ML20199C743

Obtains Commission Approval for Publication of Final Rule on Exempt Distribution & Use of Radioactive Drug Containing One Microcurie of Carbon 14 Urea (Parts 30 & 32)

ML20199C743
Person / Time
Issue date:	10/09/1997
From:	Callan L NRC OFFICE OF THE EXECUTIVE DIRECTOR FOR OPERATIONS (EDO)
To:
References
FRN-62FR63634 AF70-2-012, AF70-2-12, SECY-97-232, SECY-97-232-01, SECY-97-232-1, SECY-97-232-R, NUDOCS 9711200117
Download: ML20199C743 (58)

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RULEMAKING ISSUE (Affirmation)

October 9.1997 SECY-97-232 EQB: The Commissioners ERQM L. Joseph Callan, Executive Director for Operations

SUBJECT:

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

PURPOSE:

To obtain the Commission's approval for publication of the subject final rule.

BACKGROUND:

On May 30,1997, the Commission approved the publication of a proposed rule to amend Parts 30 and 32 that would permit the exempt distribution and use of capsules containing one microcurie carbon-14 urea for 'in vivo

• diagnostic use. On June 16,1997, the proposed rule was published in the Federal Register (62 FR 32552) for a 30-day public comment period. This action is being taken in response to a petition for rulemaking (PRM 35-12) submitted by Tri-Med Specialties, Inc.

DISCUSSION: C in response to a request for comment on the proposed rule, the NRC roceived seven public comment letters. Four commenters supported the rule, one opposed the rule, and two provided / gg comments without explicitly stating whether they supported or opposed the rule. A summary of public commer,is and staffs responses are presented in the preamble of the enclosed Federal y

Register notice. Except for two minor changes, the final amendments are the same as the s proposed amendments. N v The Commission should note that one commenter suggested that research use also should be a sfs y

permitted under this exemption because the radiological risk is insignificant. The staff did not D 3 4

change the final rule in response to this comment. Aj common rule the Protection of Human Subjects: Notices and Rules,' was promulgated by 16 Federal Ob CONTACT: y e ,-

Anthony Tse, DRA/RES LtQIE: TO DE MADE PUBLICLY AVAILABLE M/

(301)415-6233 WHEN THE FIN AL SRM IS MADE AVAIALBLE f 1i y o

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. l The Commissioners 2 agencies on Juna 18,1991 (56 FR 28002) and was intended to ensure the protection of human research subjects. The Federal policy represents a societal determination that any research (including research involving radioactive material) must provide for the following minimal prctections for the human subjects: (1) that the research is approved by an Institutional Review Board (IRB) and (2) that the human subject gives informed consent to participr',e in the research. Further, under the common rule, these protections must be provided regardless of whether or not there is any risk of consequences (including radiological consequences). This view is supported by the faut that during the public corament period of the common rule, a commenter suggested that all minimal rit,k research be exempt from the ;egulations; however, the final rule did not adopt this comment. While the common rule provides for the exemption of certain research, such as educational tests; survey, interviews, or observation of public behaviors; collection of existing data; it does not provide for an exemption of research activities involving minimal risk. However, tc.e common rule permits department or agency heads to retain final judgment as to whether a pa ticular activity is covered by this policy.

NRC did not participate in the promulgation of the common rule. Subsequently, the NRC adopted 10 CFR 35.6 that requires a licensee who cenducts research involving human subjects using byproduct material to obtain informed consent from the human subjects and obtain prior approval by an " Institutional Review Board' (IRB), Use of the capsules in conducting human research without following these provisions could be viewed as the NRC acting contrary to a societal determination expressed in the common rule that all research involving human subjects be performed under provisions containing certain minimal protections te the human subjects participating in the research. Such action by the Commission could have the effect of eroding public confidence in the NRC. Accordingly, even though the capsules p esent minimal radiological risk, the staff recommends that such research use of the capsules not be exempt from $ 35.6.

This final rule amends Part 30 to add a new section (30.21) to permit any person to receive, possess, use, transfer, own, or acqtdre capsules containing one microcurie carbon-14 urea for "in vivo" diagnostic use without a license. The final amendments include a reminder that persons will not be relieved from complying with applicable FDA, other Federal, and State requirements governing drugs.

This final rule also amends Part 32 to add two new sections (32.21 and 32.21a) to establish requirements for the manufaciure and distribution of carbon-14 urea capsules to persons exempt from licensing. Currently, NRC requires licensees who manufacture, prepare, or commercially distribute radioactive drups to meet the requirements in @ 32.72(a)(2) (e.g., be registered or licensed with the FDA or a State as a drug manufacturer or be licensed as a pha'inacy by a State Board of Pharmacy). Licensees distributing these capsules under an exempt distribution license will need to meet this same requirement. This provides high confidence that the carbon-14 urea capsules contain one microcurie of carbon-14 and da not contain other radioactive contaminants.

The Commissieners 3 ftESOURCES:

Resources to complete and implement this rulemaking are ine!uded in the current budget.

COORDINATION-The Office of the General Counsel has no legal objection to the final rulemaking. The Office of the Chief Financial Cfficer has reviewed this Commission paper for resource impacts and has no objections. .The Office of the Chief Information Officer concurs that there wiil be no information ter:tinology or management impacts.

RECOMMENDATION-That the Commission:

1. Anorove the Notice of Final Rulemaking for publication (Enclosure 1).

2. Certify that this rule, if promulgated, will not have a negative economic impact on a substantial number of small entities in order to satisfy the requirements of the Regulatory Flexibility Act,5 U.S.C. 605(b).

3. MQia:

a. The final rule will be published in the Federal Regitter; b, The Chief Counsel for Advocacy of the Small Business Administration will be informed of the certification regarding economic impact on small entities and the reasons for it as required by the Regulatory Flexibility Act.

c. A regulatory analysis has been prepared (Enclosure 2);

d. An Environmental Assessment has been prepared (Enclosure 3);

e. The appropriate Congressional committees will be informed (Enclosure 4);

f. Congressional review letters for Small Business Regulatory Enforcement Faimess Act will be sent (Enclosure 5); ,

g. A public announcement will be issued (Enclosure 6);

h. This final rule amends information collection requirements that are subject to the Paperwork Reduction Act of 1995 (44 U.S.C. 3501 et seq.). This rule has been approved by Office of Management and Dudget;

i. All Agreement States will be sent a copy of the final rule upon approval for publication:

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? The Commissioners 4 J. The petitioner will be notified of this action and will be sent a copy of the Federal Register notice; and *

-k. Copka of the Federal Register notice of final rulemaking will be distributed to . ,

affected licensees and commentars on the proposed rule. The neSe will also be sent to other interested parties upon request.

s L.J< ph allan

• Exe:utive Director for Operations

Enclosures:

As stated (6)

SECY POTE:

Commissioners' comments or consent should be provided directly to the Office of the Secretary by c.o.b. Monday, October 27, 1997.

Commission staff office comments, if any, should be submitted to

- the Commissioners NLT October 20, 1997, with an information copy to the Office of the Secretary. If the paper is of such a nature that it requires additional review and comment, the Commissioners and the Secretariat should be apprised of when comments may be expected.

DISTRIBUTION: NOTE:. This paper is tentatively scheduled Commissionerr for affirmation at an open meeting during OGC =the week of October 27, 1997. Please

'OCAA- refer to the appropriate Weekly Commission OIG Schedule, when published, for a specific OPA date and time.

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i ENCLOSURE 1 FEDERAL REGISTER NOTICE a

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[7590-01-P]

NUCLEAR REGULATORY COMMISSION 10 CFR Pads 30 and 32 RIN: 3150-AF70 Exempt Distribution of a Radioactive Drug Containing One Microcurie of Carbon-14 Urea AGENCY: Nuclear Regulatory Commission.

ACTION: Final rule.

