Cell and Gene Therapies: Challenges in Designing Extractables and Leachables Studies and Conducting Safety Assessments

Abstract

Over the past decade, Cell and Gene Therapies (C&GT) have been an emerging therapeutic area with more than twenty C&GT drug products approved and over 1000 registered trials. The remarkable progress in these modalities brings new challenges for scientists who evaluate manufacturing and storage materials, including risk assessments for extractables and leachables (E&L). Establishing a business process to qualify materials for these applications is an important risk mitigation strategy in support of these assessments. Process validation verifying process performance and product quality requirements using qualified materials also ensures that leachables from the materials do not result in an impact to process and product. The authors provide an overview of available guidelines and publications relevant to E&L risk assessments that can be used to support ex vivo C&GT products, highlighting gaps and standardization needs in the areas of biocompatibility and extractables conditions. Finally, the authors present leachable testing strategies, relevant to the specific manufacturing and storage conditions of C&GT products, and safety assessment considerations for organic and inorganic chemical entities.

Keywords: Biocompatibility; Cell and gene therapy; Extractables; Leachables; Materials manufacturing; Regulatory biocompatibility; Risk assessments; Safety (toxicology) assessments; Storage.