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17 April 20239 minute read

FDA Regulatory News and Trends - April 14 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 decides to withdraw Makena from the market. In a joint letter issued on April 5, 2023, FDA Commissioner Robert Califf and FDA Chief Scientist Namandjé Bumpus announced the Agency’s final decision to withdraw Makena (hydroxyprogesterone caproate), making it the first accelerated approval drug withdrawn entirely from the market for failure to meet post-approval requirements. In March, Makena’s manufacturer announced that it planned to remove the drug from the market and hoped to discuss a wind-down plan with FDA. The Agency’s official withdrawal decision leaves room for a wind-down period, and CDER will have the power to determine the next steps in the removal process. CDER will also need to develop a plan for how to address compounding of 17-OHPC, the generic form of Makena. FDA acknowledged that this now leaves no FDA-approved treatment for pre-term birth on the market, but the Agency determined that “exposing patients to the risks of a treatment that is not shown to be effective is not the solution.”

Narcan approved for over-the-counter use. On March 29, FDA approved Narcan, 4mg (naloxone hydrochloride) for over-the-counter, nonprescription use. FDA stated that the life-saving treatment for opioid overdose can now be sold directly to consumers in person and online – a measure that the Agency touted as another step in combatting the opioid crisis. Other formulations and dosages of naloxone will still require a prescription, but FDA referenced its willingness to work with other naloxone manufacturers to expand the availability of OTC naloxone products. In November 2022, FDA announced its preliminary assessment that certain naloxone products had the potential to be safe and effective for OTC use – paving the way for the Narcan 4mg OTC application submission and approval. While the OTC approval represents years of Agency and industry action, FDA acknowledged that the rollout of nonprescription Narcan is up to the manufacturer and that consumers should not expect to see the drug available over the counter for at least a few months.

New guidance document for soft contact lenses.  On March 28, 2023, FDA finalized a guidance entitled, “Soft (Hydrophilic) Daily Wear Contact Lenses – Performance Criteria for Safety and Performance Based Pathway.”  Following the draft guidance issued on March 4, 2020, the final guidance outlines FDA’s recommendations on performance criteria for 510(k) submissions for soft daily-wear contact lenses using the Safety and Performance Based Pathway.  The Pathway, which was described in a September 2019 guidance document, allows submitters of certain well-understood device types to establish that a new device meets FDA-identified performance criteria in order to demonstrate that the device is as safe and effective as a legally marketed device, as opposed to submitting a direct comparison of the performance of the subject device to that of a predicate device.  The March 2023 guidance notes that its application is limited to specific types of soft contact lenses and outlines the standards that submitters may use to demonstrate that their products fulfill FDA’s requirements.  The guidance states, “Consistent with FDA policy for all 510(k) submissions, for all 510(k) submissions under the Safety and Performance Based Pathway, FDA may request and review underlying data demonstrating that a new device meets the FDA-identified performance criteria and testing methodology, as necessary.” 

FDA seeks comments on third-party vendors that administer the REMS system. As Risk Evaluation and Mitigation Strategy (REMS) plans continue to gain public attention, including through the US District Court for the Eastern District of Washington’s recent mifepristone ruling, FDA recently published a new request for information from the public on how the Agency should approach requests from drug sponsors to switch third-party vendors that administer the REMS system.  REMS plans are implemented to ensure that the benefits of a drug, as actually used, outweigh a drug’s known and serious safety risks.  FDA was required to solicit stakeholder feedback on third-party vendor changes under the Consolidated Appropriations Act of 2023 (also known as the Food and Drug Omnibus Reform Act or FDORA) and was the likely result of recent cases where REMS changes significantly affected patient access to medications.  Comments are currently due by July 21, 2023.   According to FDA’s REMS Public Dashboard, 302 REMS plans have been implemented in total, and 61 remain active. 

