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a UNITED STATES
[&j NUCLEAR REGULATORY COMMISSION e
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WASHINGTON. D.C. 20555-4001
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March 13. 1997 MEMORANDUM T0:
David L. Morrison. Director Office of Nuclear Regulatory Research FROM:
David L. Meyer. Chief d M t*
Rules Review and Directives Branch Office of Administration
SUBJECT:
REVIEW OF PROPOSED RULE ENTITLED " EXEMPT DISTRIBUTION OF A RADIOACTIVE DRUG CONTAINING ONE MICR0 CURIE OF CAP"0N-14 UREA" The Office of Administration has reviewed and concurs in the proposed rule and accompanying documents that would permit NRC licensees to distribute capsules containing one microcurie of carbon-14 urea for "in vivo" diagnostic use.
We have attached a marked copy of the proposed rule package that includes our changes.
We have inserted for incorporation in the codified text of the proposed rule the appropriate authority citations for 10 CFR Parts 30 and 32. respectively.
We have requested that the Office of Information Resources Management review the proposed rule for compliance with the Paperwork Reduction Act.
You should contact Brenda Shelton (415-7230) for further guidance concerning this matter.
If you have any questions regarding the marked copy please have a member of your staff contact Michael T. Lesar on 415-7163 or Alzonia Shepard on 415-6864.
Attachment:
As stated 9801140062 900109 PDR PR 30 62FR32552 PDR G4l a
FOR:
The Commissioners FROM:
L Joseph Callan, Executive Director for Operations
SUBJECT:
PROPOSED RULE: EXEMPT DISTRIBUTION AND USE OF A RADIOACTIVE DRUG CONTAINING ONE MICROCURIE OF CARBON 14 UREA (PARTS 30 AND 32)
PURPOSE:
To obtain the Commission's approval for the publication of the proposed rule.
BACKGROUND:
t,p'd By negative conser't, the Commission approved a rule plan to amend Parts 30 and 32 to permit the exempt distribution and use of one micro-Curie (pCi) capsules of carbon-14-urea for in vivo
-diagnostic use. This rul plan was submitted to the Commission on February 7,1997 as SECY-97-031.
DISCUSSION:
Part 32 would be amended to add a new section (9 32.21) 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 9 32.72(a)(2) (e.g., be registered or licensed with the FDA as a drug manufacturer or be licensed as pharmacy by a State Board of Pharmacy).
The proposed amendment would require licensees distributing these capsules under an exempt distribution license to meet this same requirement because the capsules will have widespread distribution for "in vivo" diagnostic use by persons who will be exempt from licensing. Also, this would provide high confidence that the carbon-14 urea capsules contain only one microcurie of carbon-14 and do not contain other radioactive contaminants.
Part 30 would be amended to add a new section ($ 30.21), to permit any person to receive, possess, use, own, transfer, or acquire carbon-14 urea capsules, not to exceed one microcurie
' CONTACT:
Sam Jones, RES, 415-6198
4 The Commissioners 2
of carbon-14, for "in vivo' diagnostic use, without a license. As a result, NRC regulations would permit the drug to be Cistributed to any person. The proposed amendment would include a reminder that persons would not be relieved from complying with applicable FDA, other Federal, and State requirements goveming drugs. Also, any person who desires to use the capsules for reseerch involving human subjects would be required to apply for and receive a specific license pursuant to Part 35.
COORDINATION:
The Office of the General Counsel has no legal objection to the proposed rulemaking. The Office of the Chief Financial Officer has no resource-related objection to this rufemaking. The Office of the Chief Information Officer concurs that there will be no information technology impacts.
RECOMMENDATION:
That the Commission:
Approve for publication in the Federal Reaister the proposed amendments to 10 CFR 1.
Parts 30 and 32 (Enclosure 1).
2.
Note:
That the proposed amendments will be published in the Federal Reaister allowing a.
75 days for public comment.
That the Chief Counsel for Advocacy of the SmMI Business Administration will be b.
informed of the certification and the reasons for it, as required by the Regulatory Flexibility Act,5 U.S.C. 605(b).
A regulatory analysis has been prepared tv this rulemaking (Enclosure 2).
c.
d.
An Environmental Assessment has been prepared for this rulemaking (Enclosure 3).
The appropriate Congressional committees will be informed of this action e.
(Enclosure 4).
f.
That a public announcement will be issued by the Office of Public Affairs when the proposed rulemaking is filed with the Office of the Federal Register (Enclosure 5).
A The Commissioners 3
That resources to complete and implement this rulemaking are inc!uded in the g.
current budget.
L. Joseph Callan Executive Director for Operations
Enclosures:
As stated (5)
i The Commissioners-3 That rcsources to complete and implement this rulemaking are included in the g.
current budget.
L. Joseph Callan Executive Director for Operations
Enclosures:
As stated (5)
Distribution:
RPHEB r/b EDO r/f ASummerour RECORD NOTE: A draft copy of the proposed rule was sent to OlG for information on DOCUMENT NAME: O:\\TROTTIER\\C14CP.WPD To receive a copy of this document, indicate in the box: "C" = Copy without attachment / enclosure "E" = Copy with attachmentlenclosure "N" = No copy
MMorrisg4 CJPaperiello RLBangart NAME SJones*
CTrottier-DATE 02/27/97 02#d7 02MQ97
/ 19 7 1 197 mummmmmmuammmmmmmmmmmmmen sus summmmensammana num summmmmmassammaumamammmmmmmmmmmeumaammmmmmmmmmm e assi OFFICE OE OGC ADM IRM OC/OCFO NAME-JLieberman WJOlmstead DMeyer BJShelton RScroggins DATE
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D Qn LJCallan DATE I 197 1(4 97
/ 19 7 OFFICIAL RECORD COPY (RES File Code) RES II
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[7590-01-P]
NUCLEAR REGULATORY COMMISSION le CFR. Parts 30 and-32 RIN: ' f t
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-Exempt Distribution of a Radioactive Drug
.Containing One Microcur'ie of Carbon-14 Urea
. AGENCY:' Nuclear Regulatory Comission.
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ACTION:
Proposed rule.
)
p (V
o The Nuclear Regulatory Commission (NRC) is proposing t2 amend its I
SUMMARY
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Wa j'pign;j
- jan sw gMowNRClicenseestodistributearadioactivedrugcontaining regulations one microcurie of carbon-14 urea to any person for "in vivo" diagnostic use.
hn i<
l-n The NRC has determined that the radioactive component of such capsuley 6 /n presents a minimal radiation risk and, therefore, regulatory control of the drug for radiation safety is not necessary.
