The U.S. Food and Drug Administration recently resumed its policy of publicly releasing drug application rejection notices, known as complete response letters (CRLs), after pausing the release earlier in the year.
Last year, the agency announced its plan for “radical transparency” by publishing CRLs, allowing the public to see the FDA’s decision-making and common deficiencies in drug applications. However, the FDA suspended this practice in April of this year after a citizen petition was filed by an anonymous pharmaceutical company. Biopharma companies had complained that the release of these documents without proper collaboration with the drug’s applicant could lead to the release of confidential information that should have been redacted. The now-former FDA commissioner requested that Congress add language to explicitly allow the FDA to release CRLs and the agency resumed CRL sharing in July.
RSM CRL analysis: What 300+ rejections tell us
RSM has been tracking and analyzing CRLs since the FDA began publishing them in 2025, with more than 300 reviewed to date. Our analysis includes:
- The reason for each rejection.
- Whether a rejected product was later approved and, if so, the average time from CRL to approval.
- How companies can use the trends RSM has identified to manage risks ahead of a drug launch.
Our analysis of the 300 CRLs found that rejection reasons differ notably between products that were eventually approved and those still unapproved. Among the 219 products that ultimately received FDA approval, product quality/chemistry, manufacturing and controls (CMC) issues were the most common deficiency, accounting for 90 rejections. While these issues can be costly and difficult to resolve, their prevalence among later-approved products suggest they are often remediable rather than a hard barrier to approval.
Source: RSM US LLP, FDA
CRL-to-approval timelines reveal importance of addressing issues early
RSM’s analysis also uncovered a significant lag between the CRL and final approval: on average it takes over 2.4 years with a median of 1.5 years. That delay carries a real cost. Companies must fund remediation while also absorbing lost revenue. And for companies that were primarily rejected because of product quality/CMC, the median stretches to over 21 months, a stretch that can strain cash flow.
Reducing CRL risk: Steps companies can take now
While many products ultimately achieve approval following a CRL, RSM’s analysis highlights the substantial financial and operational burden associated with the process. To stay ahead of these challenges and disruptions and reduce the likelihood of costly delays, companies should focus on identifying potential regulatory risks as early as possible.
- Strengthen CMC readiness before submission. Conduct rigorous reviews of manufacturing processes, controls and supporting data to identify potential deficiencies before they reach regulators.
- Stress-test regulatory submissions. Use internal and external experts to challenge assumptions, review documentation and evaluate whether the application would withstand FDA scrutiny.
- Invest in early quality systems and compliance capabilities. Build robust quality and governance processes during development to help reduce remediation costs later.
- Plan for regulatory contingencies. Evaluate capital needs, cash flow impacts and launch timelines under multiple approval scenarios, including the possibility of a CRL.
- Learn from historical CRLs. Analyze patterns in past FDA rejection letters to help identify recurring risks and proactively address them before submission.
Ultimately, the most effective strategy is prevention. Companies that identify and resolve potential regulatory, quality and manufacturing issues early will be better positioned to avoid lengthy approval delays, preserve capital and bring therapies to patients more quickly.
For more on this topic, read FDA’s complete response letters underscore outsourcing and quality challenges.
RSM US contributors: Alsu Sultanbekova, Brady Mannix and Kevin Fung Liang
