Process verification and capability analysis in pharmaceutical manufacturing

ANNE MILLEY: Before joining Tunnell Consulting, you oversaw process robustness strategy at Merck, so could you tell us a little bit more about that?

JULIA O'NEILL: Yes. This problem I described about 10 years ago of working on a challenging issue in vaccine manufacturing—we had to learn a lot in order to solve that problem. Like I said, we assembled a team of people, and we actually turned that into a standing team that, for some time, in vaccine manufacturing at Merck, that we called the SWAT Team, and our mission was to solve some of the most challenging issues.

But as we made progress in resolving those issues, we wanted to move to a more proactive approach. And we were very happy that some of the supply issues that had been plaguing us in vaccines, we had been able to conquer those. What I saw was that those same techniques that we had used for solving problems could also be used prospectively to assess process capability, to identify issues with some advance notice, and get ahead of them. The timing was great, because in January of 2011, the FDA issued an updated guidance on process validation, which very strongly advocated for more use of statistics in pharmaceutical manufacturing.

So it was a convergence. The timing was great. So what we did is we took the SWAT Team and repurposed it for development and implementation of a continued process verification for all of Merck's vaccines. And that really went well, and we did that globally. We were working with all of Merck's sites in different parts of the world, and that was a success.

Right at that time, as we had finished the vaccine, continued process verification implementation, Merck was getting ready to launch Keytruda. That was manufactured globally as well, and you've probably heard that in the news. It's just an amazing product. For some people with cancer, it has been a complete lifesaver, and it's growing in uses daily, it seems.

So we use that same monitoring process, using JMP all the way, by the way, to do updated control charts of the critical quality attributes and some other parameters for each process. We started with vaccines, extended it to biologics, primarily focusing on Keytruda.

At that point, the small molecule and large molecule tech ops were getting joined at Merck. So we took that on to apply to all of Merck's human health products. At that time, continued process verification had already been established for all of them, but we took on the robustness oversight. So we did things like process capability assessment for all critical quality attributes for the top 50 products for Merck.

ANNE MILLEY: Wow, so really high standards and metrics tailored to look at maintaining those high standards.

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