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FDA医疗器械质量体系手册

(2011-01-17 09:11:30)
标签:

杂谈

本文翻译自:FDA医疗器械质量体系手册: 小实体(医疗器械企业)认证指南第一版
FDA网站上可查到原文

Medical Device Quality Systems Manual

医疗器械质量体系手册

A Small Entity Compliance Guide First Edition (Supersedes the Medical Device Good Manufacturing Practices [GMP] Manual)

小实体企业认证指南第一版(用于取代原医疗器械GMP手册)

Chapters

章节

Cover page, Preface, Foreword

首页,前言

Table of Contents

目录

1. The Quality System Regulation

1. 质量体系法规

2. Quality Systems

2. 质量体系

3. Design Controls

3. 设计控制

4. Process Validation

4. 流程验证

5. Personnel and Training

5. 人员和培训

6. Buildings and Environment

6. 建筑和环境

7. Equipment and Calibration

7. 设备和校准

8. Device Master Record

8. 器械主记录

9. Document and Change Control

9. 文档和变更控制

10. Purchasing and Acceptance Activities

10. 采购和接收活动

11. Labeling

11. 标签

12. Product Evaluation

12. 产品评价

13. Packaging

13. 包装

14. Storage, Distribution and Installation

14. 存储,分发和安装

15. Complaints

15. 投诉

16. Servicing

16. 售后服务

17. Quality Systems Audits

17. 质量体系审计

18. Factory Inspections

18. 工厂检查

19. Appendices

19. 附件


Cover page, Preface, Foreword
HHS Publication FDA 97-4179
首页,前言

MEDICAL DEVICE QUALITY SYSTEMS MANUAL:
A SMALL ENTITY COMPLIANCE GUIDE
First Edition
(Supersedes the Medical Device Good Manufacturing Practices Manual)

Andrew Lowery, Judy Strojny, and Joseph Puleo
Division of Small Manufacturers Assistance
Office of Health and Industry Programs

CENTER FOR
DEVICES AND
RADIOLOGICAL HEALTH
CDRH

December 1996
(This publication supersedes FDA 91-4179)

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES
Public Health Service
Food and Drug Administration
Center for Devices and Radiological Health
Rockville, Maryland 20850

FOREWORD
前言
The Center for Devices and Radiological Health (CDRH) of the Food and Drug Administration (FDA), develops and implements national programs to protect the public health in the fields of medical devices and radiological health. These programs are intended to assure the safety, effectiveness, and proper labeling of medical devices, to control unnecessary human exposure to potentially hazardous ionizing and non-ionizing radiation, and to assure the safe, efficacious use of such radiation.
FDA器械及放射卫生中心(CDRH)开发并实施医疗器械及放射卫生领域旨在保护公共健康的国家项目。这些项目是为了确保医疗器械的安全,有效和正确标志,控制人体暴露于潜在的电离或非电离放射性危害,以及确保安全有效地使用此类辐射。

The Center publishes the results of its work in scientific journals and in its own technical reports. These reports disseminate results of CDRH and contractor projects. They are sold by the Government Printing Office and/or the National Technical Information Service. Many are available via the FDA home page on the World Wide Web at: (反正是FDA的GOV网站)

本中心将其工作成果发表于科学期刊及自有技术报告。这些报告发布了CDHR及其合同项目的成果。这些报告是在政府印刷办公室或国家技术信息(部门)售卖的。很多报告可在FDA网站(fda.gov前面加www)获得。
We welcome your comments and requests for further information.
我们欢迎你的评论和进一步的信息。

D. Bruce Burlington, M.D.
Director
Center for Devices and
Radiological Health


PREFACE
序言
The Medical Device Amendments of 1976 mandated the establishment of "an identifiable office to provide technical and other nonfinancial assistance to small manufacturers of medical devices to assist them in complying with the requirements of the Federal Food, Drug, and Cosmetic Act." The Division of Small Manufacturers Assistance (DSMA) in the Office of Communication, Education, and Radiation Programs (OCER) was established to meet this requirement. DSMA develops educational materials and sponsors workshops and conferences to provide firms with a firsthand working knowledge of medical device requirements and compliance policies.
1976年医疗器械修正案强制要求建立“一个明确的办公室来对小医疗器械制造商提供技术的及其他非财政援助来辅助他们顺应联邦食品药品及化妆品法案。” 隶属于通讯,教育及放射性项目办公室(OCER)的小制造商辅助部门(DSMA)应此要求而建立。DSMA开发了教育资料及赞助工作会议和大会来为各公司提供关于医疗器械需求及顺应性政策的第一手的应用知识。

This manual covers the Quality System regulation and the basic Good Manufacturing Practices (GMP) requirements that all manufacturers and distributors must consider when they plan to manufacture medical devices, including medical device kits, trays or packs, for distribution in the United States. Model procedures and sample forms are also included in the manual to assist manufacturers.
本手册覆盖了所有制造商及分销商当他们计划在制造并且在美国分销医疗器械包括其套件,托盘及包装时必须考虑的质量体系及GMP基本要求。本手册也包括流程模型,表格样本。

Adherence to the medical device Quality System regulation makes good business sense and also serves public health aims -- two very good reasons for the Food and Drug Administration (FDA) to encourage compliance. However, a prerequisite to complying with a regulation is a clear understanding of its content. Recognizing this fact, the Division of Small Manufacturers Assistance (DSMA) developed this manual to help manufacturers increase their knowledge of medical device GMP requirements and FDA compliance policies. DSMA also uses this manual at quality system workshops conducted throughout the country.
FDA有两个鼓励顺应性的好理由,就是坚持医疗器械质量体系法规既能够具备好的商业理念又能服务于公共健康目的。但是,顺应法规的前提是对其内容的清楚理解。认识到该事实,DSMA开发了本手册以帮助制造商帮助增加他们对医疗器械GMP要求和FDA顺应政策的知识。DSMA也在全国的质量体系工作会议中使用本手册。

