The FDA on Thursday put the finishing touches on three final guidance documents focused on reviewing drug master files (DMFs) in advance of generic drug submissions, collecting patient-reported outcomes (PROs) in cancer trials, and when to conduct long-term clinical neurodevelopmental safety studies for neonatal products.
On generic drug submissions: The FDA said it considered comments on the draft issued in October 2022 and added a footnote to clarify that unsolicited amendments submitted to the DMF after a prior assessment is granted “may extend the target date.” The seven-page guidance builds off of the latest generic drug user fee reauthorization, and it explains how and when generic drug companies can request an assessment of a DMF six months before the planned submission of a generic drug application.
On patient-reported outcomes: The regulator also finalized an eight-page guidance from June 2021 that details how to measure patients’ reports on symptoms and functional impacts in cancer drug trials. The FDA has cautioned that “heterogeneity” in PRO assessments has lessened their functionality, but it still views PROs as having an important role.
“Systematic assessment of a core set of PROs using fit-for-purpose PRO measures can facilitate high quality data on patient-reported symptoms and functional impacts,” the agency said.
The final version now includes new recommendations to consult the FDA when selecting adverse events for reporting and edits to include hematological malignancies, according to the agency.
On neurodevelopmental safety studies: The FDA’s 11-page guidance on long-term clinical neurodevelopmental safety studies in neonatal products finalizes a draft first shared in February 2023. It digs into considerations that impact the potential for such a long-term follow-up assessment.
“Although there is no universal definition of ‘long-term,’ for the purpose of this guidance, the time frame can be generally thought of as at least 2 years of age or at such time when relevant clinical neurodevelopmental parameters can be reasonably assessed,” the FDA said in the guidance.
The regulator made several changes in the final document, including adding a new background section that addresses the recommended minimum duration of follow-up and noting that this will depend on different population- and product-specific factors. It also includes new text about the impact of the route of product administration and clarified that a protocol should specify whether assessments are conducted as part of standard clinical care or for research-related purposes only.
Other drafts: In addition to the trio of final guidance documents, the FDA on Thursday also released two draft guidances on developing drugs for postoperative nausea and vomiting and CBER’s recommendations for developing blood collection, processing and storage systems for the manufacture of blood and blood components for transfusion using the buffy coat method.