Media formulation options and manufacturing process controls to safeguard against introduction of animal origin contaminants in animal cell culture

Abstract

Technical limitations and evolution of therapeutic applications for cell culture-derived products have accelerated elimination of animal-derived constituents to minimize inadvertent introduction of adventitious viral or prion agents. Practical considerations demand adequate emphasis both on design of the serum-free/protein-free culture environment and on nutrient media manufacturing process controls. Protein components may be acceptable, given adequate attention to synthetic process, sourcing (e.g., geographic location and endemicity, species and tissue/organ) and validated treatment method. Various options exist for re-engineering of traditional serum-free formulations (containing insulin, transferrin and other protein factors) with non-protein substitutes. Caution must also be exercised with sourcing of non-protein additives, particularly amino acids and lipids, to avoid introducing adventitious contaminants. Simple guidelines facilitate adaptation, cryopreservation and recovery of many cell types within a protein-free culture environment. Scrupulous maintenance of facility and equipment and monitoring of process water, air handling systems and technical personnel are required to ensure that approved raw materials are correctly formulated and dispensed. Validated sanitization processes provide additional assurance against cross-contamination from previous batches in a multi-use facility.