US FDA Guidance for Industry Jan – Mar 2024

DateTitle of guidance and link to documentType and level
of guidance		About the guidance
29 Mar 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. FDA adopted the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Implementation Guide (IG) for Electronic Transmission of Individual Case Safety Reports (ICSRs): E2B(R3) Data Elements and Message Specification (ICH ICSR IG) in February 2014, and published the guidance for industry E2B(R3) Electronic Transmission of Individual Case Safety Reports: Implementation Guide — Data Elements and Message Specification (E2B(R3) Electronic Transmission of ICSRs IG) and an appendix to the guidance entitled Appendix I (B) to the ICH E2B(R3) ICSRs Implementation Guide — Backwards and Forwards Compatibility.

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 new drug applications (NDAs) or abbreviated new drug applications (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 ANDAs
28 Mar 2024Providing Regulatory Submissions in Electronic Format: IND Safety Reports: Guidance for IndustryFinal, Level 1This guidance:
• describes the electronic format sponsors will be required to use when they electronically submit to the FDA, IND safety reports for serious and unexpected suspected adverse reactions that are required under 21 CFR 312.32(c)(1)(i). FDA is establishing the electronic format requirements described in this guidance under section 745A(a) of the FD&C Act. When the requirements of this guidance are in effect, this guidance will supersede the effective version of the guidance for industry Providing Regulatory Submissions in Electronic Format — Certain Human Pharmaceutical Product Applications and Related Submissions Using the eCTD Specifications (eCTD guidance) as applicable to the electronic submission of IND safety reports required under 21 CFR 312.32(c)(1)(i) that are within the scope of this guidance (see section III., Scope of This Guidance).
• will not replace any requirements in the eCTD guidance other than those relating to the electronic submission of IND safety reports required under 21 CFR 312.32(c)(1)(i) that are within the scope of this guidance.
• also references several technical specification documents that provide additional details about the format for electronic submission of IND safety reports to the FDA Adverse Event Reporting System (FAERS).

This guidance:
• implements the electronic submission requirements of section 745A(a) of the FD&C Act for the electronic format of the content submitted for IND safety reports that are required under 21 CFR 312.32(c)(1)(i) for serious and unexpected suspected adverse reactions.
• applies to IND safety reports that are submitted to the Center for Drug Evaluation and Research (CDER) or the Center for Biologics Evaluation and Research (CBER).
• 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. This requirement will be effective 24 months after the publication of the notice of availability of this guidance in the Federal Register (April 1, 2026). Until the requirements in this guidance become effective, the most recent effective version of the eCTD guidance will continue to apply to sponsors electronically submitting IND safety reports for serious and unexpected suspected adverse reactions. Before the effective date of the requirements outlined in this guidance, FDA will accept IND safety reports to FAERS as part of a voluntary submission program. During the voluntary submission program, if sponsors choose to submit IND safety reports to FAERS, they should no longer submit those IND safety reports in eCTD format. Please see the FAERS Electronic Submissions web page for more information on the voluntary submission process.
28 Mar 2024Clinical Pharmacology Considerations for Antibody-Drug Conjugates Guidance for IndustryFinal, Level 1This guidance:
• provides recommendations to assist industry and other parties involved in the development of antibody-drug conjugates (ADCs) with a cytotoxic small-molecule drug or payload. Specifically, this guidance addresses the FDA’s current thinking regarding clinical pharmacology considerations and recommendations for bioanalytical methods, dosing strategies, dose- and exposure-response analysis, intrinsic factors, QTc assessments, immunogenicity, and drug-drug interactions (DDIs). The principles discussed in this guidance might not be applicable to the development of other types of ADCs (e.g., ADCs with payloads other than cytotoxic small molecule drugs and/or for indications other than oncology.
• specifically outlines clinical pharmacology considerations of ADC development programs and references other relevant guidances when appropriate.2 ADCs are subject to all pertinent laws and regulations for biological products, including those governing product development, testing, and approval as outlined in section 351 of the PHS Act (42 U.S.C. 262). Given that ADCs include a small-molecule drug,3 there are other guidances that are applicable to ADCs that would not necessarily apply to other biological products. Of note, this guidance does not focus on the development of any particular ADC, and questions about regulatory recommendations and development programs for a particular ADC should be addressed to the appropriate FDA review division. Also, for both clinical and non-clinical data, applicants for socalled “stand-alone” applications (e.g., biologics license applications (BLAs) submitted pursuant to section 351(a) of the Public Health Service Act (PHS Act)) generally must own or have a right of reference to all information used to support licensure of their applications.
25 Mar 2024Handling and Retention of Bioavailability BA and Bioequivalence BE Testing SamplesFinal, Level 1This guidance is intended to provide recommendations for applicants of NDAs and ANDAs, including supplemental applications, and CROs, regarding the procedures for handling reserve samples from relevant BA and BE studies, as required by §§ 19 320.38 and 320.63 (21 CFR 320.38 and 320.63) and recommendations regarding responsibilities of each party involved in the study pertaining to reserve samples. In the context of §§ 320.38 and 320.63, the term applicant includes, as appropriate, study sponsor and/or drug manufacturer and the term CRO refers to any party contracted to help conduct BA or BE testing, including, as appropriate, site management organizations (SMOs), investigators, and testing sites.

