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NUCLEAR REGULATORY COMMISSION t
WASHINGTON, D.C. 2055fM201
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February 28, 1997 MEMORANDUM TO: Carl J. Paperiello, Director Office of Nuclear Material Safety and Safeguards William J. Olmstead, Associate General Counsel for Licensing and Regulation Office of the General Counsel Anthony J. Galante, Chief information Officer Renald M. Scroggins Acting Chief Financial Officer Richard L. Bangart, Director Office of State Programs James Lieberman, Director Office of Enforcement Brenda Jo. Shelton, Chief Information and Records Management Branch Office of Information Resources Management David L. Meyer, Chief Rules Review and Directives Branch Division of Freedom of Information and Publication Services Office of Administration FROVI:
David L. Morrison, Director
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Office of Nuclear Regulatory escatch
SUBJECT:
PROPOSED RULE: EXEMPT DISTRIBUTION OF A RADIOACTIVE DRUG CONTAINING ONE MICROCURIE OF CARBON-14 UREA (PARTS 30 AND 32)
Your concurrence is requested on the attached Commission paper with enclosures, including the Federal Register notice. This rulemaking action has been taken in response to a petition for rulemaking submitted by Tri-Med Specialties, Inc. The final rulemaking plan was submitted to the Commission on February 7,1997.
It is requested that NMSS coordinate with the Regions on this proposed rule.
9001140122 900109 PDR PR i
30 62FR32552 PDR g
C. J. Paperiello, et al 2
The following is a summary of this request:
1.
Title:
Exempt Distribution of a Radioactive Drug Containing One Microcurie of Carbon-14 Urea 2 RES Task Leader: Sam Jones (415-6198)
- 3. Cognizant Individual: NMSS - D. B. Howe OSP Lloyd Bolling OGC
- Marjorie Rothschild
- 4. Compatibility for Agreement States: Yes
- 5. Requested Action: Concurrence 6.- Requested Completion Date: Two weeks after the date of this memorandum
- 7. Resources and Coordination: Estimated resources to develop this rule is 0.3 FTE.
Copies of this concurrence package have been forwarded to the Office of the Controller, ACRS, ACNW, and the IG for information.
Attachment:
Commission paper w/encls.
cc: w/att.
R. Scroggins, OC H. T. Bell, IG J. Larkins, ACRS & ACNW
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COMMISSION PAPER s
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The Commissioners FROff:
L. Joseph Callan, Executive Director for Operations SUBJECT.:
PROPOSED RULE: EXEMPT DISTRIBUTICN 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:
By negative consent, 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 rule plan was submitted to the Commission on February 7,1997 as SECY-97-031.
DISCUSSIGN:
Part 32 would be amended to add a new section (S 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 S 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 (S 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 i
I i
The Commissioners 2
of carbon-14, for "in vivo" diagnostic use, without a license. As a resul;, NRC regulations would permit the drug to be distributed 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 research involving human subjects would be required to apply for and receive a specific license pursuant to Part 35.
COORDINATIOJ:
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 rulemaking. The Office of the Chief Information Officer concurs that there will be no information technology impacts.
RECOMMENDATION:
That the Commission:
1.
Approve for publication in the Federal Reaister the proposed amendments to 10 CFR 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.
b.
That the Chief Counsel for Advocacy of the Small Business Administration will be 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 for 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).
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The Commissioners 3
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That resources to complete and implement this rulemaking are included in the current budget.
L. Joseph Callan Executive Director for Operations
Enclosures:
As stated (5)
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1 The Commissioners 3
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That resources to complete and implement this ruIemaking are induded in the current budget.
L. Joseph Callan Executive Director for Operations
Enclosures:
- As stated (5)
Distributlo' n:
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: 0:\\TROTTIER\\C14CP.WPD
' To receive a copy of this document, indicate in the box: "C" = Oopy without attachment / enclosure "E" = Copy with attachmentlenclosure ' "N" = No copy "See previous concurrence OFFICE DRA/RPHEB DRA/RPHEB l
D/DRA NMSS l
OSP CTrottier g MMorris14 CJPaperiello RLBangart NAME SJones*
DATE 02l27/97 02#td7 02MQ97 1 197
/ 19 7 mummmmmmemammmmmmmmmmmmmmenum-uma mammuummmmmmmeimmunumanumammmame umasummmmmmmmausimuss OFFICE OE OGC ADM IRM OClOCFO NAME JLieberman WJOlmstead DMeyer BJShelton RScroggins 4,__
DATE-
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uma mumummmmmmmmum umm OFFICE-ClO -
Dl8153,a L EDO-NAME AJGalante fn-LJCallan
_DATE
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/ 19 7-OFFICIAL RECORD COPY (RES File Code) RES I'S 3
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1 ENCLOSURE 1 FEDERAL REGISTER NOTICE l
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[7590-01-P]
NUCLEAR REGULATORY COMMISSION 10 CFR Parts 30 and 32 RIN:
Exempt Distribution of a Radioactive Drug Containing One Microcurie of Carbon-14 Urea AGENCY: Nuclear Regulatory Commission.
AClION:
Proposed rule.
SUMMARY
The Nuclear Regulatory Commission (NRC) is proposing to amend 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 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.
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.
t ADDRESSES:
Send comments to:
Secretary, U.S. Nuclear Regulatory Comission,-
-Washington,- DC 20555-0001,- Attention:- Docketing and Service Branch.
- Hand deliver coments to:- 11555 Rockville Pike, _ Rockville, Maryland, 9
between 7:45 am and 4:15 pm on Federal workdays.
The public may examine coments received,- the environmental assessment:
and finding af 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
.Research, U.S. Nuclear Regulatory Comission, Washington, DC 20553-0001, telephone (301) 415-6198 or e-mail at SZJ0nrc. gov.
SUPPLEMENTARY INFORMATION:
l Background.
II, Discussion.
III. Sumary of Proposed Amendments.
IV.
- Agreement State Lompatibility, i-V.
Finding of No Significant Environmental Impact:
Availability.
VI.-. Paper Work l Reduction Act Statement,
_VII. : Regulatory. Analysis.
VIII. Regulatory Flexibility Certification.
I X.1 Backfit Analysis.
X.-
Electronic Access.
1 L
-; X I.
List of Subjects.
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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 aliow for the general licensing and/or exem!, tion for the commercial distribution by licensed pharmaceutical manufacturers of a capsule containing one micro-Curie (yCi) 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 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 antibiotics, doctors can now cure most ulcer problems.
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- It-is.therefore necessary;to detect the_~ presence of H. pylori-ibacteria iniulcer patients 1so that;the new treatmentican,be given appropriately.:. In;the;past, this was done by-aLgastroenterologist
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'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 0
labeled CO, which is expired in 'the breath.- To do the test, a
- doctor _ asks'the: patient to swallow the capsule with 30 mls 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, mo're' than twice background is present in the breath sample, then the patient must be infected with H. pylori.
' Public Comments on the Petition d
Following the receipt of-the petition, a " Notice-of receipt of petition for.rulemaking" was published for public comment-in the Federal _P,egister 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. The two" letters -opposing the petition' stated that- (1) the product should not receive Anrexempt status:because the uncontrolled-distribution and-application
, of;this product could lead to significant risk to the public and (2) medical usesfshould be restricted to short-lived isotopes because of disposal problems e
_ presented by long-lived isotopes.
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.The NRC has considered the two opposing coments and has determined _that:L J
(1) the resulting radiation dose from the capsules-to workers, patients,
- and the public-is very low (See' Regulatory Analysis); and
-(2) -the: impacts associated with any releases of-"C-to the surrounding environment are expected-to be very small and the expected risks-are minimal (See Environmental Assessment).
Similarly, the small doses-from naturally occurring "C are of little significance to human health and the environment.
Also, the Comission concludes that the potential long-term impacts from-widespread releases of the long-lived "C (5,730-year radiological half-life) i from breath tests'are insignificant.
Coments' from Advisory Comittee on the Medical Uses of Isotopes This petition was discussed with NRC's Advisory Comittee on the Medical-Uses of-Isotopes (ACMUI) t< the October 1995 meeting.
The ACMUI indicated that it endorsed the wide as
, #ility of this diagnostic test and that the radioactive drug could-be used under a general license or an exemption,
.whichever the NRC thought to be procedurally easier, i
II.
Discussion Regulatory Issue The regulatory issue-is whether capsules containing one microcurie of
. carbon-14 urea 1 present. a sufficiently small _ radiation risk that they can be safely distributed to and used by physicians (or other persons) who are not
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- authorized users" under Part 35, 5
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Current NRC Regulations for the Manufacture and Commercial
- Distributir.n of Radioactive. Drugs Containing Byproduct Material l
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NRC regulations _in 10 (?R 32.72 address the manufacture, preparation, or transfer for commercial distribution of radioactive drugs containing. byproduct material. This regulation requires manufacturers or. preparers of.adioactive-drugs for commercial distribution to be:-
(1) registered _ or licensed with the Food and Drug Administration (FDA) as Ja~ drug manufacturer;
-(2) registered or licensed with' a state agency as a drug manufacturer; (3) licensed as pharmacy by.a State Board of Pharmacy; or (4) operating as a nuclear pharmacy within a Federal medical institution.
1These facilities haveLa specific license with the NRC. Under the specific license, the manufacturer or. pharmacy can distribute radioactive i
drugs only to persons authorized pursuant to Part 35, " Medical Use of Byproduct Material."
k Current NRC Regulations for the Medical Use of Radioactive Drugs
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Containing Byproduct Material Currently, 10 CFR Part 35 only permits physicians, who are authorized l users (1.e., physicians who meet certain training and experience criteria regarding the safe use of radioactive drugs) or person working under-the Lsupervision of an authorized user to-use radioactive drugs for medical use.
The Agreement; States have similar requirements.
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- Current NRC Regulations'on Exemptions.from Licensing j
-i 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 l~ 30.14, " Exempt concentrations" and i 30.18,
" Exempt _ quantities." These two broad materials exerrptions specifically ixclude the _ transfer of byproduct material contained in any food, beverage,
' cosmetic, drug, or any. product designed for ingestion or inhalation by, or
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i application to, a human being. - (In-the case of exempt quantities, this prohibiti.on-is contained in i 32.18, " Manufacture, _ distribution and transfer
.of_ exempt quantities of byproduct material; Requirements -for a license,"
paragraph 32.18(b)).
Capsules containing one microcurie of carbon-14 urea would not qualify as an " exempt quantity" in accordance.130.18 because of their intended use (as a
- drug) even though they contain a smaller quantity than that set-forth in l 30.71,: Schedule B.
