Federal Register / Vol. 60, No. 38 / Monday, February 27, 1995 / Proposed Rules 10517

activities are intended to assist the

public in understanding the proposed

rule and in providing comments on the

proposed rule.

DATES: See Supplementary Information

for dates of hearings.

ADDRESSES: See Supplementary

Information for locations of hearings.

FOR FURTHER INFORMATION CONTACT: Dan

Vitiello, Director, Planning and

Analysis, Planning Office, Policy,

Evaluation and Planning Staff, FSIS,

USDA, Room 6904 Franklin Court,

Washington, DC 20250, (202) 501–7138.

SUPPLEMENTARY INFORMATION: On

February 3, 1995, FSIS published a

proposed rule titled ‘‘Pathogen

Reduction; Hazard Analysis and Critical

Control Points (HACCP) Systems’’ (60

FR 6774). The proposal provides a

number of requirements applicable to

Federal and State-inspected meat and

poultry establishments. The proposed

requirements are designed to reduce the

occurrence and numbers of pathogenic

organisms in meat and poultry products,

thereby reducing the incidence of

foodborne illness associated with the

consumption of these products.

Information Briefings

To assist the public in understanding

the proposal, FSIS is holding six

briefings as follows. Each briefing will

run from 1:00 p.m. to 5:00 p.m. Any

person who wishes to attend any of the

information briefings should contact the

FSIS Planning Office at (202) 501–7138.

Date City/state Location Contact

Mar. 7 ................. San Francisco, Oakland, CA ........ Henry J. Kaiser Convention Center, 10 Tenth

Street, Oakland, CA 94607.

Linda Russell, (202) 501–7138.

Mar. 14 ............... Dallas, TX ..................................... Dallas Grand Hotel, 1914 Commerce St., Dallas,

TX 75201, (214) 747–7000; 1–800–421–0011.

Dan Vitiello (202) 501–7138.

Mar. 16 ............... Chicago, IL ................................... Holiday Inn O’Hare Airport, 5440 North River Rd.,

Rosemont, IL 60018, (708) 671–6350.

Ken Elane, (202) 501–7138.

Mar. 21 ............... Atlanta, GA ................................... Richard Russell Federal Building, 75 Spring St.,

SW., Atlanta, GA 30303.

Ron Niemeyer, (202) 501–7138.

Mar. 23 ............... New York, NY ............................... Federal Building, 26 Federal Plaza, Room 305,

New York, NY 10278.

Ken Elane, (202) 501–7138.

Mar. 30 ............... Washington, DC ........................... Hyatt Regency Crystal City, 2799 Jefferson Davis

Highway, Arlington, VA 22202, (703) 418–1234.

Linda Russell (202) 501–7138.

The format for each briefing will be

the same:

1. A panel of subject matter specialists

will explain various aspects of the

proposal.

2. Attendees will submit any

questions they have, in writing.

3. Panelists will answer the questions.

Scientific/Technical Conferences

FSIS also plans to hold three

conferences, each addressing a specific

scientific/technical issue. Information

on each specific conference will be

published separately at a later date.

The three conferences are scheduled

to be held as follows:

Issue: ‘‘New Technology to Improve Food

Safety’’

April 12–13, Chicago, IL, Holiday Inn O’Hare

Airport, 5440 North River Road, Rosemont,

IL 60018, (708) 671–6350

Issue: ‘‘The Role of Microbiological Testing

in Verifying Food Safety’’

May 1–2, Philadelphia, PA, Holiday InnIndependence Mall, Fourth and Arch

Streets, Philadelphia, PA 19106, (215) 923–

8860

Issue: ‘‘An Evaluation of the Role of

Microbiological Criteria in Establishing Food

Safety Performance Standards in Meat and

Poultry Products’’

May 18–19, Washington, DC, Georgetown

University, Conference Center, 3800

Reservoir Road, Washington, DC 20007,

(202) 687–3200

Public Hearing

Lastly, FSIS is planning to hold a twoday public hearing for those

commenters who wish to submit oral

comments in response to the proposed

rule. (Oral comments may also be

provided to FSIS by contacting the

persons listed in the proposed rule). The

public hearing will be held:

May 30–31, Washington, DC,

Georgetown University Conference

Center, 3800 Reservoir Road, NW.,

Washington, DC 20007, (202) 687–

3200

Done at Washington, DC, on: February 17,

1995.

