In July 2025, the FDA for the first time made 202 Complete Response Letters (CRLs) public. A subsequent release in September added 89 more CRLs; however, these were heavily redacted as the associated applications remain under review, limiting the insights that could be derived. The July release included CRLs issued between 2020 and 2024 for applications that have since achieved approval. Of the 202 CRLs published, 46 were associated with Biologics license
Applications (BLAs), remainder 156 were associated with New Drug Applications (NDAs). Analysis of these 46 BLA- related CRLs revealed that 11 cited deficiencies in control strategy, representing the most common quality-related theme identified in this data set.
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FDA CRLs Reveal a Pattern: Biologic Control Strategy Issues Drive Delays and Rejections
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About the Author
Maria Wik, MS
Maria Wik brings 20 years of experience in CMC development, spanning recombinant proteins, monoclonal antibodies, bi-specifics, and other novel antibody formats, mRNA vaccines, as well as cell and gene therapies. She has held leadership roles in process development, manufacturing science and technology (MSAT), and large-scale GMP manufacturing, and now partners with Syner-G clients to design and execute CMC strategies that deliver impactful treatments to patients.
Previously, Maria served as Director of MSAT at AstraZeneca’s Colorado site and as Senior Director of Manufacturing at Avexis/Novartis Gene Therapies, where she led a team of 130 to a successful facility start-up and first GMP batch within 10 months. She began her career at Amgen and holds a Master of Chemical Engineering from the University of Colorado Boulder and a Bachelor of Science from Hogskolan Dalarna in Sweden.
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