# Presentation: 529896

## ACPSNovember 15, 2000

***314.70 Update***
**Nancy B. Sager, Associate Director**
**Office of Pharmaceutical Science**
**Center for Drug Evaluation & Research**
**Food and Drug Administration**

## Regulatory Approach

- CDER’s regulatory approach to post approval CMC changes is evolving
- 21 CFR 314.70 (1985 rewrite)
- SU/PACs (early 90’s to present)
- FDAMA (1997)
- Implementation of FDAMA §116 (now)
- Next ?

## 21 CFR 314.70:Supplements and Other Changes to an Approved Application (1985 rewrite)

- “The applicant shall notify FDA about each change in each condition established in an approved application beyond variations provided for in the application”
- Provides a general listing of changes with reporting mechanisms

## Scale Up/Post Approval Change - Guidance Documents

-               Level of
-              Changes

- Minor change
- Moderate change
- Major change
- Application / Compendial Tests
- In Vitro Dissolution / Release
- In Vivo
- Annual Report
- Changes Being Effected Supplement
- Prior Approval Supplement

- Tests

- Filing

## FDA Modernization ActSection 116 (November 1997)

- Recognized the importance of the SU/PAC approach
- Amended the Food, Drug, and Cosmetic Act by adding Section 506A
- Required revision of 314.70
- Guidance was developed to document FDA’s current thinking on how to apply Section 506A

## FDAMA Section 116

- Reporting categories are based on the ***potential*** for the change to adversely affect the identity, strength, quality, purity, or potency of a product as they may relate to the safety or effectiveness of the drug product.

## FDAMA Section 116:Reporting Categories

- Substantial potential
- Prior approval supplements
- Moderate potential:
- Supplement — changes being effected in 30 days (CBE-30)
- Supplement — changes being effected (CBE-0)
- Minimal potential
- Annual reports

## FDAMA 116 Implementation Status

- Draft guidance published for public comment on June 28, 1999;  comment period closed on Aug. 27, 1999;  final guidance published Nov. 1999
- (30 comment letters, 1200 individual comments)
- Proposed regulation published for public comment on June 28, 1999;  comment period closed on Sept. 13, 1999
- (30 comment letters, 300 individual comments)

## Changes to an Approved NDA or ANDA (Nov. 1999 guidance)

- Modeled on SU/PACs
- Recommends reporting categories only
- Covers _all_ dosage forms
- No recommendations on specific information that should be developed by the applicant to assess the effect of the change

## FDAMA 116 Implementation Status

- The November 1999 guidance on *Changes to an Approved NDA or ANDA* represents FDA’s current thinking on how it will apply the requirements of section 506A of the Act for NDA and ANDA products.

## FDAMA 116 Implementation Status (cont’d)

- Until the final regulation for § 314.70 publishes, section 506A is the sole basis for FDA’s regulation of postapproval manufacturing changes for products approved in NDAs or ANDAs

## FDAMA 116 Implementation Status (cont’d)

- The final rule for § 314.70 has been drafted and is in the beginning stages of the clearance process (ETA = winter/spring)
- The guidance on *Changes to an Approved NDA or ANDA* is being revised to conform to § 314.70 and will publish at the same time as the final rule.