Exempt Distribution of a Radioactive Drug Containing One Microcurie of Carbon-14 Urea

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: Proposed rule; request for comments.

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SUMMARY: The Nuclear Regulatory Commission (NRC) is proposing an

amendment to its regulations that would 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. If adopted,

this amendment would make the drug more widely available, and reduce

costs to patients, insurers, and the health care industry. This action

is being taken in response to a petition for rulemaking (PRM-35-12)

submitted by Tri-Med Specialties, Inc.

DATES: Submit comments by July 16, 1997. Comments received after this

date will be considered if it is practicable to do so, but the

Commission is able to assure consideration only for comments received

on or before this date.

ADDRESSES: Send comments to: Secretary, U.S. Nuclear Regulatory

Commission, Washington, DC 20555-0001, Attention: Rulemakings and

Adjudications Staff.

Hand deliver comments to: 11555 Rockville Pike, Rockville,

Maryland, between 7:30 am and 4:15 pm on Federal workdays.

The public may examine comments received, the environmental

assessment and finding of no significant impact, and the regulatory

analysis at the NRC Public Document Room, 2120 L Street NW., (Lower

Level), Washington, DC.

FOR FURTHER INFORMATION CONTACT: 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:

ssment and finding of no significant impact, and the regulatory

analysis at the NRC Public Document Room, 2120 L Street NW., (Lower

Level), Washington, DC.

FOR FURTHER INFORMATION CONTACT: 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. Background

II. Discussion

III. Summary of Proposed Amendments

IV. Agreement State Compatibility

V. Electronic Access

VI. Finding of No Significant Environmental Impact: Availability

VII. Paperwork Reduction Act Statement

VIII. Regulatory Analysis

IX. Regulatory Flexibility Certification

X. Backfit Analysis

XI. List of Subjects

I. Background

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

14C-urea for in vivo diagnostic testing.'' The purpose of

this diagnostic test is to detect the presence of the bacterium

Helicobacter pylori (H. pylori), a cause of peptic ulcers.

``Peptic ulcer disease is a chronic inflammatory condition of the

stomach and duodenum that affects as many as 10 percent of people in

the United States at some time in their lives. The disease has

relatively low mortality, but it results in substantial human suffering

and high economic costs.'' (Source: Article included as an appendix to

the petition, from JAMA, July 6, 1994, Vol-272, No. 1, ``H. pylori in

Peptic Ulcer Disease--NIH Consensus Conference'').

In the petition, the petitioner stated the following:

Recent medical research has found that peptic ulcers are commonly

caused by a bacterium called H. pylori. This

esults in substantial human suffering

and high economic costs.'' (Source: Article included as an appendix to

the petition, from JAMA, July 6, 1994, Vol-272, No. 1, ``H. pylori in

Peptic Ulcer Disease--NIH Consensus Conference'').

In the petition, the petitioner stated the following:

Recent medical research has found that peptic ulcers are commonly

caused by a bacterium called H. pylori. This

bacterium lives in the stomach of most ulcer sufferers. By treating

ulcer patients with antibiotics, doctors can now cure most ulcer

problems.

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 ($1,000).

With the new test, H. pylori can be detected non-invasively using a

14C-urea tracer. 14C-urea is broken down by H.

pylori to form labeled CO2 which is expired in the breath.

To do the test, a doctor asks the patient to swallow the capsule with

30 mls of water. After 15 minutes the patient blows 2 liters of breath

into a collection bag (a mylar balloon) which is mailed to a testing

laboratory. If 14C--CO2 more than twice

background is present in the breath sample, then the patient must be

infected with H. pylori.

This proposed rule, should it become final, would grant the

petition for rulemaking (PRM-35-12) from Tri-Med and complete action on

the petition.

Public Comments on the Petition

s of breath

into a collection bag (a mylar balloon) which is mailed to a testing

laboratory. If 14C--CO2 more than twice

background is present in the breath sample, then the patient must be

infected with H. pylori.

