2748 Federal Register / Vol. 61, No. 19 / Monday, January 29, 1996 / Proposed Rules

to have an adverse effect on the

product’s safety, purity, potency, or

effectiveness, shall be documented by

the applicant in an annual report

submitted each year within 60 days of

the anniversary date of approval of the

application. The annual report shall

contain the following information for

each change:

(i) A list of all products involved;

(ii) A brief description of and

reason(s) for the change;

(iii) The manufacturing sites or areas

involved;

(iv) The date each change was made;

and

(v) A cross-reference to relevant

validation protocol(s) and/or SOP’s.

(2) The applicant shall submit the

report to the FDA office responsible for

reviewing the application. The report

shall include all the information

required under this section obtained for

each change made during the annual

reporting interval which ends on the

anniversary date.

(e) Labeling changes—(1) Label

changes requiring supplement

submission—distribution of a product

with a label change must await FDA

approval. An applicant shall submit to

CBER a supplement describing a

proposed change in the package insert,

package label, or container label, except

those described in paragraphs (e)(2) and

(e)(3) of this section, and include the

information necessary to support the

proposed change. The supplement shall

clearly highlight the proposed change in

the label. The applicant shall obtain

approval from the Director, CBER, prior

to distributing a product with the label

change.

(2) Label changes requiring

supplement submission; product with a

label change may be distributed before

FDA approval. (i) An applicant shall

submit to CBER, at the time such change

is made, a supplement for any change in

the package insert, package label, or

container label to accomplish any of the

following:

(A) To add or strengthen a

contraindication, warning, precaution,

or adverse reaction;

(B) To add or strengthen a statement

about abuse, dependence, psychological

effect, overdosage;

(C) To add or strengthen an

instruction about dosage and

administration that is intended to

increase the safe use of the product; or

(D) To delete false, misleading, or

unsupported indications for use or

claims for effectiveness.

(ii) The applicant may distribute a

product with a package insert, package

label, or container label bearing such

change at the time the supplement is

submitted. The supplement shall clearly

identify the change being made and

include necessary supporting data. The

supplement and its mailing cover

should be plainly marked: ‘‘Special

Labeling Supplement—Changes Being

Effected.’’

(3) Label changes requiring

submission in an annual report. (i) An

applicant shall submit any final printed

package insert, package label, or

container label incorporating the

following changes to CBER in an annual

report submitted each year within 60

days of the anniversary date of approval

of the application:

(A) Editorial or similar minor

changes; or

(B) A change in the information on

how the drug is supplied that does not

involve a change in the dosage strength

or dosage form.

(ii) The applicant may distribute a

product with a package insert, package

label, or container label bearing such

change at the time the change is made.

(4) Advertisements and promotional

labeling.

Advertisements and promotional

labeling shall be submitted in

accordance with the requirements set

forth in § 314.81(b)(3)(i) of this chapter,

except that Form FDA–2567 shall be

used in lieu of Form FDA–2253.

(f) Failure to comply. In addition to

other remedies available in law and

regulations, in the event of repeated

failure of the applicant to comply with

this section, the Director, CBER, may

require that the applicant submit a

supplement for any proposed change to,

and obtain approval of the supplement

from, the Director, CBER, prior to

distributing a product made using the

change.

(g) Administrative review. Under

§ 10.75 of this chapter, an applicant may

request internal FDA review of CBER

employee decisions under this section.

Dated: January 16, 1996.

William B. Schultz,

Deputy Commissioner for Policy.

[FR Doc. 96–1580 Filed 1–25–96; 10:41 am]

BILLING CODE 4160–01–F

21 CFR Parts 600 and 601

[Docket No. 95D–0415]

Draft Guidance; Changes To An

Approved Application for WellCharacterized Therapeutic

Recombinant DNA-Derived and

Monoclonal Antibody Biotechnology

Products; Availability

AGENCY: Food and Drug Administration,

HHS.

ACTION: Proposed rule; notice of

availability.