Michael R. Taylor,

Acting Under Secretary for Food Safety.

[FR Doc. 95–4498 Filed 2–24–95; 8:45 am]

BILLING CODE 3410–DM–P

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

Food and Drug Administration

21 CFR Part 211

[Docket No. 94N–0421]

RIN 0905–AE63

Current Good Manufacturing Practice

for Finished Pharmaceuticals; Positron

Emission Tomography

AGENCY: Food and Drug Administration,

HHS.

ACTION: Proposed rule.

SUMMARY: The Food and Drug

Administration (FDA) is proposing to

amend its regulations to permit

manufacturers of positron emission

tomography (PET) radiopharmaceuticals

to apply to the agency for approval of

an exception or alternative to the

requirements of the current good

manufacturing practice (CGMP)

regulations. This action is intended to

relieve PET manufacturers, nearly all of

whom are small entities, from

regulations that might result in unsafe

handling of PET radiopharmaceuticals,

that are inapplicable or inappropriate,

or that otherwise do not enhance safety

or quality in the manufacture of PET

radiopharmaceuticals.

DATES: Written comments by March 29,

1995. FDA proposes that any final rule

that may issue based on this proposal

become effective on its date of

publication in the Federal Register.

ADDRESSES: Submit written comments

to the Dockets Management Branch

(HFA–305), Food and Drug

Administration, rm. 1–23, 12420

Parklawn Dr., Rockville, MD 20857.

FOR FURTHER INFORMATION CONTACT: John

W. Levchuk, Center for Drug Evaluation

and Research (HFD–322), Food and

Drug Administration, 7500 Standish Pl.,

Rockville, MD 20855, 301–594–0095.

SUPPLEMENTARY INFORMATION:

I. Introduction

PET is a diagnostic imaging modality

consisting of onsite production of

radionuclides that are intravenously

injected into patients for diagnostic

purposes. The potential usefulness of a

PET radiopharmaceutical is based upon
10518 Federal Register / Vol. 60, No. 38 / Monday, February 27, 1995 / Proposed Rules

the product’s interaction with a

biochemical process in the body. For

example, the product may be

substituted for glucose in anaerobic

glycolysis, theoretically localizing in

ischemic tissues where glucose

metabolism is the predominant energy

source (epileptic foci, acute vascular

insufficiency states).

The manufacture of PET

radiopharmaceuticals consists of a

process that takes place within a few

hours. A target material is irradiated by

a cyclotron; chemical synthesis takes

place in a programmed, automated

apparatus; and the final solution is

compounded and filled. The biological

distribution of a PET

radiopharmaceutical in the body is

monitored by a positron tomograph, or

PET scanner, which detects the photons

emitted as a result of the radioactive

decay of the PET radiopharmaceutical.

PET manufacturing procedures differ

in a number of important ways from

those associated with the manufacture

of conventional drug products:

• Because of the short half-lives of

PET radiopharmaceuticals (some of

which are only minutes long), PET

facilities generally manufacture the

products in response to daily demand

for a relatively small number of patients.

• Manufacturing is typically done on

a small scale and only a few lots are

produced each day. Thus, the daily

production of a PET facility is normally

handled by few employees, sometimes

by one production operator and a parttime support person.

• PET radiopharmaceuticals must be

administered to patients in a short

period of time because of the brief halflives of the products. Any prolonged

manufacturing time or testing or release

delays would reduce the useful clinical

life of the product.

• Unlike most pharmaceuticals, PET

radiopharmaceuticals usually do not

enter a general drug distribution chain.

An entire lot (one vial) is usually

distributed directly from the PET

facility to a single medical department,

to a physician for administration to

patients, to a radiopharmacy for

dispensing, or to another site close to

the PET facility. The receiving facilities

are in a geographic proximity that will

allow for receipt and use within the

product’s half-life parameters.

