Law Firm Proposes Effort to Make FDA's Complete Response Letters More Complete

The law firm Hyman, Phelps & McNamara focuses on the Food and Drug Administration (FDA), and as such, is the largest dedicated FDA law firm in the U.S. In the company’s FDA Law Blog, attorneys Deborah L. Livornese, JP Ellison and Josephine M. Torrente outlined problems with the FDA’s complete response letter (CRL) and what should be done about it.

First off, a CRL is basically a rejection letter. When a biopharma company submits a New Drug Application (NDA) or Biologics License Application (BLA), if the agency has any issue with it, they return a CRL. It’s not a note that just says REJECTED! It’s a summary of why the agency is rejecting the application.

The key word, though, is summary. The attorneys write, “A CRL is, by its nature, a summary document that abbreviates the many months of review and independent analyses performed by a number of FDA disciplines such as medical, statistical, and clinical pharmacology, into a handful of pages. The actual detailed work performed by the FDA reviewers is embodied in various highly informative review documents that, by contrast, typically span several hundred pages.”

Which is where the attorneys say the problems come in. Because the biopharma companies that made the application aren’t given the detailed information, just the summary. The FDA allows for an End-of-Review (EOR) meeting, “which the Center for Drug Evaluation and Research (CDER) requires an applicant to attend as a prerequisite for appeal under the FDR process.”

But that is usually an hour-long meeting and the complete documentation is still not provided. As one can imagine, this is a source of a great deal of frustration on the part of biopharma companies attempting to address a deficiency. And FDA reviewers get frustrated with the companies who “just don’t get it.”

The reason for not giving the applicants the full FDA analysis is an agency interpretation of its regulations that the attorneys believe is highly questionable. “Our understanding (based to some extent on Agency lore),” they write, “is that CDER does not share the underlying reviews with the applicant because it believes that disclosing them to the applicant would make the documents disclosable, at least in some respects, to third parties, under the requirements of the Freedom of Information Act (FOIA). We believe such an interpretation is incorrect, and that FOIA case law does not require that outcome."

And they go on to point out that there are other instances where the FDA provides detailed information to the applicants but not the broader public, such as the summary minutes of the EOR meeting.

In short, the attorneys argue that the FDA should make all of their review materials available to the applicants related to CRLs. Particularly given the amount of effort the FDA has made in recent years to speed the approval process by offering Accelerated Approvals, vouchers, and conducting various pilot programs aimed at streamlining the process, it is puzzling the agency doesn’t provide full access to its rejection-related materials.

Livornese, Ellison and Torrente write, “Without the benefit of access to the complex analyses and thinking that underlie a CRL, an applicant may be denied the ability to efficiently move its program forward, and may spend significant time and money, or make the decision to abandon a program, based on incomplete information—despite the existence of fully developed and internally vetted detailed reviews. FDA’s public health mission is not promoted by unnecessarily withholding information that could be used to more efficiently move new drugs into an approvable position (or have sponsors make fully informed decisions to halt programs for products that are destined to not be approved).”