The guidance highlights:
(1) How the test article (T) and reference standard (RS) for BA and BE studies should be distributed to the testing sites
(2) How testing sites should randomly select samples for testing and material to maintain as reserve samples
(3) How the reserve samples should be retained.
(4) Addresses the requirement at 21 CFR 320.38(c) to retain reserve samples of sufficient quantity to permit FDA to perform five times all the release tests required in an application or supplemental application
(5) Describes the conditions under which the Agency does not generally intend to take enforcement action against an applicant or CRO for retaining less than the quantity of reserve samples of the test article and reference standard that were used in the BA or BE study as specified in 21 CFR 320.38(c).

The guidance also provides clarifying recommendations related to certain other relevant requirements in §§ 320.38 and 320.63.
19 Mar 2024Real-World Evidence: Considerations Regarding Non-Interventional Studies for Drug and Biological ProductsDraft, Level 1This guidance provides recommendations to sponsors and investigators who are considering submitting a non-interventional study, also referred to as an observational study, to FDA to contribute to a demonstration of substantial evidence of effectiveness and/or evidence of safety of a drug. Specifically, this guidance discusses attributes regarding the design and analysis of a non-interventional study that sponsors should consider when proposing a non interventional study for such regulatory purposes.
18 Mar 2024Controlled Correspondence Related to Generic Drug DevelopmentFinal, Level 1This guidance:
• provides information regarding the process by which generic drug manufacturers and related industry or their representatives can submit to FDA controlled correspondence requesting information related to generic drug development.
• also describes the Agency’s process for providing communications related to such correspondence. This guidance replaces the guidance for industry Controlled Correspondence Related to Generic Drug Development issued in December 2020. The December 2020 guidance was issued as part of FDA’s implementation of the Generic Drug User Fee Amendments of 2017 (GDUFA II). This guidance is being issued to incorporate program enhancements related to the review of controlled correspondence to which FDA committed, and industry agreed, as part of their negotiations relating to the reauthorization of the Generic Drug User Fee Amendments (GDUFA) (GDUFA III), as described in “GDUFA Reauthorization Performance Goals and Program Enhancements Fiscal Years 2023–2027” (GDUFA III commitment letter). Other significant changes from the December 2020 version include providing additional recommendations for specific types of inquiries in controlled correspondence.
15 Mar 2024Pharmacokinetics in Patients with Impaired Renal Function — Study Design, Data Analysis, and Impact on DosingFinal, Level 1This guidance assists sponsors in the design and analysis of studies2 that assess the influence of 17 impaired renal function on the pharmacokinetics (PK) and/or pharmacodynamics (PD) of an investigational drug and addresses how such information can inform the labeling. This version revises and replaces the draft guidance entitled Pharmacokinetics in Patients With Impaired 20 Renal Function — Study Design, Data Analysis and Impact on Dosing and Labeling (March 21 2010) and provides updated recommendations on the following topics:
• When a standalone study of a drug’s PK in subjects with impaired renal function is recommended and when it may not be needed
• The design and conduct of pharmacokinetic studies in subjects with impaired renal function
• Considerations for characterizing a drug’s PK in patients undergoing intermittent or 30 continuous dialytic therapies
•The use of pharmacokinetic information from phase 2 and 3 studies to inform dosing recommendations for patients with impaired renal function
• The analysis and reporting of the results of studies that characterize the impact of 36 impaired renal function and how these data inform dosing recommendations in labeling
13 Mar 2024E2D(R1) Post-Approval Safety Data: Definitions and Standards for Management and Reporting of Individual Case Safety ReportsDraftIt is important to establish an internationally standardised procedure to ensure the quality of post-approval safety information and to harmonise, where feasible, the way of gathering and reporting information. The ICH E2D guideline provides guidance on definitions and standards for post-approval individual case safety reporting, as well as good case management practices.

