19/20 May 2021
GMP News No. 411
22 April 2004
New FDAInitiative on Process Validation
Effective March 12, 2004, FDA revised a long-standing policy documentregarding the validation of pharmaceutical manufacturing processes fordrugs that are subject to pre-market approval requirements. This policyguide is now titled ProcessValidation Requirements for Drug Products and Active PharmaceuticalIngredients Subject to Pre-Market Approval (formerly titledProcess Validation Requirements for Drug Products Subject to Pre-MarketApproval). Compliance Policy Guides (CPG) are intended for agencystaff and are for the purpose of consolidating agency compliance policydecisions.
As with the previous version of this policy guide, the new versionreaffirms that agency drug product pre-market review units may approveapplications for marketing before a firm has manufactured one or moreconformance batches at commercial scale (also sometimes referred to as"validation" batches). The revised CPG again recognizes certainconditions under which a firm may market batches of drugs while gatheringdata to confirm the validity of the manufacturing process.
New to this version is the recognition of the role of emerging advancedengineering principles and control technologies in ensuring batch quality.For drugs produced using these new principles and technologies, this CPGprovides for possible exceptions to the need for manufacturing multipleconformance batches prior to initial marketing. This version also deletesthe previous reference to "three" validation (or conformance)batches at commercial scale as adequate minimum proof of process validity- a number is no longer suggested. Also, this version further clarifiesthe importance of post-market information gathering especially for thosebatches released to market concurrent with the manufacture of the initialconformance batches. And, finally, this version adds a reference to thecurrently recognized standard for CGMPs in the manufacture of activepharmaceutical ingredients: Guidance for Industry, Q7A, GMP Guidance forActive Pharmaceutical Ingredients, issued August 2001.
This is an important first step in the Agency's plan to addressthe area of process validation. The next step will be to update the Guidelineon General Principles of Process Validation(May 1987), to reflect modern manufacturing principles, technology,and science. This update will be revised in accordance with the agency'sGood Guidance Practice procedures and include public notice and commentbefore being finalized. The final step of this process will be addressingthe proposed revisions of the CGMPs, the Federal Register dated May3,1996, Current Good Manufacturing Practice; Proposed Amendment ofCertain requirements for Finished Pharmaceuticals. This effort isbeing taken in concert with FDA's initiative on the regulation ofpharmaceutical quality known as "Pharmaceutical cGMPs for the 21stCentury: A Risk-Based Approach." Progress on these issues willbe included in future announcements on the initiative.