| Date | Title of guidance and link to document | Type and level of guidance | About the guidance |
|---|---|---|---|
| 28 Sep 2023 | Human Prescription Drug and Biological Products–Labeling for Dosing Based on Weight or Body Surface Area for Ready-to-Use Containers–“Dose Banding”OCTOBER 2023 Source: FDA | Final, Level 1 | This guidance provides recommendations to assist applicants in incorporating information into proposed human prescription drug labeling for injectable drug products when: • Dosing for the drug product is based on weight or body surface area (BSA), • The drug product is available in a range of strengths in ready-to-use containers, and • The entire drug content of the ready-to-use container(s) is intended to be administered to a patient. For the purposes of this guidance, this practice is referred to as dose banding. This guidance: •applies to proposed labeling in an NDA submitted under section 505(b) of the FD&C Act; a BLA submitted under section 351(a) of the Public Health Service Act (PHS Act);4 or a supplement to one of these approved applications. •does not apply to abbreviated new drug applications (ANDAs), which are generally required to have the same labeling as the reference listed drug (RLD). •also does not apply to BLAs submitted under section 351(k) of the PHS Act; the labeling of biosimilar and interchangeable products generally incorporates relevant data and information from the FDA-approved labeling of the reference product, with certain modifications. |
| 28 Sep 2023 | Graft-versus-Host Diseases: Developing Drugs, Biological Products, and Certain Devices for Prevention or Treatment Source: FDA | Draft | The purpose of this guidance is to assist sponsors in the clinical development of drugs, biological products, therapeutic devices, and cell processing devices for the prevention or treatment of acute graft-versus-host disease (aGVHD) or chronic graft-vs-host disease (cGVHD) after allogeneic hematopoietic stem cell transplantation (HSCT). Specifically, this guidance addresses FDA’s current thinking regarding the overall clinical development program and critical design elements for early and late phase trials for the intended populations. This guidance: • is not intended to provide advice on the technical aspects of therapeutic or cell-processing devices. For feedback on the technical aspects of these devices, sponsors should request a presubmission meeting from the appropriate Center. • focuses on clinical trial design, statistical analysis, or other issues specific to aGVHD or cGVHD, and it does not contain a discussion of the general principles regarding statistical analysis, clinical trial design, or drug development. Those general topics are addressed in other guidances for industry, including E9 Statistical Principles for Clinical Trials (September 1998), E10 Choice of Control Group and Related Issues in Clinical Trials (May 2001), and draft guidance for industry Demonstrating Substantial Evidence of Effectiveness for Human Drug and Biological Products (December 2019), respectively. Lastly, this guidance addresses only those clinical pharmacology issues that would require specific consideration for drugs intended to prevent or treat aGVHD or cGVHD. |
| 20 Sep 2023 | Formal Meetings Between the FDA and Sponsors or Applicants of PDUFA Products Source: FDA | Draft, Level 1 | This guidance: • provides recommendations to industry on formal meetings between the FDA and sponsors or applicants relating to the development and review of drug or biological drug products (hereafter referred to as products) regulated by CDER and CBER. • does not apply to ANDAs, applications for biosimilar biological products, or submissions for medical devices. For the purposes of this guidance, formal meeting includes any meeting that is requested by a sponsor or applicant following the procedures provided in this guidance and includes meetings conducted in any format (i.e., in person face-to-face, virtual face-to-face (video conference), teleconference, and written response only (WRO) see in section IV, Meeting Formats). • discusses the principles of good meeting management practices and describes standardized procedures for requesting, preparing, scheduling, conducting, and documenting such formal meetings. The general principles in this guidance may be extended to other nonapplication-related meetings with external constituents, insofar as this is possible. |
| 20 Sep 2023 | Alternative Tools: Assessing Drug Manufacturing Facilities Identified in Pending Applications Source: FDA | Draft, Level 1 | The purpose of this guidance is to provide information to applicants on how FDA intends to use alternative tools to assess manufacturing facilities identified in a marketing application (i.e., an NDA, an ANDA, a BLA, or a supplement to any of these types of applications. As part of the negotiations relating to the reauthorization of the Prescription Drug User Fee Act (PDUFA) an the Biosimilar User Fee Act (BsUFA), as described in “PDUFA Reauthorization Performance Goals and Procedures Fiscal Years 2023 Through 2027” (PDUFA VII commitment letter) “Biosimilar Biological Product Reauthorization Performance Goals and Procedures for Fiscal Years 2023 Through 2027” (BsUFA III commitment letter), FDA agreed to issue guidance on the use of alternative tools to assess manufacturing facilities named in pending applications and to incorporate best practices from the use of such tools during the Coronavirus Disease 2019 (COVID-19) pandemic. This guidance: • within the context of approval and licensure decisions by FDA, describes the use of alternative tools to assess manufacturing facilities identified in an NDA, an ANDA, or a BLA to establish that these facilities meet the applicable requirements, including under section 501(a)(2)(B) of the FD&C Act (21 U.S.C. 351(a)(2)(B)) and either 505 of the FD&C Act (21 U.S.C. 355) or section 351 of the Public Health Service Act (PHS Act) (42 U.S.C. 262) • does not apply to other drug inspection programs including: -Postapproval inspections -Surveillance inspections -Follow-up and compliance inspections (e.g., for-cause inspections) Bioresearch monitoring inspections8 |
