art 30 would be amended to permit any person to receive, posse , use, transfer, own, or s'c'ci ' e the capsules for in vivo diagnostic use for humans witho a license, The NRC has dete ined that the radioactive component of this drug

( w i tion risk and, erefore, regulatory control of the capsules is not presents c K-Jm p ne sary, Under the third attemative O CFR Part 35 would be amended to permit any physician to receive \and use the capsule nder a general license. The health and safety concems for this s

attemative are the same as the Attemative 2. However, if this attemative were adopted, there could be a burden to those Agreement States that normally require registration of general license holders. An additional burden could also be imposed on general licensees located in the Agreement State if the State charges a license or registration fee.

Based on the Draft Regulatory Analysis prepared for this proposed rule, the Commission concludes that Attematives 2 and 3 are clearly preferable to the no action alternative. This is because either of the two attematives will result in significant cost savings with no measurable adverse effect on health and safety. Furthermore, the NRC's recornmended option is Attemative 2 because it avoids the unnecessary cost burdinloh Agreement States and their licensees.

[

.j "T"n ' ' j Imoact on the Public and the Environma. t . . l The amendments are expected tc, have e ::7.T. .g. Ipact on the pub c and the environment. The NRC assumes that t same number of breath tests win administered

/

regardless of the level of NRC regu'atory co ol. This view is predicateid on the belief that 2

i

-2 eech physician's primary motivation.is to provide the best possible care to his or her patients. If; the tweeth inst is judged g C:d'= to endoscopy, or other procedure, any physician not ;

[ authortred to use the test will refer his or her patient to authorized users who could perform the 1 i

? test under existing NRC regulations. Under this assumption, this rulemaking action is expected 4

. to result in no change in radiation exnesures to the workers and patients when compared with -

the status quo. Similady, X is expectea that there will be no change in impact to the ' f E

environment because the Commission assumes that the same number of tests will be administered i=gEC:s of which altemative is adopted.- -

- The earth's atmosphere contains an inventory of naturally occurring C-14 of about 3.8 -

I F million curies which is in addition to the huge inventory of about 240 million cunes in the world's oceans. The small amount of C-14 released into the atmosphere from the use of this test -

would mix with the global inventory and would have no impact on public health. The current- )

world inventory of naturally occurring C-14 results in an average dose to the public of about 3 l~ .1.25 mrom per year, and the release of 0.6 curies of C-14 from the total of 600,000 tests annu dose of assumed to be administered annually would result in an cWitional aver

- y W g M y ~ J.u J. A i

10 m m 4 6, - h , jh'd ] mph 4y /

, .g w .

I let of Q.v = sr.d P.;.rsons Corianited and Identifiration of Sources Used .

Following the receipt of the petition for rummaking, a " Notice of receipt of petition for rulemaking" was published for public comment in the Federal Register on December 2,1934, (5g FR 61831). A total of 315 public comment letters,313 supporting (mostly form letters) and

> 2 opposing letters, were received. This petition was discussed with NRC's Advisory Committee i on the Medical Uses of lootopes ACMUI) at the October 1975 meeting, Furthermore, the dra't rulemaking plan was forwarded to 2g Agreement States for comments.

A proposed rule was published in the Federal Register (62 FR 32552, June 16,1997) for '

a 30-day public comment period. The NRC received seven public comment letters; Four commenters supported the rule, one opposed the rule, and two provided comments without 2 explicitly stating support of or opposition to the rule. A summary of public comments and NRC's

. responses are presented in the preamble of the Federal Register notice.- Except a minor.

~

- change in wordmg, the final amendments are the same as the proposed amendments.

One commenter addressed the draft environmental Assessment. The commenter stated

'  : that the environmental Assessment fails *.a consider the fact that another equally non-invasive, 3

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- but w,-r6, diagnostic procedure (such as C-13 test) is available and provides a t comparable alterostive to the C-14 test. The commenter appaiently concluded that the -

~

assumption underlying the err.ironmental assessment is that in the absence of the C-14 test, .

}

this only alternative for the detection of Hc pylori is k,vasive gastroendoscopy.

1 1Ti.e-purpose of the environmental assessment is to address and document the expected  ;

impact to the environment of subject rulo.- As presented in the regulatory analysis prepared for l this rule, the NRC has determined that the environmental impact is expected to be insignificant ;i

= .

because of the extremely low radiological hazards associated with the use of capsules containing one microcurie C-14 ures.

!. 'if the environmentalimpact had boon significant, then the existence of a non-radio 6ctive -

i allemative would have been a factor in assessing the cost-benefit of this rulemaking. However, l

b 'the impact le not significent. Hence, the regulatory issue in this rulemaking it whether the C-14 ,

method should be made available to physicians who are not authorized users, and not whether there exists a non-radioactive e%mative. ,

l

!- Finding of No Significant impacts The Commission has dotarmined under the National Environmental Policy Act of 1969, as amended, and the Commission's regulations in Subpart A of 10 CFR Part 51, that the {

amendments will not be a major Federal action significan'ly affecting the quality of the human environment, and therefore an environmental impact statement is not required. The final rule  ;

} amends 10 CFR Part 32 t3 permit the manufacture and commercial distribution of C-14 urea capsules to any person (including physicians who are not " authorized users" under Part 35) and to amend 10 CFR Part 30 to permit any person, without an NRC license, to receive and use the j- capsules for in vivo diagnostic i .

u a. use . fo)r h m)an . The Commission be'ieves that the radioactive component of this drug presentaginihwhel radiation risk and, therefore, regulatory control of

[ - the capsules for "in vivo" diagnostic use is not necessary. It is expected that this final rule will

not cause any significant increase in radiation exposure to the public or radiation release to the

. environment beyond the exposures or releases resulting from the use of the carbon -14 capsules under the cunent reguisbons.

L 4

4

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5 ATTACHMENT 5 Congressional Letters

joA# ""%

k. UNITED STATES

^l-

[

NUCLEAR REGULATOHY COMMISSION WASHINGTON, o.C. 30eML com t

. . . . <f --

- The Honorable Dan Schaefer, Chairman Subcommittee on Energy and Power Committee on Commerce United States House of Representatives

Washington, DC 20515

Dear Mr. Chairman:

> Enclosed for the information of the Subcommittee are copies of a public announcement and a Federal Register notice concoming a final amendment to 10 CFR Parts 30 and 32. This rulemaking is being taken in response to a petition for rulemaking submitted by Tri Med Specialties, Inc.-

The Nuclear Regulatory Commission (NRC) is amending its regulationa to allow NRC licensees to distribute a radioactive drug containing one microcurie of carbon-14 urea to any person for "in vivo" diagnostic use. The purpose of this diagnostic test is to detect the presence of the bacterium Helicobacter pylori (H. pylori), a cause of peptic ulcers. The NRC has determinori .

that the radioactive component of such capsules presents an insignificant radiation risk and, therefore, regulatory control of the drug for radiation safety is not necessary. The manufacture and distribution of the capsules will continue to require an NRC license. This amendment makes the drug more widely available, thus reduces costs to patients, insurers, and the health care iridustry.

Sincerely, Dennis K. Rathbun, Director Office of Congressional Affairs

Enclosures:

1. Public Announcement

2. Federal Register Notice cc: Representative Ralph Hall-t

-r-

, g , ,

r f ..e_

(i m b; c 3;.; n _

h

+

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The Honoruble Dan Schaefer, Chairmani q

" Subcommittee on Energy and Powerc - .

3 Committee on Commerce- ,

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~ -

s United States House of Representatives ; _

Washington, DC. 20Fi q

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4 9 ,

! Dear Mr; Chairman; _

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.j

Enclosed for the.information of the Subcommittee are copies of a public announcement and a _ j

. Federal Register notice concoming's final amendment to 10_ CFR Peits 30 and 32.' This.  !

rulemaking is being taken in response to a petition for rulemaking submitted by Tri Med : 4 Specialtios, Inc. i 4- , t'

. _ . . : >_ r. . .

The Nuclear Regulatory Commission (NRC) is amending its regulations to allow NRC licensees  :

4 to_' distribute a radioactive drug containing one microcurie of carbon-14 uros to any person for__

!"in vivo" diagnostic usec The purpose of this diagnostic test is to detect the p esence of the__

J J bacterium Helicobacter pylori (H. pylori), a cause of peptic ulcers. The NRC.has determined _ j g' i that the radioactive component r,f such capsules presents an insignificant radiation ' risk and, , y therefore, regulatory control of the drug for radiation safety is not necessary. The manufacture-- "

i- T and distribution of the capsules will continue to require an NRC license. : Tiiis amendment :

makes the drug more widely' available, thus reducea costs to patients, insurers,'and the haaith b - care.industryi:

d

' Sircarely, i

t. .

4 Dennis K. Rathbun, Director Office of Congressional Affairs.

Enclosures:

1. Public Announcement

2.1 Federal Register Notice -

. cc: Representative Ralph Hall; d J

[ Distnbution:

CTrottier/RPHEB rf - ,

- File Centeri NCostanzi .

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NAMER ' ATse:nb? CTrottier' . JMurphy - MKnapp DRathbun -

DATE: 8/1/97' 8/ L : 1971 8/' /97 8/-- - /97 8/ 19 7-  :

f; OFFICIAL RECORD COPY .

. (RES File Code No.) 3A-3 0 2 =

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' The Honorelde Den Schaefer, Chairman Subcommittee on Energy and Power Committee on Commerce  :

United States House of Representatives Washington, DC 20515 j

+

4

Dear Mr. Chairman:

)

i 4

Enclosed for the information of the Subcommdtoe are copies of a public annoutument and a Federal Register notice concoming a final amendmerd to 10 CFR Ports 30 and 32. This o rulemaking is being taken in response to a petition for rulemaking submitted by Tri-Med l

!;::':"!::, Inc.  ;

The Nudear Regulatory Commission (NRC) is amending its regulations to allow NRC licensees to distribute a redloeotive drug containing one microcurie of carbon 14 uros to any person for "in

vivo" diagnostic use. The purpose of this diagnostin test is to doted the presence of the '

bactertum W pfart (H. pylort), a cause of peptic ulcers. The NRC has determined that the radiomative component of such capsules presents a minimal radiation risk and, therefore, regulatory contml of the drug for radiation safety is not necessary. The manufacture and i distribution of the capsules will continue to require en NRC license. This amendment makes the i drug rnore widely available, thus reduces costs to patients, insurers, and the health care industry.

1 Sincerely, Dennis K. Rathbun, Director l Office of Congressional Affairs

J r

Enclosures:

1. Public Announcement .

2. FederalRegister(Mios  ;

oc: Representative Ralph Hall Distribution:

CTrottier/RPHE8 ff

File Center NCostanti I DOCUMBET MhME o \tse\oitfr-ol.wpd T@ receive a oopy of this dooumont, indicate in the box *c" = copy without .

cttachment/emolosure, #38 m oopy with attaohmenttemolosure, 'M8 m No copy OFFICE: DRA/RPHt!B C DRA/RPHE8 _. Q2RMftE8 D*RES - ci Df0CA NAME: ATse;nb k CTMb JMf MKnapp DRathbun

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DATE: ' 8/1/97 8/ f/97 h b7 8/ /97 8/ 197 i OFFICIAL RECORD COPY (RES File Code No.)_3A  !

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y %q g k UNITED STATES s* NUCLEAR REGULATORY COMMISSION WASHINGTON, D.C. acteH001 t

y*..**

The Honorable James M. Inhofe, Chairman Subcommittee oa Clean Air, Wetlands, Private Property and Nuclear Safety Committee on Enviionment and Public Works United States Senate Washington, DC 20510

Dear Mr,

Chairman:  ;

Enclosed for the informathn of the Subcommittee are copies of a pubiic announcement and a Federal Register notice concerning a final amendment to 10 CFR Parts 30 and 32. This rulemaking is being taken in response to a petition for rulemaking submitted by Tri-Med Specialties, Inc. ,

The Nuclear Regulatory Commission (NRC) is amending its regulations to allow NRC licensees to distribute a radioactive drug containing one microcurie of carbon 14 urea to any person for "in vivo" diagnostic use. The pu: pose of this diagnostic test is to detect the presence of the bacterium Helicobacter pylori (H. pylori), a cause of peptic ulcers. The NRC has determined that the radioactive component of such capsules presents an insignificant radiation risk and, therefore, regulatory control of the drug for radiation safety is not necessary. The manufacture and distnbution of the capsules will continue to require an NRC license. This amendment makes the drug more widely available, thus reduces costs to patients, insurers, and the health care industry, Sincerely, Dennis K. Rathbun, Director Office of Congressional Affairs

Enclosures:

1. Public Announcement

2. Federal Regle.er Notice cc: Senator Bob Graham

The Honorable Jsmes M. Inhofe, Chairman Subcommittee on Clean Alt, Wetlands, Private Property and Nuclear Safety Committee on Environment and Pub!ic Works United tates Serste Washington, DC 20510

Dear Mr. Chairman:

Enclosed for the information of the Subcommittee are copies of a public announcement and a Federal Register notice concerning a final amendment to 10 CFR Parts 30 and 32. This rulemaking is leeing taken in response to a petition for rulemaking submitted by Tri-Med Specialties, Inc.

The Nuclear Regulatory Commission (NRC) is amending its regulations to allow NRC licensees to distribute a radioactive drug containing one microcurie of carbon.14 urea to any person for "in vivo" diagnostic use. The purpose of this diagnostic test is to detect the presence of the bacterium Helicobacter pylori (H. pylori), .1 cause of peptic ulcers. The NRC has determined -

that the radioactive component of such capsules presents an insignificant radiation risk and, therefore, regulatory control of the drug for radiation safety is not necessary. The manufacture and distribution of the capsules will continue to require an NRC license. This amendment makes the drug more widely available, *.hus reduces costs to patients, insurers, and the health care industry.

Sincerely, Dennis K. Rathbun, Director Office of Congressional Affairs

Enclosures:

1, Public Announcement

2. Federal Register Notice cc: Senator Bob Graham Distributicy CTrottier/RPHEB rf File Center NCostanzi DOCUMENT NAME: 0:\tse\c14fr.cl.wpd r.m

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DRA/RPHEB D/DRA/RES D/RES D/OCA OFFICE: DRA/RPHEB ATse;nb CTrottier JMurphy MKnapp DRathbun NAME:

8/ /97 8/ /97 8/ /97 8/ /97 DATE: 8/1/97 OFFICIAL RECORD COPY (RES File Code No.) 3A.3

t i

The Honorable James M. Inhofe, Chairman Subcommines en Clean Air, Wollands, ,

fMyste Proper $ and Nuclear Safoy l j

Comminee on Environment and Pulso Works

! United States Senate

!. . Washington, DC 20610 l 4

Dear Mr. Chairman:

l Enclosed for the information of the Subcommittee arpe/oples of a public announcj 4 Federal Register noece concoming a Anal to 10 CFR Parts 30 and 32. This I rulemaking is being taken in response to a pet for rulemaking submitted by.Tri-Mod -l

~

Specialties, Inc. l I

The Nuclear Regulatory Commission (NRC amending its regulations to allow NRC licensees .

to distribute a red 6eactive drug cordaining ralorocurle of ontbon 14 uros to any person for "in

Wyo" diagnostic use. The purpose of diagnosuc test is to detect the presence of the .

bacterium War pylori (H. pylori a cause of popuc ulcers. The NRC has determined that;  ;

l a presents a minimal radiation risk and, therefore,  !

E the radioeotive component of such c regulatory controlof the drug for a safety is not necessary. The manufacture and (

distribution of the capsules will us to require an NRC iicense. This amendment makes the l l

drug more widely available, thus a costs to patients, insurers, and the health care industry. l

_ Sincerely.-  :

1

! i Dennis K. Rathbun, Director .

! OfRos of Congressional Affairs [

3 1

F

Enclosures:

1. Putsc Announcement

. 2.' Federal Register Not

cc: Senator Sob Gra  ;

s Distnbuuon:

CTrottier/RPHE5 ff File Center - l NCostanal i

- DoctntElrf MMISS ot\ tee \e14fr-ol.wpd i I

1To receive a oopy'of this dooumont, indioate in the box ac".= oopy without tttachment/emolosure, #38 a~oorr with-attachment / enclosure, "Na a No-copy-  ;

^

OFFICE: DRA/RPHEB - C DRA/RPHEB' . D/DRNRES - DIRES d D/OCA NAME: ATse:nb b - CTrottier Y d"'

[ MKn=5 DRathbun 8/1/97 8/ [/97 b497 8/ /97 8/ /97 {

DATE: r t

OFFICIALRECORD COPY

~

(RES File Code No.) 3A 3  :

i I

, c. 4, n. . ,, . _ , , _ . _ . _ . . _ , , _ . - _ , . _ . . . _ _ . _ . . . . _ . . _ _ _ . _ . . . _ . - . . . . . _ _ . ~ . _ _ _ . - _ _ . _ _ _ . .

^

7 -.__ . . .- -

P

. ,p-, s ... mk UNITED STATES

'} NUCLEAR REGULATORY COMMISSION ,

y wAmmweton, o.c. anew o*.. */

The Honorable Den Schaefer, Chairman Subcommittee on Energy and Power Committee on Commerce United States Ht< Jo of Representatives

.f Washington, DC 20515 A* @O

Dear Mr. Chairman:

Enclosed for the information of the Subcommittee are s of a publ6c announcement and a Federal Register notice concoming a final amendment to CFR Parts 30 and 32. This rulemaking is being taken in response to a petition for rule og submitted by Tri Med Specialties, Inc.

The Nuclear Regulatory Commission (NRC) is amending its regulations to allow NRC licensees to distribute a radioactive drug containing one microcurie of carbo >14 uros to any person for"in vivo" diagnostic use. The purpose of this diagnostic tast is to det ict the presence of the bacterium Helicobacter pylori (H. pylori), a cause of pt ptic ulcers The NRC has determined that the radioactive component of such capsules presems e . radiation risk and, therefore, regulatory control of the drug for radiation safety is not necessary. The manufacture and distribution of the capsules will continue to require an NRC licens? This amendment makes the ,

drug more widely available, thus reduces costs to patients, insurers, and the health care industry.

Sincerely, Dennis K. Rathbun, Director Office of Congressional Affairs .

Enclosures:

1. Public Announcement

2. Federal Register Notice cc: Representative Ralph Hall

a*

b[% ~k UNITSD STATES l

[ NUCLEAR REGULATORY COMMISSION wAemmeron,e.c.mennen j l

l, k.....

