US FDA Guidance for Industry July – Sept 2024

DateTitle of guidance
and link to document		Type and level
of guidance		About the guidance
25 Sep 2024Clinical Pharmacology Considerations for Human Radiolabeled Mass Balance StudiesFinalThis guidance describes the FDA’s recommendations regarding clinical pharmacology considerations for conducting human radiolabeled mass balance studies of investigational drugs, including: (1) deciding whether and when to conduct the study, (2) designing the study, and (3) reporting results. The recommendations in this guidance are, in part, based on the FDA’s experience reviewing human radiolabeled mass balance studies submitted to the Agency in recent NDAs.

This guidance does not cover animal mass balance studies, safety testing of drug metabolites, or recommendations for selecting the radioactivity dose.
17 Sept 2024Conducting Clinical Trials With Decentralized ElementsFinal, Level 1This guidance provides recommendations for sponsors, investigators, and other interested parties regarding the implementation of decentralized elements in clinical trials. Decentralized elements allow trial-related activities to occur remotely at locations convenient for trial participants. Decentralized elements can include, among other things, telehealth visits with trial personnel, in-home visits with remote trial personnel, or visits with local health care providers (HCPs) (see sections II and III.B). In this guidance, a decentralized clinical trial (DCT) refers to a clinical trial that includes decentralized elements where trial-related activities occur at locations other than traditional clinical trial sites.
17 Sept 2024Integrating Randomized Controlled Trials for Drug and Biological Products Into Routine Clinical PracticeDraftAs part of FDA’s Real-World Evidence (RWE) Program, this guidance is intended to support the conduct of randomized controlled drug trials (RCTs) with streamlined protocols and procedures that focus on essential data collection, allowing integration of research into routine clinical practice. Such trials have sometimes been referred to as point of care trials or large simple trials. Like decentralized clinical trials, which aim to bring trial-related activities to patients’ homes or other convenient locations, such RCTs may improve convenience and accessibility for participants and allow for enrollment of more representative populations, resulting in more generalizable trial results. Leveraging established health care institutions and existing clinical expertise in the medical community can reduce startup times and speed up enrollment.
16 Sept 2024Electronic Common Technical Document; Data Standards; Center for Drug Evaluation and Research and Center for Biologics Evaluation and Research Supporting Electronic Common Technical Document Version 4.0

FDA Notice		The Food and Drug Administration’s (FDA or Agency) Center for Drug Evaluation and Research and Center for Biologics Evaluation and Research are announcing support for Electronic Common Technical Document (eCTD) Version 4.0 (v4.0)-based electronic submissions.

Support for eCTDv4.0 electronic submissions begins September 16, 2024. FDA will also continue to support eCTDv3.2.2 electronic submissions. Submit either electronic or written comments at any time.

Further information is available on the FDA website here and here.
16 Sept 2024Considerations for Generating Clinical Evidence from Oncology Multiregional Clinical Development ProgramsDraftThis guidance provides recommendations to sponsors who are planning global clinical development programs for drugs intended to treat cancer, on improving the evidence obtained from one or more multiregional clinical trials (MRCTs) intended to support a marketing application. This guidance expands on principles described in FDA’s existing guidance documents related to this topic, by providing additional recommendations for the planning, design, conduct, and analysis of an oncology MRCT that may facilitate FDA’s assessment of applicability of the data to the U.S. population with the cancer being investigated and to U.S. medical practice.
16 Sept 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-supported 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 FD&C Act with respect to standardized study data contained in certain INDs, NDAs, ANDAs and certain BLAs that are submitted to CDER or CBER.
11 Sept 2024Providing Regulatory Submissions in Electronic Format — Certain Human Pharmaceutical Product Applications and Related Submissions Using the eCTD Specifications Guidance for IndustryFinal, Level 2This guidance implements the electronic submission requirements of section 745A(a) of the FD&C Act for the electronic format of the content submitted in NDAs, ANDAs, certain BLAs, and certain INDs to CDER or to CBER. See section III.A of this guidance for more information regarding required submission types. Submissions that are not submitted electronically and electronic submissions that are not in a format that FDA can process, review, and archive will not be filed or received unless they have an exemption or waiver from the electronic submission requirements.