This proposed rule, should it become final, would grant the

petition for rulemaking (PRM-35-12) from Tri-Med and complete action on

the petition.

Public Comments on the Petition

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 support the petition (they were mostly form letters) and 2

letters opposed the petition. The two letters opposing the petition

stated that 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 that the medical uses should be

restricted to short-lived isotopes because of disposal problems

presented by long-lived isotopes.

The NRC has considered the two opposing comments and has determined

the following:

(1) The resulting radiation dose from the capsules to workers,

patients, and the public is very low (see Regulatory Analysis).

(2) The impacts associated with any releases of 14C to

the surrounding environment are expected to be very small and the

expected risks are minimal (see Environmental Assessment). Similarly,

the small doses from naturally occurring 14C are of little

significance to human health and the environment. Also, the Commission

concludes that the potential long-term impacts from widespread releases

of the long-lived 14C (5,730-year radiological half-life)

from breath tests are insignificant.

Comments From Advisory Committee on the Medical Uses of Isotopes

onmental Assessment). Similarly,

the small doses from naturally occurring 14C are of little

significance to human health and the environment. Also, the Commission

concludes that the potential long-term impacts from widespread releases

of the long-lived 14C (5,730-year radiological half-life)

from breath tests are insignificant.

Comments From Advisory Committee on the Medical Uses of Isotopes

This petition was discussed with NRC's Advisory Committee on the

Medical Uses of Isotopes (ACMUI) at its October 1995 meeting. The ACMUI

indicated that it endorsed the wide availability of this diagnostic

test and that the radioactive drug could be used under a general

license or an exemption, whichever the NRC may determine to be

procedurally easier.

II. Discussion

Regulatory Issue

The regulatory issue is whether capsules containing one microcurie

of carbon-14 urea present a sufficiently small radiation risk that they

can be safely distributed to any person (including physicians who are

not ``authorized users'' under Part 35).

Current NRC Regulations for the Manufacture and Commercial Distribution

of Radioactive Drugs Containing Byproduct Material

NRC regulations in 10 CFR 32.72 address the manufacture,

preparation, or transfer for commercial distribution of radioactive

drugs containing byproduct material. This regulation requires

manufacturers or preparers of radioactive drugs for commercial

distribution to be:

(1) Registered or licensed with the U.S. Food and Drug

Administration (FDA) as a drug manufacturer;

(2) Registered or licensed with a State agency as a drug

manufacturer;

(3) Licensed as a pharmacy by a State Board of Pharmacy; or

n of radioactive

drugs containing byproduct material. This regulation requires

manufacturers or preparers of radioactive drugs for commercial

distribution to be:

(1) Registered or licensed with the U.S. Food and Drug

Administration (FDA) as a drug manufacturer;

(2) Registered or licensed with a State agency as a drug

manufacturer;

(3) Licensed as a pharmacy by a State Board of Pharmacy; or

(4) Operating as a nuclear pharmacy within a Federal medical

institution.

These facilities have a specific license with the NRC. Under the

specific license, the manufacturer or pharmacy can distribute

radioactive drugs only to persons authorized pursuant to Part 35,

``Medical Use of Byproduct Material.''

Current NRC Regulations for the Medical Use of Radioactive Drugs

Containing Byproduct Material

Currently, 10 CFR Part 35 only permits physicians who are

authorized users (e.g., physicians who meet certain training and

experience criteria regarding the safe use of radioactive drugs) or

persons working under the supervision of an authorized user to

administer radioactive drugs for medical use. The Agreement States have

similar requirements.

