Using a Patient-Centered Risk-Benefit Structure and Appropriate Manufacturing Practices (AMPs) for Successfully Developing and Manufacturing Effective Cell Therapy Products

by Mark F. Witcher, PhD
Volume 15, Issue 2 (Summer 2016)

The development and manufacturing of advanced breakthrough cell therapies presents a wide variety of complex challenges that include:
• delivering the medical science, from research all the way through product development and clinical testing, to the patient population;
• understanding and defining the product’s modes of activity and the cell’s attributes necessary to attain therapeutic benefit and safety;
• overcoming significant manufacturing, logistical, and cost of goods issues associated with using attachment-dependent bioreactor systems; and
• defining product release challenges associated with rapidly delivering an effective product to the patients.
Successfully meeting these challenges requires new lifecycle development and manufacturing approaches based on understanding a complete set of patient goals that go beyond safety to include both efficacy and the patient’s ability to access the therapy. For many of these complex therapies, safety is perhaps the easiest of the three goals. Establishing both product and process comparability from the very beginning is required to assure the product successfully makes it through the product development sequence. The new approaches must also be based on appropriate manufacturing practices (AMPs) over the product’s lifecycle, from the earliest research phases, process development, clinical manufacturing, and finally to commercial manufacturing, to keep the development effort focused and efficient. This paper describes approaches built on product and process lifecycle paradigms that emphasize both product and process validation to assure product comparability over the entire manufacturing lifecycle, from research through commercial production. Methods previously used for chemical entity pharmaceuticals, and even protein biopharmaceuticals, are not adequate for cellular therapeutics being developed from recent advances in medical science’s understanding of complex therapeutic pathways. The safety and efficacy of cell-based therapies may be impacted by subtle and difficult-to-measure changes in the performance or behavior of the manufacturing process. In addition, the patient’s access to cell therapies is heavily impacted by the complexity and cost of developing adherent bioreactor technologies required to expand and/or modify therapeutic cells...

Witcher MF. Using a patient-centered risk-benefit structure and appropriate manufacturing practices (AMPs) for successfully developing and manufacturing effective cell therapy products. BioProcess J, 2016; 15(2): 22–9.

Posted online July 30, 2016.