Pharmaceutical Manufacturing Handbook: Production and

100 STERILE PRODUCT MANUFACTURING
2.1.6
2.1.7
2.1.8
2.1.9
2.1.10
2.1.11
2.1.12
2.1.13
2.1.1
Sterilization and Depyrogenation
2.1.6.1 Steam Sterilization
2.1.6.2 Dry - Heat Sterilization and Depyrogenation
2.1.6.3 Gas and Vapor Sterilization
2.1.6.4 Radiation Sterilization
2.1.6.5 Sterilization by Filtration
Facility and System: Qualifi cation and Validation
Environmental Control and Monitoring
2.1.8.1 Sanitization and Disinfection
2.1.8.2 Monitoring
Production Activities
2.1.9.1 Material and Component Entry
2.1.9.2 Cleaning and Preparation
2.1.9.3 Compounding
2.1.9.4 Filling
2.1.9.5 Stoppering and Crimping
2.1.9.6 Lyophilization
Personnel
Aseptic Processing Control and Evaluation
2.1.11.1 In - Process Testing
2.1.11.2 End - Product Testing
2.1.11.3 Process Simulations
Terminal Sterilization
Conclusion
Appendix
References
Additional Readings
INTRODUCTION
The manufacture of sterile products is universally acknowledged to be the most
diffi cult of all pharmaceutical production activities to execute. When these products
are manufactured using aseptic processing, poorly controlled processes can expose
the patient to an unacceptable level of contamination. In rare instances contaminated
products can lead to microbial infection resulting from products intended to
hasten the patient ’ s recovery. The production of sterile products requires fastidious
design, operation, and maintenance of facilities and equipment. It also requires
attention to detail in process development and validation to ensure success. This
chapter will review the salient elements of sterile manufacturing necessary to
provide acceptable levels of risk regarding sterility assurance.
Commensurate with the criticality associated with sterile products, the global
regulatory community has established a substantial number of the basic requirements
that fi rms are expected to adhere to in the manufacture of sterile products.
The most extensive of these are those defi ned by the Food and Drug Administration