[Federal Register Volume 62, Number 231 (Tuesday, December 2, 1997)]
[Rules and Regulations]
[Pages 63634-63640]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 97-31514]
=======================================================================
-----------------------------------------------------------------------
NUCLEAR REGULATORY COMMISSION
10 CFR Parts 30 and 32
RIN 3150-AF70
Exempt Distribution of a Radioactive Drug Containing One
Microcurie of Carbon-14 Urea
AGENCY: Nuclear Regulatory Commission.
ACTION: Final rule.
-----------------------------------------------------------------------
SUMMARY: The Nuclear Regulatory Commission (NRC) is amending its
regulations to permit NRC licensees to distribute a radioactive drug
containing one microcurie of carbon-14 urea to any person for ``in
vivo'' diagnostic use. The NRC has determined that the radioactive
component of such a drug in capsule form presents an insignificant
radiation risk and, therefore, regulatory control of the drug for
radiation safety is not necessary. This amendment makes the drug more
widely available and reduces costs to patients, insurers, and the
health care industry. This action grants a petition for rulemaking
(PRM-35-12) from Tri-Med Specialties, Inc. and completes action on the
petition.
EFFECTIVE DATE: January 2, 1998.
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 [email protected].
SUPPLEMENTARY INFORMATION:
I. The Petition for Rulemaking.
II. Proposed Rule, Public Comments, and NRC Responses.
III. Summary of the Final Amendments.
IV. Description of the Final Amendments.
V. Agreement State Compatibility.
VI. Finding of No Significant Environmental Impact: Availability.
VII. Paperwork Reduction Act Statement.
VIII. Regulatory Analysis.
IX. Regulatory Flexibility Certification.
X. Small Business Regulatory Enforcement Fairness Act.
XI. Backfit Analysis.
List of Subjects
I. 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 (Ci) of
C-14-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 in humans.
Following the receipt of the petition, the NRC published for public
comment a notice of receipt of petition for rulemaking in the Federal
Register on December 2, 1994 (59 FR 61831). The comment period closed
on February 15, 1995. The NRC received 315 public comment letters, of
which 313 supported the petition (they were mostly form letters) and 2
letters opposed the petition.
II. Proposed Rule, Public Comments, and NRC Responses
A proposed rule was published on June 16, 1997 (62 FR 32552) that
would permit NRC licensees to distribute capsules containing one
microcurie
C-14 urea to any person for ``in vivo'' diagnostic use. The public
comment 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.
This change makes the drug more widely available and reduces costs
to patients, insurers, and the health care industry.
The NRC received seven public comment letters on the proposed rule:
three from industry, three from State agencies, and one from a
physician associated with a university medical facility. Four
commenters supported the rule, one opposed the rule, and two provided
comments but did not explicitly state whether they supported or opposed
the rule. Public comments and NRC's responses are presented below.
Comment 1: Under the proposed distribution, the NRC should not be
forbidding research use of this drug by the same physicians who may use
it clinically. Research use also should be permitted under this
exemption because the radiological risk for using C-14 capsules is
insignificant.
Response: The NRC did not change the final rule in response to this
comment. A common rule entitled ``Federal Policy for the Protection of
Human Subjects; Notices and Rules'' was promulgated by 16 Federal
agencies on June 18, 1991 (56 FR 28002) and was intended to ensure the
protection of human research subjects. This rule was adopted to
implement a recommendation of the President's Commission for the Study
of Ethical Problems in 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 involving radioactive material) must provide for
[[Page 63635]]
the following minimal protections for the human subjects: (1) that the
research is approved by an Institutional Review Board (IRB) and (2)
that the human subject gives informed consent to participate in the
research. Further, 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 exempt from 10 CFR 35.6.
Comment 2: Two commenters expressed concerns that the proposed rule
language, ``not exceeding one microcurie,'' appeared to indicate that
the upper limit of the radioactivity in a capsule is exactly one
microcurie of C-14. Both stated that it is not possible to make the
capsules to exactly one microcurie because of statistical deviations
during the manufacturing process.
