罕见病药物开发指导文件
正文 · 中文译文
罕见病药物开发指导文件 指导文件 | 药物 CDER指导议程 仿制药开发产品特定指导文件 指导文件概览试点 一般而言，FDA的指导文件不确立具有法律强制力的责任。相反，指导文件描述的是该机构对某一主题的当前思考，应仅视为建议，除非引用了具体的监管或法定要求。机构指导文件中使用“应该”一词意味着某事是被建议或推荐的，但并非必需。 以下是按主题组织的与罕见病药物开发相关的部分指导文件。本列表未包含FDA关于或与罕见病药物开发相关的所有指导文件，但代表了最常用的指导文件。本列表可能会定期更新。 您可以在此处按主题、FDA中心或发布日期搜索所有FDA指导文件。 罕见病 加速批准 获益-风险 生物标志物 临床结局评估（COA）与终点 临床药理学 临床试验 复杂创新试验设计 与FDA沟通 数字健康 有效性 扩展获取 快速通道项目 外部对照试验 个体化反义寡核苷酸药物产品 研究性新药申请 主方案 与FDA会议 新药申请（NDA） 神经病学 非临床 孤儿药认定 以患者为中心的药物开发（PFDD） 患者报告结局 儿科 合理机制 真实世界证据 统计分析 凭证项目 罕见病 关于使用合理机制框架开发针对已知生物学病因的特定遗传状况的个体化治疗的考虑 本指南的目的是描述基于合理机制框架为个体化治疗生成实质性有效性证据和安全性证据的考虑因素。 罕见病：药物和生物制品开发的考虑 本指南阐明了FDA对罕见病药物开发中重要考虑因素的思考，以最终帮助罕见病药物和生物制品开发者开展成功的药物开发项目。 罕见病：用于药物开发的自然史研究：行业指南草案 FDA发布本指南草案，以帮助指导自然史研究的设计和实施，这些研究可用于支持罕见病安全有效药物和生物制品的开发。自然史研究收集在无干预情况下疾病自然史的信息，从疾病发病直到其缓解或个体死亡。尽管了解疾病的自然史可使许多疾病和状况的药物开发受益，但对于大多数罕见病，自然史信息通常不可获得或不完整；因此，这些疾病特别需要自然史信息。 罕见儿科疾病优先审评券 本指南提供了关于实施《食品药品监督管理局安全与创新法案》（FDASIA）第908节的信息，该节在《联邦食品、药品和化妆品法案》（FD&C法案）中增加了第529节。根据第529节，FDA将向符合该节规定标准的某些罕见儿科疾病产品申请的申办者授予优先审评券。 罕见疾病：早期药物开发及pre-IND会议的作用：行业指南草案 本指南草案的目的是协助治疗罕见疾病的药物和生物制品申办者规划和开展更高效、更有成效的研究性新药申请前（pre-IND）会议。罕见疾病的药物开发因这些疾病的性质而面临许多挑战。本指南草案旨在推进和促进用于治疗罕见疾病的药物和生物制品的开发。 由单酶缺陷导致底物沉积的缓慢进展、低患病率罕见疾病：为替代或纠正疗法提供有效性证据：行业指南 本文件为申办者提供指导，说明证明拟用于缓慢进展、低患病率罕见病的研究性新药或新药用途有效性所需的证据，该类疾病与底物沉积相关，并由单酶缺陷引起。本指导原则仅适用于病理生理学特征明确的低患病率罕见病，且其底物沉积的变化可在相关组织中方便地测量。 儿科罕见病——以戈谢病为模型采用协作方法进行药物开发：行业指南草案 本指导原则的目的是促进儿科罕见病的药物开发。特别是，它以戈谢病为例，讨论了一种提高儿科罕见病药物开发效率的新的可能方法。 采用饮食管理的先天性代谢缺陷：药物产品开发临床试验中优化和标准化饮食的考虑因素：行业指南 本指导原则描述了美国食品药品监督管理局（FDA）当前关于在治疗先天性代谢缺陷（IEM）的药物开发临床试验中如何优化和标准化饮食管理的建议，对于这些IEM，饮食管理是患者代谢控制的关键组成部分。在进入临床试验前和临床试验期间优化这些患者的饮食管理，对于准确评估新药产品的有效性至关重要。 加速批准 加速批准及关于确定确证性试验是否正在进行的考量 对于获得加速批准的药物，申办者被要求在批准后开展确证性研究，以验证并描述对不可逆发病或死亡或其他临床获益的预期效果。在2023年《综合拨款法案》（CAA）中，国会修订了《联邦食品、药品和化妆品法案》第506(c)条（21 U.S.C. 356(c)），赋予额外授权以帮助确保此类试验及时完成，包括FDA“可酌情要求在适用产品批准之前或批准日期后的特定时间段内，一项或多项研究正在进行中”。本草案指南定稿后，将阐述FDA对“正在进行中”一词的解释及实施该要求的政策，包括FDA在加速批准行动之前确定确证性试验是否正在进行中时拟考虑的因素。 加速批准——严重疾病的快速通道项目 加速批准是FDA的快速通道项目之一，旨在促进和加快针对严重或危及生命疾病治疗中未满足医疗需求的新药开发和审评。本指南的目的是提供有关FDA加速批准政策和程序的信息，以及通常适用于判定某药物是否为加速批准候选药物的门槛标准。本指南还描述了加速批准下获批产品加速撤回批准的程序，以及国会通过《2023年综合拨款法案》（公法117-328）所作的修订。其他加快产品开发和审评的项目在其他指南中涵盖。 获益-风险 新药和生物制品的获益-风险评价 本指南的意图是向药物申办者和其他利益相关者阐明，关于药物获益、风险和风险管理选项的考量如何纳入美国食品药品监督管理局（FDA或本局）依据《联邦食品、药品和化妆品法案》（FD&C法案）第505(c)条提交的新药申请（NDAs）以及依据《公共卫生服务法案》（PHS法案）第351(a)条提交的生物制品许可申请（BLAs）所作出的某些上市前和上市后监管决定。 生物标志物 关于生物标志物的一般信息，请参见生物标志物简介与资格认定 生物标志物资格认定：证据框架 本指南草案就根据2016年12月13日颁布的《21世纪治愈法案》（《治愈法案》）开发用于资格认定的生物标志物时应考虑的总体问题提出了建议，该法案在《联邦食品、药品和化妆品法案》（《FD&C法案》）中新增了一个章节。生物标志物的资格认定是一项判定，即在所述使用场景下，该生物标志物可被依赖于在药物开发和监管审评中具有特定的解释和应用。 药物开发工具的资格认定流程 本指南描述了药物开发工具（DDTs）的资格认定流程，这些工具拟随着时间推移在多个药物开发项目中潜在使用。 临床结局评估（COAs）与终点 有关COA资格认定项目的信息，请参见临床结局评估（COA）资格认定项目 以患者为中心的药物开发：选择、开发或修改适用于特定用途的临床结局评估 本指南（指南3）是四份以患者为中心的药物开发（PFDD）方法学指南文件系列中的第三份，这些文件描述了利益相关方（患者、照护者、研究人员、医疗产品开发者及其他人员）如何收集和提交患者体验数据以及来自患者和照护者的其他相关信息，以用于医疗产品开发和监管决策。 以患者为中心的药物开发：将临床结局评估纳入终点用于监管决策 本指南（指南4）是四份以患者为中心的药物开发（PFDD）方法学指南文件系列中的第四份，这些文件描述了利益相关方（患者、照护者、研究人员、医疗产品开发者及其他人员）如何收集和提交患者体验数据以及来自患者和照护者的其他相关信息，以用于医疗产品开发和监管决策。 临床试验中的多终点行业指南 本指南向申办方和审评人员提供本机构关于多个终点在研究和结果解释中所引发问题的思考，以及在人体药物（包括作为生物制品需获得许可的药物）临床试验中如何管理这些问题。 临床药理学 暴露-反应关系——研究设计、数据分析与监管应用 本文件向研究性新药（IND）申办方以及提交新药申请（NDA）或生物制品许可申请（BLA）的申请人提供关于在药物（包括治疗性生物制品）开发中使用暴露-反应信息的建议。可将其与支持药物注册的剂量-反应信息的国际人用药品注册技术协调会（ICH）E4指南及其他相关指南（见附录A）一并考虑。 提交于NDA或IND中的生物利用度研究——一般考虑 本指南为申办者和申请人在研究性新药申请（IND）、新药申请（NDA）及NDA补充申请中提交药品生物利用度（BA）信息提供建议。本指南包含关于如何满足21 CFR第320部分中规定的、适用于口服给药剂型的BA要求的建议。 儿科药物研究（包括生物制品）的一般临床药理学考量 本指南协助根据《联邦食品、药品和化妆品法案》（FD&C法案）第505条提交研究性新药申请（IND）的申办者和提交新药申请（NDA）的申请人、根据《公共卫生服务法案》（PHS法案）第351(a)条提交生物制品许可申请（BLA）的申请人以及此类申请的补充申请申请人，这些人员正在计划开展儿科人群的临床研究。 新生儿药物和生物制品研究的一般临床药理学考量行业指南 本指南旨在协助研究性新药申请（IND）的申办者和新药申请（NDA）、生物制品许可申请（BLA）及此类申请补充申请的申请人，这些人员正在计划开展新生儿人群的临床研究。本指南为新生儿临床药理学研究提供建议，无论这些研究是否依据《联邦食品、药品和化妆品法案》（FD&C法案）第505A条、FD&C法案第505B条开展，或两者均不依据。 