QbD Case Study Will Push Limits

When the final version of the Quality by Design (QbD) case study is made public this summer, it will be an aspirational document, says Ken Seamon, PhD, one of the project’s facilitators. “If the regulatory authorities read our final document and said ‘yes, this is all fine,’ we will have failed,” he said.

“We have encouraged the teams to push the envelope, to capture a future state based on novel thinking,” said Seamon, a former FDA official who spent 10 years at Immunex and Amgen and now is a senior associate at the Biotechnology Institute at Cambridge University in the UK.

But avoiding regulatory conservatism has been challenging, he said, because everyone is used to considering ideas in terms of how regulatory authorities will evaluate them. He has often reminded case study participants not to ask, How would the regulators react to this? but rather, Does the science support it?

Not a Mock Filing

The case study, currently supported by a non-profit spun out of Conformia Software, is known to many in the industry as the “mock QbD filing,” but Seamon stressed that this is a misnomer, based on a misunderstanding of the goals of the project.

“We are not preparing something for which we are seeking regulatory approval, nor should the approach taken be seen as the only way to implement the key principles of Quality by Design,” he emphasized. “Our goal is to provide examples and stimulate discussion.”

Although Seamon said it is too early to reveal details of the draft document, he noted that one of the topics that elicited a lot of discussion was the definition of critical quality attributes and critical process parameters.

“One of the questions was about whether you should describe parameters as ‘critical’ and ‘non-critical’ or simply rank them,” he said. “But even if you choose to rank them, you still have to draw a cut off at some point to determine how parameters will be monitored in your control strategy.”

Another important outcome of the discussions has been encouraging everyone to view each unit operation in the context of the overall process and product. “The concept of QbD is forcing a more robust alignment of all unit operations and the control strategy,” he said. “It encourages process development teams to look at their work more holistically.”

Following a three-day meeting in Bethesda, MD, in early March, the group expects to have the first draft of its report ready by the end of April, and the final document ready for the public sometime this summer.

The case study, which originated from Conformia’s Cooperative Research and Development Agreement (CRADA) with the US Food and Drug Administration, involves 35 members from seven companies: Abbott, Amgen, Eli Lilly, Genentech, GlaxoSmithKline, MedImmune (AstraZeneca), and Pfizer.

The biologics project follows the ACE small-molecule QbD case study completed in 2008 through a Conformia–FDA CRADA.