2020年(医疗药品管理)巴西药品验厂标准中英文版

（医疗药品管理）巴西药品验厂标准中英文版

巴西卫生部

原料药与中间品 GMP

巴西 GMP简介

1、巴西GMP是在Q7A的基础上建立起来的。

Q7A是ICH对原料药生产的指导性文件。ICH（人用药品注册技术要求国际协调会议）由三个地区的代表组成，即欧盟、美国和日本。ICH指导文件是三方公认的国际标准，同时ICH指导文件也日益成为国际上公认的药品注册技术标准。巴西GMP沿用了Q7A的基本原则与框架，大致内容也与其相同，但是，巴西GMP 也融入了巴西卫生部对GMP的理解与要求，使之比Q7A更具体、更严格。

2、巴西GMP与中国GMP的比较

中国没有单独针对原料药生产的GMP要求，现行98年修订版 GMP，内容过于简单，版本过于陈旧，两者差距非常大，不可同日而语。

3、巴西GMP基本框架

第一部分：说明GMP是质量管理体系的一种；指明质量管理的基本原则与职责。

（第一章至第二章）。

第二部分：对影响产品质量的6要素（5M1E）提出具体要求；对贯穿于所有方面

的文件管理提出具体要求。（第三章至第八章）

第三部分：对药品生产质量管理的其它几个重要方面提出具体要求。（第九章至第十七章）

第一章一般考虑

1.1 企业资质文件齐全，经常受到药监部门的检查。

（要准备：药监部门的检查记录与报告）

1.2 原料药生产应遵循该法规。

1.3 生产企业应保证产品符合既定质量。

1.4 质量保证、质量控制、GMP是密切相关的三个概念。

1.5 生产企业对产品质量负责。

1.6 要有齐全的证据标明：企业在影响产品质量的各个方面实行了GMP管理。

1.7 生物制品应从工作种子库的维护工序就开始要求GMP管理。

2.质量管理

QUALITY MANAGEMENT

质量管理决定和执行公司的质量方针,即与质量有关的总体方向和目标,其管理职能由公司的高级管理层正式宣布并授权。

quality Management is the aspect of management function that determines and implements the “Quality Policy”, i.e., the overall intentions and directions related to quality, formally expressed and authorized by the firm high management.

2.1 原则

Principles

2.1.1 公司的所有人员对质量负有责任。

The quality should be responsibility of all the company's collaborators.

2.1.2 生产厂家应该建立执行和保持有效的文件化的质量管理体系，并使管

理层和所有与生产有关的人员积极参与。

Each manufacturer should establish, document, implement and keep an effective system of quality management, which

involves active participation of the management and all personnel involved in manufacturing.

2.1.3 质量管理体系包括公司的组织结构、程序、过程、资源和必要的活动,

确保中间品和药物活性成分符合规定的质量和纯度要求。所有相关的活动都应该在文件中规定。

The system for quality management should comprise the organizational structure, procedures, processes, resources and necessary activities to assure that the intermediate and the pharmaceutical input are in conformity with the intended specifications of quality and purity. All related activities should be defined and documented.

2.1.4 必须有一个质量部门负责保证中间品和药物活性成分满足规定的质量

标准，并达到使用要求。

There must be a quality unit responsible for assuring that intermediates and active pharmaceutical inputs are within the demanded quality standards and that can be used for the proposed purposes.

2.1.5 质量部门必须独立于生产部门，其职能包括质量保证和质量控制。质

量部门可以有一个人或一个小组和部门组成，这取决于公司的大小和结构。

There must be an independent Quality Unit of production, which comprises responsibilities of both Quality Assurance (QA) and Quality Control (QC), that completes the production responsibilities. The Quality Unit can be represented by a single person or by a group or department, depending on the size and structure of the organization.

2.1.6 授权放行中间品和药物活性成分的人员应该确定好。

The employees authorized to release intermediates and active pharmaceutical inputs should be defined.

2.1.7 所有与质量相关的活动在完成后应予记录。

All activities related to quality should be recorded after their performance.

2.1.8 所有的偏差应该由文件证明和说明。对关键偏差应进行调查，调查过

程和调查结论应该形成文件。

All deviations should be documented and explained. Critical deviations should be investigated, and this investigation and its conclusions should be documented

2.1.9 在质量部门对于物料质量作出满意的结论之前，不得放行和使用这些

物料。除非有一套合理的系统允许这样操作。但中间品和药物活性成分没有例外。

No material should be released or used before a satisfactory conclusion of the evaluation by the Quality Unit, except when There must be implemented appropriate systems allowing such

a practice, with the exception of intermediates for selling and

active pharmaceutical inputs.

