中国新版GMP与欧盟、美国GMP比较概要
New Chinese, EU and US GMPs comparative overview
中国新版，欧盟和美国GMP
比较概要
Date: 24 – February – 2011
日期：2011年2月24日
Authors作者：: Víctor Samitier (TDV) / Octavi Colomina (TDV)
1.Quality Management 质量管理
SIMILARITIES 相似点:
EU and new Chinese GMPs set forth the requirement of establish a quality system, with their own quality objectives, applying all of requirements on safety, efficacy and quality control related with drug registration to the whole process of drug production. EU and new Chinese GMPs introduce the concepts of Quality Assurance in the same way. US GMPs does not establish the requirement of having a quality system, but it can be understood with the whole reading of 21 CFR Parts 210 &211.
欧盟和新版中国GMP都建立了质量系统要求，包括了确立相应质量目标，应用从药品注册到整个药品生产工艺的安全，成效和质量控制。欧盟和新版中国GMP引入了相同的质量保证概念。美国GMP并没有建立质量系统的需求，但是通过对21CFR Parts 210和211的解读能够体现质量系统概念。
Again EU and new Chinese GMPs introduce clearly the Risk Management Approach according to ICH Q9 concepts. Conversely, 21 CFR does not mention these concepts which are much newer than last revision of US GMPs.
欧盟和中国新版GMP又再次重申了了由ICH Q9引出的质量管理方法。相对陈旧的美国GMP 21CFR 没有涉及到这些最新概念。
DIFFERENCES 差异点:
New Chinese GMPs identifies the responsibility of top management personnel for the implementation of quality objectives (ICH Q10 concept).
新版中国GMP确立了实施质量目标最高管理层人员的责任，这一点来源于ICH Q10概念。
https://www.360docs.net/doc/326408903.html,anization and personnel 组织机构和人员
SIMILARITIES 相似点:
People should be trained in their duties and in cGMPs, previously to perform their duties and continuously, by qualified personnel. A training programme should be in place to assure training is performed periodically, although US GMP does not specify it.
人员需要根据其GMP中的职责，上岗前进行培训，培训需要有连续性，并且由具有资质的人员实施。培训计划应到位以保证培训能够定期进行，但美国GMP没有涉及培训计划。
DIFFERENCES 差异点:
Main responsibilities of Head of Production, Quality Unit and Qualified person are described in EU and new Chinese GMPs. Nevertheless, new Chinese GMPs also identify the minimum training of the person in charge of production (degree in pharmacy), quality unit (degree in pharmacy or related), and qualified person (Bachelor degree in pharmacy or related). US GMP does not include any consideration about it.
在欧盟和中国新版GMP中明确了生产，质量主管和质量授权人的主要责任。然而，新版中国GMP 同时明确了人员的最低资质要求：生产负责人（药学或相关专业），质量单元（药学或相关专业）和质量授权人（药学或相关专业本科学位）。美国GMP没有上述要求。
EU GMPs and new Chinese GMPs are much more specific with Personnel hygienic, requiring an specific training programme. They also request periodical medical check to employees in direct contact with the product (at least one per year in new Chinese GMPs)
欧盟GMPs和中国新版GMP都特别关注了人员卫生，需要特别的培训内容。都要求进行直接接触产品的员工进行周期性体检（在中国新版GMP中规定至少每年1次）
Finally, US GMP is the only one requiring consultants’ qualification. Their qualification records (curriculums) should be retained.
只有美国GMP需要对咨询师的资质有要求。资质记录（简历）需要保留。
3.Facility and utilities 厂房和设施
SIMILARITIES 相似点:
EU, US and new Chinese GMPs agree that Premises and equipment must be located, designed, constructed, adapted and maintained to suit the operations to be carried out. Their layout and design must aim to minimize the risk of errors and permit effective cleaning and maintenance in order to avoid cross-contamination, build up of dust or dirt and, in general, any adverse effect on the quality of products. They totally agree in the requirement of storage areas and auxiliary areas.
