Management of process technology.

A successful manufacturing scale cell culture process has as its basis a well-designed process. However, even the best designed large-scale process can become unreliable if not managed properly. The primary element to successful management of all large-scale processes is the careful attention to the details, especially the most important ones. The second element that requires serious consideration is the operation of that process within the confines of current regulatory environments. The major considerations are: 1. Adequate raw material specifications and testing. 2. Facility and equipment design that maximizes operational success and meets current regulatory requirements. 3. Thoroughly written procedures covering all aspects of operation and maintenance, and supported by a thorough documentation and review system. 4. A dedicated staff with a thorough understanding of systems and the importance of operational details. 5. Continual training and retraining programs. 6. Sound process and facility validation programs. 7. Comprehensive preventive maintenance programs. 8. Thorough understanding of process and facility trends, and the expected and acceptable ranges of results. 9. Development of sound procedures and practices that minimize batch losses and permit operation within current regulatory requirements. 10. Thorough and continual monitoring of all critical process parameters. 11. Process scheduling to minimize batch jeopardy or loss while maximizing throughout. 12. Maintenance of the appropriate environmental conditions of the plant and general cleanliness of plant and equipment. 13. Adequate batch loss prevention programs. 14. Adequate troubleshooting programs. 15. Adequate support organization and facilities both internally and externally to plant operations. With the appropriate application of sound process design and management principles, and with operational experience, large-scale cell culture process plants can be operated at success rates that exceed 95%.