SUMMARY: The Food and Drug

Administration (FDA) is announcing the

availability of a draft guidance

document entitled ‘‘Draft Guidance;

Changes to An Approved Application

for Well-Characterized Therapeutic

Recombinant DNA-Derived and

Monoclonal Antibody Biotechnology

Products.’’ This draft guidance is

intended to assist applicants in

determining how they should report

changes to an approved license

application for well-characterized

therapeutic recombinant DNA-derived

and monoclonal antibody biotechnology

products under the proposed revision to

the biologics regulations issued

elsewhere in this issue of the Federal

Register. In a separate document also

published in this issue of the Federal

Register, FDA is announcing the

availability of a guidance document to

assist applicants in determining how

they should report changes to an

approved license application for

biologic products other than wellcharacterized therapeutic recombinant

DNA-derived and monoclonal antibody

biotechnology products under the

proposed rule. FDA does not intend for

these draft guidance documents to be

used at this time. The agency is

providing these guidance documents for

public comment only.

DATES: Written comments by April 29,

1996.

ADDRESSES: Submit written requests for

single copies of the draft guidance

entitled ‘‘Draft Guidance; Changes to An

Approved Application for WellCharacterized Recombinant DNADerived and Monoclonal Antibody

Biotechnology Products’’ to the

Congressional and Consumer Affairs

Branch (HFM–12), Center for Biologics

Evaluation and Research, Food and

Drug Administration, 1401 Rockville

Pike, Rockville, MD 20852–1448, 301–

594–1800 or call FDA’s automated

information system at 800–835–4709.

Send two self-addressed adhesive labels

to assist that office in processing your

requests. Submit written comments on

the draft guidance to the Dockets

Management Branch (HFA–305), Food

and Drug Administration, rm. 1–23,

12420 Parklawn Dr., Rockville, MD

20857. Two copies of any comments are

to be submitted, except that individuals

may submit one copy. Requests and

comments should be identified with the

docket number found in brackets in the

heading of this document. A copy of the

draft guidance and received comments

are available for public examination in
Federal Register / Vol. 61, No. 19 / Monday, January 29, 1996 / Proposed Rules 2749

the Dockets Management Branch

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

through Friday.

Persons with access to INTERNET

may request that the draft guidance

document be sent by return E-mail by

sending a message to

‘‘Character@A1.CBER.FDA.GOV’’. The

draft guidance document may also be

obtained through INTERNET via File

Transfer Protocol (FTP). Requestors

should connect to the Center for Drug

Evaluation and Research (CDER) using

the FTP. The Center for Biologics

Evaluation and Research (CBER)

documents are maintained in a

subdirectory called CBER on the server,

‘‘CDVS2.CDER.FDA.GOV’’

(150.148.24.202). The ‘‘READ.ME’’ file

in that subdirectory describes the

available documents that may be

available as an ASCII text file (*.TXT),

or a WordPerfect 5.1 document (*.w51),

or both. A sample dialogue for obtaining

the READ.ME file with a text-based FTP

program would be:

FTP CDVS2.CDER.FDA.GOV

LOGIN: CHARACTER

<PASSWORD:CHARACTER><‘‘Your Email address’’>

BINARY

CD CBER

GET READ.ME

EXIT

The draft guidance document may also

be obtained by calling the CBER FAX

Information System (FAX-ONDEMAND) at 301–594–1939 from a

touch tone telephone.

FOR FURTHER INFORMATION CONTACT:

Tracey H. Forfa or Timothy W. Beth,

Center for Biologics Evaluation and

Research (HFM–630), Food and

Drug Administration, 1401

Rockville Pike, Rockville, MD

20852–1448, 301–594–3074; or

Yuan Yuan Chiu, Center for Drug

Evaluation and Research (HFD–

510), Food and Drug

Administration, 5600 Fishers Lane,

Rockville, MD 20857, 301–443–

3510.

Dated: January 16, 1996.

William B. Schultz,

Deputy Commissioner for Policy.

[FR Doc. 96–1581 Filed 1–25–96; 10:42 am]

BILLING CODE 4160–01–F

21 CFR Parts 600 and 601

[Docket No. 95D–0052]

Changes To An Approved Application;

Draft Guidance; Availability

AGENCY: Food and Drug Administration,

HHS.

ACTION: Proposed rule; notice of

availability.

SUMMARY: The Food and Drug

Administration (FDA) is announcing the

availability of a draft guidance

document entitled ‘‘Draft Guidance;

Changes to An Approved Application.’’