The agency believes that there are

fundamental principles of the CGMP

regulations that need to be applied to

drug manufacturing processes,

including those for PET

radiopharmaceuticals, to ensure the

safety and efficacy of the finished

products. However, as just noted,

certain features are unique to the

manufacture of PET products. Part 211

(21 CFR part 211), which is primarily

directed to the regulation of

conventional drug products, contains

requirements and specific language

which might result in unsafe handling

of PET radiopharmaceuticals, are

inapplicable or inappropriate, or which

otherwise do not enhance drug product

quality in the manufacture of PET

radiopharmaceuticals.

FDA is therefore proposing to amend

its regulations to permit manufacturers

of PET radiopharmaceuticals to apply to

the agency for approval of an exception

or alternative to the requirements of part

211 as they apply to the manufacture of

PET radiopharmaceuticals. A request for

an exception or alternative must contain

either an explanation why compliance

with a particular requirement of the

CGMP regulations is unnecessary or

cannot be achieved, or a description of

alternative procedures or controls that

satisfy the purpose of the CGMP

requirement. Both of these must include

all necessary supporting data.

Alternatively, the request may include

other information justifying an

exception or alternative. The request for

an exception or alternative may be

approved by the agency if it is

determined that the requestor’s

compliance with the CGMP requirement

is unnecessary to provide suitable

assurance that the drug meets the

requirements of the act as to safety and

it has the identity and strength and

meets the quality and purity

characteristics that it purports or is

represented to possess, or if compliance

with the requirement cannot be

achieved. In addition, the request for an

exception or alternative may be

approved if the requestor’s alternative

procedures or controls satisfy the

purpose of the CGMP requirement, or if

the requestor’s submission otherwise

justifies an exception or alternative. The

agency may withdraw approval of an

exception or alternative if it finds, on

the basis of new information, that the

criteria for approval are no longer met.

Such withdrawal will be accomplished

by providing written notice, and the

reasons for the action, to the original

requestor.

The agency will also periodically

provide guidance to the industry on the

application of the CGMP regulations to

PET radiopharmaceuticals.

Elsewhere in this issue of the Federal

Register, FDA is publishing: (1) A notice

of availability of a draft guideline to

assist persons in determining whether

certain manufacturing practices,

procedures, and facilities used for PET

radiopharmaceuticals are in compliance

with FDA’s CGMP regulations; and (2)

a notice of a public workshop and FDA

guidance on the regulation of PET

radiopharmaceuticals.

FDA is requesting written comments

within 30 days after the date of

publication of this proposed rule. In

addition, FDA is proposing that any

final rule that may publish as a result of

this proposal become effective on its

date of publication in the Federal

Register. The proposed rule would

permit manufacturers of PET

radiopharmaceuticals to apply to FDA

for approval of an exception or

alternative to the requirements of the

CGMP regulations. Accordingly, the

proposed rule, if finalized, is a

substantive rule which, in the discretion

of the agency, grants or recognizes an

exemption or relieves a restriction. (See

5 U.S.C. 553(d)(1) and 21 CFR

10.40(c)(4)(i).) In addition, the

Commissioner of Food and Drugs finds

good cause under 21 CFR 10.40(a)(2) for

providing 30 days for comments instead

of 60 days and under 5 U.S.C. 553(d)(3)

and 21 CFR 10.40(c)(4)(ii) for making a

final rule based on this proposal

effective upon its publication in the

Federal Register. The manufacturing

process for PET radiopharmaceuticals is

sufficiently different from that of other

regulated products that application of

certain CGMP requirements to PET

radiopharmaceuticals is impractical.

Because PET radiopharmaceuticals are

already in use, a longer comment period

or a later effective date may delay FDA

approval or hinder appropriate

application of CGMP regulations to PET

radiopharmaceuticals, that are necessary

to protect the integrity of the drug

manufacturing process.

II. Request for Comments

Interested persons may, on or before

March 29, 1995, submit to the Dockets

Management Branch (HFA–305), Food

and Drug Administration, rm. 1–23,

12420 Parklawn Dr., Rockville, MD

20857, written comments regarding this

proposal. Two copies of any comments

are to be submitted, except that

individuals may submit one copy.

Comments are to be identified with the

docket number found in brackets in the

heading of this document. Received

comments may be seen in the office

above between 9 a.m. and 4 p.m.,

Monday through Friday.

