仿制药的简略新药申请程序（ANDA Process）

• 前言

• 简略新药申请的指南文件

• 法律，法规，政策和程序

            o 美国联邦法典 o 政策和程序手册

• 药品开发和评审定义

• 药品开发方面的常见问题
  

• 相关主题
  

前言

An Abbreviated New Drug Application (ANDA) contains data which when submitted to FDA's Center for Drug Evaluation and Research, Office of Generic Drugs, provides for the review and ultimate approval of a generic drug product. 简略新药申请（ANDA）所包括的资料被交至 FDA 药品评审和研究中心所属的仿制药办公室，用于仿制药的评审和最终批准。

Once approved, an applicant may manufacture and market the generic drug product to provide a safe, effective, low cost alternative to the American public.一旦批准，则申请者可以生产和销售该仿制药以向美国公众提供安全，有效，廉价的替代品。

A generic drug product is one that is comparable to an innovator drug product in dosage form, strength, route of administration, quality, performance characteristics and intended use. 仿制药在剂型，剂量，服用方式，质量，性能特征和用途方法都是和原创药物相当的。

All approved products, both innovator and generic, are listed in FDA's Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book). 所有被批准的药品，包括原创药和仿制药都列在 FDA 的具有相当疗效评估的已批准药品（橙皮书）上。

Generic drug applications are termed "abbreviated" because they are generally not required to include preclinical (animal) and clinical (human) data to establish safety and effectiveness. 仿制药申请被称为“简略申请”，是因为它们基本上不需要临床前资料（动物实验）和临床资料（人体实验）来建立安全性的有效性。

Instead, generic applicants must scientifically demonstrate that their product is bioequivalent (i.e., performs in the same manner as the innovator drug). 仿制药申请者必须要科学地 论述他们的产品是生物等效的（也就是，和原创药同样的性能表现）

One way scientists demonstrate bioequivalence is to measure the time it takes the generic drug to reach the bloodstream in 24 to 36 healthy, volunteers. 科学家论证生物等效性的一种方法就是测定仿制药到达 24￣36 位健康志愿者血流中的时间。

This gives them the rate of absorption, or bioavailability, of the generic drug, which they can then compare to that of the innovator drug. 这个实验给出仿制药的吸收率（rate of absorption）或者生物利用度，因此仿制药就可以凭此与原创药进行比较。

The generic version must deliver the same amount of active ingredients into a patient's bloodstream in the same amount of time as the innovator drug. 仿制药必须和原创药在同样的时间内将同样量的活性成分传输到患者的血流。

Using bioequivalence as the basis for approving generic copies of drug products was established by the "Drug Price Competition and Patent Term Restoration Act of 1984," also known as the Waxman-Hatch Act. 把生物等效性作为批准仿制药的基础是根据 1984年的"药品价格竞争和专利恢复法案,"，来确立的，该法案也被称之为维克斯曼－哈奇法案。

This Act expedites the availability of less costly generic drugs by permitting FDA to approve applications to market generic versions of brand-name drugs without conducting costly and duplicative clinical trials. 本法令通过允许 FDA 批准品牌药的仿制版本的上市而无需进行昂贵和重复性的临床试验来加快较便宜的仿制药的获得。

At the same time, the brand-name companies can apply for up to five additional years longer patent protection for the new medicines they developed to make up for time lost while their products were going through FDA's approval process. 同时，品牌药厂家也可以为他们所开发的新药申请五年的专利保护延期以弥补他们产品在通过 FDA 批准过程所损失的时间。

Brand-name drugs are subject to the same bioequivalence tests as generics upon reformulation. 品牌药在改变配方时也要进行和仿制药一样的生物等效性实验。

For more information on generic drug bioequivalency requirements, please see the chapter entitled "FDA Ensures Equivalence of Generic Drugs" in "From Test Tube to Patient: Improving Health Through Human Drugs." 关于仿制药生物等效性方面要求的更多信息，请参见"从试管到患者：通过药品提高健康."