Such a use is outside the intent of the exemption in l'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' licensing, for "in vivo" diagnostic use.
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1 Proposed Amendments and Rationale for Permitting the Distribution -
of the' Capsules to Persons Exempt;from-Licensing lProposedAmendmentto10CFR-Part32' 4
Th'e regulations in-10 CFR Part 32 would be amended to add a new'l 32.21,-
to provide requirements for a specific' license to manufacture, process, produce, package,-repackage, or transfer capsules containing one microcurie of
' carbon-14 urea, as a radioactive ~ drug, to be distributed to any person for_"in
= vivo" diagnostic use. NRC regulations would include 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-governing the manufacture and distribution of drugs.
Rationale LThe Commission had decided t'-at the manufacture or preparation of capsules 'containing on microcurie of ' carbon-14 urea should continue to be prepared by persons who meet the current NRC regulations to manufacture and commercially distribute radioactive drugs. The Commission takes this position
-because regulatory control-is-needed to provide high confidence that the drug
-contains'only:one microcurie of carbon-14 ure'a and-does not contain any other
- . radioactive contaminants.
f a
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 i 30.21, to permit any person to receive, possess, use, own, transfer, or acquire for "in vivo" diagnostic use, capsules containing one microcurie of carbon-14 urea
. without.a license. -The exemption would prohibit research irvolving humans subjects. NRC regulations would include a reminder that persons raceiving the
' drug would not-be relieved from other Federal or State law governing drugs.
Rationale The Commission has determined that the capsules present no'significant radiological safety or environmental risk, and it is not necessary to regulate
,the use of this drug for its radioactive component. Therefore, the Commission 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 drug should be distributed to any person who is permitted to receive and use the drug under the appropriate Federal or State law governing drugs.
The phrase "'in vivo' diagnostic use" is being used in 5 30.21 instead of
" medical.use" for two reasons.
First, the term " medical use" has a specific meaning and is defined in 5 35.2 to mean "the intentional internal or external l administration of byproduct material or the radiation therefrom to patients or 9
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human research~ subjects under the superYision of an authorized user." This-term would be-inappropriate because:=
i (1) the drug could be administered to patients'by physicians or other persons who are-_not: authorized users; and.
.(2) " medical-use" includes the administration of the drug to.a human research subject, which would be prohibited by this-rulemaking..
Effects of the Proposed Amendments 4
.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 State license. Because the receipt and t:n of the drug would be exempt from
- NRC licensing, Agreement-States.will need to make appropriate provisions in
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th'eir regulations to recognize the exempt distribution of-the drug, for "in vivo" diagnostic use. Thus, after the manufacture and distribution of the drug, NRC and the Agreement States would not regulate the drug for "in vivo" 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 drtg for "in vivo" diagnostic use, after its distribution,
'would be left to other. Federal or State organizations _with responsibilities 1
Efor regulating _ the _use of drugs. NRC would regulate the use of the drug for
^ research1 involving human subjects under a specific NRC Part 35 license for
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.zs III.. Summary of Proposed _ Amendments o
Manufacturer-and Distributors A new section would be added to 10 CFR Part 32 to permit the distribution iof the drug to~ persons whofare 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" diaanostic
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use:-Reauirements for a license
-Section-32.21. Paraaraoh (a)
Through this paragraph the Commission would allow the drug to be
-distributed to persons' exempt from licensing.
Section 32.21. Paracraph (a). Item (1)
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
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and use of byproduct material.
Section 32.21. Paraaraoh (a),- Item'(2)-
To assure that the' capsules contain no more one microcurie of carbon-14
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'and present no other_ radiological. risks.: the Commission'would require that the persons! manufacturing and/or-distributing' the capsules for "in vivo"
? diagnostic use must also meet the requirements lof i 32.72(a)(2).
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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 pharmacy by a State Board of Pharmacy; or (4) operating as t nuclear pharmacy within a Federal medical institution.
Section 32.21, paragraph (a). Item (3)
Applicants would be required to provide evidence that each carbon-14 urea capsule will not exceed one microcurie.
The Commission's evaluation that the capsules would not result in significant radiation risks was based on the capsules containing one microcurie of carbo 1-14 urea.
Therefore, applicants must demonstrate that the activity of each carbon-14 capsule will not exceed one microcurie.
Section 32.21. Paragraph (a), item (4)
The Commission would prohibit carbon-14 urea from being contained in any food, beverage, cosmetic, drug or other commodity designed for ingestion, or inhalation by or 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.
Section 32.21. Paragraph (a). Item (5)
Again, because the exempt distribution of this drug has only been evaluated for "in vivo" diagnostic use in the form of a capsule containing one 12
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- microcurie of carbon-14: urea, the Commission will prohibit 1 incorporation of-thecapsulessinto:anyLmanufacturedlor.assembledcommodity, product;~ordevice
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Lintended for: commercial distribution.- Further,- evenithougn the drug is being distributed Eto persons. exempt from licensing,-the Commission will require the -
carbon-14 urea to'be identified-as radioactive,-because the_ drug is being usedl
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forLits radioactive content, and therefore, end user should be provided with
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information that the drug contains a radioactive naterial.
?Section 32.21. Paraaraoh (a). Item (6)
As with any product approved for distribution to persons exempt from~
licerising, the Commission would. require persons who apply for a license to manufacture or. distribute'such capsules tu st.tiit copies of prototype labels or brochures for Commission approval. This ill allow the NRC to confirm that the: labels Jor brochures meet the requirements of 5 32.21a (a) and (b).
Section 32.21, paragraph (b) iThrough this paragraph the Commission declares that nothing in these regulations relieves licensees or liconse applicants from complying with applicable FDA, other Federal,-and-State requirements governing manufacturing _
and distribution'of drugs.
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-Section 32.21a Same: Conditions of license In this section.the Commission states the conditions for a license to Ldistribute;the capsules to persons exempt from licensing.
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Paragraph 32.21a(a)
To inform the end user of the identity of the radioisotope,.the physical chemical form, and the dosage of radioactivity, the Commission would arc require that the immediate container of each ccpsule or capsules shall bear a durable, leg'.ble label which:
(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 Meterial."
The date requirement is consistent with labeling requirements for other radioactive drugs with a half life of greater that 100 days.
Paragraph 32.21a(b)
Consistent with the intended use of the capsules, the label affixed to the immediate container, or an accompanying brochure, shall:
(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 - Not for Research Involving Human Subjects - Introduction into Fcods, Beverages, Cosmetics, Other Drugs or Medicinals, or into Products Manufactured for Commercial Distribution is Prohibited."
"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.
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-s Section 30.21 Radioactive drua: Capsules containing one microcurie of garbon-14 urea' for "in vivo" diagnostic use would be added to permit any
, p.irson to receive the capsules.
Paragraph 30.21(a).
The Commission would exempt any person from the requirements for i license to receive, possess, use, transfer, een, or acquire capsules conte ning one microcurie of-carbon-14 urea for "in vivo" diagnostic purposes.
_ Paragraph 30.21(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.
Paragraph 30.21(c)
This paragraph would specify that a specific license is needed to manufacture, process, produce, package, repackage or transfer for commercial distribution such capsules.
Paragraph 30.21(d)
In this paragraph the Commission declares that nothing in these regulations relieves end users from complying with applicable FDA, othe;
-- Federal, or State requirements governing the administration and use of drugs.
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x IV. - Agreement State' Compatibility-T
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- Under the = Atomic Energy _ Act, certain regulatory functions;are reserved to -
ithe NRC. Among these:are the oistribution of products to persons exempt from v
licensing,~ as discussed-in 10 CFR Part1150. Hence, the propcsed rule,.if -
adopted would be a Division 4 matter of compatibility, with. regard to the-
- manufacture and distribution of the capsules _(10 CFR Part 32), and a Division
'l matter of compatibility with regard to possession and use-(10 CFR Part 30).
- Therefore, the Agreement States will need to make appropriate' provisions in I
itheirl regulations to allow any person to receive capsules containing one -
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microcurie oEcarbon-14 urea for "in vivo" diagnostic use without need for a
, license.
V.
Finding of No Significant Environmental Impact: Availability The Commission has determined under the National Environmental Policy Act of 1969, as amended, and the Commission's regulations in Subpart A of 1.0 CFR Part 51, _ that-the proposed amendments, if adopted, would not be a major Federal action significantly affecting the. quality of the human environment, g
and therefore an environmental: impact statement. is not required. The proposed
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rule would estchlish requirements for the manufacture-and commercial-
-distribution of "C-urea capsules to persons exempt from licensing and.
esiabli5}i regulations to permit any person _ to r_eceive the capsules without an'
~NRC license.s-The Commission believes thet the radioactive component of this p
drugLpresents nojsignificant radiation' risk and, _therefore, regulatory control
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-o-f the "in vivd" diagnosti.c use of the-capsules-for radiation safety is not 4
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4 necessery.
It is expected that this proposed rule, if adopted, would not cause any rignificant 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.
L The draft environmental assessment and finding of no significant impact on wnich this determination is based is available for inspection at the NRC k
Public Document Room, 2120 L Street NW. (Lower Level), Washington, DC.
Single copies of the draft environmental assessment and the finding of' no significant impact are available from Sam Jones, Of fice of Nuclear Regulatory Research,
[
U.S. Nuclear Regulatory Commission, Washington, DC 20555 3001, telephone (301) 415-6198 or e-mail at SZJ@nrc. gov.
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VI.
Paperwork Reduction Act Statement 1his proposed rule amend information collection requirements that are subject to the Paper Work Reduction Act of 1995 (44 U.S.C. 3501 et seq.).
This rulo has been submii.ted to the Ofilce of Management and Budget for review and approval of the information collection requirements.
The public reporting burden for this collection 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 colleci. ion of information. The U.S. Nuclear Regulatory Commission is seeking public comment 17
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1 on'the potential impact of the collection of information contained in the proposed rule and on the following issues:
-l 1.
!$ the proposed collection of information necessary for the proper performance of the functions of the NRC, including whether the information willhavepracticaluillity?
I 2.
Is the estimate of the burden correct?
- 3. 'Is there a way to enhance tne quality, utility, and the clarity of
. the information to' be collected?
,\\
4.
How can the burden of the collection of information be minimized, i
including the use of automated collection techniques?
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 ';y Internet Electronic mail at BJS19NRC. GOV; and to the Desk Officer, Office of Information and Regulai *y Affairs, NE08-10202, (3150-0017,
-0020 -0011, -0009, and -01320, Office of Management and Budget, Washington, DC 20503,
. Comments to OMB on the Collections of information or on the above issues i
l should be submitted by (insert date 30 days after publication in the Federal Register). Comments received after this_date will be considered if it is practica1 to do so, but assurance of consideration cannot be given to comments J
~
3
! received after this date.