III. Environmental Impact

The agency has determined under 21

CFR 25.24(a)(8) that this action is of a

type that does not individually or

cumulatively have a significant effect on

the human environment. Therefore,

neither an environmental assessment
Federal Register / Vol. 60, No. 38 / Monday, February 27, 1995 / Proposed Rules 10519

nor an environmental impact statement

is required.

IV. Analysis of Impacts

FDA has examined the impacts of the

proposed rule under Executive Order

12866 and the Regulatory Flexibility Act

(Pub. L. 96–354). Executive Order 12866

directs agencies to assess all costs and

benefits of available regulatory

alternatives and, when regulation is

necessary, to select regulatory

approaches that maximize net benefits

(including potential economic,

environmental, public health and safety,

and other advantages; distributive

impacts; and equity). The agency

believes that this proposed rule is

consistent with the regulatory

philosophy and principles identified in

the Executive Order. In addition, the

proposed rule is not a significant

regulatory action as defined by the

Executive Order and so is not subject to

review under the Executive Order.

The Regulatory Flexibility Act

requires agencies to analyze regulatory

options that would minimize any

significant impact of a rule on small

entities. The agency certifies that the

proposed rule will not have a significant

impact on a substantial number of small

entities. Therefore, under the Regulatory

Flexibility Act, no further analysis is

required.

For the reasons explained above, FDA

proposes that any final rule based on

this proposal become effective on the

date of publication in the Federal

Register.

V. Paperwork Reduction Act of 1980

This proposed rule contains

information collections that are subject

to review by the Office of Management

and Budget (OMB) under the Paperwork

Reduction Act of 1980. The title,

description, and respondent description

of the information collection are shown

below with an estimate of the annual

reporting and recordkeeping burden.

Included in the estimate is the time for

reviewing instructions, searching

existing data sources, gathering and

maintaining the data needed, and

completing and reviewing the collection

of information.

Title: Current Good Manufacturing

Practice for Finished Pharmaceuticals:

Positron Emission Tomography

Description: The proposal would

permit manufacturers of PET products

to apply to the agency for approval of

an exception or alternative to the

requirements of the CGMP regulations.

The regulation is intended to relieve

PET manufacturers, nearly all of whom

are small entities, from regulations that

might result in unsafe handling of PET

radiopharmaceuticals, that are

inapplicable or inappropriate, or that

otherwise do not enhance safety or

quality in the manufacture of PET

radiopharmaceuticals.

Description of Respondents:

Businesses; small businesses.

ESTIMATED ANNUAL REPORTING BURDEN:

Section Number of

Respondents

No. of Responses Per

Respondents Total Annual Responses Hours Per Response Total Hours

21 CFR

211.1(d) 60 1 60 4 240

We have submitted a copy of this

proposed rule to OMB for its review of

these information collections. Send

comments regarding this burden

estimate or any other aspect of this

collection of information, including

suggestions for reducing this burden, to

the agency official designated for this

purpose whose name appears in this

preamble, and to the Office of

Information and Regulatory Affairs,

OMB, Washington, D.C. 20503.

List of Subjects in 21 CFR Part 211

Drugs, Labeling, Laboratories,

Packaging and containers, Prescription

drugs, Reporting and recordkeeping

requirements, Warehouses.

Therefore, under the Federal Food,

Drug, and Cosmetic Act and under

authority delegated to the Commissioner

of Food and Drugs, it is proposed that

21 CFR part 211 be amended as follows:

PART 211—CURRENT GOOD

MANUFACTURING PRACTICE FOR

FINISHED PHARMACEUTICALS

1. The authority citation for 21 CFR

part 211 continues to read as follows:

Authority: Secs. 201, 501, 502, 505, 506,

507, 512, 701, 704 of the Federal Food, Drug,

and Cosmetic Act (21 U.S.C. 321, 351, 352,

355, 356, 357, 360b, 371, 374).

2. Section 211.1 is amended by

adding new paragraph (d) to read as

follows:

§ 211.1 Scope.

* * * * *

(d) The Director of the Center for Drug

Evaluation and Research or the Director

of the Office of Compliance, Center for

Drug Evaluation and Research, may

approve an exception or alternative to

any application of this part to the

manufacture of positron emission

tomography (PET)

radiopharmaceuticals. Requests for such

exceptions or alternatives should

ordinarily be made in writing. However,

in certain circumstances, such requests

may be made orally and permission may

be granted orally. Oral requests and oral

approvals must be followed by written

requests and written approvals.

