CBER revises internal procedures for processing clinical holds, NDAs and BLAs
The US Food and Drug Administration’s Center for Biologics Evaluation and Research (CBER) has published two internal policy guides for staff outlining procedures for placing a clinical study on hold and addressing the administrative processing of biologics license applications (BLAs) and new drug applications (NDAs).Both sets of policies went into effect on 22 September 2023.
Processing clinical holds
Standard operating policy and procedures (SOPP) 8201, version 8, covers the administrative processing of clinical holds. Under 21 CFR 312.12, clinical holds are ordered by FDA when a clinical investigation reveals information that indicates a proposed treatment poses an "unreasonable and significant risk of illness or injury" while under 21 CFR 312.42(e), the clinical hold can be lifted if the agency is satisfied that these risks have been addressed.
Under the policy, CBER will review all investigational new drug applications (INDs) within 30 days of receipt and contact the sponsor when a clinical hold is being imposed. The policy states that “where it is determined there are grounds for imposing a clinical hold, regulations require that, unless patients are exposed to immediate and serious risk, FDA will attempt to discuss and satisfactorily resolve the matter with the sponsor before issuing the clinical hold order.”
The latest version updates version 7, which was issued in June 2022, and adds new language on imposing a hold when a sponsor stops a study for safety reasons and is investigating. The version 8 SOPP also updates procedures to include letter issuance for an incomplete response to a clinical hold and a clinical hold memo template for active INDs.
BLAs and NDAs
The second procedures guide, CBER SOPP 8401 version 17, covers the administrative processing of BLAs and NDAs that are subject to fees under the Biosimilar User Fee Act (BsUFA) and the Prescription Drug User Fee Act (PDUFA). The guidance also covers applications for non-user fee products.
The guide outlines procedures governing the receipt of applications, requirements for electronic submissions, review timelines, timeline extensions, reviewing unsolicited amendments, reaching milestones for mid- and late-cycle meetings, and timelines for advisory committee meetings.
The SOPP addresses the definitions of a major amendment, unsolicited amendments, a complete response letter, the deficiencies identified in a Day 74 letter, an establishment inspection report (EIR), expedited letters, and what constitutes a substantive review issue. Additionally, the document covers the responsibilities of the review committee in resolving scientific issues.
The guide states that “applications filed over protest after a refuse to file decision are not eligible for parameters of the PDUFA Program. The original submission will be subject to the review goals per the current PDUFA goals letter; resubmission goals do not apply.” In these cases, the guide directs staff to consult SOPP 8404.1: Procedures for Filing an Application when the Applicant Protests a Refusal to File Action (File Over Protest).
The revision supersedes version 16 by adding a new Refuse-to-File briefing and clarification related to communications for deficiencies identified during filing review.
SOPP on processing of clinical holds, SOPP on administrative processing of NDAs and BLAs
×
Welcome to the new RAPS Digital Experience
We have completed our migration to a new platform and are pleased to introduce the updated site.
What to expect: If you have an existing login, please RESET YOUR PASSWORD before signing in. After you log in for the first time, you will be prompted to confirm your profile preferences, which will be used to personalize content.
We encourage you to explore the new website and visit your updated My RAPS page. If you need assistance, please review our FAQ page.
We welcome your feedback. Please let us know how we can continue to improve your experience.