ML20198L432
| ML20198L432 | |
| Person / Time | |
|---|---|
| Issue date: | 09/09/1997 |
| From: | Satorius M NRC OFFICE OF ENFORCEMENT (OE) |
| To: | Knapp M NRC OFFICE OF NUCLEAR REGULATORY RESEARCH (RES) |
| Shared Package | |
| ML20198K526 | List: |
| References | |
| FRN-62FR63634, RULE-PR-30, RULE-PR-32 AF70-2-015, AF70-2-15, NUDOCS 9801160028 | |
| Download: ML20198L432 (26) | |
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UNITED STATES p]
j; NUCLEAR REGULATORY COMMISSION f$s e
WASHlHOTON, D.C. 20665-0001 8
NG, JR.
September 9, 1997-f}F W MEMORANDUM TO:
-Malcolm R. Knapp. Acting Director 7pR v.
oc atory Research
! FROM:
Mark A. Satorius. Deputy Director Office of Enforcement-
SUBJECT:
FINAL RULE: EXEMPT DISTRIBUTION OF A RADI0 ACTIVE ORUG CONTAINING ONE MICR0 CURIE OF CARBON-14 UREA (PARTS 30 AND-
-32): COMMENTS'AND CONCURRENCE
' OE has reviewed and concurs in the suuject rulemaking package. Minor editorial suggestions are noted on the attached pages.
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data;it did not provide for n4xemption of research activitie nvolving minimal risk. However, the common rule permits a epartment or agency heads etain finaljudgment as to whether a particular activity is covered by this policy, la lieu of partici ating in the promulgation of the common rule, the NRC adopted $ 35.6 that requires a licensee who conducts research involving human subjects using byproduct material to obtain informed consent from the human subjects and obtain prior approval by an " Institutional review board"(IRB), Because use of the capsules in conducting human research without following these provisions could erode public confidence in the NRC, even though the capsules present minimal risk, the staff recommends that such research use not be exempt from $ 35.6.
This final nale amends Part 30 to add a new section ($ 30.21) to permit any person to receive, possess, use, transfer, own, or acquire capsules containing one microcurie carbon-14 urea for "in vivo" diagnostic use without a4conse. The final amendments include a reminder that persons will not be relieved from complyirig with applicable FDA, other Federal, and State rerluirements goveming drugs.
This final rule also amends Part 32 to add a new section ($ 32.21) to establish requirements for the manufacture and distribution of carbon-14 urea capsules to persons exempt fram licensing.
Currently, NRC requires licensees who manufacture, prepare, or commercially distribute radioactive drugs to meet the requirements in S 32.72(a)(2) (e.g., be registered or licensed with the FDA or a State as a drug manufacturer or be licensed as pharmacy by a State Board of Pharmacy). Licensees distributing these capsules under an exempt distribution license will need to meet this same requirement. This provides high confidence that the carbon-14 urea capsules contain one microcune of carbon 14 and do not contain other radioactive contaminants, RESOURCES:
+
Resources to complete and implement this rulemaking are included 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 Officer concurs in the resource impac., Sithis rulemaking. The Office of the Chief Information Officer concurs that there will be no infconation technology or management impacts.
RECOMMENDATION:
That the Commission:
1.
Aporove 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).
s 3.
Ndg:
a.
The final rule will be published in the Federal Reaister:
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permitted under this exemption because the radiole;ical risk for using C 14 capsules is I
insignificant.
Respong: The Commission 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 proniulgated by 16 Federal agencies on June 18,1991 (56 FR 28002) and was intended to ensure the protection of human research subjects. This rule was adopted to imp lement a recommendation of the President's Commission for the Study of Etnical Problems in Medicine and Biomedical and Behavioral Research which was er,tablished on November 9,1978, by Public 4
Law 95-622. The Federal Policy fidquires that Federal agencies that conduct, fund,.upport, of regulate research involving human subjects ensure adequate protection of the rights of the human subjects. 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.
to CFL in lieu of participating in the proinutgation of the common rule, the NRC adopted 5 35.6 A
that requires a licensee who conducts research involving human subjects using byproduct
+
material to obtain informed consent from the human subjects and obtain prior approval by an
" Institutional review board * (IRB). Although the Commission 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 rish, the Commission determines that such research use not be exempt from S 35.6.
