系列5：临床与生物等效性GCP and Bioequivalence
FDA有一系列较为细致、具体和严格的关于开展BE研究的指导原则，包括一般性指南和具体药品BE评估指南。本部分收集了一般性指南。
5.1_Bioequivalence Studies With Pharmacokinetic Endpoints for Drugs Submitted Under an Abbreviated New Drug Application
5.1_ANDA下，药代动力学终点的生物等效性研究
发布日期：12/05/2013
目前状态：草案
This guidance provides recommendations to applicants planning to include bioequivalence (BE) information in abbreviated new drug applications (ANDAs) and ANDA supplements.
就计划将生物等效性(BE)信息包括在ANDA和ANDA补充申请中，本指南为申请人提供了建议。
The guidance describes how to meet the BE requirements set forth in FDA regulations. The guidance is applicable to dosage forms intended for oral administration and to non-orally administered drug products in which reliance on systemic exposure measures is suitable for documenting BE. The guidance will be especially useful when planning BE studies intended to be conducted during the postapproval period for certain changes in an ANDA.
该指南描述了如何满足FDA法规中规定的BE要求。该指南适用于旨在口服给药剂型和非口服给药药品，在这些产品中，依靠全身暴露措施可以证明BE。当打算在批准后期间针对ANDA中的某些变更进行BE研究时，该指南将特别有用。
5.2_Safety Reporting Requirements for INDs (Investigational New Drug Applications) and BA/BE (Bioavailability/Bioequivalence) Studies: Guidance for Industry and Investigators
5.2_IND和BA、BE研究的安全报告要求：行业和研究者指南
发布日期：12/20/2012
目前状态：定稿
This guidance is intended to help sponsors and investigators comply with the requirements for investigational new drug (IND) safety reporting and safety reporting for bioavailability (BA) and bioequivalence (BE) studies under 21 CFR 312.32, 312.64(b), and 320.31(d)(3). This document provides guidance to sponsors and investigators on expedited safety reporting requirements for human drug and biological products that are being investigated under an IND and for drugs that are the subjects of BA and BE studies that are exempt from the IND requirements.
针对研究性新药(IND)安全性报告、生物利用度(BA)和生物等效性(BE)研究安全性报告，本指南旨在帮助发起人和研究者遵守21 CFR 312.32、312.64(b)和320.31(d)(3)要求。
本文件为发起人和研究者提供了快速安全报告要求指南，针对：
-在IND下进行研究的人药和生物产品，以及
-不属于IND要求的BA和BE研究药品。
This guidance defines terms used for safety reporting, makes recommendations on when and how to submit a safety report, and provides advice on other safety reporting issues that have arisen from sponsors and investigators.
本指南定义了用于安全报告的术语，就何时以及如何提交安全报告提出了建议，并就发起人和研究者提出的其他安全报告问题提供了建议。
5.3_Safety Reporting Requirements for INDs and BA/BE Studies: Small Entity Compliance Guide
5.3_IND和BA、BE研究的安全报告要求：小实体合规指南
发布日期：12/20/2012
目前状态：定稿
This guidance is intended to help small businesses understand and comply with FDA’s safety reporting regulations for human drug and biological products that are being investigated under an investigational new drug application (IND) and for drugs that are the subjects of bioavailability (BA) and bioequivalence (BE) studies that are exempt from the IND requirements.
本指南旨在帮助小型企业了解并遵守FDA的安全报告规定，针对：
-正在研究新药申请中的人药和生物产品，以及
-属于IND要求豁免的生物利用度(BA)和生物等效性(BE)研究对象的药物。
The FDA has prepared this guidance in accordance with section 212 of the Small Business Regulatory Enforcement Fairness Act (Public Law 104-121).