2.1.10 对于发生的质量偏差，必须有通知质量部门的程序，包括采取

相关的行动。

There must be procedures to notify the Quality Unit whenever quality deviations occur, including related actions.

2.2 职责

Responsibilities

2.2.1 介绍

Introduction

2.2.1.1生产和质量部门的主要岗位应该有全职人员担任。必要时可以代理行

使某些职能,但责任不能代理。

The main posts of Production and Quality Unit should be occupied by personnel working full time at the firm. There may

be necessary to delegate some functions, however, responsibility can't be delegated.

2.2.1.2根据有关的规定为中间品和药物活性成分的生产和质量控制负责人授

予称号，并在教育、经验和培训方面有任职资格。

The responsible persons for Production, quality control and quality unit of intermediates and active pharmaceutical inputs should be entitled according to the actual legislation of the respective representative class board and qualified with proper education, experience and/or training.

2.2.1.3生产和质量部门的负责人应联合进行下列质量活动：

The responsible persons for Production and quality unit should exert together certain activities related to quality, such as:

a) 程序和文件的制定和复核包括对其进行更新。

elaboration and review of procedures and documents,

including its updating;

b) 监督和控制生产环境

monitoring and control of manufacturing environment;

c) 卫生 hygiene;

d) 工艺验证 validation of the process;

e) 包括GMP原则应用方面的培训

training, including application of GMP principles;

f) 供应商资格确认 supplier qualification;

g) 合同供应商的批准和监督 approval and monitoring of contract

suppliers;

h) 规定物料和产品的存储条件

specifications of storage conditions of materials and

products;

i) 对文件和记录归档document files and records;

j) 监督是否符合然GMP monitoring of compliance with the GMP;

k) 检查和调查可能影响中间品和药物活性成分质量的因素。

inspection and investigation of factors that may affect the

quality of intermediate and pharmaceutical input.

2.2.2 质量部门的责任

Responsibilities of the Quality Unit

2.2.2.1质量部门应该对所有与质量有关的活动进行管理。

The Quality Unit should manage all activities related to quality 2.2.2.2质量部门的主要责任不能代理。这些责任应该在文件中规定，至少涉

及下列活动：

The main responsibilities of the Quality Unit should not be delegated. These responsibilities should be defined and documents contemplating at least the following activities:

a) 放行和否决所有的中间品和药物活性成分

release or reject all intermediates or active pharmaceutical

inputs;

b) 建立和监督对生产过程中使用的原材料、中间品、包装和标签材料

放行或否决的制度。

establish and monitor a system for releasing or rejecting raw

materials, intermediates, packaging and labeling materials

used during manufacturing;

c) 在产品发货前，对生产记录和质量控制记录文件进行复核。

review documentation of production record and Quality

Control of the manufactured lot, before its release for

expedition;

d) 证明质量偏差已得到调查，并采取了纠正措施。

certify that quality deviations are investigated and corrective actions are implemented;

e) 对于留样的包管、储存和记录活动进行管理manage activities of

custody, storage, and documentation of retention samples.

f) 批准对中间品和药物活性成分的质量有影响的所有程序、标准和指

令。

approve all procedures, specifications and instructions that cause impact on the quality of the intermediate or pharmaceutical input;

g) 批准自检计划，并证明已经实行。

approve the Self-inspection Program and certify that it is executed;

h) 批准与中间品和药物活性成分的生产和质量控制有关的技术标准和

第三方服务合同。

approve technical specifications, third party service contracting related to manufacturing and Quality Control of intermediates and active pharmaceutical input;

i) 批准对中间品和药物成分的质量有影响和潜在影响的变更。

approve changes affecting and that potentially may affect the quality of intermediate and pharmaceutical input;

(j)批准验证主计划、方案和报告，确保进行必要的验证活动。

approve master plan, protocol and reports of validation and assure that necessary validations are carried out;

(k) 证明记录和调查了与质量有关的投诉和产品退回，必要时采取了纠正措施。

certify that complaints and returns related to the quality should be recorded, investigated and, when necessary, corrective actions are implemented;

(l) 证明有一套有效的设备维护和校验体系。

certify that there is an effective maintenance and calibration system of equipments;

m) 证明进行了稳定性研究，保证获得的数据能够证明中间品和药物活性成分的有效期和规定的储存装运条件。

certify that stability studies are conducted; in such a way to guarantee that obtained data supports the expiration date and the storage and shipping conditions defined for intermediates and active pharmaceutical inputs;

(n) 进行产品质量评审

perform reviews of product quality;

(o) 对生产区的环境监测进行评估

evaluate the environmental monitoring program of productive areas.