I The Honorable James M. Inhofe, Chairman i

. tubcommines on Clean Air Wollands, i i

Private Property and Nuclear safety 3 1

Comminee on Erwironment and Pulse Wrvits United States Senate l e

Washington, DC 20510 r  ;

Deer Mr. Chairman

;

r Enclosed for the inkwmstion of the Subcommittee are copies of a putsc amwuncement and a Federal Regleter netloo concoming a final amendmord to 10 CFR Parts 30 and 32. This  :

rulemeldng is being taken in response to a petition for rulemaking submitted by Tri-Mod 1 Specialties,inen N Nuclear Regulatory Commission (NRC) is amending its regulations to allow NRC licensees

ThWbute a radioactive drug containing one microcur6e of carbon 14 urea to any person for "in i hestagnostic use. The purpose of this diagnostic test is to detect the presence of the babielum Helicobacter pylori (H. pylort), a osuse of peptic ulcers. The NRC has determined that ,

4

the radioactive component of such capsules presents a minimal redistion risk and, therefore,  !

' regulatwy control of the drug for radiation safety is not necessary. The manufacture and distribution of the capsules will continue to require an NRC license. This amendment makes the  !

drug more widely available, thus reduces costs to patients, insurers, and the health onte industry,  ;

SinceroY, .

4 Dennis K. Rathbun, Director l Offloe of Congressional Affairs l i

Enclosures:

.1. Putsc AnnouncemerW

2. Federal Register Notice c

'l I

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Draft press release - 9/3/97 s

NRC CHANGES REGULATIONS TO PERMIT EXEMPT DISTRIBUTION OF RADIOACTIVE DIAGNOSTIC DRUG The Nuclear Regulatory Commission is amending its regulations to allow a specific radioactive drug used to diagnose stomach ulcers to be distributed to any person for administration to humans. Before this change, only physicians authorized by the NRC or Agreement States could receive and administer the drug.

The change does not relieve persons from the requirement to comply with applicable Food and Drug Administration or other Federal and State requirements governing receipt, administration and use of drugs.

The change is in response to a 1994 petition for rulemaking from Tri Med Specieltles, Inc. The revised regulation allows any person to receive, possess, use and transfer capsules containing one microcurie carbon 14 urea each for . . , ,

u twu diagnostic use in patients. The NRC has determined that the capsules presenpe-minimat radiation risk, and therefore believes that regula' tory control of thejdrug for radiation safety is not necessary, gy Under the amendments, manufacturers of the capsules and commercial pharmacies that prepare the capsules will continue to need an NRC license to provide high confidence of capsule contents. The containers of the capsules must bear the words " radioactive material" and other specific information on the contents of the container. In addition, only those persons who are licensed will br permitted to use the capsules for research involving human subje::ts.

The Tri Med petition stated that Carbon 14 urea can be used to detect the presence of a bacterium that causes peptic ulcers, a chronic inflammatory condition of the stomach and duodenum that affects as many as 10 percent of l

l l

.. people in the United States at some time in their lives. According to a Jul y 1994 ]

article in the Journal of the American Medical Association, the disease has j relatively low mortality, but results in substantial human suffering and high j oconomic costs. Doctors can now cure most ulcer problems with antibiotics. The I test usi bon 14 urea is non invasive. A doctor asks the patient to swallow the capsule with water. After 15 minutes the patient blows into a collection bag, j

[

which is melled to a testing laboratory for analysis. l l Before the change, only physicians who were authorised users (e.g.,

l' physicians who met certain training and experience criteria regarding the safe use of radioactive drugs) or persons working under the supervision of an authorized ,

user could administer radioactive drugs for medical purposes. l, Under the amendments, physicians or other health care workers will not j need to be authorized users in order to administer the drug, and physicians will not

,!-. need to refer their patients to nuclear medicine physicians. This should result in cost savings to patients, insurers, and the health care industry.

A proposed rule on this subject was published in the Federal Register for public comment on June 18. Minor changes made to tiie rule as a result of L comments received are discussed in a Federal Register notice that will be  ;

published shortly.-

1 4

9

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l t

t ATTACHMENT 6 Small Business Regulatory Enforcement Fairness Act Letter Package

.f% f

\ umito STATES g

NUCLEAR REGULATORY COMMISSION WASHINGTON, D.C. SeneHe01 q I 1

Mr. Robert P. Murphy -

General Counsel General Accounting Office Room 7175 441 G. St., NW Washington, DC 20548

Dear Mr. Murphy:

Pursuant to SubtMie E of the Small Business Regulatory Enforcement Falmess Act of 1996,5 U.S.C. 801, the Nuclear Regulatory Commission (NRC) is submitting a final rule regarding distribution of a radioacdve drug containing one microcurie of cart >on 14 uros to any person for '

"in vivo" diagnostic use for humans. The purpose of this diagnostic telt is to detect the presence of the bacterium Helicobacter pylori (H. pylori), a cause of peptic ulc6re. The final rule makes the drug more widely available, and reduces costs to patients, insurers, and health care industry.

The distribution of the drug in capsule form presents a minimal radiation risk and, therefore, regulatory control of the drug for radiation safety is not necessary. This action is being taken in response to a petition for rulemaking (PRM 35-12) submitted by Tri-Med Specialties, Inc.

We have determined that this rule is not a " major rule" as defined in 5 U.S.C. 804(2). We have confirmed this determination with the Offies of Management and Budget.

Enclosed is a copy of the final rule that is being transmitted to the Office of the Federal Register for publication. The Regulatory Flexibility Certification and a statement of the availability of the Regulatory Analysis are included in the final rule.

Sincerely, Dennis K. Rathbun, Director Office of Congressional Affairs

Enclosure:

FinalRule

..- j i

i

. Mr. Robert P. Murphy General Counsel General Accounting Omco  :

Room 7175  !

441 G. St., f1W i Washington, DC 20548 l hear N.

Pursuant to Subtitle E of the Small Business Regulatory Enforcement Faimess Act of 1996,5 U.S.C. 801, the Nuclear Regulatory Commission (NRC) is submitting a final rule regarding  !

distribution of a radioscWye drug cordaining one microcurie of carbon-14 uros to any person for -- t "in vivo" diagnostic use for humans. The purpose of this eg+c:f: test is to detect the presence of the bactertum War pylori (H. pylort), a cause of peptic ulcers. The final rule makes the .

drug more widely available, and reduces costs to patients, insurers, and health care industry.' ~!

The distribution of the drug in capsuw form presents a minimal radiation risk and, therefore, regulatory control of the drug for radiation safety is not necessary. This action is being taken in response to a petition for rcTeg (PRM 3512) submitted by Tri-Mod Specialties, Inc.  ;

We have determined that this rule is not a " makr rule" as defined in 5 U.S.C. 804(2). We have i confirmed this determination with the omos of Management and Budget.  ;.

. Enclosed is a copy of the final rule that is being transmitted to the Office of the Federal Register l for publication. The Regulatory Flexibility Certification and a statement of the availability of the Regulatory Analysis are included in the final rule.

Sincerely, i

Dennis K. Rathbun, Director i Office of Congressional Affairs  !

Enclosure:

FinalRule DISTRIBUTION.

RPHEB R/F RES File OC RIF  :

DocatENT Entlas o:\ tee \o14fr-al To receive-a oopy of thia document, indicate in the box *c8 =

copy _vithoutLattaohnent/eaolosure, #38 m copy _with attaohnent/eaolosure, 858 m No-copy-

' OFFICE: DRA/RPHES C DRNRPHEB - D/QR&RES DIRESd' DIOCA NAME: ATse;nb k CTrottier @ J [ MKnapp DRathbun '

DATE: - 8/1?J7 8/ [/97 8hS7 8/ /g7 8/ ' /97

- OFFICIAL RECORD C4PY I

.. . . . - . - . ~ . - . - . ~ - - . -

... l l ' ' *p UNITED STATES

= NUCLEAR RESULATORY COMMISSION  !

WAsM6HetoN, D.c. seetMem  !

] i f

1-i I

The Honorable Al Gore j President of the United *

i. States Senate Washington, DC 20510 l; 2

Dear Mr. President:

i- Pursuant to Subtitle E of the Small Business Regulatory Enforcement Faimess Act of igg 6,5 [

U.S.C. got, the Nuoteer Regulatory Commission (NRC) is submitting a final rule regarding l distritwtion of a radiosellve drug containing one microcurie of omrbon 14 utse to any person for -  !

'in vivo" diapwelic use for humans. The purpose of this diagnostic tett is to detect the presence

of the bactertum War pylori (H. pylort), a cause of peptic ulcers. The final rule tr'akes the t

' d.vg more widely eyeliable, and reduces costs to patients, insurers, and health care industry.  !

' The distribution of the drug in oopsule form presents a minimal radiation risk and, therefore, regulatory control of the drug for radiation safety is not necessary. This action is being taken in .

! response to a petition for rulemaking (PRM-35-12) submitted by Tri-Med Specialties, Inc.  !

We have determined that this rule is not a " major rule" as de6ned in 5 U.S.C. 804(2). We have confirmed thir determination with the ofRce of Management and Budget.  ;

i Enclosed le a copy of the final rule that is being eensmitted to the Office of the Federal Register ,

for publicetkn The Regulatory Flexibility Certifluation and a statement of the availability of the l Regulatory Analysis are 'ncluded in the final rule.  :

i Sincerely,  !

f .

- Dennis K. Rathbun, Director Office of Congressional Affairs  ;

i

Enclosure:

Final Rule i

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a l

[

r The Honorable Al Gore President of the United l States Senate  !

Washington, DC 20610 t

Dear Mr. President:

Pursuant to Subbtle E of the Small Business Regulatory Enforcement Faimess Act of igg 6,5 i U.S.C. 801, the Nudear Regulatory Commission (NRC) is submitting a final rule regarding  !

distribution of a radioactive drug containing one microcurie of cart >on 14 uros to any person for l "in vivo" diagnos6c use for humans. The purpose of this diagnostic test is to detect the pra sence of the bacterium Helicobacter pylori (H. pylori), a cause of peptic ulcers. The final rule mak ts the drug more widely available, and reduces costs to patients, insurers, and health care industr (.

The distribution of the drug in capsule form presents a minimal radiation risk and, therefore, i regulatory control of the drug for radiation safety is not necessary. This action is being take 1 in -

response to a petition for ru6emaking (PRM 3512) submitted by Tri44ed Specialties, Inc.

. We have determined that this rule is not a " major rule" as defined in 5 U.S.C. 804(2). We have

. confirmed this determination with the Office of Management and Budget. ,

Enclosed is e copy of the final rule that is being transmitted to the Office of the Federal Rogister i'

for publication. The Regulatory Flexibility Certification and a statement of the availability of the Regulatory Analysis are included in the final rule.

' Sincerely, ,

r Dennis K. Rsthbun, Director I Office of Congressional Affairs

Enclosure:

FinalRule  ;

y DISTRIBUTION:

RPHEB R/F -

RES File OC R/F L-5 Document name: o;\tse\c14fr sl.wpd .i T e C er 49 -

V 8#dscesy In Ets het T*

• Cemy W had -

To a seer af gus . -

OFFCE RPithfRA b RPHE8:DRA[ D:QRA i D:RES . , D:OCA NAME ATee N CATrot[ N MI' DRathbun DATE- .n.7 w (.7 4Ai r .7 i .7 OFFICIAL RECORD COPY '

RES#3A-3 I

_-____ .- . __ _ - _ . . ~ _ . _ . . _ ___.._,..-......._.....,&.__._._....,. . - , - _ . , . . _ _ _ ._- _ .,

1. f a NUCLEAR REGULATORY COMMISSION unfino sTAtas e

WAsM6NoToN, D.c. SteeHOM 1

l-The Honorable Newt Gingrich j Speaker of the United States - i House of RepresenteWyes -

i Washington, DC 20615 i i

Dear Mr. Speaker- .

Pursuant to Subellie E of the small Business Regulatory Enfotoement Falmess Act of igg 6,5 U.S.C soi, the Nuoleer Reguietory Commission (NRC) is outwnitting a final rule regarding  !

. detritstion of a radioeceve drug containing one microcurie of cartxww14 urea to any person for l "In vivo" diagnostic use for humens. The purpose of this diagnostic test is to detect the presence  !

of the bootertum W- pylori (H. pylorf), a cause of peptic ulcers. The final rule makes the }

drug more widely evalleblo, and reduces costs to patients, insurers, and health core industry. .!

- The distrtbution of the drug in capsule form pmeents a minimal radiation risk and, therefore, regulatory control of the drug for radiation safety is not necessary. This action is being taken in  !

response to a peution fcer rulemaking (PRk4 3512) submitted by Tri-Mod Specialties, Inc.  !

) We have determined that this rule is not a " major rule" as defined in 5 U.S.C. 304(2). We have confirmed this determination with the Offloe of Management and Budget. 3 Enclosed is a copy of the final rule that is being transmitted to the Offloe of the Federal Register  ;

~

for publication. The Regulatory Flexibility Certitication and a statement of the availability of the

' Regulatory Analysis are included in the final rule, j

. Sincerely,

$ Dennis K. Rathbun, Drootor office of Congressional Affairs  ;

Enclosure:

Final Rule r

'I l  !

i

. , , , - ..w ,.._.,...y-r_m,...,_,....-....-.,,._,.,.,s..r.m.m, .,_..,_..~,_,.,_m__.,,, ...-,,..,.,,,,,,,.m.. .. _ , , , . ,_ .~,.,_.e,._.,

. l e b The Honorable Newt Gingrich l Speaker of the United States _;

House of Representauves Washington, DC 20615  !

. - i Dear Mr. Speaker.

i Pursuant to sutditie E of the Small Business Regulatory Enforcemord Fdmess Act of 1996,5 l U.S.C. 301, the Nuclear Regulatory Commission (NRC) is submitting a final rule regarding  !

distnbution of a radioactive drug cordaining one microcurie of carbon-14 uros to any person for  !

"in vivo" diagnostic use fee humans. The purpose of this diagnostic test is to detect the presence  !

of the bactertum Helloobacter pylori (H. pylori), a cause of peptic uloors. The Anal rule makes the drug more wldely available, and reduces costs to patients, insurers, and hoahh care industry.-  !

+

The distribution of the drug in capsule form presents a minimal radiation risk and, therefore, regula6ery control of the drug for radiation safety is not necessary. This action is being taken in  !

response to a peution fur rulemaking (PRM 3512) submitted by Tri-Mod Sp6cialties, Inc.  !

We have determined that this rule is not a " makr rule" as defined in 5 U.S.C. 804(2). Yve have confirmed this determination ydth the OfRoe of tw+Teit and Budget.  !

Enclosed is a copy of the final rule that is being transmitted to the Office of the Federal Register  ;

for publication. The Regulatory Flexibility Certification and a statement of the availability of the Regulatory Analysis are included in the final rule. ,

~

Sincerely, t

Dennis K. Rathbun, Director Office of Congressional Affairs

Enclosure:

Final Rule QlSTRIBUTIQN: i RPHE8 R/F RES File OC R/F Document name: 0:\tse\c14fr sl.wpd J Bandamm M AIRE.Edista W m Zai ESallulHIbul .XalamL. -

OFFICE RPHE8:DRA b RPHED:DRA . Q4RA D: Rein D:OCA i NAME ATeo b CATrolder O[ [ MKna$ DRathbun  :

DATE 8/147 at [47 - [8/M7 8/ 47 / 47 OFFICIAL RECORD COPY ,

RES#3A 3

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'O i:

ATTACHMENT 7 Public Announcement

4 Draft press release - g/3/g7 NRC CHANGES REGULATIONS TO PERMIT EXEMPT DISTRIBUTION OF RADIOACTIVE DIAGNOSTIC DRUG The Nuclear Regulatory Commission is amending its regulationF to allow a specific radioactive drug used to diagnose stomach ulcers to be distributod to any person for administration to humans. Before this change, only physicians authorized by the NRC or Agreenent States could receive and administer the drug.

'the change does not relieve persons from the requirement to comply with applicable Food and Drug Administration or other Federal and State requirements goveming receipt, administration and use of drugs.

The change is in response to a 1994 petition for rulemaking from Tri Med Specialties, Inc. The revised regulation allows any person to receive, possess, use and transfer capsules containing one microcurie carbon 14 uros each for diagnostic use in patients. The NRC has determined that the capsules present an insignificant radiation risk, .and therefore believes that regulatory control of the diagnostic use of the drug for radiation safety is not necessary.

Undor the amendments, manufacturers of the capsules and commercial pharmedes that prepare the capsules will continue to need ari NRC license to provide high confidence of capsule contents. The containers of the capsules must bear the words " radioactive material" and other specific information on the contents of the container. In addition, only those persons who are licensou will be permitted to use the capsules for research involving human subjects.

The Tri-Med petition stated that carbon-14 uros can be used to detect the presence of a bacterium that causes peptic ulcers, a chronic inflammatory condition of the stomach and duodenum that affects as many as 10 percent of people in the United States at some time in

o

• Q 2

their lives. According to a July 1994 article in the Journal of the American Medical Association, the disease has relatively low mortality, but results in substantial human suffering and high economic costs. Doctors can now cure most ulcer problems with antibiotics. Tne test using carbon 14 urea is non invasive. A doctor asks the patient to swallow the capute with wnter.

After 15 minutes the patient blows into a collection bag, which is mailed to a testing laboratory for analysis.

Before the change, only physicians who were authorized users (e.g., physicians who met certain training and experience criteria regarding the safe use of radioactive drugs) or persons working under the supervision of an authorized user could adminit,ter radioactive drugs for medical purposes.

Under the smendments, physicians or other health care workers will not need to be authorized users in order to administer the drug, and physicians will not need to refer their patients to nuclear medicine physicians. This should result in cost savings to patients, insurers, and the health care industry.

A proposed rule on this subject was published in the Federal Register for public comment on June 16,1996. Minor changes made to the rule as a result of comments received are discussed in a Federal Register notice that will be published shortly,

ps.moog

,, p k UNITED STATES

, s* NUCLEAR REGULATORY COMMISSION t

WASHINGTON. D.C. 3steHeM 4,***** ,

The Honorable Dan Schaefer, Chairman i Subcommittee on Energy and Power

• ldeckd e % u 5 M Committee on Commerce United States House of Representatives g g g gg4, i i

Washington, DC 20515 .

l

Dear Mr. Chairman:

i Enclosed for the information of the Subcommittee are copies of a public announcement and a i Federal Register notice concoming a final amendment to 10 CFR Parts 30 and 32. This rulemaking is being taken in response to a petition f;r rulemaking submitted by Tri-Med Specialties, Inc. . .