根据小企业管理实施公平法(公共法104-121)第212条，FDA准备了本指南。
5.4_Submission of Summary Bioequivalence Data for Abbreviated New Drug Applications
5.4_提交ANDA生物等效性汇总数据
发布日期:05/06/2011
目前状态：定稿
This guidance is intended to assist applicants who are submitting abbreviated new drug applications (ANDAs) in complying with FDA’s requirements for the submission of bioequivalence (BE) data. FDA’s final rule on “Requirements for Submission of Bioequivalence Data” (the BE data rule) requires an ANDA applicant to submit data from all BE studies the applicant conducts on a drug product formulation submitted for approval, including studies that do not demonstrate that the generic product meets the current bioequivalence criteria. All BE studies conducted on the same drug product formulation must be submitted to the Agency as either a complete study report or a summary report of the BE data.
对于正在提交ANDA的申请人，本指南旨在帮助其符合FDA对生物等效性(BE)数据的要求。 FDA关于“提交生物等效性数据的要求”的最终规则(BE数据规则)要求：ANDA申请人提交其对所提交的药品配方进行的所有BE研究的数据，包括未证明仿制药符合当前生物等效性标准的研究。必须将对同一药品配方进行的所有BE研究，作为完整的研究报告或BE数据的摘要报告，提交给FDA。
5.5_Individual Product Bioequivalence Recommendations for Specific Products
5.5_特定产品的生物等效性建议
发布日期：06/10/2010
目前状态：定稿
This guidance describes FDA’s process for making available to the public FDA guidance on how to design bioequivalence (BE) studies for specific drug products to support abbreviated new drug applications (ANDAs). Under this process, applicants planning to carry out such studies in support of their ANDAs will be able to access BE study guidance on the FDA Web site, rather than having to request this information from the Agency and wait for the Agency to respond, as has been the case in the past. The FDA believes that making this information available on the Internet will streamline the guidance process, making it more efficient than the previous process. This process also will provide a meaningful opportunity for the public to consider and comment on BE study recommendations for specific drug products.
本文件描述了FDA发布相关指南的流程，针对如何设计特定药品的生物等效性(BE)研究，以支持ANDA申请。在此流程中，对于计划进行此类研究以支持其ANDA的申请人，其能够在FDA网站上访问BE研究指南，而不必像过去那样——向FDA要求此信息、并等待FDA做出回应。FDA认为，在网站上提供此信息，将简化指南流程，使其比以前的流程更有效。此流程还将为公众提供有意义建议的机会，以考虑和评论针对特定药品的BE研究。
5.6_Handling and Retention of Bioavailability BA and Bioequivalence BE Testing Samples
5.6_生物利用度BA和生物等效性BE检验样品的处理和保留
发布日期：05/25/2004
目前状态：定稿
This guidance is intended to provide recommendations for study sponsors and/or drug manufacturers, contract research organizations (CROs), site management organizations (SMOs), clinical investigators, and independent third parties regarding the procedure for handling reserve samples from relevant bioavailability (BA) and bioequivalence (BE) studies, as required by 21 CFR 320.38 and 320.63.
针对研究发起人和/或药品生产商，合同研究组织(CRO)，现场管理组织(SMO)，临床研究者和独立第三方，本指南旨在提供有关处理相关生物利用度(BA)和生物等效性(BE)研究备用样品程序的建议，这些在21 CFR 320.38和320.63中有所要求。
The guidance highlights:
该指南重点介绍：
(1) how the test article and reference standard for BA and BE studies should be distributed to the testing facilities,
(1)如何将BA和BE的研究对象和参比标准分配给检验设施；
(2) how testing facilities should randomly select samples for testing and material to maintain as reserve samples, and
(2)检验设施：应如何随机选择要检验的样品和材料作为备用样品，
(3) how the reserve samples should be retained.
(3)如何保留备用样品。
The guidance also clarifies and emphasizes points addressed in §§ 320.38 and 320.63.
