【技术交流】中国新版， 欧盟和美国GMP比较概要（下）

5.      Material and products 原料和产品

SIMILARITIES相似点

There should bewritten procedures describing detailing the reception, identification, storage,handling, sampling, testing, and approval or rejection of income goods. Allsuppliers should be qualified. Records of shipments received of materialsshould be maintained. All goods should be tested and approved before its use,and a quarantine system should be in place. All containers should beidentified. Printing and packaging materials should be properly stored to avoidcross-contamination and mix-ups (EU and new Chinese GMPs requires restrictedaccess to unauthorized personnel), and obsolete versions should be destroyedand 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。所有窗口必须标识。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 andreprocessing operations are allowed when final product quality is not in risk.Additional controls should be performed in these processes and it should befully 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 recallprocess should be according to predetermined operating procedures andappropriated reports should be issued. Returns didn’t affected the quality canbe 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：

Severaldifferences can be found in this chapter. Requirements established for eachauthority 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 orclosures shall be stored off the floor and suitably spaced to permit cleaningand inspection.

—      药品装袋，装盒或者其它密闭窗口后需要离地存贮，且有合适的空间易于清洁和检查

—      Sample containers shall be identified so that the followinginformation 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 wastaken, and the name of the person who clooected 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 bemarked 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 identifyof 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 container, andclosures approved for use shall be rotated so that the oldest approved stock isused 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 material and excipients shall comply withrelevant 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 isrequired.

—      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 FEFOshould 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 forcomputerized warehouse management to prevent mixing and error caused by systemfailure, 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，系统失效，当机或者其它意外发生

—      Specific file should be created to preserve the originalsample of printing and packaging material with signature of approval. Obsoleteprint 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 (seeannex 15) and new Chinese GMPs conform the requirement to validate equipment,processes and cleaning methods to demonstrate its suitability to meetspecifications through a several validation stages (EQ, IQ, OQ, PQ). Validationshould be performed according pre-approved plans and documents, and finalreports 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。

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DIFFERENCES 差异点：

New Chinese GMPsdoes not consider the idea of retrospective or concurrent process validation,but define the scope of the validation according to a previous risk assessmentclosely following recent US FDA Guideline—Process validation: GeneralPrinciples and Practices.

新版中国GMP没有包括回顾性或同步验证，但是定义了验证的范围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you要原则和实践

New Chinese GMPsdoes not include any consideration regarding computerized systems validationsuch as electronic signature or electronic records, as it are regulated in EUGMPs Annex 11 or 21 CFR Part 11. For these aspects, only password and backupcopies 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 PART11中要求的计算机敏主，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 otherside, US GMPs considers validation as the verification of the suitability ofequipment/system/facility as well, but with a completely different approachthan EU GMPs or new Chinese GMPs, considering the process design as a processvalidation step. The design is focus on the product knowledge gained during developmentand scale up activities. Further process validation steps are similar to thoseset out by other authorities.

在其它方面，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它官方相同。

7.      Document management 文件管理

SIMILARITIES相似点

EU GMPs and newChinese GMPs share their point of view over documentation control, since theyconsider documents as an essential element of quality assurance systems. Theyagree with the idea of the existence of electronically source documentation andpaper-based, and that documents should be issued and approved, as well as therequirement to establish an effective date. Both regulations and US GMPs also,establish the necessity of having production and packaging batch records, aswell as standard operating procedures for process, cleaning, sampling andtesting or equipment and instruments logbooks. Results of these operationsshould 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GMMP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，丙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、、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 severalconsiderations are included in US GMPs throughout the whole text about ehdocumentary practices, there is not a specific chapter to describe completelythe requirements.

虽然在美国GMP通篇中一些部分涉及了要求，但是并没有专列章节描述完整的要求。

New Chinese GMPsencourages the use of automated production or testing equipment to printrecords and graphs. Other new and very specific aspects included in new ChineseGMPs 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 leastone year after the expiration date to save (also in EU GMPs) (in GU GMP thistime 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 packagingoperations (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 SOPsas mandatory.