Current NRC Regulations on Exemptions From Licensing

Existing exemptions from licensing requirements for the use of

byproduct material include exemptions for specific products (e.g., time

pieces), exemption for classes of products (e.g., gas and aerosol

detectors) and broader materials exemptions in Sec. 30.14, ``Exempt

concentrations,'' and Sec. 30.18, ``Exempt quantities.'' These two

broad materials exemptions specifically exclude the transfer of

byproduct material contained in any food, beverage, cosmetic, drug, or

any product designed for ingestion or inhalation by, or application to,

a human being. (In the case of exempt quantities, this prohibition is

contained in Sec. 32.18, ``Manufacture, distribution and transfer of

exempt quantities of byproduct material; Requirements for a license,''

Sec. 32.18(b))

ly exclude the transfer of

byproduct material contained in any food, beverage, cosmetic, drug, or

any product designed for ingestion or inhalation by, or application to,

a human being. (In the case of exempt quantities, this prohibition is

contained in Sec. 32.18, ``Manufacture, distribution and transfer of

exempt quantities of byproduct material; Requirements for a license,''

Sec. 32.18(b)).

Capsules containing one microcurie of carbon-14 urea would not

qualify as an ``exempt quantity'' in accordance with Sec. 30.18 because

of their intended use (as a drug) even though they contain a smaller

quantity than that set forth in Sec. 30.71, Schedule B. This use is

outside the intent of the exemption currently in Sec. 30.18. It would

introduce needless complexity to the regulations and confusion to

accommodate this unique use under the aforementioned sections.

However, because the capsules present an insignificant radiological

risk to the public and the environment, the NRC believes they could be

distributed to persons exempt from licensing for ``in vivo'' diagnostic

use.

Proposed Amendments for Permitting the Distribution of the Capsules to

Persons Exempt From Licensing

Proposed Amendment to 10 CFR Part 32

The regulations in 10 CFR Part 32 would be amended to add a new

Sec. 32.21, to provide requirements for a specific license to

manufacture, prepare, process, produce, package, repackage, or transfer

for commercial distribution capsules containing one microcurie of

carbon-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 proposed regulation would include

a reminder that licensees distributing the radioactive drug to persons

exempt from licensing would not be relieved from other applicable

Federal (e.g., FDA) or State

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 proposed regulation would include

a reminder that licensees distributing the radioactive drug to persons

exempt from licensing would not be relieved from other applicable

Federal (e.g., FDA) or State

requirements governing the manufacture and distribution of drugs.

The NRC has decided that the manufacture or preparation of capsules

containing one microcurie of carbon-14 urea should continue to be

prepared by persons who meet the current NRC regulations to manufacture

and commercially distribute radioactive drugs. The NRC believes

regulatory control is needed to provide high confidence that the drug

contains only one microcurie of carbon-14 urea and does not contain any

other radioactive contaminants.

Proposed Amendment for Exempting ``Any Person'' From Licensing

Requirements To Receive the Drug

Proposed Amendment to 10 CFR Part 30

The NRC has determined that the drug in capsule form presents no

significant radiological safety or 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 would be 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 carbon-14 urea without a license

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 would be 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 carbon-14 urea without a license. The proposed regulation

would include 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 in order to protect

human subjects.

The phrase ``in vivo diagnostic use'' is being used in Sec. 30.21

instead of ``medical use'' for two reasons. First, the term ``medical

use'' has a specific meaning and is defined in Sec. 35.2 to mean ``the

intentional internal or external administration of byproduct material

or the radiation therefrom to patients or human research subjects under

the supervision of an authorized user.'' This term would be

inappropriate because:

(1) ``Medical use'' limits administration to authorized users; use

of this drug would not be so limited; and

a specific meaning and is defined in Sec. 35.2 to mean ``the

intentional internal or external administration of byproduct material

or the radiation therefrom to patients or human research subjects under

the supervision of an authorized user.'' This term would be

inappropriate 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 be prohibited by this rulemaking.

Effects of the Proposed Amendments

The effect of these proposed amendments would be to make the drug

available to any person, for ``in vivo'' diagnostic use, without need

for an NRC or Agreement State license. Because the receipt and use of

the drug would be exempt from NRC licensing, Agreement States would

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 would not regulate the use of the drug as long as

its use was for ``in vivo'' diagnostic use. This means that, under NRC

and Agreement State regulations, primary-care physicians would not need

to be ``authorized users'' in order to administer the drug, and would

not necessarily 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 would be left to determine and regulate who could receive and use

the drug for ``in vivo'' diagnostic use. NRC would regulate the use of

the drug for research involving human subjects under a specific Part 35

license.