欧盟，美国和中国新版GMP都要求厂房和设备的安置，设计，建筑材料，配置和维护需要与相应的操作相符合。布局图和设计必须专注于最小化产生错误风险并易于有效清洁和维护避免交叉污染。积累灰尘或者污物——即避免任何不利于产品质量的有害影响。这也同样适用于存储区域和辅助区域。
DIFFERENCES 差异点:
Although they agree in the general terms, some differences between them can be found, as the specification of new Chinese GMP on the establishment of a minimum of 10 psi of differential pressure between clean areas and non-clean, or the requirement of isolate the different packaging lines to avoid mix-ups (EU GMPs specifies “Different products should not be p ackaged in close proximity unless there is physical segregation” and US GMPs “Prevention of mixups and cross-contamination by physical or spatial separation from operations on other drug products”).
虽然他们在通则方面都相同，但是还是存在一些差异点，例如新版中国GMP 在洁净区和非洁净区压差设计要至少保证最小10帕斯卡，对于隔离不同产品线避免混淆的要求也有不同之处，欧盟GMP规定“不同产品间不能靠近包装，除非有物理隔离”同样，美国GMP规定了“通过与其他药品生产操作的物理或者空间隔离预防混淆和交叉污染”
For new Chinese GMPs a design of the plant in a logical sequence of manufacturing operations connections is not a requirement despite it supposes a cross-contamination risk.
新版中国GMP 没有对厂房设计需要按照工艺操作逻辑路线合理安排的要求，尽管这是可能带来交叉污染风险的因素之一。
Finally, US GMPs establishes the requirement of dispose sewage, trash, and other refuse in and from the building and immediate in a safe and sanitary manner, as well of the existence of written procedures for installation sanitization.
最后，美国GMP建立了对污水处理，垃圾和其他废物的处理要求。必须立即根据建立的卫生处理规程用安全和清洁的方式进行管理。
4.Equipment 设备
SIMILARITIES 相似点:
EU GMPs, US GMPs and new Chinese GMPs agree that Manufacturing equipment should be designed, located and maintained to suit its intended purpose, according the criteria to avoid risk of error or contamination, equipment should be cleaned according written procedures and that equipment maintenance and repair shall not affect the product quality. Equipment should be used and cleaned according approved SOPs.
欧盟GMP，美国GMP和新版中国GMP都要求生产设备需要根据规范按照预期的目的合理设计，安置和维护，以避免错误和污染的风险。设备需要根据建立的规程清洁。设备维护和维修不能影响产品质量，设备需要按照已批准的SOP使用和清洁。
DIFFERENCES 差异点:
New Chinese GMPs are much more explicit in some sections, for example, detailing SOP distribution and withdrawal, the use of food grade lubricant when possible, the existence of a maintenance programme, existence of specific cleaning methods, existence of equipment status identification or the existence of calibration labels. Moreover, new Chinese GMPs includes requirements on the water quality (at least use drinking water). These aspects are all included in ICH Q7A (EU GMPs Part II) - Good Manufacturing Practice Guidance for Active Pharmaceutical Ingredients, but not in EU GMPs Part I or 21 CFR PARTS 210 & 211.
新版中国GMP在某些方面更加详尽。例如，细化了SOP发布和撤销；尽可能使用食品级润滑油；要有维护计划，详细的清洁方法，设备状态标识或校验标签。此外，新版中国GMP包括了对用水的质量的要求（至少使用饮用水）。这些方面都包含在了ICH Q7A (欧洲GMP第二部分)-原料药良好生产实践指南，但不包含在欧洲GMP第一部分或21CFR PARTS 210和211
On the other hand, US GMPs describe routine controls to be performed in computerized system to assure that changes in master production and control records or other records are instituted only by authorized personnel. Backup of computerized system data is also required. Moreover, US GMPs includes the requirement of non using fiber-release filters in liquid filtration operations used in the manufacturing of injectables drug products.