Approval of a request for an exception

or alternative must be obtained from

either specified Director prior to the use

of any affected PET

radiopharmaceutical.

(1) A request for an exception or

alternative is required to contain one of

the following:

(i) An explanation, with supporting

data as necessary, why compliance with

a particular requirement of this part is

unnecessary or cannot be achieved;

(ii) A description, with supporting

data as necessary, of alternative

procedures or controls that satisfy the

purpose of the requirement; or

(iii) Other information justifying an

exception or alternative.

(2) The Director may approve a

request for an exception or alternative if

the Director finds one of the following:

(i) The requestor’s compliance with

the requirement is unnecessary to

provide suitable assurance that the drug

meets the requirements of the act as to

safety, and has the identity and strength

and meets the quality and purity

characteristics that it purports or is

represented to possess, or compliance

with the requirement cannot be

achieved;

(ii) The requestor’s alternative

procedures or controls satisfy the

purpose of the requirement; or

(iii) The requestor’s submission

otherwise justifies an exception or

alternative.

(3) The Director may withdraw

approval of an exception or alternative

if the Director finds, on the basis of new

information, that the criteria for

approval in paragraph (d)(2) of this

section are no longer met. Withdrawal

of approval shall be accomplished by

providing written notice of such
10520 Federal Register / Vol. 60, No. 38 / Monday, February 27, 1995 / Proposed Rules

withdrawal, and the reasons for the

withdrawal, to the original requestor.

Dated: February 17, 1995.

William B. Schultz,

Deputy Commissioner for Policy.

[FR Doc. 95–4690 Filed 2–24–95; 8:45 am]

BILLING CODE 4160–01–F

DEPARTMENT OF THE INTERIOR

Office of Surface Mining Reclamation

and Enforcement

30 CFR Part 902

Alaska Permanent Regulatory Program

AGENCY: Office of Surface Mining

Reclamation and Enforcement (OSM),

Interior.

ACTION: Proposed rule; public comment

period and opportunity for public

hearing on proposed program

amendment.

SUMMARY: OSM is announcing the

receipt of a proposed amendment to the

Alaska permanent regulatory program

(hereinafter, the ‘‘Alaska program’’)

under the Surface Mining Control and

Reclamation Act of 1977 (30 U.S.C. 1201

et seq.) (SMCRA). The proposed

amendment consists of revisions to

rules pertaining to fees, adoption by

reference, general permitting

requirements, permit application

information requirements,

environmental resource information

requirements, reclamation and

operation plan, processing of permit

applications, permitting for special

categories of mining, exploration, small

operator assistance program, bonding,

performance standards, inspection and

enforcement, and general provisions.

The amendment is intended to revise

the Alaska program to be consistent

with the corresponding Federal

regulations, clarify ambiguities, and

improve operational efficiency. The

amendment consists of proposed

changes to the Alaska program as

required by Part 902.16 of the Code of

Federal Regulations and program

deficiency letters dated November 1,

1989, February 7, 1990, and January 15,

1993.

DATES: Written comments must be

received by 4:00 p.m., m.s.t. March 29,

1995. If requested, a public hearing on

the proposed amendment will be held

on March 24, 1995. Requests to present

oral testimony at the hearing must be

received by 4:00 p.m., m.s.t. on March

14, 1995.

ADDRESSES: Written comments should

be mailed or hand delivered to Guy

Padgett at the address listed below.

Copies of the Alaska program, the

proposed amendment, and all written

comments received in response to this

notice will be available for public

review at the addresses listed below

during normal business hours, Monday

through Friday, excluding holidays.

Each requester may receive one free

copy of the proposed amendment by

contracting OSM’s Casper Field Office.

Guy Padgett, Director, Office of Surface

Mining Reclamation and

Enforcement, Casper Field Office, 100

East B Street, Room 2128, Casper, WY

82601–1918, (307) 261–5776

Mr. Jules Tileston, Director, Division of

Mining and Water Resources, Alaska

Department of Natural Resources,

3601 C Street, Suite 800, Anchorage,

Alaska 99503–5935, (907) 762–5163

FOR FURTHER INFORMATION CONTACT: Guy

Padgett, Director, Telephone: (307) 261–

5776.

