FDA Regulatory News and Trends - October 25, 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 holds public meeting on modernizing recalls of FDA-regulated products.

• In FDA’s continued effort to update recall strategies, the Agency hosted a forum for members of regulated industry, advocacy groups, and the public to provide feedback and possible solutions to modernize recalls. While representatives from every FDA Center were in attendance, the majority of public comments revolved around food and medical device recalls.
  
  
• With respect to the food industry, multiple presenters urged the Agency to leverage social media and certain technologies to ensure more timely and widespread communication of recalls, particularly to underserved communities. To that end, stakeholders also suggested using more inclusive, consumer-friendly language that is both clear and concise to more effectively communicate the urgency of recalls and how such recalls can affect consumers. Others commented on the regional inconsistencies in how recalls are treated and classified, recommending that agencies at the federal and state level integrate efforts to help minimize consumer confusion.
  
  
• On the medical device side, speakers expressed concern regarding implantable devices due to the lack of oversight and unreliable recall notifications. Presenters urged the Agency to increase engagement with healthcare providers to create a more efficient, sustainable, and nationalized route to patients through streamlined information exchange and automated electronic notifications. Stakeholders also called for mandating standardized reimbursement for associated device removal costs, as well as steeper penalties for failing to notify patients. 
  
  
• The comment period will remain open through October 27, 2023. 

FDA updates infant formula compliance program. 

• On October 6, FDA updated its infant formula compliance program for FDA investigators, laboratory analysts, and compliance officers. 
  
  
• The compliance program is designed to comprehensively outline the Agency’s approach for inspections, sample collection, sample analysis, and compliance activities to help ensure that infant formula products in the US food supply are safe and nutritious. 
  
  
• This effort, the Agency said, is part of the FDA’s ongoing commitment to strengthen the safety, resiliency, and oversight of the infant formula industry. In 2022, an internal FDA evaluation recommended that the Agency review and update its infant formula compliance program to ensure that it reflected the latest science on the bacterium Cronobacter and that it offered consistency and clarity regarding its inspection and compliance activities.

Final guidance on incorporating dose banding information into labeling of an injectable drug product.

• On October 2, 2023, FDA issued a final guidance, titled “Human Prescription Drug and Biological Products – Labeling for Dosing Based on Weight or Body Surface Area for Ready-to-Use Containers – 'Dose Banding.’” 
  
  
• According to the guidance, New Drug Application and Biologics License Application (NDA/BLA) applicants who seek to include dose banding information in labeling must provide adequate data to support the safety and efficacy of the proposed ranges. “Adequate data” can be data or information on dosing based on weight or body surface area (BSA) that the applicant owns or to which it has a right of reference, or by relying on published literature, to support approval of a 505(b)(2) application. Model-informed drug development approaches can be used to assist in determining dosing using strengths available in ready-to-use containers. 
  
  
• The guidance further provides recommendations for labeling and a fictitious labeling example. 
  
  

Final guidance and new draft guidance on sprouts for human consumption.

• On September 28, 2023, FDA issued a final guidance, titled, “Standards for the Growing, Harvesting, Packing, and Holding of Sprouts for Human Consumption,” and a separate new draft guidance to replace the original 2017 draft guidance. 
  
  
• The 2023 final guidance updates and finalizes the following sections of the original 2017 draft guidance: cleaning and sanitizing, agricultural water in sprout operations, seeds for sprouting, environmental monitoring, and recordkeeping. The 2023 draft guidance updates the following sections: (1) equipment, tools, and buildings, (2)sampling and testing of spent sprout irrigation water (or in-process sprouts), and (3)personnel qualifications training and hygienic practices. Once finalized, the sections in the 2023 Draft Guidance will be incorporated into 2023 final guidance, creating a single, complete final guidance document.
  
  
• Interested parties should submit comments for the 2023 draft guidance on or before March 27, 2024. 

CDRH releases two guidances on its new eSTAR electronic submission platform.

• From late September to early October, Center for Devices and Radiological Health (CDRH) released two guidance documents (one final and one draft) providing information on its electronic Submission Template and Resource (eSTAR) system. Prior to eSTAR, CDRH's eCopy system required companies to load an electronic copy of their submission onto a CD or USB drive and mail it to the center. eSTAR, however, allows companies to simply upload the electronic submission to an online portal, eliminating the need for physical mail.
  