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0 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.
VII.
Regulatory Analysis The NRC has prepared a regulatory analysis for the proposed amendment.
The iThe analysis examines the benefits and impacts considered by the NRC.
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 SZJ9nrc. gov.
VIII. 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. Any small entity subject
' to this regulation which determines that, because-of its size, it is likely to bear-a disproportionate adverse economic impact should notify the Commission of this in a comment that_ indicates the following:
19 l
(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 l
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 impact 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 Certification 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).
X.
Electronic Access Comments may be submitted electronically, in either ASCII text or Wordperfect format. (version 5.1 or later), by calling the NRC Electronic Bulletin Board on fedWorld.
The bulletin board may be accessed using a 20 1
- 1
- t personal computer, a modem, and one of the commonly available communications j
- soft.nre packages, or'directly via Internet.
If using a personal computer and modem, the NRC subsystem on FedWorld can-j be accessed directly by dialing the toll free number: 1-800-303-9672.
Communication >aftware parameters should be set'as follows: parity to none, I
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 j
. accessed by selecting the " Rules Menu" option from the "NRC Main Menu." for further information about options available for NRC at FedWorld, consult the j
" Help /Information Center" from the "NRC Main Menu." Users will find the
+
"FedWorld Online User's Guides" particularly helpful.
Many NRC subsystems and l
i databases also have a " Help /information Center" option that is tailored to the particular subsystem.
.The NRC subsystem on FedWorld can also be accessed by a direct dial phone number for the main FedWorld BBS, 703-321-3339, or by using Telnet via i
Internet, fedworld. gov.
If using 703-321-3339 to contact FedWorld, the NRC subsy tem will be accessed from the main FedWorld' menu by selecting the 4
" Regulatory, Government Administration and State Systems," then selecting i
" Regulatory Information Mall." At that point, a menu will be displayed that l
hat an eption "U.S. Nuclear Regulatory Commission" that will take you to the NRC Online mair, 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 main menu, you may return to FedWorld by selecting the " Return to FedWorld" option 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.
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if you contact FedWorld using Telnet, you will see the NRC' area and j
. menus, including the Rules menu. Although you will be able to download documents and leave messages, you will not be able to write comments or upload W
files (comments).
If you contact FedWorld using FTP, all. files can be l,
accessed and downloaded but uploads are not allowed; all you will see is a f
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 n.fj trovides access for downloading files and does not display the NRC Rul e s Ar.~,.._
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
!AXD39nrc. gov.
XI.
List of Subjects 10 CFR Part 30
. Byproduct material, Criminal penalties. Government contracts, Intergovernmental relations, Isotopes, Nuclear materials, Radiation protection, Reporting and recordkeeping requirements.
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0 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 amendment to 10 CFR Parts 30 and 32.
PART 30--RULES Of GENERAL APPLICABILITY TO DOMESTIC LICENSING 0F BYPRODUCT MATERIAL 1.
The authority citation for Part 30 continues to read as follows:
- TO BE ADDED***
2.
A new section is added to read:
i 30.21 Radioactive drua: Caosules containina one microcurie of carbon-14 urea fgr "in vivo" diagnostic 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 ' f this chapter o
provided that such person receives, possesses, uses, transfers, owns, or acquires carbon-14 urea capsules, not exceeding one microcurie each, for "in vivo" diagnostic use; 23
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(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.
(c) Any person who desires to manufacture, process, produce, package, repackage, or transfer for commercial distribution such capsules shall apply
,for a specific license pursuant to 6 32.21 of this chapter.
(d) Nothing in this section relieves _ persons from complying with applicable FDA, other Federal,- and State requirements governing use of drugs.
PART 32--SPECIFIC DOMESTIC LICENSES TO MANUFACTURE OR TRANSFER CERTAIN ITEMS CONTAINING BYPRODUCT MATERIAL 1.
The authority citation for_Part 32 continues to read as follows:
C
- TO BE ADDED***
2.
A new section is added to read:
i 32.21 Radioactive drua: Manufacture, distribution and transfer of carbon-14 urea capsules not exceedina one microcurie each for "in vivo" diaanostic use: Reauirements 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.
to persons' exempt from licensing under i 30.21 or the equivalent regulations of an Agreement State will be approved if:
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(1) The uplicant satisfies the general requirements specified in paragraphs i 30.33 of this chapter:
Provided, however, that the requirements of i 30.33(a)(2) and (3) of this chapter do not apply to an application for a licente to transfer byproduct material manufactured, processed, produced, packaged, or repackaged pursuant to a license issued by an Agreement State.
(2) The applicant meets the requirements under i 32.72(a)(2);
(3) The applicant provides evidence that each carbon-14 urea capsule will 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 for ingestion, or inhalation by or application to a human being; (5) The carbon-14 urea is ':. ;he form of a capsule, identified as radioactive, and to be usei 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 Commission approves such labels and brochures.
(b) Nothing in this section relieves the licensee from complying with applicable FDA, other Federal, and State requirements governing drugs.
I 32.21a Same:
Conditions of license.
Each license issued under i 32.21 is subject to the following conditions:
(a) The immediate container of the capsule (s) shall 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."
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-(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, shall also:-
(1) state that the contents-are exempt from NRC or Agreement State ifcensing requirements (2) bear the words " Radioactive Material - For "In Vivo" Diagnostic.Use Only - Not for Research Involving Human Subjects - Introduction into foods, Beverages, Cosmetics, Other Drugs or Medicinals, or into Products Manufactured
' for Commercial Distribution is Prohibited."
Dated;at Rockville, Maryland this day of
, 1997..
For the Nuclear Regulatory Commission.
John C. Hoyle, Secretary of the Commission.
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ENCLOSURE 2 REGULATORY ANALYSIS
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J DRAFT REGULATORY ANALYSIS 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.
RacLaround 1.1 Statement of the Problem On October 6,1994, the Commission uocketed a petition for rulemaking (Docket No.
PRM 3512) from Tri Med Specialties, Inc (Tri Med). In a letter dated August 23,1994, Tri Med petitioneJ 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 (uCl) of "C urea for in vivo diagnostic testing." The purpose of this diagnost'c test is to detect the presence of the bacterium Helicobacter pylori (H. pylori), a cc.use of peptic 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 c,re 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 now 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 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 2
breath sample, then the patient must be infected with H. pylori.
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i 1.2 Current NRC Reoulations in 10 CFR Part 32, " Specific Domestic Licenses To Manuf acture or Transfer Certain items I
Containing Byproduct Materials," 5 32.72, 'Manuf',cture, preparation, or transfer for commercial distribution of radioactive drugs containing byproduct material for medical use under Part 35,* provides for commercial distribution of radioactivo drugs containing byproduct matorial 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 urea to persons authorized pursuant to Part 35.
In 10 CFR Part 35, "Modical 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 containing byproduct material.
Existing exemptions for use of byproduct materialin i 30.14, " Exemption concentrations" and 6 32.18, "Manuf acture, 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 inhalat'on by, or application to, a human being.
Thorofore, under current regulations, the "C-urea capsules must be used under a Part 35 licenso, even though they could be safely distributed as an exempt material to any person because the capsulee present a negligible radiation risk.
1.3 Earlier NRC Actions Following the receipt of the petition, a " Notice of receipt of petition for rutomaking" was published for public comment in the WM Roaister on December 2,1994 (59 FR I
61831). A total of 315 public comment lettors,313 supporting (mostly form letters) and 2 opposing letters, were received. 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 public and (2) medical usos should be rostricted to short lived isotopes because of disposal problems presented by long lived isotopos.
This petition was discussed with NRC's Advisory Committee on the Me ical lises of d
Isotopes ACMUI) at the October 1995 meeting. The ACMUIindicated that it endorsed the wide availability of this diagnost' test and that the radioactivo drug could be used under a generallicense or an exemption, woichever the NRC thought to be procedurally easier.
A rulemaking plan has bonn prepared. After receiving comments from Agreement States on the draft rulemaking plan, the Commissica 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 an exempt material to any person.
2 i
2.
Obiective The objective of the rulemaking is to (1) amend 10 CFR Part 32 to permit the manufacture and initial distribution of "C-urea capsules as an exempt material and (2) amend 10 CFR Part 30 to permit any person to receive the capsules.
3.
Alternatives 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 asers 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 solo purpose of using such capsules because of the requirement for training and experience and the associated costs of obtaining ano maintaining a Part 35 license. Alterpatively, physicians who ere 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 deley to an otherwise straight forward procedure.
Under the second alternative, Parts 30 and 32 would be amended to permit the manufacture and initial distribution of the capsules as an exempt 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 tu receive and use the capsules under a generallicense. The health and safety concerns for this alternative are the same as the Alternative 2. However,if this alte.nstive were adopted, there could be a burden to those Agreement States that normally assess licensing or registration fees for generallicense holders. A burden could also be imposed on general licensees located in the Agreement States.
4.
Value-imoact Analvsis 4.1 The Petitioner's Assessment 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).
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... The test is 95 percent accurate and quite inexpensive because of its simplicity.
The test would permit doctors to determine easily whether or not ulcer patients have i
been cured of their infection. By providing the public with an inexpensive, easily i
accessible diagnostic test, more individuals would be accurately dia'} nosed and
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treated for their H. pyloriinfection. This would save the United States an estimated
$500 million per annum over conventior.al 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. Ti-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 physicir.ns (NRC licensed and non licensed alike), implicit in Tri Med's l
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 physicisns 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 igg antibodies to H. pylori antigens) for both endoscopy and "C-urea tests. In addition, wiro service articles dated September 19,1996, stated that the FDA has approvad a non-radiological diagnostic breath test using "C for detecting the presence of H. pylori infections.
4.2 The NRC's Assessment i
fa)
Cost Savinos Associated with Amendments to 10 CFR Part 30 f
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 urea breath
~
tests and endoscopies or other non-invasive tests. For the purposes of this regulatory analysis, the NRC assumes that the same number of breath tests (i.e., 600,000 tests) will 4
be administered regardless of the level of NRC regulatory control. This view is predicated on the belief that each physician's primary motivatloa 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 reguletions. This appears fully consistent with standard medical practice, whereby patients are referred rcutinely 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 health care 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 ' e some regulatory savings because the NRC would not have to expend resources 4
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reviet a new applications for specific medical use licenses. However, these savings woula b's small because the NRC expects that few physicians who are not authorized users would apply for a specific NRC license for use of this one product.
