Complete Response Letters in Transition: Navigating FDA’s Transparency Policy and Manufacturing-Related Actions, and How to Respond

When FDA determines that a drug or biologic application (i.e., an NDA, ANDA, or BLA) is not approvable, it sends a complete response letter (CRL) to the application sponsor to communicate that the review is complete and the application is not ready for approval. The CRL communicates all of the specific deficiencies that FDA identified in the application, and when possible, recommends actions that the applicant might take to ready the application for approval. There are a range of deficiencies that could lead to a CRL, for example, quality or clinical issues, including inadequate data or manufacturing controls or problems with study design. Some of the deficiencies may be minor, while others may be classified as major and require more effort to resolve.

Historically, FDA only released CRLs in a public forum after a drug was approved. Only in the last few months has the FDA shifted this policy towards “radical transparency.” Now, the FDA releases CRLs in “real time” and publishes CRLs for pending and withdrawn applications.

In this webinar, we will explore FDA’s new approach to CRL disclosure, lessons learned from FDA’s significant policy shift, and opportunities for those who may want to challenge FDA CRL decisions. We will start with the background on CRLs — what they do, what they are, and how they have changed. Next, we will discuss FDA’s use of CRLs in evaluating manufacturing compliance. FDA has shifted from generally tying CRLs to compliance actions, which can affect how sponsors and CMOs should think about pre-approval and pre-license inspections and how to follow up on FDA inspection findings. We will then examine key takeaways from the recently released CRLs. Finally, we will discuss how FDA’s new CRL policy is affecting drug development more broadly, including opportunities to build administrative records regarding disagreement with FDA’s eventual conclusions, as well as opportunities to challenge the FDA’s new policy, which contravenes FDA’s existing disclosure regulations and departs from decades of precedent.