Federal Register / Vol. 60, No. 38 / Monday, February 27, 1995 / Notices 10593

on identical items from 10 or more

public respondents must be approved

by the Office of Management and

Budget (OMB) and must display a valid

OMB control number and expiration

date.

In accordance with the Paperwork

Reduction Act, in the Federal Register

of February 4, 1994 (59 FR 5436), a

notice announced the proposed revision

of FDA Form 3210 Application For

Establishment License for Manufacture

of Biological Products. OMB approval

for the revised FDA Form 3210 was

obtained on April 30, 1994, and given

OMB approval number 0910–0124;

expiration date April 30, 1997.

Dated: February 17, 1995.

William B. Schultz,

Deputy Commissioner for Policy.

[FR Doc. 95–4766 Filed 2–24–95; 8:45 am]

BILLING CODE 4160–01–F

[Docket No. 95N–0042]

Drug Export; OGEN (Piperazine

Oestrone Sulfate) 0.625 Milligram (mg),

1.25 mg, and 2.5 mg Tablets

AGENCY: Food and Drug Administration,

HHS.

ACTION: Notice.

SUMMARY: The Food and Drug

Administration (FDA) is announcing

that Abbott Laboratories has filed an

application requesting approval for the

export of the human drug OGEN

(piperazine oestrone sulfate) 0.625

milligram (mg), 1.25 mg, and 2.5 mg

Tablets to Australia.

ADDRESSES: Relevant information on

this application may be directed to the

Dockets Management Branch (HFA–

305), Food and Drug Administration,

rm. 1–23, 12420 Parklawn Dr.,

Rockville, MD 20857, and to the contact

person identified below. Any future

inquiries concerning the export of

human drugs under the Drug Export

Amendments Act of 1986 should also be

directed to the contact person.

FOR FURTHER INFORMATION CONTACT:

James E. Hamilton, Center for Drug

Evaluation and Research (HFD–310),

Food and Drug Administration, 5600

Fishers Lane, Rockville, MD 20857,

301–594–2073.

SUPPLEMENTARY INFORMATION: The drug

export provisions in section 802 of the

Federal Food, Drug, and Cosmetic Act

(the act) (21 U.S.C. 382) provide that

FDA may approve applications for the

export of drugs that are not currently

approved in the United States. Section

802(b)(3)(B) of the act sets forth the

requirements that must be met in an

application for approval. Section

802(b)(3)(C) of the act requires that the

agency review the application within 30

days of its filing to determine whether

the requirements of section 802(b)(3)(B)

have been satisfied. Section 802(b)(3)(A)

of the act requires that the agency

publish a notice in the Federal Register

within 10 days of the filing of an

application for export to facilitate public

participation in its review of the

application. To meet this requirement,

the agency is providing notice that

Abbott Laboratories, One Abbott Park

Rd., Abbott Park, IL 60064–3500, has

filed an application requesting approval

for the export of the human drug OGEN

(piperazine oestrone sulfate) 0.625 mg,

1.25 mg, and 2.5 mg Tablets to

Australia. This product is indicated for

replacement therapy of oestrogen

deficiency in female hypogonadism,

amenorrhoea, female castration, primary

ovarian failure, and in the management

of menopausal syndrome, senile

vaginitis, kraurosis vulvae with or

without pruritus, and abnormal uterine

bleeding due to hormonal imbalance in

the absence of organic pathology. The

firm has new drug application approval

for OGEN (piperazine oestrone sulfate)

in the above dosage strengths using a

different manufacturing process. The

application was received and filed in

the Center for Drug Evaluation and

Research on October 31, 1994, which

shall be considered the filing date for

purposes of the act.

Interested persons may submit

relevant information on the application

to the Dockets Management Branch

(address above) in two copies (except

that individuals may submit single

copies) and identified with the docket

number found in brackets in the

heading of this document. These

submissions may be seen in the Dockets

Management Branch between 9 a.m. and

4 p.m., Monday through Friday.