The benefit calculation is based on the assumption that as a result of the croposed action, a significant portion of the 600,000 patients would receive the "C breath test from physicians who are not authorized useis (e.g., gastrointestinal specialists), The actual savings would bo 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 high as approximately $20 million if there was a completo shift 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 nood for up to 600,000 referrals, patient savings in averted travel expensos (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 tdps/ 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 (administrativo 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 practice 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-urea breath test would most likely be a new patient for the authorized user.
T tal Savings:
$10.5 million/ year + $11.4 million/ year = $ 21.9 million/ year Alternatively,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 cet savings would bt approximately
$7 million per year and $15 million per year, resper,ovely, if Alternative'3 were adopted, it would permit any physician to receive anti use capsules containing 1 pCi "C-urea for
. human use under a generallicense. The health and safety concerns for this alternative are 5
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' the same as Alternative 2. However, the adoption of Alternative 3 could add unnecussary burden to those Agreement States and Agreement State licensees in States that assess a
licensing or registration fees for generallicense holders. Alternative 2 also imposes incremental cost burden for manufactures or initial distributors of the capsules because l
they would need obtain an exempt distribution license. Each initial application would be 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 the first five year period, the average burden per 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 per licensee.
(b)
Health and Safety Effggig For the purposes of this regulatory analysis, tl NRC assumes that the same number of breath tests (i.e.', 600,000 tests) will be administered regardless of the level of NRC i
regulatory control. This view is predicated on the belief that each physician's primary j
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 ref NRC regulatory control. 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 insignificant exposures as depicted below:
Scenario Maximum Exposed Routine Exposure r
Individual Worker administering "C-Full time worker,8,000 Less than 0.7 mrem /yr urea breath tests--
patients /yr Routine exposure of Patient tests negative 0.38 mrem / capsule patients from "C urea breath tests Patient tests positive 0.1b mrem / capsule Release of 150 Ci of "CO, Member of public in the Less than 0.0002 mrem into administration area administration area Rupture of a capsule Skin (100 cm ) exposed for 5.8 mrad skin dose 8
causing skin contamin-one hour prior to washing 0.075 pCi skin absorption ation of worker or patient 0.029 mrem CEDE 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. The earth's atmosphere contains an inventory of naturally occurring "C of about 3.8 million curies (eWvalent 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 6
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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 world inventory of naturally occurring "C results in an average dose to the public of about 1.25 mrem / year, and the release of 0.6 curies of "C fro,a 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 mrom. This is far below the EPA reporting level of 1 mrom/yoar required under the Clean Air Act for routino 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 the U.S., the collective annual doso from the breath tests would be about 0.051 person rom in addition, the dosos 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.
The small dosos from naturally occurring "C are of little significance to human health and the environment. Potentiallong torm 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. woulo increase over a period of time to an average of a million tests por year for 50 years, the collectivo 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 doso to the U.S. population from naturally occurring "C of over 300,000 person rom, and about 78,000,000 person rem from all naturally occurring radiat;on. Clearly, an increase of a few person rem will not significantly change those exposures, and thus 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 altomativo. 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 Alternative 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 measurable adverso effect on public health and safety.
5.
Decision Rationato Based on the above analysis, the NRC believes that the proposed rule,if adopted, would provide manuf acturers or initial distributors to c'istributei 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 acMition, the NRC believes that the receipt and use of the drug are the responsibilities 09 other Federal and
- Stato agencies (e.g., Food and Drug Administration and the State Boa ds of Pharmacy) as is the caso for other drugs that do not contain byproduct materials.
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4 ENCLOSURE 3 l
ENVIRONMETAL ASSESSMENT 4
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Draft Environmental Assessment for Proposed 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" 1.
Introduction and Statement of the Proposed Action The Nuclear Regulatory (,ommission (NRC) is proposing to amend 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 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.
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-Hed Specialties, Inc.
2.
Need for the Amendments The proposed amendments have been developed to grant the petition for rulemaking.
The Commission believes that the proposed rule, if adopted, would 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 significant, in addition, the Commission recognizes 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.
-3.
Alternatives Considered l
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.
l l
i 1
Under the first alternative, only physicians who are authorized users under l
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 exoects few physicians would apply for a Part 35 license for the sole purpose of using i
such capsules because of the requirement for training and experience and the i
ass iated costs of obtaining and maintaining a Part 35 license.
Altei:,atively, physicians who are not authorized users could refer their i
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.
P Under the second alternative, Parts 30 and 32 would be amended to permit the manufacture and initial distribution of the capsules as an exempt material to I
The NRC has determined that the radioactive component of this any person.
drug presents a minimal radiation risk and,- therefore, regulatory control of l
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 general license.
The health 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 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 Connission 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 and 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.
i 2
- 4. -Impact oil the iublic. 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 controi, 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 same 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 Reatster on De'cember 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 ACMul) at the October 1995 meeting.
Furthermore, a draft rulemaking plan Las 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 A of 10 CFR Part 51, that the: proposed amendments, if. adopted, would not be a major Federal _ action significantly affecting the qualuy of the human environment,_
and therefore an' environmental impact statement is.no rsuired. The proposed f role would permit the manufacture and._ initial distrit.Mc of "C-urea
- capsules an exempt material and to permit any person may receive the capsules.
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The Commission believes that the radioactive component of this drug presents a minimal 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 proposed rule, if adopted, would 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 would be no non-radiological impacts if the proposed rule is adopted.
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ENCLOSURE 4 CONGRESSIONAL LETTERS
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,j NUCLEAR REGULATORY COMMISSION W AsHINGT oN, 0.c. sow 44001 o
k*e..*,=e 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 thc Subcommittee are copies of a public announcement l
and a Federal Register notice concerning a proposed amendment to.10 CFR Parts 30 L and 32. This rulemaking is being taken in response to a petition for rulemaking submitted by Tri-Med specialties, Inc.
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The Nuclear Regulatory Commission (NRC) is proposing to amend 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 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. If adopted, this amendment would make the drug more widely available, thus reducing costs to patients.
Sincerely, Dennis K. Rathbun, Director Office of Congressional Affairs
Enclosures:
- 1. Public Announcement
- 2. Federal Register Notice -
f cc:- Representative Ralph Hall b
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o 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 sie copies of a public announcement and a Federal Register notice concerning a proposed amendment to 10 CFR Parts 30 and 32. This rulemaking is being taken in response to a petition for rule-taking sebmitted by Tri-Med Specialties, Inc.
-The Nuclear Regulatory Commission (NRC) is proposing to amend its regulations to allow NRC licensees to distribute's 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 such capsules 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.
Sincerely, Dennis K. Rathbun, Director Office of Congressional Affairs Encloeures:
- 1. Public Announcement
- 2. Federal Register Notice cc: Representative Ralph Hall Distribution: CTrottier/RPHEB rf File Center NCostanzi ATse
-(DOC NAME: 0:\\ JONES \\C14 PR.CL)
Of fice' RPHEB:DRA'.
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Name' SJones M -
CTrottierON-B M c ris DLMorrison DKRathbun Date
- b1/97 -
- /.? 797
/
/97
/ /97
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/97 ost ibution ~
Yes/No Yes/No.
Yes/No Yes/No Yes/No OFFICIAL RECORD COPY (RES File Code No.) 3A 3 J
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NUCLEAR REGULATORY COMMISSION
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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 it. formation of the Subcommittee are copies of a public announcement and a Federal Register notice concerning a proposed 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.
l The Nuclear Regulatory Commission (NRC) is proposing to amend 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 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. If adopted, this amendment would make the drug more widely available, thus reducing costs to patients.
- Sincerely, Dennis K. Rathbun, Director Office of Congressional Affairs
Enclosures:
- 1. Public Announcement
- 2. Federal Register Notice cc: Senator Bob Graham 4
,9 t
i i
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 concerning a proposed ' amendment to 10 CFR Parts 30 v and 32._ This rulemaking is being taken in response to a petition for rulemaking submitted r
by Tri-Med Specialties, Inc.
TSe Nuclear Regulatory Commission (NRC) is proposing to amend its regulations to allow NRC licensees to distribute a radioactive drug containing one microcerie of carbon 14 urea to any person for 'in vivo" 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 radiatian safety is not necessary, if adopted, this amendment
- would make the drug more widely available, thus reducing costs to patients.
Sincerely, Dennis K. Rathbun, Director Office of Congressional Affairs
Enclosures:
-1. Public Announcement
- 2. ' Federal Register Notice r
cc: Senator Bob Graham Qistribution: CTrottier/RPHEB rf File Center NCostanzi ATse
- [ DOC NAME: 0:WDNE8\\C14-PR.CLI D:OCA Office RPHEB:DRA '
RPHEB:DRA D:DRA:RES D:f%$,
Name SJones /')- CTrottierf,[ @MorrisM Dhh DLRathbun Date t to /97 2/2197 L/497 h97
/
/97 Dietribut'en Yes/No Yes/No'-
Yes/No Yes/No Yes/No OFFICIAL RECORD COPY (F,ES File Code No.) 3A-3 t
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RULEMAKiNG ISSUE (NEGATIVE COD t T)
February 7, 1997 SECY-97-031 IQ:
The Commissioners EEQM:
Hugh L. Thompson, Jr.
Acting Executive Director for Operations
SUBJECT:
FINAL RULEMAKING PLAN: EXEMPT DISTRIBUTION AND USE OF A RADIOACTIVE DRUG CONTAINING ONE MICROCURIE OF CARBON 14 UREA (PARTS 30 AND 32)
PURPOSE:
To inform the Commission of the staff's rulemaking plan for amending Parts 30 and 32 to a: low the distribution of a radioactive drug containing one microcurie of "C-urea as an exempt material for "in vivo" diagnostic testing.
BACKGROUND:
On October 6,1994, the Commission docketed a petition for rulemaking (Docket No.
PRM 3512) frorn Tri-Med Specialties, Inc. (Tri-MecD 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 b-l licensed pharmaceutical manuf acturers 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 peptic ulcers.
The petition for rulemaking was noticed for comment in the Federal Reaister on Decemeber 2,1994. A total of 315 comment letters were received. There were 313 letters supporting the petition !alostly form letters) and 2 letters opposing the petition.
