Abstract 

Cell and gene therapies have entered mainstream clinical practice, yet broad patient access remains limited by manufacturing complexity, biological variability and evolving global oversight. Regulators continue to expand recommendations to better support individualised CGT manufacturing, including the US Food and Drug Administration’s consolidated cellular and gene therapy guidance suite and the 2025 draft guidances addressing expedited programmes, innovative trial designs for small populations and post‑approval evidence generation. International coordination pilots, such as the CoGenT US Food and Drug Administration (FDA)–European Medicines Agency (EMA) joint review initiative, signal movement toward harmonised global oversight.

In parallel, the FDA’s 2026 announcements indicate increased flexibility in certain manufacturing controls when justified by benefit–risk considerations.

Against this backdrop, this article describes the major scientific and operational barriers that constrain CGT accessibility, examines emerging solutions across automation, closed‑system processing, process analytical technology (PAT), digital twins and platform selection, and highlights current regulatory expectations.