A New Era of FDA Disclosure
On Thursday, July 10, 2025, FDA published more than 200 decision letters, known as complete response letters (CRLs). The CRLs were issued in response to applications submitted to FDA for approval of drugs or biological products between 2020 and 2024, marking a departure in the Agency's approach to sharing information that historically has not been made public.
CRLs are issued directly to product sponsors when FDA completes its review cycle and determines that it cannot grant approval of an application in its current form. FDA issues CRLs for various reasons, most relate to safety and efficacy concerns, manufacturing deficiencies, and bioequivalence issues. These deficiencies are detailed in the letters and may also include recommendations for addressing them.
Because FDA has historically refrained from publishing CRLs for pending applications, the Agency asserts that sponsors often misrepresent the rationale behind FDA's decision to their stakeholders and the public. According to research conducted by FDA, sponsors avoided mentioning 85% of the FDA's concerns about safety and efficacy when announcing publicly that their application was not approved. Moreover, when FDA calls for a new clinical trial for safety or efficacy, that critical information is not disclosed approximately 40% of the time.
The Impact of CRL Transparency on Industry Practices and Regulatory Planning
Making the CRLs available gives the public significantly greater insight into FDA's decision-making and the most common deficiencies cited that sponsors must address before their application is approved. Lessons learned from non-approvals are not typically shared within the industry, leading companies to repeatedly making similar mistakes. Regulatory professionals can learn from these letters and help guide companies through a more successful approval process.
Also, now that this information will be made public moving forward, companies may need to rethink their approach to public disclosures, such as the content of press releases, to ensure that they are in conformity with applicable laws and regulations. Here, again, regulatory and compliance professional can help industry avoid potential pitfalls by providing expert reviews of these communications.
Key Takeaways: What You Should Be Doing Now
With FDA now publishing CRLs, sponsors, CROs, and regulatory teams have a unique opportunity to refine their strategies and minimize future submission risk. Here's how you can put this new information to work:
- Re-evaluate your pre-submission strategy. Use published CRLs to anticipate potential FDA concerns during IND, NDA, or BLA development. Integrate these insights into FDA meeting preparation and submission planning.
- Leverage regulatory intelligence. Monitor CRLs in your specific therapeutic area to identify common deficiencies, patterns in FDA reasoning, and regulatory hot spots.
- Strengthen clinical and labeling development. Review CRLs to understand how FDA has responded to clinical trial designs, endpoints, and labeling proposals. Use these learnings to ensure your development plans are aligned with current expectations.
- Align public communications. If your product receives a CRL, ensure that your press releases, investor communications, and public disclosures reflect the actual regulatory feedback—now publicly available for comparison.
- Enhance internal training. Incorporate CRL examples into team onboarding, mock FDA reviews, and regulatory strategy sessions. Use these documents as real-world teaching tools to upskill your team.
Taking a proactive, CRL-informed approach now can help reduce surprises during the review process, improve submission quality, and position your team for regulatory success.
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