This guideline provides recommendations that are harmonised to the extent possible given differences in post-market safety reporting requirements among ICH regions. Where applicable, this guideline notes where local and regional requirements may vary and, as such, marketing authorisation holders (MAHs) should refer to the relevant local or regional regulatory authority’s requirements.
6 Mar 2024Q2(R2) Validation of Analytical ProceduresFinalThe objective of validation of an analytical procedure is to demonstrate that the analytical procedure is fit for the intended purpose.

This guidance:
• presents elements for consideration during the validation of analytical procedures included as part of registration applications. Analytical procedure validation forms a part of the analytical procedure life cycle, as described within the International Council for Harmonisation (ICH) guidance for industry Q14 Analytical Procedure Development (March 2024) (ICH Q14). This ICH guidance for industry, Q2(R2) Validation of Analytical Procedures (ICH Q2), provides guidance on selection and evaluation of the various validation tests for analytical procedures. This guidance includes a collection of terms and their definitions, which are meant to bridge the differences that often exist between various compendia and documents of the ICH member regulatory authorities.
• applies to analytical procedures used for release and stability testing of commercial drug substances and products, hereafter referred to as products. The guidance can also be applied to other analytical procedures used as part of the control strategy (ICH guidance for industry Q10 Pharmaceutical Quality System (April 2009)) following a risk based approach. The scientific principles described in this guidance can be applied in a phase-appropriate manner to analytical procedures used during clinical development.

The guidance is directed to common uses of analytical procedures, such as assay, potency, purity, impurity (quantitative or limit test), identity, or other quantitative or qualitative measurements.
5 Mar 2024Updated Information | Recommended Acceptable Intake Limits for Nitrosamine Drug Substance-Related Impurities (NDSRIs)FinalOn 8/4/2023, FDA issued a final guidance on Recommended Acceptable Intake Limits for Nitrosamine Drug Substance-Related Impurities (NDSRIs) (August 2023) (NDSRI Guidance). To reflect the evolving and highly technical nature of the relevant information, FDA is providing certain updated NDSRI-specific information on this website in connection with the guidance.

