2007 FDA固体制剂制造商cGMP的检查指南02

备注： 本文件是供检查员和其他的FDA人员的参考。并不限制FDA，并不获取任何利益，义务，权利，或豁免某人

I简介

本文件旨对制药厂CGMP检查提供一个概括性指导。这个指导应该结合其它IOM（Investigations Operations Manual）的指南，其他的药物检查指导，和应遵循的规定。IOM的第十章，所列的一些指导如下：

1 原料药视察指导

2 高纯水系统视察的指导

3 QC实验室视察的指导

4 微生物QC实验室的指导

5 冻干注射剂视察的指导

6 清洁验证视察的指导

7 制药过程中的计算机系统的视察的指导

8 工艺过程验证通则的指导

II CGMP

处方和非处方

所有的药物的生产过程要遵守CGMP否则就被认为违反FD&C（食品药品化妆品法案） 501（a）(2)(B)条款。

依据704（a）(1)(B)章, 处方药物的记录一定要随时备查。如果是NDA或ANDA所列的OTC药物，根据FDC 505（k）(2)规定，FDA可以审查，复制，核对。然而，如果视察员是根据FDC 704条款到厂检查，则没有法律要求厂方，把那些在FDA没注册过的OTC 药物记录提供给视察者。所有的处方药和OTC 药的Note: This document is reference material for investigators and other FDA personnel. The document does not bind FDA, and does no confer any rights, privileges, benefits, or immunities for or on any person(s).

I. INTRODUCTION

This document is intended to be a general guide to inspections of drug manufacturers to determine their compliance with the drug CGMPR's. This guide should be used with instructions in the IOM, other drug inspection guides, and compliance programs. A list of the inspection guides is referenced in Chapter 10 of the IOM. Some of these guides are:

o Guide to Inspections of Bulk Pharmaceutical Chemicals.

o Guide to Inspections of High Purity Water Systems.

o Guide to Inspections of Pharmaceutical Quality Control Laboratories.

o Guide to Inspections of Microbiological Pharmaceutical Quality Control Laboratories. o Guide to Inspections of Lyophilization of Parenterals.

o Guide to Inspections of Validation of Cleaning Processes.

o Guide to Inspections of Computerized Systems in Drug Processing.

o Guideline on General Principles of Process Validation.

II. CURRENT GOOD MANUFACTURING PRACTICE REGULATIONS

Prescription vs. Non-prescription

All drugs must be manufactured in accordance with the current good manufacturing practice regulations otherwise they are considered to be adulterated within the meaning of the FD&C Act, Section 501(a)(2)(B). Records relating to prescription drugs must be readily available for review in accordance with Sec. 704(a)(1)(B) of the FD&C Act. If the product is an OTC drug which is covered by an NDA or ANDA, FDA may review, copy and verify the records under Sec. 505(k)(2) of the FD&C Act. However, if the product is an OTC drug for which there is no application filed with FDA, the firm is not legally

生产必须符合CGMP的要求，包括那些记录。视察者应该审查这些记录作为决定是否符合CGMP要求的一部分。在很少的场合，可以拒绝审查OTC的记录，宣称因为没有法律要求这样做。当工厂在没有法定义务去提供审查这些记录时，没有减轻需要符合在501（a）(2)(B)CGMP的要求，包括对主体文件的要求。

如果一个工厂拒绝审查OTC的记录，视察者应该综合其他的视察方法决定该厂是否符合CGMP的要求。视察者对于处方药和非处方药违反GMP原则的问题，列于FDA-483检查表。

组织和人员

工厂一定要有QC部门担负21 CFR 211规定的责任和权威。QC一定要独立于生产部门，并且用书面文件规定它的责任权属。

根据IOM指导原则要求厂家提供公司经理和主要员工的名字，头衔和内在的责任。

在制药工业，一个职员的专业教育和岗位培训对于符合质量产品的生产有重要关系。

要说明是否这个工厂有一个书面的的培训计划，并描述培训接受的类型。职员的接受的培训应当有记录。QC对每个在产的产品每年进行总结分析，并制定书面的年报流程。应详细的审查这些年报。这将会很快让你了解生产过程是否受控。年报一定要提required to show these records to the investigator during an inspection being conducted under Section 704 of the FD&C Act. Nonetheless, all manufacturers of prescription and OTC drugs must comply with the drug CGMPR requirements, including those involving records. The investigator should review these records as part of the inspection in determining the firm's compliance with the CGMP regulations. On rare occasions, a firm may refuse to allow review of OTC records stating they are not legally required to. While the firm may be under no legal obligation to permit review of such records, this does not relieve the firm of its statutory requirement to comply with the good manufacturing practices under section 501(a)(2)(B) of the Food Drug and Cosmetic Act, including the requirements for maintaining records.

If a firm refuses review of OTC records, the investigator should determine by other inspectional means the extent of the firm's compliance with CGMPR's. Inspectional observations and findings that CGMPR's are not being followed are to be cited on a List of Inspectional Observations, FDA-483, for both prescription and non-prescription drugs. Organization and Personnel [21 CFR 211 Subpart B]

The firm must have a quality control department that has the responsibility and authority as described in the referenced CFR. The quality control department must maintain its independence from the production department, and its responsibilities must be in writing. Obtain the name, title and individual responsibilities of corporate officers and other key employees as indicated in the IOM. In the drug industry, an employee's education and training for their position has a significant impact on the production of a quality product. Report whether the firm has a formalized training program, and describe the type of training received. The training received by an employee should be documented. Quality control must do product annual review on each drug manufactured, and have written annual