| 20 Sep 2023 | Considerations for the Conduct of Clinical Trials of Medical Products During Major Disruptions Due to Disasters and Public Health Emergencies Source: FDA | Final, Level 1 | Disasters and public health emergencies (PHEs) have the potential to cause major disruptions in the conduct of clinical trials for medical products. Such events can include (but are not limited to) hurricanes, earthquakes, military conflicts, infectious disease outbreaks, or bioterrorist attacks. FDA is issuing this guidance to provide general considerations to assist sponsors, institutional review boards (IRBs), and clinical investigators in assuring the safety of trial participants, maintaining compliance with good clinical practice (GCP), and minimizing risks to trial integrity during disasters and PHEs that may lead to major disruption of clinical trial conduct and operations. The appendix to this guidance further explains these general considerations in a question-and-answer format. |
| 18 Sep 2023 | Demonstrating Substantial Evidence of Effectiveness Based on One Adequate and Well-Controlled Clinical Investigation and Confirmatory Evidence Source: FDA | Draft, Level 1 | This guidance (the Confirmatory Evidence guidance) complements the draft guidance for industry Demonstrating Substantial Evidence of Effectiveness for Human Drug and Biological Products (December 2019) (the 2019 Effectiveness draft guidance) and the guidance for industry Providing Clinical Evidence of Effectiveness for Human Drug and Biological Products (May 1998) (the 1998 Effectiveness guidance). This guidance provides recommendations for sponsors to consider when planning a drug development program. Further information available here. |
| 18 Sep 2023 | Regulatory Considerations for Prescription Drug Use-Related Software Source: FDA | Draft, Level 1 | This guidance describes how FDA intends to apply its drug labeling authorities to certain software outputs that are disseminated by or on behalf of a drug sponsor for use with a prescription drug or a prescription drug-led, drug-device combination product (hereafter referred to as a “combination product”)3,4 20 that is assigned to CDER or (CBER as the lead center. This guidance expands on and was developed in response to comments submitted in response to the Federal Register notice “Prescription Drug-Use-Related Software; Establishment of a Public Docket; Request for Comments. |
| 15 Sep 2023 | Formal Meetings Between the FDA and Sponsors or Applicants of BsUFA Products Guidance for Industry Source: FDA | Draft | This guidance: • provides recommendations to industry on formal meetings between the FDA and sponsors or applicants relating to the development and review of biosimilar or interchangeable biosimilar products regulated by the Center for Drug Evaluation and Research (CDER) or the Center for Biologics Evaluation and Research (CBER). • does not apply to meetings associated with the development of products intended for submission in, or with the review of, NDAs or ANDAs under section 505 of the FD&C Act, BLAs under section 351(a) of the Public Health Service Act (PHS Act), or submissions for devices under the FD&C Act. For the purposes of this guidance, formal meeting includes any meeting that is requested by a sponsor or applicant (hereafter referred to as requester(s)) following the procedures provided in this guidance and includes meetings conducted in any format (i.e., in-person, virtual (videoconference), teleconference, or written response only (WRO) • discusses the principles of good meeting management practices (GMMPs) and describes standardized procedures for requesting, preparing, scheduling, conducting, and documenting such formal meetings. |
| 15 Sep 2023 | Classification Categories for Certain Supplements Under BsUFA III Source: FDA | Draft, Level 1 | This guidance provides recommendations for applicants and FDA review staff on classification categories A, B, C, D, E, and F for original and resubmitted prior approval supplements (hereafter referred to as PAS or supplements) submitted to approved applications under section 351(k) of the Public Health Service Act (PHS Act) (42 U.S.C. 262(k)).2 The commitment letter associated with the Biosimilar User Fee Amendments of 2022 (BsUFA III) sets forth these supplement classification categories and their associated review performance goals (refer to Section I.A. of the BsUFA III commitment letter). This guidance is intended to help applicants identify the appropriate classification category and review goal date of the supplement being submitted. The classification categories pertain to supplements for biosimilar and interchangeable biosimilar products for applicants seeking the following: • To update Prescribing Information and, if applicable, FDA-approved patient labeling (e.g., Patient Package Insert, Medication Guide, Instructions for Use) with safety information that has been updated in the reference product labeling and is applicable to one or more indications for which the biosimilar or interchangeable biosimilar product is licensed • To receive licensure for an additional indication • To remove an approved indication • To receive an initial determination of interchangeability Supplements to approved 351(k) biologics license applications (BLAs) that do not meet the criteria under Categories A through F are outside the scope of this guidance and will not be addressed here. |