The Office of Generic Drugs home page provides additional information to generic drug developers, including an interactive flowchart presentation of the ANDA review process, focusing on how CDER determines the safety and bioequivalence of generic drug products prior to approval for marketing. 仿制药办公室的主页 为仿制药开发者提供了更多的信息，包括一个互动性的 ANDA 评审过程流程图，重点在于 CDER 在批准仿制药上市前是如何确定其安全性和生物等效性的。

Generic drug application reviewers focus on bioequivalence data, chemistry and microbiology data, requests for plant inspection, and drug labeling information.仿制药申请的的评审官着重于生物等效性资料，化学和生物资料，工厂检查的要求和药品标签信息等。

This web site is designed for individuals from pharmaceutical companies, government agencies, academic institutions, private organizations, or other organizations interested in bringing a generic drug to market. 本网址是为来自制药企业，政府机关，学术单位，私营组织或其它组织中对将仿制药带入市场感兴趣的个人而设计的。 

Each of the sections below contains information from CDER to assist you in the ANDA application process. 下面的每一个章节都包括了来自CDER 的信息以为你在 ANDA 申请过程中提供帮助。

Click on a link to go directly to a section.点击链接直接进入相应的章节。

ANDA 递交方面的资源

The following resources have been gathered to provide you with the legal requirements of an ANDA application, assistance from CDER to help you meet those requirements, and internal ANDA review principles, policies and procedures.

如下资源集中在一起为你提供了 ANDA 申请的法律要求，来自于 CDER 的支持以帮助你满足他们的要求，ANDA 的内部评审原则，政策和程序。

Guidance Documents for ANDAs

ANDA 方面的指导文件

Guidance documents represent the Agency's current thinking on a particular subject. 指导文件代表了 FDA 对某一主题的当前看法。

These documents are prepared for FDA review staff and applicants/sponsors to provide guidelines to the processing, content, and evaluation/approval of applications and also to the design, production, manufacturing, and testing of regulated products. 这些文件旨在为 FDA 评审人员和申请者/发起人(Sponsor)在申请的内容整理，评审/批准等方面提供指南，同时也为受管产品的设计，生产，制造和测试等方面提供指南。

They also establish policies intended to achieve consistency in the Agency's regulatory approach and establish inspection and enforcement procedures. 他们也建立政策以获得 FDA 法规方法方面的一致性，并建立检查和执行程序。

Because guidances are not regulations or laws, they are not enforceable, either through administrative actions or through the courts. 因为指南既不是法律也不是法规，因此它们无论是在通过行政执行还是通过法院都没有强制性。

An alternative approach may be used if such an approach satisfies the requirements of the applicable statute, regulations, or both.如果另有办法可以满足适宜法令和/或法规的要求，则该办法也是可以使用的。 

For information on a specific guidance document, please contact the originating office. 关于某一指定指南的相关信息，请与发起办公室联系。

The FDA has numerous guidances that relate to ANDA content and format issues. FDA 有很多关于 ANDA 内容和格式问题的指南。

Below is a list of some recent Guidances of interest. 如下为一些最近的相关指南的列表。

See Drug Information Branch's Guidance Documents for a complete list of available guidances online and instructions on how to obtain them. 关于可在线获得指南的完整列表和如何获得它们的指导，请参见药品信息部指南文件。

Most of these documents are in Adobe Acrobat format   also know as PDF 这些文件大部分都是 Adobe Acrobat 格式的   ，也称之为 PDF 格式. 

The free upgrade to Adobe Acrobat 3.0 or higher is recommended, especially if you have difficulty opening any of the documents below 推荐使用 Adobe Acrobat 3.0 免费升级版，或更高版本，特别是当你打开下列文件有困难时。 

For information on a specific guidance document, please contact the originating office.关于某个指南文件方面的信息，请与发起办公室联系。

Guidance documents to help prepare ANDAs are listed together on CDER's Guidance Document Index webpage in the following categories:

帮助制作 ANDA 的指导文件以如下分类集中列在 CDER 的指导文件索引网页上：

• Generics 仿制药.

• Generics (Draft - Distributed for comment purposes only)仿制药（草案－仅供征求意见用).
  

• Procedural Draft: Applications Covered by Section 505(b)(2) (Issued 10/1999, Posted 12/7/1999). 程序草案： 法令第 505（b）(2)章节所涉及的申请（1999 年 10 月发行，1999 年 12 月 7 日公告）This provision permits FDA to rely, for approval of an NDA, on data not developed by the applicant. 本规定允许 FDA 在批准 NDA 时，可以信赖不是由申请者所开发的资料。

• Biopharmaceutics 生物制药.
  