If adopted, this amendment would-make the drug more widely available, thus reducing costs to patients. This action is being taken in response to a petition for rulemaking (PRM-35-12) submitted by Tri-Med Specialties, Inc.
' DATES:. - Submit comments by '(Insert date.75 days after publication date).
Comments received after this date will be considered if it is practicable to
.do'so.but the Commission is able to assure consideration only for comments received on or before this date.
l:
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'.' ADDRESSES:- Send comments to:
Secretary, _ U.S, NuclearLRegulatory Commission, h:
{
Washington (DC -20555-0001,-. Attention:-: Docketing and. Service B. anch.
L
. Hand deliver:commentsttoi 11555 Rockville Pike,.Rockville, Maryland, l
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g-4; M* betweenL 7T)5'am and 4:15 pm' on Federal workdays.
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The-public may examine comments received, the environmental assessment l
F.
and finding of no significant' impact,-and the regulatory analysis at the NRC Public-Document Room, 2120 L Street NW. (Lower Level), Washington, DC.
FOR FURTHER INFORMATION CONTACT:
Sam Jones, Office _of Nuclear _ Regulatory LResearch, U.S. Nuclear Regulatory Commission, Washington, DC 20555-0001,
~ telephone (301) 415-6198 or e-malliat-SZJ@nrc. gov.
?
SUPPLEMENTARY INFORMATION:-
I. _-
. Background.
II.
Discussion.
III.' Summary of Proposed Amendments.
IV.
Agreement State Compatibility, V.
Finding of No Significant Environmental Impact:
. Availability.
-VI.
Pape ork Reduction Act Statement.
VII.
Regulatory Analysis.
_VIII.. Regulatory Flexibility Certification.
I X'.'.
Backfit Analysis.
X.
Electronic-Access.
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I. Background The Petition for Rulemaking On October 6, 1994, the Commission docketed a petition for rulemaking In a letter (Docket No. PRM-35-12) from Tri-Med Specialties, Inc (Tri-Med).
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 The one micro-Curie ( Ci) of "C-urea for in vivo diagnostic testing."
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 :;ffects as many as 10 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"),
in the petition, 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 antibiatics, doctors can now cure most ulcer problems.
3
It is therefore nccessary to detect the presence of H. pylori bacteria in ulcer patients so that the new treatment can be given appiopriately..In the past, this was done by a gastroenterologist who took biopsy samples of the stomach lining at endoscopy, a procedure which was unccmfortable and expensive ($1000).
With the new test, H. pylori can be detected non-invasively 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 than twice background is present in the breath sample, then the patient must be infected with H. pylori.
Public Comments on the Petition Following the recelpt of the petition, a e of receipt of petition f ik N2 C-j ublished for pub 11g_s.
in the Federal Register on for rulemaking p ~
Temm ed PWad ctosed en &fru n+1 /5,IfiT.
December 2, dNi5(59 FR 61831)Q. gA Lutal mL315 public comment le 1994 A '#"
Mw p Q>G kiti (nw d supporttag (mostly form letters) and 2 eppedg lettersWc icueived. The G
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two letters opposing the petition stated that % the product should not o f f*"d m
W^2 receive an exempt status because the uncontrolled distribution and application r* 4 Men of this product could lead to significant risk to the public and p medical uses should be restricted to short-lived isotopes because of disposal problems presented by long-lived isotopes.
4 1
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The NRC has considered the two opposing comments and has determined M l
(1) e resulting radiation dose from the capsules to workers, patients, and the public is very low Gee Regulatory AnalysisQ (2)fheimpactsassociatedwithanyreleasesof"Ctothesurrounding environment are expected to be very small and the expected risks are minimal ee Environmental Assessment).
Similarly, the small doses from naturally occurring "C are of little significance to human health and the environment.
Also, the Commission concludes that the potential long-term impacts from widespread releases of the long-lived "C (5,730-year radiological half-life) from breath tests are insignificant.
Comments from Advisory Committee on the Medical Uses of Isotopes This petition was discussed with NRC's Advisory Committee on the Medical Ws The ACMUI indicated UsesofIsotopes(ACMUI)at4g0ctober1995 meeting.
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, enn de erMs%
s whichever the NRC LE;h'Ito be procedurally easier.
N
- 11. Discussion Regulatory Issue The regulatory issue is whether capsules containing one mic.ocurie of carbon-14 urea present a sufficiently small radiation risk that they can be safely distributed to and used by physicians (or other persons) who are not
" authorized users" under Part 35, 5
i
~-
Current NRC Regulations f ar the Manufacture and Commercial Distribution of Radioactive Drugs Containing Byproduct Faterial NRC regulations in 10 CFR 32.72 address the manufacture, preparation, or transfer for commercial distribution of rhdioactive drugs containing byproduct material.
This regulation requires manufacturers or preparers of radioactive drugs for commercial distribution to be:U.,.
(1)kegistered or liciased with the food and Drug Administration (FDA) as j
a drug manufacturer; (2) kegistered or licensed with a state agency as a drug nianufacturer; (3)IicensedaspharmacybyaState sard of Pharmacy; or (4) herating as a nuclear pharmacy within a Federal medical institution.
These facilities have a specific license with the NRC. Under the specific license, the manufacturer or pharmacy can distribute radioactive drugs only to persons authorized pursuant to Part 35, " Medical Use of Byproduct Material."
Current NRC Regulations for the Medical Use of Radioactive Drugs Containing Byproduct Material Currently,10 CFR Part 35 only permits physician who are authorized c.,9 users p, physicians who meet certain training and experience criteria c
regarding the safe use of radioactive drugs) or person, working under the supervision of an authorized user to use radioactive drugs for medical use.
The Agreement States have similar requirements.
6
Cu'rrent NRC Regulations on Exemptions from Licensing l
Existing exemptions from licensing requirements for the use of byproduct material include exemptions for specific products (e.g., time pieces),
exemption for classes of products (e.g., gas and aerosol detectors) and broader materials exemptions in 5 30.14, " Exempt concentrations" and 5 30.18,
" Exempt quantities." These two broad materials, exemptions specifically exclude the 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.
(In'the case cf exempt quantities, this prohibition is contained in $ 32.18, " Manu#acture, distribution and transfer of exempt quantities of byproduct material; Requirements for a license,"
c
- 32.18(b)).
Capsules containing one microcurie of carbon-14 urea would not qualify as l>];U an " exempt quantity" in accordance 5 30.18 because of their intended use (as a t
drug) even though they contain a smaller quantity than that set forth in
-6.I c 5 30.71, Schedule B. -bh-e use is outside the intent of the exemption in 1 30.18.