Comment 2: Two commenters exprassed concems that the proposed rule lenguage, "not exceeding one microcurie," appeared to indicate the upper limit of the radioactivity in a capsule is exactly one microcurie of C-14. Both stated that it is not possible to rnake the capsules to exactly one microcurie due to statistical deviations during the manufacturing process.
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1 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 radiactive material legend, ' Radioactive Material,' be included on promotional I
brochures.
Resconse: 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. Paragraph (a)(6) of $ 32.21 requires that applicants submit co les of prototype labels wi%-
es and brochures for NRC spproval. The NRC will ensure that the labels e $ 32.21a before they 1
are approved. Since paragraph (h) of 6 32.21a 6, ocifies ' hat the label must be durable thd legible, the use of an additional phrase such as ' conspicuously and prominently"is unnecessary.
Promotional brochures are for nformation only; nothing will prevent manufacturers from indicating on the promotional brochures that C 14 is a radioactive material.
lli. Summary of the Final Amendments
+
Final Amendment to 10 CFR Part 32 The regulations in 10 CFR Part 32 are amended to add a new $ 32.21, to provide requirements for a specific license to manufacture, prepare, process. produce, package, repackage, or transfer for commercial distribution capsules containing crie microcurie of C 14 urea, as a radioactive drug, to be distributed to any person for "in * ' f diagnostic use. These requirements are consistent with the existing requirements on other items under the heading
" Exemptions"in 10 CFR Part 30. The amendment includes a reminder that licensees distributing the radioactive drug to persons exempt from licensing would not be relieved from other 10
allow any person to r6ceive capsules containhg one microcurie of carbon 14 uros for"in diagnode use without need for a license. The NRC has urged the Agreement Statss the amendment expeditiously, VI. Finding of No Significant Environmentalimpact: Availability The Commission has determined under the National Environmental Policy Act of 1969 1
amrended, and the Commission's regulations in Subpar 1 A of 10 CFR Part 51, that the fin;
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amendmentsgnot a major Fedept action significantly affecting the quality of the human environment; therefore, t 1 cnvironmental impact statement is not required. The final rule establishes requirements for the manufacture and commercial distnbution of carbon 14 urea capsules to persons exempt from licensing and establishes regulations to permit any receive the capsules without an NRC license. The Comrrission believes that the radioactiv component of this drug presents no signif cant radiation risk and, therefore, reg the "in vivo" diagnostic use of the capsules for radiation safety is not necessary, it is e that this final rule will not cause any significant increase in radiation exposure to the pulpic radiation reiease to the environment beyond the exposures or releases resulting from the carbon 14 capsules utider the current regulations. Also,it is expected that there will b non radiologicalimpacts. One public comment on the draft environmental assessment received (See Comment g under the heading
- Proposed Rule, Public Comments, and Pasponses"),
The environments' assessment and finding of ne significant impact on which this determination is based is available for inspection at the NRC Public Document Room,21 Street NW, (Lower Level), Washington, DC, Single copies of the environmental as the finding of no significant impact are available from Dr Aathony N. Tse, Office of Nuclea 19
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The Commissioners PDL FROM:
L. Joseph Callan, Executive Director for Operations
SUBJECT:
FINAL RULE ON EXEMPT DISTRIBUTION AND USE OF A RADIOACTIVE DRUG CONTAINING ONE MICROCURIE OF CARBON 14 UREA (PARTS 30 AND 32)
P_URPOSE:
Te obtain the Commission's approval for publication of the final rule.
DACKGROUNQ:
On May 30,1997, the Commission appre
' publication of a proposed rule to amend Parts 30 and 32 that would permit the exempt (
sution and use of capsules containing one microcurie carbon 14 urea for 'in vivo" diagnostic use. On June 10,1997, the proposed rule was published in the Federal Realster (62 FR 32552) for a 30-day public comment period. This action is being taken in response to & petition for rulemaking (PRM 3512) subm;ite by Tri Med Specialties, Inc.