-         强制在SOP中引入变更历史章节

-         Batch production records should be marked onevery page the name of the product, specification and batch number

-         生产批记录应当在每页标识产口名称，规格和批号

-         Documents should be periodically reviewed (itis 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

Writtenprocedures should be available for manufacturing, packaging, warehousing anddistributing operations. Materials and equipments should be checked andidentified to record it in Batch records. Checks on yields and reconciliationshould be carried out. Contamination and cross-contamination prevention are themain objective of this chapter for the three regulatory authorities. Checksabout line clearance are introduced after and before packaging operations.

需要建立生产，包装、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心的主要内容。需要在包装前后都进行清场检查。

DIFFERENCES 差异点：

US GMPs are muchstricter with labeling operations. Specifically, gang-printed labels areprohibited unless the labeling from gang-printed sheets is adequatelydifferentiated by size, shape, or color. Further, 100% examination of correctlabeling, and monitoring of printing device should be performed to assure itscorrect 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 Controlis concerned with sampling, specifications and testing as well as theorganization, documentation and release procedures which ensure that thenecessary and relevant tests are carried out, and that materials are notreleased for use, nor products released for sale or supply, until their qualityhas been judged satisfactory. Product release for sale is responsibility of theQualified 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 independenceof Quality Control from Production is considered fundamental to the satisfactoryoperation 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 USGMPs, National Pharmacopeia based analytical methods should not be validatedbut 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 GMPsincludes the minimum qualification of laboratory personnel (Professionaltechnical 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 newChinese GMPs, Stability protocols should include Storage conditions (conditionsfor long-term stability study specified by “Chinese Pharmacopoeia”-instead ofICH recommendations – corresponding to storage conditions identified for drugshould be adopted). Moreover, according to US GMPs, there are no requirements ofperforming Stability monitoring of homeopathic drug products and allergenicextracts that are labeled “No U.S. Standards of Potency”, but writtenassessment 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（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 newChinese regulation includes current concepts of ICH Q9 and Q10 by includinginstructions regarding the following quality process: 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 qualityassessments based in scientific knowledge of manufacturing process. For eachprocess, corresponding records should be issued. Records maintenance isresponsibility 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 newChinese GMPs agree that contract manufacture and analysis must be correctlydefined in a written contract, agreed and controlled in order to avoidmisunderstandings which could result in a product or work of unsatisficatoryquality. 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 onlyrefers contract manufacturing when states the quality control is responsiblefor approving or rejecting drug products manufactured, processed, packed, orheld 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，或特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 newChinese GMPs establish the requirement to record detailed information abouteach batch of products shopped. It is also required in EU GMPs, although it isstated in the Guidelines on Good Distribution Practice of Medicinal Productsfor 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 newChinese GMPs state the requirement to designate a responsible for recalls andrecalls should be capable of being initiated promptly and at any time. Writtenprocedures regularly checked and updated when necessary, in order to organizeany 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在任何时候都能够迅速发起实施召回。

Recalledproducts should be identified and stored separately in a secure area whileawaiting a decision on their destination.

召回的产品需要标识，并期盼主动安全区域，等待进一步处理。

DIFFERENCES 差异点：

US GMPs onlyconsider the possibility of recalling a product, and that recall should beperformed according a procedure. Writing procedures should be established tonotify the firm responsible official about the recall. FDA basis its recallstrategy 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 recallstrategy). 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 PART7）。

12.  Self-check 自检

SIMILARITIES相似点

The threeregulations call to self inspections to be executed periodically to evaluateeffective implementation and maintenance of the quality system and to determineif 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 notrequire self inspection (21 CFR Parts 210 %211)

美国GMP没有明确要求进行自检（21CFR Parts210&211）

13.  Supplementary Provisions

SIMILARITIES相似点

New Chinese GMPsand EU GMPs are a standard is pharmaceutical production and quality control.Sterile drugs, biological products, blood products or production or productionof 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，生产产品，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。

楼主好厉害，好强大的资料！

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