III. Summary of Proposed Amendments

Manufacturer and Distributors

A new section would be added to 10 CFR Part 32 to permit the

distribution of the capsules to persons who are exempt from licensing.

ine and regulate who could receive and use

the drug for ``in vivo'' diagnostic use. NRC would regulate the use of

the drug for research involving human subjects under a specific Part 35

license.

III. Summary of Proposed Amendments

Manufacturer and Distributors

A new section would be 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 Carbon-14 Urea Capsules Not Exceeding

One Microcurie Each for ``In Vivo'' Diagnostic Use for Humans to

Persons Exempt From Licensing; Requirements for a License

Paragraph (a)

This paragraph would establish the requirements for approval of a

license application to manufacture, prepare, process, produce, package,

repackage, or transfer for commercial distribution carbon-14 urea

capsules not exceeding one microcurie each for ``in vivo'' diagnostic

use, to persons exempt from licensing.

Paragraph (a)(1)

This paragraph would limit issuance of an ``exempt distribution

license'' for distribution of the capsules to persons exempt from

licensing to only those who possess either a NRC or Agreement State

``specific license'' for possession and use of byproduct material.

Paragraph (a)(2)

To assure that the capsules contain no more than one microcurie of

carbon-14 and present no other radiological risks, this paragraph would

require 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

rsons 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 would require applicants to provide evidence that

each carbon-14 urea capsule will not exceed 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 will not exceed one microcurie.

Paragraph (a)(4)

This paragraph would prohibit carbon-14 urea from being contained

in any food, beverage, cosmetic, drug or other commodity designed for

ingestion or 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. Because of the capsule's ``in vivo'' diagnostic use,

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

4 urea. Because of the capsule's ``in vivo'' diagnostic use,

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 would prohibit 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

would require 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 would require 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 license 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 would establish the conditions required for a license

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 would establish that the immediate container of each capsule

or capsules must bear a durable, legible label that:

ould establish the conditions required for a license

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 would establish 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 would establish 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.''

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

capsule for commercial distribution. Because of the capsule's ``in

vivo'' diagnostic use, 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.

``In Vivo'' Diagnostic Use by Persons Exempt From Licensing

beverages which

would result in a radioactive product other than in the form of a

capsule for commercial distribution. Because of the capsule's ``in

vivo'' diagnostic use, 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.

``In Vivo'' Diagnostic Use by Persons Exempt From Licensing

A new section would be added to 10 CFR Part 30 to exempt any person

from NRC or the Agreement State regulations to receive the drug for

``in vivo'' diagnostic use for humans.

Section 30.21 Radioactive Drug: Capsules Containing One Microcurie of

Carbon-14 Urea for ``In Vivo'' Diagnostic Use for Humans Would Be Added

To Permit any Person To Receive the Capsules

Paragraph (a)

This paragraph would provide 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) below.

Paragraph (b)

This paragraph would establish that persons exempt from licensing

would be prohibited from using the drug for research involving humans

subjects. A specific Part 35 license would be needed to use the drug in

any research involving human subjects.

Paragraph (c)

This paragraph would specify 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.

IV. Agreement State Compatibility

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.

IV. 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,

the proposed rule, if adopted, would be a Division 4 item of

compatibility, with regard to the manufacture and commercial

distribution of the capsules (10 CFR Part 32). Because of the need for

nationwide consistency in the use of products which are widely

distributed, the proposed rule, if adopted, would be a Division 1 item

of compatibility with regard to possession and use (10 CFR Part 30).

Therefore, the Agreement States will need to make appropriate

provisions in their regulations to allow any person to receive capsules

containing one microcurie of carbon-14 urea for ``in vivo'' diagnostic

use without need for a license.