在其他方面，美国GMP描述了对计算机系统的常规控制以保证在主生产和控制记录或者其他记录上的变更只能由授权人建立。同时要求计算机系统数据的备份。此外，美国GMP包括了对在注射剂产品生产时进行的液体过滤操作中应当使用无纤脱落型过滤器的要求。
5.Materials and products 原料和产品
SIMILARITIES 相似点:
There should be written procedures describing detailing the reception, identification, storage, handling, sampling, testing, and approval or rejection of income goods. All suppliers should be qualified. Records of shipments received of materials should be maintained. All goods should be tested and approved before its use, and a quarantine system should be in place. All containers should be identified. Printing and packaging materials should be properly stored to avoid cross-contamination and mix-ups (EU and new Chinese GMPs requires restricted access to unauthorized personnel), and obsolete versions should be destroyed and recorded. Warehoused materials should be rotated.
必须有规程详细规定如何对原料进行接收，标识，储存，处理，取样，测试，批准或拒收。所有供应商必须经过确认。需要保留收到的原料发货记录。所有原料在使用前必须经过测试和批准，隔离系统必须到位。所有容器必须标识。印刷包装材料需要正确存贮以避免交叉污染和混淆（欧盟和新版中国GMP要求印刷包装材料需要有专人保管），废弃的版本必须销毁和记录。仓库原料需要合理安置和周转。
Reworking and reprocessing operations are allowed when final product quality is not in risk. Additional controls should be performed in these processes and it should be fully reported.
如果对产品质量不造成风险允许进行重加工和返工操作。但需要对这些工艺进行附加的控制并完整记录。
The recall process should be according to predetermined operating procedures and appropriated reports should be issued.Returns didn’t affected the quality can be considered to be re-packaged, re-shipped and sealed
召回程序需要根据预先确定的操作规程并出具合适的报告。未受质量影响的召回品可以重新包装，运送和密封。
DIFFERENCES 差异点:
Several differences can be found in this chapter. Requirements established for each authority are listed below:
本章节各个官方要求的差异点如下，
US GMPs 美国GMP:
-Bagged or boxed components of drug product containers or closures shall be stored off the floor and suitably spaced to permit cleaning and inspection
药品装袋，装盒或者其他密闭容器后需要离地存贮，且有合适的空间易于清洁和检查
-Sample containers shall be identified so that the following information can be determined: name of the material sampled, the lot number, the container from which the sample was taken, the data on which the sample was taken, and the name of the person who collected the sample
取样容器需要标识以便于以下信息能够确认：取样物料名称，批号，被取样处容器信息，取样时间，取样人姓名。
-Containers from which samples have been taken shall be marked to show that samples have been removed from them.
已被取样的容器上需要注明已取样信息。
-At least one test shall be conducted to verify the identity of each component of a drug product. Specific identity tests, if they exist, shall be used.
至少对药品每种原料进行一次鉴别测试。包括若有特别鉴别实验，也需要对其实施。
-Stock rotation: Components, drug product containers, and closures approved for use shall be rotated so that the oldest approved stock is used first.
库存周转：已批准的原料，药品容器和密闭包装应根据先进先出的原则管理
New Chinese GMPs 新版中国GMP:
-Imported raw materials and excipients shall comply with relevant state regulations on importation.
进口原材料和辅料需要符合国家相关进口法规。
-Qualification of transportation of special materials is required.
需要对特殊原料的运输过程进行确认。
- A criterion for stock rotation is defined: FIFO or FEFO should be used.
库存管理的标准是：先进先出或先到期先出。
-Appropriate operation procedures should be available for computerized warehouse management to prevent mixing and error caused by system failure, shutdown or other special cases.
合适的计算机仓库管理操作规程到位以避免混淆和错误发生，导致系统失效，当机或者其他意外发生。
-Specific file should be created to preserve the original sample of printing and packaging material with signature of approval. Obsolete print templates should be recalled and destroyed
需要建立专门的文档，保存经签名批准的印刷包装材料原版实样。废弃的原版实样需要召回和销毁。
6.Validation and qualification 验证和确认
SIMILARITIES相似点:
EU GMPs (see annex 15) and new Chinese GMPs conform the requirement to validate equipment, processes and cleaning methods to demonstrate its suitability to meet specifications through a several validation stages (DQ, IQ, OQ, PQ). Validations should be performed according pre-approved plans and documents, and final reports to formal release the facility, system or equipment should be issued. Both regulations agree in the requirement of periodically process revalidation.
