Comments regarding Changes to an Approved NDA or Abbreviated NDA

February 17, 2004

Division of Dockets Management (HFA-305)

Food and Drug Administration

5630 Fishers Lane, Rm. 1061

Rockville, Maryland 20852

Re: Docket No. 2000N-1449, Federal Register: December 19, 2003 (Volume 68, Number 244, Pages 70813-70815)

Dear Sir/Madam:

The following comments are provided by the Biotechnology Industry Organization (BIO). BIO represents more than 1,000 biotechnology companies, academic institutions, state biotechnology centers and related organizations in all 50 U.S. states and 33 other nations. BIO members are involved in the research and development of health-care, agricultural, industrial and environmental biotechnology products. We appreciate the opportunity to comment on the Food and Drug Administration's (FDA's) Comment Request regarding information collection activities contained in FDA's Guidance for Industry: Changes to an Approved New Drug Application or Abbreviated New Drug Application.

Overview

In this Comment Request, FDA seeks feedback on (among other things) "ways to enhance the quality, utility, and clarity of the information to be collected . . . and ways to minimize the burden of the collection of information on respondents" (p. 70813). Below, we provide feedback (applying to BLAs as well as NDAs and ANDAs) on FDA's treatment of post-approval supplements concerning changes being effected in 30 days ("CBE 30s"). BIO is concerned that there is an inconsistency between the information that applicants receive from FDA about the review period for these supplements, and the review period required by the regulations. Specifically, while the regulations state that FDA will review CBE 30s for completeness and for appropriateness of the supplement category within 30 days, CBER and CDER letters of receipt for CBE 30 post approval supplements often state that the FDA will notify the applicant (about category appropriateness, completeness, or both) within 60 days.

Background

CBE 30 post approval supplements are regulated under 21 CFR 314.70(g)(2) and 21 CFR 601.12(c), which state "If within 30 days following the FDA's receipt of the supplement, FDA informs the applicant that either (A) The change requires approval prior to distribution of the product . . . , or (B) Any of the information required . . . is missing; the applicant shall not distribute the product made using the change until FDA determines that compliance is achieved."

Similarly, the Guidance for Industry: Changes to an Approved NDA or ANDA, Questions and Answers (January 2001), states "Within 30 days, CDER will notify the applicant if prior approval is required for the change (i.e., CDER has designated the supplement a prior approval supplement or FDA has determined appropriate information is missing).

With respect to CDER, perhaps the source of the confusion is the following: CDER letters may be based on 21 CFR 314.101 (which relates to original applications, and which does reference a 60-day filing deadline), rather than 21 CFR 314.70 (which relates to post approval supplements, and makes no reference to a 60-day timeframe).

With respect to CBER, there is an internal inconsistency in SOPP 8401.2: Although this SOPP requires the Regulatory Project Manager to ensure that the proper reporting category is assigned in accordance with 601.12 (ie, within 30 days), FDA also states, "When a decision is made to file a supplemental application, the applicant must be notified in the filing letter or within 14 days of the 60-day filing date of either: 1) Potential filing issues; or 2) No potential filing issues identified during the filing review."

Conclusion

BIO requests that FDA acknowledge and follow 21 CFR 314.70 and 21 CFR 601.12 for post-approval supplements. We ask that receipt letters
  1. 1) state that within 30 days of the supplement's receipt at FDA, the supplement will be reviewed for
    1. a. appropriateness of CBE 30 category, and
    2. b. completeness
  2. 2) state that the applicant can distribute product manufactured using the change 30 days from the supplement's receipt at FDA, unless notified otherwise by FDA.

BIO appreciates this opportunity to comment on information collection activities contained in FDA's Guidance for Industry: Changes to an Approved New Drug Application or Abbreviated New Drug Application. We would be glad to work with the agency to provide further input or clarification of our comments, as needed.

Sincerely,

Gillian R. Woollett, MA, DPhil

Vice President

Science and Regulatory Affairs