(p) 批准培训计划并证明对员工进行了最初和连续的培训。

approve Training Program and certify that initial and continuous trainings of personnel are performed and

q) 评估召回中间品和药物成分的必要性

evaluate the necessity of intermediate or pharmaceutical input recall

r) 批准校验和预防性维修计划，并证明已经正确地执行

approve the calibration and preventive maintenance

program and certify its correct execution.

2.2.3 质量控制的责任

Responsibilities of the Quality Control

2.2.

3.1质量控制的主要责任不能代理。这些责任应该在文件中清楚地确定下

来，至少包括下列活动：

The main responsibilities of Quality Control can not be delegated. These responsibilities should be defined and documented clearly describing at least these activities:

a) 制定、更新和评估 elaborate, update and review:

I. 原材料、中间品、药物活性成分、过程控制和包装材料的标准

和检验方法

specifications and analytical methods for raw materials,

intermediates, active pharmaceutical inputs, in-process

controls and packaging materials;

II. 取样程序 sampling procedures;

III.生产区环境监测程序

environmental monitoring procedures of productive areas;

IV. 评估和存放参考标准品的程序

procedures to evaluate and store reference standards;

b) 批准或否决原材料、中间品、药物活性成分和包装材料

approve or reprove raw materials, intermediates, active

pharmaceutical inputs and packaging materials;

c) 签发每批物料的检验报告

issue analytical report of each lot of analyzed material;

d) 对中间品和药物活性成分进行稳定性研究

perform stability study analyses of intermediates and active

pharmaceutical inputs;

e) 对中间品和药物活性成分的投诉和产品退回参予调查

take part on investigation of complaints and returns of

intermediates and active pharmaceutical inputs;

f) 确保准确标识试剂、物料、仪器和实验室设备

assure the correct identification of reagents, materials,

instruments and lab equipments;

g) 验证检验方法 validate analytical methodologies;

h) 按照程序调查不合格结果

investigate results out of specification, according to

procedures;

i) 进行所有要求的检验

perform all the required assays;

j) 确认设施和设备的维护

verify the maintenance of facilities and equipments;

k) 证明实验室设备的校验

certify the performance of calibration in lab equipments;

l) 推动对质量控制区员工进行最初和连续的培训

promote initial and continuous trainings of personnel from

the Quality Control area;

m) 进行环境监控分析

perform analyses of environmental monitoring

2.2.4 生产责任

Production Responsibilities

2.2.4.1 生产责任应在文件中明确规定，并至少涉及下列活动：

The production responsibilities should be defined and documented contemplating at least the following activities:

a) 按照书面的程序参与中间品和药物活性成分生产所使用的标准／主配方的确

定和复核工作。

take part of elaboration and review of standard/master formula for production of intermediates or

active pharmaceutical inputs according to written procedures;

b) 按照书面程序分发中间品和药物活性成分的生产通知单。

distribute production orders of intermediates or active pharmaceutical inputs according to written

procedures;

c) 根据已批准的要求生产药物活性成分和相关的中间品。

produce active pharmaceutical inputs and, when appropriate, intermediates according to previous

approved instructions;

d) 复核所有的批记录，保证记录完整性并签字。

review all the lot records and assure that they are completed and signed;

e) 证明所有的生产偏差得到记录和评估，并且对关键偏差进行了调查，作出了

书面结论。

certify that all production deviations are recorded, evaluated and that critical deviations are

investigated and conclusions recorded;

f) 证明设备和设施已清洁,并在必要时进行卫生处理，及时标识。

certify that facilities and equipments are found clean, when necessary, sanitized, and duly

identified;

g) 证明必须的校验已完成，并保存了记录。

certify that the necessary calibrations are executed and records are kept;

h) 证明验证方案和验证报告得到评审和批准。

certify that protocols and validation reports are reviewed and approved;

i) 提出工艺或者设备的改造建议。

propose alterations in the process or equipment;

j) 对提出的产品、工艺或设备的改造建议进行评估。

evaluate proposed alterations for product, process or equipments;

k) 证明新的或改进的设备和设施合格。

certify that facilities and equipments (when new or modified) are qualified, when necessary and;

l) 证明设备和设施的维护已完成，并且保存了记录。

certify that maintenance of facilities and equipments are performed and records kept.

