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The Pharma Quality by Design blog at this URL will no longer be active. We've moved all of our posting to our redesigned PharmaQbD home page. Please visit us there for daily updates on things happening in the QbD world.

Regards,

The PharmaQbD Team

QbD Pioneer Afnan to Leave FDA

One of the true thought leaders behind pharma's PAT and Quality by Design movement, Ali Afnan, PhD, has decided to leave his post at FDA. In today's On Pharma blog, Agnes Shanley looks back at Afnan's key role within FDA, and muses about his reasons for moving on.

QbD Comes to India

Two good QbD seminars have been slated for March in Hyderabad and Mumbai, featuring consultant Line Lundsberg and Dhaval Trivedi of Intas Pharmaceuticals. Click here for more.

Design for Six Sigma: A Model Partner for QbD

When the concept of Six Sigma was developed at Motorola in the 1980's, its practitioners soon realized it had an inherent flaw that would preclude many manufacturers achieving six sigma levels of performance. Once a process reached five sigma levels, there was often little financial incentive to push ahead to the six sigma threshold. As consultant Murray Adams explains in our recently posted article, "Design for Six Sigma: A Potent Supplement for QbD", "financial gain of further improvement is frequently outweighed by the cost of implementation." The dilemma was called the five sigma barrier.

In a heavily regulated industry such as pharma, however, settling for pretty good will not do. Adams continues: " . . . a 5 sigma process may not be sufficient for many critical process steps. In fact, in the pharmaceutical industry, even the 'world class' six sigma standard (3.4 dpm) is inadequate with respect to the occurrence of some critical defects. Given the limitations of the 5 sigma barrier, how can we achieve an appropriate level of process performance while maintaining a competitive operating cost?"

The answer that the Motorola folks came up with was to adapt some of the tools of Six Sigma for the early stages of product design--thus, Design for Six Sigma was born. There isn't a good understanding of the differences between DfSS and Six Sigma in the drug industry, Adams believes, but pharmaceutical development teams would be well served to incorporate more DfSS into their practices. Once they do, he says, they'll find that many of its tools--such as Monte Carlo Simulation, Parameter Design, and Tolerance Allocation--complement Quality by Design concepts and support initiatives being undertaken under the QbD umbrella.

Those interested in learning more on Monte Carlo Simulation should also read "Leaning on Six Sigma and Predictive Modeling in a New Industry Paradigm," by Oracle's John Danese and Fred Ciochetto. This PharmaManufacturing.com article also includes references to other resources on the topic.

IFPAC: Analyze This

If you're into PAT and QbD, you'd be hard-pressed to find a trade show with more relevant sessions and productive discussion than the annual IFPAC show. Over the years IFPAC has gotten more and more pharma-centric, and this year's Baltimore event is no different, with GSK's Theodora Kourti getting things started, followed by FDA's Vincent Vilker and Helen Winkle, and then a host of other pharma presenters over the next few days. Click on the preliminary program link on the IFPAC home page.

Is Tech Transfer Broken? Can the Principles of QbD Fix It?

While scant data exists to suggest how efficient, or inefficient, technology transfer is within drug manufacturers' development efforts, it's pretty clear that most companies hardly have tech transfer down pat, and still others just don't get it at all. That's a recurring theme in a podcast posted on PharmaManufacturing.com yesterday, in which tech transfer experts Stephen Perry, Russ Somma, Emil Ciurczak, and Paul McKenzie offer harsh criticisms of the tech transfer projects they've witnessed first hand. And thankfully they offer advice as well.

Sometimes the problems are simple--development teams just fail to write critical information down in their notebooks, "something they should have learned in college!" Ciurczak says. But the experts also make clear that practices associated with Quality by Design--namely, proactive risk assessment and data management--can eliminate problems in the early stages of development and facilitate later transfer. Perry notes how developers typically send data on successful process studies to their partners, but not data from failed studies that can be just as enlightening.

Perry is the author of Pharmaceutical Manufacturing's January cover story on doing tech transfer the right way, and he suggests that one thing that often dooms tech transfer projects (internal or external) is the inability of the technology sender to share necessary information with its partner:

There is no such thing as “too much” or “too detailed” information. Such dedicated tools as assay summaries, detailed process descriptions, and bills of materials should be created and used . Other information from the sender, such as regulatory submissions, development reports, raw data, validation reports, etc., can be extremely useful. This work would have to be done anyway as part of the future process validation and to support regulatory submissions.

One of Somma's mantras is simplifying tech transfer, which seems to run counter to the idea of providing as much detailed information as possible. He, as well as Oracle's Arvindh Balakrishnan, explain how this paradoxical challenge can be overcome in a podcast which is now the lead feature on our PharmaQbD.com site.

Finally, Centocor's McKenzie is a proponent of recipe-based development as a means of ensuring consistency throughout scaleup and as handoff occurs between partners. Here is a summary of McKenzie's philosophy from last fall's Bioprocess International conference, as well as a blast from the past: Pharmaceutical Manufacturing's September 2007 cover story featuring McKenzie in his days with BMS.

The success or failure of tech transfer is hard to measure, but that doesn't mean that it shouldn't be a key focus of initiatives to accelerate and lessen the costs of drug development.

QbD for Biotech in Three Parts

Biopharm International has just published the third installment of a three-part series on Quality by Design for biotech products, written by members of PhRMA's Biologics and Biotechnology Leadership Committee. Links are as follows: Part 1, Part 2, and Part 3.