SUPPLEMENTARY INFORMATION

I. Background on the Alaska Program

On March 23, 1983, the Secretary of

the Interior conditionally approved the

Alaska program as administered by the

Alaska Department of Natural

Resources. General background

information on the Alaska program,

including the Secretary’s findings, the

disposition of comments, and

conditions of approval of the Alaska

program can be found in the March 23,

1983, Federal Register (48 FR 12274).

Subsequent actions concerning Alaska’s

program and program amendments can

be found at 30 CFR 902.15 and 902.16.

II. Proposed Amendment

By letter dated January 26, 1995 and

FAX transmittals dated February 13 and

14, 1994 (Administrative Record No. AK

IV–01), Alaska submitted proposed

Amendment IV to its permanent

program pursuant to SMCRA (SPATS

AK–004–FOR). Alaska’s proposed

Amendment IV consists of: changes to

the Alaska program as required by 30

CFR Part 902.16; changes in response to

program deficiency letters from OSM

dated November 1, 1989, February 7,

1990, and January 15, 1993; and changes

to Alaska’s own initiative. The

provisions of the Alaska Administrative

Code (AAC) that Alaska proposes to

revise are: 11 AAC 05.010(a)(9) and 11

AAC 90.011, fees; 11 AAC 90.001,

adoption of rules by reference; 11 AAC

90.002, responsibilities; 11 AAC 90.003,

interim permits; 11 AAC 90.023,

identification of interests and

compliance information; 11 AAC

90.025, authority to enter and

ownership information; 11 AAC

90.045(a), geology description; 11 AAC

90.049, surface water information; 11

AAC 90.083(b), reclamation plan

requirements, roads; 11 AAC 90.097,

transportation facilities; 11 AAC 90.099,

placement of coal mine waste in

underground workings; 11 AAC 90.117,

processing of permit applications; 11

AAC 90.125, commissioner’s findings;

11 AAC 90.126, improvidently issued

permits; 11 AAC 90.127, permit

conditions; 11 AAC 90.129, permit

revisions and renewals; 11 AAC 90.149,

alluvial valley floors; 11 AAC 90.163,

exploration that substantially disturbs

or is conducted in areas designated

unsuitable for mining; 11 AAC 90.173,

eligibility for small operator assistance;

11 AAC 90.207, self-bonding provisions;

11 AAC 90.321, hydrologic balance; 11

AAC 90.323, water quality standards; 11

AAC 90.325, diversions and conveyance

of flow; 11 AAC 90.327, stream channel

diversions; 11 AAC 90.336,

impoundment design and construction;

11 AAC 90.337, impoundment

inspection; 11 AAC 90.341,

underground mine discharges; 11 AAC

90.345, surface and ground water

monitoring; 11 AAC 90.375, public

notice of blasting; 11 AAC 90.391,

disposal of excess spoil or coal mine

waste; 11 AAC 90.401, coal mine waste,

refuse piles; 11 AAC 90.407, coal mine

waste, dams and embankments; 11 AAC

90.409, coal mine waste, return to

underground workings; 11 AAC 90.423,

protection of fish and wildlife; 11 AAC

90.443, backfilling and grading; 11 AAC

90.457, Revegetation success standards;

11 AAC 90.491, construction and

maintenance of roads and other

transportation and support facilities; 11

AAC 90.601, inspections; 11 AAC

90.613, cessation orders, 11 AAC

90.901, applicability; 11 AAC 90.902,

exception for coal extraction incidental

to the extraction of other minerals; 11

AAC 90.907, public participation; and

11 AAC 90.911, definitions.

Specifically, Alaska proposes to:

—Revise 11 AAC 05.010(a)(9) and

90.011 to move the regulatory

requirements for permit fees to the fee

provisions for the whole department,

and to set a fee for incidental

boundary revisions;

—Revise 11 AAC 90.002 and delete

90.003, to eliminate provisions for

continued operation or exploration

under interim permits;

—Repeal and readopt 11 AAC 90.023 to

clarify and add requirements for

identification of ownership and

control interests and compliance

histories;

—Revise 11 AAC 90.025 to require

ownership information for owners,

lessees, and purchasers of record of