7ots snrQ4 cut  ;

The Nuclear Regulatory Commission (NRC) is amending in regulations to allow NRC licensees to distribute a radioactive drug containing one microcuri of cart >on-14 uros to any person for "in vivo" diagnostic use. The purpose of this diagnostic te is to detect tha presence of the bacterium Helicobacter pylori (H. pylorf), a cause of po tic ulcers. The NRC has determined that .

the radioactive component of such cipsules presents _ cl:2='fadiation risk and, therefore, regulatory control of the drug for radiation safety is not necessary. The manufacture and distribution of the capsules will continue to require an NRC license. This amendment makes the drug more widely available, thus reduces costs to patients, insurers, and the health care industry. i Sincerely, Dennis K. Rathbun, Director Office of Congressional Affairs

Enclosures:

1. Public Announcement

2. Federal Register Notice cc: Representative Ralph Hall

e' l

.s' ,

i Draft press release - 9/3/97 f NRC CHANGES REGULATIONS TO PERMIT EXEMPT DISTRIBUTION OF RADIOACTIVE DIAGNOSTIC DRUG i i

I The Nuclear Regulatory Commission is amending its regulations to allow a specific radioactive drug used to diagnose stomach ulcers to be distributed to any-person for administration to humans. Before this change, only physicians j authorized by the NRC or Agreement States could receive and administer the drug. ]i The change does not relieve persons from the requirement to comply with l 4 applicable Food and Drug Administration or other Federal and State requirements-  ;

governing receipt, sdministration and use of drugs.

. The change is in response to a 1994 petition for rulemaking from Tri Med

. Specialties, Inc. The revised regulation allows any person to receive, possess, use and transfer capsules containing one microcurie carbon 14 urea each for

[

1 diagngstic use in patients. The NRC has determined that the capsules present# X ud , da pho we d be.

gg" %9tadiation risk, and therefore believes that regulatory control of he rug for x radiation safety is not necessary. l Under the amendments, manufacturers of the capsules and commercial pharmacies that prepare the capsules will continue to need an NRC license to r

provide high confidence _of capsule contents. The containers of the capsules must bear the Words " radioactive material" tsnd other specific information on the -

contents of the container. in addition, only those persons who are licensed will be permitted to use the capsules for research involving human subjects.  !

J-

. :The Tri Med petition stated that Carbon 14 urea 'can be used to detect the presence of a bacterium that causes peptic ulcers, a chronic inflammatory _

condition of the stomach and duodenum that affects as many as 10 percent of  !

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i people in the United States at some time in their lives. According to a July 1994 article in the Journal of the American Medical Association, the disease has relatively low mortality, but results in substantial human suffering and high economic costs. Doctors can now cure most ulcer problems with antibiotics. The test using[rbon 14 urea is non invasive. A doctor asks the patient to swallow the capsule with water. After 15 minutes the patient blows into a collection bag, which is mailed to a testing laboratory for analysis.

Before the change, only physicians who were authcrlzed users (e 0.,

physiclama who met certain training and experlence criteria regarding the safe use of radioactive drugs) or persons working under the supervision of an authorized user could administer radioactive drugs for medical purposes.

Under the amendments, physicians or other health care workers will not need to be authorized users in order to administer the drug, and physicians will not need to refer their patients to nuclear medicine physicians. This should result in cost se.vings to patients, insurers, and the health care industry.

A proposed rule on this subject was published in the Federal Register for publit comment on June 16. Minor changes made to the rule as a result of comrnents received are discussed in a Federal Register notice that will be pubbshed shortly.

-, .- 1 Action: p

• -- /

/ \* UNITED STATES NUCLEAR REGULATORY COMMISSION Cyst Callan Thadani Thompson I wasHueotoN, D C. POM-0001

% IN RESPONSE, PLEASE l

'..... November $, 1997 REFER TO: M971105B {

6t ensta" 4

Paperiello NMSS  ;

Bangart $P <

MEMORANDUM FOR: L. Joseph Callan Lieberman. EO  !

Exec iv Director for Operations Meyer, ADM  ;

t' / Shelton, IRM i FROM: Jo

,4' 1 ,

b ecr "a ry' Tse, RES i Frattali. RES i SUB.7ECT: ST F REQUIREMENTS - AFFIRMATION SESSION, j 11:30 A.M., AND 3:00 P.M., WEDNESDAY,  !

NOVEMBER 5, 1997, COMMISSIONERS' CONFERENCE  !

ROOM, ONE WHITE FLINT NORTH, ROCKVILLE, I MARYLAND (OPEN TO PUBLIC ATTENDANCE) M * %.g l

&& 11:30 A.M. Session

'?DR i  :

L, SECY-97-232 - Pinal Rule on Exemot Distribution and Use of_a  ;

Radioactive Drua Containina One Microcurie of Carbon 14 Urea }

(Parts 30 and 32L .l The Commission approved a final rule amending 10 CFR Parts 30 and  ;

32 to permit the exempt distribution and use of capsules '

containing one microcurie carbon 14 urea for "in vivo a diagnostic  !

use. The staff should incorporate the following comments and the editorial changes provided in the attachment.  :

i The staff response to comment 3 should be reviewed and revised by i a staff Health Physicist with expertise in radiological an,sessments to ensure it accurately and clearly responds to the i comment.  ;

The Herlth and Safety Effects section of the Regulatory Analysis should be revised to clarify that individual and collective dose estimates do not consider the radiation dose received by the ,

patient, and that the collective dose of 5 person-rem over a 50  !

year period discussed in paragraph 4 is not an annual dose.

Following incorporation of these comments and the editorial changes provided in the attachment, the Federal Rectister notice  !

-should be reviewed by the Rules Review and Directives Branch in the Office-of Administration and forwarded to the Office of the i Secretary for signature and publication, i (EDO) (RES) (SECY Suspense: 12/5/97) 9700042 i

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_. ._ _ .. _. _ - . . _.. _ - __ , ~ . . _ _ _ _ _ _ _ _ __

I o .. .

i

. i L 3:00 P.M. sed 21QD ,

14 SECY-97-228 - Final Amendments to 10 CPR Part 73, " Chances  !

to Nuclear Power Plant Security Recuirements" l The commission approved a final rule amending 10 CFR Part 73 to change certain physical security requirements associated with an internal threat. The staff should coordinate the finalization of i the public announcement with the Office of Public Affairs and issue a press release related to this rulemaking. ,

Following incorporation of the editorial changes provided in the attachment, the Federal Reaister notice should be reviewed by the Rules Review and Directives Branch in the Office of Administration and forwarded to the Office of the Secretary for signature and publication.

(EDO) (RES) (SECY Suspense: 12/5/97) 9500117 Attachments:

As stated cci Chairman Jackson Commissioner Dieus Commissioner Diaz commissioner McGaffigan EDO OGC CIO CFO OCAA OCA OIG Office Directors, Regions, ACRS, ACNW, ASLBP (via E-Mail)

PDR - Advance DCS - P1-17

j,0* 9-Editorial Changes to the Final Rule in SBCY-97-232 i i

Changes to the-Federal Reaister Notice

1. On page 1,11ne 4, replace 'a minimal' with 'an l

r insignificant.'

's'  !

On page 9, paragraph 2, line 8, delete the on 2.

' procedures.' .

l 3.- On page 12, paragraph 1, line 6, delete 'nothingwill[/ l V:-

prevent' and insert 'are-not required to' after ,

? manufacturers.' Also, delete-'from' and replace  !

iindicating' with ' indicate.'

line1, replace'nosignificant'[

4 '. - On page'13, paragraph 2, with-an insignificant.' In line 2,~ replace 'or' with V Sand.'

5. On page 14, _ item (2) , line 2, replace 'be prohibited by this rulemaking' with ' continue to require a specific license pursuant to Part 35 under this rulemaking.'

-6. On page 14, last. paragraph, line 5, delete the comma.

-7. On.page 16, last paragraph, line 2, delete 'not' and in line 3, replace 'significant' with ' insignificant.'

8. On page 22, paragraph 1', line 4, replace 'no significant'i .

with 'an insignificant.'

Changes to the Regulatory Analysis

1. On page 3, paragraph 5 line 6, replace 'a minimal' with 'an insignificant.'

2.- On page 7,-first full.paragr nh,;line 13, replace 'or' with

' a nd. . ' - Alt.,o, add at the end of the paragraph: The; routine exposure of patients was not considered when calculating the-individual or collective doses resulting from the diagnostic tests.

13 7 Onipage 7, last paragraph,-line 5, delete ' annual' and in line 6, delete 'next.' Also in.line 6, delete the 's' on

' years' and: insert ' period' after ' year,'

4

.~* .

e.  !

4. On page 8, .last paragraph,-last.line, replace ' negligible' ]

with ' insignificant.'

Changes to.the Environmental Assessment-

1. 'On page l', paragraph 1, line 4, replace 'a minimalwith 'an j

--insigni ficant'. .'

j >

2. On page 1, paragraph 2, line 4, replace ' negligible' with V l

' insignificant.'  :

i

3. .On page 2, paragraph 2,-line 7, replace 'a minimel' with-'an insignificant.' -

~ 4 ., on page 2,--last paragraph, line 1, replace 'no significant'

withan insignificant.'

5. On page 3, paragraph 2, add-at the end of the paragraph:

-This is far below the EPA reporting level of 1 mrem / year l required _under the Clean Air Act for routine exposures to a. i member of the public, and the 4 mrem / year EPA limit for public drinking water.

6. .On page 4, last paragraph, line 9, replacea minimal' with t

'an insignificant _.'

[

changes to the. Congressional Letters

1. In paragraph 2, line 5, replace 'a minimal' with 'an f ineignificant.'

• Changes to the Public Announcement

1. On page l', paragraph 3,. lines'4 and 5, replace 'a minimal'

• with *an insignificant' and-insert ' diagnostic use of tho' before ' drug.'

2. on page 2,.. paragraph 1,'line 5, the

'C' in ' carbon-14' should-be lower case. .

t k

I

., 1 -_..;_......_,~ , , , _ . .- -_-.s-.., , . ,

Editorial Changes to the Final Rule in SE Y-97-228

?

Ch nges to the Federal Reciater notice

1. On page 2, paragraph 1, line 2, replace ' revising' with 9)l L

'that would revise.' In line 6, replace 'are as follows' with ' involve changes to.'

2. On page 5, paragraph 2, line 4, insert 'who are clearedline for uneocorted access' after ' employees.' In paragraph 3, 4, replace ' discriminate' with ' distinguish.' In the last paragraph, line 3, replace 'of these' with 'commenter.'

On page 8, paragraph 2 under item 5, line 2, replace F 3.

' makingwith 'make' and in line 4, insert a comma after l

'been.'

4. On page 11, last line, replace ' assume' with ' assuming.'

Chcnges to the Congressional letteco:

1. In line 1, replace the last 'the' with 'an' so that it reads

' ... copy of an amendment to ....' .

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1

O e IN RESPONSE, PLEASE REFER TO: M971105B November 5, 1997 HEMORANDUM FOR: L. Joseph Ca.lan Executive Director for Operations FROM: John C. Hoyle, Secretary /s/

SUBJECT:

STAFF REQUIREMENTS - AFFIRMATION SESSION, 11:30 A.M., AND 3:00 P.M., WEDNESDAY, NOVEMBER 5, 1997, COMMISSIONERS' CONFERENCE ROOM, ONE WHITE FLINT NORTH, ROCKVILLE, MARYLAND (OPEN TO PUBLIC ATTENDANCE) 62 11:30 A.M. Session it SECY-97-232 - Final Rule on Exemot Distribution and Use Ureaof a Radioactive Druo Containino One Microcurie of Carbon 14 (Parts 30 and 32)

The commission approved a final rule amending 10 CFR Parts 30 and 32 to permit the exempt distribution and use of capsules containing one microcurie carbon-14 urea for "in vivo" diagnostic use. The staff should incorporate the following comments and the editorial changes provided in the attachment. l The staff response to comment 3 should be reviewed and revised by a staff Health Physicist with expertise in radiological assessments to ensure it accurately and clearly responds to the comment.

The Health and Safety Effects section of the Regulatory Analysis should be revised to clarify that individual and collective dose estimates do not consider the radiation dose received by the patient, and that the collective dose of 5 person-rem over a 50 year period discussed in paragraph 4 is not an annual dose.

Following incorporation of these comments and the editorial

. changes provided in the attachment, the Federal Reaister notice should be reviewed by the Rules Review and Directives Branch in

y' 'n _

D q;4 ePf ; i'yj VUGA1 mh,m-l-

e, , c P

the Office of Administration aini forwarded to the office of the Sec'rctary for signature and publicar.fon.

-(SECY Suspense 12/5/97)

(EDO) h

s

+.

4 . J. 1, +.

i 4i

-.. 4...

i L: 3 t 0 0 '" P . M . SessionL . -

'SECY-97-228

= Final-Amendments-to 10 CFR-Part-73.~"Chanaes ,  ;

L -to Nuclear Power Plant' Security Recuirements"?

.The Commission-approved la final rule' amending 10 CFR Part 73 to

~ #

change:certain: physical'_ security requirements associated with an -

= internal' threat.- The staff should~ coordinate the finalization of-the;public announcement with the Of fice of: Public . Af f airs and .,

-issue mLpress release related to thissrulemaking.'.

~

1 Following: incorporation of_the editorial changes provided in~the

- attachment, the Federal Reaister notice.should be reviewed by the I: ~

Rules Review'and, Directives Branch in the Office of-

' Administration and-forwarded _to:the Office of:the Secretary for signature and:publicatio'n. 12/5/97)

(SECY Suspense.

. \EDO)'

. Attachments:

4 As-stated- L i

cc Chairman Jackson Commissioner Dieus A commis'sioner Diaz P Commissioner McGaffigan:

EDO OGC a CIO CFO' -

.OCAA-OCA

{ OIG Office Directors, Regions, ACRS, ACNW, ASLBP-(via L-Mail)

PDR1- - Advance DCS - P1-17 1

4

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( $$$

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. UNITED STtTES --

' i ',' - y i NUCLE AR REGULATORY COMMISSION - <

_. WASHINGTON,0.C. 20S$50001 - f

.h 9

q y -November 5,/199_7 -.

&ECattany -

COMMISSION VOTING RECORD j

-l DECISION ~ ITEM: SECY-97-2?2 TITLE: F' ? t i RULE-ON EXEMPT DISTRIBUTION AND -!

U M vF 7-RAD.OACTIVE DRUG CONTAINING ONE MICROCURIE-OF CARBON 14 UREA

, -(PARTS 30-AND 32)

.. The Commiss' ion (with all Commissioners-agreeing) approved-the subject paper as affirmed on November 5, 1997.

Thic Record-contains a summary of voting on this matter together _

with th'Vindividual vote sheets, views and comments of the ,

4 Commissioners, and the SRM of November 5, 1997.

t Joh C. BoyM Secret of the-Commission +

l Attachments:

-1 ' Voting-Summary

2. Commissioner Vote Sheets 3.-Final SRM cc:- Chairman' Jackson Commissioner--Dicus

Commissioner.Diaz

1. 1 Commissioner McGaffigan OGC; EDO

PDR(

DCS r

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,-j .,

r VOTING

SUMMARY

'- SECY-97-232.

RECORDED VOTES NOT ,

APRVD ~DISAPRVD ABSTAIN PASTICIP COMMENTS .DATE. ,

' CHRM. JACKSON: X -X: 10/27/97~

~

COMR. DICUS X X 10/29/97 COMR. DIAZ X. 10/15/97 COMR. McCAFFIGAN ' X X 10/23/9.7 i

COMMENT RESOLUTION 7

In their vote sheets, all Cot....issioners: approved the staf f's recomendation and provided some additional-- coments.

Subsegunntly, the -coments of the Commission were incorporated into the guidance to staff as reflected in the SRM issued on November 5, 1997. .

E d

A d

4 4 i

'b i

.n . . . , . _ . , . ,,.

'FROM CHalRntH-JACKSON 19.27.1997 21817 P, 1

, , AFFIRM ATlON VOTE RESPONSE _ SHEET

.TO: John C. Hoyle, Secretary

FROM: CHAIRMAN JACKSON

SUBJECT:

SECY 97-232 - FINAL RULE ON EXEMPT DISTRIBUTION AND USE OF A RADIOACTIVE DRUG CONTAINING ONE MICROCURIE OF CARBON 14 UREA (PARTS 30 AND 32)

+

Approved V Disapproved Abstain

Not Participating _ Request Discussion __

COMMENTS:

l;- See attached connents.

i l

/

l f~, U & -=

r SIGNKMJR'E /

l

. Release Vote / x / october 27, 1997 DATE Withhold Vote /__/

Entered on "AS" Yes ,

X .No <g] , }[ gp //F70-2 048

...?. ..:.;

i y e j.' , Q = '

,J. .

7 '

Chairman Maan's Comments on SECY-97-232 .

I approve the staffs publication of the Final Rule on Exempt Distribution and Use of Radioactive _

Drug containing one microcurie of Carbon 14 Urea; _however, the staffs response to 1

~

- Comment 3 is confusing and inconsistent with its own arguments. Therefore, the staff should ;

have the response reviewed and revised by a staff Health Physicist with expertise in radiologica,  :

assessments to ensure that it accurately and cleatiy responds to the comment.'- l i

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A F F I R M A T I O N VOTE RESPONSE SHEET TO: John C. Hoyle, Secretary FROM: COMkilSSIONER DICUS

SUBJECT:

SECY-97-232 - FINAL RULE ON EXEMPT DISTRIBUTION AND USE OF A RADIOACTIVE DRUG CONTAINING ONE MICROCURIE OF CARBON 14 UREA (PARTS 30 AND 32)

Approved xx Disapproved Abstain Not Participating Request Discussion COMMENTS: see atteched coments.

T a Q .m Q-

%3NATtJeg J Release Vote / XX / @ b 19 '

19 9 >

DATE Withhold Vote / /

!- Entered on "AS" Yes X No

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Commissioner Dieus' Comments on SECY-97-232'

I approve the stars publication of the Final Rule on F.xempt Distribution and Use of a .

Radioactive Drug Containing One Microcurie of Carbon-14 Urea. Although the stafs

' response to Comment 3 is accurate, it is not stated as clearly as it should be.

Therefore, I support the Chairman's request that staff should review its response to ensure that it accurately and clearly responds to the comment.-

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"' A F F I R M A T I O N _ V O T E.. .

RESPONSE SHEET

-TO: John'C. Hoyle, Secretary FROM: COMMISSIONER DIAZ

SUBJECT:

-"~CY-97-232 - FINAL RULE ON EXEMPT DISTRIBUTION nND USE OF A RADIOACTIVE DRUG CONTAINING ONE MICROCURIE OF CARBON 14 UREA (PARTS 30 AND 32)

Approved h Disapproved Abstain Not Participating Request Discussion COMMENTS:  % d w

l SIGNATUREJ Release Vote / V \0 '. S C)7 DATE Withhold Vote / / ,

Entered on "AS"' Yes -No Af7/4 010 LC,:L QQ., f

A F F I R M A T I O N V O T E' RESPONSE SHEET TO: John C. Hoyle, Secretary -

FROM: COMMISSIONER MCGAFFIGAN

SUBJECT:

SECY-97-232 - FINAL RULE ON EXEMPT DISTRIBUTION-AND USE OF A RADIOACTIVE DRUG CONTAINING ONE MICROCURIE OF CARBON 14 UREA (PARTS 30 .

AND 32)-

- Approved  % Di Opproved Abstain Not Participating Request Discussion COMMENTS:

See attached comments and edited pages.