Response: The NRC agrees with the commenters. The proposed rule did
not intend to limit the radioactivity of C-14 to exactly one
microcurie. The final rule language has been modified to read
``capsules containing one microcurie C-14 urea (allowing for nominal
variation that may occur during the manufacturing process).''
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 half-life, when compared to one microcurie of Tc-99m or I-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 I-131 also would be insignificant.
Response: In comparing the hazard significance of the one
microcurie C-14 Urea diagnostic test to the extensive use of Tc-99m and
I-131, the NRC did not evaluate the dose to the patient because this
dose would be justified for medical reasons. Justification for
retaining some licensing control on the medical use of Tc-99m and I-131
while exempting the one microcurie carbon-14 urea capsules relies on
the relative occupational hazards to technicians and physicians
administering the radiopharmaceuticals.
Administering an encapsulated dosage of one microcurie C-14
involves virtually no occupational dose due to the low energy beta
radiation and minimal possibility for contamination of personnel or
facilities. On the other hand dosages of Tc-99m and I-131 entail
extracting 10s to 100s of millicurie amounts, often in liquid form,
from shielded sources of even higher activity. The possibility of
direct exposure to gamma radiation and the possibility of contamination
requires that radiation protection measures be in place to maintain
exposure to staff as low as is reasonably achievable.
Tc-99m and I-131, having relatively short half-lives, present
minimal environmental hazard. C-14 as urea is excreted from the patient
as carbon dioxide (CO2) which diffuses into the atmosphere.
Based on a calculation found in the regulatory analysis for this rule,
the current world inventory of naturally occurring C-14 results in an
average dose to members of the public of about 1.25 mrem/yr. A release
of 0.6 curies of C-14 from the 600,000 tests expected to be
administered annually, would result in an additional average annual
dose of 2 x 10-7 mrem. Comparing this estimate to the EPA
Clean Air Act reporting level of 1 mrem/year, this new test is
environmentally insignificant.
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 concern for health risks in the disposal of the
product, labels should contain a statement that the product may be
disposed of in the general trash.
Response: In the final rule, the label requirements include a
statement that the product may be disposed of in ordinary trash.
Comment 5: The Commenter agrees that the widespread use of this
product will require uniform regulations and that Agreement States will
need to make appropriate regulatory provisions to enable persons to
receive the drug for ``in vivo'' diagnostic use. To avoid confusing
licensees and users, these changes to NRC and Agreement State
regulations should be made 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
compatible changes in their regulations expeditiously. However, under
NRC's Adequacy and Compatibility Policy, Agreement States have up to
three years to change their regulations for amendments or program
requirements that are items of compatibility.
Comment 6: The NRC should address this rule in its ongoing effort
to revise 10 CFR Part 35 in its entirety. The commenter believes that
(1) this rule represents a piecemeal effort 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.
Response: 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.
Response: The amount of radiation safety training needed for
personnel depends on the level of radiation risk associated with the
radioactive drug. Because C-14 capsules present insignificant radiation
risk, radiation safety training for personnel handling and
administering the capsule is not necessary, and thus, not required.
Comment 8: If the NRC promulgates the proposed rule in its present
form, the exemption will divest the Agreement States of any authority
to regulate this product under a general or specific license. Had the
NRC instead simply proposed a general license, Agreement State agencies
would retain the authority to adopt the general license or continue to
require specific licensing.
Response: In the draft rulemaking plan, the NRC suggested using the
general license approach. The NRC received nine comment letters from
Agreement States on the draft rulemaking plan; three suggested that an
exemption approach would be more appropriate because it would be less
costly to the Agreement States and their
[[Page 63636]]
licensees than the general license approach.
Based on these comments, the NRC chose the exemption approach in
the final rule plan as more cost-effective than a general license
approach. The final rulemaking plan was revised accordingly and was
provided to the Agreement States. No Agreement States expressed
opposition to the NRC on the exemption approach.
Among the seven public comment letters received on the proposed
rule, two were from Agreement States and one from a non Agreement
State. All three supported the proposed rule.
