"Continued Process Verification" brings 1987 guidance into 21st century.

WASHINGTON -- The old saying, "if it isn't broken, don't fix it," doesn't always apply to pharmaceutical manufacturing, especially when the lifecycle approach is quickly becoming standard practice. Continuous assessment and improvement are now bona fide responsibilities, not optional efforts for gaining an "edge" over other companies.

During a Jan. 13, 2009, ISPE webinar, Grace McNally of CDER's Office of Compliance discussed FDA's "Process Validation: General Principles and Practices" issued November 2008. When asked about how the guidance applied to existing products and processes, McNally advised participants to focus on Continued Process Verification, the final and ongoing phase of process validation.

"If you're in a position of reevaluating for whatever reason, I would direct your attention to Stage 3," said McNally. "If you have an existing product or process that you're revalidating, I would assume there was some trigger for that. So it would make sense at that point to incorporate the principles in this new guidance. I'm not suggesting if you have a process that's performing well, that you run out and begin R&D all over for each of these process and product lines. You may want to consider some sort of risk analysis for each of your product lines and processes and see what can and should be done to improve them, if that seems necessary."

McNally pointed to Continued Process Verification as a system for ensuring process control over the long term. Data evaluation is first and foremost. The guidelines recommend ongoing testing and assessment, at least on an annual basis, of product specifications and control procedures:

"An ongoing program to collect and analyze product and process data that relate to product quality must be established [[section] 211.180(e)]. The data collected should include relevant process trends and quality of incoming materials or components, in-process material, and finished products. The data should be statistically trended and reviewed by trained personnel. The information collected should verify that the critical quality attributes are being controlled throughout the process."

Timely monitoring is a crucial element in ongoing process verification. Manufacturers must constantly check performance parameters, product characteristics, personnel training and facility conditions. "There may be a need to go back to the design stage at some point, do additional studies or experiments to make that change and then keep that process in a state of control," said McNally.

In the final stage of process validation, the goal is to maintain or improve control and reduce product and process variability. When alterations to the process are deemed necessary as a result of testing and/or monitoring, the proposed changes must be documented and explained:

"Data gathered during this stage might suggest ways to improve and/or optimize the process by altering some aspect of the process or product such as the operating conditions (ranges and set-points), process controls or in-process material characteristics." A description of the planned change, a well-justified rationale for the change, an implementation plan, and quality unit approval before implementation must be documented (21 CFR 211.100). Depending on the significance to product quality, modifications may warrant performing additional process design and process qualification activities."

By Carrie Nathans 

Managing Editor