欧洲GMP（附件15）和新版中国GMP确认了通过不同的验证阶段（DQ，IQ，OQ，PQ）对设备，工艺和清洁方法验证以证明能够满足标准要求。验证需要根据预先批准的计划和文件。正式发布相关厂房，系统或设备的最终报告。两个法规都要求进行周期性工艺再验证。
DIFFERENCES差异点:
New Chinese GMPs does not consider the idea of retrospective or concurrent process validation, but define the scope of the validation according to a previous risk assessment closely following recent US FDA Guideline - Process Validation: General Principles and Practices
新版中国GMP没有包括回顾性或并行性验证，但是定义了验证需要根据先前的风险评估，该步骤紧密的结合了美国FDA指南—工艺验证：主要原则和实践
New Chinese GMPs does not include any consideration regarding computerized systems validation such as electronic signature or electronic records, as it are regulated in EU GMPs Annex 11 or 21 CFR Part 11. For these aspects, only password and backup copies are required for data safety in new Chinese GMPs.
新版中国GMP没有包括相关在欧盟GMP附录11和美国21CFR PART 11中要求的的计算机系统验证，例如电子签名和电子记录。对于这些方面，新版中国GMP仅仅是在关于数据安全性上的密码和备份拷贝有要求。
In the other side, US GMPs considers validation as the verification of the suitability of the equipment/system/facility as well, but with a completely different approach than EU GMPs or new Chinese GMPs, considering the process design as a process validation step. The design is focus on the product knowledge gained during development and scale up activities. Further process validation steps are similar to those set out by other authorities.
在其他方面，美国GMP认为工艺验证也是对设备/系统/厂房的适应性的确认，并采取与欧洲GMP 和新版中国GMP完全不同的方法：将工艺设计作为工艺验证的一个步骤。工艺设计专注于在产品开发和中试时获得的产品认知信息。其后的工艺验证步骤则与其他官方相同。
7.Document management 文件管理
SIMILARITIES相似点
EU GMPs and new Chinese GMPs share their point of view over documentation control, since they consider documents as an essential element of quality assurance systems. They agree with the idea of the existence of electronically source documentation and paper-based, and that documents should be issued and approved, as well as the requirement to establish an effective date. Both regulations and US GMPs also, establish the necessity of having production and packaging batch records, as well as standard operating procedures for process, cleaning, sampling and testing or equipment and instruments logbooks. Results of these operations should be recorded. Documents copies should not be different than originals. Quality documentation should be approved by the quality management department (not in US GMPs)
欧洲GMP和新版中国GMP在文件控制方面相同，因为他们认为文件是作为质量保证系统最根本的单元。两者都认同文件可以是电子源文件或者纸质文件并且文件需要根据需要发布和根据需要
建立生效期后生效。两个当局都建立了生产和包装批记录的要求，包括对工艺，清洁，取样，测试，设备和仪器记录表的标准操作规程。这些操作的结果需要进行记录。文件副本应与原件相同。质量文件需要由质量管理部门批准（美国GMP没有这样要求）。
DIFFERENCES差异点
Although several considerations are included in US GMPs throughout the whole text about the documentary practices, there is not a specific chapter to describe completely the requirements.
虽然在美国GMP通篇中一些部分涉及了文件实践的要求，但是并没有专列章节描述完整的要求。New Chinese GMPs encourages the use of automated production or testing equipment to print records and graphs. Other new and very specific aspects included in new Chinese GMPs are the following:
新版中国GMP鼓励使用自动化生产或测试设备打印记录和图表。其他一些新版中国GMP涉及到的方面如下：
-Batch records should be managed by QU at least one year after the expiration date to save (also in EU GMPs) (in EU GMP this time should be longer than 5 years).
批记录由质量单元保存至至少产品有效期1年以后（同样在欧盟GMP中也有涉及，欧盟GMP中规定必须长于5年）
-Include the expected yield in packaging operations (it is also a requirement in US GMPs)
在包装操作中应包括预期收率（同样在美国GMP中也有要求）
-Introduce the change history chapter in SOPs as mandatory.
强制在SOP中引入变更历史章节
-Batch production records should be marked on every page the name of the product, specifications and batch number.
