巴西卫生部原料和中间体要求 - 中英文版

establish maximum time between process conclusion and equipment cleaning since it is significant for the cleaning procedure;

(i) 确定设备清洁和下次使用之间的最长时间，以及要重新评估的参数。

establish maximum time between equipment cleaning and next use as well as which parameters should be reevaluated.

5.2.3. 对器具进行清洁、存储和合理的消毒以防止污染

utensils should be cleaned, stored and, when appropriate, sanitized or sterilized for preventing contamination.

5.2.4. 在连续生产不同批次的同种产品时，设备的清洁应有合理的间隔时间

It should be performed equipment cleaning in proper intervals, when it occurs to continuous production of the same product of different lots.

5.2.5. 在生产不同产品的过程中，应该清洁非专用的设备，防止交叉污染。Non-dedicated equipment

should be cleaned between the manufacturing of different products for prevent cross-contamination

5.2.6. 应确定废物控制范围和清洁剂的选用标准。

There should be established acceptance criteria for waste limits and selection of cleaning agents. Equipment should be identified according to its cleaning condition.

5.3.

校验Calibration

Equipments used in Quality Control, weighting, measurement and monitoring should be calibrated according to written procedures and established schedule.

5.3.2. 设备的校验应使用的检定的标准或来源于检定标准的标准进行。

Equipment calibrations should be performed using certified patterns or traceable patterns to the certified patterns.

5.3.3. 校验记录应该保存

Calibration records should be kept.

5.3.4. 应了解实际的校验状态，并进行检查。

The actual calibration status should be known and susceptible of checking.

5.3.5. 称重和测量仪器只有在校验后才能使用

Weighting and measuring instruments should only be used when they are calibrated.

5.3.6. 设备如果与检定标准出现偏差应进行调查，确定偏差是否对中间品和药物活性成分的质量产生

了影响。

Deviations originated from patterns of approved instruments should be investigated, for determining if these can have effect on quality of intermediate and pharmaceutical input.

5.4.

计算机化系统Computerized Systems

5.3.1. 质量控制、称重、测量和监控所使用的设备应该按照书面程序和确定的计划进行校验。 5.2.7. 应按照清洁状态对设备进行标识

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5.4.1. 与良好生产实践相关的计算机化系统应该进行验证，并考虑各种参数，信息化应用的复杂性和

关键条件。Computerized systems related to the Good Manufacturing Practices should be validated, considering parameters of diversity, complexity and critical condition of the informatized application.

5.4.2. 根据使用电脑的软件和硬件，保持合理的运行设施和运行确认。It should be kept proper

operational facilities and qualifications according to the hardware and software of used computer.

5.4.3. 对计算机化系统进行充分的控制防止对数据的随意改动。并且避免每次改变的疏漏，记录每次

改变，包括数据输入。

Computerized systems should have sufficient controls to prevent access or non-authorized changes to the database. Controls should prevent omissions and process record of each change performed including data input, responsible and when it was made.

5.4.4. 电脑系统的操作和维护人员应该有书面的程序供使用

Written procedures should be available to the responsible persons of operation and maintenance of computerized systems.

5.4.5. 人工记录的数据应有第二个负责人进行核实

Manually recorded data should be verified by a second responsible person.

5.4.6. 对与计算机化系统有关的影响中间品和药物活性成分的质量、记录和实验结果可靠性的事件，

应该调查和记录。

Incidents related to computerized systems that can affect the quality of intermediates and active pharmaceutical inputs and reliability of records or from test results should be recorded and investigated.

5.4.7. 应该按照更改程序对电脑系统进行更改，更改需要得到正式的批准，并记录和测试。每次更改

的记录应该保存，包括对系统进行改造和提高。这些记录应该表明系统经过验证。

Change in the computerized systems should be made according to the procedure for changing and should be formally authorized, documented and tested. Records of every change should be kept, including modifications and improvements performed in the system. These records should show that the system is validated.

5.4.8

若发生系统故障造成记录结果丢失的情况，应使用备用的系统，保证数据安全的方法应在所有的电脑系统中确定下来。

When system failures occur and these result in record loss, an alternative system should be supplied. Means to assure the data protection should be established for all computerized systems.

6. 文件和记录DOCUMENTATION AND RECORDS 6.1.

