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20 March 20238 minute read

FDA Regulatory News and Trends - March 20, 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.

Final guidance on Continuous Manufacturing of Drug Substances and Drug Products.  On March 1, 2023, FDA issued final guidance on continuous manufacturing of drug substances and drug products as well as a discussion paper on Artificial Intelligence (AI) in drug manufacturing. The publication acknowledges the many possible applications and benefits AI offers in a manufacturing context and identifies regulatory questions focused on five areas where CDER is seeking feedback for potential policy development. The final guidance generally preserves the requirements of the draft guidance while adding useful details and examples to improve clarity. The transition from batch to continuous processes operations introduces a fundamental shift in risk: one that moves away from the traditional exposures associated with human error over to process- and connected systems-based vulnerabilities. Drug manufacturers using, or planning to use, continuous manufacturing will need to address this shift via their risk management procedures and can leverage the added detail in the final guidance to assist with that process. See our most recent client alert for a detailed analysis on artificial intelligence in drug manufacturing.

Emergency use of an OTC combined COVID-19 and flu test. FDA recently authorized emergency use of an over-the-counter, combined COVID-19 and flu test manufactured by Lucira Health. The first of its kind, single-use test can provide results in 30 minutes and can differentiate between two flu strains and COVID. CDRH Director Jeff Shuren called the authorization of the test a “major milestone in bringing greater consumer access to diagnostic tests that can be performed entirely at home”. While FDA celebrates this approval as a step to broader access to diagnostic testing, the authorization was issued following a protracted process that the company anticipated would be completed in mid-2022. Lucira, expecting to sell tests months earlier, filed for Chapter 11 bankruptcy protection. FDA, in a rare move, provided comment explaining the delay. FDA stated that Lucira had to redesign its product since one of the components was unsuitable for at-home use. The agency added that Lucira’s initial submission did not include sufficient Influenza A samples, and that correcting for these two issues required a new submission that was finalized towards the end of 2022. So, while the test is now authorized by FDA, the actual production and eventual use of the device remains an open question.

FDA chief supports product disclosure for supplements. In a February 24 blog post on the FDA website, FDA Commissioner Robert Califf said he supports product listing on dietary supplement packages to help fulfill his hope for “an improved framework to appropriately regulate dietary supplements.” In response, some dietary-supplement trade groups, such as the Council for Responsible Nutrition, supported the plan, while other groups, such as the American Herbal Products Association and the Natural Products Association, opposed it. “This enormous industry continues to grow and it’s now part of everyday life for many families,” Califf wrote. “Dietary supplements should be required to list with the FDA and companies should be accountable for revealing what is in the supplement being sold. In the long run we will have more information about the benefits and risks of dietary supplements as our methods of evidence generation improve, and I hope for a regulatory regime that can encourage better information for consumers to be informed about their choices.”

Four devices enrolled in TPLC TAP pilot. On March 1, 2023, FDA announced that the agency had enrolled four devices in the Total Product Life Cycle (TPLC) Advisory Program (TAP) pilot. The program aims to provide rapid and widespread patient access to “safe, effective, high-quality medical devices” by promoting “early, frequent, and strategic communications” between the FDA and medical device sponsors. The four recent enrollments are part of the TAP Pilot Soft Launch phase, during which the FDA intends to enroll up to 15 devices in the Office of Cardiovascular Devices. In subsequent fiscal years, the program will be expanded to enroll more devices and to include devices reviewed in other Office of Health Technology (OHTs).

Umbrella EUA for single-use surgical masks. On March 6, 2023, FDA revised and reissued the umbrella EUA Letter of Authorization for single-use surgical masks. The revised EUA does not revoke surgical masks currently operating under the umbrella EUA, only that FDA will no longer accept new surgical masks under the umbrella EUA. FDA advises manufacturers who are interested in marketing new surgical masks should “follow traditional premarket pathways, such as a premarket notification, or 510(k),” and “refer to the FDA’s guidance on surgical masks for further information.

FDA digital health technology activity heats up. FDA has established a digital health technology (DHT) Steering Committee fulfilling a PDUFA VII commitment. The committee, consisting of senior staff from CDER, CBER, and CDRH, will support the implementation of DHT PDUFA VII commitments (including DHT framework, guidance documents, demonstration projects and training, to name a few), engage externally on DHT-related issues and work to ensure consistency across FDA in respect of the review of drug submissions with DHT-derived data. FDA also published a new webpage dedicated to DHTs for drug development. These updates lay the groundwork for increasing activity in this space. 2023 is set to be a blockbuster year for DHT policy. In March alone, FDA is going to hold a public meeting on “Understanding Priorities for the Development of Digital Health Technologies to Support Clinical Trials for Drug Development” and we also anticipate publication of FDA’s Framework for the Use of DHTs in Drug and Biological Product Development.

Final virtual town hall on test development during PHEs. FDA will host its last virtual town hall meeting on test development and validation during public health emergencies (PHE). These meetings, which started in March 2020, allowed the Agency to continuously provide feedback to developers on the ever-evolving test development process for COVID-19, and eventually for Monkeypox. As indicated in the last town hall, FDA plans to wind down the EUA review process by shifting priorities and efforts elsewhere, as the PHE comes to an end. The Agency also stated that it is currently finalizing the medical device EUA transition plan, which outlines the process for terminating applicable EUA declarations, submitting market access applications, and proposing “transition implementation plans” for distributed products. The 102nd and final town hall meeting is scheduled for March 22, 2023.

FDA and Health Canada meeting on harmonization guidelines. FDA and Health Canada held a public meeting last month to discuss the development status of several new ICH guidelines. The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH), which seeks to achieve greater harmonization of medicine regulations globally, has reached various milestones for several guidance documents. Notably, the S12 guideline, expected to be adopted by regulatory agencies in the first half of 2023, provides harmonized recommendations for nonclinical biodistribution studies for gene therapies. In addition, the Q5A(R2) guideline, with finalization anticipated for later this year, suggests requirements for viral safety testing for biotechnology-derived products. The draft M12 guideline, set to be finalized in 2024, provides recommendations to promote a consistent approach in designing, conducting and interpreting drug-drug interaction studies during development. The M13A guideline, which is currently open for public comment, provides a standard for bioequivalence guidelines in an effort to harmonize requirements across jurisdictions.

New draft guidance on potency assay considerations for monoclonal antibodies and other therapeutic proteins. On March 2, 2023, FDA issued a new draft guidance on potency assay considerations for monoclonal antibodies and other therapeutic proteins targeting viral pathogens.  The draft guidance is intended to provide sponsors with detailed recommendations for developing and implementing potency assays to ensure that the potency of monoclonal antibodies and other therapeutic proteins that directly target viral proteins or host cell proteins mediating pathogenic mechanisms of infection is consistent across each lot and maintained over the shelf life of the product.  The draft guidance includes specific considerations for different types of assays, including binding assays, viral neutralization assays, and Fc-effector function assays.  In January 2021, FDA published a similar guidance related specifically to COVID-19, titled COVID-19: Potency Assay Considerations for Monoclonal Antibodies and Other Therapeutic Proteins Targeting SARS-CoV-2 Infectivity.  That guidance, however, will expire upon the ending of the public health emergency declaration, and FDA notes that many of the recommendations set forth in the 2021 guidance are applicable to contexts other than just COVID-19.  Comments on the new draft guidance are due on May 1, 2023.