Comment 9: The environmental assessment fails to consider the fact
that another equally noninvasive, but nonradiological, diagnostic
procedure (such as C-13 test) is available and provides a comparable
alternative to the C-14 test. The apparent assumption underlying the
environmental assessment is that in the absence of the C-14 test, the
only alternative for the detection of H. pylori is invasive
gastroendoscopy.
Response: Because the C-14 urea capsules are already available to
authorized user physicians, the only regulatory issue in this
rulemaking is whether the C-14 method should be made available to
individuals who are not authorized users. The purpose of the
environmental assessment is to consider and document whether the
subject rule is expected to have any significant impact to the
environment. In this environment assessment, the NRC has determined
that the environmental impact is expected to be insignificant because
of the extremely low radiological hazards associated with the use of
capsules containing one microcurie C-14 urea. The presence of an
additional non-invasive alternative procedure does not affect NRC's
determination of no significant environmental impact.
Comment 10: NRC's policy in the past has been not to exempt
byproduct material that is ingested. Any change in this policy would be
a significant departure from existing NRC regulations.
Response: This change is a departure from existing NRC regulations.
In the statement of consideration for the proposed rule, under the
heading ``Current NRC Regulations on Exemptions From Licensing,'' the
NRC stated that, although two broad material exemptions (Sec. 30.14,
``Exempt concentrations,'' and Sec. 30.18, ``Exempt quantities'')
exclude the transfer of byproduct material contained in any product
designed for ingestion or inhalation by a human being, the C-14
capsules manufactured or prepared as a radioactive drug can be
distributed to persons exempt from licensing for ``in vivo'' diagnostic
use because the capsules present an insignificant radiological risk to
the public and the environment. This exemption only applies to the
diagnostic use of capsules containing one microcurie C-14 manufactured
or prepared as a radioactive drug to make a clear distinction between
this radioactive drug that is intended for ingestion by humans and
other uses of C-14 urea and byproduct material distributed under
Secs. 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.
Response: The transcript from the ACMUI meeting shows the Committee
did include radiation safety in its considerations and did not consider
it to be an issue. Further, as stated in 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.
Comment 12: The exemption approach does not provide the NRC with
flexibility to impose a limitation on the amount of C-14 capsules any
physician can possess in an office. In the event there is a recall of
the product, or a large amount of product becomes unusable, the NRC
will have no control over the disposal of the product.
Response: It is not necessary to impose a possession limit on the
amount of C-14 capsules because the radiation risk is insignificant.
The earth's atmosphere contains an inventory of naturally occurring C-
14 of about 3.8 million curies which is in addition to the huge
inventory of about 240 million curies in the world's oceans. The small
amount of C-14 released into the atmosphere from the use of this test
would mix with the global inventory and would have no impact on public
health. The current world inventory of naturally occurring C-14 results
in an average dose to the public of about 1.25 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 10-7 mrem. In the event that a recall is necessary,
the manufacturer may use the same process for recalling any other non-
radioactive drugs. If C-14 urea capsules are returned to the
manufacturers, they will be disposed of in accordance with the
manufacturer's possession license. A user, however, can dispose the C-
14 urea capsules as ordinary trash. Medical users of the C-14 urea test
would be unlikely to acquire significant quantities of capsules 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.
Response: Because the radiation risk from C-14 capsules is
insignificant, regulatory control of the use, storage, and disposal of
the drug for purpose of radiation safety is not necessary. In fact, the
label accompanying C-14 capsules is required to indicate that the
capsules may be disposed of by users as ordinary trash. Paragraph(a)(6)
of Sec. 32.21 requires that applicants submit copies of prototype
labels and brochures for NRC approval. The NRC will ensure that the
labels meet the requirements of Sec. 32.21a before they are approved.
Since paragraph (a) of Sec. 32.21a specifies that the label must be
durable and legible, the use of an additional phrase such as
``conspicuously and prominently'' is unnecessary. Promotional brochures
are for information only; manufacturers are not required to indicate on
the promotional brochures that C-14 is a radioactive material.