概述 General

的所有物料和方法确定标准，以保证所有生产人员了解其责任，并能获得相关的信息。另外，它除了能对任何可疑批次的质量偏差进行追诉和调查外，还能最终保证授权人员获得所有必要的信息，确定销售的中间品或者药物活性成分是否已经放行或者没有作出决定。每一个文件可以放在在同一个大文件中，或者分别存放，但要便于查找，成为生产批记录的组成部分。

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6.1.1. 文件是质量体系的基本构成部分，应涉及到GMP的各方面。其目标是为生产和质量控制使用

Documentation constitutes essential part of the Quality system and it should be related to every GMP aspects. It has as a goal define specifications of all materials and methods of manufacturing and control, in order to assure that all personnel involved in the manufacturing know its attributions and it has access to the involved information. Additionally, it has the finality to guarantee that the authorized person has all necessary information to decide if it's released or non-determined lot of intermediate or pharmaceutical input to selling, in addition to enable tracing and investigation of any suspected lot of quality deviation. Every document may be joined in the same file, or remain separate, easily available, constituting the record of the manufacturing lot

6.1.2. 数据的记录应采用可靠的方法，如人工、电子处理系统和其他方法。应该建立与质量体系有关

的标准／主配方和程序。如果数据记录通过电子处理的方式进行，只由指定的人员才能修改电脑中的数据。对数据的更改应进行记录。使用密码和其他方法限制电脑的使用。关键数据的输入应指定记录人以外的人员操作，使用磁盘、胶卷、打印纸张和其他介质上的备份来保护批数据的电子记录。

Data should be recorded in a reliable way, manually, electronic processing system or other means. Standard/master formulas and procedures related to the system in use should be available, as well as the data precision recorder conferred. If the data record is made by means of electronic processing, only assigned persons can modify filed date into the computers. There should be recording of performed alterations. The access to computers should be restricted by passwords or other means. The data input considered critical should be conferred by an assigned person, different from that one that made the records. Electronic records of lot data should be protected by copy transference of copies in magnetic tape, microfilm, paper printing or other mean.

6.2.

文件体系和标准 Documentation System and Specifications 件可以采用书面、电子介质和其他适当的方式存档。

Every documentation related to manufacturing of intermediates and/or active pharmaceutical inputs should be prepared, reviewed, approved, updated and distributed according to written procedures. Original documents can be in paper formulary, electronic media or other adequate forms of document filing.

6.2.2. 对文件不得涂改。文件应该由具体的负责人签字。更改的记录应该能看清楚上次的数据，并由

负责人签字和注明日期。

Documents should not be blotted out. They should be available signed by the respective responsible persons. Altered records should enable the identification of the last data, should be signed and dated by the responsible.

6.2.3. 数据记录应在完成工作后立刻填写，并注明操作负责人。记录的修改应注明日期并签字。原来

的记录应保持清晰可读。

6.2.1. 与中间品和药物活性成分相关的所有文件应按照书面的程序起草、复核、更新和分发。正本文

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Record data should be filled in the respective blanks, immediately after executed the activities and should identify the responsible person by the performance. Corrections should be dated, signed and the original records should remain legible.

6.2.4. 控制文件的起草、复核、更换、撤回和分发。对正本文件应定期评估和更新，保留评估记录。

应有防止错误使用旧版本文件的体系。Emission, review, replacement, withdrawal and distribution of documents should be controlled. Original documents should be regularly reviewed and updated, keeping review history. There should be a system preventing inadvertent use of the last version.

6.2.5. 文件和记录应该保留，保留期限在程序中规定

Documents and records should be retained and the retention period should be established in procedures.

6.2.6. 各种生产、质量控制和发货记录应在该批产品有效期满后保留至少一年Every production,

control and distribution records should be retained for at least 1(one) year after the lot expiration date.

6.2.7. 在保留期内，文件和记录可以采用原件的形式或者复印间的形势保存。During the retention

period, documents and records should be retained as originals or as copies in case of third party's documents.

6.2.8. 建立生产过程中使用的原材料、中间品、药物活性成分、包装和标签材料以及其他材料的规

格、检验方法和验收标准，并形成文件。Specifications, analytical methodologies and acceptance criteria should be established and documented for raw materials, intermediates, active pharmaceutical inputs, packaging and labeling materials and other materials used during the manufacturing of intermediates and active pharmaceutical inputs.

6.2.9. 对于文件中使用的电子签名应进行确认。

When electronic signatures are used in documents, these should be authenticated and safe.

6.3.

设备清洁、卫生、消毒、维护和使用记录

Records of Cleaning, Sanitation, Sterilization, Maintenance and Equipment Use.

6.3.1. 设备的使用、清洁、卫生、消毒和维护记录应标明时间、上次操作的产品、产品批号以及清洁

和维护人员的身份。记录应该能够追溯，便于查找。

Record of use, cleaning, sanitation an/or sterilization and maintenance of equipments should present date, time, last product, actual product (when applicable) and lot number of each processed intermediate or pharmaceutical input, as well as the identification of the individual that executed the cleaning and the maintenance. Records should be traceable and be promptly available.

6.3.2. 应该有设备的清洁、卫生、消毒和维护记录，记录以附件的形式和或者附在生产指令上面。

Records of cleaning, sanitation and/or sterilization and maintenance should be available in the equipment and transcript and/or annexed to the production order, when it's utilized.

6.4.

原材料、中间品、活性药物成分、包装和标签的规格

Raw Material, Intermediates, active Pharmaceutical Inputs, Packaging and Labeling Materials Specifications

6.4.1. 说明主要包装材料和印刷材料的规格，至少包括：

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