SUMMARY

The Nuclear Regulatory Commission (NRC) is amending its regulatioris to permit NRC licensees to distribute a radioactive drug containing one microcurie of v ton-14 urea to any person for "in vivo" diagnostic use. The NRC has determined that the radioactive component of suc'h a drug in capsule form presents a minimal radiation risk and, therefore, regulatory control of the drug for radiation safety is not necessary. This amendment makes the drug more widely available and reduces costs to patients, insurers, ano the health care industry. This action grants a petition for rulemaking (PRM-35-12) from Tri-Med Specialties.

Inc. and completes action on the petition.

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

ADDRESS: Copies of the public record, including the final regulatory analysis and any public comments received on the proposed rule, may be examined and copied for a fee in the Commission's Public Document Room at 2120 L Street, NW. (Lower Level), Washington, DC.

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

SUPPLEMENTARY INFORMATION:

1. The Petition for Rulemaking.

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

Ill. Summary of the Final Amendments.

IV. Description of the Final Amendments.

V. Agreement State Compatibility.

VI. Finding of No Significant EnviroiimentalImpact: Availability.

Vll. Paperwork Reduction Act Statement.

Vill. Regulatory Analysis.

IX. Regulatory Flexibility Certification.

X. Small Business Regulatory Enforcement Faimess Act.

XI. - Backfit Analysis.

XII. List of Subjects.

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l. The Petition for Rulemaking  !

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

PRM 35-12) from Tri-Med Specialties, Inc (Tri-Med). In a letter dated August 23,1994, Tri-Med petitioned the NRC to amend its regulations "to allow for the general licensing and/or exemption for the commercial distribution by licensed pharmaceutical manufacturers of a capsule containing one micro-Curie (pCi) of C-14-urea for in vivo diagnostic testing." The purpose of this diagnostic test is to detect the presence of the ba~terium Helicobacter pylori (H. pylori), a cause of peptic ulcers in humans.

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

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

II. Proposed Rule, Public Comments, and NRC Responses A proposed rule was published on June 16,1997 (62 FR 32552) that would permit NRC licensees to distnbute capsules containing one microcurie C-14 urea to any person for "in vivo" diagnostic use. The public comment period closed on July 16,1997.

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

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

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

ComtrenLt. Under the proposed distribution, the NRC shauld not be forbidding research use of this drug by the same physicians who may use it clinically. Research use also should be permitted under this exemption because the radiological risk for using C-14 capsules is insigni'icant.

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

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participate in the research. Further, these protections must be provided regardless of whether or not there is any risk of consequences (including radiological consequences). This view is supported by the fact that during the public comment period of the common rule, a commenter suggested that all minimal risk research be exempt from the regulations; however, the final rule did not adopt this comment.

NRC did not participate in the promulgation of the common rule. Subsequently, the NRC adopted 10 CFR 35.6 that requires a licensee who conducts research involving human subjects using' byproduct material to obtain informed consent from the human subjects and obtain prior approval by an IRB. Although the NRC did not adopt the common rule, the intention is to follow the essential requirements of the common rule. Because the common rule does not provide an exemption for research involving minimal risk, the Commission has determined that such research use should not be excmpt from 10 CFR 35.6.

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

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

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

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Comment 3: One commenter stated that, when the total amount of energy released from complete decay of a radionuclide is considered, one microcurie of C-14 has the largest energy release, because of its long hcif-life, when compared to one microcurie of Tc 99m or l-131. The commenter concluded that, given the insignificant radiation risk from the diagnostic use of C 14 urea, the radiation risk from the diagnostic use of Tc-99m or 1-131 also would be insignificant.

Resoonse: Carbon-14 emits low energy D radiation with no y radiation, low energy p radiation cannot penetrate very far into tissue. On the other hand, both Tc-99m and 1-131 emit y radiation, which is more penetrating than the weak p radiation. Furthermore, the total energy of C-14 is released slowly over tens of thousands of years, but the total energy of Tc-99m and 1-131 is released much faster, i.e., within several days and tens of days, respectively. Thus, the radiation risk to an individual from one microcurie of C-14 is insignificant because of the long half-life and low energy emitted. This is not the case for 1-131 or Tc-99m which are both short lived y emitters and which would deposit most of the total energy in the individual.

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

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

Comment 5: The Commenter agrees that the widespread use of thir product will require uniform regulations and that Agreement States will need to make appropriate regulatory 6

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- provisions to enable persons to receive the drug for fin vivo" diagnostic use. To avoid ,

confusing licensees and users, these changes to NRC and Agreement State regulations should -

be made simultaneously. The commenter urges that the NRC take action to expedite the Agreement State regulatory changes.

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

Comment 6: The NRC should address this rule in its onge!q effort to revise 10 CFR Part 35 in its entirety. The commenter believes that (1) this rule represents a piecemeal effort to respond to a narrow issue and (2) the issue of reduced regulation for medical use of C-14 capsules is applicable to the same extent for virtually the entire range of diagnostic radioisotopes.

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

Thus, the NRC decided to proceed with this rule now because the benefits of making this capsule available to anyone, including primary-care physicians, outweigh the benefits of addressing this issue in the overall revision of 10 CFR Part 35.

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

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

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

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

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

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

Comment 9: The environmental assessment fails to consider the fact that another equally noninvasive, but nonradiological, diagnostic procedure (such as C-13 test) is available 8

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and provides a comparable alternative to the C-14 test. The apparent assumption underlying the environmental assessment is that in the absence of the C-14 test, the only alternative for the detection of H. pylori is invasive gastroendoscopy.

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

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

Resoonse: This change is a departure from existing NRC regulationn. In the statement of consideration for the proposed rule, under the h.sading " Current NRC Regulations on Exemptions From Licensing," the NRC stated that, eithough two broad material exemptions t

( 30.14,

• Exempt concentrations," and 6 30.18, "Exernpt quantities") exclude the transfer of byproduct material contained in any product designed for ingestion or inhalatio, by a human being, the C-14 capsules manufactured or prepared as a radioactive drug can be distributed to persons exempt from licensing for "in vivo" diagnostic use because the capsules present an insignificant radiological risk to the public and the environment. This exemption only applies to 9

r the diagnostic use of capsules containing one microcurie C-14 manufactured or prepared as a radioactive drug to make a clear distinction between this radioactive drug that is intended for ingestion by humans and other uses of C-14 urea and byproduct material distributed under

$$ 30.14 and 30.18.

Comment 11: The ACMUI's (Advisory Committee on Medical Uses of Radioisotopes) conclusions that either an exemption or general license is appropriate for the C-14 product do not address the fundamental aspects of nuclear safety. Its judgment was based partially on the assumptions: (1) the product may only be dispensed by prescription, (2) the product is approved by the Food and Drug Administration, and (3) the office / facility using the product will be subject to Clinical Laboratory improvement Amendment (CLIA) regulation.

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

either an exemption or general license is appropriate.

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

Resoonse: It is not necessary to impose a possession limit on the amount of C-14 capsules because the radiation risk is insignificant. The earth's atmosphere contains an inventory of naturally occurring C-14 of about 3.8 million curies which is in addition to the huge 10

inventory of about 240 million curies in the world's oceans. The small amount of C-14 released into the atmosphere .'.mm the use of this test would mix with the global inventory and would have no impact on public health. The current world inventory of naturally occurring C 14 results in an average dose to the public of about 1.25 mrem per year, and the release of 0.6 curies of C-14 from the total of 600,000 tests assumed to be administered annually would result in an additional average annual dose of 2 X 104 mrem. In the event that a recallis necessary, the manufacturer may use the same process for recalling any other non-radioactive drugs. If C-14 urea capsules are retumed to the manufacturers, they will be disposed of in accordance with the manufacturer's possession license. A user, however, can dispose the C-14 urea capsules as ordinary trash. Medical users of the C-14 urea test would be unlikely to acquire significant quantities of capsules because they can be ordered within a few days. Thus, even under a recall, the impact of disposing of C 14 urea capsules into landfills by the user would also be insignificant.