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SIGNATURE [/[/() (

Release Vote / ( / l6 }3 f17 DATE'

. Withhold Vote / /

- Entered on ."AS" Yes x No h'I hhf  ?:y l Afl0' S 0ll

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Commissioner McGaffigan's commena on SECY-97-232:

I approve publication of the final rule amend Parts 30 and 32 to permit the exempt

- distribution and use of carbon-14 cap. 'les for human use as described by the staff.

I commend the staff for expeditiously developing the final rule after review of public comments received on the proposed rule and offer the following comments for the staffs consideration.

1) The radiation risk associated with the diagnostic use of the carbon-14 capsules should be consistently characterized as " insignificant." Edits to achieve this purpose are indicated on the attached pages.

2) The Health and Safety Effects section of the Regulatory Analysis should be revised to clarify that individual and collective dose estimates do not consider the radiation dose received by the patient, and that the collective dose of 5 person-

. rem over a 5_ 0 year period discussed in paragraph 4 is not an annual dose (suggested edits are attached).

3) Other edits for clarification and consistency are indicated on the attached pages.

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Editorial 1 Changes lto the Final'_Ruleein'SECY-97-232 lChangesitoLtheVPederal Reaister Notice-lb On page l',11ne: 4; replace 1'ai minimal' with 'an

insignificant.'-

'2.

-On page-9, paragraph 2, line-8,--delete the 's' -

on

' procedures '

s L 3 '. On:pageil2,, paragraph 1,-line 6, delete 'nothing will

' prevent' and insert 'are not required to':after

' manufacturers.' Also, deletefrom'-and replace

' indicating' with:' indicate.'

4. On-page 13, paragraph 2i line'1, replace 'no significant' Lwith 'an insignificant.' 'Inoline-2c replace 'or' with-

'and.'

5 .1 -On'page 14i itemft2), line 2, replace:'be prohibited by this

?

tulemaking' with

• continue to require a specific-license

-pursuant to Part 35 under this rulemaking.-'

- 6 . -- - On-page 14, last paragraph, line 5, delete the comma.

17 : On - page : 16, last paragraph,fline 2, delete 'not' and in line 3, replace 'significant'-with ' insignificant.'-

8. On page 22, paragraph 1, line 4, replace 'no significant' with 'an insignificant.'

Changes to_the Regulatory Ani'.ysis

1. On page 3, paragraph 5, line 6, replace 'a minimal' with 'an insignificant.'

.2. On page 7, first full paragraph, line 13, replace 'or' with

'and,' Also, add at the end of the paragraph: Th6._outine exposure of patients was-not considered when calculating the individual'or collective doses resulting from the diagnostic tests.

3.- on;page:7, last paragraph, line 5,. delete ' annual'-and in line 6', deletenext.' Also=in line 6, delete the-'s'=on-

' years' and insert ' period

• after ' year.'

4. On-page=8,-lastfparagraph,-last line, replace ' negligible'-

with:' insignificant.'-

LChanges to;the Environmental Assessment

-1.: ion-page:1,: paragraph'1, line 4, replace 'a minimal' with 'an Einsignificant .' '

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2 .-  : On'page-1, paragraph 2, cline 4,7.replaceL' negligible' with

insignificant;

3 '. - On page-2,fparagraph 2, line;7, replace-8a! minimal' with 'an-insignificant.'

4., LOn=page!2,ilast paragraph, linei11 replace 'no significant' with 'anLinsignificant.'-

15. Lon:page.3,-paragraph 2, addiat the end of the: paragraph:-

This is far-below the EPA reporting level lof-1 mrem / year-required-under~the Clean Air Act.for routine exposures-to'a

-member of the public,'and the 4 mrem / year EPA limit:for.

public-drinking. water.

_ 6 . -- On page 4, last paragraph,-line:9, replace 'a-minimal' with

'an. insignificant.'

-Changes to;the Congressional Letters

1. tin paragraph 2, line 5, replace 'a minimal' with 'an insignificant '

Changes to the.Public Announcement

1. 'On-page 1, paragraph ~3, lines-4 and 5, replace 'a minimal'

- with-'ac insignificant' and insert ' diagnostic use of~the'-  !

before 'crug.'

L2 : On page 2, paragraph 1,'line 5, the 'C' in ' carbon-14' should~be lower case.

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. -#-. ., t & - e Editorial ~ Changes te_the: Final-Rule-_in SECY-97-2281 Changes tolthe' Federal Recister notice:

21. -- On-page 2,-paragraphjl, line-2, replace ' revising' with-

'that would revise.' In line 6, replace 'are as-follows' with-' involve changes to.'

2._ On page 5, paragraph 2, lir.? 4, insert 'who are cleared'for

-unescorted: access' atter ' employees.' In paragraph 3, line 4,- replace ' discriminate' with ' distinguish.' .In_the last paragraph, line 3, replace 'of these'~with='commenter.

5 . On page:8, paragraph 2 under item 5,-line 2, replace-

' making' with 'make' and in li.t* 4, insert r comma after.

'been.'

4. On page 11, last line,-replace ' assume' with~' assuming.'-

Changes to the Congressional letters:

1. In line 1,_ replace the last_'the' with 'an' so that it reads

' ... copy of an amendment to ....'

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1. janeg UNITED STATEG '

NUCLEAR REOULATORY COMMISSION g

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" WASHINGTON. D C. 20555 000) -

IN RESPONSE, PLEASE-REFER TO: M971105B s . . , *f -

November 5, 1997_

~ HCRETARY -

MEMORANDUM FOR: L. Joseph Callan Exec ve/Di,rectoy for Operations FROM: Joh 'd'. H fl ,

secre ary- ,

SUBJECT:

ST F' REQUIREMENTS --AFFIRMATION SESSION, 11:30 A.M., AND 3:00;P.M., WEDNESDAY, NOVEMBER 5, 1997, COMMISSIONERS' CONFERENCE ROOM, ONE WHITE FLINT NORTH, ROCKVILLE, MARYLAND (OPEN TO PUBLIC ATTENDANCE)

.k 11:30 A.M. Session L SECY-97-232 - Final Rule on Exemot Distribution and Use of a.

Radiqactive Drua Containina One Microcurie of Carbon 14 Urea (Parts 30 and 32)-

The Commission approved a final rule amending 10 CFR Parts 30 and 32 to permit the exempt distribution and use of capsules containing 'one microcurie carbon-14 urea for "in vivo diagnostic .

use. The staff should incorporate the following comments and the editorial changes provided in the attachment.

The staff response to comment 3 should be-reviewed and revised by a-staff Health Physicist with expertise in radiological assessments to ensure it accurately and clearly responds to the comment.

The Health and Safety Effects section of the Regulatory Analysis should be revised to clarify that individual and collective dose estimates do not consider the radiation dose received by the patient, and that the collective dose of 5 person-rem over a 50 year period discussed in paragraph 4 is not an annual dose.

Following' incorporation of these comments and the editorial changes provided in the attachment, the Federal Recister notice should be reviewed by the Rules Review and Directives Branch in the-Office of Administration and forwarded to the Office of the Secretary for signature and publication'.

(EDO) -(SECY Suspense: 12/5/97) m !_1 00(p

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1,lH SECY-97-228 - Final = Amendments'to 10 CFR--Part 73, " Chances to Nuclear-Power Plant-Security Recuirements" b The Commission {approvedia final rule. amending 10 CFR Part-_73'to i change certain~ physical security requirements associated ~with an The staff-should coordinate the finalization of

' internal-threat.  !

the public. announcement with the Office ofEPublic AffairsLand

-issue a press release related to this rulemaking.. f FollowingLincorporation-of the editorial changes provided-in:the-attachment, the Federal'Reaister-notice should be reviewed by the Rules Review and-Directives Branch in the-Office of Administration and forwarded to the Office of the Secretary-Ifor signatureJand publication. 12/5/97)

(EDO) (SECY-Suspense:

-Attachments:

As' stated cc: schairman Jackson Commissioner Dicus Commissioner'Diaz commissioner McGaffigan EDO OGC CIO CFO OCAA OCA-OIG Office Directors,-Regions,~ACRS, ACNW, ASLBP (via E-Mail)

PDR - Advance DCS - P1-17

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,: 0 -Editorial ChangesitoSthe: Final Rule in SECY-97-232' i ~ Changes tothe. Federal'Reaister Notice Onfpage~1',line14, replace '_a minimal' with;'an 1 1 ?- .

> insignif icant ._'- 1 On pageL9, paragraph 2,_line 8,-delete'the:'s' on-2 '.

• procedures.'-

i3 : .

On page:12,; paragraph 1, _line.6-, delete 'nothing will prevent' and insert.'are not required'to' after

' manufacturers.' Also,' delete 'from' and: replace

' indicating'1with ' indicate.'

4.: 'On page 13,eparagraph 2,.line-1, replace 'no significant' withL*an-_ insignificant.' In line 2, replace 'or' with

'and.'

15. .On page 14, item (2), line 2, replace 'be prohibited by'this-rulemaking' with ' continue to require a ' specific license 3

. pursuant to Part 35 under this rulemaking.'

6. oon page 14, lastLparagraph, line 5, delete the comma.

7. On page 16, last paragraph, line 2, delete 'not' and in.line 3, replace 'significant' with ' insignificant.'

8; On page 22, paragraph 1, line 4, replaceJ 'no-significant' with-'an insignificant.'

Changes to the Regulatory Analysis

.1. On page 3, paragraph 5, line 6, replace 'a minimal' with 'an 11nsignificant.'

' 2.e On page 7, first full paragraph, line 13, replace 'or' with -

'and.' Also, add at the end of the paragraph: The_ routine exposure of patients.was not considered when calculating the individual 1or collective doses resulting from the diagnostic tests.

~On.-page 7, last paragraph,-line 5,. delete ' annual' and in

3. .

line 6, delete-'next.' Also in line 6, delete the 's'oon

' years'-- . and - insert ' period' after-' year.'

4 .- 10n pagen8,..last paragraph, last line, replace ' negligible' iwith~' insignificant;'

Changes:to the' Environmental" Assessment

-- L1.- ;Onipage paragraph =1, line 4, replace 'a minimal' with 'an insignificant.' ,

i

~

. . . - . . . . - . . - - . . . . . - . ~ - .

-[~  !

'i 2, On'page:1, paragraph 2,7 11ne~4, replace ' negligible' with'

' insignificant. i 2

3.= 7 page'2, paragraph 2',rline17,; replace 'a. minimal' withan" j insignificant.'-

14 . . On;page-2,71 ast= paragraph,Eline 1,= replaceno significant' s

with 'an insignificant.'

- 5. On page;3,-paragraph 2, add at.the end of the paragraph' 1This-is-far below the EPA-reporting leveloof-1 mrem / year- -*

required under.the Clean Air.Act for routine exposures for tc a member of the public, and the 4 mrem / year EPA: limit

-public drinking water.  ;

- 6. On_page 4, last. paragraph, line 9, replace 'a minimal' with

=l

'an insignificant.

Changes to the Congressional Letters

'l. -~In paragraph-2, linel5,-replace 'a minimal' with 'an insignificant.'

-Changes'to the Public Announcement

1. On page 1, paragraph-3, lines 4 and 5,. replace '

a minimal' with 'an insignificant' and insert ' diagnostic use of rhe' ,

before ' drug.'

2. On page 2, paragraph 1, line 5, the 'C' in ' carbon-14' should be lower case.

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• ;Bditorial Changes to.the Final. Rule in.SECY-97-220- f l

/

Changes to_the Federal-Reaister noticet On page 2,-paragraph 1, line 2,-replace ' revising' with l

1.

'that-would revise.' In line 6,- replace 'are as follows'  :

with ' involve changes to. '

2. On page 5, paragraph 2, line 4, insert 'who In are cleared for paragraph 3, line-unescortediaccess'.after ' employees.' .'

4, replace ' discriminate' with ' distinguish.' In the last paragraph, line 3,--replace 'of these' with 'commenter.'

3. On page 8, paragraph 2 under item 5, line 2, rer'. :e

' making ': with 'make' - and in line 4, insert a coena af ter

'been.' l

.4. On page 11, last line, replace ' assume' with ' assuming.'

Changes to the Congressional letters:

1. In line 1, replace the last 'the' with 'an' so that it-reads

... copy of an amendment to ....' ,

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RULEMAKING ISSUE October 9.1997 SECY-97-232 ERE: The Commissioners FROM- L. Joseph Callan, Executive Director for Operations

SUBJECT:

FINAL RULE ON EXEMPT DISTRIBUTION AND USE OF A RADIOACTIVE DRUG CONTAINING ONE MICROCURIE OF CARBON 14 UREA (PARTS 30 AND 32)

PURPOSE:

TV obtain the Commission's approval for publication of the subject final rule, DACKGROUND:

On May 30,1997, the Commission approved the publication of a proposed cale to amend Parts 30 and 32 that would permit the exempt distribution and use of capsules containing one microcurie carbon-14 urea for "in vivo' diagnostic use. On June 16,1997, the proposed rule was published in the Federal Reaister (62 FR 32552) for a 30-day public comment period. This action is being taken in response to a petition for rulemaking (PRM-35-12) submitted by Tri-Med Specialties, Inc.

QlSCUSSION:

In response to a request for comment on the proposed rule, the NRC received seven public comment letters. Four commenters supported the rule, one opposed the rule, and two provided comments without explicitly stating whether they supported or opposed the rule. A surrmary of public comments and staff's responses are presented in the preamble of the enclosed Federal Register notice. Except for two minor changes, the final amendments are the same as the proposed amendments.

The Commission should note that one commenter suggested that research use also should be permitted under this exemption because the radiological risk is insignificant. The staff did not change the final rule in response to this comment. A common rule entitled " Federal Policy for the Protection of Human Subjects; Notices and Rules," was promulgated by 16 Federal CONTACT:

Anthony Tse, DRA/RES NRIE TO BE MADE PUBLICLY AVAILABLE (301)415-6233 WHEN THE FINAL SRM IS MADE AVAIALBLE N Q Cf f f~ ${f jf 7p- J C/? ,

y ,;

Thi Commissionersi 2 agencies on June 18,1991 (56 FR 28002) and was intended to ensure the protection of human ---

= research subjects. The Federal policy represents a societal determination that any research_

(including research involving radioactive material) must provide for the following minimal protections for the human subjects: (1) that the research is approved by an Institutional Review

Board (IRB) and (2) that the human subject gives informed consent to participate in the-

- research.: Further, under the common rule, these protections must be provided regardless of whether or not there is any risk of consequences (including radiological consequences). This

view is supported by the fact that during the public comment period of the common rule, a commenter suggested that all minimal risk research be exempt from the regulations; however,--

the final rule did not adopt this comment. . While the common rule provides for the exemption of certain research, such as educational tests; survey, interviews, or observation of public behaviors; collection of existing data; it does not provide for an examption of research activities

- involving minimal risk.- However, the common rule permits department or agency heads to.-

retain final judgment as to whether a particular activity is covered by this policy.

NRC did not participate in the promulgation of the common rule. Subsequently, the NRC adopted 10 CFR 35.6 that requires a licensee who conducts research involving human subjects using byproduct material to obtain informed consent from the human subjects and obtain prior

approval by an " Institutional Review Board * (IRB). Use'of the capsules in conducting human research without following these provisions could be viewed as the NRC acting contrary to a socetal determination expressed in the common rule that all research involving human subjects be performed un $er provisions containing certain minimal protections to the human subjects participating in tha research. Such action by the Commission could have the effect of eroding public confidence in the NRC. Accordingly, even though the capsules present minimal radiological risk, the staff recommends that such research uss of the capsules not be exempt from 6 35.6.

This final rule amends Part 30 to add a new section (30.21) to permit any person to receive, possess, use, transfer, own, or acquire capsules containing one microcurie carbon-14 urea for "in vivo" diagnostic use without a license. The final amendments include a reminder that persons will not be relieved from complying with applicable FDA, other Federal, and State requirements goveming drugs. I This final rule also amends Part 32 to add two new sections (32.21 and 32.21a) to establish requirements for the manufacture and distribution of carbon-14 urea capsules to persons -

exempt from licensing. Currently, NRC requires licensees who manufacture, prepare, or commercially distribute radioactive drugs to meet the requirements in 6 32.72(a)(2) (e.g., be registered or licensed with the FDA or a State as a drug manufacturer or be licensed as a pharmacy by a State Board of Pharmacy). Licensees distributing these capsules under an exempt distribution license will need to meet this same requirement. This provides high confidence that the carbon-14 urea capsules contain one microcurie of carbon-14 and do not contain other radioactive contaminants.

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< The Commissioners - f ,, -

RESOURCES:

Resources to complete and implement this rulemaking are included in the current budget.

COORDINATION-

- The Of5ce of the General Counsel has no legal objection to the final rulemaking. The Office of - -

the Chief Financial Officer has reviewed this Commission paper for resource impacts and has no objections ; The Office of the Chief Information Officer concurs that there will be no infe,mation technology or management impacts. -# -:

RECOMMENDATION:

HThat the Commission:

1.- Approve the Notice of Final Rulemaking for publication (Enclosure 1).

L 2. Certify that this rule, if promulgated, will not have a negative economic impact on a -

substantial number of small entities in order to satisfy the requirements of the Regulatory Flexibility Act,5 U.S.C. 605(b).

'3. Hola:

a. The final rule will be published in the Federal Registec .

b. The Chief Counsel for Advocacy of it 1 Small Business Administration will be

Informed of the certification regarding economic impact on small entities and the reasons for it as required by the Regulatory Flexibility Act,

c. A regulatory analysis has been prepared (Enclosure 2);

d. An Environmental Assessment has been prepared (Enclosure 3);

4

e. The appropriate Congressional committees will be informed (Enclosure 4);

f. - Congressional review letters for Small Business Regulatory Enforcement

. Faimess Act will be sent (Enclosure 5);

._ g. . A public announcement will be issued (Enclosure 6);

a

h. . This final rule amends information collection requirements that are subject to the

. Paperwork Reduction Act of 1995 (44 U.S.C; 3501 et seq.).L This rule has been approved by Office of Management and Budget; -

1. All Agreement States will be sent a copy of the final rule upon approval for-

__ publication; 9,

t The Commissioners 4 i

. J. The petitioner will be notified of this action and will be'sent a copy of the Federal Register notice; and .

t

k. Copies of the Federal Register notice of final rulemaking will be distributed to affected licensees and commenters on the proposed rule. The notice will also be .

sent to other interested parties upon request.

L. Ji ph allan Exe futive Director for Operations

Enclosures:

As stated (6)

SECY NOTE:

Commissioners' comments or content should be provided directly to the Office of the Secretary by c.o.b. Monday, October 27, 1997.

Commission staff office. comments, if any, should be submitted to the Commissioners NLT October 20, 1997, with an information copy to the Office of the Secretary, If the paper is of such a nature that it requires additional review and comment, the Commissioners and the Secretariat should be apprised of when comments may be expected.

