Archive for month: December, 2014

Guidance on Process validation began in 1987 to address consumer recalls and complaints and assure consumers that their products were consistently made with the utmost quality. This guidance underwent some significant fundamental changes in 2011. If processes were “validated” as prescribed by the FDA guidance then why were products being recalled? Why were customers complaining about their products? Why was this happening? When something happens we ask why and get to the root cause(s).

The traditional approach for process validation was a snapshot in time. At a point in time a process demonstrated that it could achieve and maintain a state of control and consistently manufacture a particular product within prescribed acceptance criteria and quality standards. Controls were established to monitor the process and critical operating and performance parameters were identified and reproduced for a prescribed number of batches.

The FDA wanted to see more emphasis on process monitoring and demonstrating statistical control after you “validated” a process. An enhanced approach – a life-cycle approach was implemented and traditional process validation was divided into three stages/phases. Traditional process validation would correspond to Stage 2 activities. The transition from Stage 2 to Stage 3 is analogous to technology transfer to commercial routine manufacture. Stage 3 is the continuous process verification/validation of the commercial process.

Stage 1 Process Design, ensuring the work is down upfront to characterize and consistently reproduce within certain operating and performance parameters.

Stage 2: Process Qualification, qualifying equipment and utilities, performing process performance qualification (traditional process validation) ensuring the process is able to meet predetermined operating and performance parameters.

Stage 3: Continued Process Verification, ongoing monitoring of the process to ensure it continues to operate within established operating and performance parameters.

Validation is no longer a snapshot in time, it is composed of three stages, and each builds upon the other yet remains fluid. There is constant interplay between stages. Systems and process should be periodically evaluated to verify that they are still operating in a valid state. As experience is gained in commercial routine manufacturing, opportunities for improvements should be sought based on periodic review and evaluation, operational and performance data, and root-cause analysis of failures.

To maintain and control the manufacturing process, the focus had to become on process knowledge and process understanding throughout the life-cycle of the product. Understand and measure inherent product/process variability. A control strategy has to be developed to explain and justify how the product quality is managed and ensuring the operating and performance parameters remains in statistical control. Process control generates product consistency and quality. Process monitoring will provide the information needed to further understand the product/process and give you the information to refine your control strategy. In a feedback process, the continuous process verification is a key component assuring the ongoing effectiveness of the control strategy.

Some of my sources.

For the full article on Why did FDA change their Guideline on Process Validation? Click on http://www.gmp-compliance.org/eca_news_2600.html

Pharmaceutical Engineering Jan/Feb 2012   Control Strategy as the keystone of the product life-cycle, from product/process understanding to continuous process verification and improvement.

PV guidance, check the CDER guidance page at http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm, the CBER guidance page at http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/default.htm, or the CVM guidance page at http://www.fda.gov/AnimalVeterinary/GuidanceComplianceEnforcement/GuidanceforIndustry/default.htm

Written By: Lisa Conti, Senior Consultant

ICQ Consultants, Corp.

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