Comment 13: It is essential that end users be adequately informed of the product's radioactive characteristics, so that some form of storage, use, and disposal precautions can be followed. Thus, the labeling must be conspicuously and prominently placed. The commenter suggested the following: (1) the phrase " conspicuously and prominently" in front of the proposed labeling

• bears the words Radioactive Material" should be added, and (2) the NRC should require that the radioactive material legend, " Radioactive Material," be included on promotional brochures.

Resoonse: Because the radiation risk from C-14 capsules is insignificant, regulatory control of the use, storage, and disposal of the drug for purpose of radiation safety is not necessary, in fact, the label accompanying C-14 capsules is required to indicate that the 11

capsules may be disposed of by users as ordinary trash. Paragraph (a)(6) of 9 32.21 requires that applicants submit copies of prototype labels and brechures for NRC approval, The NRC will ensure that the labels meet the requirements of 6 32.21a before they are approved. Since paragraph (a) of 9 32.21a specifies that the label must be durable and legible, the use of an additional phrase such as " conspicuously and prominently" is unnecessary. Promotional brochures are for information only; nothing will prevent manu'acturers from indicating on the promotional brochures that C-14 is a radioactive material.

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

These requiruments are consistent with the existing requirements on other items under the heading Exemptions" in 10 CFR Part 50. The amendment includes a reminder that licensees distributing the radioactive drug to persons exempt from licensing would not be relieved from other applicable Federal (e.g., FDA) or State requirements goveming the manufacture and distribution of drugs.

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

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l controi is rssded to provide high confidence that the drug contains one microcurie of C-14 urea and does not contain any other radioactive contaminants.

Final Amendment to 10 CFR Part 30 The NRC has determined that the drug in capsule form presents nu significant radiological safety or environmental risk, and that it is not necessary to regulate the use of this drug for its rcdioactive component. Therefore, the NRC can not justify requiring physicians, or any other rersor$, to meet NRC training and experience criteria directed at the safe use of radioact,ve drugs, cr to become an " authorized user." Hence, the capsules can be distributed to any persea Howe <er, other Federal or State agencies may limit the receipt and use of the capsules in accoroance with their own requirements.

The regulations in 10 CFR Part 30 are amended to add a new $ 30.21, to permit any person to receive, possess, use, transfer, own, or acquire for "in vivo" diagnostic use, capsules containing one microcurie of C-14 urea without a license. The final regulation includes a reminder that persons receiving the capsules would not be relieved from other Federal or State law governing drugs. Further, in accordance with the NRC's provisions for research involving human subjects (10 CFR 35.6), the exemption permitting receipt and use of the capsules for "in vivo" aiagnostic use does not extend to use of the capsules for research involving human subjects. Any person desiring to use the capsules for human research would still be required to submit an application for a specific license under Part 35. The phrase "in vivo diagnostic use" was selected to describe the activity authorized in $30.21 to differentiate it from the term

" medical use" because:

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D-*+ wz 4n.1, A 4v - el 6 (1) " Medical use" limits administration to authorized users; use of this drug tvould not be so limited; and (2)

• Medical use" includes the administration of the drug to a human research subject,_

which would be prohibited by this rulemaking.

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

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

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IV, Des ription of the Final Amendments The final amendments are the same as the proposed amendments except for two minor changes. Public comments suggested that the phrase " carbon-14 urea capsules not exceeding one microcurie' used in the proposed rule may be interpreted as an exact limit of one microcurie per capsule (See Comment 2 under the heading *Public Comment and NRC Responses). The final rule has been modified and the phrase " capsules containing one microcurie carbon-14 urea (atlowing for nominal variation that may occur during the manufacturing process)" is used. Another public comrnent suggested that labels should contain a statement that the product may be disposed of in the general trash, in the final rule, the label requirements include such a statement.

Manufacturer and Dl::tributors A new section is added to 10 Ci-R Part 32 to permit the distribution of the capsules to persons who are exempt from licensing.

$ 32.21 Radioactive drua: Manufacture. orecaration. or transfer for commercial distribution of capsules containina one microcurie carbon-14 urealach for "in vivo" diaanostic use for humans to oersons exemot from licensino: Reauirements for a license Paraaraoh (a)

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

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

Paraaraoh (a)(1) ,

This paragraph limits issuance of an "exemp' diatribution license" for distributio1 of the capsules to persons exempt from licensing to only thoso who possess either a NRC or Agreement State " specific license" for possession and use cf byproduct material.

Paracraoh (a)(2)

To assure *. hat the capsules contain one rr.icrocurie of caroon-14 and present no other radiological risks, this paragraph requires that the persons manufacturing and/or commercially distributing the capsules for "in vivo" diagnostic use must also meet the requirements of 9 32.72(a)(2). Specifically, these persons must be:

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

Paraaraoh (a)(3)

This paragraph requires applicants to provide evider.ce that each carbon-14 urea capsule contains one microcurie. The NRC's evaluation that the capsules would not result in significant radiation risks was based on the capsules containing one microcurie of carbon-14 urea. Therefore, applicants must demonstrate that the activity of each carbon-14 capsule 16

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

process.

Paracraoh (a)(4)

This paragtaph prohibits carbon-14 uraa from being contained in any food, beverage, cosmetic, dmg or other commodity designed for ingestion or inhalation by, or topical application to, a human being except for the capsuies as described in this section, because exempt distribution of this drug has on;y been evaluated for "in vivo" diagnostic use in the form of a capsule containing one microcurie of carbon 14 urea. There is no prohibition against the capsule being combined with food or beverage at the time of administration so that the capsule can de ingested by the patient.

Paraaraoh (a)(5)

Because the exempt distrihirtion of this drug has only been evaluated for "in vivo" diagnostic use in the form of a capsule containing one microcurie of carbon-14 urea, this paragraph prohibits incorporation of the capsules into any manufactured or assembled commodity, product, or device intended for commercial distribution. Further, although the drug is being distributed to persons exempt from licensing, this paragraph requires the carbon-14 urea to be identified as radioactive because the drug is being used for its radioactive content; therefore, the end user must be provided with information that the o, 1 contains a radioactive material.

17

Paraormoi. (a)(6)

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

Paragraoh (b)

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

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

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

(1) Iderstifies the radioisotope, the physical and chemical form of the radioisotope, the

- quantity of radioactivity contained in each container at a specific date; and i (2) Bears the words " Radioactive Material."

l l

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18 l

The date requirement is consistent with labeling requirements for other radioactive drugs with a half life of greater than 100 days.

Paraaraoh (b)

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

(1) State that the contents are exempt from NRC or Agreement State licensing requirements; (2) Bear the words " Radioactive Material. For "In Vivo" Diagnostic Use Only. This Material is Not To Be Used for Research involving Human Subjects, and Must Not Be introduced into Foods, Beverages, Cosmetics, or Other Drugs or Medicinals, or into Products Manufactured for Commercial Distribution. This Product May Be Disposed of in Ordinary Trash."

The intent of the requirement set out in Paragraph (b)(2) is to make clear that the capsule must remain in the form of a capsule and is not to be combined with one of the listed items such as food or beverages which would result in a rrdioactive product other than in the form of a capsule for commercial distribution. There is no prohibition against the capsule being combined with food or beverage at the time of administration so that the capsule can be ingested by the patient. This label also informs the user that this product may be disposed of in ordinary trash.

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

19

l 1

i

. l Section 30.21 Radioactive drua Caosules containina one microcurie of carbon 14 urea l for "in vivo" dimanostic use for humans Parnaraoh (a)

This paragraph provides an exemption to any person from the requirements for a license to receive, possess, use, transfer, own, or acquire capsules containing one microcurie of carbon-14 urea for "in vivo" diagnostic purposes. It should be noted that the " transfer"in this

- paragraph does not include " transfer for commercial distribution," which is covered in paragraph (c) of this section.