NOTE: TO BE MADE Pt!BLICLY AVAILABLE WHEN THE FINAL SRM IS MADE AVAILABLE CONTACT:
Sam Jones, RES 415-6198 l
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1, DISCUSSION: >
in accordance with the SRM-COMSECY 96-035_ dated June 11f 1996, a copy of the draft
' rulemaking plaa, recommending a general license approach, was provided to the :
1 Agreement States for review and comment.= The comment period closed on October 31, 1996. Ten comment letters were' received from Agreement States. Six States agreed i
- with the staff's initial position to grant the petition by making the C-urea capsules available to any physician under a general license. However, three States - Georgia,
)
, Illinois, and New York while agreeing that the petition should be granted, opposed the"
' staff's recommendation and argued that the capsules should be made available as exempt material.: One State, Oregon, stated that it v/ould continue to require that any person who
' administers a radioactive drug be specifically licensed.
in addition,' there were some comments related to the process of Agreement State involvement in NRC rulemaking that the staff believes were addressed in SECY-96-035,
.and, tharefore, are not addressed in the memorandum to the Commission or in the final-rulemaking plan.
I
' Aft'er considering Agreement States' comments, the staff has changed its recommendation. We now recommend that manufacturers and distributors be permitted
' to distribute this radioactive drug as exempt material to "any person" who is permitted to receive and use the drug under the appropriate Federal or *ttate la v goveming the -
i^
distribution and use of the drug.
AGRFEMENT STATE COMMENTS ON DRAFT RULEMAKING PLAN:.
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in accordance with Management Directive 0.3, "The Rulemaking Process," the staff F
drafted a ruiemaking plan in response to a petition for rulemaking submitted by Tri-Med Specialties, Inc. Under the draft plan, the staff would have developed a direct final rule t
p amending 10 CFR Part 35 to permit, under a general license, any physician to administer to patients capsules containing one microcurie of C-14 as a diagnostic tool for detecting pep.ic ulcars caused by the Helicobacter pylori bacterium.
In accordance with COMSECY-96-035 dated June 11,1996, a copy of the draft rulemaking plan 'was provided to the Agreement States on October 1,1996, for a 30-day period of review and comment. Comments were received from ten Agreement States.
Six States (Kentucky, Nebraska, Colorado, Washington, Utah, and Louisiana) supported the staff's initial position to grant the petition via a general license to permit physicians Lwho are not authorized users to receive and use capsules containing 1 pCi of C-urea.
Kentucky. indicated they already have provisions for a general license for "in vivo" use in
, their regulations.
g
_One State, Oregon indicated that it would not permit administration of the capsules under p
'a general license, but would continue to require that all physicians who administer f
- radioactive drugs, including the C-14 capsules, be specifically licensed.
"Three States, New York, Georgia and Illinois, opposed the general license approach
' recommended by.the_ staff.' Georgia and lilinois recommended that physicians who are not
" authorized users" be permitted to receive and use capsulee containing 1 pCi of '*C - urea 4
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I The Commissioners 3
as ex..npt material. Georgia argued that their burden would be increased by distribution and use under a generallicense because of reports required from distributors, invoicing of physicians for generallicense fees, and possible amendment of all of tneir distribution licenses. Illinois stated that distribution of the capsules as exempt materialis consistent with the NRC's technical evaluation and would ensure that physicians could have access to the capsules without a specific or generallicense. Illinois further stated that if the NRC were to require distribution and administration under a generallicense, Agreement States would need to incur the expense of modifying their regulations. Illinois seems to imply that they could avoid rulemaking if the NRC were to adopt the exemption approach.
However, as Georgia correctly observed, the exemption approach would require States to make conforming changes in their regulations as well. New York stated that they agreed that the widespread medical use of the capsules would involve no risk to the public health and safety or the environment, and would provide significant medical benefits to the population. New York also stated that using a risk-based regulatory approach, there is no need to regulate the capsules for their radioactive content. Further, New York argued that a generallicense is an ineffective means of regulatory controlin any case. New York also noted that the Food and Drug Administration will regulate the capsules as a drug.
There were further comments from the States addressing the process of Agreement State involvement in NRC rulemaking that the staff believes were addressed in SECY 96-035, ar'd therefore are not addressed here. Copies of the comment letters are enclosed.
STAFF RESPONSE:
The staff initially recommended distribution of the capsules under a generallicense because if the capsules were to be distributed as an exempt material, manuf acturers and distributors located in Agreement States would be required to obtain and maintain both an NRC and Agreement State license. Since the staff had concluded that there was no significant radiological safety or environmental risk, it did not intend that the general license would be used as a means of exercising regulatory control beyond limiting distribution to physicians. However, in light of the commants received from New York, Illinois, and Georgia, the staff changed its position from permitting distribution to any physician under a generallicense to permitting exempt distribution to any physician. After further consideration, the staff decided that manufacturers and distributors should be permitted to distribute this radioactive drug as exempt material to any person who is permitted to receive and use the drug under the appropriate Federal or State law governing the distribution and use of the drug. Permitting exempt distribution to "any person,"
rather than "any physician," would avoid the need for NRC to amend its regulations if other Federal or State authorities permit the distribution and use of the radioactive drug to persons who are not physicians. Moreover, the drug will k manufactured under a soecific Part 32 license to ensure that capsules contain only one microcurie of carbon 14 and do not contain any other radioactive contaminants.
POLICY ISSUES:
NRC regulations specify that persons administering radioactive drugs containing byproduct material to patients or hum.an research subjects must have specific authorization. Also,
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there are no provisions in NRC regulations for the "in vivo" use of byproduct material as an -
- exempt material. However, in light of the above, the staff is recommending the
- distribution of the capsules as exempt material to any person.
q in addition, the Commission should note that current regulations ($ 35.6) addressing the l'
use of byproduct materialin research' require licensees to meet specific provisions for the :
protection of human subjects. Under the staff's recommendation, the exempt distribution
' of the capsules for use in resaarch involving humans subjects would not be authorized.,
The Commission also should note that all of the options in the draft rulemaking plan given -
' to the Agreement States for review in June,1996, explicitly limited the use of the drug to-physicians.' Hence, the position of the Agreement States on the staff's recommendation in-
- this final rule plan to not limit the use to physicians only, but rely on FDA and State Boards Jof Pharmacy regulations for determining use,is not known.
AGREEMENT STATE COMPATIBILITY:
Under the Atomic Energy Act, certain regulatory functions are reserved to the NRC.
Among these are the distribution of exempt materials and quantities, as discussed in 10 CFR Part 150. - Hence, the staff's recommended approach is a Division 4 matter of e
compatibility, with regard to the manufacture and distribution of the capsules (Part 32),
and a Division 1 matter of compatibility with regard to possession and use (Part 30). All Agreemen* States will need to adopt regulations to allow any person to receive capsules containing 1 pCi of "C-ures as an exempt material.
f The Commission ~should note that under the staff's initial recommendation, Oregon (and possibly other States, since not all States commented) could have continued its current practice of requiring physicians administering radioactive drugs to humans to be specifically licensed, because the general license amendments would have been a Division 3 matter of compatibility, COORDINATION:
The Office of the General Counsel has reviewed this paper and has no legal o$ction. The Office of the Chief Financial Officer concurs that there will be no resource impacts beyond -
. those currently budgeted.L The Office of the Chief infermation Officer concurs that there will be no information technology or management impacts beyond those needed for rulemaking.
4 s
- The Commissioners 5
RECOMMENDATION:
Unless the Commission directs otherwise within 10 days from the dtte of this paper, I will implement the rulemaking plan and direct the staff to begin development of a proposed rule to permit the distribution of the radioactive drug as an exempt material for distribution to any person.
%ki.4
~
L. Thompson, Hu(ing Executive Director Act for Operations
Enclosures:
- 1. Final Rulemaking Plan
- 2. Agreement State Comment Letters SECY NOTE:
In the absence of instructions to the contrary, SECY will notify the staff on February 26. 1997 that the Commission, by negative consent, assents to the action proposed in this paper.
DISTRIBUTION:
Commissioners OGC
-OCAA OIG OPA ACNW CIO CFO EDO SECY
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t RULEMAKING PLAN
l RULEMAKING PLAN FOR EXEMPT DISTRICUTION AND USE OF A RADI0 ACTIVE DRUG CONTAINING MICR0 CURIE OF CARBON 14 UREA (PARTS 30 AND 32)
Lead Office:
Office of Nuclear Regulatory Research Staff
Contact:
S. Jones, RES/RPHEB Concurrences:
SIGNED 8/13/96 D. Morrison, RES Date SIGNED 9/19/96 C. Paperiello, NHSS Date SIGNED 9/20/96 R. Bangart, OSP Date (memo from S,tuart Treby) 9/20/96 W. Olmstead, OCG Date (memo from David Meyer)
S/20/96 D. Meyer ADM Date e
ff &X l-N P Approval:
H. L. Thompson, Date
e FINAL RULEMAKING PLAN 10 CFR PARTS 30 AND 32 EXEMPT DISTRIBUTION OF A RADIOACTIVE DRUG CONTAINING ONE MICROCURIE OF CARBON 14 UREA (PRM-35-12)
BACKGROUND 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 axemption for the commercial distribution by licensed pharmaceutical manutacturers of a capsule containing one micro-Curie (pCi) 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 10% of people in the United States at some time in their lives.
The disease has relative!y 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 stomach of most ulcer sufferea. By treating ulcer patients with antibiotics, doctors can now cure most ulcer problems.
It is the;efore 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 w' o took biopsy samples of the stomach n
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 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 2
sample, then the patient must be infected with H. pylori.
CURRENT REGULATIONS 10 CFR Part 32, " Specific Domestic Licenses To Manufacture or Transfer Certain items Containing ByprHuct Materials," 5 32.72, " Manufacture, preparation, or transfer for
commercial distribution of radioactive drugs containing byproduct maturial 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-urea to persons authorized pursuant to Part 35.
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 containing byproduct material.
Existing exemptions for use of byproduct materialin i 30.14, " Exempt 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 inhalation by, or application to, a human being.
BEGULATORY ISSME The regulatory issue is whether the "C-urea capsules present a sufficiently small radiation risk that they can be safely dinributed to and used by physicians who are not " authorized users" under 10 CFR Part 35.
i SAFETY ANALYSIS Based on a safety analysis conducted by an NRC contractor, the staff has concluded that the human use of these capsules results in insignificant exposures as depicted below:
Scenario Maximum Exposed Routine Exposure Individual Worker administering "C-Full-time worker,8,000 Lass than 0.7 mrem /yr urea breath tests patients /yr Routine exposure of Patient tests negative 0.38 mrem / capsule patients from "C-urea breath tests Patient tests positive 0.18 mrem / capsule Release of 150 pCi of "CO, Member of public in the Less than 0.0002 mrem into administration area administration area.