III. Summary of the Final Amendments
Final Amendment to 10 CFR Part 32
The regulations in 10 CFR part 32 are amended to add new
Secs. 32.21 and 32.21a, to provide requirements for a specific license
to manufacture, prepare, process, produce, package, repackage, or
transfer for commercial distribution,
[[Page 63637]]
capsules containing one microcurie of C-14 urea, as a radioactive drug,
to be distributed to any person for ``in vivo'' diagnostic use. These
requirements are consistent with the existing requirements on other
items under the heading ``Exemptions'' in 10 CFR part 30. The amendment
includes a reminder that licensees distributing the radioactive drug to
persons exempt from licensing would not be relieved from other
applicable Federal (e.g., FDA) or State requirements governing the
manufacture and distribution of drugs.
The amendment requires that the manufacture or preparation of
capsules containing one microcurie of C-14 urea be prepared by persons
who meet the current NRC regulations to manufacture and commercially
distribute radioactive drugs. The NRC believes regulatory control is
needed to provide high confidence that the drug contains one microcurie
of C-14 urea and does not contain any other radioactive contaminants.
Final Amendment to 10 CFR Part 30
The NRC has determined that the drug in capsule form presents an
insignificant radiological safety and environmental risk, and that it
is not necessary to regulate the use of this drug for its radioactive
component. Therefore, the NRC can not justify requiring physicians, or
any other person, to meet NRC training and experience criteria directed
at the safe use of radioactive drugs, or to become an ``authorized
user.'' Hence, the capsules can be distributed to any person. However,
other Federal or State agencies may limit the receipt and use of the
capsules in accordance with their own requirements.
The regulations in 10 CFR part 30 are amended to add a new
Sec. 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'' diagnostic use does not extend to use of the
capsules for research involving human subjects. Any person desiring to
use the capsules for human research would still be required to submit
an application for a specific license under part 35. The phrase ``in
vivo diagnostic use'' was selected to describe the activity authorized
in Sec. 30.21 to differentiate it from the term ``medical use''
because:
(1) ``Medical use'' limits administration to authorized users; use
of this drug would not be so limited; and
(2) ``Medical use'' includes the administration of the drug to a
human research subject, which would continue to require a specific
license pursuant to part 35 under this rulemaking.
Effects of the Final Amendments
The final amendments make the drug available to any person, for
``in vivo'' diagnostic use, without need for an NRC or 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.
IV. Description of the Final Amendments
The final amendments are the same as the proposed amendments except
for two minor changes. Public comments suggested that the phrase
``carbon-14 urea capsules not exceeding one microcurie'' used in the
proposed rule may be interpreted as an exact limit of one microcurie
per capsule (See Comment 2 under the heading ``Public Comment and NRC
Responses). The final rule has been modified and the phrase ``capsules
containing one microcurie carbon-14 urea (allowing for nominal
variation that may occur during the manufacturing process)'' is used.
Another public comment suggested that labels should contain a statement
that the product may be disposed of in the general trash. In the final
rule, the label requirements include such a statement.
Manufacturer and Distributors
A new section is added to 10 CFR Part 32 to permit the distribution
of the capsules to persons who are exempt from licensing.
Section 32.21 Radioactive Drug: Manufacture, Preparation, or Transfer
for Commercial Distribution of Capsules Containing one Microcurie
Carbon-14 Urea Each for ``in Vivo'' Diagnostic use for Humans to
Persons Exempt From Licensing; Requirements for a License
Paragraph (a)
This paragraph establishes the requirements for approval of a
license application to manufacture, prepare, process, produce, package,
repackage, or transfer for commercial distribution, capsules containing
one microcurie carbon-14 urea each for ``in vivo'' diagnostic use, to
persons exempt from licensing.
Paragraph (a)(1)
This paragraph limits issuance of an ``exempt distribution
license'' for distribution of the capsules to persons exempt from
licensing to only those who possess either a NRC or Agreement State
``specific license'' for possession and use of byproduct material.