生产批记录应当在每页标识产品名称，规格和批号
-Documents should be periodically reviewed (it is also a requirement in EU GMPs)
文档应周期性审核（同样在欧盟GMP中也有要求）
8.Production Management 生产管理
SIMILARITIES 相似点
Written procedures should be available for manufacturing, packaging, warehousing and distributing operations. Materials and equipments should be checked and identified to record it in Batch records. Checks on yiels and reconciliation should be carried out. Contamination and cross-contamination prevention are the main objective of this chapter for the three regulatory authorities. Checks about line clearance are introduced after and before packaging operations.
需要建立生产，包装，仓库和配送操作规程。需要对原料和设备进行检查并识别记录在批记录中。必须检查收率和核对物料平衡。预防污染和交叉污染都是三个当局在此章节关系的主要内容。需要在包装前后都进行清场检查。
DIFFERENCES 差异点
US GMPs are much stricter with labeling operations. Specially, gang-printed labels are prohibited unless the labeling from gang-printed sheets is adequately differentiated by size, shape, or color. Further, 100% examination of correct labeling, and monitoring of printing device should be performed to assure its correct performance.
美国GMP在标签操作上更加严格。特别是不允许使用组版印制的标签即在一张印刷材料上印刷一种以上的标签，除非其尺寸，形状或颜色有明显区别。同时要对所有贴标操作进行检查，需要对印刷装置进行监测以确保其正确运行。
9.Quality control and quality assurance 质量控制和质量
保证
SIMILARITIES相似点
Quality Control is concerned with sampling, specifications and testing as well as the organization, documentation and release procedures which ensure that the necessary and relevant tests are carried out, and that materials are not released for use, nor products released for sale or supply, until their quality has been judged satisfactory. Product release for sale is responsibility of the Qualified Person (in new Chinese GMPs and EU GMPs)
质量控制关注于根据组织机构，文件系统和发放规程进行取样，质量标准和测试操作确保必要和的相关测试已经执行；确保在物料和产品的质量符合前不能使用或出售放行。产品出售放行在新版中国GMP和欧盟GMP中定义为质量授权人的职责。
The independence of Quality Control from Production is considered fundamental to the satisfactory operation of Quality Control.
质量控制独立于生产部门是确保质量控制能够正常运行的基本要求。
As EU and US GMPs, National Pharmacopeia based analytical methods should not be validated but verified.
欧盟和美国GMP对基于国家药典的分析方法不用验证但是需要进行确认。
DIFFERENCES差异点
New Chinese GMPs includes the minimum qualification of laboratory personnel (Professional technical secondary school or high school education).
新版中国GMP包括了实验室人员的最低资质要求，至少中专或高中学历。
According to new Chinese GMPs, Stability protocols should include Storage conditions (conditions for long-term stability study specified by “Chinese Pharmacopoeia" - instead of ICH recommendations - corresponding to storage conditions identified for drug should be adopted). Moreover, according to US GMPs, there are no requirements of performing Stability monitoring of homeopathic drug products and allergenic extracts that are labeled " No U.S. Standards of Potency", but written assessment of stability shall be in place for homeopathic drug products.
根据新版中国GMP，稳定性考察方案必须包含储藏条件（在中国药典中特别对长期稳定性研究条件做了定义：采用符合药品标识的储藏条件以代替ICH建议。）此外，根据美国GMP，没有对同类疗法药品和标注为“非美国标准效果”的致敏性物质进行稳定性监测的要求，但是成文的同类疗法药品稳定性评估必须到位。
Finally, the new Chinese regulation includes current concepts of ICH Q9 and Q10 by including instructions regarding the following quality processes: change control, deviation, CAPA, evaluation of suppliers, complaints and product annual review (EU and US GMPs only consider complaints and product quality reviews). Processes are based on standard operating procedures and on product quality assessments based in scientific knowledge of manufacturing process. For each process, corresponding records should be issued. Records maintenance is responsibility of Quality Unit department.