DISTRIBUTION: NOTE: This paper is tentatively scheduled Commissioners for affirmation at an open meeting during OGC- the week of October 27, 1997. Please

i. OCAA refer to the appropriate Weekly Commission OIG Schedule, when published, for a specific OPA date and time.

OCA CIO CFO.

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ENCLOSURE 1 i

FEDERAL REGISTER NOTICE f

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[7590-01-P]

i NUCLEAR REGULATORY COMMISSION .

l 10 CFR Parts 30 and 32 l, RIN: 3150-AF70 j Exempt Distribution of a Radioactive Drug Containing One Microcurie of Carbon-14 Urea l AGENCY: Nuclear Regulatory Commission.

ACTION: Final rule.

SUMMARY

The Nuclear Regulatory Commission (NRC)'is amending its regulations to permit

-i NRC licensees to distribute a radioactive drug containing one microcurie of carbon-14 urea to any person for "in vivo" diagnostic use. The NRC has determined that the radioactive component of suc'h a drug in capsule form presents a minimal radiation risk and, therefore, regulatory control of the drug for radiation safety is not necessary. This amendment makes the' drug more widely available and reduces costs to patients, insurers, and the health care industry. This action grants a petition for rulemaking (PRM-35-12) from Tri-Med Specialties, Inc. and completes action on the petition.

-; EFFECTIVE DATE: (30 days from date of publication in the Federal Register).

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ADDRESS: Copies of the public record, including the final regulatory analysis and any public comments received on the proposed rule, may be examined and copied for a fee in the Commission's Public Document Room at 2120 L Street, llW. (Lower Level), Washington, DC.

FOR FURTHER INFORMATiON CONTACT: Dr. Anthony N. Tse, Office of Nuclear Regulatory Research, U.S. Nuclear Regulatory Commission, Washington, DC 20555-0001, telephone (301) 415-6233 or e-mail at ANT @nrc. gov.

SUPPLErdNTARY INFORMATION:

1. The Petition for Rulemaking.

11. Proposed Rule, Public Comments, and NRC Responses.

Ill. Surnmary of the Final Amendments.

~IV.- Description of the Final Amendments.

V. Agreement State Compatibility, f

VI. Finding of No Significant EnvironmentalImpact: Availability.

Vll. Paperwork Reduction Act Statement.

Vill. Regulatory Analysis.

IX. Regulatory Flexibility Certification.

X. Small Business Regulatory Enforcement Fairness Act.

XI. Backfit Analysis.

Xil. List of Subjects.

2 L -

~

1. The Petition for Rulemaking On October 6,1994, the Commission docketed a petition for rulemaking (Docket No. ,

PRM 35-12) from Tri-Med Specialties, Inc (Tri Med). In a letter dated August 23,1994, Tri-Med petitioned the NRC to amend its regulations "to allow for the general licensing and/or exemption for the commercial distribution by licensed pnarmaceutical manufacturers of a capsule .

containing one micro-Curie (pCl) of C-14-urea for in vivo diagnostic testing." The purpose of this diagnostic test is to detect the presence of the bacterium Helicobacter pylor; (H. pylori), a cause of peptic ulcers in humans.

Following the receipt of the petition, the NRC published for public comment a notice of receipt of pet!! ion for rulemaking in the Federal Register on December 2,1994 (59 FR 61831).

The comment period closed on February 15,1995. The NRC received 315 public comment letters, of which 313 supported the petition (they were mostly fom11etters) and 2 letters opposed the petition.

II. Proposed Rule, Public Comments, and NRC Responses A proposed rule was published on June 16,1997 (62 FR 32552) that would permit NRC licensees to distribute capsules containing one microcurie C-14 urea to any person for "in vivo" diagnostic use. The public comment oeriod closed on July 16,1997.

In the preamble of the proposed rule, the NRC stated that, because the capsules present an insignificant radiological risk to the public and the environment, the NRC believes the capsules could be distributed for 'in vivo' diagnostic use to persons exempt from licensing.

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p _. . _ _ _ _ _ _ __ _ _ . -_. .-- -- _ _ _ _ _ _

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This change makes the drug more widely available and reduces costs to patients, insurers, and the health care industry. -

The NRC received seven public comment letters on the proposed rule: three from -

industry, three from State agencies, and one from a physician associated with a university medical facility. Four commenters supported the rule, one opposed the rule, and two provided comments but did not explicitly state whether they supported or opposed the rule. Public comments and NRC's responses are presented below.

Comment 1:- Under the proposed distribution, the NRC should not be forbidding research use of this drug by the same physicians who may use it clinically. Research use also should be permitted under this exemption because the radiological risk for using C-14 capsules is insignificant.

Responan: The NRC did not change the final r8 .n response to this comment. A common rule entitled " Federal Policy for the Protection of Human Subjects; Notices and Rules" was promulgated by 16 Federal agencies on June 18,1991 (56 FR 28002) and was intended to ensure the protection of human research subjects. This rule was adopted to implement a recommendation of the President's Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research which was established on November 9,1978, by Public Law 95-622. The Federal Policy requires that Federal agencies that conduct, fund.

- support, or regulate research involving human subjects ensure adecuate protection of the sights of the human subjects. The Federal policy represents a societal determination that any research (including research involving radioactive material) must provide for the following

- minimal protections for the human subjects:- (1) that the research is approved by an Institutional Review Board (IRB) and (2) that the human sLbject gives informed consent to 4

3

' participate in the research. Further, these protections must be provided regardless of whetherJ for not there is any risk of consequences (including radiological consequences). This view is -

supported by the fact that during the public comment period of the common rulet a commenter

' suggested that all minimal risk research beexempt from the regulations; however, the final rulej did not adopt this comment..

NRC did not participate in the promulgation of the e .'mmon rule.' Subsequently, the NRC adopted 10 CFR 35.6 that requires a licensee who conducts research involving human - i subjects using byproduct material to obtain informed consent from the human subjects and .

, obtain prior approval by an IRB. Although the NRC did not adopt the common rule, the 4 l Intention is to follow the essential requirements of the common rule. . Because the common rule

~

I does not provide an exemption for research involving minimal risk, the Commission has

! determined that such research use should not be exempt from 10 CFR 35.6.

s i

Comment 2 Two commenters expressed concems that the proposed rule language, "not exceeding one microcurie," appeared to indicate that the upper limit of the radioactivity in a (

~

capsule is exactly one micromrie of C-14. Both stated that it is not possible to make the capsules to exactly one microcurie because of statistical deviations during the manufacturing ,

process.

Response; The NRC agrees with the commenters. The proposed rule did not intend to limit the radioactivity of C-14 to exactly one microcurie. The final rule language has been :

modified to read " capsules containing one microcurie C-14 urea (allowing for nominal variation that may occur during the manufacturing process)."

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. . - .- . .. . - - , . ~ - . . . .. ,, - . . . -

Commani 3' One commenter statet ' hat, when the total amount of energy released j from complete decay of a radionuclide is considered, one microcurie of C 14 has the largest l i

energy release, because of its long half life, when compared to one microcurie of Tc-99m or l- i 131. The commenter concluded that, given the insignificant radiation risk from the diagnostic

{

use of C 14 ures, the radiation risk from the diagnostic u'se of Tc 99m or 1-131 also would be f

- i

- insignificant.  !

Response: Carbon 14 emits low energy p radiation with no y radiation, low energy p radiation cannot penetrato very for ;nto tissue. On the other hand, both Tc-99m and 1 131 emit j y radiation, which is more penetrating than the weak p raciation. Furthermore, the total energy j of C 14 la released slowly over tens of thousands of years, but the total energy of Tc 99m and i i

1 131 is released much faster, i.e., within several days and tens of days, respectively. Thus, the j radiation risk to an individual from one microcurie of C 14 is insignificant because of the long ,

half life and low energy emitted. This is not the case for 1 131 or Tc 99m which are both short lived y emitters and which would deposit most of the total energy in the individual.

Corpment 4: Because of the small quantity of radioactive material in C-14 capsules, this -  !

product may be disposed of in the general trash. To avoid unnecessary conoom for health risks in the disposal of the product, labets should contain a statement that the product may be disposed of in the general trash.  ;

Response: In the final rule, the label requirements include & statement that the product may be disposed of in ordinary trash.

t Comment 5: The t. ommenter agrees that the widsspread use of this product williaquire uniform regulations and that Agreement States will need to make appropriate regulatory  ;

6 l

L..  :

i provisior.s to enable persons to receive the drug for *in vivo' diagnostic use. To avoid confusing licensees and users, these changes to NRC and Agreement State regulations should be made simultaneously. The commenter urges that the NRC iske action to erpedite the Agreement State regulatory changen.

Response The NRC has urged the Agreement States to adopt compatible changes in their regulations expeditiously. However, under NRC's Adequacy and Compatibility Policy, Agreement States have up to three years to change their regulations for amendments or program requirements that are items of compatibility.

( umment 6: The NRC should address this rule in its ongoing effort to revise 10 CFR Part 35 in its entirety. The ammenter believes that (1) this rule represents a piecemeal effort to respond to a nairow issue and (2) the isspe of reduced regulation for medical use of C 14 capsules is applicable to the same extent for virtually the entire range of diagnostic

. radioisotopes.

Response' If this rule is combined with the overall 10 CFR Part 35 revisiori, the C-14 capsules would only be available to authorized user physicians during the revision period.

' Thus, the NRC decided to proceed with this rule now because the benefits of making this capsule available to anyone, including primary-care physicians, outweigh the benefits of ,

addressing this issue in the overall revision of 10 CFR Part 35.

Comment 7: An appropriat9 function of the regulatory regime is to assure that personnel hrndline and administering radioactive drugs meet certain basic training and qualification requirements. The proposed exemption would impose no training or qualification requirements on users.

7 6 , - - . . - - ,- _ -_ _ , - _ _ _ - _ , _ . _ _ , _ -

~ -- .

Response: The amount of radiation safety training needed for personnel depends on the level of radiation risk associated with the radioactive drug. Because C 14 capsules present insignificant radiation risk, radiation safety training for personnel handling and administering the capsule is not necessary, and thus, not required.

Comment 8: If the NRC promulgates the proposed rule in its present form, the exemption will divest the Agreement States of any authority to regulate this product under a general or specific license. Had the NRC instead simply proposed a general license, Agreement State agencies would retain the authority to adopt the general license or continue to require specific licen-Ing.

Response in the draft ruk, aking plan, the NRC suggested using the Denerallicense approach. The NRC received nine comment letters from Agreement States on the draft rulemaking plan; three suggested that an exemption approach would be more appropriate because it would be less costly to the Agreement States and their licensees than the general license approach Based on these comments, the NRC chose the exemption approach in the final rule plan as more cost-effectiva than a general license approach. The final rulemaking plan was revised accordingly and was provided to the Agreement States. No Agreement States expressed opposition to the NRC on the exemption approach.

Among the seven public comment letters received on the proposed rule, two were from Agreement States and one from a non Agreement State. All three supported the proposed rule.

Comments: The environmental assessment falls to consider the fact that another

- equally noninvasi.e, but nonradiological, diagnostic procedure (such as C-13 test) is available 8

m.

l aret provides a comparable alternative to the C.M test. The apparent assumption underlying i the environmental assessment is that in the absence of the C-14 test, the only alternative for the detection of H. pyloriis invasive gastroendoscopy.

Etsponse' Because the C 14 urea capsules are already available to authorized user physicians, the only regulatory issue in this rulemaking is whether the C-14 method should be made available to individuals who are not authorized users. The purpose of the environmenthi assessment is to consider and document whether the subject rule is expected to have any significant impact to the environment, in this environment assessment, the NRC has determined that the environmentalirnpact is expected to be insignificant because of the extremely low radiological hazards associated with the use of capsules containing one microcurie C 14 urea. The presence of an additional non invasive altemative procedures does not affect NRC's determination cf no significant environmentalimpact.

Comment 10: NRC's policy in the past has been not to exempt byproduct material that is ingested. Any change in this policy would be a significant departure from existing NRC regulationa ReID0 Din: This change is a departure from existing NRC regulations. In the statement of consideration for the proposed rule, under the heading *Currer* NRC Regulations on Exemptions From Licensing," the NRC stated that, although two broad niaterial exemptions

($ 30.14, ' Exempt concentrations,' and 9 30.18,

• Exempt quantities") exclude the transfer of byproduct material contained in any product designed for ingestion or inhalation by a human being, the C-14 capsules manufactured or prepared as a radioactive drug can be distributed to persons exempt frem licensing for 'in vivo' diagnostic use because the capsules present an insignificant radiological risk to the public and the environment. This exemption only applies to 9

. _ _ _. . - . _ . _ _ _ _ . _ . ._ ~_ _. _ _ ___._ _ _ . _ _ _ . . _ . - . _ _ .

i

. i the degnostic use of capsules containing one microcurie C-14 manufactured or prepared as a i radioactive drug to make a clear detinction between this radioactive drug that is intended for  !

I ingestion by humans and other uses of C 14 uros and byproduct material distributed under i l

- $$ 30.14 and 30.18. l t

i Commani 11: The ACMUl's (Advisory Committee on Me(or) Uses of Radioisotopes) l I

conclusions that either an exemption or general license is appropriate for the C-14 product do t P

not address the fundamental espods of nuclear safety. its jucigment was based partially _on the assumptions:. (1) the product may only be dia ,wnsed by prescription, (2) tho' product is  ;

approved by the rood and Drug Administration, and (3) the office #acility using the product will i

- be subject to Clinical Laboratory Improvement Amendment (CLIA) regulation.

Responas: The transcript from the ACMUI meeting shows the Committee did include  !

i radiation safety in its considerations and did not consider it to be an issue. Further, as stated in t

the supplemental material supporting the proposed rule, there are no nuclear safety issues  ;

associated with the use of the C 14 capsules for r4inical diagnostic testing. Therefore, use of either an exemption or general license is appropriate.

Comment 12:- The exemption approach does not provide the NRC with flexibility to impose a limitation on the amount of C-14 capsules any physician can possess in an office, in

- the' event there is a recall of the product, or a large amount of product becomes unusable, the NRC will have no control over the disposal of the product, j

' BaaD00er it is not necessary to impose a possession limit on the amount of C-14 q capsules because the radiation risk is insignificant. The earth's atmosphere conta!ns an

- inventory of naturally occurring C-14 of about 3.8 million curies which is in addition to the huge ,

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inventory of about 240 million curies in the world's oceans. The small amount of C 14 released into the atmosphere from the use of this test would mix with the globalinventory and would i

have no impact on public health. The current world inventory of naturally occurring C-14 results in an average dose to the public of about 1.25 mrem per year, and the release of 0.6 curies of '

C 14 from the total of 600,000 tests assumed to be administered annually would result in an additional average annual dose of 2 X 104 mrem. In the event that a recallis necessary, the ,

manufacturer may use the same process for recalling any other non-radioactive drugs, if C-14 urea capsules are returned to the manufacturers, they will be disposed of in accordance with the manufacturer's possession license. A user, however, can dispose the C 14 urea capsules ,

as ordinary trash. Medical users of the C 14 urea test would be unlikely to acquire significant quantities of capsules becaus3 they can be ordered within a few days. Thus, even under a recall, the impact of disposing of C 14 urea capsules into landfills by the user would also be insignificant.

Comment 13: It is essential that end users be adequately informed of the product's radioactive characteristics, so that some form of storage, use, and disposal precautions can be followed. Thus, the labeling must be conspicuously and prominently placed. The commenter suggested the following: (1) the phrase " conspicuously and prominently" in front of the proposed labeling ' bears the words Radioactive Material'should be added, and (2) the NRC should require that the radioactive material legend, ' Radioactive Material," be included on promotional brochures.

Response: Because the radiation risk from C-14 capsules is insignificant, regulatory contre! of the use, storage, ar.o disposa' of the drug for purpose of radiation safety is not necessary. In fact, the sabel accompanying C-14 capsules is required to indicate that the 11

. - . = .. . - - . - _ . -. - - . - . - . - . . ..- _,

i

. 4 capsules may be disposed of by users as ordinary trash. Paragraph (a)(6) of $ 32.21 requires  ;

i that applicants submit copies of prototype labels and brochures for NRC approval. The NRC will ensure that the labels meet the requirements of $ 32.21a before they are approved. Since paragraph (a) of $ 32.21s specifies that the label must be durable and legible, the use of an additional phrase such as ' conspicuously and prominently" is unnecessary Promotional ,

brochures are for information only; nothing will prevent manufacturers from indicating on the l promotional brochures that C-14 is a radioactive material.

i lil. Summary of the Final Amendments' I Final Amendment to 10 CFR Part 32 i

The regulations in 10 CFR Part 32 are amended to add new $$ 32.21 and 32.21a, to [

provide requirements for a specific license to manufacture, eapare, process, produce, ,

package, repackage, or transfer for commercial distribution, capsules containing one microcurie of C 14 ures, as a radioactive drup, to be distributed to any person for "in vivo" diagnostic use.

These requirements are consistent with the existing requirements on other items under the heading " Exemptions"in 10 CFR Part 30. The amendment includes a reminder that licensees .

distributing the radioactive drug to persons exempt from licensing would not be relieved from other applicable Federal (e.g., FDA) or State requirements goveming the manufacture and distribution of drugs.

The amendment requires that the manufacture or preparation of capsules containing  ;

t one mictocurie of C-14 uros be prepared by persons who meet the current NRC regulations to r

" manufacture and commercially distribute radioactivo drugs. The NRC believes regulatory 12 i

r

. - . _ _ _ -- _ __ - - - . - = _ -

l controlis needed to provide high confidence that the drug contains one microcurie of C 14 urea and does not contain any other radioactive contaminants.

Final Amendment to 10 CFR Part 30 l I

The NRC has determined that the drug in capsule form presents no ugnificant l

radiological safety or environmental risk, and that it is not necessary to regulate the use of this l

drug for its radioactive component. Therefore, the NRC can not justify requiring physicians, or any other person, to meet NRC training and experience criteria directed et the safe use of radioactive drugs, or to become an " authorized user." Hence, the capsules can be distributed to any person. However, other Federal or State agencies may limit the receipt and use of the capsules in accordance with their own requirements.

The regulations in 10 CFR Part 30 are amended to add a new $ 30.21, to permit any person to receive, possess, use, transfer, own, or acquire for "in vivo" diagnostic usa, capsules containing one microcurie of C-14 ures without a license. The final regulation includes a reminder that persons receiving the capsules would not be relieved from other Federal or State law governing drugs. Further, in accordance with the NRC's provisions for research involving human subjects (10 CFR 35.6), the exemption permitting receipt and use of the capsules for "in ,

vivo" diagnostic use does not extend to use of the capsules for research involving human subjects. Any person desiring to use the capsules for human research would still be required to '

submit an application for a specific license under Part 35. The phrase "in vivo diagnostic use" i was selected to describe the activity authorized in $30.21 to differentiate it from the term

" medical use" because:

1 13 j

1 1

(1) " Medical use" limits administration to authorized use s; use of this drug would not be j so limited; and

(2) *t4edical use" includes the administration of t% drug to a human research subject, -

< which would be prohitnted by this rulemaking.

