FDA Regulatory News and Trends - April 29, 2024

Welcome to FDA Regulatory News and Trends, designed to help you identify significant legal developments and navigate the evolving business, legal, and regulatory world.

CBER and CDER issue update to their Study Data Technical Conformance Guide.

• CBER and CDER released a March 2024 update to their document entitled, “Study Data Technical Conformance Guide - Technical Specifications Document.” This document is incorporated by reference into the guidance document entitled, “Guidance for Industry Providing Regulatory Submissions in Electronic Format – Standardized Study Data.”


• This conformance guide provides technical recommendations to sponsors for the submission of animal and human study data in a standardized electronic format to CBER and CDER. Updates in this most recent version include new specifications for information contained in the SAS laboratory domain (LB Domain), revisions to drug naming conventions, and the addition of new trial summary parameters that sponsors may use.


• Drug and biologic companies developing an IND, NDA, ANDA, and BLA submission are encouraged to review these technical specification changes to ensure study data contained in their submissions to FDA conform with the current expectations for electronic data.

CDRH releases draft guidance on 510(k) animal studies for dental bone grafting material.

• On March 29, 2024, CDRH released the draft guidance entitled, “Animal Studies for Dental Bone Grafting Material Devices - Premarket Notification (510(k)) Submissions.” FDA defines these products as those that are intended to “fill, augment, or reconstruct periodontal or bony defects of the oral and maxillofacial region.”


• The Agency recently down-classified all bone grafting material devices for dental indications (except those containing a drug or biologic) from Class III to Class II. This change allows manufacturers to pursue marketing authorization through the less burdensome 510(k) pathway instead of the traditional PMA pathway. The draft guidance provides information on the animal models and study designs FDA would expect for animal studies supporting a 510(k) for this product type.


• Device companies developing new dental bone grafting material devices are encouraged to review this draft guidance and incorporate its principles into their animal studies and, ultimately, their 510(k) submissions. Interested stakeholders should also consider submitting comments to help shape the final guidance at Docket # FDA-2024-D-1242.

E2D(R1) Post-Approval Safety Data Draft guidance.

• On March 14, 2024, FDA released draft guidance, titled, “E2D(R1) Post-Approval Safety Data: Definitions and Standards for Management and Reporting of Individual Case Safety Reports.” The draft guidance updates the existing E2D guidance entitled, “E2D Post-Approval Safety Data Management: Definitions and Standards for Expedited Reporting,” published in 2003.


• This guideline provides recommendations that are harmonized to the extent possible given differences in post-market safety reporting requirements among ICH regions.


• Major updates of the draft guidance include clarifying the use of new or increasingly used data sources (eg, social media, market research programs, patient support programs) and updating terminology and standards for postmarket adverse event reporting.

Draft guidance on data integrity for in vivo BA and BE studies.

• On April 1, 2024, FDA published a new draft guidance, titled, “Data Integrity for In Vivo Bioavailability and Bioequivalence Studies.” The guidance aims to provide recommendations to applicants and testing site management on achieving and maintaining data integrity for the clinical and bioanalytical portions of bioavailability (BA) and bioequivalence (BE) studies submitted in support of relevant FDA submissions, including investigational new drug applications (INDs), new drug applications (NDAs), and abbreviated new drug applications (ANDAs), and the bioanalytical portion of clinical pharmacologic studies supporting CDER-regulated biologic license applications (BLAs), as well as amendments and supplements to these applications.


• The guidance provides recommendations for applications on testing site selection and monitoring and oversight. It additionally provides recommendations for testing site management and elements of a quality management system.


• Interested parties should submit comments by July 3, 2024.

Final guidance on electronic submission of expedited safety reports from IND-exempt BA/BE studies.

• FDA released final guidance on the electronic submission of expedited individual case safety reports (ICSRs) from investigational new drug (IND)-exempt bioavailability/bioequivalence (BA/BE) studies conducted to support abbreviated new drug applications (ANDAs) to FDA Adverse Event Reporting System (FAERS).


• An ICSR captures information necessary to support the reporting of an adverse event related to an individual subject that is associated with the use of an FDA-regulated product.


• The electronic submission of the ICSRs from IND-exempt BA/BE studies is a voluntary option for submitting these required reports.

Finalized guidance on electronic transmission of individual case safety reports.