It would introduce needless complexity to the regulations and confusion to accommodate this unique use under the aforementioned sections.
However, because the capsules present an insignificant radiological risk to the public and the environment, they could be distributed to persons exempt from licensin r "in vivo" diagnostic use.
7 l
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1
' Proposed Amendments and Rationale for Permitting the Distribution o.
'of the Capsules to: Persons: Exempt from: Licensing-b
-Proposed Amendment to 10 CFR Part 32 The regulations in-10 CFR Part 32 would be amended to add a new $ 32.21,-
a
-to provide requirements for a specific license to manufacture, process,'
produce, pank&ge', repackage, or transfer capsules containing one microcurie of
--carbon-14 urea,'as a radioactive drug, to be distributed to any person for "in
- t
- vivo", diagnostic use.
' [eYtlia would include a reminder that licensees distributing the radioactive-drug-to persons exempt from licensing would-not i
s be relieved from other applicable Federal (e.g., FDA) or State requirements-governir;g the manufacture and~ distribution of drugs.
Rationale
.,\\
NKC The p tssion had decided that tne manufacture or preparation of
~
V 9W capsules containing y microcurie of carbon-14 urea should continue to be f
- prepared by persons who meet the current NRC regulations to n}anpfacture and st/xte t icommercially distribute radioactive drugs. ThefeTT.gc.ssien tekes-thic p m fr a-p
-4ecnrmse regulatory control is needed to provide high confidence that the drug
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contains?only-one microcurie.of carbon-14 urea and..does not contain any other
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radioactive contaminants.
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~ Amendment'and Rationale for. Exempting "Any Person" from Licensing.
Requirements _to Receive the Drug =
Proposed Amendment to 10 CFR Part 30.
The-regulations in 10 CFR Part 30 would be amended to add a new $ 3b.21, l
to permit any person to receive, possess, use, own-transfer, or-acquire for--
"in vivn" diagnostic use, capsules containing one microcurie of carbon-14 urea without a license. The exemption would prohibit research involving-human Rkt regulations would include a reminder that persons receiving the -
jsubjects.
Yg Ynot be relieved from'.other Federal _ or State-law governing drugs..
~
'D Rationale l
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5i s/C The p3 aim has determined that thelcapsule present no significant i
D radiological safety or environmental-risk, and it-is not necessary to regulate 3
Therefore, the C:-
,the use of this drug-for its radioactive component.
can not justify requiring physicians, or any other person, to meet NRC training and experience criteria directed at the safe use of radioactive c o g m b ----
drugs, or_to become an " authorized user." Hence,=the p should b distributed to any. person who is permitted to receive and use the y under the' appropriate Federal or. State law governing drugs.
vivo'. diagnostic use" is.being used in 5 30.21 instead of-The phrase J K y" for two reasons.
First, the term " medical use" has a specific
" medical use
- meaning.and is defined in 135.2.to mean "the intentional internal or external.
administiation-of byproduct material.or the-. radiation therefrom to patients or
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l human research subjects under the supervision of an authorized user." This-term would be inappropriate because:
(1)i(hedrugcouldbeadministeredtop?tiontsbyphysiciansorother persons who are not authorized users; and (2)
- kdical use" includei tne administration of the crug to a human research subject, which would be prohibited by this rulema(ing.
Effects of the Proposed Amendments fgqul f The effect of there amendments would be to make the drug available to any person, for "in vivo" diagnostic use, without need for an NRC or Agreement Because the receipt ap use of the drug would be exempt from State license.
u.-
NRC licensing, Agreement States p need to make appropriate provisions in their regulations to recognize the exempt distribution of tne drug [or "in l
vivo" diagnostic use. Thus, after the manufacture and aistribution of the W
drug,, NRC and the Agreement States would not regulate ge-drug for "in vivo" t/c diagnostic use.
This means that, under NRC and Agreements State regulations, primary /-care physicians who are not " authorized users could administer the drug, and would not need to refer their patients to nuclear medicine physicians.
This should result in cost savings to patients. Regulation of the use of the dr'g for "in vivo" diagnostic use, after its distribution, would be lef t to other Federal or State organizations with responsibilities for regulating the use of drugs. NRC would regulate the use of the drug for research involving human subjects under a specific rt 35 license,for *-
5 (medical d 10
1 i
- Ill; Summary of Proposed Amendments
- Manufacturer and Distributors A new!section would be added to 10 CFR Part 32 to permit the distribution-
^
- Opdw of the p to persons who are exempt from licensing.
l 32.21 Radioactive drua: Manufacture, distribution, and transfer of carbon--
14 urea capsules not exceedina one microcurie each for "in vivo" diagnostic
-use: Reauirements for a license
(#
e^d ie,, 32 1$. Paracraoh (a) fp prvu3h'[bs paragraph the Ccrission,would allow the drug to be distributedtopersonsA ifr
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(j) 5=. 2 2 :n Paragraph (a) Arem u r The.NRC would limit 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 Agreement State " specific license" for possession and use of byproduct material.
(2)
- N i vii 32. 1 -Paragraph (a) Ite-m -
1,
-To-assure.that the capsules contain no more one microcurie of carbon-14 g
SAC and present no other radiological risks, theftfwaWAen would require that the persons manufacturing and/or distributing the capsules for "in vivo"
-d1' agnostic use must also meet the requirements of 5 32.72(a)(2).
11 a
i Specif_ically, these persons must be:
-(l)hgistered with' or licensed by the FDA;as a drug manufacturer; or (2)[egistered with or licensed by a state agency as a drug manufacturer; or-(3)[JcensedaspharmacybyaStateBoardof. Pharmacy;or b
(4) heratinglas a nuclear pharmacy within a. Federal medical institution.
Sect M 32.2b Paraaraoh (a) -
(3) t Applicants would be required to provide evidence that each carbon-14 urea MC capsule will not exceed one microcurie. The p.,issir.'t evaluation that the capsules.would'not result in significant radiation risks was based on the capsules containing microcurie of carbon-14 urea. Therefore, applicants must demonstrate that-the activity of each carbon-14 capsule will not exceed one microcurie.
$actiefnHMM r-Paraaraph ' (a)
(4)
ThefNhienwouldprohibitcarbon-14ureafrombeingcontainedinany hs. a n -
food, beverage, cosmetic, drug or other commodity designed for? ngestion, i
+opical 4
y orgapplication (fo a human bein), except for the capsules as inhalationj 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.
