Conclusion

The draft guidance about process validation is refreshingly simple and supports good science, yet it is demanding with respect to the level of effort required to properly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 The draft guidance is not perfect, and improvement and clarification are certainly necessary, especially regarding the guidance's application to sterile products.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and industry proceed with special caution in the areas reviewed above because blind adherence to the concepts of the draft guidance will likely lead many astray.

References

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 FDA, Draft Guidance for Industry—Process Validation: General Principles and Practices (Rockville, MD, Nov. 2008).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.

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8. J. Agalloco, "Compliance Risk Management: Using a Top Down Validation Approach," Pharm. Technol. 32 (7), 70–78 (2008).

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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).