Paraaraoh (b)

This paragraph establishes that persons who desire to use the drug for research involving humans subjects must apply for and receive a specific Part 35 license. Such a license would ensure the protection of the rights of the human subjects by requiring that the research be approved by an IRB and that the human subjects give their informed consent to participate in the research.

Paraaraoh (c)

This paragraph specifies that a specific license is needed to manufacture, prepare, process, ptoduce, package, repackage or transfer such capsules for commercial distribution.

20

T Paraoraoh (d)

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

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

Among these are the distribution of products to persons exempt from licensing, as discussed in 10 CFR Part 150. Hence, amendments related to the manufacture and commercial distribution of the capsules (10 CFR Part 32)is a Division 4 item of compatibility (Category NRC under the new adequacy and compatibility policy). However, amendments related to possession and use (10 CFR Part 30) are a Division 1 item of compatibility (Category B under the new adequacy and compatibility policy) because of the need for nationwide consistency in the use of products which are widely distributed. Therefore, the Agreement States will need to make appropriate provisions in their regulations to allow any person to receive capsules containing one microcurie of carbon 14 urea for "in vivo" diagnostic use in humans without need for a license.

VI. Finding of No Significant EnvironmentalImpact: Availability The Commission has determined under the National Environmental Policy Act of 1969, as amended, and the Commission's regulations in Subpart A of 10 CFR Part 51, that the final rule is not a major Federal action significantly affecting the quality of the human environment; therefore, an environmental impact statement is not required. The final rule establishes 21

requirements for the manufacture and commercial distribution of carbon 14 urea capsules to persons exempt from licensing and establishes regulations to permit any person to receive the capsules without an NRC license.1he Commission believes that the radioactive component of this drug presents no significant radiation risk and, therefore, regulatory control of the "in vivo" l

diagnostic use of the capsules for radiation safety is not necessary. It is expected that this final rule will not cause any significant increase in radiation exposure to the public or radiation release to the environment beyond the exposures or releases resulting fiom the use of the carbon-14 capsules under the current regulations. Also, it is expected that there will be no non-

, radiologicalimpacts. One public comment on the draft environmental assessment has been received (See Comment 9 under the heading " Proposed Rule, Public Comments, and NRC Responses").

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

determination is based is available for inspection at the NRC Public Document Room,2120 L j Street NW. (Lower Level), Washington, DC. Single copies of the environr.iental assessment l and the finding of no significant impact are available from Dr. Anthony N. Tse, Office of Nuclear l

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

Vll. Paperwork Reduction Act Statement l

This final rule amends information ce'lection requirements that are subject to the Paperwork Reduction Act of 1995 (44 U.S.C. 3501 et seq.). These requirements were approved by the Office of Management and C;:doet, cpprovat numbers 3150-0001,3150-0017, i

and 3150-0120.

22 1

The public reporting burden for this collection of information is estimated to average 16 hours1.851852e-4 days <br />0.00444 hours <br />2.645503e-5 weeks <br />6.088e-6 months <br /> per response, including the time for reviewing instructions, searching existing data

. sources, gathering and maintaining the data needed, and completing and reviewing the collection ofinformation. Send comments on any aspect of this collection of information, including suggestions for reducing the burden, to the Information and Records Management Branch (T-6 F33), U.S. Nuclear Regulatory Commission, Washington, DC 20555-0001, or by '

Internet electronic mail at BJS1@NRC. GOV; and to the Desk Officer, Office of Information and Regulatory Affairs, NEOB-10202, (3150-0001,3150-0017, and 3150-0120), Office of Management and Budget, Washington, DC 20503.

Public Protection Notification r

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

Vill. Regulatory Analysis The NP,C has prepared a regulatory analysis for the final rule. The analysis examines the benefits and impacts considered by the NRC. No public comments on the draft regulatory analysis have been received during the public comment period. The regulatory analysis is available for inspection at the NRC Public Document Room,2120 L Street NW (Lower Level),

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

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

Washington, DC 20555-0001, telephone (301) 415-8233 or e-mail at ANT @nrc. gov.

23

e IX. Regulatory Flexibility Certification As required by the Regulatory Flexibility Act of 1980,5 U.S.C. 605(b), the Commission.'

certifies that this rule does not have a'significant economic impact upon a substantial number of 3

r Small entities. The final ruie permits physicians and other health care providers to use an additional diagnostic test without having to obtain an NRC license, thus, would provide cost savings to patients, insurers, and the health care industry. The final rule does not impose any additional obligations on entities that may fall within the definition of 'small entities

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

i- X.: Small Business Regulatory Enforcement Faimess Act in accordance with the Smaii Business Regulatory Enforcement Fairness Act of 1996, the NRC has determined that this action is not "a major

• rule and has verified this determination with the Office of information and Regulatory Affairs, Office of Management and Budget.

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

-- rule, and therefore, a backfit analysis is not required because these amendments do not involve any provisions that would impose backfits as defined in 10 CFR 50.109(a)(1).

24 L

,w- r --, - - - ,e - - .,w-',o +-,,y ., , ---...-r-a r r - .m,a w

XII. List of Subjects 10 CFR Part 30 Byproduct material, Criminal penalties, Govemment contracts, Intergovernmtntal relations, Isotopes, Nuclear materials, Radiation protection, Reparting and record keeping requirements.

10 CFR Part 32 Byproduct material, Criminal penalties, Laboling, Nuclear materials, Radiation protection, Reporting and recordkceping requirements.

For the reasons set out in the prcamble and under the authority of the Atomic energy Act of 1954, as amended, the Energy Reorgan!zation Act of 1974, as amended, and 5 U.S.C.

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

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

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

AUTHORITY: Secs. 81,82,161,182,183, ' 36,66 Stat. 935,948,953,954,955, as amended, sec. 234,83 Stat. 444, as amended (42 U.S.C. 2111,2112,2201,2232,2233,2236, 2282); secs, 201, as amended,202,206,88 Stat.1242, as amended, 1244,1246 (42 U.S.C.

5841,5842,5846).

Section 30.7 also issued under Pub, L.95-601, sec.10,92 Stat. 2951 as amended by l

Pub. L.102-486, sec. 2902,106 Stat. 3123, (42 U.G.C. 5851'.f Section 30.34(b) also issued 2S

• I under sec.184,68 Stat. 954, as amended (42 U.S.C. 2234). Section 30.61 also issued under sec.187,68 Stat. 955 (42 U.S.C. 2237).

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

G 30.8 Information collection rgquirements: OMB sooroval.

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

$$30.9, 30.11, 30.15, 30.18, 30.19, 30.20, 30.21, 30.32, 30.34, 30.35, 30.36, 30.37, 30.38, 30.41,30.50,30.51,30.55, appendices A and C to this part.

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

6 3121 Radiocctive drug: Caosules containina one micacurie of carbon-14 urea for "in vivo" '

diagnostic use for humans.

(a) Except as provided in paragraphs (b) and (c) of this section, any person is exempt from the requirements for a license set forth in Section 81 of the Act and from the regulations in this part and Part 35 of this chapter provided that such person receives, possesses, uses, transfers, owns, or acquires capsules containing one microcurie carbon-14 urea (allowing for nominal vanation that may occur durina the manufacturing process) each, for "in vivo" diagnostic use for humans, (b) Any person who desires to use the capsules for research involving human subjects shall apply for and receive a specific license pursuant to Part 35 of this chapter.

26

(c) Any person who desires to manufacture, prepare, process, produce, package, repackage, or transfer for commercial distribution such capsules shall apply for and receive a snecific license pursuant to S 32.21 of this chapter.

(d) Nothing in this section relieves persons from complying with applicable FDA, other Federal, and State requirements governing receipt, administration, and use of drugs.