The Quality System regulation outlines the minimum elements of a system for designing and producing a medical device. Manufacturers of medical devices commonly find that their quality needs are broader than these basic elements because of the additional need to meet company quality claims as required by paragraph 501(c) of the Federal Food, Drug, and Cosmetic (FD&C) Act and to meet customer needs and requirements.
质量体系法规描述设计和生产医疗器械最少体系要素。医疗器械制造商通常会发现为了满足其公司质量声明(如FD&C法案501(c)章所要求)的额外要求和客户需求和要求,他们的质量需求比这些基本要素(范围)更宽。
The DSMA staff and the Office of Compliance (OC) in the Center for Devices and Radiological Health (CDRH) provided valuable assistance in preparing this manual.
CDRH的DSMA工作人员及顺应性办公室(OC)在本手册的准备中提供了富有价值的辅助。

For further information, contact the appropriate office within CDRH or call DSMA at 800-638-2041  301-443-6597 or FAX 301-443-8818. Comments on this manual, related workshops, and other DSMA activities are always welcome.
如需要进一步的信息,可联系CDRH办公室或致电DSMA(电话800-638-2041 
欢迎对本手册或相关工作会议的评论及其他DSMA活动的评论。

Lireka P. Joseph, Dr.P.H.
Director
Office of Health and Industry Programs

http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/PostmarketRequirements/QualitySystemsRegulations/MedicalDeviceQualitySystemsManual/default.htm


NOTE TO MANUFACTURERS OF MEDICAL DEVICES给医疗器械制造商的注释The Quality System (QS) regulation indicates the required end result rather than specifically prescribing how a manufacturer is to comply with this regulation. It is the responsibility of the manufacturer to use good judgment when developing a quality system which appropriately applies the QS regulation to their specific products and operations. The manufacturer, not FDA, bears overall responsibility for the production of high-quality products.
质量体系(QS)法规体现了对最终结果的要求而不是制造商必须遵循的本法规的特定指示。制造商有责任善用其判断来制定质量体系,能够对其特定产品及操作应用适当的质量体系法规。制造商而不是FDA对其生产高质量产品承担总体责任。

Nevertheless, FDA recognizes that manufacturers may benefit from having guidance, model procedures, and sample forms that others have developed or adopted in an effort to comply with the intent of the regulation. The guidance in this manual includes discussion on the entire QS regulation, plus it provides multiple examples of procedures and forms which can be adopted and modified by manufacturers as appropriate.
然而,FDA认识到制造商可以从别人为顺应法规的意图所努力制定或采用的流程模型及表格样本中获益。本手册指南包括了整个QS法规的讨论,加上其提供的多个流程和表格,可以为制造商适当修改和采用。

We have included a variety of model procedures and sample forms in this manual. However, these are not meant to be official statements of FDA policy. Rather, they represent a compilation of examples that firms may find useful in understanding how some manufacturers have successfully complied with QS and/or GMP requirements. Before any model procedure or form is adopted into a quality system program, the applicability and suitability to a particular device and manufacturing operation should be carefully examined. This manual will assist you in developing a quality system that meets the intent of the FDA Quality System regulation.
我们在手册中包括了不同的流程模型和表格样本。然而,这些并不意味着FDA政策的正式陈述。这些更代表着商家可能觉得有用的例子汇编,来理解那些厂商怎样成功地顺应了QS和GMP要求。在任何流程模型或表格在质量体系项目中采用前,应该仔细检查其对于特定的器械和生产操作适用性和适应性。本手册会帮助你建立满足FDA质量体系法规意图的质量系统。


FDA also recognizes the continuing need to use innovative approaches, particularly in dealing with small businesses that could be unnecessarily adversely affected by federal regulations. It is hoped that the information in this manual will assist manufacturers in their efforts to establish and maintain a quality system that enhances business. The Office of Compliance at 301- 594-4692 or DSMA at 800-638-2041, FAX 301-443-8818, can be contacted for additional assistance and information.
FDA也意识到特别是对于可能由于联邦法规而受到不必要的负面影响的小企业采用创新方法的持续要求。希望本手册的信息可以帮助制造商致力于建立和维护一个质量体系来加强其业务。(下面是OC和DSMA的电话,传真),欢迎垂询。

This manual can be purchased from the Superintendent of Documents, U.S. Government Printing Office, Washington D.C. 20402, telephone , and from the National Technical Information Service, U.S. Department of Commerce, 5285 Port Royal Road, Springfield, VA 22161, telephone 703-487-4650 . This manual is also available to all manufacturers through the World Wide Web at: (www.fda.gov).
本手册也可以从美国政府出版社买到。

 

Sincerely yours,

John F. Stigi
Director
Division of Small Manufacturers Assistance

ABSTRACT摘要A. Lowery, J. Strojny, and J. Puleo, Project Officers. Division of Small Manufacturers Assistance, Office of Health and Industry Programs. Medical Device Quality Systems Manual: A Small Entity Compliance Guide. HHS Publication FDA 97-4179 (December 1996).
(作者及单位)

This manual covers requirements of the Quality System regulation that manufacturers of medical devices must consider when they design devices, or when they manufacture, contract manufacture, remanufacture, process, repack, or relabel finished medical devices intended to be commercially distributed. The manual contains articles that explain the various good manufacturing practices (GMP) requirements such as design controls, process validation, calibration, device master records, component control, etc., along with related topics such as labeling. It also contains examples of forms, procedures, decals, etc. Manufacturers may use this guidance when developing their quality system.
本手册涵盖了医疗器械制造商在设计,制造或承包制造,再制造,处理,再包装或在再标志已完工的医疗器械以用于商业发布时必须考虑的质量体系法规要求。手册包含解释GMP不同要求的文章,例如设计控制,工艺流程验证,校验,设备主记录,零件控制等,还有相关如“标志” 的主题。手册也包含表格,流程,标贴等的示例。厂商可在建立其质量体系时使用本指南。