Paragraph (a)(2)
To assure that the capsules contain one microcurie of carbon-14 and
present no other radiological risks, this paragraph requires that the
persons manufacturing and/or commercially distributing the capsules for
``in vivo'' diagnostic use must also meet the requirements of
Sec. 32.72(a)(2). Specifically, these persons must be:
(1) Registered with or licensed by the FDA as a drug manufacturer;
or
(2) Registered with or licensed by a state agency as a drug
manufacturer; or
(3) Licensed as a pharmacy by a State Board of Pharmacy; or
(4) Operating as a nuclear pharmacy within a Federal medical
institution.
Paragraph (a)(3)
This paragraph requires applicants to provide evidence that each
carbon-14 urea capsule contains one microcurie. The NRC's evaluation
that the capsules would result in insignificant radiation risks was
based on the capsules containing one microcurie of carbon-14 urea.
Therefore, applicants must demonstrate that the activity of each
carbon-14 capsule contains one microcurie, allowing for nominal
variation that may occur during the manufacturing process.
Paragraph (a)(4)
This paragraph prohibits carbon-14 urea from being contained in any
food, beverage, cosmetic, drug or other commodity designed for
ingestion or
[[Page 63638]]
inhalation by, or topical application to, a human being except for the
capsules as described in this section, because exempt distribution of
this drug has only been evaluated for ``in vivo'' diagnostic use in the
form of a capsule containing one microcurie of carbon-14 urea. There is
no prohibition against the capsule being combined with food or beverage
at the time of administration so that the capsule can be ingested by
the patient.
Paragraph (a)(5)
Because the exempt distribution of this drug has only been
evaluated for ``in vivo'' diagnostic use in the form of a capsule
containing one microcurie of carbon-14 urea, this paragraph prohibits
incorporation of the capsules into any manufactured or assembled
commodity, product, or device intended for commercial distribution.
Further, although the drug is being distributed to persons exempt from
licensing, this paragraph requires the carbon-14 urea to be identified
as radioactive because the drug is being used for its radioactive
content; therefore, the end user must be provided with information that
the drug contains a radioactive material.
Paragraph (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 Sec. 32.21a (a) and (b).
Paragraph (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.
Paragraph (a)
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) Identifies the radioisotope, the physical and chemical form of
the radioisotope, the quantity of radioactivity contained in each
container at a specific date; and
(2) Bears the words ``Radioactive Material.''
The date requirement is consistent with labeling requirements for
other radioactive drugs with a half life of greater than 100 days.
Paragraph (b)
This paragraph establishes that, consistent with the intended use
of the capsules, the label affixed to the immediate container, or an
accompanying brochure, must:
(1) State that the contents are exempt from NRC or Agreement State
licensing 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 radioactive product other than in the
form of a capsule for commercial distribution. There is no prohibition
against the capsule being combined with food or beverage at the time of
administration so that the capsule can be ingested by the patient. This
label also informs the user that this product may be disposed of in
ordinary trash.
``In Vivo'' Diagnostic use by Persons Exempt From Licensing
A new section is added to 10 CFR Part 30 to exempt any person from
NRC or the Agreement State regulations to receive the drug for ``in
vivo'' diagnostic use for humans.
Section 30.21 Radioactive Drug: Capsules Containing one Microcurie of
Carbon-14 Urea for ``in Vivo'' Diagnostic use for Humans
Paragraph (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.
Paragraph (b)
This paragraph establishes that persons who desire to use the drug
for research involving human 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.
Paragraph (c)
This paragraph specifies that a specific license is needed to
manufacture, prepare, process, produce, package, repackage or transfer
such capsules for commercial distribution.
Paragraph (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 Environmental Impact: Availability
The Commission has determined under the National Environmental
Policy Act of 1969, as amended, and the Commission's regulations in
Subpart A of 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
[[Page 63639]]
required. The final rule establishes requirements for the manufacture
and commercial distribution of carbon-14 urea capsules to persons
exempt from licensing and establishes regulations to permit any person
to receive the capsules without an NRC license. The Commission believes
that the radioactive component of this drug presents an insignificant
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-radiological impacts. One public
comment on the draft environmental assessment has been received (See
Comment 9 under the heading ``Proposed Rule, Public Comments, and NRC
Responses'').
