Outlook of Cell Gene Therapies Development and Approval from Quality and Regulatory Perspective

Abstract

Background: Cell and gene therapies represent a transformative advance in modern medicine but pose major quality and regulatory challenges. The complexity of manufacturing, product comparability, and potency assessment often limits dossier robustness and delays approval. Methods: A systematic review was conducted on cell gene therapies approved in the European Union (EU) and the United States (US) up to December 2024. Publicly available regulatory data from EMA and FDA sources were analyzed to identify key regulatory milestones and quality issues during marketing authorization. Results: Fourteen cell gene therapies were approved (12 in the US, 11 in the EU). All received orphan designation, and over 80% benefited from expedited development pathways. The most frequent quality objections concerned manufacturing comparability, potency assay validation, specifications, and stability data. Although regulatory support mechanisms accelerated submissions, they did not consistently translate into higher-quality dossiers. The FDA follows a data-driven approach, while the EMA takes a broader, science-based view and continuous improvement. Conclusion: Ensuring robust quality data packages remains the main bottleneck in cell gene therapy development. Early integration of quality-by-design principles, comprehensive comparability assessments, and validated potency assays are essential to strengthen regulatory submissions. Continuous dialogue with regulatory agencies and harmonization between regions are key to accelerating patient access while maintaining product quality and consistency.