In July 2025, three high-profile advanced therapy programs — targeting Duchenne muscular dystrophy, Sanfilippo Syndrome Type A, and leukocyte adhesion deficiency-I — were delayed or rejected by the US Food and Drug Administration (FDA) not for safety or efficacy reasons, but due to Chemistry, Manufacturing, and Controls (CMC) readiness (Foster, 2025).

This is not an isolated trend. Analysis of FDA’s publicly released Complete Response Letters (CRLs) shows that from 2020 to 2024, 74% cited manufacturing or quality (CMC) deficiencies — including gaps in process control, incomplete stability data, or unvalidated analytical methods (Pharma Manufacturing, 2025). Even at the Investigational New Drug (IND) stage, an estimated 40% of submissions are delayed for CMC-related issues (Foster, 2025).

Rising Regulatory Expectations

With the FDA now publishing over 200 CRLs in a drive for greater transparency (FDA, 2025), the spotlight has shifted firmly onto CMC deficiencies — even when sponsors believed prior consultations had cleared them (Pharmaceutical Technology, 2025).

This shift underscores a critical principle: “The process is the product” — early technical decisions (e.g., vector platform, assay validation, scale-up methods) fundamentally shape regulatory approval outcomes (Silva, Stonier, Kerpel-Fronius, & Dubois, 2021).

Skills and Competencies to Prioritize

To meet evolving regulatory expectations and avoid costly delays, medicines development professionals — especially those working in cell and gene therapy — should strengthen capabilities in:

  1. CMC Fundamentals for Advanced Therapies
    • Development, manufacture, and packaging of medicines in compliance with regulatory CMC requirements
    • Understanding vector platforms, host cell line qualification, and analytical validation
  2. Regulatory Science and Strategy
    • Integrating CMC considerations into regulatory submissions from the earliest stages
    • Applying and interpreting evolving FDA and EMA guidance
  3. Cross-functional Collaboration
    • Aligning R&D, manufacturing, and quality functions early in development
    • Building shared language between scientific and operational teams
  4. Risk and Change Management
    • Planning for scale-up, tech transfer, and comparability testing
    • Identifying process-critical parameters that affect quality attributes

Turning Competence into Approval: Why Skills Matter Now More Than Ever

The FDA’s heightened scrutiny is a clear signal: in advanced therapy development, scientific innovation is only half the battle. The other half is proving that your manufacturing, quality, and regulatory processes can deliver consistent, compliant products (Silva et al., 2024).

The CMD Program from GMDP Academy equips professionals with these core competencies — along with the interdisciplinary skills needed to anticipate regulatory expectations and bring therapies to market faster. By investing in these capabilities now, medicines development professionals can navigate rising regulatory demands, avoid costly late-stage CRLs, and ensure that breakthrough therapies reach the patients who need them.

References

Pharma Manufacturing. (2025, July 14). FDA’s CRLs reveal 74% of applications rejected for quality/manufacturing issues. https://www.pharmamanufacturing.com/all-articles/article/55302937/fdas-crls-reveal-74-of-applications-rejected-for-quality-manufacturing-issues

FDA. (2025, July 10). FDA embraces radical transparency by publishing Complete Response Letters. https://www.fda.gov/news-events/press-announcements/fda-embraces-radical-transparency-publishing-complete-response-letters

Pharmaceutical Technology. (2025, July 25). CMC and analytical gaps in CRLs: Why they persist despite FDA guidance and how you can position yourself for success. https://www.pharmtech.com/view/cmc-and-analytical-gaps-in-crls-why-they-persist-despite-fda-guidance-and-how-you-can-position-yourself-for-success

Silva, H., Stonier, P. D., Kerpel-Fronius, S., & Dubois, D. J. (2021). Editorial: Grand challenges in pharmaceutical medicine: Competencies and ethics in medicines development. Frontiers in Pharmacology, 12, 666406. https://doi.org/10.3389/fphar.2021.666406

Silva, H., Stonier, P., Chopra, P., Coots, J., Criscuolo, D., Guptha, S., Jones, S., Kerpel-Fronius, S., Kesselring, G., Luria, X., Morgan, D., Power, E., Salek, S., Silva, G., Suto, T., Thakker, K., & Vandenbroucke, P. (2024). Blended e-learning and certification for medicines development professionals: Results of a 7-year collaboration between King’s College, London and the GMDP Academy, New York. Frontiers in Pharmacology, 15, 1417036. https://doi.org/10.3389/fphar.2024.1417036

Foster, B. (2025, August 3). Why gene and cell therapies are stalling at the FDA. Drug Discovery News. https://www.drugdiscoverynews.com/game-changer-drug-is-the-first-to-tackle-overeating-in-prader-willi-syndrome-16355

Disclaimers

  • The material in these reviews is from various public open-access sources, meant for educational and informational purposes only
  • Any personal opinions expressed are those of only the author(s) and are not intended to represent the position of any organization(s)
  • No official support by any organization(s) has been provided or should be inferred