• Bioavailability and Bioequivalence Studies for Orally Administered Drug Products General Considerations 口服剂型的生物利用度和生物等效性研究－基本考虑. Optional Format: PDF (Issued 10/2000, Posted 10/27/2000). 可选格式： PDF （2000 年 10 月发行，2000 年 10 月 27 日公告）。This guidance should be useful for applicants planning to conduct bioavailability (BA) and bioequivalence (BE) studies during the IND period for an NDA, BE studies intended for submission in an ANDA, and BE studies conducted in the postapproval period for certain changes in both NDAs and ANDAs. 本指南对于准备在NDA 的 IND 阶段进行生物利用度和生物等效性研究，准备为 ANDA 申请进行生物等效性研究，准备为 NDA 和ANDA 的某些申请的批准前阶段进行生物等效性研究的申请者是有帮助的。

• Drug Master Files 药品主文件. A Drug Master File (DMF) is a submission to the FDA that may be used to provide confidential detailed information about facilities, processes, or articles used in the manufacturing, processing, packaging, and storing of one or more human drugs. 药品主文件（DMF）是交至 FDA 的文件，可用于向 FDA 提供一个或多个人用药的储存，包装，处理和制造过程中所用设施，工艺或物质等方面的详细机密信息。

• Required Specifications for FDA's IND, NDA, and ANDA Drug Master File Binders。 FDA 的 IND，NDA 和 ANDA 药品主文件装订的所需要规范

• Guidance for Industry: Changes to an Approved NDA or ANDA 工业指南：已批准 NDA 或 ANDA 的变更

• Refusal to Receive.   (Issued 7/12/1993, Posted 11/26/99) Clarifies CDER's decisions to refuse to receive an incomplete application. 拒绝接受 （1993年 7 月 12 日发行，1999 年 11 月 26 日公告）阐明 CDER 拒绝接受不完整申请的决定

• Inactive Ingredient Database 非活性成分数据库. This database contains all inactive ingredients present in approved drug products or conditionally approved drug products currently marketed for human use. 本数据库包含了已上市人用已批准药品或条件性批准药品中的所有非活性成分数据库。

Laws, Regulations, Policies and Procedures 法律，法规，政策和程序

The mission of FDA is to enforce laws enacted by the U.S. Congress and regulations established by the Agency to protect the consumer's health, safety, and pocketbook. FDA 的使命是执行美国议会所制订的法律和 FDA 所建立的法规以保护消费者的健康，安全和财力。

The Federal Food, Drug, and Cosmetic Act is the basic food and drug law of the U.S. With numerous amendments it is the most extensive law of its kind in the world. 联邦食品，药品和化妆品法令 是美国基本的食品和药品法律，它有很多的增补，它是世界上同类法律中最广泛的。

The law is intended to assure consumers that foods are pure and wholesome, safe to eat, and produced under sanitary conditions; that drugs and devices are safe and effective for their intended uses; that cosmetics are safe and made from appropriate ingredients; and that all labeling and packaging is truthful, informative, and not deceptive.法律旨在向消费者确保食品是纯净和卫生，可安全食用，且是在卫生的条件下生产的；向消费者确保化妆品是安全的，且是用合适的组分生产而来的；和向消费者确保所有的标签和包装是可信，详实的，且不能有欺诈性。

Code of Federal Regulations (CFR)美国联邦法规

Code Of Federal Regulations (CFR)联邦法规（CFR）. The final regulations published in the Federal Register (daily published record of proposed rules, final rules, meeting notices, etc.) are collected in the CFR 在联邦公报（每天公布拟定的法规，最终法规，会议通告等）上公布的最终法规会被收录在 CFR 里。

The CFR is divided into 50 titles which represent broad areas subject to Federal regulations. 联邦法规被分成 50 个主题，这些主题代表了联邦法规所属的广泛领域。

The FDA's portion of the CFR interprets the Federal Food, Drug and Cosmetic Act and related statutes. 联邦法规（CFR）的 FDA部分解释联邦食品，药品和化妆品法令和相关的法规。

Section 21 of the CFR contains most of the regulations pertaining to food and drugs. 联邦法规（CFR）第 21 部分包括了绝大部分食品和药品的相关法规。 

The regulations document most actions of all drug sponsors that are required under Federal law. 这些法规收录了联邦法律所需的所有药品发起人的绝大部分措施。

The following regulations apply to the ANDA process:如下这些法规适用于 ANDA 过程：

• 21CFR Part 314  Applications for FDA Approval to Market a New Drug or and Antibiotic Drug 新药或新抗生素药品 FDA 上市批准的申请

• 21CFR Part 320 Bioavailability and Bioequivalence Requirements 生物利用度和生物等效性的要求 . For more information on retention samples, please see Bioequivalence Study Retention Samples. 关于留样的更多信息，请参见生物等效性研究留样
  