DISCUSSION:
In response to a request for comment on the propose rul, the NRC r ceived seven public comment lottt.rs. Four commenters supported th rut, foppos he rule, and two provided comments without explicitly stating whether they supp pr oppos e rule. A summary of public comments and staff's responses are presented The pream le of the enclosed Federal Register notice. Except for a minor change in wording, the final amendments are the same as the proposed amendments.
The Commission should note that one commenter suggested that research use should be also
. permitted under this exemption because the radiological risk is insignificant. The staff did not change the final rule in response to this comment. A common rule entitled " Federal Policy for the Protection of Human Subjects; Notiet s and Rules" was promulgated by 16 Federal agencies on June 18,1991 (56 FR 28002) and was intended to ensure the protection of human research subjects. While this common rule provides for the exemption of certain research, such as educational tests; survey, interviews, or observation of public behaviors; collection of existing Con'act:
Anthony Tse, DRNRES 415-6233 j
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The Commissioners 2
data; it did not provide for an exemption ol research activities involving minimal risk. However, the common rule permits that department or agency heads retain finaljudgment as to whether a particular activity is covered by this policy. In lieu of participating in the promulgation of the common rule, the NRC adopted $ 35.6 that requires a licensee who conducts research involving human subjects using byproduct material to obtain informed consent from the human subjects and obtair, prior approval by an ' Institutional review board"(IRB). Because use of the capsules in conducting human research without following thesg provisions could erode public confidence in the NRC, even though the capsules present mini ' l risk, the staff recommends that such a
research use not be exempt irom $ 35.6.
This fit al rule amends Part 30 to add a new sec\\i n ( 30.21) to permit any person to receive, possess, use, transfer, own, or acquire capsules containing one microcurie cart >on 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, her Federal, and State requirements goveming drugs.
f This final rule also amend: art 32 to add a new section (f 32.21) to establish requirements for the manufacture and distribution of carbon 14 urea capsules to persons exempt from licer. sing.
Currently, NRC requires licensees who manufacture, prepare, or commercially distribute radioactive drugs to meet the requirements in 9 32.72(a)(2)(e.g., be registered or licensed with the FDA or a State as a drug mar.ufacturer or be licensed a3 pharmacy by a State Board of Pharmacy). Licensees distributing these capsules under a exempt distribution license will need to meet this same requirement. This provides high confid
- e that the carbon 14 urea capsules contain one microcurie of carbon 14 and do not contain o er radioactive contaminants.
RESOURCES:
Resources to complete and implement this rulemaking are included in the current budget.
QOORDINATION:
The Office of the General Counsel has no legal objection to the final rulemaking. The Office of the Chief Financial Officer concurs in the resource impacts of this rulemaking. The Office of the Chief information Officer concurs that there will be no information technology or management impacts.
RECOMMENDAT!C%.
That the Comrnission:
1 6ppr,9n 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.
Nple:
a.
The final rule will be published in the Lederal Reaister,
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t NUCLEAR REGULATORY COMMISSION 10 CFR Parts 30 and 32 3/30-RIN: AD70 t
Exempt Distribution of a Radioactive Drug
. Containing one Microcurie of Cart >on 14 Uros AGENCY: Nuclear Regulatory Commission, ACTION: Final rule.
5 1
SUMMARY
- The Nuclear Regulatory Commission (NRC) is amending its regulations to permit -
NRC licensees to distribute a radioactive drug containing one microcurie of carbon 14 urea to any person for "in vivo" diagnostic use. The NRC has determined that the radioactive component of such 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 n ore widely
. This action available and reduces costs to patients, insurers, and the health ck being takenhfesponsega petition for rulemaking,(PRM 35-12)
_t_... d" by Tri-Med A #~
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Specialties, Inc. 4A <[(M7 3M" d
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T EFFECTIVE DATE: (30 days frorn date of publication in the Federal Register),
ADDRESS: Copies of the public record, ir,cluding 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.
