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9 June 202310 minute read

FDA Regulatory News and Trends - June 9, 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.

PHE expiration ends mandatory medical device shortage reporting.

  • Section 506J of the Federal Food, Drug, and Cosmetic Act gives FDA authority to require certain device shortage reporting in connection with a public health emergency (PHE).

  • The expiration of the COVID-19 PHE on May 11, 2023 means that it is no longer mandatory for device manufacturers to submit 506J notifications.

  • FDA updated its Supply and Shortages of Medical Devices: Frequently Asked Questions webpage to explain the changes following the end of the PHE; provide information on its draft guidance on 506J notifications outside of the COVID-19 context; and encourage voluntary medical device shortage reporting.

  • In accordance with the Consolidated Appropriations Act of 2023, FDA is working to issue or revise its draft guidance on 506J notifications outside of the COVID-19 context ahead of the December 29, 2023 deadline.

Final guidance on adjusting for covariates in randomized clinical trials.

  • FDA recently finalized its guidance regarding adjustment for covariates in the statistical analysis of randomized clinical trials, as applicable to both superiority and noninferiority trials.

  • Clinical trials are performed to evaluate whether an investigational product provides a clinical benefit to patients, and a part of such evaluation requires accounting for several factors (ie, covariates) to establish a reliable causal link between the product and a clinical endpoint.

  • Because participant randomization hypothetically minimizes this causal relationship between outcomes and some characteristic attributed to certain participants (rather than to the investigational intervention), FDA recommends adjusting inclusion/exclusion criteria and employing other study design methods – such as stratifying participants – to account for covariates.

Finalized guidance on whole-slide imaging in nonclinical studies.

  • FDA recently released a Q&A-style final guidance intended to provide information to sponsors and nonclinical laboratories on the use and management of whole-slide images in histopathology assessment and/or pathology peer review for toxicology studies.

  • 21 CFR 58 outlines the requirements surrounding the conduct and reporting of good laboratory practices for nonclinical studies to the FDA. The guidance provides recommendations on topics not addressed by these regulations. Specifically, with the emergence of digital pathology and the digitization of tissue sample slides, the Agency seeks to provide standards to ensure appropriate storage, validation, image quality, and file integrity with respect to whole-slide imaging.

  • Through these eight questions and answers, FDA advises sponsors and nonclinical laboratories on proper slide, file, and processing modification documentation/retention, including considerations for securing data and ensuring viewability as the technology continues to evolve.

Draft guidance on generally accepted scientific knowledge in drug and biologics applications.

  • On May 23, 2023, FDA issued a draft guidance, titled, “Generally Accepted Scientific Knowledge (GASK) in Applications for Drug and Biological Products: Nonclinical Information.” The document offers FDA’s understanding of GASK, addresses the use of GASK in non-clinical studies, and provides two examples.

  • GASK is not a regulatory term. FDA describes GASK as “medical or scientific information that is generally accepted by experts qualified by scientific training and experience in the relevant field, including FDA experts.” For example, textbook excerpts can be submitted as evidence of GASK. However, the guidance did not clarify how peer-reviewed literatures or other publications could be used as evidence of GASK.

  • The guidance describes two circumstances in which the sponsor can rely on GASK to meet certain nonclinical safety requirements: (1) where a product contains a substance (either naturally derived or synthesized) that occurs naturally in the body, and sponsors have relied on GASK regarding that substance and its known effect on biological processes instead of conducting certain nonclinical studies; and (2) where a sponsor has demonstrated a drug’s impact on a particular biological pathway.

  • Interested parties should submit comments on or before July 24, 2023.

Two draft guidances on pediatric drug development.

  • On May 17, 2023, the FDA issued two draft guidances, titled, “Pediatric Drug Development: Regulatory Considerations – Complying with PREA and Qualifying for Pediatric Exclusivity Under the BPCAand “Pediatric Drug Development Under the Pediatric Research Equity Act and the Best Pharmaceuticals for Children Act: Scientific Considerations.” Both the Best Pharmaceuticals for Children Act (BPCA) and Pediatric Research Equity Act (PREA) aim to promote pediatric drug development. BPCA provides important incentives of additional marketing exclusivity to sponsors who voluntarily complete pediatric clinical studies, and PREA gives FDA the authority to mandate pediatric studies under certain circumstances.

