FDA Regulatory News and Trends - March 12, 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.

Final guidance on charging for investigational drugs.

• On February 16, 2024, FDA finalized a guidance entitled, “Charging for Investigational Drugs Under an IND: Questions and Answers.”
  
  
• Revising the draft guidance of the same title issued in August 2022, and replacing the final guidance issued in June 2016, this guidance addresses frequently asked questions regarding implementation of FDA’s regulation on charging for investigational drugs under an investigational new drug application (IND).
  
  
• With very few changes from the 2022 version, the guidance describes, among other topics, requirements and conditions related to charging for investigational drugs; defines extraordinary cost; and clarifies the definition of an independent certified public accountant. The guidance is organized to address questions related to charging in general, charging in clinical trials, charging for expanded access use, and cost recovery calculations.
  
  

FDA Technical Conformance Guide.

• On February 26, 2024, FDA issued a final guidance entitled, “Reporting Amount of Listed Drugs and Biological Products Technical Conformance Guide.” 
  
  
• The guide aims to assist registrants of drug establishments or their authorized agents in submitting reports on the amount of each listed drug manufactured, prepared, propagated, compounded, or processed for commercial distribution.
  
  
• The guide describes how first-time users can access FDA’s CDER NextGen Portal to submit these reports, the different methods for submitting the reports through the portal, and the data elements to be included in the reports.
  
  

Final guidance on assessing COVID-19-related symptoms in outpatient participants.

• On February 22, 2024, FDA issued a final guidance entitled, “Assessing COVID-19-Related Symptoms in Outpatient Adult and Adolescent Subjects in Clinical Trials of Drugs and Biological Products for COVID-19 Prevention or Treatment.” This final guidance supersedes the guidance of the same name published in September 2020. 
  
  
• The latest guidance provides sponsors and investigators with example assessments of 14 common COVID-19-related symptoms. The document additionally provides considerations for outpatient clinical trial endpoint selections for both treatment studies and prevention studies in outpatient adults and adolescents. Finally, the guidance addresses the issue of missing data during clinical research and additional COVID-19-related assessments.
  
  

FDA safety communication on smart devices that claim to measure blood glucose. 

• FDA issued a safety communication warning consumers of risks related to smartwatches or smart rings that claim to measure blood glucose levels without piercing the skin. 
  
  
• The warning states that FDA has not authorized, cleared, or approved any smartwatch or smart ring to measure or estimate blood glucose values on its own. This is different to smartwatch applications that display data from FDA-authorized blood glucose measuring devices that pierce the skin.
  
  
• While FDA enforcement levels for smart device medical applications have historically been relatively low, this safety communication indicates that FDA is paying attention – in this case, seemingly due to the risk posed to people with diabetes relying on inaccurate blood glucose measurements.
  
  

Diagnostic Data Program updates.

• In February 2024, FDA began publicizing its Diagnostic Data Program, declaring that, over the past year, the program “has made substantial progress toward harmonizing diagnostic data, enhancing data quality, and creating analytics tools to optimize data use.”
  
  
• Diagnostic Data Program efforts include (i) working internally and externally to improve the quality and utility of diagnostic data, as well as its flow between individuals and institutions; (ii) supporting projects with collaborating institutions and investigators; (iii) driving improvements in data quality from over-the-counter, point-of-care, and lab-based diagnostic tests that help inform patient care, population health, and regulatory decision-making; and (iv) developing a regulatory data sandbox to facilitate the development of analytical tools to support regulatory review.
  
  
• FDA updated its Diagnostic Data Program webpage and invites interested individuals to visit to learn more about opportunities to engage in these efforts, including applying for future funding.
  
  

CDRH proposes updates to its Small Business Certification guidance.

• On February 22, 2024, CDRH released a draft guidance titled, “Select Updates for the Medical Device User Fee Small Business Qualification and Certification Guidance.” Such proposed updates are in response to a provision in the Food and Drug Omnibus Reform Act of 2022 that grants FDA discretion, beginning in fiscal year 2025, to waive establishment registration fees for small businesses experiencing financial hardship.
  
