In all toil there is profit.

Today let’s examine the emerging warning letter trends in 2020. It may be too early, however understating them, promptly learning, and taking action based on other's failures may help reduce your organization's exposure to regulatory risks. From our past review of warning letter trends (2017-2018), it was evident that lack of a well-developed process validation lifecycle approach which includes Stage 3 (Continued Process Verification)/CPV program contributed significantly to the issuance of a warning letter:

A well-established Stage 3 (CPV) contributes to effective continuous improvement initiatives and minimizes process-related quality failures that have been highlighted by the FDA as the biggest reason for drug shortages in the US. Beyond ensuring availability, the data sets and analysis from the proactive Stage 3 (CPV) program are utilized for data-driven formulation development of similar products. The CPV stage constitutes the largest opportunity to gather data to build product/process knowledge, an organizational asset leading to potential product improvements, innovations, and intellectual property.

Enhanced product/process knowledge gained by the collection and evaluation of Stage 3 (CPV) data provides manufacturers with invaluable opportunities. Our case studies provide some applications of CPV data. Multivariate analysis of extensive batch data provides invaluable data-driven insights to enhance your control strategy.

A general statement that I still come across often at organizations is that “Annual Product Quality Review (APQR) takes care of our Stage 3 continued process verification (CPV) requirements”. Let’s be crystal clear, it does not, unlike APQR the Stage 3 (CPV) program requires system/s for detecting drifts sooner (batch after batch at a minimum). However, the ongoing Stage 3b data and assessments may be utilized for the completion of APQR report sections. The US FDA has used the same language for PV in warning letters! Recommending the use of a consultant, indicating a lack of awareness/slow adoption. Below are three examples:

The US FDA Process Validation guidance (2011) is a fundamental shift in the Process Validation approach. The latest 2020 Warning Letter trends continue to indicate that there is an evident gap in understanding and adoption of the basic ideas. 

Do you believe your organization has truly adopted and implemented process validation lifecycle concepts? Are the current process validation steps you follow fundamentally different from what you were used to in the past?

Is your Stage 3 (CPV) program capable of detecting signals and truly minimizing product/process failures? Do you apply statistical methods to support data-driven PV (Stage 1(QbD), Stage 2 (PPQ) and Stage 3 (CPV)) conclusions?

Feel free to connect with me to know why the lifecycle approach fits PV & what are the expectations. Recent industry textbooks and guidance that I have authored for your reference:

Solid Oral Dose Process Validation

PV Good Practice Guide

See my other posts.