Recently I was asked by a client whether they should continue to do Re-Qualifications or change to Continued Process Verification on their qualified cleaning circuits. To answer this, the factors to consider revolve around what the rest of the industry is doing, what inspecting agencies are expecting and what makes the most practical, achievable, and scientifically sound sense. Many of us have considered this question, but what conclusion have we arrived at?
The Poll Results
The question of what other biologics, medical device and pharmaceutical manufacturers are doing regarding the demonstration of continued cleaning effectiveness is one where speculation and generalizations are often made. ProPharma Group has clients coast to coast in the United States making the full spectrum of products and that are under inspection by virtually every regulatory agency world-wide. A simple, anonymous poll was quickly conducted and here are the findings. A total of twenty-three (23) manufacturing sites responded. Of those sites approximately fifty (50) percent are doing a standard protocol driven requalification of their cleaning circuits on frequency based intervals, approximately twenty (20) percent are doing some form of continuous monitoring of the process, and shockingly, thirty (30) percent are doing nothing after initial cleaning performance qualifications.
The high percentage of requalification efforts was completely expected as that protocol based approach of frequency monitoring has been the default for many years in the health products manufacturing industry. The unexpected results were the latter two. Although the Food and Drug Administration (FDA) Guidance on Process Validation has been in effect for the last three (3) years, adoption especially of the Stage Three expectations of Continued Process Verification, has been slow in taking root. Interestingly enough, one-fifth of the health product manufacturers polled have embraced those philosophies.
These manufacturing sites are now pulling samples at the end of each cleaning-in-place (CIP) run as part of a program to demonstrate continued effectiveness. It bears mentioning that these continued process verifications consisted of more than a visual inspection to qualify as a program. Visual inspection post every cleaning has been an expectation since the 1987 FDA Guidance on Cleaning Validation. But most notable is the fact that approximately thirty (30) percent of respondents are doing nothing at all. Those manufacturing sites certainly find themselves at the greatest risk of product safety and compliance expectation failures. Waiting until an adverse event, either with the patient or during the manufacturing process, only puts these manufacturers in a reactive mode that demonstrates little responsibility or process knowledge.
In my next blog, I’ll be covering the different Agency Expectations and exploring the question of what makes practical, achievable and scientifically sound sense.