FDA Regulatory News and Trends - December 13, 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.

FDA releases guidance documents on device shortage reporting during public health emergencies.

• On November 17, 2023, the Center for Devices and Radiological Health (CDRH) published two guidance documents to help clarify Section 506J of the FD&C Act: “Notifying FDA of a Permanent Discontinuance or Interruption in Manufacturing of a Device Under Section 506J of the FD&C Act” and “Select Updates for the 506J Guidance: 506J Device List and Additional Notifications.”
  
  
• Section 506J was established during the COVID-19 pandemic and requires certain manufacturers to notify FDA of a permanent discontinuance or interruption in the manufacturing of a device that is likely to lead to a meaningful disruption in the supply of that device during or in advance of a public health emergency.
  
  
• These draft guidances clarify how FDA interprets terminology used in 506J (eg, “in advance of a public health emergency" and "interruption in manufacturing"). They also explain that FDA has proposed a list of devices that are critical to public health and therefore are subject to the 506J reporting requirements.
  
  
• All device manufacturers are encouraged to review FDA's proposed list of devices subject to 506J and determine whether these new reporting requirements apply to their products. When finalizing these draft guidances, FDA plans to combine both and release as a single guidance document. The Agency is currently seeking comments, which can be submitted to Docket #FDA-2022-D-0053.
  
  

FDA investigation of elevated lead levels in cinnamon applesauce pouches.

• On November 22, 2023, the FDA published an update on its ongoing investigation of elevated blood lead levels in individuals with reported exposure to apple cinnamon fruit puree pouches manufactured in Ecuador and sold under the WanaBana, Weis, and Schnucks brands. As of November 22, there were 52 reports of illness potentially linked to recalled products, all among complainants less than four years old. Incoming adverse reports of illnesses will continue to be evaluated.
  
  
• FDA’s working hypothesis is that cinnamon used in the recalled products is the likely source of contamination. However, the Agency has not yet been able to collect and test samples of the cinnamon used in the pouches, and it continues to work with Ecuadorian authorities to investigate the cinnamon’s source. While there is currently no indication that the issue extends beyond these recalled products, in the interest of public health, FDA is screening incoming shipments of cinnamon from multiple countries for lead contamination.
  
  
• The Agency noted these products have a long shelf life and stated it is working with affected retailers to remove them from shelves. Consumers and retailers are encouraged to refer to the Agency’s recommendations regarding proper disposal and cleanup of recalled product. Complaints and adverse events can be reported to FDA Consumer Complaint Coordinators or submitted using a MedWatch Online Voluntary Reporting Form.
  
  

Public meeting on front-of-package nutrition labeling.

• On November 16, 2023, the Reagan-Udall Foundation for the FDA convened a virtual public meeting on front-of-package (FOP) nutrition labeling, simplified nutrition information on the front of food packaging intended to aid consumers with food choices.
  
  
• As part of the White House’s National Strategy to end hunger and increase healthy eating and physical activity by 2030, FDA has been tasked with conducting research and proposing a standardized FOP system for food packages.
  
  
• The meeting included an update from FDA on its work to date and a segment for public comments from stakeholders on a variety of topics, such as international experience with front-of-package labeling, labeling design considerations, and the potential intersection of FOP labeling with other nutrition-related policies. FDA has not yet published a timeline for its rulemaking on this issue.
  
  

Final guidance on assessing the credibility of computational modeling and simulation in medical device submissions.

• On November 16, 2023, FDA issued final guidance, entitled, “Assessing the Credibility of Computational Modeling and Simulation in Medical Device Submissions.”
  
  
• Computational modeling and simulation (CM&S) are useful tools for streamlining pre-market activities and gathering evidence which more traditional testing methods do not facilitate. 
  
  
• In 2021, FDA published draft guidance on best practices for assessing the credibility of a CM&S model in a device submission, outlining a nine-part approach to credibility assessment. The 2023 final guidance largely maintains the approach set out in the draft and responds to industry feedback by clearly defining the scope of the framework and providing additional explanatory detail and examples, particularly in relation to identifying and categorizing credibility evidence.
  
  
• CM&S in medical device submissions remain a complex and developing area. The final guidance does not address methods that are still emerging, such as in silico clinical trials. 
  
  
• On January 11, 2024, FDA will host a webinar and accept questions on the final guidance.
  
  

FDA delays enforcement of cosmetic product facility registration and product listing.

• In December 2022, the Consolidated Appropriations Act, 2023, which included the Modernization of Cosmetics Regulation Act of 2022 (MoCRA), was signed into law. Among other provisions, MoCRA established requirements for cosmetic product facility registration and product listing by adding section 607 to the Federal Food, Drug, and Cosmetic (FD&C) Act (21 U.S.C. 364c).
  
  
• With some exceptions for small businesses and facilities subject to drug and device provisions, section 607 provides that registration must be submitted no later than December 29, 2023 or February 27, 2024, depending on when the facility first engaged in manufacturing or processing the given cosmetic product. Similarly, a product listing must be submitted by December 29, 2023 or within 120 days of distributing such product, depending on when the product was first marketed.
  
  
• However, last month, FDA finalized its “Compliance Policy for Cosmetic Product Facility Registration and Cosmetic Product Listing” guidance document, which discusses the Agency’s intention to delay enforcement of these requirements for six months – until July 1, 2024 – to help ensure that industry has sufficient time to comply with the requirements. While FDA continues to develop its specialized electronic portal to streamline the submission process, the guidance states that the Agency will be ready to accept registration and listing information by December 29, 2023 and encourages companies to meet this statutory deadline if possible.
  