PART 32-SPECIFIC DOMESTIC L! CENSES TO MANUFACTURE OR TRANSFER CERTAIN ITEMS CONTAIN;NG BYPRODUCT MATERIAL

4. The authority citation for Part 32 continues to read as follows:

AUTHORITY: Secs. 81,161,182,183, 68 Stat. 935, 948, 953, 954, as amended (42 U.S.C. 2111,2201,2232,2233); sec. 201,88 Stat.1242, as amended (42 U.S.C. 5841).

5. In 9 32.8, paragraph (b)is revised to read as follows:

9 32.8 information collection reauirements: OMB aooroval.

(b) The approved information collection requirements contained in this part appear in 99 32.i i, 32.12, 32.14, 32.15, 32.16, 32.17, 32.18, 32.19, 32.20, 32.21, 32.21 a, 32.22, 32.23, 32.25, 32.26, 32.27, 32.29, 32.51, 32.51 a, 32.52, 32.53, 32.54, 32.55, 32.56, 32.57, 32.58, 32.61,32.62,32.71,32.72,32.74, and 32.210.

21

6. A new S 32.21 is added to read as follows:

6 32 21 Radioactive drua: Manufacture orecaration. or transfer for commercial distribution of capsules containina one microcurie carbon-14 urea each fq";n vivo" diaonostic use foLbumans to oersons exemot from licensina' Reauirements for a license.

(a) An application for a specific license to manufacture, prepare, process, produce, package, repackage, or transfer for commercial distribution capsules containing ona microcurie carbon 14 urea (allowing for nominal variation that may occur during the manufacturing process) each for "in vivo" diagnostic use, to persons exempt from licensing under S 30.21 of this chapter or the equivalent rt.1dations of an Agreement State will be approved if:

(1) The applicant satisfies the general requirements specified b 9 30.33 of this chapter, provided that the requirements of 9 30.33(a)(2) and (3) of this chapter do not apply to an application for a license to transfer byproduct material manufactured, prepared, processed, produced, packaged, or repackaged pursuant to a license issued by an Agreement State; (2) The applicant meets the requirements under S 32.72(a)(2) of this Part; (3) The applicant provides evidence that each capsule contains one microcurie carbon-14 urea (allowing for nominal variation that may occur during the manufacturing process);

(4) The carbon-14 urea is not contained in any food, beverage, cosmetic, drug (except as described in this section) or other commodity designed for ingestion or inhalation by, or topical application to, a human being; (5) The carbon-14 urea is in the form of a capsule, identified as radioactive, and to be used for its radioactive properties, but is not incorporated into any manufactured or assembled commodity, product, or device intended for commercial distribution; and (6) The applicant submits copies of prototype labels and brochures and the NRC approves these labels and brochures.

28

(b) Nothing in this section relieves the licensee from complying with applicable FDA, other Federal, and State requirements governing drugs.

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

G 32.21a Same: Conditions of licente.

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

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

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

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

(1) State that the contents are exempt from NRC or Agreement State licensing requirements; and (2) Bear the words " Radioactive Material. For "In Vivo" Diagnostic Use Only. This Materialis Not To Be Used for Research involving Human Subjects and Must Not Be introduced into Foods, Beverages, Cosmetics, or Other Drugs or Medicinals, or into Products Manufactured for Commercial Distribution. This Material May Be Disposed of in Ordinary Trash "

Dated at Rockville, Maryland this day of .1997.

For the Nuclear Regulatory Commission.

John C. Hoyle, Secretary of the Commission.

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e 4

ENCLOSURE 2 REGULATORY ANALYSIS

. t REGULATORY ANALYSIS FOR FINAL RULEMAKING

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

1. Backaround 1

1.1 Statement of the Problem On Octow 6,1994, the Commission docketed a petition for rulemaking (Docket No. PRM 35-

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

" Peptic ulcer disease is a chronic inflammatory condition of the stomach and duodenum that affects as many as ten percent of people in the United States at some time in their lives. The disease has relatively low mortality, but it results in substantial human suffering and high 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 ui t.ers are commonly caused by a bacteriun called H. pylori. This bacterium INes in the stomach of most ulcer sufferers. By treating ulcer patiente with antibiotics, doctors can now cure most ulcer problems.

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

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

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,- ~_ - . - . - , . , - . - - , . - ... - - . , .- . .. -

1.2 Current NRC Regulations in 10 CFR Part 32, " Specific Domestic Licenses To Manufacture or Transfer Certain items Containing Byproduct Materials," $ 32.72, " Manufacture, preparation, or transfer for commercial distnbution of radioactive drugs containing byproduct material for medical use under Part 35,"

provides for commercial distribution of radioactivo 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-uros to persons authorized pursuant to Part 35.

In 10 CFR Part 35, " Medical Use of Byproduct Material," sets forth radiation safety requirements, including requirements for the training and experience of authorized user physicians to assure the safe possession and use of radioactive dregs containing byproduct material.

Existing exemptions for use of byproduct material in S 30.14, " Exemption concentrations" and 9 32.18, " Manufacture, distribution and transfer of exempt quantities of byproduct material:

Requirements for license," do not permit the exempt transfer of byproduct material contained in any food, beverage, cosmetic, drug, or any product designed for ingestion or inhalation by, or application to, a human being.

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

1.3 Earlier NRC Actions Following the receipt of the petition, a " Notice of receipt of petition for rulemaking" was published for public comment in the Federal Register on December 2,1994 (59 FR 61831). A total of 315 public comment letters were received Of these,313 supported the petition (they were mostly form letters) and two letters opposed the petition. The two letters opposing the petition stated that (1) the product should not receive an exempt status because the uncontrolled distribution and application of this product could lead to significant risk to the public and (2) medical uses should be restricted to short-lived isotopes because of disposal problems presented by long-lived isotopes.

This petition was discussed with NRC's Advisory Committee on the Medical Uses of Isotopes (ACMUI) at the October 1995 meeting. The ACMUl indicated that it endorsed the wide availability of this diagnoste test and that the radioactive drug could be used under a general license or an exemption, whichever the NRC may determine to be procedurally easier.

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

~- . -.- - -.- - - _- - -.- . - . -

1A Prooosed Rulo and Public Comments The proposed rule was published in the Federal Register (62 FR 32552, June 16,1997) for a 304ay public comment period. The NRC received seven public comment letters. Four commenters supported the rule, one opposed the rule, and two provided comments without explicitly stating whether they support or oppose the rule. A summary of public comments and NRC's responses are presented in the picamble of the Federal Register notice. Except a minor ,

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

2. Qbjective The objective of the rulemaking is to amend 10 CFR Part 32 to permit the manufacture and commercial distribution of "C-urea capsules to any person (including physicians who are not ,

" authorized users' under Part 35) and to amend 10 CFR Part 30 to permit any person, without an NRC license, to receive and use the capsules for in vivo diagnostic use for humans;

3. Attemally.as Three alternatives have been considered in the regulatory analysis: deny the petition, i.e.,

maintain the status quo, permit the distribution of the capsules to persons exempt from licensing, and permit the distribution of the capsules to generallicensees.

Under the first alternative, only physicians who are authorized users under Part 35 would be  !

allowed to possess and administer the "C-urea test. Any physician could apply to become an authorized user. However, the NRC expects few physicians would apply for a Part 35 license for the sole purpose of using the capsules because of the requirement for training and experience and the associated costs of obtaining and maintaining a Part 35 license.

Afternatively, physicians who are not authorized users can continue to refer their patients to physicians who are authorized users to undergo the diagnostic test. However this would not relieve the current expense, inconvenience, and delay encountered in an otherwise straight-forward procedure.