This manual incorporates changes required by the Safe Medical Devices Act of 1990 and the Medical Device Amendments of 1992. This manual is an update of HHS publication FDA 91-4179, "Medical Device Good Manufacturing Practices Manual, Fifth Edition."
本手册合并了1990年医疗器械安全法案及1992年医疗器械修正案的修改要求。本手册是HHS出版物FDA 91-4179“医疗器械GMP手册第五版”的更新。
This manual is used in the Division of Small Manufacturers Assistance (DSMA) medical device workshops.
本手册在DSMA医疗器械工作会议上使用。


1. The Quality System Regulation
1. 质量体系法规

INTRODUCTION
介绍

FLEXIBILITY OF THE GMP
GMP的灵活性

MANUAL CONTENTS
手册内容

GMP APPLICATIONS AND EXEMPTIONS
GMP申请及豁免

     Exemptions
     豁免
     

     Component Manufacturers

     零件厂商


     Remanufacturers

     再制造商


     Custom Device Manufacturers

     定制器械生产商


     Contract Manufacturers

     合同制造商


     Contract Testing

     合同测试


     Repackagers, Relabelers, and Specification Developers

     重包装者,重标志者,及规格制定者


     Initial Distributors of Imported Devices

     进口器械的初始分销者


INTRODUCTION
介绍

The current Good Manufacturing Practices (GMP) requirements set forth in the Quality System (QS) regulation are promulgated under section 520 of the Food, Drug and Cosmetic (FD&C) Act. They require that domestic or foreign manufacturers have a quality system for the design and production of medical devices intended for commercial distribution in the United States. The regulation requires that various specifications and controls be established for devices; that devices be designed under a quality system to meet these specifications; that devices be manufactured under a quality system; that finished devices meet these specifications; that devices be correctly installed, checked and serviced; that quality data be analyzed to identify and correct quality problems; and that complaints be processed. Thus, the QS regulation helps assure that medical devices are safe and effective for their intended use. The Food and Drug Administration (FDA) monitors device problem data and inspects the operations and records of device developers and manufacturers to determine compliance with the GMP requirements in the QS regulation.
质量体系法规所阐明的现行的GMP要求是在食品药品及化妆品法案第520节下所发布的。它们要求国内及国外的制造商具有质量体系来设计,生产要在美国商业分销的医疗器械。法规要求为器械制定不同的规格和控制;使得在质量体系下设计的器械满足这些规格;器械被正确地安装,检查和使用;质量数据能够被分析以确定和纠正质量问题;以及投诉被处理。因而,质量体系法规帮助确保医疗器械对其目的应用安全有效。FDA监督器械的问题数据,检查器械开发和制造的运行和记录以确定其质量体系法规与GMP要求相顺应。

The QS regulation is in Part 820 of Title 21 of the Code of Federal Regulations (CFR). This regulation covers quality management and organization, device design, buildings, equipment, purchase and handling of components, production and process controls, packaging and labeling control, device evaluation, distribution, installation, complaint handling, servicing, and records. The preamble describes the public comments received during the development of the QS regulation and describes the FDA Commissioner's resolution of the comments. Thus, the preamble contains valuable insight into the meaning and intent of the QS regulation.
质量体系法规是在联邦法令第21款第820部分。本法规覆盖了质量管理和组织,器械设计,建筑,装备,采购和搬运零件,生产流程控制,包装和标志控制,器械评价,分销,安装,投诉处理,维修及记录。导言描述在建立本质量体系法规时收到的公众评论,及FDA专员对这些评论的解答。因而导言内容包含了质量体系法规目的意义的真知灼见。

The QS regulation is reprinted in the appendix of this manual.
在本手册的附录中重印了质量体系法规。

FLEXIBILITY OF THE GMP
GMP的灵活性

Manufacturers should use good judgment when developing their quality system and apply those sections of the QS regulation that are applicable to their specific products and operations. Section 820.5 of the QS regulation requires that, "Each manufacturer shall establish and maintain a quality system that is appropriate for the specific device(s) designed or manufactured, and that meets the requirements of this part." The word "appropriate" means that the rule is a flexible regulation. However, if manufacturers decide to not implement certain GMP requirements which are qualified by the term "where appropriate," they should document their justification for non-implementation.The justification should show that not implementing a requirement is not reasonably expected to result in product that does not meet specifications or failure to carry out any necessary corrective action [820.1(a)(30)]. Operating within this flexibility, it is the responsibility of each manufacturer to establish requirements for each type or family of devices that will result in devices that are safe and effective, and to establish methods and procedures to design, produce, and distribute devices that meet the quality system requirements.FDA has identified in the QS regulation the essential elements that a quality system shall embody for design, production and distribution, without prescribing specific ways to establish these elements. Because the QS regulation covers a broad spectrum of devices and production processes, it allows some leeway in the details of quality system elements. It is left to manufacturers to determine the necessity for, or extent of some quality elements and to develop and implement specific procedures tailored to their particular processes and devices. For example, if it is impossible to mix up labels at a manufacturer because there is only one label or one product, then there is no necessity for the manufacturer to comply with all of the GMP requirements under device labeling.