2.3 产品质量评审

Product Quality Review

2.3.1 为核实工艺的一致性，应该定期对中间品和药物活性成分的质量进行评

审。评审应采用书面形式，每年进行一次，并至少包括下列方面

Regular reviews of intermediates and active pharmaceutical inputs should be conducted aiming to verify consistency of the process. Such reviews should be conducted and documented annually and include at least:

a) 对中间品和药物活性成分的关键工艺控制和关键测试结果进行评审

review of controls in critical processes and critical test results of intermediate

and pharmaceutical input;

b) 评审所有不符合规定要求的批次。

review of all the lots not showing as established in the specification;

c)评审所有的关键偏差和相关的调查

review of all the critical deviations and related investigations;

d)评审工艺变更或已验证的检验方法的变更。

review of alterations performed in the processes or validated analytical methods;

e) 评审稳定性监控结果。

review of results from stability monitoring program;

f) 评审所有与质量有关的产品退回，投诉和产品召回。

review of all the returns, complaints and recalls related to quality;

g) 评审纠正措施。

review of corrective actions.

2.3.2 对结果进行分析，必要时,采取纠正措施并记录、跟踪和作出结论。

Results should be analyzed and, if necessary, corrective actions should be taken,

recorded, followed and concluded.

2.4 质量自检

Quality Self-inspections

2.4.1 质量自检活动的目标是确认中间品和药物活性成分的生产厂家从物料

的采购到中间品和药物成分发货的过程符合GMP的要求，自检活动应该至少每年进行一次

Its goal is to verify the conformity of the manufacturer of

intermediates and active pharmaceutical inputs with the main

GMP, from material acquisition to expedition of intermediates

or pharmaceutical input. The self-inspections should be

performed, at least, annually.

2.4.2 应该对自检活动制定书面程序。自检应该包括：

It should be elaborated a written procedure on self-inspections.

The self-inspection should comprise:

a) 人员 personnel;

b) 设施 facilities;

c) 厂房和设备维护 building and equipment maintenance;

d) 原材料、包装材料和成品的储存

storage of raw material, packaging material and finished

product;

e) 设备生产 equipments;

f) 生产和过程控制 production and in-process control;

g) 质量控制 Quality Control;

h) 文件 documentation;

i) 卫生 sanitation and hygiene;

j) 验证和在验证计划 programs of validation and revalidation;

k) 仪器和测量系统的校验

calibration of instruments and measure systems;

l) 中间品和药物活性成分从市场召回

recall of intermediate and pharmaceutical input from the

market;

m) 顾客投诉 complaints;

n) 标签控制 label control;

o) 废物处理 waste management:

p) 先前自检的结果和采取的纠正措施

results from early self-inspections and adopted corrective

actions.

2.4.3 自检小组应该由合格的专业人员组成，对实际的操作区和GMP有很好

的了解。小组成员可以是公司的专业人员或者外部的专家

The self-inspection team should be constituted by qualified

professionals, experts in its actuation area and familiarized with GMP. Team members can be professionals of the company or

outer experts.

2.4.4 对自检活动应进行记录，至少包括下列方面

Self-inspection should be documented and contain at least:

a) 自检结果 self-inspection result;

b) 评估和结论 evaluations and conclusions;

c) 发现的不合格项 detected non-conformities;

d) 建议的纠正措施和期限，在规定的期限内对自检报告中的不合格项

采取和完成纠正措施。

recommended corrective actions and established term for

attending.

Corrective actions for non-conformities observed in the self-

inspection report should be implemented and concluded

within the informed term.

3 人员

PERSONNEL

3.1 概述

General

3.1.1 建立和维护中间品和药物活性成分的质量和生产活动依靠从事这些活动的员

工。

必须有足够数量的合格人员，通过接收指导培训和积累的经验来完成、监督和管理中间品和药物活性成分的生产活动。每个人的责任和权力应通过书面形式确定，并由所有的相关人员执行。

Establishment and maintenance of quality and manufacturing of intermediate and

active

pharmaceutical input depend on employees that perform them. There must be a

adequate number of

qualified personnel by instruction, training, and/or experience, to execute, supervise and manage

manufacturing activities of intermediates and active Pharmaceutical Inputs by which the

manufacturer is responsible. The individual responsibilities and authorities should

be established in

written procedures, comprised and applied by all the involved ones.

3.1.2 公司应该有组织结构图。员工的责任不能重叠，这样可避免影响中间品和药

物活性成分的质量。员工的工作可以由别人代理完成，条件是代理的人员达到满意的质量水平。人员的GMP执行责任不能缺位或重叠。

The company should have an organization chart. Employees shouldn’t accumulate responsibilities in

order to avoid that the quality of the intermediates and active pharmaceutical

inputs is put in danger.

Their attributions may be delegated to assigned substitutes as long as those

present satisfactory

qualification level. It can not be absence or accumulation of personnel

responsibilities referring to

GMP application.