Under the second alternative,10 CFR Parts 32 and 30 would be amended.10 CFR Part 32 would be amended to permit the manufacture and comrnercial distribution of "C-urea capsules to any person (including physicians who are not " authorized users" under Part 35); 10 CFR Part 30 would be amended to permit the manufacture and comrnercial distribution of the capsules to any person, for in vivo diagnostic use for humans. The NRC has detemiined that the radioactive component of this drug presents a minimal radiation risk and, therefore, regulatory control of the capsules is not necessary.

Under the third alternative,10 CFR Part 35 would be amended to permit any physician to receive and use the capsules under a generallicense. The health and safety concems for this alternative are the same as the Altemative 2. However, if this alternative were adopted, there could be a burden to those Agreement States that normally require registration of general 3

license holders. An additional burden could also be imposed on generallicensees located in the Agreement State if the State charges a license or registration fee.

4. Value-Imoact Analvcis 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).

. . The test is 95 percent accurate and quite inexpensive because of its simphcity. The test would permit doctors to determine easily whether or not ulcer patients have been cured of their infection. By providing the public with an inexpensive, easily accessible diagnostic test, more individuals would be accurately diagnosed and treated for their H. pyloriinfection. This would ssve the United States an estimated $500 million per annum over conventional therapy.

The petitioner estimates annual benefits to be on the order of $500 million/ year. This assumes approximately 600,000 "C-urea breath tests / year, at an average cost of $100, in lieu of performing endoscopy at an average cost of $1000/ test. It assumes that the lower cost and greater availability of an unregulated breath test would result in a complete substitution for endoscopy. Tri-Med's benefit analysis provides a measure of the total benefits associated with the test and does not focus on the incremental benefits of administering the test pursuant to 10 CFR 35.100 regulation (status quo) versus releasing the test to all physicians (NRC licensed and non licensed alike). Implicit in Tri-Med's estimated annual benefits is the presumption that none of these "C tests and corresponding savings would accrue if the petition were denied, in reality, under the status quo, the test would be available and administered by physicians or clinics holding a license under NRC's Part 35 or an equivalent Agreement State regulations.

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

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

4.2 The NRC's Assessment (a) Cost Savinas Assaciated with Amendments to 10 CFR Part 30 The value impact analysis focuses on the incremental benefits of granting relief consistent with Attemative 2 or 3, as specified in Section 3 above. The analysis looks solely at changes relative to the base case or status q'.lo. In this analysis, the comparison is between regulated and unregulated "C urea breath tests, not unregulated "C-urea breath tests and endoscopies or other noninvasive tests. For the purposes of this regulatory analysis, the NRC assumes that the same number of breath tests (i.e.,600,000 tests) will be administered regardless of the level of NRC regulatory control. This view is predicated on the belief that each physician's primary 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 4

l 4

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 j procedures.  ;

The benefits of adopting the petition accrue as a result of reduced patient cost and reduced l 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 be some regulatory  !

savings because the NRC would not have to expend resources reviewing new applications for i specific medical use licenses. However, these uavings would be 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 dculation is based on the assumption that as a result of this rulemaking action, a sonificant portion of the 600,000 patients woeld receive the "C breath test from physicians who  !

are not authoria cd users (e.g., gastrointestinal specialists). The actual savings would be dependent on the number of tests ultimately administered by physicians who are not authorized i users, thereby eliminating the need for a referral to physicians who are authorized users (e.g.,

nuclear medicine specialists).  ;

The annual savings could be as high as approximately $20 million if there were a complete shift of the administration of the tests from physicians who are authorized users (i.e., base case) to physicians who are not authorized users.

The basis for this estimate is as follows.

Assuming adoption of the petition eliminates the need for up to 600,000 referrals, patient savings in averted travel expenses (transportation and personal time incurred with medical referral) would be:

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

$10.5 million/ year i

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 $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. .

5

Totsi Savings:

$10.5 rnillion/ year + $11.4 milliontysar = $ 21.9 mi! lion / year Attematively, 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 per yeat and $15 million per year, respectively.

If Attemative 3 were adopted, it would permit any physician to receive and use capsules conta ning 1 pCl "C-urea for human use under a general liconse. The health and safety concems for this altomative are the same as Alternative 2. However, the adoption of Attemative 3 could add unnecessary burden to those Agreement States and Agreement State licenstes in States that assess licensing or registration fees for generallicense holders.

Alternative 2 also imposes incremental cost burden for manufacturers or commercial ,

distributors of the capsules because they would need to ot,tain en exempt distribution license.

Each application is estimated to take up to 16 hours1.851852e-4 days <br />0.00444 hours <br />2.645503e-5 weeks <br />6.088e-6 months <br /> to prepare. Assuming 3 applicants per year, the total reporting burden would be 48 hours5.555556e-4 days <br />0.0133 hours <br />7.936508e-5 weeks <br />1.8264e-5 months <br />. For recordkeeping burden, assuming each of the 3 applicants in a year would need 2 hours2.314815e-5 days <br />5.555556e-4 hours <br />3.306878e-6 weeks <br />7.61e-7 months <br /> to reprogram its computer to print additional words on the label or brochure, the one-time total recordkeeping burden would be 6 hours6.944444e-5 days <br />0.00167 hours <br />9.920635e-6 weeks <br />2.283e-6 months <br />.

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

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

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

(b) tiealth and Safety Effect2 For the purposes of this regulatory analysis, the NRC assumes that the same number of breath tests (i.e.,600,000 tests) will be administered regardless of the level of NRC regulatory control.

This view is predicated on the belief that each physician's primary motivation is to provide the best possible care to his or her patients. In addition, the routine and accidental exposures per carbon-14 urea breath test is not expected to be affected by the level of NRC regulatory control.

Thus, radiation exposures to the workers and members of the public would be the same regardless of which alternative is adopted.

The NRC has concluded that the human use of these capsules results in in6;gnificant exposures as depicted below:

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

The earth's atmosphere contains an inventory of naturally occurring "C of about 3.8 million curies (equivalent to the activity in 3.8 trillion breath tests), which is in addition to the huge inventory of about 240 million curies in the world's oceans. The "C released into the atmosphere from the use of this test would mix with the globalinventory and expcae the public and other blotic components of the environment to "C intakes from inhalation, drinking water, and all possible food pathways in the same manner as naturally occurring "C. The current world inventory of naturally occurring "C results in an average dose to the public of about 1.25 mrom/ year, and the release of 0.0 curies of "C from the total of 600,000 tesa assumed to be administered annuelly would result in an additional average annual dose of 2 X 10 ' mrem.

This is far below the EPA reporting level of 1 mrem / year required under the Clean Air Act for routine exposures to a n' ember 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 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, released is very low and it would mix immediately with the atmosphere.

The small doses from naturally occurring "C are of little significance to human health and the environment. Potentiallong-term impacts from widespread releases of the long lived "C (5,730 year radiological half l;fe) 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 mi; lion tests per year for 50 years, the collective annual dose to the U.S. population would be about 5 person-rem over the next 50 years. This dose is very small when compared to the annual 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.

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As a result of this analysis, the NRC 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 reccmmended option is Alternative 2 because it would avoid the unnecessary cost burden to some Agreement States and their generallicensees.

Therefore, by promulgating the final rule, the cost savings would be maximized without any measurable adverse effect on public health and safety.

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

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, l Fi'lCLOSURE 3 ENVIRONMENTAL ASSESSMENT f

Environmental Assessment For Final Amendments to 10 CFR Parts 30 and 32

" Distribution of a Radioactive Drug Containing One Microcurie of Carbon 14 Urea as Exempt Material for *In Vivo" Diagnostic Testing" Statement of the Final Action The Nuclear Regulatory Commission (NRC) is amending its regulations to allow NRC licensees to distribute a radioactive drug containing one microcurie of carbon 14 urea to any person for "in vivo" diagnostic use. The NRC has determined that the radioactive component of such capsules presents a minimal radiation risk and, therefore, rer"Jiatory control of the drug for radiation safety is net necessary. This amendment makes the drug more widely available, thus reducing costs to patients, insurers, and the health care industry. This action in being taken in response to a petition for rulemaking (PRM-35-12) submitted by Tri-Med Specialties, Inc.