制造商应在建立其质量体系时善用其判断,并将QS法规的适用部分应用于其特定的产品和作业。QS法规第820.5节要求,每个制造商应建立并维护与其研发或生产的特定器械的相应适当的质量体系,并且满足本部分的要求。“适当”这个词意味着法规的规则是灵活的。然而,如果制造商按“适当”所定义那样决定不采用GMP的某些要求,那么他们就必须将不采用的理由记录成文。这些理由应该反映出不采用一个要求不会(有理由预期)导致产品不符合规格或不能实现必要的纠正行动[820.1(a)(30)]。按此灵活性运作,每个制造商有责任为每一产品种类或产品家族建立需求,使其产品安全有效。并且建立设计,生产,销售产品的方法和流程,达到质量体系要求。FDA 在QS法规中明确了作为基本要素,质量体系应该包括研发,生产和发布,而没有规定建立这些要素的特定的途径。因为QS法规涵盖了宽泛品类的产品及生产流程,在具体的质量体系要素中允许某些偏差。留待制造商决定其必要性或扩展某些质量要素,并且建立和实施按照其工艺及产品特点裁剪的特定流程。例如,如果制造商因为只有一个标签或一个产品而不可能将标签混合起来,那么就不必要顺应GMP中关于器械标志的要求。


The medical device QS regulation requires an "umbrella" quality system intended to cover the design, production, and distribution of all medical devices from simple surgical hand tools to very complex computerized axial tomography (CAT) scanners. It is not practical for a regulation to specify details of quality system elements for such a wide range of products. Rather, the QS regulation specifies general objectives such as use of trained employees, design reviews, design validation, calibrated equipment, process controls, etc., rather than methods, because a specific method would not be appropriate to all operations.
医疗器械QS法规要求以一个伞形质量体系来涵盖设计,生产及分销从简单的外科手术器具到很复杂的计算机轴向断面成像扫描机(CAT)的所有医疗器械。对于如此宽泛的产品范围来说,一个法规规定具体的质量体系要素是不实际的。更确切的,QS法规规定了诸如使用受训员工,设计评审,设计验证,设备校验,流程控制等的一般目标,而不是方法,因为一个特定方法不可能适用于所有作业。

In most cases, it is left to the manufacturer to determine the best methods to attain quality objectives. In some cases, however, the QS regulation does specify the particular type of method to be used, such as written procedures or written instructions. This does not mean, however, that manufacturers cannot vary from the method specified if the intent of the GMP requirement can be met by another method such as using an engineering drawing plus a model device as manufacturing instructions. Written procedures are not restricted to paper copies. Written procedures may be filed and distributed by automated data processing equipment. This flexibility is allowed by section 820.180.
在大多数情况下,达到质量目标的最佳方法是留给制造商来决定的。然而,在有些情况下,质量体系法规确实规定采用某种方法,诸如书面的步骤或书面的指令。然而,如果GMP要求的目的能够用其他方法达到,这并不代表制造商不能对所定的方法变通,例如,采用工程图纸加上器械模型来代替生产指令。书面步骤不限于纸件拷贝。书面步骤也可以通过自动数据处理设备来成文或发布。这种灵活性是820.180节所允许的。
Typically, large manufacturers will have a quality system that exceeds the medical device QS regulation. Small manufacturers will typically have a proportionally simpler system. FDA recognizes: that a small manufacturer may not need the same amount of documentation that a large manufacturer does in order to achieve a state-of-control; and, that some of records maintained to fulfill the GMP requirements for written procedures may not be as long and complex for a small manufacturer.
大制造商会有代表性地建立超过医疗器械QS法规要求的质量体系。小制造商一般拥有相对简单的系统。FDA认为:小制造商可以不需要拥有像大公司同样数量的文档来达到控制状态;某些为满足GMP要求的书面步骤而保持的记录,小制造商也不必同样长而复杂。

After a manufacturer establishes a quality system, it should be maintained. Each manufacturer should assure that with growth and process or product changes their quality system is still adequate. This assurance is obtained through change control, daytoday observance of operations, and by periodic audits of the quality system. The auditor should first identify the elements of the company's quality system. Next the audit should determine how well each element is functioning, and then determine its adequacy with respect to the intent of the device GMP requirements and meeting the company's quality claims.
当一个制造商建立了质量体系以后,体系也需要维护。每个制造商应该确保其质量体系随着发展及产品或流程的变化仍保持适当。这种保障是通过变更控制,每日运作的观察,以及定期的质量体系审计来获得的。审计者应该首先确定公司质量体系的要素。其次审计应该决定每个要素运行的完善性,然后决定其相对与器械GMP要求的目的是否适当并且满足公司的质量主张。


MANUAL CONTENTS
手册内容
To aid auditors, QA managers, and others, this manual provides guidance in the interpretation of the GMP requirements, and demonstrates the flexibility of the QS regulation in its application to diverse devices, manufacturing processes, and manufacturers. In the absence of guidance from FDA, manufacturers may rely on industry, national, and international consensus standards or guidances to meet GMP requirements.
为了帮助审计者,QA经理及其他人,通过对于GMP需求解释,以及展示应用于不同器械,不同生产流程及生产者时QS法规的灵活性,本手册提供了指导。没有FDA的指南,制造商会依靠行业,国家及国际共识的标准或指南来满足GMP要求。


This manual was also developed to aid manufacturers in completing, maintaining, or expanding their quality system. Contents include educational materials, aids, and examples of how to implement elements of a quality system, together with detailed examples of procedures, control forms, and associated data. The examples of typical procedures, drawings, and forms found in this manual were derived from quality systems in the device industry. These materials are not meant to describe universally applicable elements of a quality system that can be used unchanged by any manufacturer. Of course, a form or aid as presented in this manual may be suitable for direct use for a specific device and operation; however, in general, manufacturers will need to use care in adopting and modifying a selected form or procedure to meet the specific quality system needs of their devices and operations.
本手册的开发也是为了帮助制造商完成,维护或者扩展其质量体系。内容包括教育资料,帮助,如何实施质量体系要素的例子以及流程,控制表格及相关数据的具体例子。本手册中的典型流程,图纸及表格的例子是从器械行业质量体系中得来的。这些资料并不代表了制造商可以不加变更就普遍适用的质量体系要素。当然,本手册所提出的表格或帮助可能对某类器械及操作来说可以直接使用。然而,总的来说制造商需要在采用及修改某个所选的表格或流程来满足其器械及操作的质量体系的某个要求时谨慎从事。