| 15 Sep 2023 | Biosimilarity and Interchangeability: Additional Draft Q&As on Biosimilar Development and the BPCI Act (Revision 1) Source: FDA | Draft, Level 2 Revised | This draft guidance provides answers to common questions from prospective applicants and other interested parties regarding the Biologics Price Competition and Innovation Act of 2009 (BPCI Act). The Q&A format is intended to inform prospective applicants and facilitate the development of proposed biosimilar products and proposed interchangeable products, as well as describe FDA’s interpretation of certain statutory requirements added by the BPCI Act. |
| 15 Sep 2023 | Labeling for Biosimilar and Interchangeable Biosimilar Products Source: FDA | Draft, Level 1 | This guidance is intended to help applicants develop draft labeling for proposed biosimilar and interchangeable biosimilar products for submission in an application under section 351(k) of the Public Health Service Act (PHS Act) (42 U.S.C. 262(k)) (351(k) application). The recommendations for biosimilar and interchangeable biosimilar product labeling in this guidance pertain only to the Prescribing Information, except for certain recommendations in section V, FDA-Approved Patient Labeling of Biosimilar and Interchangeable Biosimilar Products, pertaining to FDA-approved patient labeling (e.g., Patient Information, Medication Guide, Instructions for Use). |
| 12 Sep 2023 | Annual Status Report Information and Other Submissions for Postmarketing Requirements and Commitments: Using Forms FDA 3988 and FDA 3989 Guidance for Industry Source: FDA | Final, Level 1 | This guidance: • is intended for applicants that are required to report annually on the status of postmarketing studies and clinical trials for human drug and biological products under section 506B of the FD&C Act (21 U.S.C. 356b) and its implementing regulations at 21 CFR 314.81(b)(2)(vii) and 601.70. In other words, this guidance is intended for applicants that are required by statute or regulation, or that have agreed in writing, to conduct postmarketing studies or clinical trials concerning a product’s clinical safety, clinical efficacy, clinical pharmacology, and nonclinical toxicology as postmarketing requirements (PMRs) or postmarketing commitments (PMCs). • describes the purpose and content of Form FDA 3988, Transmittal of PMR/PMC Submissions for Drugs and Biologics and Form FDA 3989, PMR/PMC Annual Status Report for Drugs and Biologics;4 when to use these forms; and how to submit these forms. Submission of completed Form FDA 3989 will meet the annual status reporting requirements for postmarketing studies or clinical trials described in section 506B of the FD&C Act and its implementing regulations. • does not apply to postmarketing studies or clinical trials that are not subject to the reporting requirements of section 506B of the FD&C Act. For example, the guidance does not apply to voluntary studies or clinical trials conducted by an applicant or on an applicant’s behalf that are neither required nor agreed upon in writing. This guidance also does not apply to chemistry, manufacturing, and controls (CMC) commitments and stability studies that are not subject to section 506B requirements. |
| 8 Sep 2023 | Institutional Review Board (IRB) Review of Individual Patient Expanded Access Submissions for Investigational Drugs and Biological Products Source: FDA | Final, Level 1 | This guidance provides recommendations to institutional review boards (IRBs) and clinical investigators regarding the key factors and procedures IRBs should consider when reviewing individual patient expanded access submissions, including for reviews conducted by a single member of the IRB, to fulfill its obligations under 21 CFR part 56. Although FDA has issued guidance on expanded access requests, including expanded access for individual patients, the Agency is aware that IRBs seek further clarity on this topic. |
| 8 Sep 2023 | Clinical Pharmacology Considerations for Peptide Drug Products Source: FDA | Draft, Level 1 | This guidance: • provides recommendations to assist industry in the development of peptide drug products. Specifically, this guidance, when finalized, will describe the FDA’s current thinking regarding the impact of clinical pharmacology considerations, including hepatic impairment, drug-drug interactions (DDIs), QTc prolongation risk, and immunogenicity risk on a peptide drug product’s pharmacokinetics (PK), safety, and efficacy. • specifically outlines clinical pharmacology considerations for development programs for proposed peptide drug products submitted in a new drug application (NDA) under section 505(b) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) and references other relevant guidances when appropriate. The term peptide, for purposes of this guidance, refers to any polymer composed of 40 or fewer amino acids. In general, if a peptide meets the definition of a drug and does not otherwise meet the statutory definition of a “biological product” or a “device,” it would be regulated as a drug under the FD&C Act and be subject to all the “drug” requirements under the FD&C Act and FDA’s regulations, including the requirement that new drugs must be approved under section 505(c) of the FD&C Act before they can be marketed in interstate commerce. However, peptide drug products can have product characteristics that may be similar, in certain respects, to biological products, and as such, this guidance includes references to other FDA guidances on biological products that discuss scientific principles that could also be applicable to peptide drug products. |