• Bioavailability and Bioequivalence Requirements; Abbreviated Applications; Final Rule. [TXT] [PDF] (Issued and posted 12/19/2002) 生物利用度和生物等效性要求；简略申请；最终法令[TXT] [PDF] （2002 年 12 月 19 日发行公布）。

• 21CFR Part 310 New Drugs 新药

MaPPs 政策和程序手册

CDER's Manual of Policies and Procedures (MaPPs) provide official instructions for internal practices and procedures followed by CDER staff to help standardize the drug review process and other activities, both internal and external. CDER 的政策和程序手册(MaPPs) 提供了CDER人员所遵循的内部规范和程序以帮助实现药品评审过程和其它内部和外部活动的标准化。

MaPPs define external activities as well. MaPPs 政策和程序手册同样也定义了外部活动。 

All MAPPs are available for the public to review to get a better understanding of office policies, definitions, staff responsibilities and procedures. 公众可以获得所有的政策和程序手册（MaPPs）以更好的理解办公政策，定义，人员职责和程序。

MaPP documents to help prepare ANDAs are listed together on CDER's Manual of Policies and Procedures webpage.帮助制作 ANDA 的政策和程序手册（MaPPs）集中列在 CDER 的政策和程序手册（MaPPs）网页上。

• Chapter 5200 - Generic Drugs 仿制药

ANDA Forms and Electronic Submissions ANDA 表格和电子申请

• ANDA Checklist for Completeness and Acceptability ANDA 的完整性和可接受性的核对表    [Word]  (Posted 4/19/2006)

• FDA Form 356h.    Application to Market a New Drug for Human Use/Antibiotic Drug for Human Use 人用新药/人用新抗生素的上市申请

• The CDER Office of Generic Drugs has developed a guidance document entitled Providing Regulatory Submissions in Electronic Format ?ANDAs [PDF version] (Issued 6/2002, Posted 6/27/2002) to assist applicants making regulatory submissions in electronic format of abbreviated new drug applications. CDER 所属的仿制药办公室已经制订了一份题为：以电子形式提交 ANDA 申请 [PDF version] （2002 年 6 月发行，2002 年 6 月 27 日公告）以帮助申请者进行 ANDA 的电子格式递交。This guidance should be used in conjunction with the following guidances: 本指南需和如下这些指南结合起来使用：

• Guidance for Industry: Providing Regulatory Submissions in Electronic Format –General Considerations 工业指南：以电子格式递交申请－基本考虑事宜.  

• Regulatory Submissions in Electronic Format; New Drug Applications 以电子格式递交申请：新药申请.   

• For more information on electronic submissions, see Electronic Regulatory Submission and Review. 关于电子递交方面的更多信息，请参见电子格式递交及评审.

Related Topics 相关主题

• Investigational New Drug Application 新药临床试验申请(IND). Provides resources to assist drug sponsors with submitting applications for approval to begin new drug experiments on human subjects. 向药品试验委托者（Drugsponsor）提供资源以帮助其递交开始新药的人体试验的批准申请

• New Drug Application 新药申请(NDA). Provides resources to assist drug sponsors with submitting applications for approval to market a new drug. 向药品试验委托者（Drug sponsor）提供资源以帮助其递交新药上市的批准申请

• Drug Application Regulatory Compliance 药品申请的法规符合 The approval process for new drug applications includes a review of the manufacturer's

• compliance with Current Good Manufacturing Practice. This web page provides resources to help meet compliance. 新药申请的批准过程包括生产 厂家现行GMP 符合性的评审。

• Information for Clinical Investigators 临床研究员需知. Provides regulations and guidelines to scientists who design and run experiments (clinical trials) to test the safety and effectiveness of new drugs on human subjects. 为设计和进行实验（临床试验）以检测新药对人体的安全性和有效性的科学家提供法规和指导。

• Small Business Assistance Program 小型事务支持程序.

• Electronic Regulatory Submission and Review 电子递交和评审

• (ERSR). Provides information on electronic drug applications, application reviews, Electronic Document Room, and other ERSR projects. 提供电子药品申请，申请评审，电子文件室和其它 ERSR 项目方面的信息。

• Post Drug-Approval Activities 药品批准后活动. The goal of CDER's post drug-approval activities is to monitor the ongoing safety of marketed drugs. CDER药品批准后活动的目的是监测已上市药品的安全性。This is accomplished by reassessing drug risks based on new data learned after the drug is marketed, and recommending ways of trying to most appropriately manage that risk. 这一点是通过以药品上市后所获知的新资料为基础重新评药品风险，并建议能最适宜地管理该风险的方式来实现的。