US FDA issued guidance for industry, January – March 2023

DateTitle of guidance and link to documentType and level
of guidance
About the guidance
31 Mar 2023Identification of Medicinal Products — Implementation and Use

Source: FDA
Final This guidance is for sponsors, applicants, and registrants who are involved in the regulatory submission of medicinal product data. The guidance supports the development and implementation of the International Organization for Standardization (ISO) Identification of Medicinal Products (IDMP) standards for substances, terminologies, and other information for use throughout the global medicinal product development lifecycle. The purpose of these standards is to enable improved accuracy, completeness, and consistency in the international exchange of medicinal product information among stakeholder.
24 Mar 2023Clinical Trial Considerations to Support Accelerated Approval of Oncology TherapeuticsThis draft guidance concerns clinical trial design considerations to support accelerated approval applications. The accelerated approval pathway is commonly used for approval of oncology drugs in part due to the serious and life-threatening nature of cancer and because of available intermediate clinical endpoints likely to predict clinical benefit.

The draft guidance discusses the design of clinical trials, and ways to improve the data available at the time of accelerated approval and reduce clinical uncertainty for patients by initiating postmarketing confirmatory studies in a timely manner.

Specifically, the draft guidance addresses the design, conduct and analysis of data through two randomized clinical trial approaches – conducting two separate randomized controlled clinical trials or using one trial for both accelerated approval and to verify clinical benefit. The draft guidance also provides considerations for sponsors to determine the adequacy of single-arm studies to support an application.

For drugs granted accelerated approval, postmarketing confirmatory trials have been required to verify and describe the anticipated clinical benefit. The draft guidance discusses a potential advantage of randomized clinical trials–compared to single-arm trials–by highlighting that use of the one-trial approach, in appropriate cases, may not require separate clinical trials because longer term follow-up in the same trial could fulfill a postmarketing requirement to verify clinical benefit. Moreover, confirmatory trials that are in progress at the time of accelerated approval are more likely to result in a timely verification of clinical benefit, therefore minimizing the period of uncertainty for patients.
23 Mar 2023Pharmacogenomic Data Submissions

Source: FDA
DraftThis guidance is intended to facilitate progress in the field of pharmacogenomics and the use of pharmacogenomic data in drug development. This document is intended to clarify the contexts in which pharmacogenomic study findings and data must be included in submissions related to investigational new drug applications (INDs), new drug applications (NDAs), and biologics license applications (BLAs) based on the FDA’s regulations. In addition, this document provides recommendations to sponsors and applicants on the format and content of the pharmacogenomic data submissions.

For the purposes of this guidance, the term pharmacogenomics is defined as the study of variations of DNA and RNA characteristics as related to drug response; 25 3 DNA or RNA variations can be germline, somatic, or microbial. Pharmacogenomics does not refer to data resulting from proteomic, metabolomic, or other -omic studies, although similar considerations in this guidance could be applicable for determining whether to submit findings and data from such studies.
16 Mar 2023Definitions of Suspect Product and Illegitimate Product for Verification Obligations Under the Drug Supply Chain Security Act Guidance for Industry

Source: FDA
Final, Level 1FDA is issuing this guidance to interpret the terms used in the definition of suspect product set forth in section 581(21) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 360eee(21), and the definition of illegitimate product set forth in section 581(8) of the FD&C Act, to assist trading partners in meeting verification obligations (including notification) under section 582(b)(4), (c)(4), (d)(4), and (e)(4) (21 U.S.C. 360eee-1(b)(4), (c)(4), (d)(4), and (e)(4))), respectively.
15 Mar 2023Development of Local Anesthetic Drug Products With Prolonged Duration of Effect

Source: FDA
DraftThe purpose of this guidance is to assist sponsors that are developing local anesthetic drug products to produce postoperative analgesia for a prolonged duration, for which submission of a new drug application (NDA) through the pathway described in section 505(b) of the FD&C Act is appropriate.
This guidance is not applicable to applications that meet criteria for submission under section 505(j) of the FD&C Act, petitioned abbreviated new drug applications under section 505(j)(2)(C) of the FD&C Act, or applications submitted under section 351 of the Public Health Service Act.
15 Mar 2023Electronic Systems, Electronic Records, and Electronic Signatures in Clinical Investigations: Questions and Answers

Source: FDA
DraftThis document provides guidance to sponsors, clinical investigators, institutional review boards (IRBs), contract research organizations (CROs), and other interested parties on the use of electronic systems, electronic records, and electronic signatures in clinical investigations of medical products, foods, tobacco products, and new animal drugs. The guidance provides recommendations regarding the requirements, including the requirements under 21 CFR part 11 (part 11), under which FDA considers electronic systems, electronic records, and electronic signatures to be trustworthy, reliable, and generally equivalent to paper records and handwritten signatures executed on paper.
10 Mar 2023Evaluation of Gastric pH-Dependent Drug Interactions With Acid-Reducing Agents: Study Design, Data Analysis, and Clinical Implications Guidance for Industry

