US FDA Guidance for Industry – Apr – Jun 2024

DateTitle of guidance
and link to document		Type and level
of guidance		About the guidance
26 Jun 2024Diversity Action Plans to Improve Enrollment of Participants from Underrepresented Populations in Clinical StudiesDraftThis guidance is intended to assist sponsors conducting certain clinical studies involving drugs, biological products, and devices to meet requirements for the submission of Diversity Action Plans under section 505(z) and section 520(g)(9) of the FD&C Act as added by section 3601 of the Food and Drug Omnibus Reform Act of 2022 19 (FDORA). Specifically, sections 505(z)(3) and 520(g)(9)(A) of the FD&C Act require that 20 sponsors submit Diversity Action Plans for certain clinical studies in the form and manner specified by FDA in guidance. Diversity Action Plans are intended to increase enrollment of participants who are members of historically underrepresented populations in clinical studies to help improve the strength and generalizability of the evidence for the intended use population. Such plans must specify “the sponsor’s goals for enrollment in [a] clinical study,” “the sponsor’s rationale for such goals”, and include “an explanation of how the sponsor intends to meet those goals.”The Secretary is required to update or issue guidance to sponsors regarding the format and content of their Diversity Action Plan pertaining to clinical study enrollment goals “disaggregated by age group, sex, and racial and ethnic demographic characteristics of clinically relevant study populations.” Section 3604 of FDORA also requires that FDA annually submit to Congress, and publish on the Agency’s website, a report that summarizes in the aggregate the Diversity Action Plans received and whether the clinical studies conducted met the demographic enrollment goals from the submitted Diversity Action Plans.
20 June 2024Considerations in Demonstrating Interchangeability With a Reference Product: UpdateDraft, Level 1This draft guidance describes considerations regarding a switching study or studies intended to support a demonstration that a proposed therapeutic protein product is interchangeable with a reference product (proposed interchangeable biosimilar or proposed interchangeable product) for the purposes of submitting a marketing application or supplement under section 351(k) of the Public Health Service Act (PHS Act) (42 U.S.C. 262(k)). Although the 351(k) pathway applies generally to all biological products, this guidance focuses on therapeutic protein products.
20 Jun 2024Circumstances that Constitute Delaying, Denying, Limiting, or Refusing a Drug or Device InspectionFinalThis guidance covers facilities that are subject to drug or device inspection under section 704 of the FD&C Act.1 This guidance defines the types of behaviors (actions, inactions, and circumstances) that FDA considers to constitute delaying, denying, or limiting inspection, or refusing to permit entry or inspection for the purposes of section 501(j) of the FD&C Act. The examples used in this guidance are not intended to serve as an exhaustive list; rather, they illustrate the most common situations that FDA has encountered in preparing for and conducting drug or device inspections as well as situations that FDA anticipates may occur. FDA does not interpret the four terms describing prohibited behavior (delay, deny, limit, refuse) necessarily to be mutually exclusive. Therefore, the behaviors described in the scenarios in this guidance may be examples of more than one type of prohibited behavior. Also note that, for purposes of this guidance, the term “facility” is intended to include all establishments, factories, and warehouses covered by section 501(j) of the FD&C Act.
18 Jun 2024Facility Readiness: Goal Date Decisions Under GDUFAFinalThis guidance:
• provides information to applicants on how FDA intends to assign a goal date based on a facility’s readiness for inspection as certified on Form FDA 356h submitted as part of an original abbreviated new drug application (ANDA) under section 505(j) of the FD&C Act (21 U.S.C. 355(j)).
• explains how FDA incorporates a program enhancement agreed upon by the Agency and industry as part of the negotiations relating to reauthorization of the Generic Drug User Fee Amendments (GDUFA), as described in “GDUFA Reauthorization Performance Goals and Program Enhancements Fiscal Years 2023-2027” (GDUFA III commitment letter).
14 Jun 2024Clinical Pharmacology Considerations for the Development of Oligonucleotide TherapeuticsFinalThis guidance provides recommendations to assist industry in the development of oligonucleotide therapeutics under section 505 of the FD&C Act (21 U.S.C. 355) and 21 CFR parts 312 and 314. Specifically, this guidance represents the FDA’s recommendations for certain evaluations during development of oligonucleotide therapeutics, including: (1) characterizing the potential for QTc interval prolongation, (2) performing immunogenicity risk assessment, (3) characterizing the impact of hepatic and renal impairment, and (4) assessing the potential for drug-drug interactions. This guidance provides recommendations on when to conduct these assessments and what types of assessments are suitable to address the topics listed above.

Oligonucleotide therapeutics are an emerging therapeutic modality with increasing numbers of drugs in development. Many antisense and small interfering RNA (siRNA) oligonucleotide therapeutics have been FDA-approved in recent years. In addition, many oligonucleotide therapeutics are currently in development to treat rare and common diseases alike.

