3. How will you guarantee sterility?
Because of the nature of cell and gene therapies, manufacturers have only one option for assuring the safety and sterility of their final products: they must design their facility and their process to meet the rigors of a fully aseptic manufacturing operation. Aseptic manufacturing requires the highest cGMP standards. In 2022, the European Medicines Agency (EMA) published a revision of Annex 1, providing guidance on the “Manufacture of Sterile Medical Products”. Annex 1 came to formalize the need for manufacturers to assess their facilities and processes around a detailed contamination control ctrategy (CCS).
Establishing a CCS is one of the most critical actions you’ll take on your way to commercial-scale aseptic manufacturing. Many manufacturers will work with experts who understand the rigors of contamination control to complete this step. It involves formally scrutinizing your raw materials, your equipment, your facility design, and your process itself—every factor across your manufacturing chain that could impact your final product’s sterility. Your goal is to identify and characterize all contamination and cross-contamination risks, then develop appropriate mitigation strategies.
Process closure is one of the most important mitigation strategies, especially for manufacturers operating an aseptic production facility. The more you’re able to protect your process from both the surrounding environment and the risks of manual interventions, the greater your control over the quality of your final product. Process closure is also beneficial from a facility perspective; a closed process does not require high background classifications, airlocks, gowning areas, and other cost- or space-intensive facility features. In reality, though, many of the technologies necessary to fully close the cell and gene therapy manufacturing process are still in development. While this technology matures, the industry must grow comfortable with the concept of managing process-related risks through closed and automated technology rather than environmental controls. Until then, you’ll likely face the challenge of integrating certain open and manual steps into your aseptic process.