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I FOR FURTHER INFORMATION CONTACT: Dr. Anthony N. Tse, office of Nuclear Regulatory Research, U.S. Nuclear Regulatory Commission, Washington, DC 205554001, telephone (301) j 415-6233 or e mail at ANT @nrc. gov.
1 SUPPLEMENTARY INFORMATION:
[
1.
The Petition for Rulemaking.
= II.-
Proposed Rule, PutAc Comments, and NRC Responses.
Ill.
Summary of the Fir,v',4mendments.
IV.
Description of the Final Amendments.
A V.
' Agreement State Compatibility.
VI.
Finding of No Significant EnvironmentalImpact: Availability.
Vll.
Paperwork Reduction Act Statement.
Vill.
Regulatory Analysis, i
IX.
Rs;'statory Flexibility Certification.
cht Ana ysi
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x, Xil. : List of Subjects.
4
- 1. The Petition for Rulemaking On October 6,1994, the Commission docketed a petition for rulemaking (Docket No.
PRM 35-12) from Tri Med Specialties, Inc (Tri Med). In a letter dated August 23,1994 Tri Med
' petitioned the NRC to amend its regulations "to allow for the general licensing and/or exemption
- for the commercial distribution by licensed pharmaceutical manufacturers of a capsule containing one micro-Curie (pCl) of C 14. urea for in vivo diagnostic testing." The purpose of this diagnostic 2
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tes'is to detect the presence of the bacterium Helicobacter pylori (H. pylori), a cause of peptic ulcer [ I"N YA Following the receipt of the petition, the NRC published for public comment a notice of receipt of petition for rulemaking in the Federal Register on December 2,1994 (59 FR 61831).
The comment period closed on February 15,1995. The NRC received 315 public comment f1 letters, of which 313 support the petition (they were mostly form letters) and 2 letters opposed A
the petition.
- 11. Proposed Rule, Public Comments, and NRC Responses A proposed rule was published on June 16,1997 (62 FR 32552) that would permit NRC licensees to 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 insigni'icant radiological risk to the public and the environment, the NRC believes the capsules could be distributed to persons exempt from licensing for "in vivo" diagnostic use. This change makes the drug more widely available and reduces costs to patients, insurers, and the health care industry, g4 The NRC received seven public comment letter three from industry, three from State agencies, and one from a university. Four commenters supported the rule, one opposed the,
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rule, and two provided comments but did not explicitly state whether they support or oppose,the rule. Public comments and NRC's responses are presented below.
Comment 1: Under the proposed distribution, the NRC should not be forbidding research use of this drug by the same physicians who may use it clinically. Research use[should beM ' #
3
b permitted under this exemption because the radiological risk for using C-14 capsules is insignificant.
l M/'C R_espons3: Thepommission did not change the final rule in response to this comment.
A common rule entitled " Federal Policy for the Protection of Human Subjects; Notices and Rules" was promulgated by 16 Federal agencies t,n June 18,1991 (56 FR 28002) and was intended to ensure the protection of human research subjects. This rule was adopted to implement a -
recommendration of the President's Commission for the Study of Ethical Prebloms 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 q
human subjects, 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 e
adopt this comment.
9CfD In lieu of participating in the promulgation of the common rule, the NRC adopted 35.6 that requires a licensee who conducts research involving human subjects using byproouct matenal to obtain informed consent from the human subjects and obtain prior approval by an
" Institutional review board"(IRB). Although the heion did not adopt the common rule, the intention is to follow the essential requirements of the common rule Because the common rule NEC involving minimal risk thfemission determines does not provide an exemption for resear that such research use not be exempt from -35.6.
Comment 2: Two commenters expressed concems that the proposed rule language, "not 8af exceeding one microcurie," appeared to indicate,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 {rcwr ch io statistical deviations during the manufacturing process.
