BLA CMC Problem Areas Include Lack of Transparency in Supplement Cover Letters, FDA Reports

FDA is urging sponsors filing Biologic License Application (BLA) supplements to clearly highlight the significant changes and their scope in the cover letter to expedite the agency review and approval process.

The advice reflects the agency’s experience that supplement filers are not always giving it a clear picture up-front, resulting in significant review delays or a Complete Response (CR) letter indicating that the application is not approvable in its current form.

In turn, providing too much information on aspects of existing facilities that have not changed – for example, through hyperlinks to prior submissions – can also slow down the process as the reviewer must take time determining what has changed and what has not.

Speaking for the Center for Biologics Evaluation and Research (CBER) Division of Manufacturing Product Quality (DMPQ) at the PDA Annual Meeting in San Antonio, Texas in April, David Doleski emphasized the importance of clarity around these changes in a presentation on regulatory expectations for BLA CMC filings.  Doleski left CBER’s Office of Compliance just prior to the presentation to join CDER’s compliance office as Acting Branch Chief of its New Drug Manufacturing Assessment Branch.

In his presentation at the meeting, Doleski highlighted “desirable and undesirable” attributes in BLA submissions trends in approvals, and examples of specific issues causing applications to be significantly delayed or not approved.

[CLICK HERE for the complete story.  The full story can be purchased for $195 by contacting Jonathan Trethowan (  For subscription/license information, click here.]