FDA Regulatory News and Trends - January 19, 2024

Welcome to FDA Regulatory News and Trends, designed to help you identify significant legal developments and navigate the evolving business, legal, and regulatory world.


FDA updates draft guidance on potency assurance for cellular and gene therapy products.

• In December 2023, FDA released an update to its draft guidance, newly entitled, “Potency Assurance for Cellular and Gene Therapy Products.”
  
  
• This draft guidance provides recommendations for helping to assure the potency of human cellular therapy and gene therapy products. Specifically, it describes how to progressively implement a potency strategy during development, as well as potency assurance requirements for licensed products.
  
  
• Further, the guidance explains how potency should be built into a manufacturer’s quality risk management to be used in identifying critical quality attributes and establishing a quality target product profile. The Agency also provides considerations for potency assay control and change management, as well as establishes acceptance criteria for such assays.
  
  
• Comments are due by March 27, 2024.
  
  

Guidance on the development of drugs and biological products for rare diseases.

• On December 21, 2023, FDA issued a final guidance for industry, titled, “Rare Diseases: Considerations for the Development of Drugs and Biological Products." This guidance finalizes the draft guidance entitled, “Rare Diseases: Common Issues in Drug Development,” issued on February 1, 2019.
  
  
• The guidance is intended to assist sponsors of drugs and biological products as they navigate challenges posed by rare diseases. The Agency provides a discussion of selected issues commonly encountered in rare disease drug development, as well as addresses natural history studies, nonclinical studies, clinical development, and pharmaceutical quality considerations, among others. 
  
  
• Sponsors are encouraged to engage early with the Agency to discuss their drug development program.
  
  

FDA publishes draft guidance on trials conducted under a master protocol.

• In December 2023, FDA released draft guidance, entitled, “Master Protocols for Drug and Biological Product Development,” which provides recommendations on the design and analysis of clinical trials conducted under a master protocol.
  
  
• Trials conducted under master protocols can maximize the amount of information gleaned from a study and increase trial efficiency by sharing a number of components, including control arms, protocol elements, infrastructure, and oversight.
  
  
• The draft guidance provides recommendations on master protocol FDA regulatory submissions and focuses on randomized umbrella and platform trials meant to provide evidence of safety and effectiveness of drugs, including biologics. 
  
  
• Comments are due by February 22, 2024.
  
  

Guidance on major statements in DTC advertising.

• On December 26, 2023, FDA issued a final guidance, entitled, “Direct-to-Consumer Prescription Drug Advertisements: Presentation of the Major Statement in a Clear, Conspicuous, and Neutral Manner in Advertisements in Television and Radio Format Final Rule Questions and Answers.”
  
  
• This question-and-answer guidance is intended to help small entities understand and comply with the standards established in the CCN final rule, “Direct-to-Consumer Prescription Drug Advertisements: Presentation of the Major Statement in a Clear, Conspicuous, and Neutral Manner in Advertisements in Television and Radio Format” (88 FR 80958, November 21, 2023). 
  
  
• The CCN final rule modifies 21 CFR 202.1(e)(1) to reflect this requirement and establishes standards to help ensure the major statement in these advertisements is presented in the manner required.
  
  

Q&A documents for FDA’s breakthrough therapies and EMA's PRIME programs.

• On December 19, 2023, FDA released four joint FDA/European Medicines Agency (EMA) question-and-answer (Q&A) documents on generating quality and manufacturing information for certain products included in FDA’s breakthrough therapy designation program and EMA's PRIority MEdicines (PRIME) scheme. 
  
  
• FDA’s breakthrough therapy designation program and EMA’s PRIME scheme are designed to help speed development of innovative products that address unmet medical needs.
  
  
• The recently released documents are designed to provide clarity and insight to industry about the ongoing discussions between FDA and the EMA on this topic. 
  
  

CDER and CBER finalize pair of guidance documents related to real-world evidence.

• In December 2023, CDER and CBER released two final guidance documents clarifying expectations around the use of registries as sources for real-world evidence (RWE) and conversion of RWE into standardized submission formats. Both documents were issued to fulfill a 21st Century Cures Act requirement for FDA to establish a RWE program, which will allow the Agency to evaluate the potential use of RWE in regulatory decision making.
  
  
• The first guidance, titled, “Data Standards for Drug and Biological Product Submissions Containing Real-World Data,” acknowledges the many challenges of standardizing data from real-world sources and provides recommendations for conforming real-world data to the standardized formats required by CDER and CBER.
  
  
• The second guidance, titled, “Real-World Data: Assessing Registries To Support Regulatory Decision-Making for Drug and Biological Products,” addresses three major topics: (1) assessing a registry's fitness for supporting regulatory decisions, (2) considerations when linking registries to other data sources, and (3) ways to facilitate FDA review of registry data.
  
  
• Drug and biologic manufacturers planning future submissions requiring clinical data should review both guidances and consider whether they may be able to leverage RWE to support the clinical evidence requirement more efficiently.
  
  

Guidance on SARS-CoV-2 monoclonal antibody products.

• In December 2023, FDA issued a guidance, entitled, “Development of Monoclonal Antibody Products Targeting SARS-CoV-2 for Emergency Use Authorization,” which provides recommendations to sponsors on the development of monoclonal antibody (mAb) products targeting SARS-CoV-2 intended for the prevention or treatment of COVID-19, including recommendations on addressing the impact of emerging variants.  
  
  
• The release follows a February 2021 guidance that was published to facilitate the development and availability of COVID-19 therapeutics for the duration of the COVID-19 public health emergency (PHE).  Though the PHE has expired, FDA recognizes that SARS-CoV-2 remains in broad circulation throughout the US.  
  
  
• While FDA may issue an emergency use authorization (EUA), FDA expects manufacturers to continue to collect data in any ongoing trials and work toward submission of biologics license applications as soon as possible. FDA is required to periodically review the circumstances and appropriateness of an EUA, including the progress made toward licensure of a product.  
  
  
• The latest guidance provides specific details on the criteria for the issuance of an EUA (essentially assessing the totality of available scientific evidence), guiding principles in FDA’s evaluation (generally, a flexibility regarding the data necessary to support the development of mAb products), and development program considerations to support use under an EUA (CMCs, pharmacology/toxicology, virology, and clinical).
  
  

Expansion of in-person face-to-face formal meetings between industry and FDA.

• On December 18, 2023, FDA announced that, beginning January 22, 2024, CDER and CBER will expand in-person face-to-face (FTF) industry meetings to include all Prescription Drug User Fee Act, Biosimilar User Fee Act, and Over-The-Counter Monograph Drug User Fee Program meeting types. All in-person FTF formal meetings will have a hybrid component, where only the person with a primary speaking role should join in person. 
  
  
• If an in-person meeting is requested, the sponsor should specify that in their request.  A final determination on the format will be made by the review division and communicated to the sponsor should the format be different than requested.  Existing meeting requests will not be converted to the in-person format.