The draft guidance is intended to assist

applicants in determining how they

should report changes to an approved

license application under the proposed

revision to the biologics regulations

issued elsewhere in this issue of the

Federal Register. FDA does not intend

for this draft guidance to be used at this

time. The agency is providing this

guidance at this time for public

comment only.

DATES: Written comments by April 29,

1996.

ADDRESSES: Submit written requests for

single copies of the draft guidance

entitled ‘‘Draft Guidance; Changes to An

Approved Application’’ to the

Congressional and Consumer Affairs

Branch (HFM–12), Center for Biologics

Evaluation and Research, Food and

Drug Administration, 1401 Rockville

Pike, Rockville, MD 20852–1448, or call

FDA’s automated information system at

800–835–4709. Send two self-addressed

adhesive labels to assist that office in

processing your requests. Submit

written comments on the draft guidance

to the Dockets Management Branch

(HFA–305), Food and Drug

Administration, rm. 1–23, 12420

Parklawn Dr., Rockville, MD 20857.

Two copies of any comments are to be

submitted, except that individuals may

submit one copy. Requests and

comments should be identified with the

docket number found in brackets in the

heading of this document. A copy of the

draft guidance and received comments

are available for public examination in

the Dockets Management Branch

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

through Friday.

Persons with access to INTERNET

may request that the draft guidance

document be sent by return E-mail by

sending a message to

‘‘Changes@A1.CBER.FDA.GOV’’. The

draft guidance document may also be

obtained through INTERNET via File

Transfer Protocol (FTP). Requestors

should connect to the Center for Drug

Evaluation and Research (CDER) using

the FTP. The Center for Biologics

Evaluation and Research (CBER)

documents are maintained in a

subdirectory called CBER on the server,

‘‘CDVS2.CDER.FDA.GOV’’

(150.148.24.202). The ‘‘READ.ME’’ file

in that subdirectory describes the

available documents which may be

available as an ASCII text file (*.TXT),

or a WordPerfect 5.1 document (*.w51),

or both. A sample dialogue for obtaining

the READ.ME file with a text-based FTP

program would be:

FTP CDVS2.CDER.FDA.GOV

LOGIN: CHANGES

<PASSWORD:CHANGES> <‘‘Your Email address’’>

BINARY

CD CBER

GET READ.ME

EXIT

The draft guidance document may

also be obtained by calling the CBER

FAX Information System (FAX-ONDEMAND) at 301–594–1939 from a

touch tone telephone.

FOR FURTHER INFORMATION CONTACT:

Tracey H. Forfa or Timothy W. Beth,

Center for Biologics Evaluation and

Research (HFM–630), Food and

Drug Administration, 1401

Rockville Pike, Rockville, MD

20852–1448, 301–594–3074; or

Yuan Yuan Chiu, Center for Drug

Evaluation and Research (HFD–

510), Food and Drug

Administration, 5600 Fishers Lane,

Rockville, MD 20857, 301–443–

3510.

SUPPLEMENTARY INFORMATION: In the

Federal Register of April 6, 1995 (60 FR

17535), FDA published a guidance

document intended to provide guidance

to applicants on which changes in

manufacturing procedures and

establishments may be implemented

with and/or without prior approval by

the Director, CBER under § 601.12 (21

CFR 601.12). The Federal Register

notice and guidance document were

intended to reduce the burden of

reporting changes on manufacturers and

to facilitate the approval process.

In a continuing effort to achieve the

reduction in reporting burden and to

respond to comments received on the

April 6, 1995, guidance document, FDA

is proposing a revision to § 601.12

published elsewhere in this edition of

the Federal Register. In addition, FDA

is announcing the availability of a draft

guidance document entitled, ‘‘Changes

to An Approved Application.’’ The

guidance document sets forth CBER’s

current interpretation of the proposed

rule to amend § 601.12 as it applies to

biologic products other than those

considered to be well-characterized

therapeutic recombinant DNA-derived

and monoclonal antibody biotechnology

products. The reporting mechanisms

proposed in the rule are based on the

potential for the change to affect a

product’s safety, purity, potency, and

effectiveness. In a separate document

also published in this issue of the

Federal Register, FDA is announcing