Pharmaceutical & Medical Packaging News staff

By Kevin O’Donnell
Director and Chief Technical Adviser to Industry, SCA Packaging N.A., Thermo-Safe Brands (Arlington Heights, IL). 

FDA defines validation in its “Guideline on General Principles of Process Validation; CDER, CBER, and CDRH” (May 1987), as follows:

“Establishing documented evidence which provides a high degree of assurance that a specific process will consistently produce a product meeting its predetermined specifications and quality attributes.”

FDA’s Center for Drug Evaluation and Research (CDER) “General Principles of Process Validation” is the process most commonly applied to developing packaging. Unfortunately, packaging and distribution do not fall neatly into CDER’s definition, as they were not intended to be elements of that process. Because no other process has ever been established, the industry and PDA’s Pharmaceutical Cold Chain Discussion Group (PCCDG) Technical Report #39 use it as current best practice, although slightly modified to a CQ/OQ/PQ process.

CDER General Principles of Process Validation requires the following:

Component Qualification (CQ; covers materials and components in controlled manufacturing that meet specifications). Manufacturers must establish “confidence that ancillary components are capable of consistently operating within established limits and tolerances.”

Operating Qualification (OQ; covers repeatable testing in a controlled environment with limited variability inputs). Manufacturers must establish “confidence that the process is effective and reproducible.”

Performance Qualification (PQ; covers real-world shipments through an uncontrolled distribution system). Manufacturers must establish “confidence through appropriate testing that the product produced by a specified process meets all release requirements for functionality.”

When the criteria of a CQ/OQ/PQ process are successfully met, the entire process is considered validated.

PCCDG, Technical Report #39, defines qualification as “documented testing that demonstrates with a high degree of assurance that a specific process will meet its pre-determined acceptance criteria.” It defines validation as “documented testing, performed under highly controlled conditions, which demonstrates a process consistently produces a result meeting pre-determined acceptance criteria.”

Herein lies a bit of a contradiction. The CQ and OQ are validated processes, but the PQ can only be a qualified process. Regardless of this contradiction in definitions, adhering to CDER’s guidance is preferable. Performing an OQ, that portion of FDA’s CDER General Principles of Process Validation requirement, which also meets USP’s General Chapter <1079> guidance and Technical Report #39, in and of itself is not, in the eyes of FDA, a validation. It needs to be built on a CQ and followed up with a PQ.

Once the customer accepts that the predetermined criteria for the CQ and OQ are met, they, and only they, may determine that they have validated packaging. After successfully completing the PQ, the customer may declare that the packaging is validated and the overall process is qualified.