The U.S. Food and Drug Administration (FDA) today published more than 200 complete response letters (CRLs) issued between 2002 and 2024. FDA reports that it has only published CRLs sent to companies whose drug and biological products were eventually approved. Many of these have already been made public, either by the companies or by FDA in the review documents released after approval. Nonetheless, the agency’s decision to create a public database of CRLs marks a historic shift in practice, and it remains to be seen whether FDA will expand this practice to documents currently protected as confidential. Below we outline questions for pharmaceutical and biotechnology companies to consider in light of FDA’s action and consider the potential for increased litigation resulting from this regulatory update.
The CRL process
Following FDA review, a new drug application (NDA) or biologics license application (BLA) that does not meet statutory or regulatory standards for approval is issued a CRL noting the deficiencies that preclude approval. These deficiencies range from safety concerns or inadequate efficacy data to manufacturing or bioequivalence problems, and CRLs often include FDA’s position on the additional work needed for approval. FDA historically has not released CRLs at the time of issuance, instead publishing them as part of the approval package made publicly available after NDA or BLA approval.
FDA’s decision today to publish over 200 CRLs is characterized as part of Commissioner Makary’s promise of “radical transparency” regarding approvals of drugs and biologics (and decisions not to approve). In publishing the CRLs, FDA referenced a 2015 analysis by agency reviewers to assert that sponsors “often misrepresent the rationale behind FDA’s decision [not to approve a product] to their stakeholders and the public,” knowing the CRL is confidential until FDA publishes the approval package. In that vein, FDA says its move will give the public, especially patients and investors, a dedicated database that provides a view into how the agency makes its decisions and will help drug developers learn from non-approvals and thus speed up new applications.
The published CRLs all relate to since-approved applications, according to FDA, and “were redacted for trade secrets and confidential commercial information.”
Confidentiality concerns
FDA’s press release sheds no light on how the agency made determinations regarding redactions of “trade secrets and confidential commercial information.” CRLs may include detailed technical assessments, references to proprietary technology, or clinical development strategies that applicants may be reluctant to make public.
Indeed, even redacted, a CRL can contain hints, or even details, about an applicant’s internal decision-making, intellectual property strategy, or technological hurdles. For instance, a redacted letter may still reveal that an applicant struggled with dose selection, encountered patient enrollment issues, or failed to meet an efficacy threshold in a particular subgroup. There is considerable risk that third parties could use these breadcrumbs to advance their own interests, from competitors to litigants who may seek to use this intelligence to bolster claims against the sponsor.
It is not clear that FDA consulted generally with industry, let alone particular applicants, in making the redactions and publishing the CRLs. It is not at all clear that applicants will agree that their confidential information has not been exposed.
Open questions & litigation potential
Calling its release today an “initial batch,” FDA notes that it “is in the process of publishing additional CRLs from its archives.” We will follow up with additional client alerts exploring the many important questions that remain, including:
- Whether FDA will standardize its redaction process and provide guidance to industry on what FDA plans to disclose moving forward.
- Whether FDA will merely put all of the CRLs for approved drug and biological products in one database for public review, or has now disclosed substantive new information about those previously approved medicinal products. For the CRLs included in the batch that had not previously been made public, additional research may identify information that would not typically be disclosed in FDA’s “summary basis of approval” document. The agency has recently touted the creation and use of its new AI tool, Elsa, as we described online here. It’s unclear whether FDA employed the Elsa tool in publishing the CRLs or redacting information, or if Elsa will play a role in this process moving forward.
- Whether litigation will be brought against the agency related to the CRL database and this potential new FDA letter disclosure process. For example, there may be challenges raised about the adequacy of the FOIA staff’s review and redaction of the CRLs.
- Whether there will be an uptick in securities litigation brought by investors alleging information in the CRLs does not line up with previous company statements.
Be on the lookout in the coming weeks for additional Hogan Lovells analyses of the issues described above, and other updates that may arise as we continue to monitor FDA’s evolving transparency policies.
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