  
• The new fee waiver provision defines “small business” as one that reported $1 million or less of gross receipts or sales in its most recent federal income tax return. CDRH's proposed guidance revisions explain how small businesses can show financial hardship to qualify for the fee waiver. 
  
  
• Small medical device companies are encouraged to review the proposed guidance updates to familiarize themselves with the process for qualifying for the registration fee waiver, expected to be implemented for this coming fiscal year (beginning October 1, 2024). Any comments on the proposed guidance changes can be submitted to the docket at FDA-2018-D-1873.
  
  

New directory of ingredients used in products marketed as dietary supplements.

• In February 2024, FDA updated its Ingredient Directory, including renaming the webpage to “Information on Select Dietary Supplement Ingredients and Other Substances.”
  
  
• The intent of this directory is to help industry and consumers stay informed about ingredients and other substances found in products labeled as dietary supplements. The directory contains links to FDA’s actions and communications, including the Agency’s evaluation of health claims, safety communications, and compliance and enforcement actions.
  
  
• The recent changes follow stakeholder feedback received after FDA initially published the directory in March 2023. In addition to the new title, the directory updates include added categories to classify the type of FDA action or communication for each listed ingredient; recording the date each listed ingredient was added to the directory; and streamlining the introductory text on the page.
  
  

Guidance on foods derived from plants produced using genome editing.

• In February 2024, FDA issued a “Guidance for Industry: Foods Derived from Plants Produced Using Genome Editing” to clarify how FDA’s “Statement of Policy - Foods Derived from New Plant Varieties” applies to foods derived from new plant varieties produced using genome editing.  The guidance reminds developers of genome edited plants that they are subject to the allergen labeling requirements under section 403(w) of the FD&C Act.  It additionally describes the two processes available to developers that want to voluntarily consult with FDA prior to marketing their products, and provides information on when each of the pathways are appropriate.
  
  
• The guidance explains that voluntary premarket consultations provide a mechanism that can be used to help developers determine the regulatory status of food from new plant varieties and ensure that any safety concerns have been resolved prior to marketing.  The guidance additionally describes the circumstances (eg, the types of modifications) under which the Agency strongly recommends that developers of genome-edited plants engage in a voluntary premarket consultation, and provides examples in each category. These include:

1. Modifications to endogenous genes that create significant homology to a known allergen that is relevant to human health or a toxin that is relevant to human or animal health
   
   
2. Modifications that cause a non-negligible increase in levels of potentially harmful components, including toxicants, allergens, anti-nutrients, and other components that can exhibit non-nutritive physiological effects on humans or animals
   
   
3. Modifications that cause a non-negligible change in the nutritional value (level of nutrient and/or bioavailability) of the food

• When none of the listed modifications applies, FDA strongly recommends that developers schedule a voluntary premarket meeting to provide the Agency with information about the food and its food safety characteristics. Such a meeting would help familiarize FDA with the types of foods from genome-edited plants entering the market and the steps developers have taken to ensure their safety and lawfulness. During the meeting, the Agency expects developers to describe the safety characteristics of human and animal food from their new variety – including whether the food has characteristics that would suggest a voluntary premarket consultation instead of a voluntary premarket meeting – and explain the steps they have taken to ensure that food from their new variety is safe and lawful.
  
  

PFAS substances no longer sold for food contact use in US market.

• FDA announced that grease-proofing substances containing per- and polyfluoroalkyl substances (PFAS) are no longer being sold by manufacturers for food contact use in the US market. The completion of the voluntary market phase-out of these substances used on food packaging paper and paperboard eliminates the primary source of dietary exposure to PFAS from authorized food contact uses.
  
  
• The elimination of these substances marks the fulfillment of industry’s 2020 commitment from manufacturers to FDA to voluntarily stop selling paper and paperboard packaging for food products to prevent the leaking of grease and oil, and for water-resistant purposes.  The substances containing PFAS were applied to fast-food wrappers, microwave popcorn bags, take-out paperboard containers, pet food bags, and other similar types of packaging.