评估在IND和NDA中食物对药物的影响——临床药理学考量 本指南为计划在研究性新药申请（IND）下对口服药物产品开展食物效应（FE）研究以支持新药申请（NDA）及根据《联邦食品、药品和化妆品法案》第505条（21 U.S.C. 355）开发的药物的此类申请补充的申办者提供建议。 群体药代动力学 本指南旨在协助新药申请（NDA）、生物制品许可申请（BLA）、简化新药申请（ANDA）和研究性新药（IND）申请的申办者和申请人在群体药代动力学（PK）分析的应用方面提供指导。 抗体-药物偶联物的临床药理学考量行业指南 本指南提供建议，以协助行业及其他参与开发携带细胞毒性小分子药物或有效载荷的抗体-药物偶联物（ADC）的相关方。具体而言，本指南阐述了FDA关于ADC开发项目临床药理学考量和建议的当前思考，包括生物分析方法、给药策略、剂量和暴露-反应分析、内在因素、QTc评估、免疫原性和药物-药物相互作用（DDI）。 治疗性蛋白的药物-药物相互作用评估行业指南 本指南的目的是通过提供一种系统化的、基于风险的方法，帮助研究性新药申请（IND）的申办者和生物制品许可申请（BLA）的申请人确定治疗性蛋白质（TP）是否需要开展药物相互作用（DDI）研究。 在疾病的低频分子亚型中开发靶向治疗 靶向治疗的药理作用通常与特定的分子改变相关，而许多疾病由一系列不同的分子改变所致（其中一些可能较为罕见）。因此，靶向治疗在同一疾病但具有不同分子改变的患者中可能产生不同的效应。本指南的目的是描述在临床定义的疾病中评估靶向治疗获益与风险的一般方法，其中某些分子改变可能以低频发生。 临床药物基因组学：早期临床研究中的上市前评估及标签建议 本指南旨在帮助制药行业及其他从事新药开发的研究人员在评估人类基因组变异（特别是DNA序列变异）如何影响药物的药代动力学（PK）、药效动力学（PD）、有效性或安全性时提供指导。本指南就何时以及如何考虑基因组信息以解决药物开发和监管审评中出现的问题提供建议。 临床试验 M11临床电子结构化协调方案 本指南包含三份文件：一份指南、一份模板和一份技术规范文件。该指南提供了实施协调统一的数字化临床试验方案的理由和建议。该模板具有标准化的内容结构和格式，包括标题和常见文本元素。该技术规范文件包含协调统一的术语和标准化数据字段，以实现临床方案信息的电子交换。该指南的目的是为临床试验方案信息的内容和交换建立国际协调统一的标准，促进监管机构、申办者、伦理监督机构、研究者和其它利益相关方的审查和评估。 提高临床试验参与度——入选标准、入组实践和试验设计 本指导原则推荐申办方在旨在支持新药申请或生物制品许可申请的临床试验中可采取的方法，以增加代表性人群的入组。本指导原则既考虑了研究人群的人口学特征（例如性别、种族、族裔、年龄、居住地），也考虑了人群的非人口学特征（例如存在器官功能障碍、合并症、残疾的患者，体重范围极端者，以及患病率低的疾病或病症人群）。入组具有广泛基线特征的受试者，可能形成更准确反映药物获批后可能使用该药物的患者情况的研究人群，并允许评估这些特征对安全性和有效性的影响。
正文 · 英文原文
Guidance Documents for Rare Disease Drug Development Guidances | Drugs CDER Guidance Agenda Product-Specific Guidances for Generic Drug Development Guidance Snapshot Pilot In general, FDA’s guidance documents do not establish legally enforceable responsibilities. Instead, guidances describe the agency’s current thinking on a topic and should be viewed only as recommendations, unless specific regulatory or statutory requirements are cited. The use of the word should in agency guidances means that something is suggested or recommended, but not required. Below are selected guidances that are relevant to rare disease drug development, organized by topic. This list does not include all FDA guidances on or relevant to rare disease drug development but represents our most commonly used guidances. This list may be updated periodically. You can search all FDA Guidances by topic, FDA Center, or issue date here. Rare Disease Accelerated Approval Benefit-Risk Biomarkers Clinical Outcome Assessments (COAs) and Endpoints Clinical Pharmacology Clinical Trials Complex Innovative Trial Design Communication with FDA Digital Health Effectiveness Expanded Access Expedited Programs Externally Controlled Trials Individualized Antisense Oligonucleotide Drugs Products Investigational New Drug Applications Master Protocols Meetings with FDA New Drug Applications (NDAs) Neurology Non-Clinical Orphan Designation Patient Focused Drug Development (PFDD) Patient Reported Outcomes Pediatrics Plausible Mechanism Real World Evidence Statistical Analysis Voucher Program Rare Disease Considerations for the use of the Plausible Mechanism Framework to Develop Individualized Therapies that Target Specific Genetic Conditions with Known Biological Cause The purpose of this guidance is to describe considerations for generating substantial evidence of effectiveness and evidence of safety for individualized therapies based on a plausible mechanism framework. Rare Diseases: Considerations for the Development of Drugs and Biological Products This guidance clarifies FDA’s thinking on important considerations in rare disease drug development to ultimately assist rare disease drug and biologic product developers in conducting successful drug development programs. Rare Diseases: Natural History Studies for Drug Development: Draft Guidance for Industry FDA is publishing this draft