Source: FDA
FinalThis guidance:
· describes the FDA’s recommendations regarding: (1) when clinical drug-drug interactions (DDI) studies with acid-reducing agents (ARAs) are needed; (2) the design of such clinical DDI studies; (3) how to interpret these study results; and (4) communicating these findings in drug product labeling.
· does not cover other DDI mechanisms for some ARAs such as reduced absorption due to the formation of chelate complexes (e.g., aluminum or magnesium hydroxides, calcium carbonate) for weak-acid drugs and decreased renal elimination of certain drugs as a result of the alkalinization of urine (e.g., sodium bicarbonate).
1 Mar 2023Q13 Continuous Manufacturing of Drug Substances and Drug Products

Source: FDA
Final Level This guidance:
· describes scientific and regulatory considerations for the development, implementation, operation, and lifecycle management of continuous manufacturing (CM). Building on existing International Council for Harmonization (ICH) Quality guidances, this guidance provides clarification on CM concepts and describes scientific approaches and regulatory considerations specific to CM of drug substances and drug products.
· applies to CM of drug substances and drug products for chemical entities and therapeutic proteins. It is applicable to CM for new products (e.g., new drugs, generic drugs, biosimilars) and the conversion of batch manufacturing to CM for existing products. The principles described in this guidance may also apply to other biological/biotechnological entities.

CM involves the continuous feeding of input materials into, the transformation of in-process materials within, and the concomitant removal of output materials from a manufacturing process. While this description may apply to an individual unit operation (e.g., process chromatography, tableting, perfusion cell culture), this guidance focuses on the integrated aspects of a CM system in which two or more unit operations are directly connected. In this context, any changes made in a unit operation of a CM system may have impact on downstream and upstream unit
operations (e.g., back pressure resulting in forward mixing) and output material quality.
28 Feb 2023Potency Assay Considerations for Monoclonal Antibodies and Other Therapeutic Proteins Targeting Viral Pathogens

Source: FDA
DraftThe purpose of this guidance is to provide to sponsors recommendations that assist in the development of monoclonal antibodies (mAbs) and other therapeutic proteins that directly target viral proteins or host cell proteins mediating pathogenic mechanisms of infection. A critical quality control measure for these products is the development and implementation of a potency assay(s) adequate to ensure that each lot is produced consistently with the potency necessary to achieve clinical efficacy and that such potency is maintained over the shelf life of the product. This guidance provides detailed recommendations to drug developers with the goal of helping to ensure that drug developers provide adequate information to assess potency at each stage of a product’s life cycle.

This guidance applies only to mAbs and other therapeutic proteins regulated by the Center for Drug Evaluation and Research that are designed to bind to viral proteins or their receptors on host cells, inhibit viral entry, and/or elicit Fc-mediated effector function, and are subject to licensure under section 351(a) or section 351(k) of the Public Health Service Act (42 U.S.C. 262(a) or (k)).

This guidance does not apply to other biological products such as immunomodulatory drugs (e.g., cytokines or cytokine antagonists), vaccines, hyperimmune globulins, gene therapies, cell therapies, and convalescent plasma.
24 Feb 2023Neovascular Age-Related Macular Degeneration: Developing Drugs for Treatment

Source: FDA
DraftThis guidance is intended to provide recommendations to sponsors regarding eligibility criteria, trial design considerations, and efficacy endpoints to enhance clinical trial data quality and to foster greater efficiency in development programs for drugs for the treatment of neovascular age-related macular degeneration.
10 Feb 2023Considerations for Long-Term Clinical Neurodevelopmental Safety Studies in Neonatal Product Development

Source FDA
DraftThe purpose of this guidance is to provide a framework for considering whether and what type of long-term neurologic, sensory and developmental evaluations could be useful to support a determination of safety of a drug, biological product, or device (referred to as ‘medical product’ in this guidance) for use in neonates , and if so, which domains of neurodevelopment may be most applicable.

This guidance:
· will not specifically address efficacy or effectiveness assessments for products primarily intended to improve neurologic outcomes, e.g., neuroprotective agents.
· is focused on long-term evaluations of neurodevelopmental safety. Although assessments of nephrotoxicity, pulmonary toxicity, and toxicity to other tissues and organs may also be warranted in neonatal medical product development, the approach to those assessments is outside the scope of this guidance.