| 1 Sep 2023 | DSCSA Standards for the Interoperable Exchange of Information for Tracing of Certain Human, Finished, Prescription Drugs Guidance for Industry Source: FDA | Final, Level 1 | This guidance identifies the standards necessary to facilitate adoption of secure, interoperable, electronic data exchange among the pharmaceutical distribution supply chain, and clarifies the trading partners, products, and transactions subject to such standards. This guidance is issued subject to sections 582(h)(4)-(5) of the FD&C Act (21 U.S.C. 360eee-1(h)(4)-(5)), as added by the Drug Supply Chain Security Act (DSCSA) (Title II of Public Law 113-54). In November 2014, FDA issued a draft guidance for industry, titled DSCSA Standards for the Interoperable Exchange of Information for Tracing of Certain Human, Finished, Prescription Drugs: How to Exchange Product Tracing Information, as required by section 582(a)(2)(A) of the FD&C Act. In July 2022, FDA issued a revised draft guidance for industry, titled DSCSA Standards for the Interoperable Exchange of Information for Tracing of Certain Human, Finished, Prescription Drugs, that updated the policies articulated in the 2014 draft guidance. This guidance finalizes the policies articulated in the July 2022 revised draft guidance to reflect the enhanced drug distribution security requirements in section 582(g)(1) of the FD&C Act that will go into effect on November 27, 2023, including that only electronic methods of product tracing will be permitted and verification of product at the package level will be required, unless a waiver, exception, or exemption applies. It also makes certain changes to improve clarity. |
| 31 Aug 2023 | Nontuberculous Mycobacterial Pulmonary Disease Caused by Mycobacterium avium Complex: Developing Drugs for Treatment Source: FDA | Final, Level 1 | The purpose of this guidance is to assist sponsors in the clinical development of drugs2 for the treatment of nontuberculous mycobacterial pulmonary disease (NTM-PD) caused by Mycobacterium avium complex (MAC). Specifically, this guidance addresses the Food and Drug Administration’s (FDA’s) current thinking regarding clinical trial design issues, choice of trial population, and endpoints for the treatment of naïve and refractory NTM-PD caused by MAC. The design of clinical trials of new drugs for the treatment of NTM-PD was discussed during an FDA public workshop. This guidance does not contain discussion of the general issues of statistical analysis or clinical trial design. Those topics are addressed in the International Council for Harmonisation (ICH) guidances for industry E9 Statistical Principles for Clinical Trials (September 1998), E9(R1) Statistical Principles for Clinical Trials: Addendum: Estimands and Sensitivity Analysis in Clinical Trials (May 2021), and E10 Choice of Control Group and Related Issues in Clinical Trials (May 2001). In addition, this guidance does not address drugs intended to treat patients with NTM-PD caused by pathogens other than MAC because the clinical characteristics of these patients may differ from patients with NTM-PD caused by MAC. Sponsors interested in developing drugs targeting non-MAC NTM-PD should discuss their plans with the Division of Anti-Infectives (the Division). |
| 30 Aug 2023 | Wholesale Distributor Verification Requirement for Saleable Returned Drug Product and Dispenser Verification Requirements When Investigating a Suspect or Illegitimate Product—Compliance Policies Source: FDA | Final, Level 1 | This guidance, like the 2019 and 2020 Compliance Policies, addresses the readiness of wholesale distributors to comply with the requirement under section 582(c)(4)(D) of the FD&C Act to verify the product identifier6 upon receipt of a returned product that the wholesale distributor intends to further distribute. The requirement under section 582(c)(4)(D) of the FD&C Act for wholesale distributors to verify saleable returned products prior to redistribution went into effect on November 27, 2019. For reasons discussed below, FDA does not intend to take action against wholesale distributors who do not, prior to November 27, 2024, verify the product identifier prior to further distributing saleable returned product as required under section 582(c)(4)(D) of the FD&C Act. This represents a 1-year extension of the 2020 Compliance Policies, from November 27, 2023, until November 27, 2024, with respect to enforcement of this requirement for wholesale distributors. |
| 30 Aug 2023 | Enhanced Drug Distribution Security at the Package Level Under the Drug Supply Chain Security Act Source: FDA | Final | This guidance: • is intended to assist supply chain stakeholders, particularly trading partners, with requirements for enhanced drug distribution security at the package3 level under section 582 of the FD&C Act (21 U.S.C. 360eee-1), as added by the Drug Supply Chain Security Act (DSCSA) (Title II of Public Law 113-54). Requirements for enhanced drug distribution security go into effect on November 27, 2023. • clarifies the enhanced drug distribution security requirements listed in section 582(g)(1) of the FD&C Act (“enhanced security requirements”). In addition, as specified in section 582(h)(3) of the FD&C Act, this guidance “outlines and makes recommendations with respect to the system attributes necessary to enable secure tracing” of product at the package level, including allowing for the use of verification, inference, and aggregation, as necessary. FDA considers these recommendations to be important to assist in implementing the robust supply chain security envisioned under the DSCSA. Throughout this guidance, the terms, “FDA,” “the Agency,” “we,” and “us” refer to the Food and Drug Administration and the terms “your” and “yours” refer to regulated industry. |
