US FDA Guidance for Industry Oct – Dec 2024

DateTitle of guidance
and link to document		Type and level
of guidance		About the guidance
6 Dec 2024Standardized Format for Electronic Submission of NDA and BLA Content for the Planning of Bioresearch Monitoring (BIMO) Inspections for CDER Submissions Guidance for IndustryFinalThis guidance describes the electronic submission of certain data and information in standardized formats and applies to electronic submissions of data and information from all major (i.e., pivotal) studies used to support safety and efficacy claims in NDAs, BLAs regulated by the CDER, and supplements containing new clinical study reports. It also applies when these data and information are submitted in certain INDs in advance of a planned NDA, BLA, or supplement submission.

CDER uses the data and information described in this guidance to plan bioresearch monitoring (BIMO) inspections6 to facilitate the timely identification of sites for inspection and to ensure that field investigators from the FDA Office of Inspections and Investigations (OII) (formerly Office of Regulatory Affairs), which is the office responsible for the conduct of the inspections, have the information needed to conduct the inspections. Twenty-four months after the issuance of this guidance, the data in NDAs and BLAs described in this guidance must be submitted electronically in the format specified in this guidance.
5 Dec 2024Accelerated Approval – Expedited Program for Serious ConditionsDraftAccelerated approval is one of FDA’s expedited programs intended to facilitate and expedite development and review of new drugs to address an unmet medical need in the treatment of a serious or life-threatening condition.

The purpose of this guidance is to provide information on FDA’s policies and procedures for accelerated approval as well as threshold criteria generally applicable to concluding that a drug is a candidate for accelerated approval.

This guidance also describes the procedures for expedited withdrawal of approval of a product approved under accelerated approval and the revisions Congress made through the Consolidated Appropriations Act, 2023. Additional programs to expedite product development and review are covered in other guidances.
3 Dec 2024

(Medical Devices)		Marketing Submission Recommendations for a Predetermined Change Control Plan for Artificial Intelligence-Enabled Device Software FunctionsFinal FDA recognizes that the development of AI-enabled devices (also referred to as AI-enabled device software functions or AI-DSFs) is an iterative process. This guidance describes an approach that would often be least burdensome for manufacturers to support iterative improvement through modifications to an AI-DSF while continuing to provide a reasonable assurance of device safety and effectiveness. As such, this guidance demonstrates FDA’s broader commitment to developing innovative approaches to the regulation of device software functions as a whole.

Specifically, this guidance provides recommendations on the information to include in a Predetermined Change Control Plan (PCCP) in a marketing submission for a device that includes one or more AI-DSFs. This guidance recommends that a PCCP describe the planned AI-DSF modifications, the associated methodology to develop, validate, and implement those modifications, and an assessment of the impact of those modifications. FDA reviews the PCCP as part of a marketing submission for a device to ensure the continued safety and effectiveness of the device without necessitating additional marketing submissions for implementing each modification described in the PCCP.
20 Nov 2024Recommended Acceptable Intake Limits for Nitrosamine Drug Substance-Related Impurities (NDSRIs)
Some values in Table 1: FDA Recommended AI Limits for Certain Hypothetical NDSRIs and Other Identified Nitrosamine Impurities have changed.
The changes can be identified in the Revision Table at the end of the page.
18 Nov 2024Frequently Asked Questions — Developing Potential Cellular and Gene Therapy ProductsDraftThis guidance is intended to provide industry with answers to frequently asked questions (FAQs) and commonly faced issues that arise during the development of cellular and gene therapy (CGT) products and is intended to help facilitate the development of safe, effective, and high-quality CGT products. The FAQs represent common questions directed to the Agency and span multiple disciplines, including regulatory review, chemistry, manufacturing, and controls (CMC), pharmacology/toxicology (PT), clinical, and clinical pharmacology.
12 Nov 2024Drug and Device Manufacturer Communications With Payors, Formulary Committees, and Similar Entities – Questions and AnswersFinalThis guidance:
• provides answers to common questions regarding firms’ communication of health care economic information (HCEI) regarding their prescription drugs and medical devices to payors, formulary committees, or other similar entities with knowledge and expertise in the area of health care economic analysis (collectively referred to as payors).
• also addresses common questions relating to dissemination to payors of information about medical products that are not yet approved or cleared for any use and dissemination to payors of information about unapproved uses of approved/cleared medical products.
12 Nov 2024Nonclinical Safety Assessment of Oligonucleotide-Based TherapeuticsDraft, Level 1The purpose of this guidance is to provide recommendations on approaches for the nonclinical safety evaluation of oligonucleotide-based therapeutics (ONTs) to support clinical development and marketing of these products.