该指南还阐明并强调了§§320.38和320.63中提到的要点。
5.7_Statistical Information from the June 1999 Draft Guidance and Statistical Information for In Vitro Bioequivalence Data Posted on August 18, 1999
5.7_1999年6月指南草案中的统计信息、体外生物等效性数据的统计信息(1999年8月18日)
发布日期：04/11/2003
目前状态：草案
Statistical analysis method recommendations for in vitro nonprofile bioequivalence data, to accompany the draft guidance for industry entitled Bioavailability and Bioequivalence Studies for Nasal Aerosols and Nasal Sprays for Local Action (April 2, 2003), are under development. At a later time, the analysis methods will be posted. Until these methods are prepared, two documents, both in need of updating, are being made available in the present document. These documents are the original statistical information taken from the earlier June 1999 draft of this guidance, and also from the added Statistical Information for In Vitro Bioequivalence Data material posted on August 18, 1999. The subsequent implementation will include the estimation of within canister (between life stage) component of variance.
伴随着标题为“鼻腔气雾剂和鼻腔喷雾剂的生物利用度和生物等效性研究”的行业指南草案(2003年4月2日)，有关体外非特征性生物等效性数据的统计分析方法建议正在开发中。稍后，将发布分析方法。在准备好这些方法之前，本文件中提供了两个都需要更新的文件。这些文件是本指南的1999年6月早期草案中的原始统计信息，以及1999年8月18日补充的体外生物等效性数据统计信息材料。后续实现将包括对内部(生命周期之间)方差的估计。
5.8_Bioavailability and Bioequivalence Studies for Nasal Aerosols and Nasal Sprays for Local Action
5.8_鼻喷雾剂和鼻喷雾剂局部作用的生物利用度和生物等效性研究
发布日期：04/03/2003
目前状态：草案
This draft document provides recommendations to applicants planning product quality studies to document bioavailability (BA) or bioequivalence (BE) in support of new drug applications (NDAs), or abbreviated new drug applications (ANDAs) for locally acting drugs in nasal aerosols (metered-dose inhalers) and nasal sprays (metered-dose spray pumps).
本文件为计划产品质量研究的申请人提供建议，记录其生物利用度(BA)或生物等效性(BE)，对于鼻喷雾剂(定量吸入器)和鼻喷雾剂(定量喷雾泵)中的局部作用药物，支持其NDA和ANDA申请。
The draft guidance was originally issued for comment on June 24, 1999. Since many substantive changes have been made to the guidance, it is being reissued for comment as a level 1 draft guidance.
该指南草案最初于1999年6月24日发布以征求意见。由于对该指南进行了许多实质性更改，因此，该指南草案已作为1级指南草案重新发布，以征求意见。
5.9_Statistical Approaches to Establishing Bioequivalence 02/01/2001
5.9_建立生物等效性的统计方法
目前状态：定稿
This guidance provides recommendations to sponsors and/or applicants who intend to use equivalence criteria in analyzing in vivo or in vitro bioequivalence (BE) studies for investigational new drug applications (IND’s), new drug applications (NDA’s), abbreviated new drug applications (ANDA’s) and supplements to these applications. The guidance discusses the use of average, population, and individual BE approaches to compare in vivo and in vitro bioavailability (BA) measures.
就IND，NDA和ANDA及其补充申请的体内或体外生物等效性(BE)研究分析中使用等效标准，本指南为发起人和/或申请人提供建议。该指南讨论了使用平均值、总体和个体BE方法来比较体内和体外生物利用度(BA)指标。
This guidance replaces the draft guidance that was issued in 1999 entitled “Average, Population, and Individual Approaches to Establishing Bioequivalence.”
本指南替代了1999年发布的指南草案，题为“建立生物等效性的平均，人口和个体方法”。
5.10_Topical Dermatologic Corticosteroids: in Vivo Bioequivalence
5.10_局部皮肤皮质类固醇激素：体内生物等效性
发布日期：06/02/1995
目前状态：定稿
This guidance provides recommendations to pharmaceutical sponsors on methods to document in vivo bioequivalence of topical dermatologic corticosteroids, hereinafter referred to as topical corticosteroids.
就有关记录局部皮肤病性皮质类固醇的体内生物等效性的方法，该指南为药品发起人提供了建议。