guidance to help inform the design and implementation of natural history studies that can be used to support the development of safe and effective drugs and biological products for rare diseases. A natural history study collects information about the natural history of a disease in the absence of an intervention, from the disease's onset until either its resolution or the individual's death. Although knowledge of a disease's natural history can benefit drug development for many disorders and conditions, natural history information is usually not available or is incomplete for most rare diseases; therefore, natural history information is particularly needed for these diseases. Rare Pediatric Disease Priority Review Vouchers This guidance provides information on the implementation of section 908 of the Food and Drug Administration Safety and Innovation Act (FDASIA), which added section 529 to the Federal Food, Drug, and Cosmetic Act (the FD&C Act). Under section 529, FDA will award priority review vouchers to sponsors of certain rare pediatric disease product applications that meet the criteria specified in that section. Rare Diseases: Early Drug Development and the Role of Pre-IND Meetings : Draft Guidance for Industry The purpose of this draft guidance is to assist sponsors of drug and biological products for the treatment of rare diseases in planning and conducting more efficient and productive pre-investigational new drug application (pre-IND) meetings. Drug development for rare diseases has many challenges related to the nature of these diseases. This draft guidance is intended to advance and facilitate the development of drugs and biological products for the treatment of rare diseases. Slowly Progressive, Low-Prevalence Rare Diseases with Substrate Deposition That Results from Single Enzyme Defects: Providing Evidence of Effectiveness for Replacement or Corrective Therapies : Guidance for Industry This document provides guidance to sponsors on the evidence necessary to demonstrate the effectiveness of investigational new drugs or new drug uses intended for slowly progressive, low-prevalence rare diseases that are associated with substrate deposition and are caused by single enzyme defects. This guidance applies only to those low-prevalence rare diseases with well-characterized pathophysiology, and in which changes in substrate deposition can be readily measured in relevant tissue or tissues. Pediatric Rare Diseases--A Collaborative Approach for Drug Development Using Gaucher Disease as a Model : Draft Guidance for Industry The purpose of this guidance is to facilitate drug development in pediatric rare diseases. In particular, it discusses a new possible approach to enhance the efficiency of drug development in pediatric rare diseases using Gaucher disease as an example. Inborn Errors of Metabolism That Use Dietary Management: Considerations for Optimizing and Standardizing Diet in Clinical Trials for Drug Product Development: Guidance for Industry This guidance describes the Food and Drug Administration’s (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. Accelerated Approval Accelerated Approval and Considerations for Determining Whether a Confirmatory Trial is Underway For drugs granted accelerated approval, sponsors have been required to conduct confirmatory studies postapproval to verify and describe the anticipated effect on irreversible morbidity or mortality or other clinical benefit. In the Consolidated Appropriations Act, 2023 (CAA), Congress amended section 506(c) of the FD&C Act (21 U.S.C. 356(c)), to provide additional authorities to help ensure timely completion of such trials, including that FDA “may require, as appropriate, a