2 Re.pture of a capsule Skin (100 cm ) exposed for 5.8 mrad skin dose causing skin contamination one hour prior to washing 0.075 pCi skin absorption of worker or patient 0.029 mrem CEDE 2
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a Pathways to the Enviror ment
' Based on an environmental report prepared by an'NRC contractor, the staff 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.
4 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 etmosphere from the use of this test would mix with the global inventory and a
4
^
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 world inventory of naturally occurring "C results in an average -
3 L dose to the public of sbout 1.25 mrom/ 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
- ANALYSIS section below) would result in an additional average annual dose of 2 X 104 mrom.EThis 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 mrom/ year EPA limit for public drinking watsr. In a total population of about 260 million people 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 to the environment also are expected to be very small because the concentration of CO, a
L relaated is very low and it would mix immediately with the atmosphere.
a Collective Excosures to Members of the Public The small doses from naturally occurring "C are of litt.d significance to human health and the environment. Potential long-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 collect"se annual dose to the U.S. population would be about 5 person-rem cver the next 50 years. This dose is very small when 4.
- compared to the annual collective 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 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.
COMMENTS FROM THE ADVISORY COMMITTEE ON THE MEDICAL USES OF ISOTOPES l
(ACMull This petition was discussed with the 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 ussd under a general license or an exemption, whichever the NRC thought to be procedurally easier.
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COMMENTS FROM THE PUBLIC 4
. The " 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_opposirg letters, were received.
The two letters opposing the petition made the following two comments:
(1)
The product should not receive an exempt status because the 'uncontrollnd distribution and application of this product could lead to significant risk to the public,.
- and (2)' Medical uses should be restricted to short-lived isotopes because of disposal problems presented by long lived isotopes.
The staff disagrees with both comments.
d)
As shown in the " SAFETY ANALYSIS" section of inis plan, the radiation dose to workers, patients, and the public is very low.
(2)
As discussed in the " Pathways to the Environment" section of this plan, the impacts
-associated with any releaseJ of "C to the surrounding environment are expected to be very small and the expected risks are minimal. Also, as discussed in the
" Collective Exposures to Members of the Public" section of this plan, 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 the long-lived
'fC (5 730 year radiological half life) from breath tests were concluded to be
- insignificant.
DRAFT RULEMAKING PLAN In accordance with Management Directive 6.3, "The iiolemaking Process," the staff drafted a ruiemaking plan in response to a petition for rulemaking submitted by Tri-Med Specialties, Inc. Three attematives were considered in the draft rulemaking plan:
- Attemative 1 -
Deny the petition.
Alternative 2 -
_ Grant the petition via rn axemption to permit physicians who
- are not " authorized ue to receive and use capsules
- containing 1 pCi of "C-urea.
Alternative 3 Grant the petition via a generallicense to permit physice2 who are not " authorized users" to receive and use capules containing 1 pCi of "C-urea 4
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i Under the draft plan, the staff would have developed a direct final rule amending 10 CFR.'
. Part 35 to permit, under a general license, any physician to administer to patients capsules containing one microcurie of C 14 as a diagnostic tool for detecting peptic ulcers caused by the Helicobacter pylori bacterium (Alternative 3).-
Distribution of byproduct material as exempt material requires en NRC license, even in an
- Agreement State. Hence, manufacturers and distributors licens61 by Agreement States
.would need to obtain and maintain both NRC and Agreement State licenses to distribute -
the C capsules as exempt material. This is not the case for byproduct material to be possessed and used under a generallicense. The staff viewed this patential duallicensing 4
as an unnecessary burden with no safety benefit. Therefore, the sta.f did not recommend :
distribution to anc., use as exempt material in the draft rulemaking plan, in terms of public-health and safety, either Altemative 2 or 3 could be adopted becaust the radiological risk is negligible.
- in accordance with COMSECY-96-035 dated June 11,1996, a copy of the draft
- rulemaking plan was provided to the Agreement States on October 1,1996, for a 30-day period of review and comment. Comments were received from ten Agreement States.
AGREEMENT STATE CO?fff"NTS ON DRAFT RULEMAKING PLAN Six States (Kentucky, Nebraska, Colorado, Washington, Utah, and Louisiana) supported the' staff's recommended approach (i.e., grant the petition, and permit physicians who are not authorized users to receive and use capsules containing 1 pCi of C-urea via a general i
license). Kentucky indicated they already have provisions for a general license for "in vivo" use in their regulations.
L One State, Oregon indicated that it would not permit administration of the capsules under a general license, but wou'd continue to require that all physicians who administer radioactive drugs, including the C-urea capsules, be specifically licensed.
Three States, New York, Georgia and Illinois, opposed the general license approach recommended.by the staff. Georgia and lilinois recommended that physicians who are not
" authorized users" be permitted to receive and use capsules containing 1 pCi of C - urea as exempt material. Georgia argued that their burden would be increased by distribution and use under a generallicense because of reports required from distributors, invoicing of I
i
' physicians for generallicense fees, and possible amendment of all of their distribution l
licenses. lilinois stated that distribution of the capsules as exempt materialis' consistent with the NRC's technical evaluation and would ensure that physicians could have access to.the capsules without a specific or generallicense. lilinois further stated that if the NRC were to require distribution and administration under a generallicense, Agreement States i
would need to incur the expense of modifying their regulations. lilinois seems to imply I
that they could avoid rulemaking if the NRC were to adopt the exemption approach.
i However, as Georgia correctly observed, the exemption approach would require States to make conforming changes in their regulations as well. New York stated that they agreed
' that the widespread medical use of the capsules would involve no risk to the public health and safety or the environment, and would provide significant medical benefits to the 5
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population.: New Wrk also stated that using a risk-based regulatory approach, there is no need to regulate the capsules for their radioactive content. Further, New Wrk argued.that a generallicense is an~ ineffective means of regulatory control in any case. New Wrk also
[
~noted that the Food and Drug Administration will regulate the capsules as a drug, 4
RECOMMENDED APPROACH The stad has determined that theiadiological risk of this drug presents such a small i
radiation hazard that the capsules can be treated without regard to their radioactivity.-
Hence, no control of the capsules is necessary for radiation safety after they are manufactured and distributed. In light of this, and in light of the comments from Illinois, and Georgia, the staff has decided not to' recommend distribution and use of the "C-urea
- capsules under a general license. Rather, the staff is now recommending that Part 30 be
-amended to permit the "C-urea capsules to be distributed to and used by any person,-
?
without need of an NRC (or Agreement State) license, who is permitted to receive and use-
- the drug under an appropriate Fedaral or State law governing the distribution and use of the drug. _ Thus regulation of receipt and use of the drug v;ill be left to other Federal and State agencies with the responsibility and authority to regulate drugs (as is the case for other drugs that do not contain byproduct materials). The staff believes that permitting exempt receipt of the capsules by "any person who is permitted to receive and use the-drug under an appropriate Federal or State law," rather than limiting receipt and use to physicians only will provide any controls needed for regulation of the capsules as a drug, and avoid the need for NRC to amend its regulations if other Federal or State agencies -
permit under their authority the distribution and use the radioactive drug to persons who are not physicians.
The staff believes that NRC should require the_ drug to be manufactured under a specific Part 32 license to ensure that capsules contain only one microcurie of carbon 14 and do not contain any other radioactive contaminants. - Hence, conforming amendments would be made to Part 32 to provide requirements for a specific license to manuf acture, process, produce, package, repackage, or transfer capsules containing one microcurie of "C-urea, as a radioactive drug,' to be distributed as an exempt material to any person for "in vivo" diagnostic testing. Licensees distributing the radioactive drug as an exempt material would not be relieved from other applicable Federal (e.g., FDA) or State drug manufacturing and distribution requirements.
PRELIMINARY REGULATORY ANALYSIS Lin the letter dated August 23,1994, the petitioner stated,
-If exempted, the C-14 breath test could be done by most doctors for less than $100 cost to the patient.1This is a considerable savings over endoscopy and biopsy
- ($1000). -
- In a letter on November 30,' 1994, the petitioner stated:
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The' test is 95% accurate and quite inexpensive because of its simplicity.- The :
J 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 -
I
. accessinie _ diagnostic test. more individuals would be accurately diagnosed and
- treeted for their H. pylori infection. This would save the United States an estimeted
$500 million per annum over conventional therapy.
l Med estimates annual benefits to be on the order of $500 million/ year. This assumes approximately 600,000 "C-urea breath tests! year, at an ave'. age 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 i
L benefits associated with the test and does not focus on the incremental benefits of auministering 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 i
status quo, the test would be available and administered by physicians'or clinics holding a
' license under NRC's Part 35. Further, Ti-Med's estimate did not allow for the substitution of other non-invasive tests (e.g., serological test for igg antibodies to H. pylori antigedt) for both endoscopy and "C urea tests, in addition, wire service articles dated September 19,1996, stated that the FDA has approved a non-radiological diagnostic breath test using "C for detecting the presence of H. pylori infections.
The staff's benefit analysis focuses on the incremental benefits of granting relief based on the petition. 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 urea breath tests and endoscopies or other non-invasive tests.
For the purposes of this regulatory analysis, the staff 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. 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 practice, whereby patients are referred routinely to laboratories and specialists for a wide array of tests and procedures.
in the NRC's analysis, the benefits of adopting the petition accrue as a result of reduced
. patient cost and reduced health care cost resulting from the elimination of the need for
. eferrals from a_ physician who is not an authorized user (e.g., gastrointestinal specialist).
r
. 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, the NRC
- savings would be small because the staff expects that few physicians who are not authorized users would apply for a specific NRC license for use of this one product.
-The staff's benefit calculation is based on the assumption that a significant portion of the
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600,000 patients would receive the "C breath test from physicians who are not 7
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. l e'uthorized users (e.g., gastrointestinal specialists) instead of authorized users (e.g.,
nuclear medicine _ 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.
The annual savings could be as high as approximately $20 million if there was a complete shift of the administration of the tests froi6 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 t'.a petition eliminates the need for 600,000 referrals, patient 1
sav_ngs in averted travel expenses (transportation and personal time incurred with medical i
. 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/hc,ur) =
$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 Assuming $1g.00 (administrative cost / patient) as the differential between the cost of an office visit to a general family practice physician by an established patient -
($45.30), 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..
Total Savings:
$10.5 million/ year + $11.4 million/ year = $ 21.9 million/ year
_ Alternatively,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 million/ year and $15 million/ year, respectively, s
COMPARISON OF ALTERNATIVES Altemative 1 ---
Deny the Petition I
' This alternative would maintain the status quo. Only physicians who are authorized users under Part 35 would be allowed tc cnssess and administer the "C-urea test. Any
. physician could apply to become an authorized user. However, the NRC expects few 4
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physicians would apply fer 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 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.
