Guidance for Industry

Revising ANDA Labeling Following

Revision of the RLD Labeling

U.S. Department of Health and Human Services

Food and Drug Administration

Center for Drug Evaluation and Research (CDER)

 May 2000

OGD
Guidance for Industry

Revising ANDA Labeling Following

Revision of the RLD Labeling

Additional copies are available from:

Office of Training and Communications

Division of Communications Management

Drug Information Branch, HFD-210

5600 Fishers Lane

Rockville, MD 20857

(Tel) 301-827-4573

(Internet) http://www.fda.gov/cder/guidance/index.htm

U.S. Department of Health and Human Services

Food and Drug Administration

Center for Drug Evaluation and Research (CDER)

May 2000

OGD
TABLE OF CONTENTS

I. INTRODUCTION...............................................................................................................................................4

II. BACKGROUND..................................................................................................................................................4

III. HOW TO OBTAIN INFORMATION ON A CHANGE IN RLD LABELING.................................5

IV. HOW TO SUBMIT REVISED LABELING................................................................................................6
Guidance for Industry1

Revising ANDA Labeling Following

Revision of the RLD Labeling

I. INTRODUCTION

This guidance is intended to assist sponsors of abbreviated new drug applications

(ANDAs) in deciding when and how to submit labeling supplements following labeling

revisions to their reference listed drugs (RLDs).

II. BACKGROUND

During the marketing life of a drug product approved under a new drug application

(NDA), the package insert labeling is frequently revised. When an NDA serves as an

RLD for an ANDA, approved changes in the RLD labeling generally necessitate changes

in the labeling of one or more ANDAs using the RLD. Under the Federal Food, Drug,

and Cosmetic Act and Agency regulations, an ANDA product must have the same

labeling as the RLD. Section 505(j)(2)(A)(v) of the Act states that an abbreviated

application for a new drug must contain

information to show that the labeling proposed for the new drug is the

same as the labeling approved for the listed drug...except for changes

required because of differences approved under a petition...or because the

new drug and the listed drug are produced or distributed by different

manufacturers.

Similar statements are also found in the regulations at 21 CFR 314.94(a)(8)(iv).

Previously, OGD notified the appropriate ANDA sponsors when the approved labeling of

their RLD changed. This was usually done using a formal supplement request letter. In

cases where an NDA served as the RLD for multiple generic products, the preparation of

 

1

This guidance has been prepared by the Office of Generic Drugs in the Office of Pharmaceutical Science,

Center for Drug Evaluation and Research (CDER), at the Food and Drug Administration. This guidance

document represents the Agency’s current thinking on changes in labeling of approved abbreviated new

drug applications (ANDAs) following revisions in the RLD’s labeling. It does not create or confer any

rights for or on any person and does not operate to bind FDA or the public. An alternative approach may

be used if such approach satisfies the requirements of the applicable statutes, regulations, or both.
a large number of request letters took a significant amount of review staff time. With the

increase in the numbers of approved NDAs and ANDAs, this approach was using an

increasingly disproportionate share of OGD’s resources. Because of the time it took, the

approach sometimes even delayed the notification of ANDA sponsors. With the

exception of a few special situations (noted below), OGD is no longer providing this

type of notification. The sponsor of an ANDA is now responsible for ensuring that the

labeling contained in its application is the same as the currently approved labeling of the

RLD. OGD has determined that this change in responsibility is necessary to minimize

the implementation time for the introduction of revised labeling into the market place.

OGD believes that prompt revision, submission to the Agency, and implementation of

revised labeling are important to ensure the continued safe and effective use of generic

drug products. Because the regulations state that the labeling of the generic must be the

same as the innovator, the revision should be made at the very earliest time possible. If

there is any potential delay in the revision of a generic drug labeling, the sponsor should

contact OGD.

III. HOW TO OBTAIN INFORMATION ON A CHANGE IN RLD LABELING

The sponsor of an ANDA should routinely monitor the Labeling Review Branch

Homepage (see below) for information on changes in labeling. OGD’s Labeling Review

Branch will:

• Place monthly updates of approved labeling changes for RLDs with approved

ANDAs on the Labeling Review Branch Homepage at:

http://www.fda.gov/cder/ogd/rld/labeling_review_branch.html

Continue to notify ANDA applicants by facsimile, telephone, and/or letter for any

labeling revision approved for the RLD that warrants immediate widespread professional

notification, such as those changes connected to issuing a Dear Doctor Letter or similar

significant changes.

All approved labeling for RLDs is still available from Freedom of Information Staff.

Sponsors who wish to obtain labeling using this mechanism should send a written or

facsimile request to:

Food and Drug Administration

Freedom of Information Staff (HFI-35)

5600 Fishers Lane

Rockville, MD 20857

Phone: 301-827-6500; FAX: 301-443-1726

When a labeling revision is needed, the ANDA sponsor should take appropriate action to

revise the ANDA labeling and submit the revised labeling to the FDA.
IV. HOW TO SUBMIT REVISED LABELING

All ANDA labeling changes needed because of approved changes to the labeling of the

RLD may be submitted as a Special Supplement – Changes Being Effected. Such

supplements should include:

• 12 copies of final printed labeling

• the date the revised labeling will be used (go into effect)

• a side-by-side comparison of the ANDA labeling with the approved labeling

of the RLD with all differences annotated and explained, as described in 21

CFR 314.94 (a)(8)(iv)

Sponsors should contact the OGD Labeling Review Branch at 301-827-5846 if there are

any questions about the information in this guidance.