warning是什么意思ICH-Q7a原料药的GMP指南(中英对照)

药

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/

细胞培养

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维护

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生产原料药

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化

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物理加工和包装

GMP

的要求增加

2. QUALITY MANAGEMENT

2.1 Principles

2.10

Quality

should

be

the

responsibilities

of

all

persons involved in manufacturing.

2.11

Each

manufacturer

should

establish,

document,

and

implement

an

effective

system

for

managing

quality

that

involves

the

active

participation

of

management

and

appropriate

manufacturing personnel.

2.12

The

system

for

managing

quality

should

encompass

the

organizational

structure,

procedures,

process

and

resources,

as

well

as

activities

to

ensure

confidence

that

the

API

will

meet

its

intended

specifications

for

quality

and

purity.

All

quality-related

activities

should

be

defined and documented.

2.13

There

should

be

a

quality

unit(s)

that

is

independent

of

production

and

that

fulfills

both

quality

assurance

(

QA

)

and

quality

control

(

QC)

responsibilities. The quality unit can be in the form

8

2

．质量管理

2.1

总则

2.10

参与原料药生产的每一个人 都应当对质量

负责。

2.11

每一个生产商都应当建立并执行一套有管

体系，并使其文件化。

2.12

质量管理体系应当包括组织机构、规程、

工艺和资源，

以及确保原料药会符合其预期的质

量与纯度要求所必需的活动。

所有涉及质量管理

的活动都应当明确规定，并使其文件化。

< br>

2.13

应当设立一个独立于生产部门的质量部

门，同时履行质量保证

< br>(

QA

)

和质量控制

(

QC

)

的

职责。依照组织机构的大小，可以是分开的

QA< /p>

和

QC

部门，或者只是一个人或小组。< /p>

Q7a

of separate QA and QC units or a single individual

or group, depending upon the size and structure of

the organization.

2.14

The

persons

authorized

to

release

intermediates and APIs should be specified.

2.15

All

quality-related

activities

should

be

recorded at the time they are performed.

2.16

Any

deviation

from

established

procedures

should

be

documented

and

explained.

Critical

deviations

should

be

investigated,

and

the

investigation

and

its

conclusions

should

be

documented.

2.17

No

materials

should

be

released

or

used

before the satisfactory completion of evaluation by

the

quality

unit(s)

unless

there

are

appropriate

systems in place to allow for such use (e.g., release

under quarantine as described in Section 10 or the

use

of

raw

materials

or

intermediates

pending

completion of evaluation).

2.18

Procedures

should

exist

for

notifying

responsible

management

in

a

timely

manner

of

regulatory

inspections,

serious

GMP

deficiencies,

product

defects

and

related

actions

(e.g.,

quality-related

complaints,

recalls,

and

regulatory

actions).

2.2 Responsibilities of the Quality Unit(s)

2.20

The quality

unit(s)

should be involved in

all

quality-related matters.

2.21

The quality unit(s) should review and approve

all appropriate quality-related documents.

2.22

The main

responsibilities of the independent

quality

unit(s)

should

not

be

delegated.

These

responsibilities should be described in writing and

should include, but not necessarily be limited to:

1.

Releasing

or

rejecting

all

APIs.

Releasing

or

rejecting

intermediates

for

use

outside

the

control of the manufacturing company

2.

Establishing

a

system

to

release

or

reject

raw

materials,

intermediates,

packaging,

and

labeling materials

3.

Reviewing

completed

batch

production

and

laboratory

control

records

of

critical

process

9

2.14

应当指定授权发放中间体和 原料药的人

员。

2.15

所有有关质量的活动应当在 其执行时就记

录。

2.16

任何偏离既定规程的情况都 应当有文字记

录并加以解释。对于关键性偏差应当进行调查，

并 记录调查经过及其结果。

2.17

在质量部门对物料完成满意 的评价之前，

任何物料都不应当发放或使用，

除非有合适的系< /p>

统允许此类使用

（如

10.20

条款所述的待检情况

下的使用，

或是原料或中间 体在等待评价结束时

的使用）

。

2.18

应当有规程能确保公司的责任管理部门能

及时得到有关药政检查、严重的

GMP

缺陷、产

品缺陷及其相关活动

< br>（如质量投诉，

召回，

药政

活动 等）的通知。

2.2

质量部门的责任

2.20

质量部门应当参与所有与质 量有关的事

物。

2.21

所有与质量有关的文件应当 由质量部门审

核批准。

2.22

独立的质量部门的主要职责 不应当委派给

他人。

这些责任应当以文字形式加以说明，

而且

应当包括，但不限于：

1.

所有 原料药的放行与否。用于生产商控制范

围以外的中间体的放行与否；

2.

建立一个放行与拒收原材料、中间体、包装

材料和标签的系统；

3.

在供销售的原料药放行前，审核已完成的关

键步骤的批生产记录和实验室检验记录；

Q7a

steps before release of the API for distribution

4.