  

FDA extends guidance for glass vials and stoppers closure system and component changes.

• FDA has extended the effective date of its “COVID-19 Container Closure System and Component Changes: Glass Vials and Stoppers” guidance to August 7, 2024, unless superseded by a revised final guidance before that date. 
  
  
• According to FDA, the supply of glass vials and stopper components for container closure systems (CCS) may be constrained during the COVID-19 public health emergency, leading manufacturers to update approved applications to include changes made to CCS components to meet demand. 
  
  
• In its guidance, FDA compiled its recommendations for reporting and implementation of certain post-approval changes to CCS components consisting of glass vials and stoppers for approved sterile drug products and biologics. The guidance also discusses pathways available for holders of approved new drug applications (NDAs), abbreviated new drug applications (ANDAs), and biologics license applications (BLAs) to obtain Agency feedback. 
  
  
• In order to avoid further impeding product supply, the Agency says it will consider risk-based approaches to implementation of chemistry, manufacturing, and controls (CMC) changes to a CCS and may expedite the assessment of a supplement or determine a different reporting category, where appropriate.
  
  

Draft guidance on translation of non-English of GLP study reports.

• On November 21, 2023, FDA issued a draft guidance, titled, “Translation of Good Laboratory Practice Study Reports: Questions and Answers.” The draft is intended to clarify FDA’s recommendations concerning the translation of study reports from a non-English language into English for studies conducted in compliance with good laboratory practice (GLP) regulations. 
  
  
• The document clarifies what constitutes a translated GLP study report, qualification of the translator(s), and whether signature is required the translated GLP study report, among others. The draft guidance also provides that written procedures should be in place for the translation of GLP study reports, and that the sponsor or the testing facility should retain the translated GLP study report along with the original study report. Finally, the document explains that a second person must review each translated GLP study report for completeness. 
  
  
• Interested parties should comments on or before February 20, 2024. 
  
  

Final guidance on real-time oncology review.

• On November 8, 2023, FDA issued a final guidance entitled, “Real-Time Oncology Review (RTOR).” RTOP was first launched in February 2018 to facilitate earlier submission of top-line results and datasets, after database lock, to support an earlier start to FDA application review. The final guidance is largely consistent with the 2022 draft guidance, with some minor clarifications on terminologies, eligibility criteria, and the submission process. 
  
  
• According to the final guidance, RTOP is limited to clinical trials with “easily interpreted” endpoints where the drug demonstrates substantial improvements over available therapies and will not require an advisory committee meeting or a new Risk Evaluation and Mediation Strategy (REMS).
  
  
• The final guidance also provides recommendations to applicants on the process for submission of selected new drug applications (NDAs) and biologics license applications (BLAs) with oncology indications for review under RTOR. Sponsors should read the final guidance, together with the standard operating procedures on the Real-Time Oncology Review website, when submitting NDAs/BLAs. 
  
  

FDA updates Leafy Greens STEC Action Plan.

• FDA released an update to its Leafy Greens STEC Action Plan, which was first released in 2020 in response to a number of reoccurring E. Coli outbreaks linked to leafy greens.  The November 17, 2023 update includes additional information on sampling assignments and method developments as well as a status update on the Agency’s long-term longitudinal studies in Arizona and California.  
  
  
• FDA also released a fact sheet on adjacent and nearby land uses and their impact on the safety of produce grown nearby.  Several recent produce outbreak investigations have identified conditions and practices on nearby lands as contributing factors, including the presence of wild and domesticated animals, recreational activities, worker practices, agricultural water, and trash storage.  The Produce Safety Rule requires these potential hazards to be addressed in order to minimize risk.
  
  

FDA Deputy Commissioner Jones shares his priorities for the Human Foods Program.

• FDA’s new Deputy Commissioner for the new Human Foods Program Jim Jones shared his priorities in a webinar with the Alliance for a Stronger FDA. 
  
  
• Jones outlined changes in the unified human foods program reorganization, such as combining the Office of Regulatory Affairs (ORA) inspectorate and Center for Food Safety and Applied Nutrition (CFSAN) compliance offices. He also mentioned elevating priorities like preventing foodborne illness through a new Office of Food Safety and risk prioritization efforts; enhancing chemical safety, including food additives and contaminants, through a chemical safety workplan; and elevating the role of nutrition by creating a Nutrition Center of Excellence.  
  
  
• Jones highlighted several regulatory priorities, including finalizing rules on produce safety, agricultural water use, front-of-pack labeling, and revisions to the healthy label by early 2023. He also discussed moving forward on added sugars and front-of-pack proposals. Because the reorganization package must be reviewed by OMB and the House and Senate, Jones noted that he aims to finalize the changes by June 2024.
  
  

Virtual public meeting on the reduction of added sugar consumption.

• FDA, along with federal partners in HHS and USDA, hosted a virtual public meeting and listening sessions in early November to address ways to reduce added sugar consumption.  The event reflects the new Human Foods Program’s priority on elevating the importance of nutrition to reduce chronic disease and is consistent with the September 2022 White House National Strategy on Hunger Nutrition and Health. 
  
  
• The agencies heard from a variety of government, industry, academic, consumer, and public health stakeholders.  Comments included creating voluntary sugar reduction targets as well as enhanced consumer education efforts.  Information on international efforts to reduce sugar consumptions was additionally provided.  
  
  
• In hosting the virtual meeting, the agencies aimed to share information in an effort to determine what future actions the federal government can take to reduce added sugar consumption within the US.