This manual is arranged as if the reader were starting a new business. That is, as if an entrepreneur were sequentially:
本手册是以假设读者开办一个新公司来安排的。也就是按一个企业主以以下顺序:


1. obtaining information on GMP requirements;
2. determining the appropriate quality system needed to control the design, production and distribution of the proposed device;
3. designing products and processes;
4. training employees;
5. acquiring adequate facilities;
6. purchasing and installing processing equipment;
7. drafting the device master record;
8. noting how to change the device master records;
9. procuring components and materials;
10. producing devices;
11. labeling devices;
12. evaluating finished devices;
13. packaging devices;
14. distributing devices;
15. processing complaints and analyzing service and repair data;
16. servicing devices;
17. auditing and correcting deficiencies in the quality system; and,
18. preparing for an FDA inspection.
1.        获得GMP要求的信息;
2.        决定适当的质量体系来控制研发,生产和销售所建议的器械;
3.        设计产品及工艺流程;
4.        培训员工;
5.        采购适当的设备;
6.        采购和安装工艺流程设备;
7.        起草器械主记录;
8.        解释如何更改器械主记录;
9.        购买零件及材料;
10.        生产器械
11.        标志器械
12.        评估器械成品
13.        包装器械
14.        销售器械
15.        处理投诉和分析维修数据
16.        维修器械
17.        审计和修正质量体系的不足;并且
18.        准备FDA检查


If manufacturers perform these activities as required by the QS regulation and as expounded in this manual, they should be prepared for a GMP inspection of their operations by an FDA investigator.
如果制造商按本手册所解释的QS法规的要求那样完成这些活动,他们应该说已经为FDA的检查者对其运作进行GMP检查做好了准备。


Manufacturers and importers of medical devices shall also comply with the Medical Device Reporting (MDR) regulation, 21 CFR Part 803, which requires that serious complaints be reported to FDA. MDR is related to the GMP complaint and failure investigation requirements, which are covered in Chapter 15. If manufacturers comply with the QS regulation and guidance in this manual and in other sources, there is a high probability that they will reduce the frequency of reportable events.
医疗器械制造商及进口商也需要顺应医疗器械报告法规(MDR, 21CFR803部分),该法规要求向FDA报告严重的客户投诉。MDR是与GMP关于投诉及失效调查的要求相关,为15章涵盖。如果制造商顺应QS法规及本手册或其他资源的指南他们就能够很大可能降低需要报告事件频率。


GMP APPLICATIONS AND EXEMPTIONS
GMP申请及豁免
The QS regulation applies to finished devices intended to be commercially distributed for human use unless there is an approved exemption in effect. GMP exemptions are codified in the classification regulations 21 CFR 862 to 892. The exemption of most Class I devices from design controls is in section 820.30(a).
除非获得有效的豁免批准,QS法规适用于以销售为目的的人用医疗器械制成品。GMP豁免的法律条文见于法规21CFR862至892条目类别。多数I类器械关于设计控制的豁免见于820.30(a)条目。

Certain components such as blood tubing and major diagnostic xray components are considered by FDA to be finished devices because they are accessories to finished devices. The manufacturer of such accessories is subject to the QS regulation when the accessory device is labeled and sold separately from the primary device for a healthrelated purpose to a hospital, physician, or other user.
某些零件诸如血管材料及诊断性X线主零件是被FDA视为是医疗器械制成品,因为这些是医疗器械制成品的附件。当附件器械是有标志的并与主机分开销往医院,医生或其他使用者以用于与健康相关的目的时这类附件的制造商是受QS法规的制约的。

The designation of a device as a "custom" or "customized" device does not confer a GMP exemption.
以定制或定制化所指定的器械并不授予GMP豁免。


Contract manufacturers and specification developers shall comply with the sections of the QS regulation that apply to the functions they perform.
合同制造商或规格开发者应顺从于与其从事的活动相应的QS法规。


Contract test laboratories are considered an extension of a manufacturer's quality system and presently are not routinely scheduled for GMP inspections. The finished device manufacturer shall meet the requirement of the QS regulation, particularly 820.50, Purchasing, when they obtain products or services. Internal test laboratories, however, that are part of a corporate manufacturer that provides services to individual corporation factories should meet GMP requirements. Internal laboratories are inspected as part of the FDA GMP inspection of the member factories.
合同测试实验室可被视为制造质量体系的延伸,现今还没有归于GMP检查的日程表中。成品制造商当其购买产品或服务时应满足QS法规特别是820.50关于采购的要求。然而,归属于企业制造商并对单个企业工厂提供服务的内部测试实验室应满足GMP要求。内部实验室是作为GMP成员工厂检查的一部分而接受FDA检查。

Situations are discussed in the remainder of this chapter where various manufacturers are exempt from the QS regulation or are not routinely inspected. However, these manufacturers are still subject to the FD&C Act. If these manufacturers or any manufacturer render devices unsafe or ineffective, the devices are adulterated and/or misbranded and the manufacturers are subject to the penalties of the FD&C Act.
在本章的余下部分讨论在何情况下不同的制造商可以受QS法规的豁免或不被例行检查。然而,这些制造商仍然受制于FD&C法案。如果这些制造商或任何制造商提供了不安全或无效的器械,器械是次品或商标不准确,这些制造商将接受FD&C法案的处罚。