Alternative' 2 -
Grant the petition to permit the "C-urea capsules to be distribute' to_
d
- and used by any person, without need of an NRC (or Agreement State) license, who is permitted to receive'and use the drug under an -
appropriate Federal or State law governing the distribution and use of the drug.
- Parts 30 and 32 would be amended to pe mit the manufacture and distribution of capsules -
containing one microcurie of "C-urea as on exempt material to any person. The staff has determined that the radioactive component of this drug presents a minimal radiation risk and, therefore, regulatory control of the human use of capsules for radiation safety is not i
necessary.
Alternative 3 -
Grant the petition via a generallicense to permit physicians who are not
" authorized users' to receive and use capsules containing 1 pCi of "C-urea for in vivo diagnostic testing, This alternative would permit any physician to receive and use capsules containing 1 pCi "C-urea for human use under a general license. The health and safety concerns for this alternative are the same as Alternative 2. However,if this alternative were adopted, there could be a burden to those Agreement States and Agreement State licensees in States that assess licensing or registration fees for general license holders.
RECOMMENDED COURSE OF ACTION l
' The staff recommends proceeding with a rulemaking amending Parts 30 and 32 in conformance with Alternative 2 for the following reasons:
Health and Safety Based upon'the analysis of the radiological impacts discussed above, there do not appear to be any safety or technical reasons why the capsules, breath test materials, counting fluids and vials, and urine from patients cannot be treated without regard to their radioactivity.
Avoided Costs Under Altemative 1, physicians who are not authorized users would have to refer patients to authorized users to undergo the diagnostic test. These referrals and 9
attendant expense could'be avoided under either Altematives 2 or Altranative 3..
However, compared with Alternative 3, Altemative 2 appears to be less burden for.
- Agreement States and their licensees.
1 AGRFEMENT STATE IMPLEMENTATION-
]
Rules pertaining to the distribution of products to persons exempt from NRC requirements--
fallinto the class of regulatory functions reserved to the NRC pursuant to the AEA and delineated in 10 CFR Part 150. Therefore, the staff's recommended amendment to Part 32' pertaining to the manufacture and distribution uf capsules containing 1 pCl of "C - urea for "in vivo" diagnostic testing by persons exempt from licensing would be a Division 4 matter of compatibility. The amendment to Part 30 would be a Division 1 matter of ~
compatibility'since Agreement States would need to conform their regulations to recognize i
- that possession and 'use of "C-urea capsules is exempt from licensing.. States (e.g.,--
Oregon, and possibly others) would not be able to require that physicians administering-
- radioactive drugs to humans be specifically or generally licensed.
OGC LEGAL SUFFICIENCi ANALYSIS DEMONSTRATING THAT NO KNOWN BASIS EXISTS FOR LEGAL OBJECTION OGC.has reviewed the rulemaking plan and has not identified any environmental issues that would present significant difficulties in pursuing the proposed rule.
Since this rulemaking would address the resolution of PRM 3512, the staff will need to.
ensure that appropriate procedural actions are taken to close the actions associated with that petition. These actions include specifi1 ally granting or denying the petition for
- rulemaking, either in the Federal Register notice associated with the rulemaking or in a separate Federal Register notice, and informing the petitioner of the Commission's e
' decision. The detailed procedures for responding to the rulemaking petition are contained
- in Part 11 of the Regulations Handbook (NUREG/BR-0053, Rev. 3).
MSESSMENT OF LIKELY IMPACTS ON NRC AND AGREEMENT STATE LICENSEES J
This rulemaking would not result in any additional regulatory burden to NRC medical use
' licensees.- Authorized users would continue to be author zed to receive and use this product for medical use.
SUPPORTING DOCUMENTS A regulatory analysis, an environmental assessment, and an OMB information collection approval package will be provided for this rulemaking, t
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Resources to complete and implement this rule are included in the current budget.
LEAD OFFICE STAFF AND STAFF FROM SUPPORTING OFFICF,1 Staff Laval Workina Groun Concurrina Official RES Sam Jones Bill M. Morris NMSS - Donna Beth Howe Donald A. Cool OGC - Marjorie Rothschild Stuart A. Treby OSP - Lloyd Bolling Richard L Bangart ADM - Mike Lasar David L Meyer STEERING GROUPS / WORKING GROUP There is no need for a steering group for this rulemaking. The Working Group is iden'tified above.
ENHANCED PUBLIC PARTICIPATION This rulemaking will be placed on the electronic bulletin board at FedWorld and will also be published in the Federal Reaister.
EDO OR COMMISSION ISSUANCE Because the amendment involves a policy issue (i.e., the capsules would be distributed to any person who would be exempt frcm NRC regulations), it is recommended that the Commission issue the rule.
GCHEDULE Proposed Rule:
Weeks from the date EDO/Comm approves the Rulemaking plan
' Send proposed rule to office for 2 weeks concurrence 11
4
' Send proposed rule to EDO 6 weeks Send proposed rule to Commission 8 weeks Receive Commission approval 10 weeks Publish in the Federal Reaister for a 75 day 13 weeks public comment period; and submit-information collection approval package to
- OMB t
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1 AGREEMENT STATE COMMENT LETTERS
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CABINET FOR HEALTH SERVICES pg COMMONWEALTH OF KENTUCKY
- PRANIGORT406210001 h'
MS CAmineerr poR PUBUC HF.ALTH October 4, 1990 r
LLOYD BOLLING U S NUCLEAR REGULATORY COMMISSION OFFICE OF STATE PROGRAMS WASHINGTON D C 20555
Dear Mr. Bolling:
Kentucky has no opposition to allowing use of carbon-14 in-one microcurie amounts under a. general license as proposed in the rulemaking plan for 10 CFR Part-35 (SP-96-107).
s We already have provisions for a general. license for in vivo use in our regulations under 902.KAR 100:050.
This regulation would be required to be amended to include, carbon-14 as an authorized material.
In the interim of revising the regulation, we would allow the use under a general license as a licensing policy.-
A form is required to be submitted for this license; however, only a l-signature is required.
No additional information is required to be submitted, thus a review is not required.
A fee is charged, on an l
annual basis, for a general license.
Sincerely,
- )
l icki D. Jeffs, Supervisor Radioactive Materials Unit l
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From:
Joyce Davidson <davidsonenredec.nre. state.ne.us>
To:-
WND1.WNP9 (lab)
Dates-10/17/96 12:32pm
-Subjects-Draf t Rulemaking Plan (10 CFR Part 35)
-Hi Lloyd:~
Brian Hearty asked that I send you an E Mail saying that we. favor Alternative 3 and concur that NRC should proceed directly '.o final rule.
Should you have any questions regarding this E mail message please contact Brian or me at my E-mail address or call (402) 4712168.
Have a nice day 111 Joyce J
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JAKE JACOBI <wejacobissmtpgate.dphe. state.co.us>
From:
To WND1.WNP9 (1ab)
Date:
10/21/96 6:56pm Subject Draft Rule for C 14 capsules Greetings Lloyd The proposed rule re " Medical Use of Capusley Containing oneand should go Microcurie of Carbon 14", PRM 35 12, appears appropriate, forward.
If you have any questions, please call.
Jake CC:
udi.internet3(arquillineemtpgate.dphe.atate.co.us'...
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Front Frazee, Terry <tef0303shub.doh.wa. gov >
To:
WND1.WNP9 (lab)
Date:
10/22/96 8:23pm
Subject:
SP 96-107 To:
Lloyd Bolling, OSP, NRC This is our response to your request for comments on the " Draft Rulemaking Plan for 10 CFR 35" received by FAX on October 1, 1996.
Specifically, the drai plan, in " Pre decisional" form, concerns " Medica?. U 9 of Capsules Containing One Microcurie of Carbon 14" and is based on PRM 35 12.
- 1) we support alternative 3 which would We have two numary comments:
and establish a " general license" for use of this low risk diagnostic test;
- 2) we believe " parallel rulemaking" with the CRCPD should have been considered rather than jumr ng immediately to a " direct final rule".
d is A general license similar to that for "in vitro" testing (10 CFR 31.11) considered appropriate for this rulemaking. This includes a registration process. This will provide a method of " authorization" for a wide range of physician-users; will be low cost (where a registration fee is required) ;
allows the manufacturers f the capsule to be fully licensed by an Agreement States if located therein; and provides the regulatory agency with rome knowledge of usage within its jurisdiction plus a database for later use in evaluating a further relaxation in the degree of control over this new product (for instance, eliminating the registration requirement).
We agree with the choice of " Division 3" for Agreement State compatibility although a corresponding assessment should also be provided to relate it to the new classification expected under the implementation procedures for the Final Policy Statement on the Adequacy and Compatibility of Agreement State Programs.
Finally, while we support speedy resolution of PRMs and agency initiated has rulemaking efforts, we have never supported the level of secrocy that NRC employed in the various phases of its rulemaking effort.
In the initial phase, it allows NRC staff to fixate on a solution of their own devising, and to establish themselves in a narrowly defined position which they then feel must be defended.
At the final phase, it results in the Commission receiving a " decision" paper that tries to reflect the scope of an issue and the varying and often couplex positions of other interested parties as interpreted by NRC' staff c. lone. We believe rulemaking should be an open process throughout its course and, no matter what your rationalization, the use of " Pre-decisional
- documents is viewed as " secrecy" and simply feeds th*
public's, the licensees' and, alas, some Agreement States' distrust cf the NRC's actions. We recommend that the Commission seek independent views on issues brought before it and that the NRC staff publish (and/or actively distribute to a wide audience) issues and alternatives, responses and draft rule language, and proposed final rule language for public comunent, each in turn, to be sure there is adequate public involvement. One step toward this goal is working with CRCPD in the proposed " parallel rulemaking" process.
If you have any questions about this e-mail:
This message from: Terry Frazee Quick ways to reach me:
Voice = 360-753-3461 FAX = 360 *iS3-1496 Also, visit oar Home Page at
--> http://www.doh.wa. gov /ehp/rp l
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l Craig Jones ccjonesadeg. state.ut.us>-
l1 Fros t - -
- WND1.WNP9 (lab) j To -
Dates
- 10/24 /96 12 :17pm -
, Subjects-
_ Comments /SP 96 107
,Hi Lloyd,-
i d the-JA number-of staff within the Division of Radiation Control have rev ewe i
W draft rulemaking plan for medical use of capsules-containing carbon 14.
.e support option 3 as cutlined in the. pre decisional rulemakf 9: plan (docket No.
PIOf 35-12)..-Thanks for the early opportunity to ccament.
