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3 May 20237 minute read

FDA Regulatory News and Trends - May 3, 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.


New FDA guidance on risk-based monitoring of clinical investigations. On April 13, 2023, FDA released a new guidance document titled, “A Risk-Based Approach to Monitoring of Clinical Investigations Questions and Answers Guidance for Industry.” The guidance supplements FDA's 2013 guidance on risk-based monitoring to provide additional clarity on implementation of the discussed monitoring approach. In the 2013 guidance, FDA acknowledged that "there is a growing consensus that risk-based approaches to monitoring, focused on risks to the most critical data elements and processes necessary to achieve study objectives, are more likely than routine visits to all clinical sites and 100% data verification to ensure subject protection and overall study quality." Essentially, risk-based monitoring allows for cheaper and more effective monitoring of studies by focusing oversight efforts on the areas that matter most. The 2023 guidance provides recommendations to help those conducting studies understand how to implement a risk-based approach to monitoring. Specifically, it elaborates on development of a monitoring approach, content of a monitoring plan and handling of issues found during monitoring.

Draft guidance on clinical outcome assessments in patient-focused drug development. On April 5, 2023, FDA released a draft guidance titled, “Patient-Focused Drug Development: Incorporating Clinical Outcome Assessments Into Endpoints for Regulatory Decision-Making,” as part of the Agency’s commitment under the 2017 PDUFA VI authorization and the 21st Century Cures Act. This is the fourth (Guidance 4) and last installment of the clinical outcome assessment (COA) series that discusses the methodologies of patient-focused drug development (PFDD). The latest document focuses on the methods, standards and technologies for collecting and analyzing COA data, and how to select COA-based endpoints and determine clinically meaningful differences in these endpoints, especially with regard to efficacy evaluations. Sponsors are encouraged to read Guidance 3 (draft) and Guidance 4 together as the documents complement one another, with Guidance 3 focusing on how to determine whether a COA is fit for purpose, and Guidance 4 discussing “the rationale for the proposed use of COA scores to construct endpoints that will support inferences about the effect of a medical product on how patients feel or function.” FDA will discuss the draft guidance in a webinar on May 4, 2023. Comments (FDA-2023-D-0026) are due by July 5, 2023.

CDRH announces medical device sterilization pilot expansion. In exploring ways to address environmental concerns, the Agency launched a pilot in late 2019 to allow certain manufacturers with devices under Pre-Market Approval (PMA) to move away from their ethylene oxide (EtO) sterilization practices. Now, the FDA Center for Devices and Radiological Health (CDRH) is announcing a new, expanded pilot to advance alternatives to, and minimize reliance on, both EtO and the other main sterilization method: gamma radiation. The voluntary Radiation Sterilization Master File Pilot Program allows companies that sterilize single-use medical devices using either method to submit Master File(s) when making certain changes to sterilization sites, methods or processes under specific conditions, in lieu of submitting PMA supplements for such changes. The pilot program seeks to provide insights into regulatory approaches that may help address potential device shortages related to shifts in sterilization practices and facilitate supply-chain resiliency. The White House also recently completed its review of proposed EtO regulation, which proposes stricter standards for the use of EtO as a sterilant and fumigant – meaning that the device industry must additionally consider adjusting its sterilization approaches to comply with the environmental regulators’ expectations.

Draft procedural guidance on notifications of supply-chain disruptions. On April 6, 2023, FDA released a draft guidance document entitled, “Notifying FDA of a Discontinuance or Interruption in Manufacturing Finished Products or Active Pharmaceutical Ingredients Under Section 506C of the FD&C Act.” In an effort to help FDA prevent and mitigate shortages, the guidance provides nonbinding recommendations on complying with section 506C of the Federal Food, Drug, and Cosmetic Act and related regulations by notifying FDA of changes in the production of certain finished drugs, biological products and active pharmaceutical ingredients that reflect a permanent discontinuance or an interruption, which may impact supply chain distribution. The guidance outlines who must notify FDA, what products are subject to notification requirements, when to notify FDA and what information should be included in notifications.  The guidance additionally explains that failure to comply will result in the issuance of a noncompliance letter and an opportunity to respond.  If FDA determines that a manufacturer did not have a reasonable basis for failing to notify FDA as required, the Agency will post the noncompliance letter and response on FDA’s website with appropriate redactions. The draft guidance makes clear that it is being distributed for comment purposes only and is not for implementation.  Though comments may be submitted at any time, FDA recommends commenting by June 5, 2023 to ensure consideration before the Agency begins finalizing the guidance.

Long-awaited draft guidance on OTC monograph order request. FDA recently issued draft guidance entitled, “Over-the-Counter Monograph Order Requests (OMORs): Format and Content.” The document is part of FDA’s implementation of OTC monograph reforms included in the 2020 CARES Act and describes the necessary components for an OMOR. OMORs allow manufacturers to request OTC monograph changes or updates, and the OTC monograph reforms included in the bill add new structure and timetables to a previously drawn-out, unpredictable administrative order process. The long-awaited guidance fulfills one of FDA’s Over-the-Counter Monograph User Fee Agreement (OMUFA) commitments and provides manufacturers a resource to determine completeness and adequacy of OMORs. According to the guidance, OMORS will be organized into modules and share common elements with other electronic submissions for FDA-regulated products. The draft guidance additionally offers advice on how to organize certain modules if generally-recognized-as-safe-and-effective (GRASE) ingredients are involved and describes what OMOR submission information will and will not be published upon consideration and approval of the given order request.

FDA letter to industry on transfer of plant genes linked to food allergens. On April 13, 2023, FDA issued a letter to manufacturers and developers of new plant varieties regarding the potential for transfer of genes for proteins that are food allergens into new plant varieties used for food. The Agency explained that, for example, a developer could add the gene for an allergenic animal protein to a new plant variety to create a non-animal source of protein, which could result in the presence of an unexpected allergen in that food. The letter recommends that developers of the products closely consider their risk-management plans and labeling, as well as controls to ensure the product does not inadvertently enter the food supply. The letter reminds industry of FDA's premarket consultation program and encourages developers of these products to engage with the Agency early in the product-development process.