Risk Based Approaches To Establishing Sample Sizes For Process Validation

This e-book is a compilation of various statistically based techniques to help determine risk-based sample sizes to support process validation activities. Process validation is one of the most commonly cited 483 Inspectional Observations issued by the FDA. The citations often reveal the organization failed to “ensure that when the results of a process cannot be fully verified by subsequent inspection and test, the process shall be validated with a high degree of assurance and approved according to established procedure” (21 CFR 820.75 – Process validation).

This guide is intended to aid the practitioner avoid regulatory compliance issues. To that end, each technique provides the context for its application, formula(s), variables, and a fully worked example to help understand and apply the technique. Additionally, each technique demonstrates the linkage to risk to help demonstrate “a high degree of assurance.”

I want to stress that different inspection, confidence, reliability, and risk levels should be used based upon your organization’s risk acceptance determination threshold, industry practice, guidance documents, and regulatory requirements.

The methods presented in this guide have been used and successfully defended during audits and inspections. I cannot emphasize enough the importance of proceduralizing (documenting) the statistical methods and rationale your organization uses for process validation activities.

Hopefully, the techniques presented here will help ensure the medical products produced by your organization are safe and effective.