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4 Response: The NRC agrees with the commenters. The propowd rule did not intend te limit the radioactivity of C 14 to exactly one microcurie. The final rule language has been modified to read " capsule containing one microcurie C-14 urea (allowing for nominal variation that inay occur during the manufacturing process).'
Comment 3' One commenter stated that, whwn the total amount of energy released from complete decay of a radionuclide is considered, one microcurie of C-14 has the largest energy release because of its long half life when compared to one microcurie of Tc 99m or 1131. 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 113(g'ais~o')be insignificant o
Response: The radiation risks fiom a radioisotope depends on the types of radiation emitted (e.g., a, p, Y radiation) and their energy. Since C 14 emits low energy p radiation with no y radiation, low energy D radiation cannot enetrate very farinto the tissue. Thus, the radiation v
0 risk to an individual from one microcurie,C 14 would be insignificant. On the other hand, both Tc-99m and 1131 emit y radiation, which is more penetrating than the weak p radiation. Therefore, Tc 99m and 1-131 are more hazardous than C-14 even though C-14 has the largest total energy released from complete decay per microcurie.
nbul Oh Comment 4:
0 the small quantity of radioactive materialin C-14 capsules, this product may be disposed of in the general trash. To avoid unnecessary concerr' for health risks in the disposal of the product, labels should contain a statement that the product may be disposed of in the general trash.
Response: In the final rule, the label requirements include a statement that the product may be disposed of in ordinary trash.
5 f
Comment 5: The Commenter agrees that tir widespread use of this product will require uniform regulations and that Agreement States will need to make appropriate regulatory provisions to enable persons to receive the drug for"in vivo
- diagnostic use. To avoid confusing licensees and users, these changes to NRC and Agreement State regulations should be made simultaneously. The commenter urges that the NRC take action to expedite the Agreement State regulatory changes.
Response: The NRC has urged the Agreement States to adopt the changes in their re0ulations expeditiously. However, under NRC's t.dequacy and Compatibility Policy, Agreement States have up to three years to change their regulations for amendments or program requirements that are items of compatibility.
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Comment 6: The NRC should address this tule indhe ongoing effort verall Part 35 3
e mane co menter believes that (1) this rule represents a piecemeal effort to respond to a vmon. Th nar.ow 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.
l3 C ril Responsg: If this rule is combined with the overall Part 35 revision, the C-14 capsules b
would not be available to primary-care physicians until the overall revision is completed (the rule is scheduled to be completed in 1300). Thus, the NRC decided to proceed with this rule now because the benefits of making this capsule available to all physicians outweigh the benefits of l0 $[$
addressing this issue in the overal! revision of Part 35.
A Comment '/: An appropriate function of the regu!atory 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.
6
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suggested the following: (1) the phrase "conspicuot. sty 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.
Ersponse. 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. Paragraph (a)(6) of 9 32.21 requires that applicants submit copi of prototype lauels,
wow /Jor s and brochures for NRC approval. The NRC will ensure that the labels meet 2
before they are approved. Since paragraph (a) of 5 32.21a specifies t iat the label must be durable and legible, the use of an additional phrasa such as " conspicuously and prorf,,nently"is unnecessary.
Promotional brochures are for information only; nothing will prevent manufacturers 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 a new 9 32.21, to provide requirements for a specific license to manufacture, prepare, process, produce, package, repackage, or transfer for commercial distributionfapsules containing one microcurie of C 14 urea, as a radioactive drug, to be distributed to any person for "in vivo" diagnostic use. These requirements are consistent with the existing requirements on other items under the heading
" Exemptions"in 10 CFR Part 30. The amendment includes a reminder that licensees distributing the radioactive drug to persons exempt from licensing would not be relieved from other 10
s distribution espsules containing one microcurie carts.n 14 urea each for *in vivo" diagnostic use, j
to persons exempt from licensing.
P_araoraph (a)(1)
This paragraph limits issuance of an " exempt distribution license" for distribution of the capsules to persons exempt from licensinp ' only those who possess either a NRC cr Agreement State " specific license" for pos.t tioni and use of byproduct meterial.