Exemptions
豁免
FDA has determined that certain types of establishments are exempt from GMP requirements; and
FDA决定某些情况可以从GMP要求中豁免;并且


FDA has defined GMP responsibilities for others. Exemption from the GMP requirements does not exempt manufacturers of finished devices from keeping complaint files (820.198) or from general requirements concerning records (820.180). Sterile devices are never exempted from GMP requirements. A device that normally would be subject to GMP requirements may be exempt under the following conditions:
FDA定义了GMP其他责任。GMP要求的豁免并不豁免医疗器械成品制造商对投诉文件(820.198)保留的要求或通用要求中所考虑的记录(820.180)的要求。消毒器械从不受GMP要求豁免。器械在如下情况下通常可受GMP要求的豁免:


·        When FDA has issued an exemption order in response to a citizen's petition for exemption,
·        When FDA, in the absence of a petition, has exempted the device and published the exemption in the Federal Register,
·        When the device is exempted by FDA classification regulations published in the Federal Register and codified in 21 CFR 862 to 892,
·        When the device is an investigational intraocular lens (IOL) and meets the requirements of the investigational device exemption (IDE) regulation for IOL's, and
·        Through a policy statement, FDA may decide not to apply GMP requirements to some types of devices and processes although the devices may not have been exempted from GMP requirements.

·        当FDA应公民的豁免陈请签发了豁免令,
·        当FDA在没有陈请的情况下豁免某器械并将豁免发布于联邦公报上,
·        当器械被FDA在联邦公报的分级法规中所豁免并记载于21CFR862至892条,
·        当器械属于研究性眼内镜(IOL)并且满足研究性器械豁免(IDE)法规对于IOL的要求,以及
·        通过政策陈述,FDA可以决定不对某种未受GMP要求豁免的器械和过程施行GMP要求。


Manufacturers should be aware of the GMP exemption status of their devices. In addition, manufacturers should keep on file records of any specific GMP exemption granted to them by FDA. Upon request during a factory visit, the exemption records need to be shown during normal business hours to the FDA investigator in order to verify that an exemption has been granted.
制造商应知晓其产品的GMP豁免状态。此外,制造商应保留FDA授予的任何特定GMP豁免的文件记录。如FDA检查官在工厂访问中提出要求,则应在正常的工作时间出示豁免记录以确认所授予的豁免。

Component Manufacturers
零件制造商

A "component" is defined by 820.3(c) as "any raw material, substance, piece, part, software, firmware, labeling, or assembly which is intended to be included as part of the finished, packaged, and labeled device." Component manufacturers are excluded from the QS regulation by 820.1(a)(i). Current FDA policy is to rely upon the finished device manufacturer to assure that components are acceptable for use. Component manufacturers are not routinely scheduled for GMP inspections; however, FDA encourages them to use the QS regulation as guidance for their quality system.
零件是由820.3(c)定义为“任何原材料,物质,件,零件,软件,固件,标签或组件其目的是作为完成的,包装的和标志的器械的一部分。”零件制造商是按820.1(a)(i)条排除在QS法规外的。现行的FDA政策是依靠成品制造商来确保零件是可用的。零件制造商不在GMP检查的日程中;然而,FDA鼓励零件制造商用QS法规来指导其质量体系。


When finished device manufacturers produce components specifically for use in medical devices they produce, whether in the same building or another location, such production of components is considered part of the device manufacturing operations, and the production should comply with the QS regulation.
当成品制造商生产专门用于其产品的零件时,不管是在同一楼内或另外地点,这样的零件生产是视为器械生产作业的一部分,并且其生产应顺从QS法规的要求。
Accessory devices [807.20(a)(5)] such as hemodialysis tubing or major diagnostic xray components, that are packaged, labeled, and distributed separately to a hospital, physician, etc., for healthrelated purposes are sometimes inappropriately referred to as components. However, FDA considers them finished devices because they are suitable for use or capable of functioning and are distributed for health-related purposes; and the QS regulation applies to their manufacture. Similarly, a device or component including software that is sold as an addition to a finished medical device to augment or supplement its performance is also termed an accessory. An accessory to a medical device is considered a finished device and, therefore, is subject to the QS regulation.
附件器械[807.20(a)(5)],诸如血透仪管或X光诊断仪的主零件,这些包装了的,标志了的,并且分开销往医院或医生的用于健康目的,有时被不正确地作为零件对待。然而,FDA认为它们是成品器械因为它们可以使用于或作用于并且销售来为健康相关的目的;并且QS法规要应用When finished device manufacturers produce components specifically for use in medical devices they produce, whether in the same building or another location, such production of components is considered part of the device manufacturing operations, and the production should comply with the QS regulation.
当成品制造商生产专门用于其产品的零件时,不管是在同一楼内或另外地点,这样的零件生产是视为器械生产作业的一部分,并且其生产应顺从QS法规的要求。
Accessory devices [807.20(a)(5)] such as hemodialysis tubing or major diagnostic xray components, that are packaged, labeled, and distributed separately to a hospital, physician, etc., for healthrelated purposes are sometimes inappropriately referred to as components. However, FDA considers them finished devices because they are suitable for use or capable of functioning and are distributed for health-related purposes; and the QS regulation applies to their manufacture. Similarly, a device or component including software that is sold as an addition to a finished medical device to augment or supplement its performance is also termed an accessory. An accessory to a medical device is considered a finished device and, therefore, is subject to the QS regulation.
附件器械[807.20(a)(5)],诸如血透仪管或X光诊断仪的主零件,这些包装了的,标志了的,并且分开销往医院或医生的用于健康目的,有时被不正确地作为零件对待。然而,因为它们可以使用于或作用于并且销售来为健康相关的目的,FDA认为它们是成品器械;并且QS法规要应于其生产。同样的,装置或零件包括软件是作为成品医疗器械的附加部分销售的,以增加或补充其性能,也作为附件器械对待。既然医疗器械的附件是作为成品来对待,因而受QS法规制约。


Remanufacturers
再加工者

A remanufacturer is any person who processes, conditions, renovates, repackages restores or does any other act to a finished device which has been previously distributed to significantly change the finished device's performance or safety specifications or intended use from that established by the original finished device manufacturer. Remanufacturers are considered manufacturers. As such, these manufacturers are subject to inspection by FDA and shall meet the applicable requirements of the medical device QS regulation. These manufacturers shall establish and implement quality systems to assure the safety and effectiveness of the devices that are distributed. Such activities include drafting of master records, rebuilding per the master records, inspection and testing, calibration of measurement equipment, control of components, updating of labeling, processing of complaints, and any other GMP requirement applicable to the activities being performed.