The environmental assessment and finding of no significant impact
on which this determination is based is available for inspection at the
NRC Public Document Room, 2120 L Street NW. (Lower Level), Washington,
DC. Single copies of the environmental assessment and the finding of no
significant impact are available from Dr. Anthony N. Tse, Office of
Nuclear Regulatory Research, U.S. Nuclear Regulatory Commission,
Washington, DC 20555-0001, telephone (301) 415-6233 or e-mail at
[email protected].
VII. Paperwork Reduction Act Statement
This final rule amends information collection requirements that are
subject to the Paperwork Reduction Act of 1995 (44 U.S.C. 3501 et
seq.). These requirements were approved by the Office of Management and
Budget, approval numbers 3150-0001, 3150-0017, and 3150-0120.
The public reporting burden for this collection of information is
estimated to average 16 hours per response, including the time for
reviewing instructions, searching existing data sources, gathering and
maintaining the data needed, and completing and reviewing the
collection of information. Send comments on any aspect of this
collection of information, including suggestions for reducing the
burden, to the Information and Records Management Branch (T-6 F33),
U.S. Nuclear Regulatory Commission, Washington, DC 20555-0001, or by
Internet electronic mail at [email protected]; 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
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.
VIII. Regulatory Analysis
The NRC has prepared a regulatory analysis for the final rule. The
analysis examines the benefits and impacts considered by the NRC. No
public comments on the draft regulatory analysis have been received
during the public comment period. The regulatory analysis is available
for inspection at the NRC Public Document Room, 2120 L Street NW.
(Lower Level), Washington, DC. Single copies of the regulatory analysis
are available from Dr. Anthony N. Tse, Office of Nuclear Regulatory
Research, U.S. Nuclear Regulatory Commission, Washington, DC 20555-
0001, telephone (301) 415-6233 or e-mail at [email protected].
IX. Regulatory Flexibility Certification
As required by the Regulatory Flexibility Act of 1980, 5 U.S.C.
605(b), the Commission certifies that this rule does not have a
significant economic impact upon a substantial number of small
entities. The final rule permits physicians and other health care
providers to use an additional diagnostic test without having to obtain
an NRC 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).
X. Small Business Regulatory Enforcement Fairness Act
In accordance with the Small Business Regulatory Enforcement
Fairness Act of 1996, the NRC has determined that this action is not
``a major'' rule and has verified this determination with the Office 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).
XII. List of Subjects
10 CFR Part 30
Byproduct material, Criminal penalties, Government contracts,
Intergovernmental relations, Isotopes, Nuclear materials, Radiation
protection, Reporting and record keeping requirements.
10 CFR Part 32
Byproduct material, Criminal penalties, Labeling, Nuclear
materials, Radiation protection, Reporting and recordkeeping
requirements.
For the reasons set out in the preamble and under the authority of
the Atomic Energy Act of 1954, as amended, the Energy Reorganization
Act of 1974, as amended, and 5 U.S.C. 552 and 553, the NRC is adopting
the following amendments to 10 CFR Parts 30 and 32.
PART 30--RULES OF GENERAL APPLICABILITY TO DOMESTIC LICENSING OF
BYPRODUCT MATERIAL
1. The authority citation for part 30 continues to read as follows:
Authority: Secs. 81, 82, 161, 182, 183, 186, 68 Stat. 935, 948,
953, 954, 955, as amended, sec. 234, 83 Stat. 444, as amended (42
U.S.C. 2111, 2112, 2201, 2232, 2233, 2236, 2282); secs. 201, as
amended, 202, 206, 88 Stat. 1242, as amended, 1244, 1246 (42 U.S.C.
5841, 5842, 5846).
Section 30.7 also issued under Pub. L. 95-601, sec.10, 92 Stat.
