Human Blood Origin Materials for Cell & Gene Therapy Manufacturing Supplier Questionnaire

The new realm of cell and gene therapy drugs has created new challenges in the way raw materials are used in the manufacturing process. Where there could be multiple viral inactivation/viral clearance steps in the manufacturing process for small molecules and biologics, this is not possible for cell and gene therapies as the cells cannot withstand the extremes of pH and heat required to ensure viral inactivation/clearance. Manufacturers have
to mitigate the risk upstream before the raw materials are introduced into the manufacturing process. A risk-based approach is recommended to characterize raw materials and implement risk appropriate mitigation steps.

The use of raw materials of human or animal-origin is not encouraged by regulators for the manufacturing of cell and gene therapies. This is due to the inherent risk of transmitting adventitious agents such as viruses, mycoplasma, bacteria and Transmissible Spongiform Encephalopathy (TSE) agents, the potential for adverse immune reaction, and the potential variability in composition and quality due to their biological origin. Raw materials of human origin are considered high-risk to patient safety and therefore multiple orthogonal risk mitigation measures must be incorporated before use is cell therapy processes. Materials derived from human blood such as human serum albumin and transferrin are frequently used either as components of cell culture medium or in other processes. Suppliers of such reagents have incorporated multiple mitigation steps such as sourcing pharmaceutical grade or licensed drug product, sourcing from safe geographical regions, testing for contaminants and inactivation. In addition, this information needs to be available for review during inspections and in regulatory filings. This questionnaire is a comprehensive list of those requirements and will be a useful document for reference. The questionnaire can be used as a tool for human blood origin material selection and qualification when incorporated in the production of advanced therapy products (cell/gene). The document is an addition to the supplier and material qualification package by Rx-360 and does not replace it.