Manufacture and regulation of cell, tissue and gene therapy products: global perspectives, challenges and next steps

Abstract

Cell, tissue and gene therapy products (CTGTPs) are therapeutic products intended for use in humans for prophylactic, diagnostic, curative, palliative or diagnostic purposes. Generally, they are breakthrough therapies with immense potential in treating diseases with no cure or rare diseases with high treatment burdens. Thus far, the number of approved cell, tissue and gene therapies globally are few and far between, with some approved products being recalled due to safety and efficacy issues. This situation highlights the need to rectify the challenges that are present in the manufacturing and regulation of these medicines. This article presents an overview of how CTGTPs work using examples of existing approved products across different product categories, as their mechanisms of action and characteristics contribute to manufacturing challenges. The differences between CTGTPs and conventional biologicals will be highlighted to understand the need for different regulatory frameworks to be designed. Additionally, these frameworks by the major regulatory authorities and international organizations will be analysed to elucidate whether CTGTPs are regulated to different extents across countries. Challenges faced in the manufacturing and regulation of CTGTPs include quality assurance issues, lack of expertise and limitations in technology. Potential solutions include implementing a tighter regulatory framework, fostering the international harmonization of regulations, increasing outsourcing to meet good manufacturing practice (GMP) guidelines, and incorporating automation into manufacturing processes to improve quality control to address the challenges encountered.