Epraoraoh (alg)
To assure that the capsules contain one microcurie of carbon-14 and p'esent no other radioloC cal risks, this paragraph requires that the persons manufacturing and5r commercially i
distnbuting the capsules for "in vivo" diagnostic use must also meet the requirements of G 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)L3)
This paragraph reqdres applicants to provide evidence that each carbon-14 urea capsule contains one microcurie. The NRC's evaluation that the capsules would not result in significant radiation risks was '0ased on the capsules containing one microcurie of carbon 14 urea.
Therefore, appli" ants must demonstrate that the activity of nach carbon 14 capsule contains one microcurie, allowing for nominal variation that may occur during the manufac'uring process.
14
e (2) Bear the words " Radioactive Mater lal. 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 Comme.rcial Distribution."
hwgWh The intent of the requirement set out in (b)(2) is to make clear that the capsule must remain in the form of a capsule and is not to be combined with one of the listed items such as food or beverages which would result in a radioactive product other than in the form of a capsulo for commercial distribution. There is no prohibition against the capsule being combined with food or boverage at the time of administration so that the capsule can be ingested by the patient.
"In vivo" disanostic qse by persons exe_ mot from licensjng 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.
Section 30 21 Radioactive drua: Capsults containina one microcurie of carbon 14 urea for "in vivo" dimanostic use for humans Earcaraoh (a)
This paragraph provides an exemption to any person from 15e requirements for a license to receive, possess, use, transfer, own, or acquire capsules containing one microcurie of carbon-14 urea for "in vivo" ciagnostic purposes; it should be noted that the " transfer" in this paragraph gf fapc kn.
does not include " transfer for commerchi distribution," which is covered in paragraph (c) bei w.
17
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Paragraph ib)
.' This paragraph establishes that persons exempt from licensing would be prohibited from f
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. i using the drug for research involving humans subjects,- A specdic Part 35 license wwid be '
.i needed to use the drug in any research involving human subjects in order to ensure the protectiun the rights of the human sub}ects.
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This paragraph specifies that a specific license is needed to manufacture,"
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prepare, process, produce, package, repackage or transfer such capsules for commercial '
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- distribution.
i Paraorseh.(50 This paragraph declarea that the regulations do not relieve end users from complying with applicable FDA, other Federal, or State requirements goveming the receipt, administration, and use of drugs, i
V. Agreement State Compatibility I
. Under the Atomic Energy Act, corialn regulatory functions are reserved to the NRC.
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Among these are the distribution of products to persons exempt from licensing, as discussed in
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10 CFR Part 150. Hence, amendments related to the manufacture and commercial distribution l
of the capsules (10 CFR Part 32) is a Division 4 item of compatibility. However, amendments
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.t related to possession and use (10 CFR Part 30) is a Division 1 itom of compatibility because'of j
L the'need for nationwide consistency in the use of products which are widely distributed.
iTherefore, the Agreement States will need to make appropriate provisions in their regulations to -
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J allow any person to receive capsules containing one microcurie of t,srbon 14 uros for "in vivo" diagnostic use without need for a license. The NRC has urged ther Agreement States to adopt the amendment expeditiousif.
VI. Finding of No Significant EnvironmentalImpact: Availability The Commission has determined under the National Environmental Policy Act of 1969, as amended, and the Commission's regulations in Subpart A cf 10 CFR Part 51, that the final s is not a major Federal ection significantly affecting the quality of the human environment; therefore, an environmental impact statement is not required. The final rule establishes requirements for the manufacture and commerrJa! distribution of carbon.14 urea capsules to persons axempt from licensing and establishes regulations to permit any person to i
receive the capsules without an NRC license. The Commission believes that the radioactive component of this drug presents no significant radiation risk and, therefore, regulatory control of -
the "in vivo" diagnostic use of the capsules for radiation safety is not necessary. It is expected that this final rule will not cause any significant increase in radiation exposure to the public or radiation release to the environment beyond the exposures or releases resulting from the use of the carbon 14 capsules under the current regulations. Also,it is expected that there 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").