Making

sure

that

critical

deviations

are

investigated and resolved

5.

Approving

all

specifications

and

master

production instructions

6.

Approving all procedures affecting the quality

of intermediates or APIs

7.

Making

sure

that

internal

audits

(self-inspections) are performed

8.

Approving

intermediate

and

API

contract

manufacturers

9.

Approving

changes

that

potentially

affect

intermediate or API quality

10.

Reviewing

and approving validation protocols

and reports

11.

Making sure that quality-related complaints are

investigated and resolved

12.

Making sure that effective systems are used for

maintaining and calibrating critical equipment

13.

Making

sure

that

materials

are

appropriately

tested and the results are reported

14.

Making

sure

that

there

is

stability

data

to

support

retest

or

expiry

dates

and

storage

conditions on APIs and/or intermediates, where

appropriate

15.

Performing product quality reviews (as defined

in Section

2.5

)

2.3 Responsibility for Production Activities

The responsibility for production activities should

be described in writing and should include, but not

necessarily be limited to:

1.

Preparing,

reviewing,

approving,

and

distributing the instructions

for the production

of

intermediates

or

APIs

according

to

written

procedures

2.

Producing

APIs

and,

when

appropriate,

intermediates

according

to

pre- approved

instructions

3.

Reviewing

all

production

batch

records

and

ensuring that these are completed and signed

4.

Making sure that all production deviations are

reported

and

evaluated

and

that

critical

deviations are investigated and the conclusions

are recorded

5.

Making sure that production facilities are clean

and, when appropriate, disinfected

6.

Making sure that the necessary calibrations are

performed and records kept

7.

Making

sure

that

the

premises

and

equipment

4.

确保已对重大偏差进行了调查并已解决；

5.

批准 所有的规格标准和

主生产指令

；

6.

批准 所有可能影响原料药和中间体质量的规

程；

7.

确保进行内部审计（自检）

；

8.

批准中间体或原料药的委托生产商；

9.

批准可能影响到中间体或原料药 质量的变

更；

10.

审核并批准验证方案和报告；

11.

确保调查并解决质量问题的投诉；

12.

确保用有效的体系来维护和校验关键设备；

13.

确保物料都经过了适当的检验并报告结果；

14.

确 保有稳定性数据支持中间体或原料药的复

验期或有效期和储存条件；

15.

开展产品质量审核（详见

2.5

节）

。

2.3

生产作业的职责

生产作业的职责应当以文字形式加以说明，

并应

当包 括，但不限于以下内容：

1.

按书面程序起草、审核、批准和 分发中间体

或原料药的生产指令；

2.

按照已批准的指令生产原料药或者中间体；

3.

审核 所有的批生产记录确保其完整并有签

名；

4.

确保 所有的生产偏差都已报告、评价，对关

键的偏差已做了调查，并记录结论；

5.

确保生产设施的清洁，必要时要消毒；

6.

确保

进行必要的校验

，并有记录；

7.

确保对厂房和设备进行保养，并有记录；

10

Q7a

are maintained and records kept

8.

Making

sure

that

validation

protocols

and

reports are reviewed and approved

9.

Evaluating

proposed

changes

in

product,

process or equipment

10.

Making

sure

that

new

and,

when

appropriate,

modified facilities and equipment are qualified

2.4 Internal Audits (Self Inspection)

2.40

To

verify

compliance

with

the

principles

of

GMP

for

APIs,

regular

internal

audits

should

be

performed

in

accordance

with

an

approved

schedule.

2.41

Audit

findings

and

corrective

actions

should

be

documented

and

brought

to

the

attention

of

responsible

management

of

the

firm.

Agreed

corrective actions should be completed in a timely

and effective manner.

2.5 Product Quality Review

2.50

Regular

quality-reviews

of

APIs

should

be

conducted

with

the

objective

of

verifying

the

consistency

of

the

process.

Such

reviews

should

normally

be

conducted

and

documented

annually

and should include at least:

●

A review of critical in-process control and

critical API test results

●

A review of all batches that failed to meet

established specification(s)

●

A

review

of

all

critical

deviations

or

nonconformances

and

related

investigations

●

A review of any changes carried out to the

processes or analytical methods

●

A

review

of

results

of

the

stability

monitoring program

●

A

review

of

all

quality-related

returns,

complaints and recalls

●

A review of adequacy of corrective actions

2.51

The results of this review should be evaluated

and

an

assessment

made

of

whether

corrective

action

or

any

revalidation

should

be

undertaken.

Reasons

for

such

corrective

action

should

be

documented.

Agreed

corrective

actions

should

be

completed in a timely and effective manner.

3. PERSONNEL

8.

确保验证方案和报告的审核与批准；

9.

对产品、工艺或设备拟作的变更进行评估；

10.

确保新的或已改进的生产设施 和设备经过了

确认。

2.4

内部审计（自检）

2.40

为确实符合原料药