V. Electronic Access

Comments may be submitted electronically, in either ASCII text or

WordPerfect format (version 5.1 or later), by calling the NRC

Electronic Bulletin Board on FedWorld or connecting to the NRC

interactive rulemaking web site, ``Rulemaking Forum.'' The bulletin

board may be accessed using a personal computer, a modem, and one of

the commonly available communications software packages, or directly

via Internet.

If using a personal computer and modem, the NRC subsystem on

FedWorld can be accessed directly by dialing the toll free number: 1-

800-303-9672. Communication software parameters should be set as

follows: parity to none, data bits to 8, and stop bits to 1 (N,8,1)

d using a personal computer, a modem, and one of

the commonly available communications software packages, or directly

via Internet.

If using a personal computer and modem, the NRC subsystem on

FedWorld can be accessed directly by dialing the toll free number: 1-

800-303-9672. Communication software parameters should be set as

follows: parity to none, data bits to 8, and stop bits to 1 (N,8,1).

Using ANSI or VT-100 terminal emulation, the NRC NUREGs and Reg Guides

for Comment subsystem can then be accessed by selecting the ``Rules

Menu'' option from the ``NRC Main Menu.'' For further information about

options available for NRC at FedWorld, consult the ``Help/Information

Center'' from the ``NRC Main Menu.'' Users will find the ``FedWorld

Online User's Guides'' particularly helpful. Many NRC subsystems and

databases also have a ``Help/Information Center'' option that is

tailored to the particular subsystem.

The NRC subsystem on FedWorld can also be accessed by a direct-dial

telephone number for the main FedWorld BBS, 703-321-3339, or by using

Telnet via Internet, fedworld.gov. If using 703-321-3339 to contact

FedWorld, the NRC subsystem will be accessed from the main FedWorld

menu by selecting the ``Regulatory, Government Administration and State

Systems,'' then selecting ``Regulatory Information Mall.'' At that

point, a menu will be displayed that has an option ``U.S. Nuclear

Regulatory Commission'' that will take you to the NRC Online main menu.

The NRC Online area also can be accessed directly by typing ``/go nrc''

at a FedWorld command line. If you access NRC from FedWorld's main

menu, you may return to FedWorld by selecting the ``Return to

FedWorld'' option from the NRC Online Main Menu. However, if you access

NRC at FedWorld by using NRC's toll-free number, you will have full

access to all NRC systems but you will not have access to the main

FedWorld system.

If you contact FedWorld using Telnet, you will see the NRC area and

menus, including the Rules menu

n on NRC bulletin boards call Mr. Arthur Davis,

Systems Integration and Development Branch, U.S. Nuclear Regulatory

Commission, Washington, DC 20555, telephone (301) 415-5780; e-mail

AXD[email protected]. For information about the interactive rulemaking site,

contact Ms. Carol Gallagher, (301) 415-6215; e-mail [email protected].

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 proposed amendments, if adopted,

would not be a major Federal action significantly affecting the quality

of the human environment; therefore, an environmental impact statement

is not required. The proposed rule would establish requirements for the

manufacture and commercial distribution of 14 C-urea

capsules to persons exempt from licensing and establish regulations to

permit any person to 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 proposed rule, if

adopted, would not cause any significant increase in radiation exposure

to the public or radiation release to the environment beyond the

exposures or releases resulting from the use of the Carbon-14 capsules

under the current regulations. Also, it is expected that there would be

no non-radiological impacts if the proposed rule is adopted.

The draft environmental assessment and finding of no significant

impact on which this determination is based is available for inspection

at the NRC Public Document Room, 2120 L Street NW., (Lower Level),

Washington, DC. Single copies of the draft environmental assessment and

the finding of no significant impact are available from Dr. Anthony N.

Tse, Office of Nuclear Regulatory Research, U.S

The draft environmental assessment and finding of no significant

impact on which this determination is based is available for inspection

at the NRC Public Document Room, 2120 L Street NW., (Lower Level),

Washington, DC. Single copies of the draft 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 proposed 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 submitted to the Office of Management and

Budget for review and approval of the information collection

requirements.

