FDA Regulatory News and Trends - September 11, 2023

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


Update on FDA dietary supplements program under proposed reorganization.

• On August 14, 2023, The Commissioner of Food and Drugs published an update on certain aspects of FDA’s Human Foods Program (HFP) that the Agency aims to improve as part of the program’s proposed redesign.
  
  
• Under the new proposed HFP structure, the Office of Dietary Supplement Programs will report to the Office of Food Chemical Safety, Dietary Supplements, and Innovation (OFCSDSI). However, instead of reporting to the CFSAN Center Director, the OFCSDSI Director is set to report to a Deputy Commissioner. In continuing to prioritize the dietary supplements program, FDA intends to modernize the assessment of food chemicals, facilitating safe and innovative ingredients for use in foods and dietary supplements with the new OFCSDSI.
  
  
• In addition, the Agency seeks to streamline operations through a unified HFP in which resources are more effectively shared with FDA’s Office of Regulatory Affairs. Furthermore, aligning surveillance efforts and safety assessments through the same risk management framework, FDA expects to leverage existing program efficiencies while also integrating various computational, analytical, toxicology, and research tools to improve oversight of dietary supplements.
  
  
• As additional details are finalized, the Commissioner plans to share more information on the program later this year.

FDA updates 25-year-old guidance on the use of informed consent in clinical investigations.

• On August 15, 2023, FDA published an Agency-wide guidance titled, “Informed Consent - Guidance for IRBs, Clinical Investigators, and Sponsors.” This guidance supersedes FDA’s earlier guidance titled, “A Guide to Informed Consent (1998).”
  
  
• The updated guidance aims to help institutional review boards (IRBs), clinical investigators, and study sponsors comply with FDA's informed consent regulations for clinical investigations. Two notable additions include a series of frequently asked questions and information on how FDA is pursuing harmonization with the Common Rule (45 CFR 46).
  
  
• Industry stakeholders involved in the conduct of clinical investigations are encouraged to review the guidance not only to help ensure regulatory compliance but also to identify opportunities for streamlining their consent process.

 
CDER, CBER, and OCE release draft guidance related to diversity in clinical trials.

• On August 8, 2023, the Center for Drug Evaluation and Research (CDER), Center for Biologics Evaluation and Research (CBER), and Oncology Center of Excellence (OCE) released a draft guidance document titled, “Postmarketing Approaches to Obtain Data on Populations Underrepresented in Clinical Trials for Drugs and Biological Products.”
  
  
• FDA has previously emphasized that pre-market clinical trials should represent all relevant ages, genders, and racial and ethnic groups, and the Agency reiterates that point in its new guidance. It acknowledges, however, that it may be difficult to completely address diversity in the premarket setting.  With this, FDA may require post-market data collection to address gaps in diversity data.
  
  
• Companies planning clinical trials to support FDA marketing authorization are encouraged to increase diversity in their subject populations and plan for the potential need to collect additional diversity data post-market.

Two new Biosimilar User Fee Act guidance documents.

• On August 11, 2023, FDA issued two draft new Biosimilar User Fee Act (BsUFA III) guidance documents: “Classification Categories for Certain Supplements Under BsUFA III” and “Formal Meetings Between the FDA and Sponsors or Applicants of BsUFA Products Guidance for Industry.” BsUFA III sets out the Agency’s commitments to biosimilar developers, which include ensuring the effectiveness of the biosimilar biological product review program and enhancing biosimilar product development, among others. 
  
  
• The “formal meeting” guidance is an update to the 2018 draft guidance, reflecting changes in the BsUFA III Commitment Letter. Biosimilar sponsors will have six types of formal meetings with FDA to discuss the development and review of a biosimilar or interchangeable biosimilar product. These include Biosimilar Initial Advisory (BIA) meetings and Biological Product Development (BPD) meetings, which are composed of five different meeting types. Significantly, “face-to-face” meetings now include both “in-person” meetings and “virtual (videoconference)” meetings with cameras on and screen sharing. The updated draft guidance further outlines the information required for submissions and the type-specific timelines. 
  