1 The environmental assessment and finding of no significant lmpact on which this determination is based is available for inspection at the NRC Public Document Room,2120 L
- Street NW. (Lower Level) Washington, DC. Single copies of the environmental assessment and the finding of no significant impact are available from Dr. Anthony N. Tse, Office of Nuclear 19
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. Regulatory Research, U.S, Nuclear Regulatory Commission, Washington, DC 20555 0001, i
16'ephone (301) 4154233 or e mail at ANT @nre gov.
Vil, Paperwork Reduction Act Statement This final rula amends information collection requirements that are subject to the Paperwork Reduction Act of 1995 (44 U.S.C. 3501 et seq.). These requirements were approved 3150-001)#A d 3 by the Office of Management and Budget, approval numbers 3150-000 5
The public reporting burden for this collection of !nformation is estimated to average 16 e
hours pet response, including the time for reviewing instructions, searching existing d' ata sources, gathering and maintaining the data needed, and completing and reviewing the collection -
of information. Send comments on any aspect of this collection of information, including suggestions for reducing the burden, tr :he Information and Records Management Branch (T 6 F33), U.S. Nuclear Regulatory Commission, Washington, DC 20555 0001, or by Internet -
t electronic mail at BJSi@NRC, GOV; and to the Desk Officer, Office of Information and Regulatory Affairs, N60810202, (3150-0001,3150 0017, and 3150-0120), Office of Management and Budget, Washington, DC 20503.
4 Public Protection Notification l
--The NRC may not conduct or sponsor, and a person is not required to respond to, a -
. collection of information unless it displap a currently valid OMB control number, 20 e-.,..,
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Small Business Regulatory E t'orcement Faimess Act y
in accordrince witn the Small Business Regvlatory Enforcement Fairness Act of 1996, the NRC has determined that this action is not *a major" rule and has verined this determination with the Office of information and Regulatory Affairs, Office of Management and Budget.
s y 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).
Y ll' JL List of Subjects 10 CFR Part 30 Byproduct material, Criminal penalties, Govemment contracts, Intergovemmental relations, Isotopes, Nuclear materials, Radiation protection, Reporting and record keeping requirements.
10 CFR Part 32 Byproduct material, Criminal penalties, Labeling, Nuclear materials, Radiation protection, Reporting and recordkeeping requirements.
For the reasons set out in the preamble and under the authority of the Atomic energy Act 55.2anc/
of 1954, as amended, the Energy Reorganization Act of 1974, as amendedj and 5 U.S.C 553, 3
the NRC is adopting the following amendments to 10 CFR Parts 30 and 32.
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- 5. !n $ 32.8, paragraph (b)is revised to read as follows:
A 32 8 information collection reavireme6tst OMD iporoval.
(b) The approved information collection requirements contained in this part appear in
$$ 32.11, 32.12, 32.14, 32.15, 32.16, 32.17, 32.18, 32.19, 32.20, 32.21, 32.21 a, 32.22, 32.23, 32.25, 32.20, 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.
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- 6. A new $ 32.21 is added to read as follows:
i 6 32 21 Radioactive druo: Manufacture. preparation or transfer for commercial distribution of g,ap}ules containina one microcurie carbon 14 u[pa esq,h for "in vivo" disanostic use for humans to persons exempt from lic Jino: 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 one microcurie carbon 14 urea (allowing for nominal variation that may occur during the manufacturing process)
Cf d 5 c d m /* r each for "in vivo" diagnostic use, to persons exempt from licensing under $ 30.21pr the '
equivalent regulations of an Agreement State will be approved if:
(1) The applicant satisfies the general requirements specified in S 30.33 of this chapter, provided that the requirements of $ 30.33(a)(2) and (3) of this chapter do not apply to an application for a license to transfer byproduct material manufactured, prepared. orocessed, produced, packaged, or repackaged pursuant to a license issued by an Agreement State; (2) T e applicant meets the requirements under $ 32.72(a)(2);Lc/ dis th J (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);
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e (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 ommocity, 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.