study or studies to be underway prior to approval, or within a specified time period after the date of approval, of the applicable product.” This draft guidance, when finalized, will describe FDA’s interpretation of the term “underway” and policies for implementing this requirement, including factors FDA intends to consider when determining whether a confirmatory trial is underway prior to an accelerated approval action. Accelerated Approval – Expedited Program for Serious Conditions Accelerated approval is one of FDA’s expedited programs intended to facilitate and expedite development and review of new drugs to address an unmet medical need in the treatment of a serious or life-threatening condition. The purpose of this guidance is to provide information on FDA’s policies and procedures for accelerated approval as well as threshold criteria generally applicable to concluding that a drug is a candidate for accelerated approval. This guidance also describes the procedures for expedited withdrawal of approval of a product approved under accelerated approval and the revisions Congress made through the Consolidated Appropriations Act, 2023 (Public Law 117-328). Additional programs to expedite product development and review are covered in other guidances. Benefit-Risk Benefit-Risk Assessment for New Drug and Biological Products The intent of this guidance is to clarify for drug sponsors and other stakeholders how considerations about a drug’s benefits, risks, and risk management options factor into certain premarket and postmarket regulatory decisions that the Food and Drug Administration (FDA or Agency) makes about new drug applications (NDAs) submitted under section 505(c) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) as well as biologics license applications (BLAs) submitted under section 351(a) of the Public Health Service Act (PHS Act). Biomarkers For general information on Biomarkers, please see About Biomarkers and Qualification Biomarker Qualification: Evidentiary Framework This draft guidance provides recommendations on general considerations to address when developing a biomarker for qualification under the 21st Century Cures Act (Cures Act), enacted on December 13, 2016, that added a new section to the Federal Food, Drug, and Cosmetic Act (FD&C Act). Qualification of a biomarker is a determination that within the stated context of use, the biomarker can be relied on to have a specific interpretation and application in drug development and regulatory review. Qualification Process for Drug Development Tools This guidance describes the qualification process for drug development tools (DDTs) intended for potential use, over time, in multiple drug development programs. Clinical Outcome Assessments (COAs) and Endpoints For information on the COA Qualification Program, please see Clinical Outcome Assessment (COA) Qualification Program Patient-Focused Drug Development: Selecting, Developing, or Modifying Fit-for-Purpose Clinical Outcome Assessments This guidance (Guidance 3) is the third in a series of four methodological patient-focused drug development (PFDD) guidance documents that describe how stakeholders (patients, caregivers, researchers, medical product developers, and others) can collect and submit patient experience data and other relevant information from patients and caregivers to be used for medical product development and regulatory decision-making. Patient-Focused Drug Development: Incorporating Clinical Outcome Assessments Into Endpoints for Regulatory Decision-Making This guidance (Guidance 4) is the fourth in a series of four methodological patient-focused drug development (PFDD) guidance documents that describe how stakeholders (patients, caregivers, researchers, medical product developers, and others) can collect and submit patient experience data and other relevant information from patients and caregivers to be used for medical product development and regulatory decision-making. Multiple Endpoints in Clinical Trials Guidance for Industry This guidance provides sponsors and review staff with the Agency’s thinking about the problems posed by multiple endpoints in the analysis and interpretation of study results and how these problems can be managed in clinical trials for human drugs, including drugs subject to licensing as biological products. Clinical Pharmacology Exposure-Response Relationships — Study Design, Data Analysis, and Regulatory Applications This document provides recommendations for sponsors of investigational new drugs (INDs) and applicants submitting new drug applications (NDAs) or biologics license applications (BLAs) on the use of exposure-response information in the development of drugs, including therapeutic biologics. It can be considered along with the International Conference on Harmonisation (ICH) E4 guidance on Dose-Response Information to Support Drug Registration and other pertinent guidances (see Appendix A). Bioavailability Studies Submitted in NDAs or INDs – General Considerations This guidance provides recommendations to sponsors and applicants submitting bioavailability (BA) information for drug products in investigational new drug applications (INDs), new drug applications (NDAs), and NDA supplements. This guidance contains recommendations on how to meet the BA requirements set forth in 21 CFR part 320 as they apply to dosage forms intended for oral administration. General Clinical Pharmacology Considerations for Pediatric Studies of Drugs, Including Biological Products This guidance assists sponsors of investigational new drug applications (INDs) and applicants of new drug applications (NDAs) under section 505 of the Federal Food, Drug, and Cosmetic Act (the FD&C Act), biologics license applications (BLAs) under section 351(a) of the Public Health Service Act (PHS Act), and supplements to such applications who are planning to conduct clinical studies in pediatric populations. General Clinical Pharmacology Considerations for Neonatal Studies for Drugs and Biological Products Guidance for Industry This guidance is intended to assist sponsors of investigational new drug applications (INDs) and applicants of new drug applications (NDAs), biologics license applications (BLAs), and supplements to such applications who are planning to conduct clinical studies in neonatal populations. This guidance provides recommendations for neonatal clinical pharmacology studies, whether the studies are conducted pursuant to section 505A of the Federal Food, Drug, and Cosmetic Act (FD&C Act), section 505B of the FD&C Act, or neither. Assessing the Effects of Food on Drugs in INDs and NDAs – Clinical Pharmacology Considerations This guidance provides recommendations to sponsors planning to conduct food-effect (FE) studies for orally administered drug products under investigational new drug applications (INDs) to support new drug applications (NDAs) and supplements to these applications for drugs being developed under section 505 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355). Population Pharmacokinetics This guidance is intended to assist sponsors and applicants of new drug applications (NDAs), biologics license applications (BLAs), abbreviated new drug applications (ANDAs), and investigational new drugs (IND) applications in the application of population pharmacokinetic (PK) analysis. Clinical Pharmacology Considerations for Antibody-Drug