FDA Issues Draft Guidance on Good ANDA Submission PracticesBy
The US Food and Drug Administration (FDA) has announced additional steps to encourage generic-drug competition as part of its continued implementation of the Drug Competition Action Plan, which the agency announced in June 2017, and which it says is designed to increase competition in the market for prescription drugs and facilitate entry of lower-cost alternatives.
In its first move, the FDA has issued draft guidance, Good ANDA Submission Practices, to streamline aspects of the submission and review process for generic-drug applications (i.e., abbreviated new drug applications [ANDAs]). The agency also published a companion to the draft guidance in the form of a Manual of Policies and Procedures (MAPP) for “Good ANDA Assessment Practices” to assist the agency’s reviewers.
The draft guidance highlights common, recurring deficiencies seen in generic-drug applications that may lead to a delay in their approval. It also makes recommendations to applicants on how to avoid these deficiencies with the goal of minimizing the number of review cycles necessary for approval.
The FDA says one key reason why generic approvals are delayed is that many applications need to undergo multiple cycles of review. “While often this is because the application lacks sufficient scientific evidence to support approval, there are also many times when the FDA must ask applicants for additional information in order to determine that the requirements for approval have been met, even if an application meets the threshold requirements for filing,” FDA Commissioner Scott Gottlieb said in a January 3, 2018 agency statement. “In fact, 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. These multiple cycles of review are costly and inefficient. They require a great deal of additional, avoidable work by both agency staff and the applicant and can delay the entry of generic competition.”
The guidance discusses deficiencies, including: patent and exclusivity, labeling, product quality, and bioequivalence.
Along with the draft guidance, the MAPP for “Good ANDA Assessment Practices” has been published to enhance the efficiency of the agency’s review process. The document outlines ANDA assessment practices for FDA staff. The document formalizes a more streamlined generic-drug review process, including the introduction of new templates that are expected to make each cycle of the review process more efficient and complete.
The MAPP says that when the FDA determines that an ANDA cannot be approved in its current form, reviewers should: provide more detail to generic-drug applicants to explain the deficiencies with the application; outline details on how this information should be provided; and provide more detail, when available, on the additional information that the generic-drug applicant must provide to the agency to support an approval decision during the next application cycle.
The MAPP establishes these practices across offices charged with ANDA review, including the Office of Generic Drugs as well as the Office of Pharmaceutical Quality. “The goal is to make sure that generic drug makers are made fully aware of the problems that are delaying the approval of their application and understand how to fix them,” said the FDA Commissioner in his statement. The agency emphasizes that the new MAPP does not alter the Generic Drug User Fee Amendments II review goals or program enhancements, nor does it alter the regulatory requirements for ANDA approval. “Rather, the goal of the MAPP is to guide FDA staff to help ensure we work more efficiently with the goal of improving review times,” said Gottlieb in his statement.
The FDA says its generic-drug team has already made investment in process improvements to yield faster assessment and approval times. For the full year of 2017, the FDA says it approved a record number of generic drugs, including first generics and high-priority medications. In addition to the increase in the volume of drugs being approved, the agency said that the average number of review cycles needed to approve each eligible application is decreasing.
“The policies we’ve announced today [January 3, 2017] and those that we’re anticipating in early 2018 represent our ongoing work on the Drug Competition Action Plan—one of the FDA’s highest priorities in 2018,” Gottlieb said in his statement. “In the coming year, we’ll be taking additional steps to improve our own practices and to help guide industry to make sure their generic-drug applications can be acted upon as efficiently as possible. For example, we’ll be building on our initiatives to accelerate generic entry of complex generics, which include medicines like metered dose inhalers used to treat asthma, as well as some costly injectable drugs, which are sometimes hard to copy.”
The agency says it will continue to take steps aimed at making it harder for brand companies to sometimes adopt practices that prevent generics from coming to market in the time frame that the law intended. This includes guidance development to address three important areas during the first quarter of 2018: potential misuse of the citizen-petition process, companies that restrict access to testing samples of branded drugs, and misuse of the single, shared-system Risk Evaluation and Mitigation Strategy negotiation process.