  
• The final guidance, titled, “Electronic Submission Template for Medical Device 510(k) Submissions,” details the process for 510(k) submissions using eSTAR. The eSTAR platform had been available for 510(k) submissions for roughly a year, but, as of October 1, 2023, it use is mandatory for these types of submissions. The draft guidance, “Electronic Submission Template for Medical Device De Novo Requests,” similarly explains the process for DeNovo submissions using eSTAR and informs that FDA intends to identify a specific date on which it will require DeNovo submissions to be made using eSTAR by September 30, 2025.
  
  
• Medical device companies planning to make a 510(k) submission to the agency are encouraged to immediately familiarize themselves with the eSTAR platform as these submissions must now be made using the new system. Companies planning De Novo submissions should also become familiar with the new system and consider testing it out on their next submission, even though it is not yet mandatory, as it too will eventually be required.
  
  

New guidance on AST system devices incorporating PCCPs.

• FDA has issued an immediately-in-effect guidance allowing for certain iterative updates to antimicrobial susceptibility test (AST) systems using pre-determined change control plans (PCCPs). The new guidance supersedes 2009 guidance on updating labeling and lays out FDA’s latest thinking on the process for AST device sponsors to update susceptibility test interpretive criteria, also referred to as breakpoints, in labeling.
  
  
• ASTs are used to inform antibiotic treatment protocols. This new guidance seems to be part of the FDA’s broader push to address antimicrobial resistance by offering a creative new way to streamline AST system updates.
  
  
• FDA will hold a public webinar on this final guidance on November 9, 2023.
  
  

Guidance on technical considerations for medical devices with PCLC technology.

• Taking feedback from 2021 draft guidance into account, new FDA guidance, titled, “Technical Considerations for Medical Devices with Physiologic Closed-Loop Control Technology,” clarifies guidance scope and technical considerations for physiologic closed-loop control (PCLC) technology. 
  
  
• The guidance provides additional examples of medical device functions that may be considered PCLC technology, identifies risks that sponsors should consider, and adds details on when PCLCs may be used in integrated clinical environments (ie, environments where a patient uses multiple interoperable devices for their care).
  
  
• PCLC devices use feedback from physiologic sensors for automatic control of physiologic variables via delivery or removal of energy or a substance. FDA acknowledges that PCLC devices can play a significant role in reducing cognitive overload, minimizing human error, and enhancing medical care. 
  
  

Draft guidance on drugs for stimulant use disorders.

• On October 5, 2023, FDA released a new draft guidance, “Stimulant Use Disorders: Developing Drugs for Treatment.”  The guidance is intended to assist sponsors in the development of drugs for the treatment of stimulant use disorders by providing recommendations on clinical trial design. It additionally outlines recommendations on the overall development program to support indications for treatment of stimulant use disorders.  
  
  
• The draft guidance focuses on drugs developed for the treatment of moderate to severe cocaine use disorder, moderate to severe methamphetamine use disorder, or moderate to severe prescription stimulant use disorder. 
  
  
• The guidance document provides recommendations related to early-phase development considerations, efficacy trial considerations, potential efficacy trial endpoints, benefit-risk considerations, labeling, and the applicability of expedited programs.  
  
  
• Comments on the draft guidance should be submitted by December 4, 2023.
  
  

Draft guidance on medical product development for graft-versus-host diseases.

• On September 29, 2023, FDA released a new draft guidance, titled, “Graft-versus-Host Diseases: Developing Drugs, Biological Products, and Certain Devices for Prevention or Treatment.” The draft guidance is intended to assist sponsors in the clinical development of drugs, biological products, therapeutic devices, and cell processing devices for the prevention or treatment of acute graft-versus-host disease (aGVHD) or chronic graft-versus-host disease (cGVHD) after allogenic hematopoietic stem cell transplantation (HSCT). 
  
  
• The draft guidance provides recommendations related to the clinical development program and critical design elements for early- and late-phase trials for the intended populations, including clinical trial design, statistical analysis, and other issues specific to aGVHD or cGVHD.  
  
  
• The draft document also includes a section containing recommendations for completing the marketing application for these products, including the submission of information related to the assessment of efficacy and the assessment of safety.
  
  
• Comments on the draft guidance should be submitted by November 28, 2023.