最后，新版中国法规包括了目前ICH Q9和Q10 的概念，包括如下质量过程：变更控制，偏差，CAPA（预防与纠偏措施），供应商评估，投诉和产品年度回顾（欧盟和美国GMP仅涉及投诉和产品质量回顾）。质量过程基于标准操作规程，产品质量评估基于对生产工艺的科学认知。对于每个工艺，都须有相应的记录。记录维护是质量单元部门的职责。
10.Contractual production and inspection 合同生产和审
计
SIMILARITIES 相似点
EU GMPs and new Chinese GMPs agree that contract manufacture and analysis must be correctly defined in a written contract, agreed and controlled in order to avoid misunderstandings which could result in a product or work of unsatisfactory quality. Responsibilities over the whole manufacturing process should be defined (raw materials income, manufacturing, sampling, testing, etc.)
欧盟GMP和新版中国GMP都同样要求委托生产和委托检验必须有书面签署的合同，并按照合同内容进行控制以避免误解而影响产品和工作质量。需要明确整个生产工艺的职责（原料接收，生产，取样，测试，等等）
DIFFERENCES 差异点
US GMPs only refers contract manufacturing when states the quality control is responsible for approving or rejecting drug products manufactured, processed, packed, or held under contract by another company.
在美国GMP中涉及到的合同生产内容如下：质量控制负责对由其他公司生产，处理，包装，或持有的药品进行批准或者拒收。
11. Product shipment and recall 产品发运和召回
SIMILARITIES相似点
US GMPs and new Chinese GMPs establish the requirement to record detailed information about each batch of products shipped. It is also required in EU GMPs, although it is stated in the Guidelines on Good Distribution Practice of Medicinal Products for Human Use.
美国GMP和新版中国GMP对详细记录每批次运输信息提出了要求。同样也包括在欧盟GMP中的人用医疗产品良好流通实践指南。
Eu GMPs and new Chinese GMPs state the requirement to designate a responsible for recalls and recalls should be capable of being initiated promptly and at any time. Written procedures regularly checked and updated when necessary, in order to organise any recall activity should be established. Recalls should be summed in reports.
欧盟GMP和新版中国GMP要求都指定责任人负责召回和能够能在任何时候都能够迅速发起实施召回。
Recalled products should be identified and stored separately in a secure area while awaiting a decision on their destination.
召回的产品需要标识，并分开存储于安全区域，等待进一步处理。
DIFFERENCES不同点
US GMPs only consider the possibility of recalling a product, and that recall should be performed according a procedure. Writing procedures should be established to notify the firm responsible official about the recall. FDA basis its recall strategy in the approval of the recall plan that firms should present to FDA ( but need not delay initiation of a recall pending review of its recall strategy). Recall efficacy should be reviewed. (See 21 CFR Part 7).
美国GMP要求应当考虑召回产品的可能性，召回应当根据规程进行操作。需要建立规程将召回情况通知公司相关负责人。FDA要求的是公司批准召回计划后需要递交召回策略给FDA（公司不用等待FDA审核召回策略就需要开始进行召回）。召回效果需要评估（详见21CFR PART 7）。
12. Self-check 自检
SIMILARITIES 相似点
The three regulations call to self inspections to be executed periodically to evaluate effective implementation and maintenance of the quality system and to determine if processes and products meet established parameters and specifications. Reports should contain all the observations made during the inspections and, where applicable, proposals for corrective measures.
三个法规当局都需要周期性进行自检以评估质量系统实施和维护效果，证明工艺和产品是否能够满足预先建立的参数和质量标准。自检报告应当包括发现的所有偏差，如果可行，同时包括整改措施方案。
DIFFERENCES 差异点
US GMPs does not require self inspection (21 CFR Parts 210 & 211)
美国GMP没有明确要求进行自检（21CFR Parts 210&211）
13. Supplementary Provisions 补充条款
SIMILARITIES相似点
New Chinese GMPs and UE GMPs are a standard is pharmaceutical production and quality control. Sterile drugs, biological products, blood products or production of drugs such as the special requirements of quality management activities, requirements are enacted separately in Annexes.
新版中国GMP和欧洲GMP都是作为药品生产和质量控制的标准。无菌药品，生物产品，血液产品或者其他特殊质量管理要求的药品生产需求作为附录另行发布。