  • The 39-page draft guidance on exclusivity focuses on PREA compliance and describes the process to obtain pediatric exclusivity and the relevant protections under BPCA. This guidance additionally addresses statutory requirements related to adverse event reporting, pediatric study plans (PSPs), deferral extensions, and noncompliance with requirements under PREA.

  • The scientific considerations draft guidance discusses selected clinical, scientific, and ethical issues regarding the development of drugs, biological products, and vaccines for pediatric use under PREA and/or BPCA.

  • Interested parties should submit comments on or before July 17, 2023.

Proposed amendment to human prescription drug labeling regulations.

  • FDA is proposing to amend its human prescription drug labeling regulations to require a new type of Medication Guide – "Patient Medication Information” – for prescription drug products used, dispensed, or administered on an outpatient basis.

  • Patient Medication Information would provide patients with clear, concise, accessible, and useful written information for prescription drugs and certain biological products and would be delivered in a consistent and easy-to-understand format to help patients use their prescription drug and certain biological products safely and effectively.

  • FDA Commissioner Robert Califf cited the “confusing, conflicting, incomplete, or repetitive” nature of the current system where Medication Guides accompany pages of other treatment literature.

  • The docket for the Patient Medication Information is currently open for comments.

Update to CDER and CBER's Study Data Technical Conformance Guide.

  • On May 24, 2023, the Center for Drug Evaluation and Research (CDER) and Center for Biologics Evaluation and Research (CBER) updated their technical specifications document, titled, “Study Data Technical Conformance Guide(SDTCG), which is a supplement to the guidance document titled, “Providing Regulatory Submissions in Electronic Format – Standardized Study Data.”

  • The SDTCG was first issued in 2014 and is periodically updated to provide the latest specifications, recommendations, and general considerations on how to submit standardized study data using FDA-supported data standards. The recent update revises modifications FDA made to its data standards requirements to help industry adapt to the COVID-19 public health emergency.

  • Specifically, now that the PHE has ended, the update reinstates the requirement that datasets submitted to the Agency be in the Standard for Exchange of Nonclinical Data (SEND) format. A grace period for this change will be allowed until November 8, 2023.

New project related to diversity in cancer research within Asian American, Native Hawaiian, and other Pacific Islander populations.

  • On May 9, 2023, FDA’s Oncology Center of Excellence (OCE) announced the launch of Project ASIATICA, an initiative focusing on diversity in cancer research within the Asian American, Native Hawaiian, and other Pacific Islander (AA and NHPI) populations.

  • Project ASIATICA will focus on advocacy, research, and policy, with a goal of bringing greater awareness and understanding of the challenges faced by AA and NHPI patients with cancer.

  • FDA noted that more than 20 million people in the US identify as part of the AA or NHPI communities, and that cancer is the leading cause of death for these communities.

New draft guidance on clinical trials for diabetes drugs.

  • On May 26, 2023, FDA released a new guidance, entitled, “Diabetes Mellitus: Efficacy Endpoints for Clinical Trials Investigating Antidiabetic Drugs and Biological Products.”

  • The draft guidance is intended to help sponsors develop antidiabetic drugs for adults and children with type 1 diabetes mellitus (T1D) and/or type 2 diabetes mellitus (T2D).

  • When finalized, the guidance will address FDA’s current recommendations regarding defining efficacy endpoints for clinical trials investigating antidiabetic drugs, and will replace the relevant sections in the February 2008 draft guidance, "Diabetes Mellitus: Developing Drugs and Therapeutic Biologics for Treatment and Prevention," which was withdrawn in March 2020 due to outdated recommendations for safety assessment.

  • The new draft guidance provides recommendations and guidelines for using various clinical trial efficacy endpoints, including A1C, hypoglycemia, and additional endpoints that are used supportively in clinical trials that may be appropriate for inclusion in drug labeling, such as fasting plasma glucose, postprandial glucose, and CGM-based metrics.

  • FDA notes that sponsors also may propose other clinically meaningful endpoints for drugs intended for patients with diabetes.

  • Comments to the draft guidance should be submitted by August 24, 2023.