“If QbD is the ocean of knowledge, then generics are just pulling out of the driveway. We haven’t even seen the beach yet,” said Aloka Srinivasan, PhD, a team leader at the FDA Office of Generics (OGD) and a speaker at today’s keynote session of the 3rd Annual Pharmaceutical Technology Conference in Philadelphia, PA.

Dr. Srinivasan and her colleague Robert Iser, also a team leader at OGD, spoke to the PharmTech audience today about the question-based review (QbR) initiatve started by OGD in 2007 and how it’s being used as a “diving board” into QbD implementation for the generic drug industry. The idea behind QbR is to get a company’s thought process “into the application.” Similar to the messages delivered at yesterday’s sessions, Srinivasan and Iser pointed out that industry needs to change the way it thinks. They spoke about how quality is a life cycle requirement; it shouldn’t start when a failure occurs, which tends to be the traditional pharma industry response.

To date, more than 95% of generic drug applications, or ANDAs, are being submitted to FDA in the QbR format. This is good news, they report, but generic drug applicants still need to spend more time on understanding their manufacturing processes. Just because there is already an innovator product on the market doesn’t mean that information can simply be copied. Although the route of administration and dosage strength may be the same, generic firms still need to look at their own product design, process, container-closure systems, and quality attributes. Comprehensive impurity testing, excipient comparability testing, and scale-up testing are of utmost importance.

This is exactly how QbD can enter the process for generics early on, explained Iser. Working QbD into the product design to help understand what you’re making, the product’s purpose (including the ultimate consumer), and how to make it with upfront testing is key to having a quality-based product. You can’t just tell FDA that your product is equivalent based on certain studies, you have to demonstrate how it is equivalent, you have to justify it, said the speakers. Including any failed bio studies with ANDA submissions—a requirement as of July 15, 2009—will go a long way in this regard.

FDA does foresee QbD being applied to the generic drug industry in the future, said Srinivasan and Iser, but because of the unique timing/patent issues and design space issues, there are additional considerations that need to be worked out. Right now, the QbR format is meant to help the generic industry start thinking about the concepts needed for science and risk-based approaches to product developing and manufacturing. The next stage is to implement these concepts, said the speakers. But the fundamental questions to keep in mind for now are:

• Is your product designed to ensure the desired performance?
• Are you able to scale up and still meet that desired peformance?
• And are you able to manufacture that product within the defined quality paremeters over time?