ONTs present unique challenges for nonclinical safety evaluations. Although current guidance for small molecule drugs and therapeutic proteins may mention ONTs, this guidance provides detailed recommendations specific to nonclinical assessment of ONTs that have been developed based on experience to date with this category of products. These recommendations address ONT characteristics that differ from small molecule drugs and therapeutic proteins.

This guidance includes recommendations for single-stranded or double-stranded ONTs created synthetically or derived naturally, with native or modified backbone or nucleoside structures that increase or decrease expression and/or function of proteins. Examples of included oligonucleotides are antisense, small interfering RNA, microRNA, transfer RNA, decoys, and aptamers. Immune stimulatory oligonucleotides (e.g., CpG motifs acting via Toll-like receptors) are excluded, as are CBER-regulated products (e.g., DNA/RNA vaccines, virally delivered ONTs, messenger RNA and RNA used for gene editing). An oligonucleotide that is conjugated to other types of molecules (e.g., saccharides, lipids, peptides, antibodies) is included if the oligonucleotide would itself fall within the scope of this guidance.
30 Oct 2024M13A Bioequivalence for Immediate-Release Solid Oral Dosage FormsFinalThis guideline is intended to provide recommendations on conducting bioequivalence (BE) studies during both development and post-approval phases for orally administered immediate release (IR) solid dosage forms designed to deliver drugs to the systemic circulation, such as tablets, capsules, and granules/powders for oral suspension.

Deviations from the recommendations in this guideline may be acceptable if appropriate scientific justification is provided. Applicants are encouraged to consult the regulatory authority(ies) when an alternate approach is proposed or taken.
21 Oct 2024Drug Interaction Information in Human Prescription Drug and Biological Product LabelingDraftThis guidance is intended to assist applicants of human prescription drug and biological products in determining the appropriate placement and content of drug interaction (DI) information in labeling as described in the regulations for the content and format of labeling for human prescription drug and biological products.

The purpose of this guidance is to provide recommendations to help ensure that appropriate DI information is consistently placed in the proper sections and subsections within labeling so that the information is clear and accessible to health care practitioners (HCPs) and includes content that guides the safe and effective use of the drug. Applicants should follow the recommendations in this guidance when developing this section of labeling for a new drug submitted to the FDA under a new drug application under section 505(b) of the FD&C Act or a biologics license application under section 351(a) of the PHS Act, and when revising existing information in the labeling for a currently approved drug in a supplement to such applications.

This guidance does not address methodological considerations for evaluating or interpreting DIs during drug development or after drug approval. Recommendations for evaluating the DI potential during drug development are included in an FDA guidance for industry
17 Oct 2024Core Patient-Reported Outcomes in Cancer Clinical TrialsFinalThis guidance:
• provides recommendations to sponsors for collection of a core set of patient reported clinical outcomes (herein referred to as core patient-reported outcomes) in cancer clinical trials and related considerations for instrument selection and trial design. Although this guidance focuses on patient-reported outcome (PRO) measures, some of these recommendations may be relevant to other clinical outcome assessments (i.e., clinician-reported outcome, observer-reported outcome, performance outcome) in cancer clinical trials. Recommendations supplement previous guidance on use of PRO measures in clinical trials by providing additional considerations specific to the cancer clinical trial setting. Guidance specific to PRO endpoints and details of analytic methods are not comprehensively covered. FDA does not endorse any specific PRO measure and examples within this document are illustrative and should not be construed as endorsements.
• is specific to FDA regulated trials for anti-cancer therapies intended to demonstrate an effect on survival, tumor response, or delay in the progression of a malignancy. Demonstration of a clinically meaningful improvement in patient-reported symptoms or functional impacts alone (i.e., in the absence of evidence of anti-cancer activity) would be more applicable to supportive care drugs and is outside the scope of this guidance. Refer to the guidance for industry Patient-Reported Outcome Measures: Use in Medical Product Development to Support Labeling Claims (PRO guidance) for situations where the PRO endpoint will be used as the primary evidence of effectiveness. PRO measurement may not be feasible in all cancer trial populations (e.g., in patients with significant cognitive impairment)
17 Oct 2024Review of Drug Master Files in Advance of Certain ANDA Submissions Under GDUFAFinalThis guidance:
• is intended for holders of Type II active pharmaceutical ingredient (API) drug master files (DMFs) that will be referenced in an ANDA, or a prior approval supplement (PAS) to an ANDA. This guidance 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 20232027” (GDUFA III commitment letter). Specifically, this guidance describes instances when an early assessment, or “DMF prior assessment,” could be requested by a DMF holder and the circumstances under which FDA would commence an early assessment of Type II API DMFs months prior to an ANDA or PAS submission referencing the DMF. It also provides recommendations for such DMF holders when making a request.
• does not apply to Type II API DMFs used to support NDAs, submissions related to ANDAs that are not described above, or any other types of DMFs.
17 Oct 2024Considerations for Long-Term Clinical Neurodevelopmental Safety Studies in Neonatal Product DevelopmentFinalThe purpose of this guidance is to provide a framework for considering whether and what type of long-term neurologic, sensory and developmental evaluations could be useful to support a determination of safety of a “medical product” (i.e., drug, biological product, or device) for use in neonates, and if so, which domains of neurodevelopment may be most applicable.

