FDA Opens the Vault on Decision Letters—Releases Wave of Drug and Biologic CRLs

Last week, FDA released draft guidance titled “Scientific Considerations in Demonstrating Biosimilarity to a Reference Product: Updated Recommendations for Assessing the Need for Comparative Efficacy Studies.” This draft guidance reflects an evolution in FDA’s approach to determining whether a comparative clinical study with efficacy endpoints (a comparative efficacy study or CES) is necessary to support a demonstration of biosimilarity. Specifically, the agency notes that a comparative analytical assessment (CAA) is generally more sensitive when it comes to detecting differences between products than a CES.

On October 23, 2025, FDA released its final guidance regarding Patient-Focused Drug Development: Selecting, Developing, or Modifying Fit-for-Purpose Clinical Outcome Assessments. The guidance is the third guidance in a four-part series of FDA guidance focused on patient-focused drug development (PFDD) that describe how stakeholders, such as patients, caregivers, researchers, medical product developers and others can submit patient experience data and other relevant information that can be used for medical product development and regulatory decision making.

On October 16, 2025, the Food and Drug Administration (FDA) unveiled the first group of nine voucher recipients under the Commissioner’s National Priority Voucher (CNPV) pilot program, a program announced by the agency earlier this year that provides a path for accelerated drug review for companies supporting national interests as determined by the Commissioner. The identified areas of priority by the agency include meeting large unmet medical needs, bolstering domestic manufacturing and increasing the affordability of medicines for American patients. As previously noted, the new program, which is not defined in statute or regulations, aims to significantly speed up FDA’s standard 10-12 month review timeline to just 1-2 months after filing an application for a drug or biologic. The agency has touted the  benefit of recipients of the vouchers receiving enhanced access with FDA review staff and a “team-based review” model.

On September 30, 2025, the Food and Drug Administration (FDA) published a Request for Public Comment to obtain feedback from interested parties on current approaches to measuring and evaluating the performance of AI-enabled medical devices. Specifically, FDA is seeking feedback on best practices, methodologies and approaches for measuring and evaluating real-world performance of AI-enabled medical devices from the public.

FDA recently released two draft guidance documents for industry related to cell and gene therapy (CGT) products as the agency seeks to advance the efficient development and review of safe and effective CGT products and fulfill related commitments set forth in the 2022 reauthorization of the Prescription Drug User Fee Act (PDUFA VII). This latest guidance may be of particular interest to CGT developers and various patient groups.

On Tuesday, September 23, 2025, FDA published guidance titled “Consideration of Enforcement Policies for In Vitro Diagnostic Tests During a Section 564 Declared Emergency.” The guidance, a draft of which was published on May 6, 2024, specifies the factors that FDA intends to assess in deciding whether to issue an enforcement discretion policy with regard to in vitro diagnostics (IVD) manufacturers offering unapproved IVDs, among other devices, during a declared emergency. These factors include:

Last week, the U.S. Food and Drug Administration (FDA) issued a proposed rule to revoke the color additive listing for Orange B, a synthetic dye historically used on the casings and surfaces of frankfurters and sausages. This action is part of the broader “Make America Healthy Again” (MAHA) initiative to phase out petroleum-based foods from the American food supply by the end of 2026 and efforts to modernize the agency’s regulations.

The White House’s Make America Healthy Again (MAHA) Commission, led by the Department of Health and Human Services (HHS) Secretary Robert F. Kennedy Jr., released its highly anticipated strategy outlining a multi-agency approach focused on addressing childhood chronic disease. The strategy builds on the Commission’s inaugural health assessment, a report which examined the rising rates of childhood chronic diseases in the country and identified four primary drivers: poor diet due to consumption of ultra-processed foods (UPFs), exposure to environmental chemicals; increased technological use; and overmedicalization. To combat these challenges, the strategy released on September 9, 2025, outlines a four-prong approach which provides further insight into the areas the administration sees as key areas of MAHA going forward: advancing research, realigning incentives, increasing public awareness and fostering private sector collaborations.