FDA Regulatory News and Trends - March 28, 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.

Finalized guidance on antibody-drug conjugates.

• On March 1, 2024, FDA issued a final guidance entitled, “Clinical Pharmacology Considerations for Antibody-Drug Conjugates Guidance for Industry,” which provides recommendations to assist industry and other parties involved in the development of antibody-drug conjugates (ADCs) with a cytotoxic small-molecule drug or payload.
   
• Specifically, the guidance addresses clinical pharmacology considerations and recommendations for bioanalytical methods, dosing strategies, dose- and exposure-response analysis, intrinsic factors, QTc assessments, immunogenicity, and drug-drug interactions (DDIs). The guidance does not include considerations for ADCs outside of oncology indications, suggesting that the Agency believes other ADC types may have different requirements.
  
  
• Although ADCs incorporate both a biologic and a small-molecule drug, they are ultimately regulated by FDA as biological products and must meet requirements governing product development, testing, and approval as outlined in section 351 of the Public Health Service (PHS) Act (42 U.S.C. 262).
  
  

Pair of guidance documents related to the development and validation of analytical procedures.

• On March 7, 2024, FDA released two guidance documents, entitled, “Q2(R2) Validation of Analytical Procedures” and “Q14 Analytical Procedure Development.” Such content was developed as part of FDA's participation in the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) and aims to harmonize FDA's approach with other countries worldwide.
  
  
• The Q2 guidance covers selection and evaluation of validation tests for analytical procedures. Its scope focuses on analytical procedures used for release and stability testing of drugs, but the guidance notes that the principles could also be applied to other analytical procedures.
  
  
• The Q14 guidance provides science- and risk-based approaches for developing analytical procedures suitable for the evaluation of drug quality. Similar to Q2, the guidance focuses on release and stability testing, but it could be applied to other types of analytical procedures.
  
  
• Drug and biologics manufacturers are encouraged to review both guidance documents to determine whether improvements can be made to strengthen and/or streamline their procedures for analyzing product quality.
  
  

Drug development for early Alzheimer’s disease.

• On March 12, 2024, FDA issued a revised draft guidance, titled, “Early Alzheimer’s Disease: Developing Drugs for Treatment.” This draft guidance revises the previous draft guidance for industry of the same name issued on February 16, 2018.
  
  
• The latest draft guidance discusses diagnostic criteria for early Alzheimer’s disease (AD) and clinical staging of AD to inform enrollment in clinical trials and selection of appropriate endpoints for the stage(s) of disease proposed to be enrolled in clinical trials. Direct measures of clinical benefit or validated surrogate endpoints may support a traditional approval, while surrogate endpoints or intermediate clinical endpoints may support an accelerated approval where post-approval trials will be required to verify and describe clinical benefit.
  
  
• Interested parties should submit comments on or before June 10, 2024. 
  
  

New regulations for animal drug labeling.

• On March 12, 2024, FDA announced new proposed regulations to provide animal drug sponsors with predictable requirements for the labeling of prescription and over-the-counter new animal drugs. The proposed rule, if finalized, would create for the first time a comprehensive set of regulations establishing requirements for content and format of the labeling for approved and conditionally approved new animal drugs. It would also help animal drug sponsors more efficiently prepare labeling for review. 
  
  
• The proposed rule aims to provide definition of labeling terms and consolidate requirements for the content and format of labeling for approved or conditionally approved new animal drugs into one section of the regulations.  Sponsors would need to comply with these proposed regulations on a staggered schedule, over the course of six years.
  
  
• Interested parties should submit comments on or before June 10, 2024.
  
  

Draft guidance on facilitating understanding in informed consent.

• FDA and the Office for Human Research Protections (OHRP) published a draft guidance titled, “Key Information and Facilitating Understanding in Informed Consent,” to help address concerns that informed consent forms are often lengthy and difficult for potential research participants to understand. 
  
  
• This draft guidance provides research sponsors, investigators, and institutional review boards (IRBs) with recommendations on how to implement two proposed requirements in the FDA proposed rule, “Protection of Human Subjects and Institutional Review Boards,” and the corresponding current requirements under the revised Common Rule – provisions that require informed consent to begin with key information about the research and to present information in a way that facilitates understanding. The draft guidance encourages the use of different information delivery formats and text formatting.
  