This guidance:
• will not specifically address effectiveness, safety or benefit/risk assessments for products primarily intended to improve neurologic outcomes, e.g., neuroprotective agents.
• is focused on long-term evaluations of neurodevelopmental safety. Although assessments of specific toxicities to other tissues and organs may also be warranted in neonatal medical product development, the approach to those assessments is outside the scope of this guidance.
17 Oct 2024Postoperative Nausea and Vomiting: Developing Drugs for PreventionDraft, Level 1The purpose of this guidance is to help sponsors in the clinical development of drugs for the prevention of postoperative nausea and vomiting (PONV) in adults.

Specifically, this guidance provides recommendations regarding the design of clinical trials for drugs for the prevention of PONV, including considerations for eligibility criteria, trial design features, efficacy evaluations, and safety assessments.

This guidance does not address the development of drugs for the treatment of PONV. Additionally, this guidance does not address the development of drugs for the prevention of 24 PONV in pediatric patients.
16 Oct 2024Requests for Reconsideration at the Division Level Under GDUFAFinalThis guidance:
• provides recommendations on the procedures for applicants of abbreviated new drug applications (ANDAs) that wish to pursue a request for reconsideration within the review discipline at the division level or original signatory authority. As described further below in section III, requests within the scope of this guidance should concern certain actions that relate to an ANDA and have scientific significance. During the assessment of an ANDA, FDA considers important issues that are central to product evaluation. Sometimes, an applicant may disagree with FDA, and because these disagreements often involve intricate matters, it is critical to have procedures in place to ensure open and prompt consideration of an applicant’s concern(s). The procedures and policies described in this guidance are intended to formalize FDA’s current and historical practices and to continue to promote rapid and fair resolution of eligible requests between an applicant and FDA.
• is being issued to reflect the second reauthorization of the Generic Drug User Fee Amendments (GDUFA III) and to clarify what matters are appropriate for requests for reconsideration.
• does not describe the formal dispute resolution procedures for resolving eligible requests between FDA and sponsors or applicants that cannot be resolved through the request for reconsideration process at the division level. This guidance also does not describe the procedures for resolving administrative matters, such as disputes regarding user fee assessments.
1 Oct 2024Electronic Systems, Electronic Records, and Electronic Signatures in Clinical Investigations: Questions and AnswersFinalThis document provides guidance to sponsors, clinical investigators, institutional review boards (IRBs), contract research organizations (CROs), and other interested parties on the use of electronic systems, electronic records, and electronic signatures in clinical investigations of medical products, foods, tobacco products, and new animal drugs. The guidance provides recommendations regarding the requirements under 21 CFR part 11 (part 11), pursuant to which FDA considers electronic systems, electronic records, and electronic signatures to be trustworthy, reliable, and generally equivalent to paper records and handwritten signatures executed on paper.

This guidance expands upon recommendations in the guidance for industry Part 11, Electronic Records; Electronic Signatures — Scope and Application (August 2003) (2003 part 11 guidance) that pertain to clinical investigations conducted under 21 CFR parts 312 and 812. Other related guidances are listed in the Appendix.