In the five years since it started collecting generic drug user fees, the FDA has hired 1,000 new employees, amped up its staff training and completely reorganized the way it reviews abbreviated new drug applications (ANDAs).
Yet prior to the start of fiscal 2018, about half of all ANDAs with GDUFA I goal dates still required three or more review cycles before they were approved.
"It currently takes on average about four cycles for an ANDA to reach approval – not necessarily because the product will not meet our standards, but sometimes because the application is missing information necessary to demonstrate that it does," FDA Commissioner Scott Gottlieb said Wednesday in announcing the release of a new draft guidance on best ANDA submission practices and a new agency Manual of Policies and Procedures (MAPP) that's intended to help staff handle ANDAs more efficiently.
"Multiple cycles of review are costly and inefficient," Gottlieb said. "They require a great deal of additional, avoidable work by both agency staff and the applicant and can delay the entry of generic competition." That delay can cost patients and payers a lot of money.
To speed things up, the FDA will no longer "review" ANDAs. It will "assess" them, according to the new MAPP, which defines assessment as the "process of both evaluating and analyzing submitted data and information to determine whether the application meets the requirements for approval and documenting that determination."
While the new MAPP doesn't alter the regulatory requirements for ANDA approval, it makes three significant changes, according to the FDA, to ANDA assessment practices.
First, it instructs assessment teams to, when available, use templates and assessment tools to focus the primary assessment of quality, bioequivalence or labeling data on the critical attributes of the application. Besides helping staff determine whether an application meets approval requirements, that change will enable assessors to better explain ANDA deficiencies and advise applicants on additional information needed to support an approval decision.
Secondly, the MAPP clarifies the roles and responsibilities of primary and secondary assessors, as well as division directors. (Under the new policy, division directors will no longer perform the role of a typical tertiary reviewer.) Clarifying those roles should reduce duplicative and unnecessary work, according to the MAPP.
The final change is that the MAPP charges the Office of Generic Drugs and the Office of Pharmaceutical Quality to clearly communicate to applicants the deficiencies that must be corrected for an ANDA to be approved. That should improve the quality of resubmissions and reduce the number of subsequent cycles needed before an ANDA is approved.
The overall goal is to increase the efficiency and effectiveness of the agency's generic drug review teams so they can "focus more of their attention on novel or challenging scientific and policy issues associated with the development and assessment of generic drug products," according to the new policy.
While the MAPP explains what the FDA will do to improve approval times for generic drugs, the draft guidance lays out what drug companies can do to get an approval in fewer cycles. The draft highlights common, recurring deficiencies that lead to delays and advises applicants on how to avoid them.
Although it's not a complete list of all ANDA deficiencies, the guidance discusses issues pertaining to patents and exclusivities, labeling, product quality and bioequivalence. Comments on the draft are due by March 5.
More to come
Both the MAPP and the guidance are part of the FDA's Drug Competition Action Plan, which Gottlieb said is one of the agency's highest priorities for 2018. Citing high drug prices as one of the biggest challenges facing the agency, he announced the plan soon after being confirmed as the FDA commissioner in May. (See BioWorld Today, May 10, 2017.)
"I know FDA doesn't play a direct role in drug pricing. But we still need to be taking meaningful steps to get more low cost alternatives to the market, to increase competition and to give consumers more options," Gottlieb said in his first official remarks to agency staff. (See BioWorld Today, May 17, 2017.)
The new MAPP and guidance are the first of several steps the FDA plans to take this year to beef up prescription drug competition. Other efforts will include building on initiatives to accelerate generic entry of complex drugs, such as metered dose inhalers and hard-to-copy injectables.
"We'll also continue to take steps aimed at making it harder for brand companies to sometimes adopt tactics that prevent generics from coming to market in the time frame that the law intended," Gottlieb said Wednesday. To stop such shenanigans, as Gottlieb has called them, the FDA will issue guidance in the next few months dealing with potential abuses of the citizen petition process, companies that restrict access to testing samples of branded drugs and abuses of the negotiation process for single, shared risk evaluation and mitigation strategies.