2951 as amended by Pub. L. 102-486, sec. 2902, 106 Stat. 3123, (42
U.S.C. 5851). Section 30.34(b) also issued 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 Sec. 30.8, paragraph (b) is revised to read as follows:
Sec. 30.8 Information collection requirements: OMB approval.
* * * * *
(b) The approved information collection requirements contained in
this part appear in Secs. 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 Sec. 30.21 is added under the undesignated center heading
``Exemptions'' to read as follows:
[[Page 63640]]
Sec. 30.21 Radioactive drug: Capsules containing 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 37 kBq (1 Ci)
carbon-14 urea (allowing for nominal variation that may occur during
the manufacturing process) each, for ``in vivo'' diagnostic use for
humans.
(b) Any person who desires to use the capsules for research
involving human subjects shall apply for and receive a specific license
pursuant to part 35 of this chapter.
(c) Any person who desires to manufacture, prepare, process,
produce, package, repackage, or transfer for commercial distribution
such capsules shall apply for and receive a specific license pursuant
to Sec. 32.21 of this chapter.
(d) Nothing in this section relieves persons from complying with
applicable FDA, other Federal, and State requirements governing
receipt, administration, and use of drugs.
PART 32--SPECIFIC DOMESTIC LICENSES TO MANUFACTURE OR TRANSFER
CERTAIN ITEMS CONTAINING BYPRODUCT MATERIAL
4. The authority citation for Part 32 continues to read as follows:
Authority: 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 Sec. 32.8, paragraph (b) is revised to read as follows:
Sec. 32.8 Information collection requirements: OMB approval.
* * * * *
(b) The approved information collection requirements contained in
this part appear in Secs. 32.11, 32.12, 32.14, 32.15, 32.16, 32.17,
32.18, 32.19, 32.20, 32.21, 32.21a, 32.22, 32.23, 32.25, 32.26, 32.27,
32.29, 32.51, 32.51a, 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.
* * * * *
6. A new Sec. 32.21 is added to read as follows:
Sec. 32.21 Radioactive drug: Manufacture, preparation, or transfer for
commercial distribution of capsules containing carbon-14 urea each for
``in vivo'' diagnostic use for humans to persons exempt from licensing;
Requirements for a license.
(a) An application for a specific license to manufacture, prepare,
process, produce, package, repackage, or transfer for commercial
distribution capsules containing 37 kBq (1 Ci) 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 Sec. 30.21 of this chapter or the equivalent
regulations of an Agreement State will be approved if:
(1) The applicant satisfies the general requirements specified in
Sec. 30.33 of this chapter, provided that the requirements of
Sec. 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 Sec. 32.72(a)(2) of
this part;
(3) The applicant provides evidence that each capsule contains 37
kBq (1 Ci) 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.
(b) Nothing in this section relieves the licensee from complying
with applicable FDA, other Federal, and State requirements governing
drugs.
7. A new Sec. 32.21a is added to read as follows:
Sec. 32.21a Same: Conditions of license.
Each license issued under Sec. 32.21 of this part is subject to the
following conditions:
(a) The immediate container of the capsule(s) must bear a durable,
legible label which:
(1) Identifies the radioisotope, the physical and chemical form,
the quantity of radioactivity of each capsule at a specific date; and
(2) Bears the words ``Radioactive Material.''
(b) In addition to the labeling information required by paragraph
(a) of this section, the label affixed to the immediate container, or
an accompanying brochure also must:
(1) State that the contents are exempt from NRC or Agreement State
licensing requirements; and
(2) Bear the words ``Radioactive Material. For ``In Vivo''
Diagnostic Use Only. This Material Is Not To Be Used for Research
Involving Human Subjects and Must Not Be Introduced into Foods,
Beverages, Cosmetics, or Other Drugs or Medicinals, or into Products
Manufactured for Commercial Distribution. This Material May Be Disposed
of in Ordinary Trash.''
Dated at Rockville, Maryland, this 24th day of November, 1997.
For the Nuclear Regulatory Commission.
John C. Hoyle,
Secretary of the Commission.
[FR Doc. 97-31514 Filed 12-1-97; 8:45 am]
BILLING CODE 7590-01-P