Draft guidance for research involving children. On March 30, 2023, FDA and the Office for Human Research Protections (OHRP) published a draft guidance entitled, “Research Involving Children as Subjects and Not Otherwise Approvable by an Institutional Review Board.” Research involving children is currently regulated under 21 CFR Part 50 Subpart D and 45 CFR Part 46, Subpart D, which provide four situations in which such research can be approved by an IRB. The 2022 draft guidance discussed the first three situations, while the new joint draft guidance focused on the fourth situation (21 CFR 50.54), which applies to clinical investigations not otherwise approvable that present an opportunity to understand, prevent, or alleviate a serious problem affecting the health or welfare of children. Under the current practice, studies pursuant to 21 CFR 50.54 are referred to FDA, which then convenes a joint committee meeting. The new draft guidance introduced an “abbreviated process” where a committee meeting is not necessary if the Agency determines the newly referred research is “sufficiently similar” to the previously reviewed research. This abbreviated process is based on FDA’s understanding that “the subpart D regulations do not specify that the expert panel review of the research must occur after the IRB referral for review.” Comments for draft guidance are due on May 30, 2023.

Final guidance on Identification of Medicinal Products. On March 31, 2023, FDA published the long-awaited final guidance on the implementation and application of Identification of Medicinal Products (IDMP). The document, entitled, “Identification of Medicinal Products — Implementation and Use,” aims to enable improved accuracy, completeness, and consistency of the post-market drug safety report in the international space. The IDMP standards were developed within the ISO network member organizations, and FDA has been working to harmonize and align the Agency’s standards to IDMP standards. The document does not include operational changes for the industry but explains FDA’s position and progress on aligning the Agency’s standards to IDMP standards. One key message is that FDA will continue to take the “phased” approach to the global implementation of IDMP.

Framework for the use of digital health technologies in drug development. As part of the Prescription Drug User Fee program reauthorization in which FDA committed to advancing new policies related to digital health technologies (DHTs), FDA recently published its roadmap for the use of DHTs in drug and biological product development. The document is intended to serve as a reference and guide on what the Agency has implemented thus far and what it has planned with respect to using DHT-derived data. According to FDA, this multifaceted DHT program “will include workshops and demonstration projects; engagement with stakeholders; establishment of internal processes to support the evaluation of DHTs for use in drug development; promotion of shared learning and consistency regarding DHT-based policy, procedure, and analytic tool development; and publication of guidance documents.”

Duke and FDA conduct a public workshop on the use of digital health technologies in clinical trials. Under a cooperative agreement with FDA – and to satisfy another part of the Agency’s PDUFA VII commitment – Duke-Margolis Center for Health Policy hosted a workshop on using DHTs to support drug development and review. During the two-day event, stakeholders discussed the advantages and challenges of using DHTs in clinical trials – from providing more equitable access to trials and leveraging greater data accuracy, to the impact on patient engagement and reporting burden. Companies also presented use cases for DHTs currently being used in clinical studies. Specifically, experts discussed the challenge of finding ways to ensure DHTs meet patient needs related to comfort, convenience, and usability to encourage adoption and proper use of the technologies during studies. Generally, industry opined on the need for greater regulatory clarity around DHTs, and FDA expressed optimism for a continued partnership in finding solutions to regulatory challenges.

Draft guidance on dietary statements for food labels. On March 24, the FDA issued draft guidance on how and when dietary guidance statements should be used on food labels. The draft guidance aims to ensure that these statements promote good nutrition. Noting that “eating patterns in the US do not align with dietary recommendations,” the FDA said that the goal of the draft guidance is to encourage healthier habits in consumers, enhance consistency in labeling and improve customer understanding of the contents of the foods they eat and of nutrition overall.

New content requirement for cyber device submissions. On March 30, 2023, CDRH released a guidance document titled, “Cybersecurity in Medical Devices: Refuse to Accept Policy for Cyber Devices Under Section 524B of the FD&C Act.” The guidance explains that CDRH will begin requiring cybersecurity-related information in submissions for cyber devices and will refuse to accept (RTA) submissions that fail to provide this info. The term "cyber device" is defined as a device that (1) includes software validated, installed, or authorized by the sponsor as a device or in a device; (2) can connect to the internet; and (3) contains any such technological characteristics validated, installed, or authorized by the sponsor that could be vulnerable to cybersecurity threats. While the policy is effective immediately, CDRH explains that it will not RTA affected submissions until October 1, 2023. Until then, the information is still required in submissions, but CDRH will work interactively with sponsors to obtain it if it is not already included.