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

Attemalinti Considered Three attematives have been considered regarding the petition: deny the petition, i.e.,

maintain 01 status quo, permit the distributicn of the capsules as exempt material, and permit l

the distribution of the capsules to generallicensees.

Under the first attemative, the c.urrent situation would continue: only physicians who are l authorized users under Part 35 would be cl' owed to possess and admir.ister the C-14 ur6a test.

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Any physician could apply to become an authorized user. However, the NRC expects few physicians would apply for a Part 35 license for the sole purpose of using such capsules because of the requirement for training and experience and the asscciated costs of obtaining and maintaining a Part 35 license. Attematively, physicians who are not authorized users can continue to refer their patients to physicians who are authorized users to undergo the diagnostic test. However this would not relieve the current expense, inconvenience, and delay encountered in an otherwise straight forward procedure.

Under the second alternative,10 CFR Parts 32 and 30 would be amended. Part 32 would be amended to establish requirements for the manufacture and distribution of C 14 urea capsules to persons exempt from licensing, i.e., any person (including physicians who are not

" authorized users" under Part 35); Part 30 would be amended to permit any person to receive, possess, use, tran@r, own, or acquire the capsules for in vivo diagnostic use for humans without a license. The NRL he: d:termined that the radioactive component of this drug presents a minimal radiation risk and, therefore, regulatory control of the capsules is not necessary.

Under the third alternative,10 CFR Part 35 would be amended to permit any physician to receive and use the capsules under a generallicense. The health and safety concerns for this alternative are the same as the Alternative 2. However, if this attemative were adopted, there could be a burden to those Agreement States that normally require registration of general license holders. An additional burden could also be imposed on generallicensees located in the Agreement State if the State charges a license or registration fee.

Based on the Draft Regulatory Analysis prepared for this proposed rule, the Commission concludes that Alternatives 2 and 3 are clearly preferable to the no action alternative. This is because either of the two attematives will result in significant cost savin 0s with no measurable adverse effect on health and safety. Furthermore, the NRC's recommended option is Attemative 2 because it avoids the unnecessary cost burden to some Agreement States and their licensees, knpact on the Public and the Environment The amendments are expected to have no significant impact on the public and the environment. The NRC assumes that the same number of breath tests will be edministered regardless of the level of NRC regulatory control. This view is predicated on the belief that 2

\

l 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 re0ulations. Under this assumption, this rulemaking action is expected to result in no change in radiation exposures to the workers and patients when compared with the status quo. Similarly, it is expected that there v6ill be no change in impact to the environment because the Com nission assuraes that the same number of tests will be administered regardless of which alternative is adopted.

The earth's atmosphere contains an inventory of naturally occurring C-14 of about 3.8 million curies which is in addition to the huge inventory of about 240 million curies in the world's oceans. The small amount of C-14 released into the atmosphere from the use of this test would mix with the globalinventory and would brve no impact on puHic health. The current world inventory of naturaily occurring C 14 results in an average dose to the public of about 1.25 mrem per year, and the rebase of 0.6 curies of C-14 from the total of 600,000 tests assumed to be administered annually would result in an additional average annual dose of 2 X 104mrem.

List of Agencies and Persoas Consulted.andJdentification 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 HeaistcI on December 2,1994, (59 FR 61831). A total of 315 public comment letters,313 suppor*;ng (mostly form letters) and 2 opposing letters, were received. This petition was discussed with NRC's Advisory Committee on the Medical Uses of Isotopes ACMUI) at the October 1995 meeting. Furthermore, the draft rulemaking plan was forwarded to 29 Agreement States for cumments.

A proposed rule was published in the Federal Regisler (62 FR 32552, June 16,1597) for a 30-day public comment period. The NRC received seven public comment letters. Four commenters supported the rule, one opposed the rule, and two provided comments without explicitly stating support of or opposition to the rule. A summary of public comments and NRC'.

responses are presented in the preamble of the Federal Register notice. Except a minor change in wording, the final amendments are the same as the proposed amendments.

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

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but non-radiological, d; agnostic procedure (such as C-13 test) is~available and provides a ,

comparable alternative to the C.14 kst. The commenter apparently concluded that the [

assumption underlying the environmental assessment is that in the absence of the C+14 test, the only attemative for the detection of H. pylori is invasive gastroendoscopy. ,

The-purpose of the environmerdal assessment is to address and document the expected impact to the environment of subject rule. As presented in the regulatory analysis prepared for this rule, the NRC has determined that the environmentalimpact is expected to be insignificant because of the cxtremely low radio!ogical hazards associated with the use of capsules containing one microcurie C 14 urea.

If the environmentalimpact had been significant, then the existence of a non radioactive attemative would have been a factor in assessing the cost benefit of this rulemaking. However, the impact is not significant. Hence, the regulatory issue in this rulemaking is whether the C 14 method should be made available to physicians whc are not authorized users, and nnt whether there exists a non redioactive attemative.

Findina of No Significant imoach -

The Commission has determined under the National Environmental Policy Act of 1969, as amended, and the Commission's regulations in Subpart A cf 10 CFR Part 51, that the amendments will not ba a major Fedeial action significantly affecting the quality of the human environment, and therefore an environmentalimpact statement is not required. The final rule amends 10 CFR Part 32 to permit the manufacture and commercial distribution of C-14 urea l capsules to any person (including physicians who are not " authorized users" under Part 35) and to amend 10 CFR Part 30 to permit any person, without an NRC licente, to receive and use the capsules for in vivo diagnostic use for humans. The Commission believes that the radioactive component of this drug presents a minimal radiation risk and, therefore, regulatory control of the capsules for "in vivo" diagnostic use is not necessary. It is expected that this final rule will

, not cause any significant increase in radiation exposure to the public or radiation release to the enviror ment beyond the exposures or releases resulting from the use of the carbon-14 capsules under the current regulations.

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ENCLOSURE 4 CONGRESSIONAL LETTERS

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The Honorable Dan Schaefer, Chairman Subcommittee on Energy and Power Committee on Commerce United States Houn of Representatives Washington, DC 20515

Dear Mr. Chairman:

Enclosed for the information of the Subcommittee are copies of a public announcement and a Federal Register notice concoming a final amendment to 10 CFR Parts 30 and 32. This rulemaking is being taken in response to a petition for rulemaking submitted by Tri-Med Specialties, Inc.

The Nuclear Regulatory Commission (NRC) is amending its regulations to allow NRC licensees to distribute a radioactive drug containing one microcurie of carbon-14 urea to any person for "in vivo" diagnostic ut.o. The purpose of this diagnostic test is to detect the presen0e of the bacterium Helicobacter pylori (H. pylori), a cause of peptic ulcers. The NRC has determined that the radioactive component of such capsules presents a minimal radiation risk and, therefore, regulatory control of the drug for radiation safety is not necessary. The manufacture and dirvibution of the capsules will continue to require an NRC license. This amendment makes the drug more widely available, thus reduces costs to patients, insurers, and the health care industry.

Since.a!y, Dennis K. Rathbun, Director Office of Congressional Affairs Enclosures-

1. Public Announcement

2. Federal Register Notico cc: Representative Ralph Hall

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• WASHINGTON, D.c. 30tM4001

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t 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 t> ear Mr. Chairman:

Enclosed for the information of the Subcommittee are copies of a public announcement and a Federal Register notice concoming a final amendment to 10 CFR Parts 30 and 32. This rulemaking is being taken in response to a petition for rulemaking submitted by Tri-Med Specialties, Inc.