| 30 Aug 2023 | Considerations for the Use of Real-World Data and Real-World Evidence To Support Regulatory Decision-Making for Drug and Biological Products Source: FDA | Final, Level 1 | For the purposes of this guidance, FDA defines real-world data (RWD) and RWE as follows: • RWD are data relating to patient health status and/or the delivery of health care routinely collected from a variety of sources. • RWE is the clinical evidence about the usage and potential benefits or risks of a medical product derived from analysis of RWD. This guidance: • discusses the applicability of FDA’s IND regulations under part 312 (21 CFR part 312) to various clinical study designs that utilize RWD. • also clarifies the Agency’s expectations concerning clinical studies using RWD submitted to FDA in support of a regulatory decision regarding the effectiveness and safety of a drug (e.g., as part of an NDA or BLA when such studies are not subject to part 312. This guidance focuses primarily on clinical study designs that are non-interventional. |
| 24 Aug 2023 | Enhanced Drug Distribution Security Requirements Under Section 582(g)(1) of the Federal Food, Drug, and Cosmetic Act–Compliance Policies Source: FDA | Final, Level 1 | This guidance: • is for trading partners, namely manufacturers, wholesale distributors, dispensers, and repackagers who are subject to requirements for enhanced drug distribution security under section 582(g)(1) of the FD&C Act (21 U.S.C. 360eee-1), as added by the Drug Supply DSCSA) (Title II of Public Law 113-54). These requirements go into effect on November 27, 2023. FDA is issuing this guidance to address industry readiness to comply with these requirements. • announces the FDA compliance policies regarding enforcement of the enhanced drug distribution security requirements under section 582(g)(1) of the FD&C Act that will go into effect on November 27, 2023. FDA believes the compliance policies provided in this guidance will help supply chain stakeholders, particularly trading partners, by accommodating the additional time that may be needed to continue to develop and refine appropriate systems and processes to conduct interoperable, electronic tracing at the package level, to achieve robust supply chain security under the DSCSA while helping ensure continued patient access to prescription drugs. |
| 9 Aug 2023 | Formal Meetings Between the FDA and Sponsors or Applicants of BsUFA Products Guidance for Industry Source: FDA | Draft | This guidance: • provides recommendations to industry on formal meetings between the FDA and sponsors or applicants relating to the development and review of biosimilar or interchangeable biosimilar products regulated by CDER or CBER. • does not apply to meetings associated with the development of products intended for submission in, or with the review of, new drug applications or abbreviated new drug applications under section 505 of the FD&C Act, BLAs under section 351(a) of the PHS Act, or submissions for devices under the FD&C Act. For the purposes of this guidance, formal meeting includes any meeting that is requested by a sponsor or applicant (hereafter referred to as requester(s)) following the procedures provided in this guidance and includes meetings conducted in any format (i.e., in-person, virtual (videoconference), teleconference, or written response only (WRO)) • discusses the principles of good meeting management practices (GMMPs) and describes standardized procedures for requesting, preparing, scheduling, conducting, and documenting such formal meetings This draft guidance for industry revises and replaces the draft guidance of the same name issued in June 2018. This revision includes: • Changes to the data expectations in Biosimilar Initial Advisory (BIA) meeting requests • Addition of Biological Product Development (BPD) Type 2a meeting • Changes to when the meeting background package is submitted for BPD Type 4 meeting • Changes to the description of the available meeting formats • Addition of an option for a request for clarification |
| 9 Aug 2023 | Classification Categories for Certain Supplements Under BsUFA III Source: FDA | Draft Level 1 | This guidance: • provides recommendations for applicants and FDA review staff on classification categories A, B, C, D, E, and F for original and resubmitted prior approval supplements (hereafter referred to as PAS or supplements) submitted to approved applications under section 351(k) of the Public PHS Act (42 U.S.C. 262(k)). The commitment letter associated with the Biosimilar User Fee Amendments of 2022 (BsUFA III) sets forth these supplement classification categories and their associated review performance goals (refer to Section I.A. of the BsUFA III commitment letter). • is intended to help applicants identify the appropriate classification category and review goal date of the supplement being submitted. The classification categories pertain to supplements for biosimilar and interchangeable biosimilar products for applicants seeking the following: • To update Prescribing Information and, if applicable, FDA-approved patient labeling (e.g., Patient Package Insert, Medication Guide, Instructions for Use)5 30 with safety information that has been updated in the reference product6 31 labeling and is applicable to one or more indications for which the biosimilar or interchangeable biosimilar product is licensed • To receive licensure for an additional indication • To remove an approved indication • To receive an initial determination of interchangeability Supplements to approved 351(k) biologics license applications (BLAs) that do not meet the criteria under Categories A through F are outside the scope of this guidance and will not be addressed here. |