再加工者是对成品器械进行加工、翻新、整修、重新包装修复品或任何其他行为来明显改变该经过销售的由原来的成品制造商所设定的成品器械的性能、安全指标或使用目的的人。再加工者也被视为制造商。同样地,这些制造商要接受FDA的检查,并满足医疗器械质量体系规章可适用的要求。这些制造商也应建立和实施质量体系,确保其销售的器械的安全和有效。这样的行动包括器械主记录的起草、对照器械主记录重制造、检查和测试、测量仪器的校准、部件的控制、标签的更新、投诉的处理和其他在其活动中可适用的 GMP 要求。

Remanufacturers are also required to comply with the labeling requirements of 21 CFR 801.1(c). This labeling regulation requires that where the person or manufacturer named on the label of the device is not the original manufacturer, the name shall be qualified by an appropriate phrase which reveals the connection that person has with the device, e.g., remanufactured by XYZ Company.

再加工者同时也被要求遵守联邦法规第21 篇第 801.1(c)节中对标签所作的规定。该标签规章要求器
械标签的制造商名字不是初始制造商,并且名称应选用那些揭示其与器械的关系的合适的措词,譬如,由某某公司再加工。

Custom Device Manufacturers
定制器械制造商

Section 520(b) of the FD&C Act and the IDE regulation (21 CFR Part 812) define a custom device. Custom devices are exempt from certain statutory requirements. For example, manufacturers of custom devices are not required to comply with premarket approval requirements (Section 515) and are exempt from premarket notification requirements [Section 510(k)]. Custom devices are NOT exempt from the GMP requirements. Current FDA policy, however, is to not inspect manufacturers of custom devices. Manufacturers of custom devices should comply with the GMP requirements while considering the flexibility allowed.
食品、药品和化妆品法的第520(b)节和联邦法规第21篇812.3(b)篇研究用器械豁免(IDE)法规都对定制式器械进行了定义。定制式器械被豁免某些法定的要求。例如,定制式器械制造商不要求遵守上市前批准规定(515节)和免除上市前通告规定[510(k)节]。但是定制式器械没有被豁免GMP要求。定制式器械制造商应顺应 GMP 要求同时又考虑允许的灵活度。

Contract Manufacturers
合同制造商

A person(s) that manufactures a finished device under the terms of a contract with another manufacturer is a contract manufacturer. The agreement between the manufacturers should be documented in a written contract. Contract manufacturers of finished devices shall comply with applicable requirements of the quality system and shall register their establishment with FDA. Depending on the circumstances, both the contractor and manufacturer may be held jointly responsible by FDA for the activities performed.
合同式制造商是指以合同方式为其他制造商生产成品器械的人(或集体)。制造商间的协议应以书面合同的形式作为凭证。成品器械的合同式制造商应遵从质量体系中可适用的要求,并向FDA 登记其产品。根据情况,FDA 可以要发包人和制造商对所实施的行为承担共同责任。

Contract Testing Laboratories
合同检测实验室

Contract laboratories that designs or test components or finished devices for a manufacturer are considered an extension of the manufacturer's quality system. These laboratories may provide services to a number of customers, many of which are not medical device manufacturers. These contract laboratories are not subject to routine GMP inspections. Through the conduct of quality audits or other means, the finished device manufacturer is responsible for assuring that equipment and procedures used by a lab are adequate and appropriate (820.50). However, an internal test laboratory, if part of a manufacturer that does testing for various facilities within the corporation, is subject to inspection when FDA GMP inspections are conducted at the individual manufacturing facilities. That is, the test laboratory is simply a part of a medical device manufacturer of which all device-related divisions shall comply with the QS regulation.
根据制造商的具体要求进行设计或检测部件或成品器械的合同实验室,被当作该制造商质量体系的延伸部分。这些实验室可以向许多客户提供服务,他们中的很多并非医疗器械制造商。这些合同式实验室不必接受GMP的例行检查。通过进行质量审查或其他手段,成品器械制造商有责任确保实验室所用的设备和步骤是适当的和可靠的(820.50 节)。然而,作为企业的一部分,为企业内不同厂家提供测试的内部检测实验室,当FDA对某个单独的生产厂进行GMP检查时,也应将其包括在内。也就是说,检测室是医疗器械制造企业的一部分,而所有与器械相关的部门均应遵守质量体系规章。

Repackagers, Relabelers, and Specification Developers
再包装者、再标识者和技术说明制定者
Repackaging and relabeling of a device and specification development are defined as manufacturing in 21 CFR Part 807, Establishment Registration and Device Listing for Manufacturers of Devices. Some definitions from 807.3(d) are reprinted below because they affect the applications of the QS regulation.
在联邦法规第21篇第820.3(o)节和第807 篇以及《器械制造商的企业注册与器械列表》中,均将器械的再包装和再标识以及技术说明制定行为定义为制造。下面摘录的是联邦法规21第807.3(d)中的一些定义,因为它们会影响质量体系法规的应用。

