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Two years ago, the US Food and Drug Administration's Office of Generic Drugs (OGD) developed and implemented a program to test question-based reviews for abbreviated new drug applications (ANDAs). OGD is reviewing the benefits and challenges faced by pharmaceutical firms involved in the initiative to see what changes need to be made going forward.
Two years ago, the US Food and Drug Administration’s Office of Generic Drugs (OGD) developed and implemented a program to test question-based reviews for abbreviated new drug applications (ANDAs). OGD is reviewing the benefits and challenges faced by pharmaceutical firms involved in the initiative to see what changes need to be made going forward. Pharmaceutical Technology spoke to Dr. Aloka Srinivasan, team leader at OGD, about the lessons learned and what industry should expect next.
PharmTech: OGD initiated the question-based review (QbR) process for submitting quality overall summaries (QOS) within ANDAs in 2007. What was the primary reason for this initiative?
Dr. Srinivasan: The question-based review initiative by the Office of Generic Drugs was undertaken to implement the concepts and principles of FDA’s CGMPs for the 21st Century initiative. A second reason for QbR was the ever-increasing workload at OGD. The expectation in OGD is that, by seeking the industry’s response to the critical questions regarding justification for establishing controls, we may be able to reduce the number of deficiencies cited and eventually cut down on the review time.
PharmTech: How many firms submitted QbR applications for ANDAs during the past two years?
Dr. Srinivasan: Currently, almost all the ANDAs submitted to OGD have the question-based review–quality overall summary (QbR-QOS) in Module 2 of the CTD format. We acknowledge the support and cooperation of the generic industry in this respect.
PharmTech: One clear benefit of QbR is the flexibility it allows pharmaceutical firms in defining and justifying the choices they have made when formulating a product. What other benefits does QbR offer industry?
Dr. Srinivasan: I think that a generic industry representative is in a better position to respond to this question. However, based on the feedback we have received from the industry, QbR has helped them in sharing and justifying the information in the submissions, which is generally considered critical for product performance. The QbR has also set the baseline to direct the generic industry toward quality by design (QbD).
PharmTech: Were any benefits gained on the review side for OGD?
Dr. Srinivasan: The reviewers of OGD have benefited greatly from QbR-QOS. The product and process development summaries in QbR-QOS have provided insight into the sponsor’s rationale for product design and development of manufacturing process. Justifications provided in QbR-QOS also have lead to better understanding of the product and process and has reduced the number of deficiencies communicated to ANDA sponsors. Electronic QbR-QOS has saved documentation time and reduced transcriptional errors and assessment time beyond primary review.
PharmTech: Several challenges were identified during the QOS-QbR pilot period as well. For instance, FDA reviewers found that many firms did not fully fill out the product and process development section (Module 3 in the QbR). In addition, some firms justified their choices with a “quality by testing” approach rather than a “quality by design” approach. Why do you think these problems occurred, and what do they mean for the QbR process going forward?
Dr. Srinivasan: In OGD, we consider these as “growing pains” which are common with any shift of paradigm. We are seeing more and more ANDAs with better responses to the questions in QbR-QOS and relevant information regarding pharmaceutical development in the body of data.
PharmTech: What should industry expect next for QbR-based submissions for generic drugs?
Dr. Srinivasan: OGD is working closely with the generic drug industry to move the QbR base submission to the next level; to implement the principles of QbD in the development of the generic products. OGD and the Generic Pharmaceutical Association (GPhA) had a two-day meeting recently to discuss the implementation of QbD for the generic drug industry. The industry’s response to this initiative was very positive. OGD is expecting that this combined effort will provide a QbD platform to address the pharmaceutical development of the generic products.
Dr. Srinivasan will be presenting an FDA Keynote Address at Pharmaceutical Technology’s 3rd Annual Conference next month in Philadelphia. She’ll be discussing the new paradigm for generic drug applications and reviews.
To register or to get more information about Pharmaceutical Technology’s 3rd Annual Conference (Aug. 11-12, Philadelphia, PA), visit the event website.
See related article
FDA Office of Generic Drugs Question-Based Review Initiative: An Update (Journal of Validation Technology article)
Opinions expressed in this interview are those of the authors and do not necessarily reflect the views or policies of the FDA.