M un 32. & Paraaraph-(a)
( 5)_
fst cause'the exempt distribution of this drug has only been
- L--
evaluated for "in vivo" diagnostic use in the form of a capsule containing one 12 w
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-microcurie of carbon-14 urea, the g=nsits will prohibit incorporation of the capsules into any manufactured or assembled commodity, product,-or device JC intended for commercial distribution.- Furtheryaven-though_the drug is being distributed to persons-exempt from licensing, the $$bsica will require the carbon-14 urea to be identified as radioactiv[ecause the drug is being used L
mst foritsradioactivecontentj therefore,- end user theeM be provided with e
information that the drug contains a radioactive material.
Sac W n 32. & Paracraph (a)._J (sl As with any product approved for distribution to persons exempt from ppc
-licensing, the
...;.;33 ion would require persons who apply for a license to
-tvse manufacture or distribute swdcapsules to submit copies of prototype labels p/c or brochures for $,..'.25 is approval. This will allow the NRC to confirm that the labels or brochures meet the requirements of 5 32.21a (a) and (b).
h*nm 3 4 Paracraoh (b) aragraph h: Ce--4s4en declares that noth%g 5 these *~'"~~
regulations,rel$eveflicensees or license applicants from complying with e.
(
applicable FDA, other Federal, and State requirements governing manufactur4*ga-and distribution of drugs, Section 32.21a Same: Conditions of license Asd.
N In=thissectiontheps#ACissica states the ennditions for a license to p
y distribute the capsules to persons exempt from licensing.
e 13 r
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-Paraaraoh &
)-
To-inform-the-end user of-the identity of the radioisotope,3the. physical l
and chemical form [ndithe dosage of radioactivity -the hMfm would l'
bear a -
require that the immediate container of each capsule or capsules On durable, legible label-wMek:-
(1)hentifies the radioisotope, the physical and chemical form of the radioisotope, the quantity of. radioactivity contained in each container at a f
specific date; and
-(2) hars the words " Radioactive Material."
The date requirement is consistent with labeling requirements for other ra'dioactive drugs with a half life of greater that 100 days.
c)
Paragraph m
- bi
= Consistent with the intended use of the capsules, the label affixed.to the immediate container, or an accompanying brochure, (1)jtatethatthecontentsareexemptfromNRCorAgreementState licensing requirements; b'Ve r* * $
(2) harl the words " Radioactive Material -- For "In Vivo" Diagnostic Use 'on M Thi s ran+e m al is e d M us+ clet E e.
OnlyL-Notfo Researc}InvolvingHumanSubject Introduc y into Foods, f, g g,;
A 8'd '
~ Beverages, Cosmetics, Other Drugs or Medicinals, or into Products Manufactured-4 he.
for Commercial Distribution,k d.ibitd."
de'm(
Ocht volse; "In vivo" diagnostic-use by person exempt from licensing A new section'would-be.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.
14
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Section 30.21-Radioactive dreo: Capsules containing' one microcurie of carbon-14 urea for "in' vivo" diaanostic use would be added-to permit any
~
Jperson to receive the_ capsules.-
1
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-Paragraph (a)-
~
pfL The ytsien would-exeiapt'any person from the-requirements for a
-license to receive, possess, use, transfer,- own, or acquire capsules -
containing one microcurie of carbon-14' urea for "in vivo" diagnostic purposes.
Paraarach' (b)'
Persons exempt from licensing would be prohibited ~from using the drug for research involving humans subjects. A specific Part 35 license would be needed to use the drug in any research involving human subjects.
Paraoraph 30,4f c)
This. paragraph would specify that a specific license is needed to manufacture, process, produce, package, repackage or transfer for commercial distribution such capsules.
LParaorash (d) b aragraph C ou...i is i e declares that nothir.g ir thew 7
regulations relieve [end users from complying with applicable FDA, other-Federal, or State requirements governing the administration and use of drugs.
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IV.
Agreement State-Compatibility-Under the~ Atomic Energy Act, certain regulatory _ functicns are reserved to thel NRC.- Among these are the distribution of products to persons exempt from
~
licensing,.as discussed in 10 CFR Part'150.- Hence, the proposed rule, if-adopted would be a Division 4 matter of compatibility, wit' regard to the
- nufacture and distribution of the capsules (10 CFR Part 32), and a Division 1 matter of compatibility with regard to possession and use (10 CFR Part 30).
Therefore, the Agreement States will need to make appropriate' provisions in
^
their regulations to allow any person to receive capsules containing one f p microcurie of carbon-14 urea for "in' vivo" diagnostic use withcut need for a r
, license.
MA>
Availability
.VJ Finding of No Significant Environmental Impact:
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 proposed amendments, if adopted, would not be a major Federal action significantly affecting the quality of the human environmentf therefore,an environmental impact statement is not required. The proposed rule would establish requirements for the manufacture and commercial distribution of "C-urea capsules _to persons exempt from licensing and
.establishL regulations to. permit any person to receive the capsules without an
'NRC license. The Commission believes that-the radioactive component sf 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 16
~
1 Enecessary.
It~-is expected that this proposed rule, if adopted, would not cause any;significant increase in radiation exposure to.the public or
- rediation 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 would be no non radiological impacts if the proposed rule is adopted.
The draft 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 draf!. environmental assessment and the finding of no significant impact are available from Sam Jones, Office of Nuclear-Regulatory Research, U.S.. Nuclear Regulatory Commission, Washington, DC 20555-0001,_ telephone (301) 415-6198 or e-mail at SZJ@nrc. gov.
VI/. Paperwork Reduction Act Statement This proposed rule amends information collection requirements that are subjectto_thePapehorkReductionActof 1995 (44 U.S.C. 3501 et seq.).
This rule has been submitt'ed to the Office of Management and Budget for review
~
and approval of the information collection requirements.
Ths public reporting burden for-this enllection of information is estimated to average hours 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. Tne Nucleae Regulatory Commission is seeking public comment 17
- 3 (on;the' potential impact-of the collection of-information contained in the-
~
proposed rule and on the-following 1ssues:
- 1. _.ls the proposed collection' of.-:information necessary. for the proper performance _of the functions of the NRC.-including whether the information
' willThave practical utility? -
- 2. -Is the estimate of the burden correct?
- 3. - Is there a way to enhance the quality, utility, and.the clarity of
-the information to be collected?
4.