  
• Public comment on the draft guidance is requested by April 30, 2024.
  
  

FDA announces qualified health claims for yogurt and reduced risk of type 2 diabetes.

• FDA announced in a letter of enforcement discretion its decision not to challenge certain qualified health claims regarding the consumption of yogurt and reduced risk of type 2 diabetes, provided that the qualified health claims are worded so as not to mislead consumers and comply with other regulatory requirements.
  
  
• The letter addresses a petition that sought FDA’s evaluation of a health claim linking yogurt consumption (ie, consumption of any yogurt variety meeting FDA’s standard of identity, with health benefits attributable to overall food profile, rather than any specific nutrient or compound) with a lower risk of type 2 diabetes. 
  
  
• The letter discusses the factors that FDA intends to consider in the exercise of its enforcement discretion. Of note, FDA considers two cups (ie, three servings) per week of yogurt to be the minimum amount for deploying the qualified health claim in question. 
  
  

EUA for SARS-CoV-2 Combo Home Test.

• On February 29, 2024, FDA issued an Emergency Use Authorization (EUA) for a Flu SARS-CoV-2 Combo Home Test. The Combo Home Test is authorized for non-prescription home use with self-collected anterior (nares) nasal swab specimens from individuals aged 14 years or older, or with adult-collected anterior nasal swab specimens from individuals aged two years or above. It is only authorized for individuals with signs and symptoms of respiratory infection consistent with COVID-19 within the first four days of symptom onset when tested at least twice over three days, and with at least 48 hours between tests.
  
  
• The test is the first over-the-counter (OTC) at-home antigen test that detects both flu and COVID-19 viruses to receive an EUA following collaboration with the National Institutes of Health Independent Test Assessment Program.
  
  

Finalized guidance on new dietary ingredient notification procedures.

• On March 5, 2024, FDA issued a final guidance entitled, “Dietary Supplements: New Dietary Ingredient Notification Procedures and Timeframes,” which finalized certain aspects of an August 2016 draft guidance. Under section 413(a)(2) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 350b(a)(2)), the manufacturer or distributor of a new dietary ingredient (NDI) that has not been present in the food supply as an article used for food, or as a dietary supplement that contains the NDI, must submit a premarket safety notification to FDA at least 75 days before introducing the product into interstate commerce, commonly referred to as a new dietary ingredient notification (NDIN). The guidance provides the Agency’s current thinking about the NDIN submission and review process, including by answering the following questions:
  
  
  • Who needs to submit an NDIN?
  • How should the information be organized and presented?
  • Where should an NDIN be submitted?
  • What happens after an NDIN is submitted?
    
    

Revised draft guidance on new dietary ingredient notifications.

• On March 5, 2024, FDA issued a revised draft guidance entitled, “Dietary Supplements: New Dietary Ingredient Notifications and Related Issues,” which replaces other aspects of the previously mentioned August 2016 draft guidance.  This draft guidance updates the Agency’s current thinking, and requests additional comment, on the following topics:
  
  
  • What qualifies as an NDI?
  • When is an NDI notification required?
  • What are the procedures for submitting an NDI notification?
  • What types of data and information does FDA recommend you consider when you evaluate the safety of NDIs and dietary supplements containing an NDI?
  • What does FDA recommend you include in an NDI notification?
    
    

FDA alert on certain cinnamon products due to presence of elevated levels of lead. 

• On March 6, 2024, FDA issued a safety alert and recommended voluntary recalls for certain ground cinnamon products sold at six different retail chains nationwide due to the presence of elevated levels of lead. Though no illnesses or adverse events had been reported in association with these products, FDA said prolonged exposure to these products may be unsafe and could contribute to adverse health effects.
  
  
• The safety alert follows an October 2023 recall of cinnamon apple puree and applesauce products due to elevated lead levels linked to the cinnamon in those products and the concern for lead toxicity in children. Shortly after the recall, FDA initiated a targeted survey of ground cinnamon products from discount retail stores and analyzed the samples for lead and chromium.
  
  
• In addition to continuing its Toxic Elements monitoring program geared toward colored spices sold in the US, FDA stated that it will continue to work with manufacturers, distributors, and retailers to remove unsafe products from the market, and to further investigate the sources of lead contamination as appropriate.