Specifically, FDA intends to include on this website updated information on:
(1) recommended AI limits for certain NDSRIs based on their predicted carcinogenic potency categorization listed by APIs that hypothetically could be at risk of forming such NDSRIs;
(2) recommended AI limits for certain NDSRIs based on compound-specific data or read-across analysis from a surrogate;
(3) recommended interim AI limits for certain NDSRIs;
(4) recommended testing methods for confirmatory testing of certain NDSRIs; and
(5) recommended safety testing methods for NDSRIs.
4 Mar 2024Q14 Analytical Procedure DevelopmentFinal, Level 1This guidance:
• describes science and risk-based approaches for developing and maintaining analytical procedures suitable for the evaluation of the quality of drug substances and drug products. The systematic approach suggested in the International Council for Harmonisation (ICH) guidance for industry Q8(R2) Pharmaceutical Development (November 2009) (ICH Q8(R2))together with principles of the ICH guidance for industry Q9(R1) Quality Risk Management (May 2023) (ICH Q9(R1)) can also be applied to the development and life cycle management of analytical procedures. When developing an analytical procedure, a minimal (also known as traditional) approach or elements of an enhanced approach can be applied. Furthermore, the guidance describes additional considerations for the development of multivariate analytical procedures and for real time release testing (RTRT).
• complements the ICH guidance for industry Q2(R2) Validation of Analytical Procedures (March 2024) (ICH Q2).
29 Feb 2024Key Information and Facilitating Understanding in Informed Consent Guidance for Sponsors, Investigators, and Institutional Review BoardsDraftThis guidance:
• provides recommendations on provisions of the Department of Health and Human Services (HHS) regulations on the protection of human subjects as well as certain proposed revisions to FDA’s current regulations for the protection of human subjects. Specifically, this guidance addresses the presentation of key information and includes recommendations for the content, organization, and presentation of informed consent information in FDA-regulated clinical investigations of drugs, devices, and biologics (collectively medical products) and in HHS supported or -conducted nonexempt human subjects research. The recommendations in this guidance should inform the communication of consent information to subjects, including prospective subjects or their legally authorized representatives, and may be conveyed by written, oral, or electronic means.
• is intended to assist institutional review boards (IRBs), investigators, and sponsors engaged in or responsible for oversight of human subject research subject to FDA and/or HHS regulations with the development of consent information that would comply with CFR 32 46.116(a)(5) and FDA’s proposed revisions to 21 CFR 50.20(e), if finalized as proposed.6 FDA-33 regulated clinical investigations conducted or supported by HHS are subject to both HHS and FDA regulations, per 45 CFR 46.101, 21 CFR 50.1, and 21 CFR 56.101.
28 Feb 2024Clinical Pharmacology Considerations for Antibody-Drug Conjugates Guidance for IndustryFinal, Level 1This guidance:
• provides recommendations to assist industry and other parties involved in the development of antibody-drug conjugates (ADCs) with a cytotoxic small-molecule drug or payload. Specifically, this guidance addresses the FDA’s current thinking regarding clinical pharmacology considerations and recommendations for bioanalytical methods, dosing strategies, dose- and exposure-response analysis, intrinsic factors, QTc assessments, immunogenicity, and drug-drug interactions (DDIs). The principles discussed in this guidance might not be applicable to the development of other types of ADCs (e.g., ADCs with payloads other than cytotoxic small molecule drugs and/or for indications other than oncology).
• specifically outlines clinical pharmacology considerations of ADC development programs and references other relevant guidances when appropriate. ADCs are subject to all pertinent laws and regulations for biological products, including those governing product development, testing, and approval as outlined in section 351 of the PHS Act (42 U.S.C. 262). Given that ADCs include a small-molecule drug,3 there are other guidances that are applicable to ADCs that would not necessarily apply to other biological products.

Of note, this guidance does not focus on the development of any particular ADC, and questions about regulatory recommendations and development programs for a particular ADC should be addressed to the appropriate FDA review division. Also, for both clinical and non-clinical data, applicants for socalled “stand-alone” applications (e.g., biologics license applications (BLAs) submitted pursuant to section 351(a) of the Public Health Service Act (PHS Act)) generally must own or have a right of reference to all information used to support licensure of their applications.
21 Feb 2024Assessing COVID-19-Related Symptoms in Outpatient Adult and Adolescent Subjects in Clinical Trials of Drugs and Biological Products for COVID-19 Prevention or TreatmentFinal, Level 1This guidance:
• provides sponsors and investigators with considerations for approaches on how common symptoms related to COVID-19 can be measured and analyzed in clinical trials evaluating drugs or biological products for the prevention or treatment of COVID-19 in outpatient adult and adolescent subjects.
• is not intended for development programs evaluating products to treat or prevent post infectious COVID-19 conditions (e.g., long COVID, multisystem inflammatory syndrome) in children and adults, or development programs for preventative vaccines.
• does not address considerations for clinical trial design other than those pertaining to the measurement and analysis of COVID-19-related symptoms among outpatients. Considerations for patients with COVID-19 who require hospitalization are out of scope for this guidance.

FDA is implementing this guidance without prior public comment because the Agency has determined that prior public participation is not feasible or appropriate
15 Feb 2024CMC Postapproval Manufacturing Changes To Be Documented in Annual ReportsFinalThis guidance provides recommendations to holders of NDAs and ANDAs regarding the types of changes to be documented in annual reports.
Specifically, the guidance describes CMC postapproval manufacturing changes that the FDA have determined will likely have a minimal potential to have an adverse effect on product quality and, therefore, should be documented by applicants in an annual report.