(y Nothing in this sectiori relieves the licensee from complying with applicable FDAl other
- Federal, and State requirements goveming drugs.
- 7. A new 6 32.21a is added to read as follows:
A 32 21a Same: Conditions of license.
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Each license issued under 5 32.21 ls subject to the following conditions:
A (a) The immediate container of the caprule(s) must bear a durable, legible label which:
(1) Identifies the radioisotope, the physical and chemical form, the quantity of radioactivity of each capsule at a specific date; and (2) Bears the words " Radioactive Material."
(b) In addition to the labeling information required by paragraph (a) of this section, the label affixed to the immediate container, or an accompanying brochure also must:
(1) State that the contents are exempt from NRC or Agreement State licensing requirements; and (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 20
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' into Foods, Severages, Cosmetics, or Other Drugs or Medicinals, or into Products Manufactured i
' for Commercial Distribution."
r h-f Dated at Rockville, Maryland this -
day of '
,1997. ~
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- For the Nuclear Regulatory Commission.
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John C. Hoyle,
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Secretary of the Commission.
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i Draft press release --
8/7/97 NRC CHANGES REGULATIONS TO PERMIT EXEMPT DISTRIBUTION OF RADIOACTIVE DIAGNOSTIC DRUG g toc 62 W 5 o 6.n d 'S L The No aar Regulatory Commission is amending its regulationsflo allow a specific r' ative drug used to diagnose stomach ulcers to be distributed to any person for a, ministration to humans. Before this$hw(kwdange, only phyalcians authorized by the NRC or Agreem int States could receive and administer the drug.
The change does not relieve persons from tha requirernent to comply with applicable Food and Drug Administration or other Federal and State requirements governing recolpt, administratior, and use of drugs [f y th/an y The change is in response to a 1994 petition rom Tri Mec Specialties, Inc.
g s [rIy erson to receive, possess, use and transfer capsules containing one t
o microcurie carbon 14 urea each for diagnostic use in patients. The NRC has determined that the capsules present a minimal radiation risk, and therefore believes that regulatory control of the drug for iadiation 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 contents. The containers of the capsules must bear the words " radioactive material" and other specific information on the contents of the container, in addition, only those persons who are licensed will be permitted to use the capsules for research involving human subjects.
The Tri Med petition stated that Carbon 14 urea can be used to detect the presence of a bacterium that causes peptic ulcers, a chronic inflammatory condition.of the stomach and duodenum that affects as many as 10 percent of peoplo in the United States at some time in their lives. According to a July 1994
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article in the Journal of the American Medical Association the disease has -
relatively_ low mortality, but results in substantial human suffering and high-economic costs. Doctors can now cure most ulcer problems with antiblotics. The
. 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 into a collection bag,
- whlah is malled to a testing laboratory for analysis.
Before the change, only physiclans who were authorized users-(e.g.,
physic ans who met certain training and experience criteria regarding the safe use
- f rad onctive drugs) or persons v wkb;; undct the supervision of an authorized user could administer radioactive drugs for medical purposes.
Under the amendments, physicians or other health care workers will not n'eed to be authorized users in order to administer the drug, and physicians will not need to refer their patients to nuclear medicine physicians. This should result in cost savings to patients, insurers, and the health care industry.
A proposed rule on this subject was published in the Federal Register for Wrl public comment on Jun,e 16. Minor changes made to the tule as a result of b
d ant comments receive (are discussed in a Federal Register notice that will be
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published shortly.
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The Commissioners 4
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Copies of the Federal Register notice of final ruk making will be distributed to affected licensees and commenters on the proposed rule. The notice will also be sent to other Interested parties upon request.
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L Joseph Callan
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Executive Director for Operations
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Enclosures:
As stated (6)
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Distribution:
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AThadani, DEDE EDO r/f, DMendiola /
ASummerour CGallagher
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RECORD NOTE: A draft copy of the proposed rule was sent to OlG for Information on Aunust
.1997.
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