3.1.3 所有的人员应该了解GMP的原则并接收最初和连续的培训。培训应该由合

格的专业人员定期进行，其内容至少应包括员工所从事的工作，与员工的工作职责和卫生要求相关的GMP知识。对培训记录要进行保存。应该定期对培训进行评估。所有的员工应该热情支持公司维护质量标准。

All personnel should know GMP principles and receive initial and continuous

training. Training should be regularly conducted by qualified professionals and

should cover, at least, operations performed by the employee, the GMP related to the collaborator’s functions and hygiene instructions as required. Training

records should be kept. Training should be evaluated periodically. All employees

should be motivated to support the company in maintaining quality standards.

3.2 培训

Training

3.2.1 生产厂家应该通过书面的明确的计划对工作影响到中间品和药物活性成分

质量的所有员工进行培训。

The manufacturer should, through a written and defined program,

promote trainings of all personnel whose activities may interfere

with the quality of the intermediate and active pharmaceutical input.

3.2.2 除了 GMP理论和实践方面的基本培训外，新聘用的人员应该参加公司的整

合活动，接受岗位责任方面的培训，并持续进行，接受评估。

Additionally to the basic training on GMP theory and practice, the newly hired

personnel should take part in the integration program and receive proper training for attributions and be continuously trained and evaluated.

3.2.3 培训计划应该考虑到所有的人员，并且经过生产和质量管理部门负责人的批

准，保存好培训记录。

The training programs should contemplate all personnel, as well as

be approved by responsible persons of production, quality unit and

Quality Control, and records should be kept.

3.2.4 在洁净区和具有危险污染源的区域工作的人员应得到相关的培训。

Personnel working in clean areas and areas where there is contamination hazard, where highly active, toxic, infectious or sensitizing materials are handled, should receive specific

Training.

3.4 健康、卫生、着装和行为

Health, Hygiene, Clothing and Conduct

3.4.1 所有的人员应该在录用时进行体检，并在以后根据相关的法律法规，针对

所从事的工作，接受定期体检

All personnel should undertake health exams for admission and, later, to periodic exams, required for performed activities, according to the specific legislation into force.

3.4.2. 所有的人员应该受到个人健康和安全操作方面的培训。遵守卫生和安全规

定。培训应该包括如何应付传染病和外露伤口的情况。

All personnel should be trained in personal health and security practices. All personnel should respect hygiene and security rules.

Training should include conduct situations in case of contagious diseases or exposed wound.

3.4.3. 患有可疑的和确认的传染病或者有外露伤口的人员不得从事可能对中间品

和药物活性成分的质量造成损害的活动，直到他们的健康状况对中间品和药物

活性成分的质量和安全不会构成风险。

All personnel with suspected or confirmed infectious disease or exposed wound can't

perform activities that may compromise the quality of intermediates and active pharmaceutical inputs. They should be excluded from these activities until the health status does not represent risk to the quality and security of the intermediate and active pharmaceutical input.

3.4.4. 教育和鼓励所有的人员对于影响中间品和药物活性成分的异常情况向直接

领导汇报。

All employees should be instructed and encouraged to relate to their immediate supervisor any conditions out of the established procedures that can interfere with the manufacturing of intermediates or active pharmaceutical inputs.

3.4.5. 人员应该避免与中间品和药物活性成分直接接触。

Personnel should avoid direct contact with intermediates or active pharmaceutical inputs.

3.4.6. 为了保证产品不受污染，员工应该穿干净的工作服。工作服应该适合每个

生产区域，可以重新使用的工作服应该存放在合理封闭的环境中，直到经过清洗和必要的消毒处理。工作服的报废应该按照操作程序进行。

In order to assure product protection against contamination, employees should wear clean uniforms proper to each production area. Uniforms, when reused, should be kept in adequate and close environments, until they are washed and, when necessary, disinfected or sterilized. Uniform discards should follow operational procedures.

3.4.7.工作服应该由公司提供和清洗。

Uniforms should be supplied by the company. Its washing is a company's responsibility.

3.4.8. 为了保护员工，生产厂家应该按照从事的操作活动，考虑使用有效的集体

保护设备和个人保护设备。

In order to assure protection to the employees, the manufacturer should turn available Collective Protection Equipment (CPE) and Individual Protection Equipment (IPE) according to the developed activities.

3.4.9. 吸烟、吃喝、咀嚼口香糖或者栽种植物，食品、饮料、香烟和个人药品应

限制在特定的地区，与生产区域分开。

Smoke, eat, drink, chew gums or keep plants, food, beverages, tobacco and personal medications should be restrict to certain assigned areas, separated from manufacturing areas.