The draft guidance about process validation is refreshingly simple and supports good science, yet it is demanding with respect
to the level of effort required to properly validate a pharmaceutical production process. The variety of approaches that the
pharmaceutical industry uses for process validation extends from the merely cosmetic, providing little if any real support
to product quality, to overblown efforts that have nearly crippled firms with their complexity and restrictive approach. The
draft guidance is not perfect, and improvement and clarification are certainly necessary, especially regarding the guidance's
application to sterile products. The guidance requires a restructuring of validation programs to tie development science more
closely to commercial-scale manufacturing. It clarifies FDA expectations for validation in a more coherent manner than previous
documents. The expectation for life-cycle treatment with heavy statistical emphasis mandates that sound science be applied
to validation more clearly than ever before.
For applications in the validation of processes and products that result from them, the author commends those who prepared
the guidance for a job well done. It is essential, however, that FDA and industry proceed with special caution in the areas
reviewed above because blind adherence to the concepts of the draft guidance will likely lead many astray.
James Agalloco is the president of Agalloco and Associates, PO Box 899, Belle Mead, NJ 08502, tel. 908.874.7558, email@example.com
1. FDA, Draft Guidance for Industry—Process Validation: General Principles and Practices (Rockville, MD, Nov. 2008).
2. J. Agalloco, "The Validation Life Cycle," J. Parenter. Sci. Technol.
47 (3), 142–147 (1993).
3. K. Chapman, "The PAR Approach to Process Validation," Pharm. Technol.
8 (12), 24–36 (1984).
4. R.E. Madsen, "Real Compliance and How to Achieve It," PDA J. Pharm. Sci. Technol.
55 (2), 59–64 (2001).
5. Code of Federal Regulations, Title 21, Food and Drugs (General Services Administration, Washington, DC, September 2008), Part 211, pp. 51919–51933.
6. FDA, "Pharmaceutical CGMPs for the 21st Century—A Risk-Based Approach," Final Report (Rockville, MD, Sept. 2004).
7. ASTM, "E 2500-07 Standard Guide for Specification, Design, and Verification of Pharmaceutical and Biopharmaceutical Manufacturing
Systems and Equipment," (ASTM, West Conshohocken, PA, 2007).
8. J. Agalloco, "Compliance Risk Management: Using a Top Down Validation Approach," Pharm. Technol.
32 (7), 70–78 (2008).
9. J. Harris et al., "Validation Concepts for Computer Systems Used in the Manufacture of Drug Products," in Proceedings: Concepts and Principles for the Validation of Computer Systems in the Manufacture and Control of Drug Products (Pharmaceutical Manufacturers Association, Chicago, 1986).
10. PDA, "Process Simulation Testing for Aseptically Filled Products, PDA Technical Report #22," PDA J. Pharm. Sci. Technol.
50 (6), supplement (1996).
11. J. Agalloco, Comments to FDA, submitted Feb. 5, 2008, Docket No. 2007N-0280.
12. Federal Register,
73 (174), pp. 51919–51933, Sept 8, 2008.
13. FDA, Guidance for Industry for the Submission Documentation for Sterilization Process Validation in Applications for Human and
Veterinary Drug Products (Rockville, MD, Nov. 1994).