The Nuclear Regulatory Commission (NRC) is amending its regulations to allow NRC licensees to distribute a radioar;tive drug containing one microcurie of carbon-14 ures to any person for *in vivo" diagnostic use. The purpose of this diagnostic test is to detect the presence of the bacterium Helicobacter pylori (H. pylori), a cause of peptic ulcers. The NRC has deterinined that ,

the radioactive component of such capsules presents a minimal radiation risk and, therefore, regulatory control of the drug for radiation safety is not necessary. The manufacture and distribution of the capsules will continue e require an NRC license. This amendment makes the drug more widely available, thus reduces costs to patients, insurers, and the health care industry.

Sincerely, Dennis K. Rathbun, Director Office of Congressloral Affairs

Enclosures:

1. Public Announcement

2. Feders Register Notice cc: Senator Bob Graham

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i ENCLOSURE 5 SBREF LETTERS I

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NUCLEAR REGULATORY COMMIS810N W AsHil.1 ton, D.C. 30MH001

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Mr. Robert P. Murphy General Counsel General Accounting Office Room 7175 441 G. St., FM Washington, DC 20548

Dear Mr. Murphy:

Pursuant to Subtitle E of the Small Business Regulatory Enforcement Falmess Act of 1996,5 U.S.C. 801, the Nuclear Regt.latory Commission (NRC) is submitting a final rule regarding distribution of a radioactive drug containing one microcurie of carbon 14 ures to any person for "in vivo" diagnostic use for humant. The purpose of this diagnostic test is to detect the presence of the bacterium Helicobacter pylori (H. pylori), a cause of peptic ulcers. The final rule makes the drug more widely available, and reduces costs to patients, insurers, and health care industry.

The distribution of the drug in caprufe form presents a minimal radiation risk and, therefore, regulatory control of the drug for radiation safety is not necessary. This action it being taken in response to a petitiori for rulemaking (PRM 3512) submitted by Tri-Med Specialties, Inc.

We have determined that this rule is not a " major rule" as defined in 5 U.S.C. 804(2). We have confirmed this determination with the Office of Management and Budget. ,

Enclosed is a copy of the final rule that is being transmitted to the Office of the Federal Register for publication. The Regulatory Flexibility Certification and a statement of the availability of the Regu story Analysis are included in the final rule.

Sincerely, Dennis K. Rathbun, Director Office of Congressional Affairs

Enclosure:

Final Rule t

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UNITSD STATES g NUCLEAR REGULATORY COMMISSION WASHINeToN. D.C. asse64eM i

The Honorable Al Gore- -

Presiderd of the United -!

States Senate Washington, DC 20510 l

Dear Mr. President:

t Pursuard to Subtitle E of the Small Business Regulatory Enforcement Falmess Act of igg 6,5 - >

U.S.C. 801, the Nuclear Regulatory Commission (NRC) is subm4 ting a final rule regarding distribution of a radioactive drug containing one microcurie of certson-14 uros to any persor .or i "in vivo" diagnostic use for humans. The purpose of this diagnostic test is to detect the p'asence  ;

of the bactertum Helicobactor pylori (H. pylori), a cause of peptic ulcers. The final rule m',kes the .  ;

drug more widely available, and reduces costs to patients, insurers, and health care industry.

The distribution of the drug in capspie form presents a minimal radiation risk and, therefore, ,

regulatoiy control of the drug for radiation safety is not necessary. This action is being taken in response to a petition for rulemaking (PRM-35-12) submitted by Tri-Med Specialties, Inc. i We have determined that this rule is not a " major rule" as defined in 5 U.S.C. 804(2). We have i confirmed this determination with the Office of Management and Budget.

Enclosed is a copy of the final rule that is being transmitted to the Office of the F6deral Register for publication. The Regulatory Flexibility Certification and a statement of the availability of the- *

- Regulatory Analysis are included in the final rule.  :

St )corely, k

Dennis K. Rathbun, Director Office of Congressional Affairs l

Enclosure:

Final Rule 1

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C NUCLEAR REGULATOFtY COMMISSION WASHINGTON, D.C. 30846-0001 The Honorable Newt Gingrich speaker of the United States House of Representatives Washington, DC 20515 De&r Mr. Speaker.

Pursuant to Subtitle E of the Small Business Regulatory Enforcement Fairness Act of 1996,5 U.S.C. 801, the Nuclear Regulatory Col.;miolon (NRC) is submitting a final rule regarding '.

distribution of a radioactive drug containing onc microcurie of carbon-14 urea to any person for "in vivo" diagnostic use for humans. The purpose of this diagnostic test is to dete:t the presence of the bacterium Helicobacter pylori (H. pylori), a cause of peptic ulcers. Tne final rule makes the drug more widely available, and mduces costs to patients, insurers, and health care industry, the distribution of the drug in capsule form p'esents a minimal radiation risk and, therefore, regulatory control of the drug for radiation safety is not necessary. This action is being taken in response to a petition for rulemaking (PRM-3512) submitted by tamed Specialties, Inc.

We t. eve determined that this rule is not a " major rule" as defined in 5 U.S.C. 804(2). We ha.s confirmed this determination with the Office of Management and Budget.

Enclosed is a copy of the final rule that 10 bung transmitted to the Office of the Federal Register for publication. The Regulatory Flexibility Certification and a statement of the availability of the Regulatory Analysis are included in the final rule.

Sincerely, Dennis K. Rathbun, Dirwetor Office of Congressional Affairs

Enclosure:

Final Rule

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1 ENCLOSURE C PUBLIC NJN0UNCEMENT i

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Draft press release -- 9/3/97 i

NRC CHANGES REGULATIONS TO PERMIT EXEMPT DISTRIBUTION OF RADIOACTIVE DIAGNOSTIC DRUG The Nuclear Regulatory Commission is ame, ek e its regulations to allow a specific radioactivo drug used to diagnose stomach ulcers to b9 distributed to any person for administration to humans. Before this change, only physicians authorized by the NRC or Agreement States could receive and administer the drug.

The change does not relieve persons from the requirement to comply with applicable Food and Drug Adminletration or other Federal and State requirements governing receipt, administration and use of drugs.

The change is in response to a 1394 petition for rulemaking from Tri-Med Specialties, Inc. The revised regulation allows any person to receive, possess, use and transfer capsules containing one microcurie carbon 14 urea each for diagnostic use in patients. The NRC has determined that the capsules present a minimal radiation risk, and therefore believes ti.at regulatory control of the drug for radiation safety is not necessary Under the amendments, manufacturers of the capsules and commercial pharmacies that prepare the capsules will continue to need an NRC license to provide high confidence of capsule centents. The containers of the capsules must bear the words " radioactive material" and other specific Information on the contents of the container, in addition, only those persons who are licensed will be permitted to use the capsules for research involving human subjects.

The Tri-Mod petition stated that Carbon-14 urea can be used to detect the presence of a bacterium that causes peptic ulcers, a chronic inflammatory condition of the stomach and duodenum that affects as many as 10 percent of

_ people in the United States at some time in their lives. According to a July 1994 ,

article in the_ Journal of the American Medical Association, the disease has relativelylow mortality, but results in substantial human suffering and high-  ;

economic costs. Doctors can now cure most ulcer problems with antibiotics. The j test using Carbon-14 urea is non invasive. A doctor asks the patient to swallow the capsule with water. After 15 minutes the patient blows inte i collection bag, which is mailed to a testing laboratory for analysis.

Before the chanf, only physicians who were authorized users (e.g.,

physicians who met certain training and experience criteria regarding the sefe use of radioactive drugs) or persons working under the supervision of an authorized user could administer radioactive drugs for medical purposes.

Under the amendmentr. physicians or other health care workers will not need to be authorized users in order to administer the drug, and physicians will not i need to refer their patients to nuclear medicine physicians. This should result in r- cost savings to patients, insurers, and the health care industry, o

A proposed rule on this subject was published la the Federal Register for public cnmment on June 16. Minor changes made to the rule as a result of j comments received are discussed in a Federal Register notice that will be

! published shortly.

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