Effects of the Final Amendments  !

The final amendments make the drug available to any person, for "in vivo" diagnostic use, W,thout need for an NRC or Agreernent State license Because the receipt and use of the .

i

. drug are exempt from NRC licensing, Agreement States need to make appropriate provisiens in L

their regulations to recognize the exempt distribution of the drug, for "in vivo" diagnostic use, i

Thus, after the manufacture and distribution of the drug, the NRC and the Agreement States  ;

will not regulate the use of the drug as long as house.is for "in vivo" diagnostic use, This

- means that, under NRC and Agreement State regulations, primary-care physicians do not need i to be

• authorized users" in order to administer the drug, and do not need to refer their patients -

to nuclear medicine physicians. This should result in cost savings to patients. Other Federal and State organizations with responsibilities for regulating drugs will determine and regulate i who can recolve and use the drug for "in vivo" diagnostic use,- NRC will continue to regulate the i I

use of the drug for research involving human subjects under a specific Ps135 license.

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14

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_..;._. _ - _ . . . _ . = _ . _ . _ . . . _ _ _ . _ _ , _ _ _ . ..;.,__ __ ..,;._

IV. D(scription of the Final Amendments The final amendments are the same as the proposed amendments except for two minor changes. Public comments suggested that the phrase " carbon 14 urea capsules not exceeding one microcurie" used in the proposed rule may be interpreted as an exact limit of one microcurie per capsule (See Comment 2 under the heading *Public Comment and NRC Responses). The final rule has been modified and the phrase " capsules containing one microcurie carbon 14 urea (allowing for nominal variation that may occur during the manufacturing process)"is used. Another public comment suggested that labels should contain a statement that the product may be disposed of in the general trash. In the final rule, the label requirements include such a statement.

Manufacturer and Distributors A new section is added to 10 CFR Part 32 to permit the distribution of the capsules to persons who are exempt from licensing.

6 32.21 Radioactive drug: Manufacture. orecaration. or transfer for commercial distribution of gaosules containina one microcurie carbon-14 urealach for "in vivo" diaanostic use for humans itsgrions exemot from licensina: Reauirements for a license Paragraoh (R)

This paragraph establishes the requirements for approval of a license application to manufacture, prepare, process, produce, package, repackrje, or transfer for commercial 15

distribution, capsules containing one microcurie carbon-14 urea each for "in vivo" diagnostic use, to persons exempt from licensing.

Parmaraoh(a)(1)

This paragraph limits issuance of an " exempt distribution license" for distribution of the caprulas to persons exempt from licensing to only thocs who possess either a NRC or Agreement State " specific license" for possession and use of byproduct material.

Parmaraoh (a)(2)

To assure that the capsules contain one microcurie of carbon-14 and present no other radiological risks, this paragraph requires that the persons manufacturing and/or commercially distributing the capsules for "in vivo" diagnostic use must also meet the requirements of

$ 32.72(a)(2). Specifical!y, these persons must be:

(1) Registered r" , or licensed by the FDA as a drug manufacturer; or (2) Registered with or licensed by a state agency as a drug manufacturer, or (3) Licensed as a pharmacy by a State Board of Pharmacy; or (4) Operating as a nuclear pharmacy within a Federal medical institution.

Paraorach (a)(3)

This paragraph requires applicants to provide ovidence that each carbon-14 urea capsule contains one microcurie, The NRC's evaluation that the capsules would not result in significant radiation risks was based on the capsules containing one microcurie of carbon-14 urea. Therefore, applicants must demor' strate that the activity of each carbon-14 capsule 16

l l

contains one microcarie, allowing for nominal variation that may occur during the manufacturing l process, Paragraph (a)(4) l l

This paragraph prohibits carbon-14 urea from being contained in any food, beverage, cosmetic, drug or other commodity designed for ingestion or inhalation by, or topical application to, a human being except for the capsules as described in this section, because exempt distribution of this drug has only been evaluated for "in vivo" diagnostic use in the form of a capsule containing one microcurie of carbon-14 urea. There is no prohibition against the capsule being cornbined with food or beverage at the time of administration so that the capsule can be ingested by the patient.

Paragraoh (a)(5)

Because the exernpt distribution of this drug has only been evaluated for "in vivo" diagnostic use in the form of a capsule containing one microcurie of carbon-14 urea, this paragraph prohibits incorporation of the capsules into any manufactured or assembled commodity, product, or device intended for commercial distribution. Further, although the drug is being distributed to persons exempt from licensing, this paragraph requires the carbon-14 urea to be identified as radioactive because the drug is being used for its radioactive content; therefore, the end user must be provided with information that the drug contains a radioactive material.

17 a

I l

l

.I Paragraph falf6) J 1

As with any produd approved for distribution to persons exempt from licensing, this l

paragraph requires persons who apply for a license to msnufacture or commercially distribute .

these capsules to submit copies of prototype labels or brochun,s for NRC_ approval. This will- -

allow the NRC to confirm that the labels or brochures meet the requirements of $ 32.21o(s) 1 and (b);

.i-!

Paragraph (b)  :

- This paragraph declares that the regulations do not relieve licensees or applicants from  :

complying with applicable FDA, other Federal, and State requirements goveming the  :

1 manufacture and distribution of drugs. i l

i Section 32.21a Same: Conditions of licanae  ;

i This section establishes the conditions required for a licensee to commercially distribute the capsules to persons exempt from licensing. 1

.l Paragraoh (a)

. To inform the end user of the identity of the radioisotope, the physical and chemical ) i form, and the dosage of radioactivity, this paragraph establishes that the immediate container i ,

l of each capsule or capsules must bear a durable, legible label that:

q (1) Identifies the radioisotope, the physical and chemical form of the radioisotope, the '

quantity of radioactivity. contained in each container at a specific date; and (2) Bears the"words " Radioactive Material."  ;

)

18 m, .

i

!- i

, - The date requirement is consistent with labeling requirements for other radioactive drugs with a half life of greater than 100 days, l t l

I

! Paragraoh (b)

{

This paragraph establishes that, consistent with the intended use of the capsules, the q

label affixed to the immediate container, or an accompanying brochure, must: 1 (1) - State that the contents are exempt from NRC or Agreement State licensing '  ;

requirements;

, (2)- Bear the words " Radioactive Material. For "In Vivo" Diagnostic Use Only. This Material is Not To Be Used for Rosearch involving Human Subjects, and Must Not Be i Introduced into Foods, Beverages, Cosmetics, or Other Drugs or Medicinala, or into Products  !

. t

- Manufactured for Commercial Distribution. This Product May Be Disposed of in Ordinary >

i t

Trash."- .

The intent of the requirement set out in Paragraph (b)(2) is to make clear that the capsule must remain in the form of a capsule and is not to be combined with one of the listed j

.i items such as food or beverages which would resuN in a radioactive product other than in the

.m form of a capsule for commercial distribution. There is no prohibition against the capsule being combined with food or beverage at the time of administration so that the capsule can be f

- ingested by the patient, This label also informs the user that this product may be disposed of in

. - ordinary trash. <

[

3

- "In vivouimaa=*ic i== by normons avamot from li=nsino '

4 A new section is added to 10 CFR Part 30 to exempt any person from NRC or the 0 - Agreement State regulations to receive the drug for "in vivo" diagnostic use for humans, 4 i I i

, 1g 4

g .,m.,. ,,-ce,q-* *-4 'e,-+ w ,r.--w ,=nw,-- s+-ere--=-v..emi-.---w,e-w-wm-v v a, v +=-r---wwww.-+-+ - + ',e-er= -=w,%-we"- e c

• mA so 21 phw drua: c=='- osr.iminina ans mWwin of wh.14 uras for "in vnto" diagnostic una for humans j l

I Paragraph (a) -

4-l This paragraph provides an exemption to any person from the requirements for a  !

l 4 license to receive, possess, use, transfer, own, or acquire capsules containing one microcurls j i

of carbon-14 urea for "in vivo" diagnostic purposes, it should be noted that the " transfer"in this

+

paragraph does not include " transfer for commercial distribution," which is covered in paragraph - 1 J(c) of this section; l I l' Paragraoh (b)

This paragraph establishes that persons who desire to use the drug for research f involving humans subjects must apply for and receive a specdic Part 35 license. Such a license i

would ensure the protection of the rights of the human subjects by requiring that the research  !

be approved by an IRB and that the human subjects give their informed consent to participate in the research, t

Paragraph (c)

This paragraph specifies that a specdic license is needed to manufacture, prepare, l process, produce, package, repackage or transfer such capsules 7or commercial distribution.  :

a d

-20 '

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- - _ _ . , - , - . _ , . _ . _ , . . _ _ . _ . _ _ . _ __._.~._________ _ _

~

o .

Paragraoh (d)

This paragraph declares that the regulations do not relieve end users from complying with applicable FDA, other Federal, or State requirements governing the receipt, administration, and use of drugs.

V. Agreement State Compatibility Under the Atomic Energy Act, certain regulatory functions are reserved to the NRC.

Among these are the distribution of products to persons exempt from licensing, as discussed in 10 CFR Part 150. Hence, amendments related to the manufacture and commercial distrioution of the capsules (10 CFR Part 32)is a Division 4 item of compatibility (Category NRC under the new adequacy and compatibility policy). Ho. wever, amendments related to possession and use (10 CFR Part 30) are a Division 1 item of compatibility (Category B under the new adequacy and compatibility policy) because of the need for nationwide consistency in the use of products which are widely distributed. Therefore, the Agreement States will need to make appropriate provisions in their regulations to allow any person to receive capsules containing a microcurie of carbon 14 urea for "in vivo" diagnostic use in humans without need for a license.

VI. Finding of No Significant Environmentalimpact: Availability The Commission has determined under the National Environmental Policy Act of 1969, as amended, and the Commission's regulation:, in Subpart A of 10 CFR Part 51, that the final rule is not a major Federal actinn significantly affecting the quality of the human environment; therefort , an environmental impact statement is not required. The final rule establishes 21

requirements for the manufacture and commercial distribution of carbon 14 urea capsules to persons exempt from licensing and establishes regulations to permit any person to receive the capsules without an NRC license. The Commission believes that the radioactive component of this drug presents no significant radiation risk and, therefore, regulatory control of the "in vivo" diagnostic use of the capsules for radiation safety is not necessary. It is expected that this final rule will not cause any significant increase in radiation exposure to the public or radiation

. release to the environment beyond the exposures or releases resulting from the use of the carbon.14 capsules under the current regulations. Also, it is expected that there wiil be no non-radiologicalimpacts. One public comment on the draft environmental assessment has been received (See Comment 9 under the heading

• Proposed Rule, Public Comments, and NRC Responses").

The environmental assessment and finding of no significant impact on which this determination is based is available for inspection at the NRC Public Document Room,2120 L Street NW. (Lower Level), Washington, DC. Single copies of the environmental assessment and the finding of no significant impact are available from Dr. Anthony N. Tse, Office of Nuclear Regulatory Research, U.S. Nuclear Regulatory Commission, Washington, DC 20555-0001, telephone (301) 415-6233 or e-mail at ANT @nte. gov.

Vil, Paperwork Reduction Act Statement This final rule amends information collection requirements that are subject to the Paperwork Reduction Act of 1995 (44 U.S.C. 3501 et seq.). These requirements were approved by the Office of Management and Budyt, approval numbers 3150-0001,3150-0017, and 3150-0120, 22

The public reporting burden for this collection of information is estimated to average 16 hours1.851852e-4 days <br />0.00444 hours <br />2.645503e-5 weeks <br />6.088e-6 months <br /> per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing the collection of information. Send comments on any aspect of this collection of information, including suggestions for reducing the burden, to the Information and Records Management Branch (T-6 F33), U.S. Nuclear Regulatory Commission, Washington, DC 20555-0001, or by internet electronic mail at BJSi@NRC. GOV; and to the Desk Officer, Office of Information and Regulatory Affsirs, NEOB 10202, (3150-0001,3150-0017, and 3150-0120), Office of Management and Budget, Washington, DC 20503.

Public Protection Notification The NRC may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB control number.

Vill. Regulatory Analysis The NRC has prepared a regulatory analysis for the final rule. The analysis examines ths benefits and impacts considered by the NRC No public comments on the draft regulatory analysis have been received during the public comment period. The regulatory analysis is available for inspection at the NRC Public Document Room,2120 L Street NW. (Lower Level).

Washington, DC. Single copies of the regulatory analysis are available from Dr. Anthony N.

Tse, Office of Nuclear Regulatory Research, U.S. Nuclear Regulatory Commission, Washington, DC 20555-0001, telephone (301) 415-6233 or e-mail at ANT @nrc. gov.

23

9 IX. Regulatory Flexibility Certification As required by the Regulatory Flexibility Act of 1980,5 U.S.C. 605(b), the Commission certifies that this rule does not have a significant economic impact upon a substantial number of small entities. The final rule permits physicians and other health care providers to use an additional diagnostic test without having to obtain an NRC lic6nse, thus, would provide cost savings to patients, insurers, and the health care industry The final rule does not impose any additional obligations on entities that may fall within the definition of 'small entities

• as set forth in Section 601(3) of the Regulatory Flexibility Act; or within the definition of 'small business' as found in Section 3 of the Small Business Act,15 U.S.C. 632; or within the size standards adopted by the NRC on April 11,1995 (60 FR 18344).

X. Small Business Regulatory Enforcement Falmess Act in s cordance with the Small Business Regulatory Enforcement Fairness Act of 1996, the NRC has determined that this action is not "a major" rule and has verified this determination with the Office o'Information and Regulatory Affairs, Office of Management and Budget.

XI. Backfit Analysis The NRC has determined that the backfit rule,10 CFR 50.109, does not apply to this rule, and therefore, a backfit analysis is not required because these amendments do not involve any provisions that would impose backfits as defined in 10 CFR 50.109(a)(1).

24

Xil. List of Subjects 10 CFR Part 30 Byproduct material, Criminal penalties, Govemment contracts, Intergovernmental relations, Isotopes, Nuclear materials, Radiation protection, Reporting and record keeping requirements.

10 CFR Part 32 Byproduct material, Criminal penalties, Labeling, Nuclear materials, Radiation protection, Reporting and recordkeeping requirements.

For the reasons set out in the preamble and under the authority of the Atomic energy Act of 1954, as amended, the Energy Reorganization Act of 1974, as amended, and 5 U S.C.

552 and 553, the NRC is adopting the following amendments to 10 CFR Parts 30 and 32.

PART 30-RULES OF GENERAL APPLICABILITY TO DOMESTIC LICENSING OF BYPRODUCT MATERIAL

1. The authority citation for Part 30 continues to read as follows:

AUTHORITY: Sees. 61, 82,101,182,183,186, 68 Stat. 935, 940, 953, 954, 955, as amended, sec. 234,03 Stat. 444, as amended (42 U.S.C. 2111,2112,2201,2232,2233,2236, 2282); secs. 201, as amended,202,206,88 Stat.1242, as amended, 1244,1248 (42 U.S.C.

5841, 5842, 5846).

Section 30.7 also issued under Pub. L.95-601, sec.10,92 Stat. 2951 as amended by Pub. L.102 486, sec. 2902,106 Stat. 3123, (42 U.S.C. 5851). Section 30.34(b) also issued 25 s

under sec.184,68 Stat. 954, as amended (42 U.S.C. 2234). Section 30.61 also issued under sec.187,68 Stat. 955 (42 U.S.C. 2237).

2. In 9 30.8, paragraph (b)is revised to read as follows:

9 30.8 information collection reauirements: OMB acoroval.

(b) The approved information collection requirements contained in this part appear in 9930.9,30.11, 30.15,30.18, 30.19,30.20,30.21,30.32,30.34,30.35,30.36,30.37,30.38, 30.41,30.50, 30.51, 30.55, appondices A and C to this part.

3. A new 9 30.21 is added under the undesignated center heading " Exemptions" to read as follows:

9 30 21 Radioactive drua: Caosules containina one microcurin of carbon-14 urea for "in vivo" diagnostic use for humans, (a) Except as provided in paragraphs (b) and (c) of this section, any person is exempt from the requirements for a license set forth in Section 81 of the Act and from the regulations in this part and Part 35 of this chapler provided that such cerson receives, possesses, uses, transfeni, owns, or acquires capsules containing one microcurie carbon-14 urea (allowing for nominal variation that may occur during the manufacturing process) each, for "in vivo" diagnostic use for humans.

(b) Any person who desires to use the capsules for research involving human subjects shall apply for and receive a specific license pursuant to Part 35 of this chapter.

26

3 (c) Any person who desires to manufacture, prepare, process, produce, package, repackage, or transfer for commercial distribution such capsules shall apply for and receive a specific license pursuant to 9 32.21 of this chapter.

(d) Nothing in this section relieves persons from complying with applicable FDA, other Federal, and State requirements governing receipt, administration, and use of drugs.

PART 32-SPECIFIC DOMESTIC LICENSES TO MANUFACTURE OR TRANSFER CERTAIN ITEMS CONTAINING BYPRODUCT MATERIAL

4. The authority citation for Part 32 continues to read as follows:

AUTHORITY: Sees. 81,161,182,183,68 Stat. 935,948,953,954, as amended (42 U.S.C. 2111,2201,2232,2233); sec. 201,88 Stat.1242, as amended (42 U.S.C. 5841).

S. In 6 32.8, paragraph (b)is revised to read 9s follows:

G 32.8 Information collection reauirements: OMB aooroval.

(b) The approved information collection requirements contained in this part appear in

$$ 32.11, 32.12, 32.14, 32.15, 32.16, 32.17, 32.18, 32.19, 32.20, 32.21, 32.21 a, 32.22, 32.23, 32.25, 32.26, 32.27, 32.29, 32.51, 32.51 a, 32.52, 32.53, 32.54, 32.55, 32.56, 32.57, 32.58, 32.61, 32.62, 32.71, 32.72, 32.74, and 32.210.

27

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6. A new 9 32.21 is added to read as follows:

G 32 21 Radioactive drua: Manufacture. orecaration. or transfer for commercial distribution of capsules containina one microcurie carbon 14 urea each for *in vivo" disonostic use for humans to oersons exemot from licensino: Reautrements for a license.