Appendix A lists examples of CMC postapproval manufacturing changes previously submitted under manufacturing supplements that the FDA have determined generally to be of low risk to product quality. Appendix B provides examples of minor changes to be documented in an annual report that were previously published in FDA’s Scale-up and Postapproval Changes (SUPAC) guidances and other postapproval change CMC guidances (see Section V. Resources for a list of those guidances).
13 Feb 2024Charging for Investigational Drugs Under an IND: Questions and AnswersFinalThis guidance:
• provides information for industry, researchers, physicians, institutional review boards, and patients about the implementation of FDA’s regulations on charging for investigational drugs under an IND for the purpose of either clinical trials or expanded access for treatment use (21 CFR 312.8), which went into effect on October 13, 2009. Since 2009, FDA has received a number of questions concerning its implementation of the charging regulation. As a result, FDA issued the guidance for industry Charging for Investigational Drugs Under IND — Questions and Answers (June 2016; revised draft August 2022) providing recommendations in a question-and-answer format, addressing the most frequently asked questions
• finalizes the revised draft guidance issued in August 2022 and replaces the 2016 guidance. Significant changes to the 2016 version include additional recommendations related to
(1) the need for submission of a statement by an independent certified public accountant under certain circumstances and
(2) distribution of the manufacturing, administrative, or monitoring costs from the first year over the expected duration of the expanded access IND or protocol.
12 Feb 2024Use of Data Monitoring Committees in Clinical TrialsDraft, Level 1This guidance provides recommendations to help sponsors of clinical trials determine;
(1) when a data monitoring committee (DMC) (also known as a data and safety monitoring board (DSMB) or a data and safety monitoring committee (DSMC) or an independent data monitoring committee (IDMC)) would be useful for trial monitoring and
(2) what procedures and practices should be considered to guide their operation. This guidance revises the guidance for clinical trial sponsors Establishment and Operation of Clinical Trial Data Monitoring Committees issued in March 2006 (the 2006 guidance). When finalized, this guidance will supersede the 2006 guidance.

Significant changes in DMC structure and practice since the 2006 guidance was issued include:
• The increased use of DMCs in trials (Califf et al. 2012) of modest size as reflected in the clinical trials data bank housed at ClinicalTrials.gov6
• A trend for DMC charters to become longer and more detailed
• An increased use of DMCs to implement certain adaptive clinical trial designs
• An increased use of some DMCs to oversee an entire clinical development program rather than a single clinical trial
• The potential for expansion of functions of a DMC; for example, for review of aggregate data for safety reporting for trials under an investigational new drug application (IND)
• An increased globalization of medical product development and use of multiregional trials with DMCs

For the purposes of this guidance, a clinical trial DMC is a group of individuals with relevant expertise that reviews accumulating data on a regular basis from one or more clinical trials and recommends to the sponsor whether to continue, modify, or stop a trial or trials. A clinical trial DMC is established by the sponsor but should be independent of the sponsor and the trial conduct (see section VII of this guidance).
8 Feb 2024Advanced Manufacturing Technologies Designation ProgramDraftAdvanced manufacturing is a term for an innovative pharmaceutical manufacturing technology or approach that has the potential to improve the reliability and robustness of the manufacturing process and supply chain and increase timely access to quality medicines for the American public. Advanced manufacturing can integrate novel technological approaches, use established techniques in an innovative way, or apply production methods in a new domain where there are no defined best practices or experience. Advanced manufacturing can potentially be used for new or currently marketed small molecule drugs or biological products.

FDA encourages the early adoption of advanced manufacturing technologies (AMTs) that have the potential to benefit patients by improving manufacturing and supply dependability and optimizing development time of drug and biological products. These technologies can be integral to ensuring quality and supporting a robust supply of drugs that are life-supporting, life-sustaining, of critical importance to providing health care, or in shortage. AMTs can directly improve product quality (e.g., through better manufacturing controls and fewer human interventions).