(d) "Manufacture, preparation, propagating, compounding, assembly, or processing" of a device means the making by chemical, physical, biological, or other procedures of any article that meets the definition of a device in section 201(h) of the Act.
“器械的制造、准备、复制、组合、装配或加工”指通过化学的、物理的、生物的或其它的方法制造符合《食品、药品和化妆品 法》第 210(h)有关器械定义的任何物品。

These terms include the following activities:
这些术语包括下列的行为:

(1) Repackaging or otherwise changing the container, wrapper, or labeling of any device package in furtherance of the distribution of the device from the original place of manufacture to the person who makes final delivery or sale to the ultimate consumer;
(1) 重新包装或其它改变任何器械包装的容器、包装材料或标签,以进一步将器械从原始制造地分发到最后的交货或销售给最终用户的人;

(2) Initial distribution of imported devices; or
(2)进口器械的初次销售;或者

(3) Initiation of specifications for devices that are manufactured by a second party for subsequent commercial distribution by the person initiating specifications.
(3) 技术说明制定者制定规格委托第二方根据其设定的技术规格为其制造器械,再由技术规格制定者进行商业销售。

As defined above, repackaging and relabeling are manufacturing operations. Further, a repacker, repackager or relabeler is a manufacturer per 820.3(o) and subject to the applicable requirements of the QS regulation. Individuals are repackers or relabelers if they:
根据上面的定义,再包装和再标识是制造行为。这样,再装箱者、再包装者或再标识者都是制造商,均应遵守质量体系法规中适用的要求。符合下列情况的个人是再装箱者或再标识者:
* package and/or label previously manufactured finished devices or accessories;
* receive finished devices in bulk (e.g., surgical tubing, syringes, media, etc.,) and repacks them into individual packages and label them ;
* receive previously manufactured devices that have been packaged and labeled by another manufacturer, and combine them into a kit with other unpackaged devices which are received in bulk.
* 包装或标志已制造的成品器械或附件。
* 批量接收成品器械(如手术用管,注射器,培养 基等)进行再包装成单个包装并标志;
* 接收已由其他制造商包装和标识先前制造 的器械,并把批量收到的未包装的其他器械和其组合成套件。

Individuals are not considered repackers or relabelers or a manufacturer for purposes of applying the QS regulation if they pack only previously packaged and labeled individual devices into packages for the convenience of the user. (Note that this activity is essentially the same as a drug store employee placing packaged items into a bag labeled with the name of the drug store.)
如果个人为了用户使用方便而只把先前包装和标识的器械包装成包,那么他们不被当作适用质量体系规章意义上的再包装者、再标识者或制造商。(注释:这种行为在本质上与药店雇员将已包装的商品放入印有该店名称的包装袋中相同。

A distributor who only adds a label bearing their name and address is exempt from the GMP requirements. A manufacturer simply affixing a sticker label bearing the distributor's name and address would not require record keeping demonstrating compliance with labeling controls requirements.
经销商,如果只将他们的名称和地址添加在标签上,可以豁免 GMP要求。如果制造商仅是简单地把带有销售商名称和地址的粘贴标签贴上,他不需要保留记录来证明其遵守标签控制要求。

Specification developers provide specifications to contract manufacturers, who produce devices to meet the specifications. The contract manufacturer may package and label the device, or the finished device may be shipped to the specification developer for packaging and labeling.
技术规格制定者把技术规格提供给合同式制造商,由他来生产符合技术规格要求的器械。合同式制造商可以对该器械进行包装和标识,也可以将成品器械运给技术规格制定者让其自行包装和标识。

Specification developers are manufacturers and are subject to the GMP requirements that apply to the activities they conduct, such as various design controls including correct transfer of the design information to a contract manufacturer [820.30(h)]. This activity, in turn, requires an adequate device master record (820.181) and adequate change control [820.40(b)]. Further, if the product carries the specification developer's label, the developer is responsible for maintaining a complaint file and processing complaints, plus maintaining the device specifications and other appropriate documents in the device master record.
技术规格制定者属于制造商,应遵守与他们行为相关的GMP要求,如各种设计控制,包括将设计信息准确传递给合同式制造商【830.30(h)】。相应的这种行为需要适当的器械主记录【820.181】和适当的文件变化控制【830.40(b)】。此外,如果产品标识有技术规格制定者的标志,则技术规格制定者应负责保留投诉文件,处理投诉,并在器械主记录中保留器械技术规格和其它有关的文件。

Initial Distributors of Imported Devices
进口器械的初始分销商

The initial distributor is the foreign manufacturer's official correspondent with the FDA. With regards to the GMP, this initial distributor is responsible for maintaining complaint files and general record keeping requirements. A procedure shall be established and maintained for receiving, reviewing, and evaluating complaints. All complaints, including oral complaints, are to be processed in a uniform and timely manner. These complaints shall be evaluated to determine whether or not they require reporting to FDA under 21 CFR part 804 or 803, Medical Device Reporting. The initial distributor is also required to evaluate all complaints to determine whether an investigation is necessary, as well as complying with all other requirements in 820.198, Complaint Files. See Chapter 15 in this manual for more complete guidance on handling complaints.

一级经销商是FDA对国外制造商的正式联络人。相关于GMP,该一级经销商应负责建立投诉文档并负责保留通常记录的要求。应建立并维护有关接收、回顾和评估投诉的程序。所有的投诉,包括口头投诉,要以统一的、及时的方式加以处理。应对这些投诉进行评估,并根据医疗器械报告制度(联邦法规21804803部)要求决定它们是否需要向FDA报告。一级经销商应对所有投诉进行评 估来决定是否需要举行调查,同时也要遵守所有其他820.198关于投诉文档的要求。更完整的处理投诉的指南见本手册第15章。


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