(a) An application for a specnic license to manufacture, prepare, process, produce, package, repackage, or transfer for commercial distribution capsules containing one microcurie carbon 14 urea (allowing for nominal variation that may occur during the manufacturing process) each for "in vivo" diagnostic use, to persons exempt from licensing under 9 30.21 of this chapter or the equivalent regulations of an Agreement State will be approved if; (1) The applicant satisfies the general requirements specified in 6 30.33 of this chapter, provided that the requirements of 9 30.33(a)(2) and (3) of this chapter do not apply to an application for a license to transfer byprodu.ct material manufactured, prepared, processed, produced, packaged, or repackaged pursuant to a license issued by an Agreement State; (2) The applicant meota the requirements under 9 32.72(a)(2) of this Part; (3) The applicant provides evidence that each capsule contains one microcurie carbon-14 urea (allowing for nominal variation that may occur during the manufacturing process);

(4) The carbon 14 urea is not contained in any food, beverage, cosmetic, drug (except as described in this section) or other commodity designed for ingestion or inhalation by, or topical apphcation to, a human being; (5) The carbon-14 urea is in the form of a capsule, identified as radioactive, and to bo used for its radioactive properties, but is not incorporated into any manufactured or assembled commodity, product, or device intended for commercial distribution; and (6) The applicant submits copies of prototype labels and brochures and the NRC approves these labels and brochures.

28 i

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i (b) Nothing in this section relieves the licensee from complying with applicable FDA, other Federal, and State requirements governing dregs. j I

4

7. A new $ 32.21a is added to read as follows:

$ 32 21a Same: Conditions of license.

Each licent,3 issued under 9 32.21 of this Part is subject to the following conditions:

(a) The immediate container of the capsule (s) must bear a durable, legible label which:

r (1) Identifies the radioisotope, the physical and chemical form, the quantity of radioactivity of each capsule at a specific date; and (2) Bears the words

• Radioactive Material,"

(b) in addition to the labeling information required by paragraph (a) of this section, the label affixed to the immediate container, or an accompanying brochure also must:

(1) State that the contents are exempt from NRC or Agreement State licensing requirements; and (2) Bear the words " Radioactive Material. For "In Vivo" Diagnostic Use Only. This Material is Not To Be Used for Research involving Human Subjects and Must Not Be r

introduced into Foods, Beverages, Cosmetics, or Other Drugs or Medicinals, or into Products #

Mar l'ictured for Commercial Distribution This Material May Be Disposed of in Ordinary Trash."

Dated at Rockville, Maryland this day of _ _ 1997.

For the Nuclear Regulatory Commission.

John C. Hoyle, Secretary of the Commission.

29

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4 ENCLOSURE 2 REGULATORY ANALYSIS

9 REGUI.ATORY ANALYSIS FOR FINAL RULEMAKING

• EXEMPT DISTRIBUTION AND USE OF A RADIOACTIVE DRUG CONTAINING DNE MICROCURIE OF CARBON 14 UREA" 10 CFR PARTS 30 AND 32

1. Backaround 1.1 SIRiement of the Problern On October 6,1994, the Commir uon docketed a petition for rulemaking (Docket No. PRM 35-

12) from Tri-Med Specialties, In' (Tri-Med). In a letter dated August 23,1904, Tri Med petitioned the NRC to amend its regulations "to allow for the general licensing and/or exemption for the commercial distribution by licensed pharmaceutical manufacturers of a capsule containing one micro-Curie (pCl) of "C urea for in vivo diagnostic testing." The purpose of this diagnostic test is to detect the presence of the bacterium Helicobacter pylori (H. pylori), a cause of peptic ulcers.

" Peptic ulcer disease is a chronic inflammatory condition of the stomach and duodenum that affects as many as ten percent of people in the United States at some time in their lives. The disease has relatively low mortality, but it results in substantial human suffering and high l economic costs." (Source: Article included as an appendix to the petitiori, from JAMA, July 6, 1994-Vol 272, No.1, "H. pylori in Peptic Ulcer Disease NIH Consensus Conference"),

In the petition dated August 23,1994, the petitioner stated the following:

Recent medical research has found that peptic ulcers are commonly caused by a bacterium called H. pylori. This bacterium lives in the stomach of most ulcer sufferers. By treating ulcer patients with antibiotics, doctors can now cure most ulcer problems.

It is therefore necessary to detect the presence of H. pylori bacteria in ulcer patients so that the new treatment can be given appropriately, in the past, this was done by a gastroenterologist who took biopsy samples of the stomach lining at endoscopy, a procedure which was uncomfortable and expensive ($1000).

With the new test, H. pylori can be detected noninvasively using a "C-urea tracer, "C-urea is broken down by H. pylori to form labeled CO, which is expired in the breath. To do the test, a doctor asks the patient to swallow the capsule

. with 30 mis of water. After 15 minutes the patient blows 2 liters of breath into a collection bag (a mylar balloon) which is mailed to a testing laboratory. if "C-CO, more thare twice background is present in the breath sample, then the patient must be infected with H. pylori.

1.2 Current _NRC Regulations in 10 CFR Part 32, " Specific Domestic Licenses To Manufacture or Transfer Certain items Contain,ng Byproduct Materials," S 32.72, " Manufacture, prepara' ion, or transfev for commercial distribution of radioactive drugs containing byproduct material for medical use under Part 35,"

provides for commercial distribirtiun of radioactive drugs containing byproduct material for ut,e by persons authorized pursuant to Part 35. Thus, the regulations currently would permit Part 32 licensees to o mmercially distribute capsules containing 1 pCi of "C urea to persons authnrlzod pursuant to Pari 35.

In 10 CFR Part 30, "Med. cal Use of Byproduct Material," sets forth radiation skfety requirements, including requiroments for the training and experience of authorized user physicians to assure the safe possession and use of radioactive drugs contairying byproduct material.

Existing exemptions for use of byproduct material in 6 30.14," Exemption concentrations" and 3 32.18," Manufacture, distribution and transfer of exempt quantities of byproduct material:

Requirements for license," do not permit the exempt transfer of byproduct material contained in any food, beverage, cosmetic, drug, or any product designed for ingestion or Inhalation by, or application to, a human oeing.

Therefore, uncler current regulations, the "Crurea capsules must be used under a Part 35 license.

's .3 Earlier NRC Actions Following the receipt of the petition, a " Notice of receipt of petition for rulemaking" was published for public comment in the Federal Register on December 2,1994 (59 FR 61631). A total of 310 public comment lettars were received. Of these,313 supported the petition (they were mostly form letters) and two letters opposed the petition. The twd letters opposing the petition stated that (1) the product should not receive an exempt status because the uncontrolled distribution and application of this product could lead to significant risk to the public and (2) medical u;as should be restricted to short-lived isotopes because of disposal problems presented by long-lived isotores.

This petition was discussed with NRC's Advisory Committee on the Medical Uses of (sotopes (ACMUI) at the October 1996 meeting, The ACMUI indicated that it endorsed the wide availability of this diagnostic test and that the radioactive drug could be used under a genetal license or an exemption, whichever the NP.C may determine to be procedurally eaMer, A rulemaking plan was prepared. After receiving comments from Agreement States on the draft rulemaking plan, the Commission approved a final rulemaking plan to develop a proposed ruls to amend 10 CFA Parts 30 and 32 allowing the distribution of the Carbon 14 capsulss as an exempt material to any person.

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.[ ;1A Proposed Rule and Public Comments .

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,. 1The proposed rule was published in the Federal Register (62 FR 32552, June 16,1997) for s ' .

- 30 day public commam period. The _NRC received seven public comment letters. Four . >

i commenters supported the rule, one opposed the rule,' and two provided comments without -

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1 explicitly stating whether they support or oppose _the rulec. A summary of public comments and  :'

NRC's responses are presented in the preamble of the Federal Register notice. _ Except a minor l 4- _ change in wording; rne final amendments are the same as the proposed amendments. No -,'

comments related to the draft Regulatory Guide has been received. ,

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_ _ 2. Objective <

1

, 1The objective of the rulemaking is to amend 10 CFR Part 32 to permit the manufacture and - .

- commercial distribution of "C-urea capsules to any person (including physicians who are not

> ' authorized users". under Part 35) and to amend 10 CFR Part 30 to permit any person, without -

, an NRC license, to receive and use the capsules for in vivo diagnostic use for humanc.

3. Altematives  ;

Three attematives have been considered in the regulatory analysis: deny the petition, i.e.,-

- maintain the status quo, permit the distribution of the capsules to persons exempt from licensing, and permit the distribution of the capsules to general licensees.

Under the first attemative, only physicians who are authorized users under Part 35 would be

allowed to possess and administer the "C-ures test. Any physician could apply to become an

. - authorized user. However, the NRC expects few physicians would apply for a Part 35 license

. for the sole purpose of using the capsules because of the requirement for training and -

experience and the. associated costs of obtaining and maintaining a Part 35 license.

Altematively, physicians who are not authorized users can continue to refer their patients to

physicians who are adhorired users to undergo the diagnostic test. However this would not relieve the current expense, inconvenience, and delay encountered in an otherwise straight-4 forward procedure.

Under the second attemative,10 CFR Parts 32 and 30 would be amended.10 CFR Part 32 would be amended to permit the manufacture and commercial distribution of "C-urea capsules ,',

l to any person (including physicians who are not " authorized users" under Part 35); 10 CFR Part 30 would be amended to permit the manufacture and commercial distribution of the capsules to any person, for in vivo diagnostic use for humans. The NRC has determineo that

. the ladioactive component of this drug presents a minimal radiation risk and; therefore,-

regulatory control of the capsules is not necessary.

. Under the third altomative,.10 CFR Part 35 would be amended to permit any physician to -

p receive and use the capsules under a general license.. The health and safety concems for this altemative are the same as the Altemative 2. However, if this attemative were adopted, there could be a burden to those Agreement States that normally require registration of general '

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4,- Value-impact Analysis 4,1 The Petitioner's Amnessment

In the letters dated August 23,1994 and November 30,1994, the petitioner stated, respectively:

If exempted, the C 14 breath test could be done by most doctors for less than $100 cost

.to the patient. This is a considerable savings over endoscopy and biopsy ($1000).

... The test is 95 percent accurate and quite inexpensive because of its simplicity. The test would permit doctors to deterraine easily whether or not u!cer patients have been cured of their infection. By providing the public with an inexpensive, easily accessible'

% diagnostic test, more individuals would be accurately diagnoNJ and treated for their

H.' pylori infection.' This would save the United States an estimated $500 million per annum over conventional therapy.

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The petitioner estimates annual benefits to be on'the order of $500 million/ year. This assumes i

approximately 600,000 "C-urea breath tests / year, at an average cost of $100, in lieu of

' performing endoscopy at an average cost of $1000/ test.: It assumes that the lower cost and  ;

greater availability of an unregulated breath test would result in a complete substitution.for 4

endoscopy. Tri-Med's benefit analyr.,is provides a measure of the total benefits associated with r the test and does not focus on the incremental benefWs of administering the test pursuant to  ;

c10 CFR 35.100 regulation (status quo) versus releasing the test to all physicians (NRC licensed

. and non licensed alike), implicit in Tri-Med's estimated annual benefits is the presumption that i

none of these "C tests and corresponding savings would accrue if the petition were denied, in reality, under the status quo, the test would be available and administered by physicians or clinics holo!ng a license under NRC's Part 35 or an equivalent Agreement State regulations.

Further, Tri-Med's estimate did riot allow for the substitution of other non-invasive tests (e.g.,

serological test for igg antibot'ies to H. pylori antigens) for both endoscopy and "C-ures tests.

4.2 The NRC's Assessment (a) Cost Savinas>==*^H with Amendments to 10 CFR Part 30 The value impact analysis focuses on the incremental benefits of granting relief consistent with-Altemativt 2 or 3, as specified in Section 3 above. The analysis looks solely at changes relative to the base case or status quo. In this analysis, the comparison is between regulated and unregulated "C-ures breath tests, not unregulated "C-urea breath tests and endoscopies

- or other noninvasive tests.; For the purposes of this regulatory analysis, the NRC assumes that '

the same number of breath tests (i.e.',800,000 tests) will be administered regardless of the

' level of NRC regulatory control. - This view is predicated on the belief that each physician's-

' primary motivation is to provids the _best possible care to his or her patients. If the breath test is

-judged preferable to endoscopy, or other procedure, any physician net authorized to use the test will refer his or her patient to authorized users who could perform the test under existing Y 4 4:

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_ NRC regulations LThis appears fully consistent _with standard medical practice, whereby :

F patients are referred routinely to laboratories and specialists for a wide array of tests and 4

, procedures.

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The benefits of adopting the petition accrue as a result of reduced patient oost and redcced . -

- heMth-care cost resulting from the elimination of the need for referrals from a physician who is ]

- not an authorized user (e.g., gastrointestinal specialist)s There would also be some regulatory" i

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savings because the NRC would not have to expend _ resources reviewing new applications fo.1 q

specific medical use licenses. However, these savings would be small because the NRC -

j expects that few physicians who are not authorized users would apply for a swclfic NRC' i license for use of this one product.-

' The benefit calculation is based on the assumption that as a result of this rulemaking action, a L

L significant portion of the 600,000 patients would isceive tne "C breath test from physicians who ,

are not authorized users (e.g;, gastrointestinal specialists). The actual savings would be ,

: dependent on the number of tests ultimately administered by physicians who are not authorized

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= users, thereby eliminating the need for a referral to physicians v'ho are authorized users (e.g., c

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nuc!aar medicine specialists).

b --The annual savings could be as high as approximately $20 million if there were a complete shift -

E .of the administration of the tests from physicians who are authorized users (i.e., base case) to physicians who are not authorized users; L The basis for this estimate is as follows; 4

Assuming awtion of the petition eliminates the need ft'r up to 600,000 referrals, patient

savings in s,orted travel expenses (transportation and peraonal time incurred with medical referral) would be:

L Assuming round trip of 20 milas @ $0.25/ mile, and personal time of 0.5/ hours / trip valued at $25.00/ hour 600,000 trips / year x (20 miles / trip x $0'.25/ mile + 0.5 hours5.787037e-5 days <br />0.00139 hours <br />8.267196e-6 weeks <br />1.9025e-6 months <br /> / trip x $25.00/ hour) =

! 10.5 million/ year -

Health Care Savings in averted administrative expenses (administrative costs incurred with medical referral) would be:

600,000 patients / year x $19.00/ patient = $11.4 million/ year s  : Assuming 519.00 (administrative cost / patient) as the differential between the cost of an office visit to a general family practice physhian by an established patient ($45.g0), and the cost to a new patient ($64.90 per visit) for completion of new patient paperwoik,-

' reviewing health history, maintaining medical records, etc. The patient v#,o is referred to j an authorized user (e.g., nuclear medicine specialist) for the "C-urea breath test would most likely be a new patient for the authorized user.

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t Total Savings:

, $10.5 million/ year + $11.4 million/ year = $ 21.g milliorvyear Altematively, if only 200,000 or 400,000 of the 600,000 tests were perf$rmed by a physician

.who is not an authorized user, the annual cost savings would be approximately $7 million per year and $15 million per year, respectively.

^ if Attemative 3 were adooted,~ it would permit any physician to receive and ute capsules -

containing 1 pCl %rea for human use under a general license.- The health and safety concems for this'altamative are the same as Altemative 2. However, the adoption of

Altemative 3 could add unnecessary burden to those Agreement States and Agreement State j licensvos in States that assess licensing or registration fees for general license holders.

- Allemative 2 also imposes incremental cost burden for manufacturers or commercial .  !

. distnbutors of the capsules because they would need to ot tain an exempt distribution. license. y

~r Each application is estimated to take up to 16_ hours to prepare. Assuming 3 applicants por'

' year, the total reporting burden would be 48 hours5.555556e-4 days <br />0.0133 hours <br />7.936508e-5 weeks <br />1.8264e-5 months <br />. For recordkeeping burden, assuming each -- !

of the 3 applicants in a year would need 2 hours2.314815e-5 days <br />5.555556e-4 hours <br />3.306878e-6 weeks <br />7.61e-7 months <br /> to reprogram its computer to print additional words on the label or brochure, the one-time total recordkeeping burden would be 6 hours6.944444e-5 days <br />0.00167 hours <br />9.920635e-6 weeks <br />2.283e-6 months <br />.

Assuming a labor rate of $125 per hour, the total burden would be about $6,750 per year. .

There would be costs for the Federal and State goveraments if Attemative 2 or 3 is adopted. l

- Under both Attematives 2 or 3, the NRC and some Agreement States would need to amend their regulations to permit the use ' .he capsules by persons other than physician who are 4

authorized users. *

(b)- Health and Safety Effects  ;

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I For the purposes of this regulatory analysis, the NRC assumes that the same number of breath

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tests (i.e.,' 600,000 tests) will be administered regardless of the level of NRC regulatory control.

. This view is predicated on the belief that each physician's primary motivation is to provide the 4

best possible care to his or her patients. - In addition, the routine and accidental expesures per

, carbon-14 uros breath test is not expected to be affected by the level of NRC regulatory control.

Thus, radiation exposures to the workers and members of the public would be the same regardless of which alternative is adopted.

The NRC has concluded that the human use of these capsules results in insignificant exposures as depicted below:

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a Scenarlo? - Maximum Exposed - - Routine Exposure - b"

- Individual-Worker administering "C-- Full-time worker,8,000 Less than 0.7 mrom/yr _ [

_ urea breath tests ~ patients /yr i

Routine exposure of patients - Patient tests negative - 0.38 mrem / capsule -

from "C-urea breath tests - Patient tests positive' O.18 mrem / capsule .

- Release of 150 pCi of "CO, ' Member of public in the - Less than 0.0002 mrom .

into administration -

. administration area facility from fire -

Rupture of a capsule Skin (100 cmr) exposed for - 5.8 mrad skin dose, -i

causing skin contamin- one hour prior to washing;- _0.02g mrom (CEDE) i ation of worker or patient 0.075 pCi skin absorption ,

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- Furthermore, the NRC concluded that the impacts associated with any releases of "C to the

surrounding environment are expected to be very small and the expected risks are minimal. J The earth's atmosphere contains an inventory of naturally occurring "C of about 3.8 million

_ curies (equivalent to the activity in 3.8 trillion breath tests), which is in addition to the huge

_ inventory of about 240 million curies in the world's oceans. The "C released into the atmosphere from the use of this test would mix with the global inventory and expose the public and other biotic components of the environment to "C intakes from Inhalation, drinking water, and all possible food pathways in the same manner as naturally occurring "C. The current s world inventory of naturally occurring "C results in an average dose to the public of about 1.25 mrom/ year, and the release of 0.6 curies of "C from the total of 600,000 tests assumed to

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be administered annually would result in an additional average annual dose of 2 X 104 mrem.

This is far below the EPA reporting level of 1 mrem / year required under the Clean Air Act for routine exposures to a member of the public, or the 4 mrem / year EPA limit for public drinking water. -In a total population of about 260 million people in tne U.S., the collective annual dose c from the breath tests would be about 0.051 person-rem. In addition, the doses from normal use l

. of breath tests, or from any accidental release of "C to the environment also ars expected to be very small because the concentration of CO, released is very hv and it woulo mix immediately with the atmosphere.