1 l udi. interne t3 ("BSINCIAIedeq. state.ut.us ").
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STATE OF NEW YORK Sc.0 DEPARTMENT OF LABOR DIVISION OF SAFETY AND HEALTH AA$-
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Radiological Hea!th Unit -
Building #12. Room 457 State Office Building Campus Albany. NY 12240 g
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i October 14,1996
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4 Mr. Lloyd Bolling _
Office of State Programs USNRC Mail Stop 3 D 23 Washington, D.C. 20555 9
' REi Agreement States Letter SP-96-107 Draft Rulemaking Plan 10 CFR Part 35
Dear Mr. Bolling:
We agree with NRC's contractor's conclusion that the widespread medical use of I
L capsules containing one microcurie of carbon 14 would involve no risk to public health and safety or the environment,' and would provide significant medical benefits to the population.
Using a risk-based regulatory approach, there is, therefore, no need to regulate this product for its radioactive content. This is especially true since it will be regulated by the U.S. FDA as a drug. Therefore, it should be distributed as exempt, not as generally-licensed l
(GL).
The only reasons given by NRC for not exemping the recipients of this product from all further regulation, is that manufacturers (and initial distnlutors other than manufacturers) would have to obtain NRC licenses authorizing exempt distribution, and this would impose a i
regulatory burden on NRC.
Since it appears that there is only one manufacturer of this product at the present time, this would seem to be an inconsequential burden. The draft rulemaking plan also implies that there would be no regulatory burden resuhing fmm a GL designation, and states that users under a GL would not have to register with NRC, as they did under the GL that used to be in Part 35 and Agreement State regulations. However, on page 11 of the plan it states that "in developing the actual rule language, consideration should be given to the issue of whether any general license conditions (such as those in the former 10 CFR 35.31, " General License for Medical Use of Certain Quantities of Bypmduct Material") are appmpriate." 'therefore, the -
possibility of a regulatory burden on usets of the product, and on regulatory agencies, under a GL
- unknown at this time.- This makes the comparison of' regulatory ahematives in the plan w
. invalid.
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4, General Licenses always contain temis and conditions, since they are a means of exening regulatory control over the users of a GL product. However, they are an ineffective regulatory tool that attempts to establish a gray area between exemption and specific licensing, and 6is oRen leads to inadequate control over hr.zardous radiation sources and -
over-regulation of trivial radiation sources.
Having concluded that this product needs no regulatory control aAer its distribution, it makes no sense to license end-users in any way. If decisions on whether, product should be distributed as exempt are to be based on the regulatory burden on NRC, rather than on an appropriate risk 4enefit analysis, we will distort our entire regulatory system.
The product should clearly be exempt, and NRC's process re-engineering group should
~
ensure a streamlined exempt 4istribution licensing process for it.
Sincerely, Rita Aldrich Principal Radiophysicist RAdmp n
~,.
l From:
3pell, Bill cbills°. state.la.us>
To Fraree, Terty <tef0303thub.doh.wa. gov >
Date:
10/23/36 12:12pm
Subject:
RE: SP 96 107 To the final paragraph, We sopport your position on this matter completely.
I would add, 'It wouldn't hurt to anvolve the regulated community early in The result will be eraser for those regulated to the rulerTking procesa.
We tried this in developing the well lodging regulations, and it accept.'
worked well.
Tha regulated community felt their views were adequately addressed.
CULater......
Bill Pt ;4: Franee, Terry phl; wpo(dhec4005. columbia 34.autryvr); rratliffs rquillins ray.d. paris; lab To:
103075.1375; egrad.bsinclai; Cc:
paul. merges; mmobley; jvolpes dm0020; dflater;trknycbrh; teff100ws davidson; ccmail.kwangler; kxr01%albnydh2.bitnet; robert. sche 111 hallisey; bill _s; k_a31en; tom _ hill; hwl.ebailey; gdwa23a; rkelley Subject SP 96 107 Date: Tuesday, October 22, 1996 F 23PM To: Lloyd Bolling, OSP, NRC This is our response to your request for comments on the ' Draft 1996.
Rulemaking Plan for 10 CFR 35' received by FAX on October 1, Specifically, the draft plan, in ' Pre decisional" form, concernsand ie based
' Medical Use of Capsules Containing One Microcurie of Carbon 14' on PRM 35 12.
- 1) we support alternative 2 which would We have two summary comments:
and 2) esttblish a ' general license" for use of this low risk diagnostic test; we believe ' parallel rulemaking* with the CRCPD should have been considered rather than jumping immediately to a " direct final rule'.
A general license similar to that for 'in vitro' testing (10 CFR 31.11) is This includes a registration considsred appropriate for this rulemaking.
This will provide a method of 'authorisation' for a wide range of process.
(shere a registration fee is required);
physician
- users; will be low cost allows the manufacturers of the capsule to be fully licensed by an Agreement States if located therein; and provides the regulatory agency with some knowledge of usage within its jurisdiction plus a database for later use in evaluating a further relaxatian in the dayree of control over this new product (for instance, eliminating the registration requirement).
We agree with the choice of ' Division 3" for Agreement State compatibility although a corresponding assessment aboNid also be provided to relate it to the new clamaiticetion expected under the implementation procedures for the Final Policy Statement on the Adequacy and Compatibility of Agreement State Frog -9s.
Finally, while we support speedy resolution of PRMs and agency initiated rulemaking ef forts, we have never supported the level of secrecy that ifRC hes In the itatLt1 employed in the various phases of its rulemaking ef fort.
phac.,, it allows NRC staff to fixate on a solutien of their own devisang, and to establish themselves in a narrowly defined position which they then feel results in the Commission receiving must be defended.
At thw 2inal phase, it a ' decision' paper that tries to reflect the scopa of an issue and the varying and of ten complex positions of other interested parties as interpreted by NRC
bcb (SPo$
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PHL-S 60 DEPARTM R SAFETY 10 yE (g; g,
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Jim Edgar
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Thomas W.Ortciger Govemor
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Director et=
October 28,1996 PaulI4haus g
D8Puty Director g
Omoe of state Programs Mail Stop 3D23 1
- s Office of Governmental and Public Affairs y
U.S. Nuclear Regulatory Comrnist. ion Washington, D.C. 20555 ev Re:
Drah Rulemaking Plan entitled " Medical Use of Capsules Containing One Microcurie of Carbon 14."
i
Dear Mr. lehaus:
i
'the Blinois Department of Nuclear Safety (the Department) hereby submits its co:nznents on the referenced rulemaking plan. h proposed rulemaking represents changes to 10 CFR Part 35 to authorize the commercial distribution and use of a one I
micro Curie C-14 capsule for in-vivo diagnostic testing for peptic ulcers under a General Ucense.
'the Department believes the best option is Ahernative 2, in which the NRC would only need to issue e license for the manuft:ture and distribution of the C-14 capsules in accordance with 10 CPR Part 32. Diaribution to persons exempt is consistent with the NRC's todmical evaluation and would ensure that physicians could i
have access to this material withoM a specinc o< general license. 'Ihe==nhar of new manufacemer/ distributor easept distribution licenses win be far fewer than the amnber of liosenes (or registradons) that would be issued nationwide to physicines who would potentia!!y une this material.
L-;' ri= of Alternative 3 would require the NRC and each of the,29 Agrammans States to have costly rulemaking proceedings to add a general licease to the ng "-:-- of each agency. General H-should be used only when some level of control is desired for the product, h NRC's technical analysis indicates that no controls are wananted, so Altercative 2 is apperpiate and the least costly approach.
1 99-h-4 BP-BG4
.1 Paul Lohaus 3
Page 2 October 28,1996 l
'Ihe Department appreciates the vyywriunity to provide its perspective on this draft rulesnaking plan. If you have questions regarding these items, please contact me l
or Steven C. Collins at (217) 785-9948.
U i
Thomas W. Ort Director i
TWO:meb cc:
Jim Lyreh l
State Agreements Officer i
I I
(.
October 29,' 1996 Mr. Lloyd Bolling Office of State Progrtms USN8C M hop 3 0 23 Washbeton DC 20555 Deer Mr. Bolkng:
This is in response te AN Ayeement States Letter 8P 96107 Draft Rule Making Plan 10 CFR Part 35. We support Altanetire 2. Although inis piscu en initial reguistory bwden en the NRC, it reduces the bunion en physiciens distrhuters and the Ayeomant States. This should not place any undue reguistory bunion en Agreement State licensees wishing to distribute the one microcwie corben 14 capsules. The capsules can be directly distributed by the manufactww to physicians. As there dou ret appear to be any redelogicolimpects en patients, workers w the public, the snelysing Isberstwy would ret need to be licensed. Agreement 8tata are always amending their rules as e metter of competbility. Thwefws, we considw the reguistwy burtlen to be minimal to irw:lude the esamption during rulemeking.
We do not agree with Altemative 3, granting a generallicense. Our reguletory burden is incrossed accepting Altemative 3. Although Altwnstive 3 may not cause e regulatory burden on NRC,it willimpose prester paperwork Lost to Georgie licenoms, the distrbutors of the capsules, and will result in generallicense fees being assused to
' physicians.
The specific regulatwy burden on Georgia licensees would be as follows:
1.
We would continue to require the distrbutor to send us a report quartwly w required under the rules for distribution undw a generallicense.
2.
We will be required to invoice the physicians tw the general bconses fee, which wouw: not be charged to a person receiving under en esenet distrbution license.
s 3.
We may hen to amend el of sw distrbution licenses to allow for distrbution of this product undw e i
general heense. This will add en additional cost to ow boeneses tw the amendment les that would
- not be causal by esenet distributi:.a.
We recommand proceeding with a direct final rule amendng Port 35 in confwmance with Altemative 2.
8%
1 Themes E. Hitt, Manager Redmactin Metwiels Preysm
.TEHlkic 4
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From Martha G i,.. slee cMartha_G DIBBLEE6ohdmail.hr. state.or.us>
To WND1.WNP9 (lab)
Date:
12/6/96 4:0$pm Subjects OSP FILE CODE: SP A 4 (Petition for rulemaking for C 14 capsules for helicobacter) i Hello, Lloyd, oregon doesn't intend to authorise'in vivo diagnostic procedures under general license. Persons who use this diagnostic procedure must be specific \\1?./
i authorised under 35.100 or equivalent regulations (uptake, dilution, excretion). Oregon authorises only in vitro procedures by general license.
Thank you for the transcript of the NRC Briefing that we all attended on Wednesday 13 November. I was glad to see the NUREG finally published.
Martha i
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udi. internet3 (' Christie _L,,HINKLEcohdmail.hr. state....
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