| 8 Aug 2023 | Postmarketing Approaches to Obtain Data on Populations Underrepresented in Clinical Trials for Drugs and Biological Products Source: FDA | Draft | FDA regulations require sponsors to present information from premarket clinical trials on the safety and effectiveness of drugs in terms of gender, age, and racial subgroups. These clinical trials should include patient populations that are historically underrepresented in clinical research (e.g., populations based on race, ethnicity, sex, or age.) However, if, despite the sponsor’s best efforts, these populations are not adequately represented in premarket clinical trials, it may be appropriate to collect such data in the postmarketing setting. The purpose of this guidance is to describe FDA requirements and provide recommendations for obtaining safety and effectiveness information on drugs, when appropriate, in the postmarketing setting in historically underrepresented patient populations in clinical trials. Specifically, this guidance will discuss the following: • Mechanisms by which FDA can require or request information on safety and effectiveness be collected in the postmarketing setting • Design and statistical considerations for subpopulation analyses • Postmarketing approaches to obtain information on the benefit-risk profile in underrepresented clinical trial populations |
| 4 Aug 2023 | Recommended Acceptable Intake Limits for Nitrosamine Drug Substance-Related Impurities Source: FDA | Final | This guidance provides manufacturers and applicants of drugs, including prescription and over-the-counter (OTC) drug products, with a recommended framework for predicting the mutagenic and carcinogenic potential of nitrosamine drug substance-related impurities (NDSRIs) that could be present in drug products and recommends acceptable intake (AI) limits for NDSRIs. NDSRIs are a class of nitrosamine impurities that have been identified in many drug products and also could be present in active pharmaceutical ingredients (APIs). These impurities share structural similarity to the API (having the API or API fragment in the chemical structure) and are therefore unique to each API. NDSRIs generally form in the drug product through nitrosation of APIs (or API fragments) that have secondary or tertiary amines when exposed to nitrosating agents such as residual nitrites in excipients used to formulate the drug product. NDSRIs often lack carcinogenicity and mutagenicity study data (typically from animal studies) from which an AI limit can be determined. This guidance provides a recommended methodology for AI limit determination that uses structural features of NDSRIs to generate a predicted carcinogenic potency categorization and corresponding recommended AI limit that manufacturers and applicants can apply, in the absence of other FDA recommended AI limits, in their evaluations of approved and marketed drug products as well as products in development or under review by FDA. Uncertainty about the presence and acceptability of the level of an NDSRI in drug products raises regulatory challenges and has led to some applicants conducting unnecessary studies or, in some cases, discontinuing drug products from the market. Because nitrosamine impurities have been identified in many drug products, disruptions in supply and access have increased, sometimes resulting in drug shortages. These challenges can impact patient access to medications, particularly with respect to drug products that are considered medically necessary. This guidance recommends a risk-based safety assessment of NDSRIs and can be used by manufacturers and applicants to identify AI limits for NDSRIs in their drug products and APIs in conjunction with the recommendations in the guidance for industry Control of Nitrosamine Impurities in Human Drugs (February 2021) (Nitrosamine Guidance).6 FDA recognizes that the AI limits recommended by the Agency and those generated by manufacturers and applicants may evolve with advances in the science and generation of data for nitrosamines. As industry groups and consortia perform investigations that provide insights into mutagenicity and carcinogenicity risks of nitrosamine impurities, FDA encourages sharing such information to help expand the available knowledge base. |
| 3 Aug 2023 | Waivers, Exceptions, and Exemptions from the Requirements of Section 582 of the Federal Food, Drug, and Cosmetic Act Source: FDA | Final | This guidance: • describes the process an authorized trading partner or other stakeholder should use to request a waiver, exception, or exemption from the requirements of section 582 of the FD&C Act (21 U.S.C. 360eee-1), as amended by the Drug Supply Chain Security Act (DSCSA) (Title II of Public Law 113-54). • also describes the factors the FDA intends to consider when evaluating such requests from an authorized trading partner or other stakeholder, and when determining FDA-initiated exceptions and exemptions. Additionally, this guidance describes the process the FDA intends to follow once every two years to review and make determinations on the appropriateness of renewing a previously approved waiver, exception, or exemption, where applicable. • finalizes the draft guidance for industry Waivers, Exceptions, and Exemptions from the Requirements of Section 582 of the FD&C Act , issued in May 2018 as required by section 582(a)(3) of the FD&C Act. The revisions described in this document update the policy articulated in the May 2018 draft guidance. |