  
• The “classification” guidance focuses on the classification categories established for both original supplements and resubmitted prior approval supplements (PAS). The draft guidance document discussed the specific performance goals for each of the six new categories of supplements. Each submission will be assigned to one category, and, if multiple types of labeling changes are being requested, separate supplements should be submitted. Supplements that do not meet the six criteria are outside the scope of this guidance. 
  
  
• Interested parties should submit comments on or before October 10, 2023.

Partially hydrogenated oils are no longer GRAS.

• On August 9, 2023, FDA issued a direct final rule to complete administrative actions that reflect the Agency’s June 2015 final determination that the use of partially hydrogenated oils (PHOs) in foods is no longer generally recognized as safe (GRAS).
  
  
• The direct final rule revoked the pre-1958 authorization for the use of PHOs in certain food, removed PHOs as an optional ingredient in the standards of identity for peanut butter and canned tuna, and revised FDA's regulations affirming food substances as GRAS pertaining to menhaden oil and rapeseed oil to no longer include partially hydrogenated forms of these oils.
  
  
• While no significant adverse comments are expected, the Agency also issued a companion proposed rule to help FDA put these changes in place in case the direct final rule is withdrawn.
  
  
• The direct final rule will be effective December 22, 2023. Interested parties should submit their comments on or before October 23, 2023. 

Update to off-the-shelf software use in medical devices guidance.

• On August 11, 2023, FDA’s “Off-The-Shelf (OTS) Software Use in Medical Devices” guidance document was updated to align with the recently finalized “Content of Premarket Submissions for Device Software Functions” guidance.
  
  
• The OTS guidance provides information regarding the recommended documentation sponsors should include in a premarket submission for FDA’s evaluation of OTS software used in a medical device.
  
  
• The updated version of the OTS guidance aligns with the documentation system from the new premarket submissions for software guidance, offering recommendations on the two-tier Basic and Enhanced documentation components, rather than the previous “three levels of concern” system.
  
  
• Cover sheets have been added to other device-specific guidances to remind readers that the new 2023 premarket submissions for software guidance has superseded the prior 2005 guidance.

Decision on Third Circuit case involving the use of suppliers not included in FDA submission. 

• On July 20, 2023, the Third Circuit filed its opinion in United States v. Murty Vepuri, Ashvin Panchal, and KVK-Tech, Inc.
    
• In this case, the government alleged that Murty Vepuri (de facto director of KVK-Tech, Inc.), Ashvin Panchal (Director of Quality Assurance at KVK-Tech), and KVK-Tech (the manufacturer of Hydroxyzine) sourced Hydroxyzine’s active ingredient from a facility that was not included in the approvals they obtained from FDA and that they misled FDA about their practices. 
  
  
• The case was on appeal after the District Court for the Eastern District of Pennsylvania found for defendants on the portion of the conspiracy charge that alleges all three defendants conspired to violate provisions of the Federal Food, Drug, and Cosmetic Act, which prohibits introducing a “new drug” into interstate commerce unless an FDA approval is “effective with respect to such drug.”  
  
  
• The Third Circuit affirmed, rejecting the argument that a deviation from the approved drug application means that the approval is no longer effective, finding that the approval ceases being effective only when it has been withdrawn or suspended.  

FDA’s Office of Prescription Drug Promotion issues rare warning letter related to drug promotion.

• On August 4, 2023, FDA’s Office of Prescription Drug Promotion (OPDP) sent a warning letter to AstraZeneca Pharmaceuticals related to its promotion of prescription medication Breztri Aerosphere (Breztri).  The warning letter was published on August 15, 2023. 
  
  
• The warning letter explains that two statements contained in a sales aid create a misleading impression regarding the overall benefits a patient may expect as a result of treatment with the drug.  FDA found issue with statements suggesting that the drug leads to a reduction in all-cause mortality and a significant reduction in severe exacerbations.  FDA found that these statements were not supported by the cited trial data.  
  
  
• In the warning letter, FDA asks AstraZeneca to take specific remediation actions, including creating a comprehensive plan of action to disseminate truthful, non-misleading, and complete corrective communications about the concerns discussed in the letter to be disseminated to the audience that received the identified promotional communications.  FDA also includes recommended content and formatting for the remedial communications.  
  
  
• This is the first warning letter OPDP has issued in 2023.  The Office issued an untitled letter in June 2023 and, prior to that, had not issued a warning letter since June 2, 2022.