How can the burden' of the collection of information be minimized, zincluding_ the 'use off automated collection techniques?-
-.i Send comments of any aspect of this proposed 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 BJSl@NRC. GOV; and to the Desk Officer, Office of Information and Regulatory Affairs, NE0B 10202, (3150-0017,
-0020 -0011, -0009, and -01320, Office-of Mhnagement and Budget, Washington, DC 20503.-
Comments to:0MB on the t'ollections of information or on the above issues j
should be submitted by (insert date 30 days after publication in the Federal Register). Comments received _after this date will beLconsidered if it is practical to do so, but' assurance of consideration cannot'be given to comments
^
receiv'ed.after this date.
18 w
a m -
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.
Vilj Regulatory Analysis The NRC has prepared a regulatory analysis for the proposed-a( b mend mi The analysis examines the benefits and impacts considered by the NRC.
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 Sam Jones, Office of Nuclear Regulatory Research, U.S. Nuclear Regulatory Commission, Washington, DC 20555-0001, telephone (301) 415-6198 or e-mail at SZJtenrc. gov.
Reculatery 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 entitiet.p Any small entity subject to this regulation which determines that, because o its size, it is likely to bear a disproportionate auverse economic impact shot ld notify the Commission of this in a comment that indicates the following:
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i (a) The licensee's size and how the regulation would result in a significant economic burden upon the licensee as compared to the economic burden on a larger licensee.
(b) How the regulations could be modified to take into account the licensee's differing needs or capabilities.
(c) The benefits that would accrue, or the detriments that would be avoided, if the regulations were modified as suggested by the licensee.
(d) How the regulation, as modified, would more closely equalize the impat,t of regulations or create more equal access to the benefits of Federal programs as opposed to providing special advantages to any individual or group.
(e) How the regulation, as modified, would still adequately protect public health and safety.
IX.
Backfit i fi $4 1he 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).
Electronic Access in )
1lh !
Comments may be submitted electronically, in either ASCII text or I
j, l Wordperfect format (version 5.1 or later), by calling the NRC Electronic ulletin Board on FedWorld. _The bulletin board may be accessed using a 20 l
(
personal computer, a modem, t.nd one of the commonly available communications software packages, or directly via Internet.
If using a personal computer and modem, the NRC subsystem o, FedWorld can be accessed directly by dialing the toll free number: 1-800-303-9672.
Communication software parameters should be set as follows: parity to none, data bits to 8, and stop bits to 1 (N,8,1). Using ANSI or VT-100 terminal emulation, the NRC NUREGs and Reg Guides for Comment subsystem can then be accessed by selecting the " Rules Menu" option from the "NRC Main Menu." For further information about options available for NRC at FedWorld, consult the
" Help /information Center" from the "NRC Main Menu." Users will find the
'd "FedWorld Online User's Guides" particularly helpful. Many NRC subsystems and
\\N\\
databases also have a " Help /information Center" option that is tailored to the
\\
i
\\' '/
particular subsystem.
de The NRC subsystem on FedWorld ca* also be accessed by a direct-dial' phone A
number for the main FedWorld BBS, 703-321-3339, or by using Telnet via Internet, fedworld. gov.
If using 703 321-3339 to contact FedWorld, the NRC subsystem will be accessed from the main FedWorld menu by selecting the
" Regulatory, Government Administration and State Systems," then selecting
" Regulatory information Hall." At that point, a menu will be displayed that has an option "U.S. Nuclear Regulatory Commission that will take you to the d
NRC Online main menu. The NRC Online area also can be accessed directly by typing "/go nrc" at a FedWorld command line.
If you access NRC from FedWorld's me.in menu, you may return to FedWorld by selecting the " Return to FedWorld" optior from the NRC Online Main Menu. However, if you access NRC at FedWorld by using NRC's toll-free number, you will have full access to all NRC systems but you will _ not have access to the main FedWorld system.
21 1
4 d
_____.______________.-________..___._____._________.___._______.._J
_ _ _.m.__.._. _. _._.._. _
f f
If you contact FedWorld using Telnet, you will see the NRC area and' t
menus, including the Rules menu.
Although you will be able to download i
p documents and leave messages, you will not be able to write comments or upload l
I files (comments).
If you contact FedWorld using FTP, all-files can be accessed and downloaded but uploads are not allowed; all you will see is a l
list of. files without descriptions (normal Gopher look).
An index file listing all files within.a subdirectory, with descriptions, is included.-
There is a 15-minute time' limit for FTP access.
Although FedWorld can be accessed through the World Wide Web, like FTP
=that mode only provides access for downloading files and does not display the-j NRC' Rules menu.
i For more information on NRC bulletin boards call Mr. Arthur Davis,
' Systems-Integration and Development Branch, U.S. Nuclear Regulatory Commission, Washington, DC 20555, telephone (301) 415-5780; e-mail AX039nrc. gov.
\\-
List of Subjects 10 CFR Part 30 Byproduct material, Criminal penalties, Government contracts, i
Intergovernmental relations, Isotopes, Nuclear materials, Radiation
- protection,-Reporting and recordkeeping requirements.
i s
22 i
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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 inergy Act of 1954, as amendeMthe Energy Reorganization Act of 1974, a
v Prepas.4 /*
553 Vthe NRC is adopttng the following as amended l and 5 U.S.C. 552 an h
(
amendment 5to 10 CFR Parts 30 and 32.
A PART 30--RULES OF GENERAL APPLICABILITY TO DOMESTIC LICENSING OF BYPRODUCT MATERIAL 1.
The authority citation for Part 30 continues to read as follows:
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A new tm is addedito read:3 5 30.21 Radioactive drua: Capsules containina one microcurie of carbon-14 urea for "in vivo" diaanostic use.
(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 carbon-14 urea capsules, not exceeding one microcurie each, for "invivo"diagnosticus@
23
l PART 30 - RULE 4 OF GENERAL APPLICABILITY TO DOMISTIC LICENSING OF BYPRODUCT MATERIAL AUTHORITY: Secs. 81, 82, 161, 182, 183, 106, 68 Stat. 935,.948, 953, 954, 955, as amended, sec. 234, 83 Stat. 444, as amended (42 U.S.C. ll111, 2112, 2201, 2232, 2233, 2236, 2282); seco. 201, as amended., 202, 206, 88 Stat. 1242, as amended, 1244, 1:46 (42 U.S.C.
3841, 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 under sec. 184, 68 Stat. 954, as amended (42 U.S.C. 2234). Section 30.61 also issued unde
- sec. 187, 60 Stat. 955 (42 U.S.C.
2237).
N.
