FDA develops science- and risk-based QbR system to assess product quality.

WASHINGTON -- The implementation of Question-based-Review (QbR) for ANDA evaluation is part of FDA's initiative to adopt a science-based approach to review.

Integrating QbR for chemistry, manufacturing and controls (CMC) evaluation of new drug applications will allow reviewers to not only assess critical formulation and manufacturing process variables, but to identify potential risks involved with the design and manufacturing of the product. Ensuring product quality through performance-based specifications, QbR promotes continuous improvement, enhances review quality and eventually could reduce CMC supplements.

First introduced in 2005, QbR incorporates many of the guidelines outlined in FDA's "Pharmaceutical GMPs for the 21st Century: A Risk-Based Approach." QbR was designed to streamline the ANDA submission and review process by encouraging generic firms to organize applications with a Common Technical Document (CTD), a widely-used submission format. The unique approach to ANDA review also addresses FDA's increasing workload and proposes a way to best use agency resources.

A draft guidance released in August, entitled "Submission of Documentation in Applications for Parametric Release of Human and Veterinary Drug Products Terminally Sterilized by Moist Heat Processes," was developed to help manufacturers meet preapproved parameters for the sterilization process. The document includes Quality by Design (QbD) concepts in its guidelines on control strategy, risk management, process understanding and prior knowledge.

According to the generics office, QbD will be a consistent theme in the QbR guidance, which will focus heavily on the Quality Overall Summary (QOS). Defining, designing, identifying and control--fundamental QbD concepts--will be integral to the QOS.

"Mainly, we want to incorporate the QbD concepts into the QbR," said Neal J. Sweeney, Ph.D., OGD Supervisory Microbiologist, at the 2008 Generic Pharmaceutical Assn. (GPhA) Fall Technical Conference Oct. 30. "Our focus would be the QOS."

"You implement QbD in product development, in process development and in manufacturing," adds OGD Deputy Director for Science Lawrence Yu, Ph.D. "Product and process development does help our reviewers."

Yu says OGD is working towards a fully electronic submission system. "The old format is not an efficient way to go." Generic firms are strongly recommended to submit their ANDAs in the electronic CTD format to facilitate the implementation of the QbR and to avoid undue delays in the approval of their applications.

Thorough, well-organized submissions are more likely to secure approval, and in less time than it would take for reviewers to address unanswered questions with pharmaceutical companies. "We emphasize time and time again the QOS," said Yu. "High-quality submissions will guarantee fast approval and reduced review time."

One of the reasons submissions are held up in review is discrepancy between the QOS and submitted data. Inconsistency, often due to multiple contributors and writers, is a major concern for reviewers. "In my mind, defining [the] accurate target product quality profile is the most important step," Yu said.

By Carrie Nathans, Managing Editor