Validation of Sterilization Processes and Sterile Products

The intent of this chapter is to review the salient features of process validation relative to the preparation of sterile dosage forms. The introduction of process validation to the parenteral drug industry (in fact to the entire pharmaceutical industry) is generally attributed to Ted Byers and Bud Loftus. Mr. Byers and Mr. Loftus were members of the Office of Compliance in what was, in 1972, called the Bureau of Drugs. In response to a series of sterility assurance compliance issues for Large Volume Parenterals in the early 1970s, the FDA began to espouse the benefits of “validation” to the industry. The pharmaceutical industry perceived validation to be a concept related solely to large volume parenterals (LVPs), but its scope was quickly expanded by the FDA to include all types of parenteral dosage forms. In later years, the FDA has increased its expectations to include validation of virtually all products, systems, and procedures employed in the pharmaceutical industry. These requirements are codified in regulations. The Current Good Manufacturing Practice (cGMPs) regulations first appeared in 1978 in Chapter 21 of the Code of Federal Regulations [1]. US 21 CFR 211.110(a) To assure batch uniformity and integrity of drug products, written procedures shall be established and followed that describe the in-process controls, and tests, or examinations to be conducted on appropriate samples of in-process materials of each batch. Such control procedures shall be established to monitor the output and to validate the performance of those manufacturing processes that may be responsible for causing variability in the characteristics of in-process materials and the drug product.