This guidance:
• provides recommendations to persons and organizations interested in participating in FDA’s Advanced Manufacturing Technologies Designation Program, which is intended to facilitate the development of drugs, including biological products, manufactured using an AMT that has been designated as such under the program (hereinafter designated AMT).
• outlines the eligibility criteria for AMT designation, the submission and assessment process for requests, and the benefits of receiving an AMT designation and includes a questions and answers section to cover additional details about key concepts important for program utilization.

Specifically, the guidance describes:
• The process for submitting an AMT designation request, including a description of eligibility criteria and the data and other information to be included.
• When and how FDA will communicate receipt of and provide advice on an AMT designation request.
• When and how FDA will assess AMT designation requests.
• The process by which FDA will engage with holders of designated AMTs and applicants for drugs manufactured using, referencing, or relying upon a designated AMT.
• Potential benefits related to drug development and application assessment.3

6 Feb 2024Notifying FDA of a Discontinuance or Interruption in Manufacturing of Finished Products or Active Pharmaceutical Ingredients Under Section 506C of the FD&C ActDraft, Level 2FDA is issuing this guidance to assist applicants and manufacturers in providing FDA timely, informative notifications about changes in the production of certain finished drugs and biological products as well as certain active pharmaceutical ingredients (API)3 that may, in turn, help the 19 Agency in its efforts to prevent and mitigate shortages.

The guidance discusses the notification requirements under section 506C of the FD&C Act (21 U.S.C. 356c) and FDA’s regulations. Generally, section 506C of the FD&C Act requires applicants and manufacturers of certain finished drugs and biological products to notify FDA of (1) a permanent discontinuance in the manufacture of such products
(2) an interruption in the manufacture of such products that is likely to lead to a meaningful disruption in supply of those products in the United States
(3) a permanent discontinuance in the manufacture of API for such products, or
(4) an interruption in the manufacture of API for such products that is likely to lead to a meaningful disruption in the supply of the API for those products.

This guidance recommends that applicants and manufacturers provide additional details and follow additional procedures to ensure FDA has the specific information it needs to help prevent or mitigate shortages. In addition, the guidance explains how FDA communicates information about products in shortage to the public.
5 Feb 2024Reporting Amount of Listed Drugs and Biological Products Under Section 510(j)(3) of the FD&C ActFinalThe FDA is issuing this guidance to assist registrants of drug establishments in submitting reports to FDA on the amount of each listed drug manufactured, prepared, propagated, compounded, or processed for commercial distribution, as required by section 510(j)(3) of the FD&C Act (21 U.S.C. 360(j)(3)), as added by section 3112(e) of the Coronavirus Aid, Relief, and Economic Security Act (CARES Act).

This guidance describes the process that should be used for reporting information under section 510(j)(3) by each person who registers with FDA under section 510 of the FD&C Act with regard to a listed drug (including a drug product that is in finished package form, a drug product that is not in finished package form, an active pharmaceutical ingredient (API), and other types of listed drugs, except for biological products or categories thereof exempted by an order under section 510(j)(3)(B)).

Listed drugs subject to reporting include human drug products (including non-exempt biological products) marketed under an approved application, animal drug products marketed under an approved application, medical gases, homeopathic products, products marketed in accordance with requirements under section 505G of the FD&C Act (21 U.S.C. 355h),6 often referred to as over-the-counter monograph drugs, and animal drug products that are not approved, conditionally approved, or indexed under sections 512, 571, and 572 of the FD&C Act.
30 Jan 2024Collection of Race and Ethnicity Data in Clinical Trials and Clinical Studies for Food and Drug Administration-Regulated Medical Products; Draft Guidance for Industry; AvailabilityDraft document fro,m the Federal RegisterThe FDA is announcing the availability of a draft guidance for industry entitled “Collection of Race and Ethnicity Data in Clinical Trials and Clinical Studies for FDA-Regulated Medical Products.”

The purpose of this guidance is to provide FDA’s expectations for, and recommendations on, use of a standardized approach for collecting and reporting race and ethnicity data in submissions including information collected and reported from clinical studies and clinical trials for FDA-regulated medical products. Using standard terminology for race and ethnicity helps ensure that data are collected and reported consistently in submissions to FDA.