This revision (revision 8) modifies previous versions by updating hyperlinks throughout; updating language to include eCTD v4.0 in sections III.F, H, J, and L; and updating eCTD v4.0-46 related documents in section IV.
11 Sept 2024ANDA Submissions | Amendments to Abbreviated New Drug Applications Under GDUFAFinal Level 2This guidance is intended to explain to applicants how the assessment goals established as part of the Generic Drug User Fee Amendments of 2022 (GDUFA III) apply to amendments to either abbreviated new drug applications (ANDAs) or prior approval supplements (PASs) submitted to the FDA under section 505(j) of the FD&C Act (21 U.S.C. 355(j)). This guidance describes amendment classifications and categories and explains how amendment submissions may affect an application’s assessment goal dates. This guidance supersedes the July 2018 guidance for industry ANDA Submissions – Amendments to Abbreviated New Drug Applications Under GDUFA.
6 Sep 2024Incorporating Voluntary Patient Preference Information over the Total Product Life Cycle

(Medical Devices)		DraftThis guidance document provides recommendations on how voluntary PPI may be considered by FDA staff in decision-making. The objectives of this guidance are:
1) to encourage submission of PPI, if available, by sponsors or other interested parties to FDA and to aid in FDA decision-making,
2) to outline recommended qualities of patient preference studies, which may result in valid scientific evidence,
3) to provide practical recommendations for collecting and submitting PPI to FDA; and
4) to discuss FDA’s inclusion of PPI in its decision summaries and provide recommendations for the inclusion of such information in device labeling.

This guidance also includes hypothetical examples that illustrate how PPI may inform FDA’s decision-making.
30 Aug 2024Control of Nitrosamine Impurities in Human DrugsFinal, Level 1 revised This guidance:
• recommends steps manufacturers and applicants of active pharmaceutical ingredients (APIs) and drug products should take to detect and prevent unacceptable levels of nitrosamine impurities in drug products.
• also describes conditions that may introduce nitrosamine impurities.

The unexpected finding of nitrosamine impurities, which are probable or possible human carcinogens, in certain drug products has made clear the need for a risk assessment strategy for the potential presence of nitrosamines in any drug product.

Further information is available at this link concerning CDER Nitrosamine Impurity Acceptable Intake Limits and at this link concerning Information about Nitrosamine Impurities in Medications.
22 Aug 2024Predetermined Change Control Plans for Medical Devices

DraftOn December 29, 2022, section 3308 of the Food and Drug Omnibus Reform Act of 2022, Title III of Division FF of the Consolidated Appropriations Act, 2023, Pub. L. No. 117-328 (“FDORA”) added section 515C “Predetermined Change Control Plans for Devices” to the FD&C Act.

Section 515C of the FD&C Act (21 U.S.C. 360e-4) has provisions regarding predetermined change control plans (PCCPs) for devices requiring premarket approval (PMA) or premarket notification (510(k)).

A PCCP is the documentation describing what modifications will be made to a device and how the modifications will be assessed.

This draft guidance:
• provides FDA’s current thinking on a policy for PCCPs and recommendations on the information to include in a PCCP in a marketing submission for a device.
• recommends that a PCCP describe the planned device 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.
19 Aug 2024Product-Specific Guidance Meetings Between FDA and ANDA Applicants Under GDUFAFinal, Level 1This guidance provides recommendations to industry on product-specific guidance (PSG) meetings between
•FDA and a prospective applicant preparing to submit to FDA or
•an applicant that has submitted to FDA an ANDA under section 505(j) of the FD&C Act (21 U.S.C. 355(j)).