The public reporting burden for this collection of information is

estimated to average 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. The Nuclear Regulatory Commission is seeking

public comment on the potential impact of the collection of information

contained in the proposed rule and on the following issues:

1. Is the proposed collection of information necessary for the

proper performance of the functions of the NRC, including whether the

information will have practical utility?

2. Is the estimate of the burden correct?

3. Is there a way to enhance the quality, utility, and the clarity

of the information to be collected?

4. How can the burden of the collection of information be

minimized, including the use of automated collection techniques?

Send comments on any aspect of this proposed information

collection, including suggestions for reducing the burden, to the

Information and Records Management Branch (T-6 F33), U.S

a way to enhance the quality, utility, and the clarity

of the information to be collected?

4. How can the burden of the collection of information be

minimized, including the use of automated collection techniques?

Send comments on any aspect of this proposed information

collection, 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.

Comments to OMB on the information collections or on the above

issues should be submitted by July 16, 1997. Comments received after

this date will be considered if it is practical to do so, but assurance

of consideration cannot be given to comments received after this date.

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 proposed rule.

The analysis examines the benefits and impacts considered by the NRC.

The regulatory analysis is available for inspection at the NRC Public

Document Room, 2120 L Street NW. (Lower Level), Washington, DC. Single

copies of the regulatory analysis are available from 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),

treet 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

proposed rule would permit 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. Any small entity subject to this regulation

which determines that, because of its size, it is likely to bear a

disproportionate adverse economic impact should notify the Commission

of this in a comment that indicates the following:

(a) The licensee's size and how the regulation would result in a

significant economic burden upon the licensee as compared to the

economic burden on a larger licensee.

(b) How the regulations could be modified to take into account the

licensee's differing needs or capabilities.

(c) The benefits that would accrue, or the detriments that would be

avoided, if the regulations were modified as suggested by the licensee.

(d) How the regulation, as modified, would more closely equalize

the impact of regulations or create more equal access to the benefits

of Federal programs as opposed to providing special advantages to any

individual or group.

ering needs or capabilities.

(c) The benefits that would accrue, or the detriments that would be

avoided, if the regulations were modified as suggested by the licensee.

(d) How the regulation, as modified, would more closely equalize

the impact of regulations or create more equal access to the benefits

of Federal programs as opposed to providing special advantages to any

individual or group.

(e) How the regulation, as modified, would still adequately protect

public health and safety.

X. 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).

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. 553, the NRC is proposing to

adopt 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:

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. 553, the NRC is proposing to

adopt 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:

Sec. 30.21 Radioactive drug: Capsules containing one microcurie 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 carbon-14 urea capsules, not exceeding one

microcurie each, for ``in vivo'' diagnostic use for humans.

provided in paragraphs (b) and (c) of this section,

any person is exempt from the requirements for a license set forth in

Section 81 of the Act and from the regulations in this part and part 35

of this chapter provided that such person receives, possesses, uses,

transfers, owns, or acquires carbon-14 urea capsules, not exceeding one

microcurie each, for ``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.

* * * * *

NING 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 carbon-14 urea capsules not exceeding one

microcurie 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 carbon-14 urea capsules not exceeding one microcurie each

for ``in vivo'' diagnostic use, to persons exempt from licensing under

Sec. 30.21 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);

(3) The applicant provides evidence that each carbon-14 urea

capsule will not exceed one microcurie;

(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);

(3) The applicant provides evidence that each carbon-14 urea

capsule will not exceed one microcurie;

(4) The carbon-14 urea is not contained in any food, beverage,

cosmetic, drug (except as described in this section) or other commodity

designed for ingestion or inhalation by, or 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 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

under Sec. 32.21 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.''

Dated at Rockville, Maryland this 10th day of June, 1997.

For the Nuclear Regulatory Commission.

John C. Hoyle,

Secretary of the Commission.

[FR Doc. 97-15697 Filed 6-13-97; 8:45 am]

BILLING CODE 7590-01-P