This draft guidance revises the final guidance for industry and FDA staff entitled “Collection of Race and Ethnicity Data in Clinical Trials” issued on October 26 2023.
29 Jan 2024Considerations for the Development of Chimeric Antigen Receptor (CAR) T Cell ProductsDraftChimeric antigen receptor (CAR) T cell products are human gene therapy products in which the T cell specificity is genetically modified to enable recognition of a desired target antigen for therapeutic purposes.

This guidance is intended to assist sponsors, including industry and academic sponsors, developing ex vivo-manufactured CAR T cell products.

In this guidance, the FDA, provide CAR T cell-specific recommendations regarding chemistry, manufacturing, and control (CMC), pharmacology and toxicology, and design of clinical studies for oncology indications (including hematologic malignancies and solid tumors). Recommendations specific to autologous or allogeneic CAR T cell products are noted in this guidance.

This guidance also provides recommendations for analytical comparability studies for CAR T cell products.

While this guidance specifically focuses on CAR T cell products, some of the information and recommendations provided may also be applicable to other genetically modified lymphocyte products, such as CAR Natural Killer (NK) cells or T cell receptor (TCR)-modified T cells. These related product types can be highly specialized, and in many cases, considerations beyond those recommended in this guidance would depend on the specific product and manufacturing process. To discuss considerations specific to these related products or non-oncology indications, FDA recommends that sponsors communicate with the Office of Therapeutic Products (OTP) in the CBER before submitting an Investigational New Drug Application (IND) (e.g., by requesting a pre-IND meeting (Ref. 1)).
29 Jan 2024Human Gene Therapy Products Incorporating Human Genome EditingDraftIn this guidance, FDA prvides recommendations to sponsors developing human gene therapy products incorporating genome editing (GE) of human somatic cells. Specifically, this guidance provides recommendations regarding information that should be provided in an Investigational New Drug (IND) application in order to assess the safety and quality of the investigational GE product, as required in Title 21 of the Code of Federal Regulations 312.23 (21 CFR 312.23). This includes information on product design, product manufacturing and testing, nonclinical safety assessment, and clinical trial design.
26 Jan 2024Conducting Remote Regulatory Assessments-Questions and Answers; Revised Draft Guidance for Industry; AvailabilityRevised Draft Guidance from the Federal RegisterThe FDA is announcing the availability for comment of a revised draft guidance for industry entitled “Conducting Remote Regulatory Assessments—Question and Answers.”

FDA has revised and is reissuing the draft guidance in response to public comments and recent amendments to the FD&C Act. When finalized, this guidance will describe FDA’s current thinking regarding its use of remote regulatory assessments (RRAs).
FDA has used RRAs to conduct oversight, mitigate risk, meet critical public health needs, and help maximize compliance of FDA-regulated products. This revised draft guidance provides answers to frequently asked questions regarding RRAs.
26 Jan 2024Best Practices for Food and Drug Administration Staff in the Postmarketing Safety Surveillance of Human Drug and Biological Products; Final Document; Availability
Final document from from the Federal Register		The FDA is announcing the availability of a final document entitled “Best Practices for FDA Staff in the Postmarketing Safety Surveillance of Human Drug and Biological Products.”

The 21st Century Cures Act (Cures Act), enacted on December 13, 2016, requires that FDA make publicly available on its internet website best practices for certain postmarketing drug safety surveillance activities.

This final document sets forth risk-based principles for FDA’s conduct of ongoing postmarketing safety surveillance for human drug products and human biological products, in part, to address the Cures Act requirements.

This document finalizes the draft document entitled “Best Practices in Drug and Biological Product Postmarket Safety Surveillance for FDA Staff” that was issued on November 7, 2019.
26 Jan 2024Conducting Remote Regulatory Assessments Questions and AnswersDraftIn response to the Coronavirus Disease 2019 (COVID-19) pandemic, FDA adapted its operations for field activities to provide oversight of regulated industry while mitigating the spread of COVID-19. One set of tools used during the COVID-19 public health emergency for oversight of FDA-regulated products was remote regulatory assessments (RRAs). The term “RRA” (as defined in the Question and Answers section) is used to describe a category of activities for which FDA may use different terminologies, but that are all considered to be types of RRAs, including “remote interactive evaluations” and “remote record reviews.”