. The small doses from naturally occurring"C are of little significance to human health and the

- environment. _ Potential long-term impacts from wideSoread releases of the long-lived "C

- (5.730-year radiological half-life) from breath tests ure concluded to be insignificant.

Assuming that the testing in the U.S. would increase over a period of time to an average of a million tests per year for 50 years, the collechve annual dose to the U.S. population would be

. .about 5 person-rem over the next 50 years. This dose is very small when compared to the annual collective dose to the U.S. population from naturally occurring "C of over 300,000 p person-rem, and about 78,000,000 person-rem from all naturally occurring radiation. _ Clearly,

an increase of a few person-rem will not significantly change'these exposures, and thus there is =

no expected impact from the widespread use of the breath test on the entire U.S. population.

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, (- l As 's result of this analysis, the NRC concludes that Altematives 2 and 3 are ' clearly preferable -

. to the no action alternative. This is because either of the two altematives will result in t

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significant cost savings with no measurable adverse effect on health and safety. Funhermore,-

. the.NRC's recommended option is Alternative 2 because it would avoid the unnecessary cost burden to some Avig.nent States and their general licensees.

Therefore, by promulgating the final rule, the cost savings would be maximized without any.

measurable adverse effect on public health and safety.

- 5.- Decision Rationale s

Based on the above analysis, the NRC is amending its regulations to permit the manufacture ,

and commercial distribution of Carbon-14 urea capsules to any person (including physicians--

who are not " authorized users" under Part 35) and permit any person, without an NRC license, to receive and use the capsules for in vivo diagnostic use for humans because the radiological;

. risk from such distribution would be negligible and the savings to patients could be significant.

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t ENCLOSURE 3

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ENVIRONMENTAL ASSESSMENT t

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Environmental Assessment For Final Amendments to 10 CFR Parts 30 and 32

" Distribution of a Radioactive Drug Containing One Microcurie of .

' Carbon 14 Urea as Exempt Meterial for "In Vivo" Diagnostic Testing" 1

Statement of the Final Action I

The Nuclear Regulatory Commission (NRC) is amending its regulations to allow NRC licensees to distribute a radioactive drug containing one microcurie of carbon-14 urea to any

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person for "in vive" diagnostic use. The NRC has determined that the radioactive component of '

such capsules presents a minimal radiation risk and, therefore, regulatory control of the drug for radiation safety is not necessary. This amendment makes the drug more widely aval;able, thus reducing costs to patients, insurers, and the health care industry. This action is be!r.g taken in response to a petition for rulemaking (PRM4512) submitted by Tri-Med Specialties, Inc.

Need for the Amendments .

The amendments have been developed to grant the petition for rulemaking. The final rule permits manufacturers or commercial distributors to distribute carbon-14 urea capsules as exemp' material to any person. The Commission is promulgating this ruiemaking because it believes that the radiolog! cal risk from such distribution would be negligible and the savings to

- patients could be significant. In addition, the Commission recognizes that other Federal and State agencies (e.g., Food and Drug Administration and the State Boards of Pharmacy) are responsible for the receipt and use of drugs that do not contain byproduct materials, and would y :^

provide necessary oversight fo- the safe use of these carbon-14 urea capsales as drugs.

- AltemativeruConsidered s

Three altamatives have been considered regarding the petition: den /the petition, i.e.,

maintain the status quo, permit the distribution of the capsules as exempt material, and permit

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the distribution of the capsules to generallicensees.

Under the first attemative, the current situation would continue: orIly physicians who are -

authorized users under hart 35 would be allowed to possess and administer the C-14 urea test.

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because of the requirement for training and experience and the associated costs of obtaining:

3-and maintaining a Part 35 license. Altematively, physicians who are not authorized users can

= continue to refer their patients to physicians wha are authorized users to undergo the diagnostic r ' test.

However this would not relieve the current expense, inconvenience, and delay-encountered in an otherwise straight-forward procedure.

Under the second attemative,10 CFR Parts 32 and 30 would be amended. Part 32 lwould be amended to establish requirementii for the manufacture and distribution of v-14 urea

. capsules to persons exempt from licensing, i.e., any person (including physicianc who are not

" authorized users" under Part 35); Part 30 would be amended to permit any person to receive, Epossess, use, transfer, own, or acquire the capsules for in vivo diagnostic use for humans without a license.- The NRC has determined that the radioactive component of this drug -

presents a minimal radiation ruk and, therefore, regulatory control of the capsules is not necwsary.-

Under the third altemative,10 CFR Part 35'would be amended to permit any physician to -

receive and use the capsules under a general license.- The health and safety concems for this

. altemative are the same as the Altemative 2. However, if this attemative were adopted, there

could be a burden to those Agrtament States that normally require registration of general license holders. An additional burden could also be imposed on general licensees located in the Agreement State if the State charges e.!iceisse or registration fee.

r Based on the Draft Regulatory Analysis prepared for this proposed rule, the Commission c concludes that Altematives 2 and 3 are clearly preferable to the no action altemative. This is because either of the two attematives will result in significant cost savings with no measurable adverse effect on health and safety. Furthermore, the NRC's recommended option is

- Altemative 2 because it avoids the unnecessary cost burden to some Agreement States and

.  : their licensees. s s impact on the Publih and the Environment

The amendments are expected to have no significant impact on the public and the -

~ environment. The NRC assumes that the same number of breath tests will be administered iregardless of the level of NRC regulatory control. This view is predicated on the belief that -

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Teach physician's' primary motivate : to provide the best possible care to his or her patients, if the breath test is judged preferable 1 indoscopy, or other procedure, any physician not i- authonzed to use the test will refer his c e her patient to authorized users who could perform the-test under existing NRC regulations. Under this assumption, this rulemaking action is expected 1 m to result in no change in radiation exposures to the workers and patients wnen compared with the status quo." Similarly, it is expected that there will be no change in impact to the environment because the Commission ' assumes that the same number of tests will be

~ administered regardless of which alternative is adopted.

The earth's atmosphere contains an inventory of naturally occurring C-14 of about 3.8 '

million curies which is in addition to the huge inventory of about 240 million curies in the world's oceans. The small amount of C-14 released into the atmosphere from the use of this test Lwould mix with the globalinventory and would have no inipact on public health. The current world inventory of naturally occurring C-14 results in an average dose to the public of about 1.25 mrom per year, and the release of 0.6 curies of C-14 from the total of 600,000 tests

- assumed to be administered annually would result in an additional average annual dose of 2 X 104 mrom.

List of Aaencies and Persons Cor=d' art and idenGTicMon of Sources used Following the receipt of the petition for rulemaking, a " Notice of receipt of petition for rulemaking" was published for public comment in the Federal Register on December 2,1994, (59 FR 61831). A total of 315 pubiic comment letters,313 supporting (mostly form letters) and 2 opposing letters, were received. This petition was discussed with NRC's Advisory Committee

- on the Medical Uses of Isciopes ACMUI) at the October 1995 meeting. Furthermore, the draft rulemaking plan was forwarded to 29 Agreemer:t States for comments.

A proposed rule was published in the Federal Register (62 FR 32552,' June 16,1997) for a 30 day public comment period. The NRC received seven public comment letters. Four

. commenters supported the rule, one opposed the rule, and two provided comments without i explicitly stating support of or opposition to the rule. A summary of public comments and NRC's responses are presented in the preamble of the Federal Register notice. Except a minor.

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change in wording, the final amendments are the same as the proposed amendments.

- One commenter addressed the draft environmental Assessment. The commenter steted I th at the environmental Assessment fails to consider the fact that another equally non-invasive, 3

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l but non-radiological, diagnostic procedure (such as C-13 test) is available and provides a comparable alternative to the C-14 test. The commenter apparently concluded that the assumption underlying the environmental assessment is that in the absence of the C-14 test, the only alternative for the detection of H. pylori is invasive gastroendoscopy.

The-purpose of the environmental assessment is to address and document the expected impact to the environment of subject rule. As presented in the regulatory analysis prepared for this rule, the NRC has determined that the environmental impact is expected to be insignificant because of the extremely low radiological hazards associated with the use of capsules containing one microcurie C-14 urea.

If the environmentalimpact had been significant, then the existence of a non-radioactive alternative would have been a factor in assessing the cost benefit of this rulemaking. However, the impact is not significant. Hence, the regulatory issue in this rulemaking is whether the C-14 method should be made availaole to physiciar.s who are not authorized users, and not whether there exists a non-radioactive alternative.

Findina of No Sianificant imoacts -

The Commission has determined under the National Enviro,imental Policy Act of 1969, as amended, and the Commission's regulations in Subpart A of 10 CFR Part 51, that the amendments will not be a major Federal action significantly affecting the quality of the human environment, and therefore an environmental impact statement is not required. The final rule amends 10 CFR Part 32 to permit the manufacture and commercial distribution of C-14 urea capsules to any person (including physicians who are not " authorized users" under Part 35) and to amend 10 CFR Part 30 to permit any person, without an NRC license, to receive and use the capsules for in vivo diagnostic use for humans. The Commission believes that the radioactive component of this drug presents a minimal radiation risk and, therefore, regulatory control of 7 the capsules for "in vivo" diagnostic use is not necessary. It is expected that this final rule will not cause any significant increase in radiation exposure to the public or radiation release *o the environment beyond the exposur64 or releases resulting from the use of the carbon-14 capsules under the current regulations.

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-CONGRESSIONAL LETTERS-

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NUCLEAR REGULATORY COMMISSION WASHINGTON. o.C. 30eeH001 4 . . . . . fo[

The Honorable Dan Schaefer, Chairman Subcommittee on Energy and Power Committee on Commerce United States House of Representatives-

~ Washington, DC 20515

Dear Mr. Chairman:

Enclosed for the information of the Subcommittee are copies of a public announcement and a .

Federal Register notice concoming a final amendment to 10 CFR Parts 30 and 32. This rulemaking is being taken in response to a petition for rulemaking submitted by Tri-Med

, ' Specialties, Inc.

The Nuclear Regulatory Commission (NRC) is amending its regulations to allow NRC licensees to distribute a radioactive drug contair.ing one microcurie of carbon-14 urea to any person for "in vivo" diagnostic use. The purpose of this diagnostic test is to detect the presence of the bacterium Helicobacter pylori (H. pylori), a cause of peptic ulcers. The NRC has determined that

the radioactive component of such capsules presents a minimal radiation risk and, therefore, regulatory control of the drug for radiation safety is not necessary. The manufacture and distribution of the capsules will continue to require an NRC license. This amendment makes the drug more widely available, thus reduces costs to patients, insurers, and the health care industry.

Sincerely, a

Dennis K. Rathbun, Director Office of Congressional Affairs

Enclosures:

'~ 1. Public Announcement 2.- Federal Register Notice cc: Representative Ralph Hall i

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'* -} - NUCLEAR REGULATORY COMMISSION WASHINGTON, D.C. 30eeHe01 The Honorable James M. Inhofe, Chairman Subcommittee on Clean Air, Wetlands, Private Property and Nuclear Safety Committee on Environment and Public Works United States Senate Washington, DC 20510

Dear Mr. Chairman:

Enclosed for the information of the Subcommittee are copies of a public announcement and a Federal Register notice concoming a final amendment to 10 CFR Parts 30 and 32. This rulemaking is being taken in resoonse to a petition for rulemaking submitted by Tri-Med Specialties, Inc.

The Nuclear Regulatory Comrr.ission (NRC)is amending its regulations to allow NRC licensees to distribute a radioactive drug containing one microcurie of carbon-14 uros to any person for"in vivo" diagnostic use. The purpose of this diagnostic test is to detect the presence of the bacterium Helicobacter pylori (H. pylori), a cause of peptic ulcers. The NRC has determined that the radioactive component of such capsules presents a minimal radiation risk and, therefore, regulatory control of the drug for radiation safety is not necessary. The manufacture and distribution of the capsules will continue to require an NRC license. This amendment makes the drug more widely available, thus reduces costs to patients, insurers, and the health care industry.

Sincerely, Dennis K. Re'hbun, Director Office of Congressional Affairs

Enclosures:

1. Public Announcement

2. Federal Register Notice cc Senator Bob Graham v

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- Mr. Robert P. Murphy . ~

General Counsel -  :

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- General Accounting Office .I Room 7175 - i 4 441 G. St., NW.

[ ' V#eshington, DC' 20548

%c, Deat_ Mr. Mumny:

Pursuant to SubtRio E of the Small Business Regulatory Enforcement Faimess Act of 1996,5 ; *

- U.S.C.' 801, the Nuclear Regulatory Commission (NRC) is submitting a final rule regarding edistribution of a radioactive drug containing one microcurie of carbon .14 uros to any person for =

? "in vivo" diagnostic use for humans. The purpose of this diagnostic test is to detect the presence 2: s of the bacterium Helicobacter pylori (H. pylori), a cause of peptic ulcers. The fin,i,i rule makes the :  :

! drug more widely available, and reduces costs to ps!!ents, insurers, and heaNh care industry.- I The distribution of the drug in capsule form presents a minimal radiation risk and, therefore,

regulatory control cf the drug for radiation safety is not necessary. This action is being taken in

responW r a petition for rulemaking (PRM-35-12) submitted by Tri-Med Specialties, Inc. .;

We ha, mined that this rule is not a " major rule" as defined in 5 U S C; 804(2) We have .

confirmed this determination with the Office of Management and Budget. .

. Enclosed is~a copy of the final rule that is being transmitted to the Office of the Federal Register for publication. The Regulatory Flexibility Certification and a statement of the availability of thu

• Regulatory Analysis are included in the final rule.

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Sinceroty, Dennis K Rathbun, Director

! Office of Congressional Affairs ,

Enclosure:

- Final Rule  :

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NUCLEAR REGULATORY COMMISSION g WASHINGTON, D.C. 30006 4001 '

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The Honorable Al Gore President of the United .

States Senate W

._ ashington, DC 20510 Dear Mr. Presid' c

' Pursuant to Subtitle E of the Small Business Regulatory Enforcement Falmers Act of 1996,5 U.S.C. 801, the Nuclear Regulatory Commission (NRC)is submitting a final ruie regarding

_ distribution of a radioactive drug containing one microcurie of cart >on-14 uros to any person for "in vivo" diagnostic use for humans. The purpose of this diagnostic test is to detect the presence of the bacterium Helicobacter pylori (H. pylori), a cause of peptic ulcers. The final rule makes the drug more widely available, and reduces costs to patients, insurers, and health care industry.

The distribution of the drug in capsule form presents a minimal radiation risk and, therefore, regulatory control cf the drug for radiation safety is not necessary. This action is being taken in response to a petition for rulemaking (PRM-35-12) submitted by Tri-Med Specialties, Inc.

We have determined that this rule is not a " major rule" as defined in 5 U.S.C. 804(2). We have

, confirmed this determination with the Office of Management and Budget.

Enclosed is a copy of the final rule that is being transmitted to the Office of the Federal Register for publication. The Regulatory Flexibility Certification and a statement of the availability of the r,

Regulatory Analysis are included in the final rule.

Sincerely, Dennis K. Rathbun, Director Office of Congressional Affairs

Enclosure:

Final Rule

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• y The Honorable Newt Gingrich .

Speaker of the United States House of Representstives Washington, DC 20515

Dear Mr. Speaker:

Pursuant to Subtitle E of the Small Business Regulatory Enforcement Falmess Act of 1996,5 U.S.C. 801, the Nuclear Regulatory Commission (NRC) is submitting a finel rule regarding -

distribution of a radioactive drug containing one microcurie of carbon-14 urea to any person for "in vivo" diagnostic use for humans. The purpose of this diagnostic test is to detect the presence of the bacterium Helicobacter pylor'(H.

. pylori), a cause of peptic ulcers. The final rule makes the i drug more widely available, and reduces costs to patients, insurers, and health care industry.

The distribution of the drug in capsule form presents a minimal radiation risk and, therefore, regulatory control of the drug for radiation safety is not necessary.- This action is being taken in response to a petition for rulemaking (PRM-35-12) submitted by Tri-Med Specialties, Inc.

-We have dete:Tnined that this rule is not a " major rule" as defined in 5 U.S.C. 804(2). We have confirmed this determination with the Office of Management and Budget.

Enclosed is a copy of the final rule that is being transmitted to the Office of the Federal Register for publication. The Regulatory Flexibility Certification and a statement of the availability of the Regulatory Analysis are included in the final rule.

Sincerely.

Dennis K. Rathbun, Director Office of Congressional Affairs

Enclosure:

Final Rulo k

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- NRC CHANGES REGULATIONS TO PERMIT EXEMPT DISTRIBUTION OF RADIOACTIVE DIAGNOSTIC DRUG

- The Nuclear Regulatory Commission is amending its regulations to allow a -

O specific radioactive strug used to diagnose stomach ulcers to be distributed to any -

person for administration to humans. Before this change, only physicians f authorized by the NRC or Agreement States could receive and administer the drug.;

The change does not relieve persons from the requirement to comply v'ith applicable Food and Drug Administration or other Federal and State requirements governing receipt, administration and use of drugs.

The change is in response to a 1994 petition for rulemaking from Tri Med Specialties, Inc. The revised regulation allows any person to receiva, possess, use and transfer capsules containing one microcurie carbon 14 urea each for diagnostic use in patients. The NRC has determined that the capsules present a' minimal radiation risk, and therefore believes that regulatory control of the drug for radiation safety is not necessary.

Under the amendments, manufacturers of the capsules and comre.ercial pharmacies that prepare the capsules will continue to need an NRC license to provide high confidence of capsule contents. The containers of the capsules must bear the~words " radioactive material" and other specific information on the contents of the container. In addition, only those persons who are licensed will be permitted _to use the capsules for research involving human subjects.

LThe Tri Med petition stated that Carbon-14 urea can be used to detect the presence of a bacterium that causes peptic ulcers, a chronic inflammatory condition'of the stomach and duodenum that affects as many as 10 percent of I

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- people _in the United States at some time in their lives. According tr ' July 1994-  ;

.' article in the Journal of the dmerican Medical Association, the ' disease . ( .

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relatively low mortality, but results in substantial human suffering and high 1 economic costsJ Doctors can now cure most ulcer problems with antibiotics. The

, tu using Carbon 14 ures is non-invasive.f A doctor asks the patient to swallow _

the capsule _with water. After 15 minutes the patient blows into a collection bag, I wh'ich is mailed to a testing laboratory for analysis.

Before the change, only physicians who were authorized users (e.g.,

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c physicians who met certain training and experience criteria regarding the safe use 1 of radioactive drugs) or persons working under the supervision of an authorized user could administer radioactive drugs for medical purposes. l

, Under the amendments, physicians or other health care workers will not i need to be authorized users in order to administer the drug, and physicians will not

p. need to refer their patients to nuclear medicine physicians. This should result in ,

cost savings to patients, insurers, and the health care industry.

A proposed rule on this subject was published in the Federal Register for public comment on June 16. Mir'or changes made to the rule as a result of comments received are discussed in a Federal Register notice that will be published shortly.

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