The agency encourages any person

who submits relevant information on

the application to do so by March 9,

1995, and to provide an additional copy

of the submission directly to the contact

person identified above, to facilitate

consideration of the information during

the 30-day review period.

This notice is issued under the

Federal Food, Drug, and Cosmetic Act

(sec. 802 (21 U.S.C. 382)) and under

authority delegated to the Commissioner

of Food and Drugs (21 CFR 5.10) and

redelegated to the Center for Drug

Evaluation and Research (21 CFR 5.44).

Dated: February 9, 1995.

Edward Miracco,

Acting Deputy Director, Office of Compliance,

Center for Drug Evaluation and Research.

[FR Doc. 95–4768 Filed 2–24–95; 8:45 am]

BILLING CODE 4160–01–F

[Docket No. 94D–0422]

Draft Guideline on the Manufacture of

Positron Emission Tomography

Radiopharmaceutical Drug Products;

Availability

AGENCY: Food and Drug Administration,

HHS.

ACTION: Notice.

SUMMARY: The Food and Drug

Administration (FDA) is announcing the

availability of a draft guideline entitled

‘‘Draft Guideline on the Manufacture of

Positron Emission Tomographic (PET)

Drug Products’’ prepared by FDA’s

Center for Drug Evaluation and Research

(CDER). The draft guideline is intended

to assist persons in determining whether

certain manufacturing practices,

procedures, and facilities used in the

small-scale production of liquid

injectable radiopharmaceutical drug

products used for positron emission

tomography (PET radiopharmaceuticals)

are in compliance with FDA’s current

good manufacturing practice (CGMP)

regulations for finished

pharmaceuticals.

DATES: Written comments by May 30,

1995.

ADDRESSES: Submit written requests for

single copies of the draft guideline

entitled ‘‘Draft Guideline on the

Manufacture of Positron Emission

Tomographic (PET) Drug Products’’ to

the CDER Executive Secretariat Staff

(HFD–8), Center for Drug Evaluation

and Research, Food and Drug

Administration, 7500 Standish Pl.,

Rockville, MD 20855. Send two selfaddressed adhesive labels to assist that

office in processing your requests.

Submit written comments on the draft

guideline to the Dockets Management

Branch (HFA–305), Food and Drug

Administration, rm. 1–23, 12420

Parklawn Dr., Rockville, MD 20857.

Requests and comments should be

identified with the docket number

found in brackets in the heading of this

document. A copy of the draft guideline

and received comments are available for

public examination in the Dockets

Management Branch between 9 a.m. and

4 p.m., Monday through Friday.

FOR FURTHER INFORMATION CONTACT: John

W. Levchuk, Center for Drug Evaluation

and Research (HFD–322), Food and
10594 Federal Register / Vol. 60, No. 38 / Monday, February 27, 1995 / Notices

Drug Administration, 7500 Standish Pl.,

Rockville, MD 20855, 301–594–0095.

SUPPLEMENTARY INFORMATION: FDA is

announcing the availability of a draft

guideline entitled ‘‘Draft Guideline on

the Manufacture of Positron Emission

Tomographic (PET) Drug Products.’’

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

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.

Because of their short half-lives, PET

radiopharmaceuticals are

characteristically manufactured in PET

centers in response to daily demand for

relatively few patients. PET centers are

usually located in medical centers.

PET manufacturing procedures differ

in a number of important ways from

those associated with the manufacture

of conventional drug products, mainly

due to the short half-lives involved:

1. A maximum of only a few lots are

manufactured per day, with one lot

equaling one multiple-dose vial. This is

administered to the patient usually

within a matter of hours. Prolonged

manufacturing time significantly erodes

the useful clinical life of PET

radiopharmaceuticals.

2. The quantities of radioactive active

ingredients contained in each lot of a

PET radiopharmaceutical generally vary

from nanogram to milligram amounts,

depending upon various product

parameters.

3. Because one lot equals one

multiple-dose vial containing a

homogeneous solution of a PET product

(e.g., 2-deoxy-2 [18F]fluoro-D-glucose),

results from end-product testing of

samples drawn from the single vial have

the maximum possible probability of

being representative of all the doses

administered to patients from that vial,

barring sampling or testing error.