Specifically, this guidance provides information on requesting and conducting PSG meetings with FDA (i.e., pre and post-submission PSG teleconferences and pre and post-submission PSG meetings), as contemplated in the Generic Drug User Fee Amendments (GDUFA) Reauthorization Performance Goals and Program Enhancements Fiscal Years 2023-2027 (GDUFA III commitment letter). This guidance provides procedures that will promote well-managed PSG meetings and help ensure that such meetings are scheduled and conducted in accordance with the time frames set forth in the GDUFA III commitment letter.
9 Aug 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.

An ICSR is a description of an adverse experience related to an individual patient or subject.
8 Aug 2024Optimizing the Dosage of Human Prescription Drugs and Biological Products for the Treatment of Oncologic DiseasesFinalThis guidance:
• is intended to assist sponsors in identifying an optimized dosage(s) for human prescription drugs or biological products for the treatment of oncologic diseases during clinical development and prior to submitting an application for approval of a new indication and usage.
• should be considered along with the International Conference on Harmonisation (ICH) E4 guidance on Dose-Response Information to Support Drug Registration (November 1994) when identifying an optimized dosage(s).
• does not specifically provide recommendations addressing dosage optimization for radiopharmaceuticals, cellular and gene therapy products, oncolytic viruses, microbiota, or cancer vaccines. However, some of the recommendations outlined may be applicable to these therapeutic modalities.
• also does not specifically address pediatric drug development, for which there are unique considerations; however, some of the recommendations outlined may be applicable to dosage optimization for pediatric patients.
• also does not address selection of the starting dose for first-in-human trials.
2 Aug 2024M12 Drug Interaction Studies: Questions and AnswersFinal, Level 1In response to questions posted to the International Council for Harmonisation (ICH) draft guidance for industry M12 Drug Interaction Studies comment period, several questions and answers have been developed to provide clarity around some of the concepts related to evaluation of drug interaction covered in the guidance.

This question and answer (Q&A) document is intended to provide additional clarification and improve harmonization of drug interaction assessment.

The scope and organization of this Q&A document follow that of the ICH guidance for industry M12 Drug Interaction Studies (August 2024) (ICH M12).
2 Aug 2024M12 Drug Interaction StudiesFinal, Level 1This guidance provides recommendations to promote a consistent approach in designing, conducting, and interpreting enzyme- or transporter-mediated in vitro and clinical drug-drug interaction (DDI) studies during the development of a therapeutic product. A consistent approach will reduce uncertainty for the pharmaceutical industry to meet the requirements of multiple regulatory agencies and lead to more efficient utilization of resources. In addition, this approach will lead to the effective and safe treatment for patients who take multiple medications.
25 Jul 2024Providing Over-the-Counter Monograph Submissions in Electronic FormatFinal, Level 1This guidance provides information on providing electronic submissions to the Food and Drug Administration (FDA) under section 505G of the FD&C Act (21 U.S.C. 355h). This guidance is intended to assist submitters by describing the electronic OTC monograph submissions requirement in section 505G(j) of the FD&C Act and providing recommendations and other information on how to send such OTC monograph submissions to FDA in electronic format.
24 Jul 2024Container Closure System and Component Changes: Glass Vials and StoppersFinal, Level 2FDA is issuing this guidance to collate recommendations for appropriate reporting categories and the content of postapproval change submissions across numerous FDA guidance documents. This guidance conveys recommendations to holders of approved NDAs, BLAs, and ANDAs regarding the reporting and implementation of some common changes to container closure system (CCS) components consisting of glass vials and stoppers for approved sterile drug products, including biological products, administered parenterally. This guidance also discusses pathways available to application holders to obtain Agency feedback. Additionally, this guidance discusses risk-based tools available to facilitate the implementation of changes to CCSs consisting of glass vials and stoppers. This guidance does not apply to CCS types other than glass vials and stoppers.
24 Jul 2024Real-World Data: Assessing Electronic Health Records and Medical Claims Data To Support Regulatory Decision-Making for Drug and Biological ProductsFinal, Level 1The 21st Century Cures Act (Cures Act), signed into law on December 13, 2016, is intended to accelerate medical product development and bring innovations faster and more efficiently to the patients who need them. Among other provisions, the Cures Act added section 505F to the FD&C Act (21 U.S.C. 355g). Pursuant to this section, FDA created a framework for a program to evaluate the potential use of real-world evidence (RWE) to help support the approval of a new indication for a drug already approved under section 505(c) of the FD&C Act or help support or satisfy postapproval study requirements.