Oligonucleotide therapeutics include a wide variety of synthetically modified RNA or RNA/DNA hybrids that are specifically designed to bind to a target RNA sequence to alter RNA expression and/or downstream protein expression. Even within the therapeutic modality, oligonucleotide therapeutics can differ in several ways, including but not limited to:
• Mechanism of action (e.g., splice modulating, RNA interference, RNase H-mediated cleavage)
Structure (e.g., single-stranded RNAs, double-stranded RNAs, RNA/DNA hybrids)
• Chemical modifications to the base and/or backbone
• Size
• Sequence
• Delivery strategy (e.g., lipid nanoparticles, liposomes, other polymeric nanoparticles, polyethylene glycol (PEG), N-acetylgalactosamine (GalNAc) conjugation)
• Conjugation with other moieties (e.g., small molecules, proteins, antibodies)

Here, you can view the guidance snapshot, listen to the guidance recap podcast and view the podcast transcript.
13 Jun 2024Diabetic Foot Infections: Developing Drugs for TreatmentFinal, Level 1The purpose of this guidance is to assist sponsors in the clinical development of drugs for the treatment of diabetic foot infections (DFIs) without concomitant bone and joint involvement. Specifically, this guidance addresses the FDA’s current thinking regarding the overall development program and clinical trial designs for the development of drugs to support an indication for treatment of DFI. Development of drugs for the treatment of acute bacterial skin and skin structure infections, defined as cellulitis/erysipelas, wound infection, and major cutaneous abscess, is addressed in a separate guidance.

This guidance does not contain discussion of the general issues of statistical analysis or clinical trial design. Those topics are addressed in the ICH guidances for industry E9 Statistical Principles for Clinical Trials (September 1998) and E10 Choice of Control Group and Related Issues in Clinical Trials (May 2001), respectively. Diabetic foot infections encompass cellulitis, ulcers, and bone and joint infections located at or distal to the malleoli. Bone and joint infections are excluded from the scope of this guidance.
31 May 2024E14 Clinical Evaluation of QT/QTc Interval Prolongation and Proarrhythmic Potential for Non-Antiarrhythmic DrugsFinalThis guidance provides recommendations to sponsors concerning the design, conduct, analysis, and interpretation of clinical studies to assess the potential of a drug to delay cardiac repolarization. This assessment should include testing the effects of new agents on the QT/QTc interval as well as the collection of cardiovascular adverse events. The investigational approach used for a particular drug should be individualized, depending on the pharmacodynamic, pharmacokinetic, and safety characteristics of the product, as well as on its proposed clinical use.

The assessment of the effects of drugs on cardiac repolarization is the subject of active investigation. When additional data (nonclinical and clinical) are accumulated in the future, this document may be reevaluated and revised
28 May 2024Platform Technology Designation Program for Drug DevelopmentDraftThis guidance:
• provides details about the implementation of the platform technology designation program established by section 506K of the FD&C Act.
• outlines eligibility factors for receiving a platform technology designation, potential benefits of receiving a designation, how to leverage data from designated platform technologies, how to discuss a planned designation request as part of a milestone meeting, the recommended content of a designation request submission, and the review timelines for a designation request.

This program is intended to result in efficiencies in drug development, manufacturing, and review processes for drug product applications that incorporate designated platform technologies.
2 May 2024REMS Logic Model: A Framework to Link Program Design With AssessmentDraft, Level 1The purpose of this guidance is to describe FDA’s risk evaluation and mitigation strategy (REMS) logic model. The REMS logic model is a framework that FDA recommends, which provides applicants with a systematic, structured approach to the design, implementation, and evaluation of a REMS. The aim of applying the REMS logic model is to develop clear goals, objectives, and strategies that align with the intended outcomes and to help applicants incorporate the REMS assessment planning into the design of the REMS. The principles in this guidance apply to designing a REMS, developing a REMS assessment, and modifying a REMS.