4. An entire lot may be administered

to one or several patients, depending

upon the activity remaining in the

container at the time of administration.

Consequently, the administration of the

entire quantity of a lot to a single patient

should be anticipated for every lot

manufactured. This is an important

consideration when establishing the

testing limits for certain attributes such

as endotoxins and impurities.

5. PET radiopharmaceuticals usually

do not enter a general drug distribution

chain. Rather, the entire lot (one vial) is

usually distributed directly from the

PET center either to a single medical

department or physician for

administration to patients or to a

radiopharmacy for dispensing.

Distribution may occur to other centers

when the geographic proximity will

allow for distribution and use within

the drug product’s half-life parameters.

Conventional compliance with CGMP

regulations would be expected where

special characteristics such as those

listed above do not exist; for example,

in large-scale PET operations. Elsewhere

in this issue of the Federal Register,

FDA is publishing (1) A proposed rule

that would authorize the Director,

CDER, or the Director, Office of

Compliance, CDER, to approve

exceptions or alternatives to the

application of the provisions of 21 CFR

part 211 to the manufacture of PET

radiopharmaceuticals, and (2) a notice

of a public workshop and FDA guidance

on the regulation of PET

radiopharmaceuticals.

The guideline entitled ‘‘Draft

Guideline on the Manufacture of

Positron Emission Tomographic (PET)

Drug Products’’ discusses, generally,

quality control units, personnel

qualifications, staffing, buildings and

facilities, equipment, components,

containers, closures, production and

process controls, packaging and labeling

control, holding and distribution,

testing and release for distribution,

stability testing and expiration dating,

reserve samples, yields, second-person

checks, and reports and records.

FDA is making this draft guideline

available for public comment before

issuing a final guideline. If, following

the receipt of comments, the agency

concludes that the draft guideline will

assist persons in determining whether

manufacturing practices used in the

small-scale production of liquid

injectable PET radiopharmaceuticals are

in compliance with FDA’s CGMP

regulations for finished

pharmaceuticals, then the agency will

prepare a final guideline and will

announce its availability in the Federal

Register.

Guidelines are generally issued under

§ 10.90(b) (21 CFR 10.90(b)), which

provides for the use of guidelines to

state procedures or standards of general

applicability that are not legal

requirements but are acceptable to FDA.

The agency is now in the process of

revising § 10.90(b). Therefore, if the

agency makes the guideline final, the

guideline would not be issued under the

authority of current § 10.90(b), and

would not create or confer any rights,

privileges, or benefits for or on any

person, nor would it operate to bind

FDA in any way.

Interested persons may, on or before

May 30, 1995, submit to the Dockets

Management Branch (address above)

written comments on the draft

guideline. 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. The draft

guideline and received comments may

be seen in the office above between 9

a.m. and 4 p.m., Monday through

Friday.

Dated: February 17, 1995.

William B. Schultz,

Deputy Commissioner for Policy.

[FR Doc. 95–4689 Filed 2–24–95; 8:45 am]

BILLING CODE 4160–01–F

[Docket No. 93N–0005]

Regulation of Positron Emission

TomographyRadiopharmaceutical

Drug Products; Guidance; Public

Workshop

AGENCY: Food and Drug Administration,

HHS.

ACTION: Notice.

SUMMARY: The Food and Drug

Administration (FDA) is publishing

guidance on the regulation of positron

emission tomography (PET)

radiopharmaceutical drug products.

FDA has developed this guidance to

make clear the regulatory approach

designed to help ensure the safe and

effective use of these products. The

agency is also announcing a public

workshop to facilitate an understanding

of regulatory requirements regarding

these products.

DATES: The public workshop will be

held on March 21, 1995, 8:30 a.m. to 4

p.m. Registration will be between 8 a.m.

and 8:30 a.m. Due to limited space,

interested persons must preregister

before March 7, 1995, by telephoning