FEDERA1,sR GISTER CITATION c'tober 8, 1993; 58
'408 E
DESTRED AUTHOR CITATION. Yes. N EXPAND % CRIMINAL ITY PROVISIOllB JCLUDED: July 14, 982; N
30454.
s' SECTION LEVEC-AUTHORITIES TO BbRD40VED: Non N
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i (b) Any person who desires to use the capsules for research involving l
human subjects ~ shall apply for and receive a specific license pursuant to Part 35.of this' chapter.
(c) Any person who desires to manufacture, process, produce, package, i
repackage, or transfer for-commercial distribution such capsules shall apply for a specific license pursuant to i 32.21 of this chapter.
'l i
(d) Nothing in this section relieves persons from complying with applicable FDA, other Federal, and State-requirements governing use of drugs.
{
t PART 32--SPECIFIC DOMESTIC LICENSES TO MANUFACTURE OR TRANSFER CERTAIN ITEMS CONTAINING BYPRODUCT ftATERIAL i
i l
- 34. The authority citation for Part 32 continues to read as follows:
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i G31.at1 5 is added to rea4[ a-y 1.
A new l'32.21 Radioactive drua: Manufacture, distribution, and transfer of carbon-14 urea capsules not exceedina one microcurie each for "in vivo" diaanostic
-use: Reouirements for a license, (a) An. application for a specific license to manufacture, process,
- produce, package, repackage, or transfer for commercial distribution carbon-14 urea capsules not exceeding one microcurie each for "in vivo" diagnostic use, l
to persons exempt from licensing under' 5 30.21 or the equivalent regulations
.of an Agreement State will be approved if:
24 i
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PARTS 32 - SP9CIFIC DUMESTIC LICENSES TO MANUFACTURE OR TRANSFER CERTAIN ITEMS CONTAINING BYPRODUCT MATERIAL l
l i
AUTHORITY Secs. 81,.161, 182, 183, 60 Stat. 935, 948, 953, i
I
' 954, as amended (42 U.S.C. 2111,- 2201, 2232, 2233); sec. 201, 88 Stat. 1242, as amended (42 U.S.C. 5841).
j
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L REGISTER ATION:. Nove 24, 1 57 FR $50 %
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-: DESIR UTHPRITY C ON: Yes.
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t (1) The applicant satisfies the general requirements specified in 1
6 30.33 of this chapter rovided, hpweve n that the requirements I
of i 30.33(a)(2) and (3) of this chapter do not apply to an application for a license to transfer byproduct material manufactured, processed, produced, packaged, or repackaged pursuant to a license issued by an Agreement Statej j
(2) The applicant meets the requirements under i 32.72(a)(2);
(3) The applicant provides evidence that each carbon-14 urea capsule will r
not exceed one microcurie; (4) The carbon-14 urea is not contained in any food, beverage, cosmetic, drug (except as described in this section) or other commodity designed foAr 1oprest ingestion, or inhalation y orgapplication;k-e(human)behg; j
(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, product, or device intended for commercial distribution; and (6) The applicant submits copies of prototype labels and brochures and NR c.
tho*
the g.....iiih-approves wc.h labels and brochures.
(b) Nothing in this section relieves the licensee from complying with applicable FDA, other Federal, and State requirements governing drugs.
b /A%r:
3, 5,
A mu S JJ J/ a ir a/A/ 4 A'm/
- s i 32.21a Same:
Conditions of license.
Each l_icense issued under i 32.21 is subject to the following conditions:
(a)-The immediate container of the capsule (s) akibearadurable, l_egible label which: (1) Mentifies the radioisotope, the physical and-chemical form, the quantity of radioactivity of each capsule at a specific 7
date,' and (2)[ars the words " Radioactive Material."
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L (b) In addition to the-labeling information required by paragraph-(a) of i
this section, th,e}abel affixed to the immediate container, or an accompanying j
brochure,(Ad o:
(1)htatethatthecontentsareexemptfromNRCorAgreementState licensing requirements;- cm/
(2) fear the words " Radioactive Material - For "In Vivo" Diagnostic Use i
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~Only - Not for Research Involving Human Subjects - Introduction into Foods,
. Beverages,-Cosmetics, Other Drugs or Medicinals, or into Products Manufactured i
je, for Commercial Distribution is Prohibited."
Y gJ.
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._ d p/ g d Dated at Rockville, Maryland this day of
, 1997.
l oU For the Nuclear Regulatory Commission.
i t
John C._ Hoyle, Secretary of the Commission.
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- a 26
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=
=
i DRAFT REGULATbRY ANALYSIS l
FOR PROPOSED RULEMAKING
- EXEMPT DISTRIBUTION AND USE OF A RADIOACTIVE DRUG CONTAINING ONE MICROCURIE OF CARBON 14 UREA" 10 CFR PARTS 30 AND 32 1,
Backaround 1.1 Statement of the Problem 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 generallicensing and/or exemption for the commercial distribution by licensed pharmaceutical rnanufacturers of a capsule containing one micro-Curie ( Ci) 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 pept.c ulcers.
' Peptic ulcer disease is a chronic inflammatory condition of the stomach and duodenum that affects as many as 10% 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").
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 ctomach 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 non-invasively 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 m_inutes 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 breatn sample, then the patient must be infected with H. pylori.
u:.
1.2 Current NRC rieaulations In 10 CFR Part 32, " Specific Domestic Ucenses To Manufacture or Transfer Certain items Containing Byproduct Materials
- i 32.72, " Manufacture, preparation, or transfer for commercial 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 Ci of "C-urea to persons authorited pursuant te Part 35, 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 powession and use of radioactive drugs containing byproduct material.
Existing exemptions for use of byproduct materialin 6 30.14, " Exemption concentrations" and i 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 inhclation by, or application to, a human being.
Therefore, under current regulations, the "C-urea capsules must be used under a Part 35 license, even though they could be safely distributed as an exempt material to any person because the capsules present a negligible radiation risk.
N 1.3 Earlier NRC Actions A cre (fee
,aeI""3,;
Following the receipt of the petition, a " Notice of teceipt of petition for rulemaking* was published for public comment in the Federal Ren(gp_t on Dece,nger 2,1994 (59JJL /
61831). A total of 315 public comment letters 7 313 supportnes (postly form letters) and 49,3 d
2 appW lettergwem :ccer M. The two letters opposing the polition stated that (1)
( gre gro5 the product should not receive an exempt status because the uncontrolled distribution and Wt@
application of this product could lead to significant risk to the public and (2) medical uses pt should be restricted to short-lived isotopes because of disposal problems presented by long livod isotopes.
