FDA publishes NDA filing checklist to avoid application derailments
The US Food and Drug Administration (FDA) published the internal checklists its staff reference when reviewing drug and biologics applications to determine whether the submission is complete, or subject to a refuse-to-file (RTF) decision, in an updated manual of policies and procedures (MAPP) on Thursday.FDA said the move is intended to boost transparency into the agency’s filing procedures and cut down on the number of incomplete submissions it receives, which “consume resources and delay promising treatments.”
“Drug applications should not be derailed or delayed by preventable procedural oversights,” said FDA Commissioner Marty Makary. “Making these checklists public is a common-sense step to make the FDA process easier to understand and more transparent.”
The checklists have been added to the latest version of the MAPP 6025.4, which outlines good review practices for FDA staff.
FDA announced that over the past ten years, more than 200 applications have received an RTF notification. Additionally, applications involving a new molecular entity that receive an RTF notice typically face an average delay of 426 days before they are resubmitted.
The MAPP states that “the following policy emphasizes CDER’s expectation that applications are to be complete at the time of submission and that a piecemeal approach to building a complete application through amendments following initial submission is unacceptable. These policies reflect CDER’s current approach to RTF assessments and are consistent with the principles that underlie the Program.”
The guide outlines the criteria for when the FDA will issue an RTF, details the role of discipline primary reviewers in assessing NDAs, and describes the roles of discipline team leaders and Office of New Drug (OND) project managers in the review process.
It states that CDER staff will RTF applications that are “materially incomplete or inadequately organized.” This criterion is outlined in the September 2018 draft guidance for industry and review staff on “Good Review Management Principles and Practices for New Drug Applications and Biologics License Applications.”
The guide also how to handle “easily correctable” RTF deficiencies. The guide states that “these filing issues may be conveyed by telephone conference, facsimile, secure email, or other expedient means of communication.”
The MAPP said that CDER will use discipline-specific standard filing review templates when conducting filing reviews.
A series of appendices provides examples of easily correctable deficiencies, complex and significant deficiencies that may provide the basis for an RTF, a discipline review checklist for biostatistics and clinical pharmacology, and a checklist for product quality filing.
Examples of easily correctable deficiencies include issues with electronic navigation, compatibility problems with the FDA’s system, missing references for applications, incomplete or missing Form FDA 356h, and absent financial disclosure statements on Form FDA 3454.
The guide also lists examples of “complex and significant deficiencies” that can result in an RTF. These deficiencies include omitting application summaries; chemistry, manufacturing, and controls (CMC) information; nonclinical pharmacology and toxicology data, and human pharmacokinetic and bioavailability information.
FDA announcement; CDER MAPP on good review practices
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