• On April 1, 2024, FDA issued final guidance entitled, “FDA Regional Implementation Guide for E2B(R3) Electronic Transmission of Individual Case Safety Reports for Drug and Biological Products.”


• This technical specifications document provides information on electronically submitting ICSRs, and ICSR attachments, that describe an adverse experience related to an individual patient to CDER and CBER.


• Specifically, the guidance describes FDA’s technical approach for submitting ICSRs, for incorporating its regionally controlled terminology, and for adding FDA Adverse Event Reporting System (FAERS) regional data elements that are not addressed in the International Conference on Harmonisation’s (ICH) E2B (R3) Implementation Guideline for certain FDA-regulated products, including drug products marketed for human use with approved NDAs and ANDAs, prescription and over-the-counter drug products marketed for human use without an approved application, and biological products with approved BLAs.

Finalized guidance on electronic submission of IND safety reports.

• On April 1, 2024, FDA issued a guidance document entitled, “Providing Regulatory Submissions in Electronic Format: IND Safety Reports Guidance for Industry,” finalizing the draft guidance of the same name published in October 2019.


• The final guidance describes the electronic format sponsors will be required to use when they electronically submit IND safety reports to CDER and CBER for serious and unexpected suspected adverse reactions, as required under 21 CFR 312.32(c)(1)(i) and section 745A(a) of the Federal Food, Drug, and Cosmetic Act (FDCA) (21 U.S.C. 379k-1(a)).


• This guidance changes the electronic submission requirements for this category of IND safety reports by requiring sponsors to submit the IND safety reports to FAERS in accordance with this guidance. These requirements will be effective and binding 24 months after notice of this guidance’s availability is released on April 1, 2026. Until then, the most recent effective version of the eCTD guidance will continue to apply.

FDA authorizes AI/ML-enabled sepsis software.

• FDA granted Prenosis Inc’s de novo submission for Sepsis ImmunoScore, artificial intelligence/machine learning (AI/ML) software that identifies patients at risk for having or developing sepsis.


• FDA classified Sepsis ImmunoScore, and substantially equivalent devices of this generic type, into Class II under the generic name “software device to aid in the prediction or diagnosis of sepsis.”


• The Sepsis ImmunoScore device uses up to 22 predetermined inputs from the patient’s electronic health record to generate a risk score and to assign the patient to one of four discrete risk stratification categories, based on the increasing risk of sepsis. The device is intended to be used in conjunction with other laboratory findings and clinical assessments, to aid in the risk assessment for presence of or progression to sepsis within 24 hours of patient assessment.

Draft guidance on new dietary ingredient notification master files.

• On April 3, 2024, in response to requests from the dietary supplement industry, FDA announced a draft guidance entitled, “New Dietary Ingredient Notification Master Files for Dietary Supplements.” While NDIN Master Files are not required and are submitted solely at the discretion of the Master File owner, FDA notes that they may be used “to facilitate the process of submitting NDI-related identity, manufacturing, and/or safety information to the FDA for use in evaluating a potential future NDIN.”


• Electronic comments on the draft guidance may be submitted by June 3, 2024.

Federal Court enters Consent Decree between FDA and Philips Respironics.

• On March 9, 2024, a federal court entered a consent decree of permanent injunction against Philips RS North America LLC (Philips Respironics), and related corporate entities; Roy Jakobs, CEO of Royal Philips, Philips Respironics’ parent company; and several other corporate executives.


• The March 2024 decree resolves a complaint filed by the DOJ on behalf of FDA that alleged the defendants violated the FDCA by manufacturing and selling devices not manufactured in accordance with current good manufacturing practice (cGMP) requirements. In addition, the complaint alleged the company failed to provide FDA with information about specific corrections (or removals) the company made to devices, as required by FDA regulations.


• With limited exceptions, the decree restricts the production and sale of Philips Respironics’ sleep therapy devices, including CPAP and BiPAP machines, and other devices until the defendants have completed the repair, rework, replacement, and refund activities set forth in the Recall Remediation Plan, and are in compliance with requirements applicable to cGMP, reporting corrections and removals, and medical device reporting.


• The decree imposes testing requirements by an independent expert, as well as requires the retention of an independent expert to inspect certain facilities for evaluating operational compliance with the FDCA and to correct any deficiencies that are identified. In addition, the decree allows FDA to subject other facilities owned by the defendants to certain provisions of the decree if the FDA determines that those facilities are not operating in compliance with the FDCA or implementing regulations.