Genentech has taken a lead role in advancing the state of Quality by Design for biopharmaceuticals. At this week's BIO conference, Lynne Krummen, Genentech’s senior director of regulatory affairs, shared information on her company’s participation in FDA’s pilot program for biologics QbD. (Pfizer's Amit Banerjee also spoke on Bio QbD; click here for a summary of both talks.) The company has gotten two proposals—one for a new product, one for an expanded change protocol on an approved drug—accepted into the program, though it will be some time before it files for approval with the Agency, she says.

Regarding the drug for the new biologics license application (BLA), Krummen did not share proprietary details but did say that it is MAb-based and that Genentech is leveraging its history and development of MAbs. It is also in the process of applying risk assessment tools to identify Critical Quality Attributes (CQA’s), identify process parameters, Critical Process Parameters (CPP’s) and Design Space, and leveraging the above to develop an appropriate process control strategy.

For the change protocol, Genentech is proposing an “expanded comparability protocol,” a mechanism that FDA has established (and is under consideration in the E.U.). It involves working closely with regulators in the U.S. and E.U. on Design Space issues. Krummen also stated that the manufacturing facility that will eventually receive the product has previously been inspected by FDA and is in cGMP compliance.

Next, Krummen discussed the efforts of the CMC Working Group, comprising representatives from her company, as well as Pfizer, GlaxoSmithKline, Eli Lilly, MedImmune, Amgen, and Abbott.

The group’s current case study is based on a fictitious antibody drug substance and drug product call “A-MAb”, Krummen noted. The case study is being designed to illustrate key principles of QbD beyond those presented in last year's ACE case study, and will be available as a teaching tool for industry and agencies.

Why MAb? In order to exploit the large amount of product and process knowledge that’s already available, she says. The goals of the study are to provide:
•    examples of CQA’s
•    Various ways to treat data
•    Information on how to categorize risk
•    Examples of how a design space can be articulated in the context of a filing a risk-based, lifecycle approach to managing changes to DS/DP.

“It’s not a filing . . . not intended to be the gold standard,” Krummen says of the A-MAb study. “It’s structured like a book chapter; it will be cut down, and showcase different tools, different approaches, and different levels of data.”

The case study is expected to be published late this summer, she says, and we'll be sure to publish it as well.

--PWT