FDA is issuing this guidance as part of its RWE Program4 and to satisfy, in part, the mandate under section 505F of the FD&C Act to issue guidance about the use of RWE in regulatory decision-making. The RWE Program will cover clinical studies that use real-world data (RWD) sources, such as information from routine clinical practice, to derive RWE.

This guidance is intended to provide sponsors and other interested parties with considerations when proposing to use electronic health records (EHRs) or medical claims data in clinical studies to support a regulatory decision on effectiveness or safety of a drug.
21 Jul 3034Postapproval Manufacturing Changes to Biosimilar and Interchangeable Biosimilar Products Questions and AnswersDraft, Level 1This guidance provides answers to commonly asked questions from applicants and other interested parties regarding postapproval manufacturing changes made to licensed biosimilars and licensed interchangeable biosimilars. This Q&A guidance is intended to inform prospective and current applicants of the nature and type of information that applicants should provide in support of manufacturing changes to licensed biosimilars and licensed interchangeable biosimilars in different reporting categories.
21 July 2024Recommendations for Investigational and Licensed COVID-19 Convalescent Plasma; Guidance for IndustryFinalThis guidance provides FDA’s recommendations to blood establishments for the submission of a BLA for the manufacture of COVID-19 convalescent plasma for transfusion intended to treat patients with immunosuppressive disease or receiving immunosuppressive treatment in either the outpatient or inpatient setting. The guidance also provides FDA’s recommendations for INDs for investigational COVID-19 convalescent plasma for transfusion.

FDA is implementing this guidance without prior public comment because the Agency has determined that prior public participation is not feasible or appropriate (see 21 CFR 10.115(g)(2) and (g)(3)). FDA made this determination because we recognize that SARS-CoV-2 continues to circulate and COVID-19 remains a serious health risk, especially for patients with immunosuppressive disease or receiving immunosuppressive therapy. FDA’s recommendations on the development of drugs and biological products for treatment and prevention of COVID-19 is necessary to address an unmet public health need.
16 Jul 2024Pediatric Inflammatory Bowel Disease: Developing Drugs for TreatmentDraft, Level 1 guidanceThe purpose of this guidance is to help sponsors in the clinical development of drugs to treat pediatric patients with inflammatory bowel disease (IBD). Specifically, this guidance provides the FDA’s recommendations about the necessary attributes of clinical studies for drugs being developed for the treatment of pediatric ulcerative colitis (UC) or pediatric Crohn’s disease (CD), including study population, study design, efficacy considerations, and safety assessments.

This guidance does not address extraintestinal manifestations, stricturing or fistulizing disease, or the treatment or prevention of long-term complications of pediatric UC or CD. Additionally, this guidance is not intended to address the treatment of monogenic IBD or IBD unclassified. The recommendations for clinical study design in this guidance are based upon the assumption that a robust development program is being conducted in adults and that efficacy data from adults will be available to help inform the pediatric program and to support extrapolation of efficacy.