This guidance is not intended to clarify how risk management or a REMS factors into the benefit-risk assessment of a drug. Although this guidance does not directly address how the Agency determines when a REMS is necessary to ensure that the benefits of the drug outweigh its risks the concepts discussed in this guidance may be relevant to consider when determining if risk mitigation strategies beyond labeling are necessary.
26 Apr 2024Content and Format of Composition Statement and Corresponding Statement of Ingredients in Labeling in NDAs and ANDAsDraft, Level 1This guidance:
• is intended to assist new drug application (NDA) and abbreviated new drug application (ANDA) applicants in submitting an accurate and complete composition statement in their applications and a corresponding statement of ingredients in the DESCRIPTION section of the prescribing information and in other types of FDA-approved labeling (e.g., patient labeling, carton and container labeling) as applicable. Throughout this guidance, the term composition statement refers to information submitted in a drug product’s NDA or ANDA, and the term statement of ingredients refers to information contained in a drug product’s DESCRIPTION section of its prescribing information and other types of FDA-approved labeling, as appropriate.
• provides recommendations for the content and format of the composition 26 statement in the application and the corresponding statement of ingredients in labeling. It provides recommendations for minimizing the number of assessment cycles and communications that are appropriate for approval, as well as ensuring that FDA-approved labeling contains the required qualitative (Q1) and quantitative (Q2) ingredient information.
• includes examples of common, recurring problems FDA has identified during its assessment of NDAs and ANDAs concerning the content and format of the composition statement in the application and the corresponding statement of ingredients in labeling, and this guidance provides applicants with recommendations on how to avoid these problems.
• also describes FDA’s intent, when possible, to use the composition statement submitted in electronic common technical document (eCTD) section 3.2.P.1 of NDAs and ANDAs as the statement of ingredients.
• does not include a comprehensive list of all potential problems in a composition statement or a statement of ingredients. FDA encourages applicants to review applicable FDA regulations and all applicable guidance documents for industry to understand FDA’s current thinking on this topic.
24 April 2024Promotional Labeling and Advertising Considerations for Prescription Biological Reference and Biosimilar Products Questions and Answers Guidance for IndustryDraft, Level 1This revised draft guidance addresses questions firms may have when developing FDA-regulated promotional labeling and advertisements (promotional communications)for prescription reference products licensed under section 351(a) of the Public Health Service Act 21 (PHS Act) (42 U.S.C. 262(a)) and prescription biosimilar products, including interchangeable biosimilar products, licensed under section 351(k) of the PHS Act (42 U.S.C. 262(k)).

This guidance:
• does not make any recommendations for nonprescription products. Unless otherwise specified, the term biosimilar product as used in this guidance refers to a product that is licensed under section 351(k) of the PHS Act as biosimilar to or biosimilar to and interchangeable with a reference product.
• discusses considerations for presenting data and information about reference products or biosimilar products in these promotional communications to help ensure that they are accurate, truthful, and non-misleading.

This revised draft guidance replaces the draft guidance for industry Promotional Labeling and Advertising Considerations for Prescription Biological Reference and Biosimilar Products: Questions and Answers (February 2020). Changes from the 2020 draft guidance include additional recommendations and an example for interchangeable biosimilar products. In addition, editorial changes were made to improve clarity.
11 April 2024FDA Regional Implementation Guide for E2B(R3) Electronic Transmission of Individual Case Safety Reports for Drug and Biological ProductsFinalThe purpose of this technical specifications document is to assist submitters transmitting electronic individual case safety reports (ICSRs) and ICSR attachments to the FDA Adverse Event Reporting System (FAERS) database.

This document describes FDA’s technical approach for submitting ICSRs, for incorporating its regionally controlled terminology, and for adding FAERS regional data elements that are not addressed in the E2B(R3) Electronic Transmission of ICSRs IG for the following FDA-regulated products:
• Drug products marketed for human use with approved NDAs or ANDAs
• Prescription drug products marketed for human use without approved applications, including prescription drug products that are compounded by facilities registered as outsourcing facilities under section 503B of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 353b)
• Nonprescription drug products marketed for human use without approved NDAs or ANDAs
• Biological products with approved biologics license applications (BLAs)
• Combination products with approved NDAs, ANDAs, or BLAs
• Drug and biological products studied under investigational new drug applications (INDs) or IND-exempt bioavailability/bioequivalence (BA/BE) studies supporting ANDAs6
1 Apr 2024Data Integrity for In Vivo Bioavailability and Bioequivalence StudiesDraft, Level 1The purpose of this guidance is 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 INDs, NDAs, and ANDAs, and the bioanalytical portion of clinical pharmacologic studies supporting CDER-regulated BLAs as well as amendments and supplements to these applications. In addition, the recommendations in this guidance apply to the bioanalytical portion of nonclinical studies. FDA also encourages applicants and testing sites to consider these recommendations when conducting other studies, including in vitro and pharmacology and toxicology studies.
1 Apr 2024Study Data Technical Conformance Guide – Technical Specifications DocumentFinalThis Study Data Technical Conformance Guide (Guide) provides specifications, recommendations, and general considerations on how to submit standardized study data using FDA-supported1 data standards located in the FDA Data Standards Catalog (Catalog). The Guide supplements the guidance for industry Providing Regulatory Submissions in Electronic Format — Standardized Study Data (eStudy Data). The eStudy Data guidance implements the electronic submission requirements of section 745A(a) of the Food, Drug, & Cosmetic (FD&C) Act with respect to standardized study data contained in certain INDs, NDAs, ANDAs and certain BLAs that are submitted to CDER or the CBER.
1 Apr 2024Electronic Submission of Expedited Safety Reports From IND-Exempt BA/BE Studies Guidance for IndustryFinalThis guidance provides instructions for the electronic submission of expedited individual case safety reports (ICSRs) from investigational new drug (IND)-exempt bioavailability (BA)/bioequivalence (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.