The Evolution of Process Validation

Copyright © 2009 Norm Howe
In November 2008, the U.S. Food and Drug Administration (FDA) published draft guidance on process validation. Entitled Process Validation: General Principles and Practices, this draft guidance replaces the previous guidance issued in 1987. The new draft guidance, which is consistent with the goals outlined in FDA’s initiative Pharmaceutical CGMPs for the 21st Century - A Risk-Based Approach, incorporates modern risk management and quality systems tools and concepts. It also addresses product life cycle issues, such as process design, process qualification, and continued process verification. The draft guidance is also aligned with International Conference on Harmonization quality guidance documents, including Q8: Pharmaceutical Development, Q9: Quality Risk Management, and Q10: Pharmaceutical Quality System. The draft introduces a new definition of process validation as "the collection and evaluation of data, from the process design stage through production, which establishes scientific evidence that a process is capable of consistently delivering quality products." Moreover, process validation is split up into three stages: "Process Design," or the commercial process that is based on experiences gained from development and scale-up; "Process Qualification," or when the reproducible, commercial scale is confirmed on the basis of process design; and "Continued Process Verification," which is meant to show that the process is in a state of control during routine production. According to the draft, “A successful validation program depends upon information and knowledge from product and process development. This knowledge and understanding is the basis for establishing an approach to control that is appropriate for the manufacturing process.”

Within the document, manufacturers are recommended to understand the sources of variation; detect the presence and degree of variation; understand the impact of variation on the process and ultimately on product attributes; and control the variation in a manner commensurate with the risk it represents to the process and product. The draft further recommends “an integrated team approach to process validation that includes expertise from a variety of disciplines, including process engineering, industrial pharmacy, analytical chemistry, microbiology, statistics, manufacturing, and quality assurance.” Manufacturers should also note that the draft states, “However, it is not a regulatory expectation that the process be developed and tested until it fails, but rather that a process be controlled within commercial manufacturing conditions, including those combinations of conditions posing a high risk of process failure.” The draft guidance applies to process validation of human and animal drug and biological products, including active pharmaceutical ingredients (API or drug substance). The following categories of products are not covered: Type A medicated articles and medicated feed; medical devices; dietary supplements; and human tissues intended for transplantation regulated under section 361 of the Public Health Service Act. The draft is 20 pages divided into seven chapters: Introduction; Background; Statutory and Regulatory Requirements for Process Validation; Recommendations; Concurrent Release for Performance Qualification Batches; Documentation; and Analytical Methodology. Read the full draft here: About The Author:

Norm Howe, Senior Partner at Validation and Compliance Institute, consultants for the pharmaceutical and medical device industries. He got his BS at UC, Berkeley, and a Ph.D. in chemistry at UCLA. He has held many management positions in FDA regulated industries, most at BASF.