February 14, 2006 — /MEDICAL INDUSTRY E-MAIL NEWS SERVICE(TM)/ — COSTA MESA, Calif. — The FDA has released a new report that takes carefully examines the way the agency reviews applications for drugs and biologics that have not previously been approved by the FDA.
The report was commissioned to examine differences in applications approved by the agency during the 1st round of review (1st-cycle) compared to those applications that took multiple reviews (multi-cycle) before approval. One of the most compelling findings was the positive impact “milestone meetings” held between a product sponsor and the FDA can have in making the drug review process more efficient by improving the quality of initial applications.
The report, Independent Evaluation of FDA’s 1st Cycle Review Performance — Retrospective Analysis, showed the positive impact consulting with the FDA before beginning the final phase of human testing (end of Phase 2) can have on 1st-cycle approval rates. 52% of companies that held a meeting with the FDA at the end of Phase 2 trials received approval during the 1st review cycle.
However, only 29% of sponsors that did not have consultation meetings in this phase gained approval during the 1st review cycle for their product. In addition, the report also noted a positive link between a 1st-cycle approval and an earlier consultation before the application is even submitted — of 58 products with these types of meetings, almost half received 1st cycle approval.
“These meetings have become one of the most valuable aspects of the drug development process,” said Acting FDA Commissioner Andrew von Eschenbach, MD. “Earlier consultation and feedback from FDA on the sponsor’s development program is critical to ensuring safe and effective study designs and increasing the probability that the resulting marketing application will meet regulatory requirements. These meetings are a unique aspect of the FDA’s review program, but they are very labor intensive and require adequate Agency resources in order to sustain the current success.”
Most products with multiple cycles had major deficiencies identified in only one or two areas. Deficiencies in safety assessment were the most common reason for FDA requesting additional cycles, followed by efficacy and chemistry/manufacturing related issues.
The report also showed, however, that consulting with the FDA prior to application submission does not always prevent the need for multiple review cycles prior to approval. The report notes that even when major issues with an application are identified by FDA in milestone meetings, the sponsor did not always adequately address them prior to submission of the application. In fact, 71% of applications where key issues were identified by FDA during pre-submission meetings were not adequately resolved by the sponsor by the time of 1st action.
As a result of this independent analysis the report recommends that in order to further improve 1st-cycle approval rates FDA should play a “much more proactive role” throughout the development process. The report suggests that this will help the agency to better work with the sponsor to identify and communicate issues and potential deficiencies earlier on in the review process.
The report also recommended that the agency actively follow up with sponsors after milestone meetings to ensure the sponsor has adequately addressed issues identified during the meetings. The report notes, however, that implementing the recommendations would have significant resource implications for FDA given current workload and staffing in the reviewing divisions.
“There has been dramatic growth in the number of meetings with sponsors in the past several years. The additional workload for meetings is going to have to be supported by additional staffing,” said Dr. John Jenkins, Director of the FDA’s Office of New Drugs in FDA’s CDRH.
More and more companies are seeking early advice from FDA. The independent report shows that increased communication with the FDA often results in a more informed and efficient drug development process, especially for products that represent a major innovation and have significant public health impact. Requests for consultations to review clinical milestones and next steps in the development process are up more than 60% over the past few years under PDUFA III. In fiscal year 2005, FDA received over 2,400 requests for formal meetings with industry on PDUFA products in development.
The independent study was conducted by Booz, Allen Hamilton in relation to the Prescription Drug User Fee Amendments of 2002 (PDUFA III). This assessment includes a detailed evaluation of the events that occurred during the review process of new molecular entities for new drug applications (NMEs for NDAs), and biological license applications (BLAs) submitted in FY 2002-04.