| 2 Aug 2023 | Fixed-Combinations and Single-Entity Versions of Previously Approved Antiretrovirals for the Treatment or Prevention of Human Immunodeficiency Virus-One Under the President’s Emergency Plan for Acquired Immunodeficiency Syndrome Relief Source: FDA | Draft | This guidance: • provides recommendations for applications for single-entity (SE) antiretroviral (ARV) and fixed-combination (FC) ARV drug products for the treatment or prevention of human immunodeficiency virus-1 (HIV-1 or HIV) infection that are intended for distribution outside of the United States under the President’s Emergency Plan for AIDS Relief (PEPFAR).2 Specifically, this guidance addresses versions of previously approved SE and FC ARV drug products and FC ARV drug products for which the individual drug product components of the combination are already FDA-approved (i.e., for which substantial evidence of safety and efficacy of the specific individual drug product components or combination already exists). • discusses regulatory procedures relevant to such applications and makes recommendations on how to identify and address common issues. • revises the guidance for industry Fixed Dose Combinations, Co-Packaged Drug Products, and Single-Entity Versions of Previously Approved Antiretrovirals for the Treatment of HIV issued in October 2006. When finalized, this guidance will replace the October 2006 guidance. |
| 27 Jul 2023 | Assessing User Fees Under the Biosimilar User Fee Amendments of 2022 Source: FDA | Final, Level 2 | This guidance: • provides information to stakeholders regarding FDA’s implementation of the Biosimilar User Fee Amendments of 2022 (BsUFA III) under Title IV of the FDA User Fee Reauthorization Act of 2022. • describes the types of user fees authorized by BsUFA III, how FDA determines which products are subject to a fee, and FDA’s policies regarding exceptions and waivers. This guidance also describes the process for submitting payments to FDA and the consequences for failing to pay BsUFA fees, and the process for requesting reconsideration if FDA denies a request for a waiver or return of user fees. This guidance does not address FDA’s implementation of other user fee programs (e.g., Prescription Drug User Fee Amendments, Generic Drug User Fee Amendments). Throughout this guidance, references to user fees or the user-fee program are specific to the biosimilar biological product user fee program under section 744H of the FD&C Act. |
| 26 Jul 2023 | CDER’s Program for the Recognition of Voluntary Consensus Standards Related to Pharmaceutical Quality Source: FDA | Final | This guidance describes a program at FDA’s CDER to make public a comprehensive listing of recognized voluntary consensus standards related to pharmaceutical quality. FDA’s participation in the development and use of technical voluntary consensus standards has been integral to the execution of FDA’s mission. For example, FDA has used such standards to develop and/or evaluate performance characteristics of dosage forms, testing methodologies, manufacturing practices, product standards, scientific protocols, ingredient specifications, labeling of drug products, and other technical or policy criteria. This program facilitates submissions by external stakeholders and FDA staff proposing voluntary consensus standards related to pharmaceutical quality for recognition. CDER believes that this program will help promote beneficial innovation in pharmaceutical development and manufacturing and streamline the preparation and assessment of marketing applications for products regulated by CDER. |
| 24 Jul 2023 | M7(R2) Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals To Limit Potential Carcinogenic Risk Source: FDA | Final | The synthesis of drug substances involves the use of reactive chemicals, reagents, solvents, catalysts, and other processing aids. As a result of chemical synthesis or subsequent degradation, impurities reside in all drug substances and associated drug products. Although the International Council for Harmonisation (ICH) guidances for industry Q3A Impurities in New Drug Substances (Revision 2) (ICH Q3A) (June 2008) and Q3B(R2) Impurities in New Drug Products (ICH Q3B(R2)) (August 2006) (Reference (Ref.) 1, 2) provide guidance for qualification and control for the majority of the impurities,3 limited guidance is provided for those impurities that are DNA reactive. The purpose of this guidance is to provide a practical framework that is applicable to the identification, categorization, qualification, and control of these mutagenic impurities to limit potential carcinogenic risk. This guidance is intended to complement ICH Q3A, ICH Q3B(R2) (Note 1), and the ICH guidance for industry M3(R2) Nonclinical Safety Studies for the Conduct of Human Clinical Trials and Marketing Authorizations for Pharmaceuticals (January 2010) (Ref. 3). This guidance emphasizes considerations of both safety and quality risk management in establishing levels of mutagenic impurities that are expected to pose negligible carcinogenic risk. It outlines recommendations for assessment and control of mutagenic impurities that reside or are reasonably expected to reside in final drug substance or product, taking into consideration the intended conditions of human use. |