This petijion was discussed with NRC's Advisory Cornmittee on the Medical Uses of g
Isotopes (ACMul) at the October 1995 moeting. The ACMUIindicated that it endorsed the v
wide availability of this diagnostic test and that the radioactivo drug could be used under a generallicense or an exemption, whichever the NRC 4hegt to be procedurally easier.
<^
- y el e. W r a c g
A rulemaking plan hos-beeEprepared. Af ter receiving comments from Agreement States on the draft rulemaking plan, the Comrnission approved a final rulemaking plan to develop a propused rule to amend 10 CFR Parts 30 and 32 allowing the distribution of the Carbon-14 capsules as an exempt material to any person.
2
2.
Obiective L
The objective of the rulemakirsg is to b) amend 10 CFR Part 32 to permit the manufacture and initial distribution of "C-urea capsules as an exempt material and 1/') amend 10 CFR Part 30 to permit any person to receive the capsules.
3.
Afternatives Three alternatives have been considered in the regulatory analysis: 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 alternative, only physicians who are authorized users under Part 35 would be allowed to possess and administer the "C-urea 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 Maiis capsules because of the requirement for training and experience and the associated costs of obtaining and maintaining a Part 35 license. Alternatively, physicians who are not authorized users could refer their patients to physicians who are authorized users to undergo the diagnostic test, but this would add expense, inconvenience, and delay to an otherwise straight-forward procedure.
Undor the second alternative, Parts 30 and 32 would be amended to permit the manufacture and initial distribution of the capsules as an exemnt material to any person.
The NRC has determined that the radioactive component of this drug pr.esents a minimal radiation risk and, therefore, regulatory control of the *in vivo" diagnostic use of capsules for radiation safety is not necessary.
Under the third alternative,10 CFR Part 35 would be amended to permit any physician to receive and use the capsules under a generallicense. The health and safety concerns for this altomative are the same as the Alternative 2. However,if this alternative were adopted, there could be a burden to those Agreement States that normally assess licensing or red stration fees for generallicense holders. A burden could also be imposed on general i
licenseeslocated in the Agreement States.
4.
Value-Imoact Analvgis 4.1 Tbo Petitioner's Assessment in the letters dated August 23,1994 and November 30,1994, the petitioner stated, respectivaly:
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),
3
... The test is 95 percent accurate and quito inexpensive because of its simplicity.
The test would permit doctors to determino easily whether or not ulcer patients have been cured of their infection. By providing the public with an inexpensive, easily accessible diagnostic test, more individuals would be accurately diagnosed and trea%d for their H. pylori infection. This would save the United States an estimated
$500 million per annum over conventional therapy.
The petitioner estimates annual benefits to be on the order of $500 million/ year. This assumes 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 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 administaring 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 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-Moc"s estimate did not allow for the substitution of other non invasive tests (e.g.,
scrological test for igg antibodios to H. pylori antigens) for both endoscopy and "C-ures tests. In addition, wiro service articles dated September 19,1996, stated that the FDA has approved a non radiological diagr.ostic breath test using "C for detecting the presence of H. pyloriinfections.
4.2 The NRC's Asigningni (a)
Cost Savinas Associated with Amendments to 10 CFR Part 30 The valuo impact analysis focuses on the incremontal benefits of granting relief consistent with Attornative 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 tasts. not unregulated "C-urea breath tests and endoscopies or other non invasive tests. F< > the purposes of this regulatory analysis, the NRC assumes that the same number of W,sh tests (i.e., 000 000 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. 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. This appears fully consistent with standard medical practico, whereby patients are referred routinely to laboratories and specialists for a wide array of tests and procedures.
The benefits of adopting the petition accrue as a result of reduced patient cost and reduced healtipare cost resulting from the elimination of the need for referrals from a physician who is not an authorized user (e.g., gastrointestinal specialist). There would also be some regulatory savings because the NRC would not have to expend resources 4
reviewing new applications for specific medica [use licenses. However, these savings would be small because the NRC expects that1hw physicians who are not authorized users would apply for a specific NRC licenso for use of this one product.
The benefit calculation is based on the assumption that as a result of the proposed action, 600,000 patients would receive the "C breath test from a significant portion of the 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 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 h'gh as approximately $20 million if there was a complete shift of the administration of the tests from physicians who are authorized users fi.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 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 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 avorted administrativo expenses (administrative costs incurred with medical referral) would be:
600,000 patients / year x $19.00/ patient = $11.4 million/ year Assuming $19.00 (administrative cost / patient) as the differential between the cost of an office visit to a general family practico physician by an established 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 uroa breath test would most likely be a new patient for the authorized user.
Total Savings:
$10.5 million/ year + $11.4 million/ year = $ 21.9 million/vear 200.000 or 400,000 of the 600,000 tests were performed by a Alternatively,if only 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 Alternative'3 were adopted,it Ci "C urea for would permit any physician to receive and uso capsules containing 1 human use under a generallicense. The health and safety concerns for this alternative are 5
r j
the same as Alternative 2. However, the adoption of Alternative 3 could add unnecessary burden to those Agreement States and Agreement State licensees in States that assess Alternative 2 also imposes licensing or reglettation feas for generallicense holders.
incremental cost burden for manufactures or initial distributors of the capsules because ld be j
. they would need obtain an exempt distribution license. Each initial application wou l
estimated to take about 40 hours4.62963e-4 days <br />0.0111 hours <br />6.613757e-5 weeks <br />1.522e-5 months <br /> and each license renewal (once in every five years) would take about 10 hours1.157407e-4 days <br />0.00278 hours <br />1.653439e-5 weeks <br />3.805e-6 months <br />. Thus, for tne first five year period, the average burden per l
licensee would be about 10 hours1.157407e-4 days <br />0.00278 hours <br />1.653439e-5 weeks <br />3.805e-6 months <br /> per year. Assuming a labor rate of $123 per hour, the total burden would be about $1,230 per year oer licensee.
