Remember back in high school or even further back, maybe to junior high, to the kid who seemed cool and interesting—let's call her Marcia Brady. You really wanted to become friendly with her, but you held back. Maybe you were shy, uncertain about her response to you, and in your uncertainty, you decided that she probably didn't want to talk to you anyway. And then you decided she was really stuck up. And then you didn't want to talk to her all that much. And then you were more intimidated than ever.
This nearly universal experience popped into my head recently when I sat in on an impromptu discussion with some industry insiders dissecting the industry's attitude about the US Food and Drug Administration. The discussion started where so many do: Why does pharma so often lag technologically behind other industries? The group offered that the classic answer has always been that pharmaceutical scientists must operate within the tight regulatory strictures of FDA. Pharmaceutical scientists are nervous about process innovation, the usual argument goes, because getting FDA to approve a novel manufacturing approach may delay the overall approval process. Better to stick with a tried-and- true, and previously approved, process.But that answer runs contrary to FDA's recent efforts at transparency as well as its now several-years'-old quality-by-design (QbD) inititative, both of which invite dialogue between industry scientists and regulators. Regulations are proffered in the form of "guidelines" and "guidances" and are left purposely vague precisely because the agency does not want to prescribe methodology. Rather, regulators stress that one size does not fit all. They want manufacturers to tailor their processes to the particular ingredients they're working with. To do that effectively, regulators also encourage manufacturers to understand as much as possible about the chemical and physical properties of the ingredients that make up their formulations. And most important, FDA officials want industrial scientists to share with them details about how the behavior of the ingredients informed their process design.
It seemed to our insiders that rather than embrace flexibility, many in industry are afraid of it and crave more explicit direction from regulators. Some in the industry may feel that flexibility involves too much risk and responsibility. Others may continue to perceive FDA as an enforcement agency, an industrial police force ready to trap and punish innovators. Clearly, that mindset has to change before QbD becomes widely adopted. Our insiders predicted that it may take a full 10 years before industry "dinosaurs" become extinct, which will pave the way for QbD to become a nearly universal modus operandi.
If anything brought home FDA's genuine interest in reaching out to industrial scientists, it was a panel discussion organized by Pharmaceutical Technology at Interphex 2010 in which three FDA staffers made suggestions for new and abbreviated drug applications. The unmistakable message in that and the subsequent Q&A session was that agency officials want manufacturers to know and understand their ingredients as they pass through the manufacturing process.
And FDA wants you to share your rationale with them—before filing an application, while the application is undergoing regulatory assessment, and afterward if you make changes in the process, ingredients, formulation, suppliers, or delivery devices. FDA wants you to talk to them. They really, really do.
Michelle Hoffman is editor-in-chief of Pharmaceutical Technology. Send your thoughts and story ideas to [email protected]