| 24 Jul 2023 | M7(R2) ADDENDUM: APPLICATION OF THE PRINCIPLES OF THE ICH M7 GUIDELINE TO CALCULATION OF COMPOUND-SPECIFIC ACCEPTABLE INTAKES Source: FDA Addendum | Final, Level 1 | The International Council for Harmonisation (ICH) guidance for industry M7(R2) Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk (ICH M7(R2)) (July 2023) discusses the derivation of acceptable intakes (AIs) for mutagenic impurities with positive carcinogenicity data, (section VII.B.1 (7.2.1)). In this addendum to ICH M7(R2), AIs or permissible daily exposures (PDEs) have been derived for a set of chemicals that are considered to be mutagens and carcinogens and are common in pharmaceutical manufacturing or are useful to illustrate the principles for deriving compound-specific intakes described in ICH M7(R2). The set of chemicals include compounds in which the primary method used to derive AIs for carcinogens with a likely mutagenic mode of action is the default approach from ICH M7(R2) of linear extrapolation from the calculated cancer potency estimate, the TD50. Some chemicals that are mutagens and carcinogens (classified as Class 1 in ICH M7(R2)) may induce tumors through a nonmutagenic mode of action. Therefore, additional compounds are included to highlight alternative principles to deriving compound specific intakes (i.e., PDE, see below). Other compounds (e.g., aniline) are included even though the available data indicates that they are nonmutagenic; nevertheless, the historical perception has been that they are genotoxic carcinogens. |
| 24 Jul 2023 | M7(R2) Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals To Limit Potential Carcinogenic Risk—Questions and Answers Source: FDA Q & A | Final, Level | Since the International Council for Harmonisation (ICH) guidance for industry M7 Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk (ICH M7) was finalized, worldwide experience with implementation of the recommendations for DNA reactive (mutagenic) impurities has given rise to requests for clarification relating to the assessment and control of DNA reactive (mutagenic) impurities. This question and answer (Q&A) document is intended to provide additional clarification and to promote convergence and improve harmonization of the considerations for assessment and control of DNA reactive (mutagenic) impurities and of the information that should be provided during drug development, marketing authorization applications, and/or master files submissions. The scope of this Q&A document follows that of the ICH guidance for industry M7(R2) Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk (ICH M7(R2)) (July 2023). |
| 13 Jul 2023 | Manufacturing Changes and Comparability for Human Cellular and Gene Therapy Products Source: FDA | Draft | The management of manufacturing changes presents many challenges for human cellular therapy or gene therapy (CGT) products due to the complexity of these products. The FDA is providing you, sponsors of INDs and applicants of BLAs for CGT products, with recommendations regarding product comparability and the management of manufacturing changes for investigational and licensed CGT products. The purpose of this guidance is to provide FDA’s current thinking on: 1) management and reporting of manufacturing changes for CGT products based on a lifecycle approach, and 2) comparability studies to assess the effect of manufacturing changes on product. quality. |
| 12 Jul 2023 | Postmarketing Studies and Clinical Trials: Determining Good Cause for Noncompliance with Section 505(o)(3)(E)(ii) of the Federal Food, Drug, and Cosmetic Act Source: FDA | Draft, Level 1 | This guidance: • provides information for holders of applications for human prescription drugs (hereafter applicants) who are required to conduct postmarketing studies or clinical trials under section 505(o)(3) of the Federal FD&C Act. These postmarketing studies and clinical trials are also commonly referred to as postmarketing requirements (PMRs), or 505(o)(3) PMRs (hereafter PMRs). An applicant required to conduct a PMR under section 505(o)(3) must provide certain information to FDA, including a timetable for study or clinical trial completion and periodic reports on the status of the study or clinical trial. If an applicant fails to comply with the timetable or other requirements of section 505(o)(3)(E)(ii), the applicant is in violation of section 505(o)(3), unless the applicant has demonstrated good cause for its noncompliance or other violation. • describes factors FDA considers when determining whether an applicant has demonstrated good cause for its noncompliance with the timetable for completion of PMR milestones as required under section 505(o)(3). • also provides information on relevant procedures including how to communicate with FDA regarding PMR compliance |
| 11 Jul 2023 | Inborn Errors of Metabolism That Use Dietary Management: Considerations for Optimizing and Standardizing Diet in Clinical Trials for Drug Product Development: Guidance for Industry Source: FDA | Draft | This guidance: • describes the FDA’s current recommendations regarding how to optimize and standardize dietary management in clinical trials for the development of drugs that treat inborn errors of metabolism (IEM) for which dietary management is a key component of patients’ metabolic control. Optimizing dietary management in these patients before entry into and during clinical trials is essential to providing an accurate evaluation of the efficacy of new drug products. • 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 and E10 Choice of Control Group and Related Issues in Clinical Trials, respectively. |
| 3 Jul 2023 | Study Data Technical Conformance Guide – Technical Specifications Document Source: FDA | Final | This 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) ofthe 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. • provides technical recommendations to sponsors for the submission of animal and human study data and related information in a standardized electronic format in INDs, NDAs, ANDAs, and BLAs. • is intended to complement and promote interactions between sponsors and FDA review divisions. However, it is not intended to replace the need for sponsors to communicate directly with review divisions regarding implementation approaches or issues relating to data standards. |
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medicines-medical devices-regulatory affairs