You can view a snapshot of the guidance here, listen to the guidance recap podcast here and view the podcast transcript here.
2 Feb 2023Study Data Technical Conformance Guide – Technical Specifications Document (Oct 2022)

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. 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 to 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.
31 Jan 2023M13A Bioequivalence for Immediate-Release Solid Oral Dosage Forms

Source: FDA

ICH M13A Step 2
DraftThis guideline is intended to provide recommendations on conducting bioequivalence (BE) studies during both development and post approval phases for orally administered immediate-release (IR) solid oral dosage forms designed to deliver drugs to the systemic circulation, such as tablets, capsules, and granules/powders for oral suspension.
31 Jan 2023Considerations for the Design and Conduct of Externally Controlled Trials for Drug and Biological Products

Source: FDA
DraftThis guidance:
· provides recommendations to sponsors and investigators considering the use of externally controlled clinical trials to provide evidence of the safety and effectiveness of a drug product. In an externally controlled trial, outcomes in participants receiving the test treatment according to a protocol are compared to outcomes in a group of people external to the trial who had not received the same treatment. The external control arm can be a group of people, treated or untreated, from an earlier time (historical control), or it can be a group of people, treated or untreated, during the same time period (concurrent control) but in another setting.
· addresses considerations for the design and analysis of externally controlled trials to study the effectiveness and safety of drugs, including discussion of threats to the validity of trial results from potential bias. Although various sources of data can serve as the control arm in an externally controlled trial, this guidance focuses on the use of patient-level data from other clinical trials or from real-world data (RWD) sources, such as registries as well as electronic health records (EHRs) and medical claims. The guidance also describes considerations related to communicating with FDA and ensuring access by FDA to data from an externally controlled trial.
· does not address other types of external controls, such as using summary-level estimates instead of patient-level data. This guidance does not discuss details of the design and analysis of a natural history study8 nor the reliability and relevance of various sources of RWD that could be used in an externally controlled trial. Finally, this guidance also does not discuss considerations for using external control data to supplement a control arm in a traditional randomized controlled clinical trial.
30 Jan 2023Acromegaly: Developing
Drugs for Treatment

Source: FDA

DraftThe purpose of this guidance is to provide recommendations to sponsors regarding clinical development of drugs for the treatment of patients with acromegaly. This draft guidance is intended to serve as a focus for continued discussions among the Division of General Endocrinology, pharmaceutical sponsors, the academic community, and the public.
12 Jan 2023Content and Format of the Dosage and Administration Section of Labeling for Human Prescription Drug and Biological Products

Source: FDA
Draft Level 1This guidance is intended to assist applicants in developing the DOSAGE AND ADMINISTRATION section of labeling as described in 21 CFR 201.57(c)(3), a regulation governing the content and format of this section of human prescription drug and biological product labeling, to ensure that this section contains the dosage- and administration-related information needed for safe and effective use of a drug.3,4 21 Applicants should follow the recommendations in this guidance when developing the DOSAGE AND ADMINISTRATION section for a new drug submitted to FDA under a new drug application under section 505(b) of the FD&C Act or a biologics license application under section 351(a) of the PHS Act, and when revising existing information in the labeling for a currently approved drug in a supplement to such applications. This guidance provides examples (denoted with a sawtooth line in the left margin) of required and recommended information in the DOSAGE AND ADMINISTRATION section.
4 Jan 2023REMS Document Technical Conformance Guide

Source: FDA
Final This Risk Evaluation and Mitigation Strategy (REMS) Document Technical Conformance Guide (Guide) provides updated, detailed instructions on the format of a REMS Document, along with standardized language that describes common REMS requirements for applicants to use whenever possible, to help ensure consistency and facilitate efficient review of the REMS Document. This Guide supports submission of a REMS Document in Structured Product Labeling (SPL) format. In addition, this Guide provides an outline to assist applicants in drafting a Bifurcated REMS Document.

This Guide supplements the guidance for industry Format and Content of a REMS Document (see below).
4 Jan 2023Format and Content of a REMS Document Guidance for Industry

Source: FDA
Final This guidance provides:
· recommendations for the format and content of a risk evaluation and mitigation strategy (REMS) document for a prescription drug product, including a biological drug product. A REMS document, which is part of a REMS that is required by FDA, establishes the goals and requirements of the REMS.
· recommendations to applicants on drafting proposed REMS documents and converting an already-approved REMS document to a new, standardized format that is clearer, more informative, and supports submission of a REMS document in Structured Product Labeling (SPL) format.
· an overview of the types of information that should be included in a REMS document. Additional and more detailed information is provided in a separate guide, REMS Document Technical Conformance Guide, which will be updated periodically and is available on FDA’s website. The guide can be used for drafting a REMS document for single product and shared system REMS and includes an outline for drafting a Bifurcated REMS document. This guidance and the technical conformance guide are intended to help ensure that REMS documents are clear, understandable to stakeholders, and to the extent possible, consistent in content and format, and support submission of a REMS document in SPL format.

This guidance does not provide detailed information on the format and content of other documents that are part of a REMS submission, such as the REMS materials5 or the REMS supporting document. Furthermore, the guidance does not include information on how to design, implement, and evaluate a REMS or to submit revisions and modifications for a REMS.