(b)
Health and Safety Effects For the purposes of this regulatory analysis, the NRC assumes that the same number of l
800,000 tests) will be administered regardle.ss of the level of NRC i
breath tests (i.e.,
regulator / control. This view is predicated on the belief that each pt./sician'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 i
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:
i Scenario Maximum Exposed Routine Exposure Individual Worker administering "C-Full time worker,8,000 Less than 0.7 mrem /y urea breath tests patients /yr Routine exposure of Patient tests negative 0.38 mrem / capsule patients from "C urea breath tests Patient tests positive 0
3 mrem / capsule Release of 150 pCi of "CO, Member of public in the Less than 0.0002 mrem 2
into administration area administration area Rupture of a capsule Skin (100 cm') exposed for 5.8 mrad skin dose causing skin contamin-one hour prior to washing 0.075 Ci skin absorption 0.029 mrem CEDE ation of worker or patient Furthermore, the NRC concluded that the impacts associated with any releases of 3C to
= the surrounding environment are expected to be very small and the expected risks aro minimal L 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 bieath tests), which is in addition to the huga inventory of about 240 million curies in the world's oceans. The "C released e
into the atmosphere from the use of this test would rnix with the global inventory and 6
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expose the public and other biotic components of the envifonment to "C intakes itam J
inhalation, drinking water, and all possible food pathways in the same mannor as naturally occurring "C. The current world inventory of naturally occurring "C rewits 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 be administered annually (see the REGULATORY 4
ANALYSIS section below) would result in an additional average annual dose of 2 X 10 miem. 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 puuic, or the 4 mrem / year EPA limit for public drinking water, in a total population of about 260 million peop'e in the U.S., the collective annual dose 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 I
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.
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 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 collectivo dose to the U.S. population from naturally occurring "C of over 300,000 person rem, and about 78,000,000 person rem from all naturally occuttin0 radiatiors. Clearly, an increaso of a few person rem will not significantly change these exposures, and thas there is no expected impact from the widespread use of the breath test on the entire U.S. population.
As a result of this analysis, the NRC concludes that Altomatives 2 and 3 are clearly preferable to the no action alternative. 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 Altomotive 2 because it would avoid the unnecessary cost burden to some Agreement States and their generallicensees.
Therefore, by adopting the proposed rule, the cost savings would be maximized without any measuroble adverse effect on public health and safety.
5.
Decision Rationata Based on the above analysis, the NRC believes that the proposed rule,if adopted, would provide manuf acturers or initial distributors to distribute Carbon-14 urea capsules as exempt material to any person because the radiological risk from such distribution would be negligible and the savings to patients would be significant, in addition, the NRC believes that the receipt and use of the drug are the responsibilities of other Federal and
' State agencies (e.g., Food and Drug Administration and the State Boards of Pharmacy) as is the case for other drugs that do not contain byproduct materials.
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i Draft Environmental Assessment For Proposed Amendments to 10 CfR Parts 30 and 31
' Distribution of a Radioactive Drug Containing One Microcurie of l
Carbon-14 Urea as Exempt Material for "In Vivo" Diagnostic Testing" l
1.
Introduction And Statement of the Proposed Action 4
The Nuclear Regulatory Commission (NRC) is proposing to amend its regulations j
to allow NRC licensees to distribute a radioactive drug containing one The l
microcurie of carbon-14 urea to any person for "in vivo" diagnostic use.
NRC has determined that the radioactive component of such capsules presents a minimal radiation risk and, therefore, regulatory control of the drug for If adopted, this amendment would make the a
radiation safety is not necessary.
This action is
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drug more widely available, thus reducing costs to patients.
being taken in response to a petition for rulemaking (PRM-35-12) submitted by Tri-Mad Specialties, Inc.
2.
Need for the Amendments The proposed amendments have been developed to grant the petition for The Commission believes that the proposed rule, if adopted, would rulemaking, provide manufacturers or initial distributors to distribute Carbon-14 urea capsules as exempt material to any person because the radiological risk from such distribution would be negligible and the savings to patients would be In addition, the Commission recognizes that the receipt and use significant.
of the drug are the responsibilities of other Federal and State agencies (e.g., food and Drug Administration and the State Boards of Pharmacy) as is the case for other drugs that do not contain byproduct materials.
'3.
Alternatives Considered c
.Three alternatives have been considered for the petition: maintain the status quo, permit the distribution of the capsules as exempt material, and permit the distribution of the capsules to general licensees.
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- Under the first alternative, only physicians who are authorized users under Part 35 would be allowed to possess and administer the "C-urea test. Any i
physician could apply to become an authorized user. However, the NRC expects 1
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 j
associated costs 6 obtaining and maintaining a Part 35 license.
I Alternatively, physicians who are not authorized users could refer their j
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- patients to physicians who are authorized users to undergo the diagnostic i
test, but this would add expense, inconvenience, and delay to an otherwise straight-forward procedure.
Under the second alternative Parts 30 and 32 would be amended to permit the
- manufacture and initial distr %ution of the capsules as an exempt material to any person. - The NRC has determined that the radioactive component of this drug presents a minimal radiation risk and, therefore, regulatory control of the "in vivo diagnostic use of capsules for radiation safety is not necessary.
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t Under the third alternative,10 CFR Part 35 would be amended to permit any The health physician to receive and use the capsules under a general license.
and safety concerns for this alternative are the same as the Alternative 2.
However, if this alternative were adopted, there could be a burden to those l
i Agreement-States that normally assess licensing or registration fees for general license holders.
A burden could also be imposed on general licensees located in the Agreement States.
Based on the Draft Regulatory Analysis prepared for this proposed rule, the l
Commission concludes that Alternatives 2 and 3 are clearly preferable to the no action alternative. This is because either of the two alternatives will result in significant cost savings with no measurable adverse effect on health Land safety.
Furthermore,. the NRC's recommended option is Alternative 2 because it would avoid'the unnecessary cost burden to some Agreement States
- and their general licensees.
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4.
Impact on the Public and the Environment The proposed amendments would have no significant impact on the public and the environment.
The NRC assumes that the same number of breath 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.
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, there would be no change in radiation exposures to the workers and patients when compared the status quo to the proposed action.
Similarly, there would be no change in impact to the environment and no non-radiological impacts because the Commission assumes that the sv.ne number of tests will be administered regardless which alternative is adopted.
5.
List of Agencies 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 Federal Register on December 2, 1994 (59 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 on the Medical Uses of Isotopes ACMUI) at the October 1995 meeting.
Furthermore, a draft rulemaking plan has been forwarded to 29 Agreement States for comments.
6.
Finding of No Significant impacts The Commission has determined under the National Environmental Policy Act of 1969, as amended, and the Commission's regulations in Subpart K of 10 CFR Part 51, that the proposed amendments, if adopted, would not be a major Federal action significantly affecting the quality of the human environment, and therefore an environmental impact statement is not required.
The proposed rule would permit the manufacture and initial distribution of "C-urer capsules an exempt material and to permit any person may receive the capsules.
3 l
The Commission believes that the radioactive component of this drug presents a minimal radiation risk and, therefore, regulatory control of the "in vivo" it is diagnostic use of the capsules for radiation safety is not necessary, expected that this proposed rule, if adopted, would not cause any significant j
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 would be no non radiological impacts if the proposed rule is adopted.
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