The 21st Century Initiative – PAT and Validation

Written by Frank Jakubiec - Validation Engineer

Late last year, while exhibiting for ISPE at the New Jersey Science & Engineering Festival (October, 2010 in Clifton, NJ), I had a short discussion with an attendee regarding the adoption of Process Analytical Technology (PAT) and its impact on Validation.  While the person was of the opinion that PAT will reduce or eliminate the need for validation, I contend that the adoption of PAT is an opportunity to incorporate validation into processes at an early stage in their life cycle.

The FDA considers PAT to be ‘a system for designing, analyzing, and controlling manufacturing through timely measurements (i.e., during processing) of critical quality and performance attributes of raw and in-process materials and processes, with the goal of ensuring final product quality.’1  Practically speaking, PAT is a form of continuous process monitoring that can include feedback loops connected to process controls.  Thus, PAT appears to be a potentially powerful and comprehensive tool for pharmaceutical research, development, and production.

The FDA’s position on ensuring drug quality includes the following two relevant points:

• Quality cannot be adequately assured merely by in-process and finished-product inspection or testing.
• Each step of a manufacturing process is controlled to assure that the finished product meets all quality attributes including specifications.2

Viewing the FDA’s definition of PAT through the lens of the above two points, it is clear that adopting PAT is not, in and of itself, the ‘magic bullet’ for ensuring final product quality.  PAT is merely one part of the toolkit that the FDA intends to be used across the industry.

 

Qualification and validation are generally necessary to demonstrate and document control over the design and performance of one’s products and processes.  Despite its capabilities, when PAT is implemented, it must be validated for it to provide any value and contribute adequately to process and product quality, performance, and understanding. In addition to being used during production, PAT can be introduced into the early stages of the Product Development Life Cycle and, when the implementation is properly qualified and validated, the data obtained can be leveraged in many aspects of your operations including: Product and Process Design, Risk Assessment and Dynamic Control Plans, Root Cause Analysis and CAPA, Process Optimization, Qualifications/Validations, Internal/External Audits, and Regulatory Submissions.

The FDA’s 21st Century Initiative, most notably PAT, is part of the paradigm shift from Quality by Testing to Quality by Design, which will be discussed in an upcoming blog post.

¹United States. FDA. Guidance for Industry: PAT — A Framework for Innovative Pharmaceutical Development, Manufacturing, and Quality Assurance. Washington: GPO, 2004.
²United States. FDA. Guidance for Industry: Process Validation: General Principles and Practices. Washington: GPO, 2011.