Sponsors seeking to develop a drug only for pediatric UC or CD patients in the absence of an adult program should meet with the appropriate review division to discuss their proposals.
16 Jul 2024Application User Fees for Combination ProductsFinal, Level 2 revised guidanceThis document provides guidance to industry and FDA staff on application user fees for combination products as defined under 21 CFR 3.2(e). Combination products may be reviewed in a single application or in separate applications for the constituent parts (see section II.B). The guidance explains that combination products for which a single application is submitted should be assessed the applicable user fee associated with that particular type of application. The document also addresses how the Agency applies user fees for combination products when separate applications are submitted for the constituent parts. If the applicant chooses to submit two applications for a cross-labeled combination product, each would be assessed the applicable user fee for each application. In the infrequent situation when FDA determines that a single application is not appropriate and separate applications are warranted, the guidance describes how the total application fee amount might be reduced when the applicant qualifies for certain waiver provisions under the Prescription Drug User Fee Act (PDUFA) of the the FD&C Act.
15 Jul 2024Drugs for Treatment of Partial Onset Seizures: Full Extrapolation of Efficacy from Adults to Pediatric Patients 2 Years of Age and OlderFinal, Level 2 guidanceThis guidance provides recommendations to sponsors on the clinical development of drugs for the treatment of partial onset seizures (POS) in pediatric patients.
Specifically, this guidance addresses FDA’s current thinking regarding clinical development programs that can support extrapolation of the efficacy of drugs approved for the treatment of POS in adults to pediatric patients 1 month of age and older. This guidance does not address the development of drugs to treat other types of seizures.
8 Jul 2024Addressing Misinformation About Medical Devices and Prescription Drugs: Questions and AnswersDraftThis guidance responds to common questions firms may have when voluntarily addressing misinformation about or related to their approved/cleared medical products. In addition to describing already existing avenues for communications by firms, this guidance sets out an enforcement policy for certain kinds of internet-based communications that firms might choose to use to address internet-based misinformation about or related to the firm’s approved/cleared medical product when that misinformation is created or disseminated by an independent third party. The recommendations and illustrative examples in this guidance are intended to help support firms that choose to address misinformation about or related to their approved/cleared medical products.

Further information is available here.
8 Jul 2024Purpose and Content of Use-Related Risk Analyses for Drugs, Biological Products, and Combination ProductsDraftThis document provides guidance to industry and FDA staff on the purpose and content of a use-related risk analysis (URRA) and how a URRA, along with other information, can be used to determine human factors (HF) data needs during product development and to support a marketing application.

This guidance:
• applies to drug- and biologic-led combination products that are the subject of an IND, NDA, or a BLA and supplements to these applications.
• also applies to human prescription drug products, including biological products, that are the subject of an IND, NDA, or BLA and supplements to these applications, and to human nonprescription drug products that are the subject of an IND or NDA and supplements to these applications.
• does not describe the methods used to design, conduct, or analyze human factors studies (for example, human factors validation studies or comparative use human factors studies).

The URRA is a risk management tool that supports the entire human factors engineering process and should be considered as part of an overall risk management framework. The URRA can be used in all phases of the medical product lifecycle. As part of evaluating the products as described above, FDA will evaluate human factors data submitted by sponsors to support the product user interface when submission of such data is warranted. The URRA can be used as one data element to help determine whether submission of human factors data is warranted.

2 Jul 2024M14 General Principles on Plan, Design, and Analysis of Pharmacoepidemiological Studies That Utilize Real-World Data for Safety Assessment of MedicinesDraft Level 1The purpose of this document is to recommend international standards for, and promote harmonization of, the general principles on planning, designing, and analyzing observational (non-interventional) pharmacoepidemiological studies that utilize fit-for-purpose data for safety assessment of medicines (drugs, vaccines, and other biological products).

This document outlines recommendations and high-level best practices for the conduct of these studies, to streamline the development and regulatory assessment of study protocols and reports. These recommendations and practices also seek to improve the ability of the study protocol and/or results to be accepted across health authorities and support decision-making in response to study results. The Glossary defines several terms for the purpose of this guideline. Terms that appear in bold italic type upon first use are defined in the Glossary.