I recently spoke with a biopharma consultant based in Europe. Driving to visit a client, he had just come from a workshop on Quality by Design in Frankfurt and could not hide his excitement about what he’d seen.
The meeting, hosted by PDA and EFPIA, the European drug industry association, introduced several mock examples of QbD implementations for analysis and discussion. The examples were based on actual QbD projects taking place—for instance, in the production of lyophilized injectables and monoclonal antibody API's. The workshop’s organizers likened them to concept cars, not yet ready for the road, that offer a tantalizing glimpse at what the future holds. Pending final tweaking, the examples will be made public late this year or early next.
As this consultant sped through the Belgian countryside, he sounded as if he had been given a key to the future. He works with smaller manufacturers, many of whom had no Quality by Design strategy whatsoever, much less experience with implementing it. With these mock examples, he said, he now had something tangible to show how Quality by Design could work for them, given their limited budgets and workforces.
QbD has had plenty of fanfare since it was thrust upon the industry by FDA three years ago, but it has evolved with a schism—between major manufacturers who have the time and resources to “get” and participate in the development of QbD, and those who have waited patiently for evidence that QbD will work for them.
Volker Eck, Senior Director, Science and Technology at PDA, also left the Frankfurt meeting on a high. There was agreement among attendees that the examples were practical models for what kind of data needs to be developed, and what should be contained within a common technical document, Eck told me recently. (See “Is QbD Still Lost in Translation?”)
But the examples by no means present a complete picture, Eck says. Participants noted that it would be difficult to translate the information within the examples to their daily work and products and processes they currently have in development. QbD is still “very blurry” for many, Eck says.
Many at the meeting expressed concern that the time and manpower needed in the early stages of drug development to collect and assess the requisite data would be a severe burden. Eck paraphrases their questions: “What is the investment you need and what is the return? Would development take 15 years instead of five, or 200 people instead of 20?”
The answer of course is no. The point of QbD is to simplify, not magnify, whether in terms of process development or quality control. At least the meeting communicated one thing clearly, Eck says: “You don’t need sophisticated tools and a whole statistics department to achieve substantial improvement.”
As more examples come forth, this message should become loud and clear. In November, a case study applying QbD to monoclonal antibody development will be released at the ISPE annual meeting. Another meeting held in London earlier this fall, hosted by EFPIA and EMEA, also focused on QbD case studies, presented by QbD leaders at major manufacturers (among them Gert Thurau of Merck, Graham Cook of Wyeth, Jason Hampson of Amgen) in tandem with European regulatory representatives. Pfizer’s Liz Coulson, for example, presented alongside French regulators on using the tenets of QbD for Continuous Quality Verification.
A host of presentations from the London meeting can be found at http://www.efpia.eu/Content/Default.asp?PageID=706; offering hi-res snapshots of how QbD can be implemented, but they’re far from a complete picture. It may be another five years or more before case studies become available for a comprehensive cradle-to-grave QbD implementation.
But those who are waiting for QbD concept cars to roll off the production lines are missing the point. At the London meeting, EMEA’s Dr. Jean-Louis Robert, emphasized that there is no one way to pursue QbD. How it is translated will depend on the complexity of the process and product, he said, and on the opportunities chosen or wanted by the applicant. As Robert said, “QbD is not a slogan. Don’t claim it . . . Just do it.”
The true test of QbD will not be how it is discussed in the offices of FDA or conference halls in Frankfurt, or how it is written in ICH documents or mock examples, but in how it plays out in Peoria, Ghent, Qingxi, or Chennai.