Such activities, along with others identified in this draft guidance, are considered RRAs for purposes of this guidance. In the presence of travel restrictions during the COVID-19 pandemic, FDA utilized RRAs to assess establishments and their compliance with applicable FDA requirements.

Based on this experience, FDA has noted the value of RRAs and concluded that they should be used for certain scenarios outside the COVID-19 pandemic and for all types of FDA-regulated products. FDA has developed this guidance to provide answers to frequently asked questions related to RRAs. When finalized, this guidance is intended to help enhance industry’s understanding of RRAs, thereby facilitating FDA’s process for conducting RRAs.
24 Jan 2024Revising ANDA Labeling Following Revision of the RLD Labeling Guidance for IndustryFinal, Level 1This guidance:
• is intended to assist applicants and holders of an abbreviated new drug application (ANDA) in updating their labeling following revisions to the approved labeling of a reference listed drug (RLD).
• provides recommendations on identifying RLD labeling updates and submitting ANDA amendments or supplements to update generic drug labeling.
• finalizes the draft guidance for industry of the same title issued on January 27, 2022.5 The final guidance provides clear expectations for when updates to labeling are required, the process for updating labeling, and the types of submissions for labeling updates.
23 Jan 2024ANDA Submissions – Amendments and Requests for Final Approval to Tentatively Approved ANDAsFinal, Level 2This guidance:
• is intended to assist applicants in preparing and submitting amendments to tentatively approved abbreviated new drug applications (ANDAs), including requests for final approval.
• provides recommendations on the timing and content of amendments to tentatively approved ANDAs to facilitate submission in a timely fashion to enable final approval on the earliest date on which the ANDA may lawfully be approved based on patent and/or exclusivity protections (“earliest lawful ANDA approval date”).
• replaces the final guidance of the same title issued in September 2020.
• is being issued to incorporate the performance goals currently outlined in the GDUFA Reauthorization Performance Goals and Program Enhancements Fiscal Years 2023-2027 (GDUFA III commitment letter), and it describes how FDA will handle requests for final approval and amendments to tentatively approved ANDAs subject to the performance goals in the GDUFA III commitment letter. It also contains clarifying revisions to section II.B concerning patent certifications and exclusivities and their effect on timing of ANDA approval.
10 Jan 2024Q5A(R2) Viral Safety Evaluation of Biotechnology Products Derived from Cell Lines of Human or Animal OriginFinalThis guidance:
• describes the evaluation of the viral safety of biotechnology products including viral clearance and testing, and it outlines what data should be submitted in marketing applications for those products. Biotechnology products include biotherapeutics and certain biological products derived from cell lines of human or animal origin (e.g., mammalian, avian, insect). In this guidance, the term virus excludes nonconventional transmissible agents like those associated with mammalian prions (e.g., bovine spongiform encephalopathy, scrapie). Applicants are encouraged to discuss transmissible spongiform encephalopathy associated issues with the appropriate regulatory authorities because they are not in scope of this guidance.
• includes products such as cytokines, monoclonal antibodies (mAbs), and subunit vaccines produced from in vitro cell culture using recombinant DNA technologies.
• also includes certain genetically engineered viral vectors and viral vector derived products (e.g., viral vaccines, gene therapy products), provided they are amenable to viral clearance, without a negative effect on the product. These products can include viral vectors, for example, adeno-associated virus (AAV), produced using transient or stable transfected cell lines, or by infection using a recombinant virus. It also includes viral vectorderived products, for example, baculovirus-expressed virus-like particles (VLPs), protein subunits, and nanoparticle-based protein vaccines and therapeutics. AAV gene therapy vectors include those that depend on helper viruses such as herpes simplex virus or adenovirus for their production. Specific guidance on genetically engineered viral vectors and viral vector-derived products is provided in Appendix F (Annex 6).
10 Jan 2024
Requests for Reconsideration at the Division Level Under GDUFA
DraftThis 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 in section III, requests within the scope of this guidance document 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.