Conjugates Guidance for Industry This 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 ADC development programs, including bioanalytical methods, dosing strategies, dose- and exposure-response analysis, intrinsic factors, QTc assessments, immunogenicity, and drug-drug interactions (DDIs). Drug-Drug Interaction Assessment for Therapeutic Proteins Guidance for Industry The purpose of this guidance is to help sponsors of investigational new drug applications (INDs) and applicants of biologic license applications (BLAs) determine the need for drug-drug interaction (DDI) studies for a therapeutic protein (TP) by providing a systematic, risk-based approach. Developing Targeted Therapies in Low-Frequency Molecular Subsets of a Disease The pharmacological effect of a targeted therapy is often related to a particular molecular alteration, and many diseases are caused by a range of different molecular alterations (some of which may be rare). Therefore, a targeted therapy may have differential effects among patients with the same disease who have different molecular alterations. The purpose of this guidance is to describe general approaches to evaluating the benefits and risks of targeted therapeutics within a clinically defined disease where some molecular alterations may occur at low frequencies. Clinical Pharmacogenomics: Premarket Evaluation in Early-Phase Clinical Studies and Recommendations for Labeling This guidance is intended to assist the pharmaceutical industry and other investigators engaged in new drug development in evaluating how variations in the human genome, specifically DNA sequence variants, could affect a drug’s pharmacokinetics (PK), pharmacodynamics (PD), efficacy, or safety. The guidance provides recommendations on when and how genomic information should be considered to address questions arising during drug development and regulatory review. Clinical Trials M11 Clinical Electronic Structured Harmonised Protocol This guidance includes three documents: a guidance, a template, and a technical specification document. The guidance provides the rationale and recommendations for implementing a harmonized digital clinical trial protocol. The template features standardized content structure and formatting, including headers and common text elements. The technical specification document contains harmonized terminologies and standardized data fields to enable electronic exchange of clinical protocol information. The intent of the guidance is to create an internationally harmonized standard for the content and exchange of clinical trial protocol information, facilitating the review and assessment by regulators, sponsors, ethical oversight bodies, investigators, and other stakeholders. Enhancing Participation in Clinical Trials — Eligibility Criteria, Enrollment Practices, and Trial Designs This guidance recommends approaches that sponsors of clinical trials intended to support a new drug application or a biologics license application can take to increase enrollment of a representative population in their clinical trials. This guidance considers both demographic characteristics of study populations (e.g., sex, race, ethnicity, age, location of residency) and non-demographic characteristics of populations (e.g., patients with organ dysfunction, comorbid conditions, disabilities, those at the extremes of the weight range, and populations with diseases or conditions with low prevalence). Enrolling participants with a wide range of baseline characteristics may create a study population that more accurately reflects the patients likely to take the drug if it is approved and allow assessment of the impact of those characteristics on the safety and effec