FDA Exploring Data-Driven Quality Reviews To Speed Generic Approvals

FDA is seeking input from an advisory committee on the use of a more data-driven model the agency is exploring to standardize quality assessment in generic drug reviews. Agency officials explain that model could help expedite the review of generic drugs to meet review goals under GDUFA II. 

FDA will be getting feedback from advisors next month on plans for a more data-driven model approach to guiding and expediting the quality aspects of generic drug reviews.

FDA's Pharmaceutical Science and Clinical Pharmacology Committee will meet Sept. 20 on the agency's plans to liberate a quality review process that has become mired in text. FDA is hoping the new approach will help it meet review goals established in the second five-year authorization of the Generic Drug User Fee Act, or GDUFA II.

FDA said in an Aug. 15 Federal Register notice that it will seek input on "the potential enhancement of a submission format consistent with KASA to improve the efficacy and consistency of regulatory quality assessment.” KASA means knowledge-aided assessment and structured application.

FDA's Office of Pharmaceutical Quality last year developed a dashboard interface for understanding quality risk and mitigation strategies for critical quality attributes and for understanding control strategies for drug substances and drug products. Another interface will standardize quality assessment and lifecycle management. (Also see "FDA Quality Office Looks Back At 2017: Reviews Accelerated, Inspections Realigned" - Pink Sheet, 1 Mar, 2018.) 

Agency officials explained that the KASA initiative is meant to speed up the generic drug review process to meet stricter time frames for reviewing drugs under GDUFA II. They say it should enable higher quality and more complete initial submissions from sponsors.

FDA Commissioner Scott Gottlieb explained the advantages of the KASA platform in a June 18 FDA Voice blog post. He said that “KASA will enable a structured review that will make the application review process more efficient, and allow for the earlier spotting of deficiencies. This will allow the FDA to provide earlier feedback to generic drug makers that will, in turn, help to reduce multiple cycles of application review.”

Gottlieb added that “having a structured template that completely replaces the largely narrative-based review will allow for more consistent and predictable entry and analysis of data. Current assessments require manual review of the entire application while KASA will enable automated analyses of some portions of the application, which will save time and ensure consistency.”

Gottlieb said that the administration’s fiscal year 2019 budget request included $37.6 million to fund KASA as well as another initiative that promotes the more widespread use of existing generic drugs by looking for ways to keep generic labeling up to date with the latest information about each drug’s risks and benefits.

Janet Woodcock, director of FDA's Center for Drug Evaluation and Research, told the annual meeting of the Association for Accessible Medicines in February that the current review process is not sustainable, especially in light of GDUFA II, which puts additional pressure on the agency to approve applications faster.

Woodcock said the key to speeding up reviews is to increase first-cycle approvals and reduce refuse-to-receive action. This can be achieved by providing manufacturers with more clarity on the agency's expectations for applications and by structuring and standardizing the review process.

Woodcock echoed Gottlieb’s observations that the current application process is very labor intensive, particularly for quality, because it involves the creation of multiple text documents that are not amenable to knowledge management.

The KASA model relies instead on tabular assessments, she explained. Moving from the text-based approach "to a tabular structured assessment will allow for knowledge management and a lifecycle approach and it will help us be consistent and it will help improve the efficiency and the process of reviewing the application and it will help communicate requirements.”

Woodcock said that the agency plans to develop and implement KASA modules over the next several years. The next step would be to assist industry in better structuring submissions.

The advisory committee plans to devote the upcoming meeting to the KASA initiative while also exploring standards for in-vitro/in-vivo relationships, and will seek input on establishing patient-focused dissolution standards for oral solid modified-release dosage forms.

FDA will consider comments regarding the meeting through Sept. 19 at https://www.regulations.gov/docket?D=FDA-2018-N-2944. FDA will provide the committee all comments received by Sept. 5.

From the editors of The Gold Sheet.