FDA QC实验室检查指南.docx

1、FDA QC实验室检查指南GUIDE TO INSPECTIONS OF PHARMACEUTICAL QUALITY CONTROL LABORATORIES 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). 1. INTRODU

2、CTION The pharmaceutical quality control laboratory serves one of the most important functions in pharmaceutical production and control. A significant portion of the CGMP regulations (21 CFR 211) pertain to the quality control laboratory and product testing. Similar concepts apply to bulk drugs. Thi

3、s inspection guide supplements other inspectional information contained in other agency inspectional guidance documents. For example, Compliance Program 7346.832 requiring pre-approval NDA/ANDA inspections contains general instructions to conduct product specific NDA/ANDA inspection audits to measur

4、e compliance with the applications and CGMP requirements. This includes pharmaceutical laboratories used for in-process and finished product testing. 2. OBJECTIVE The specific objective will be spelled out prior to the inspection. The laboratory inspection may be limited to specific issues, or the i

5、nspection may encompass a comprehensive evaluation of the laboratorys compliance with CGMPs. As a minimum, each pharmaceutical quality control laboratory should receive a comprehensive GMP evaluation each two years as part of the statutory inspection obligation. In general these inspections may incl

6、ude - the specific methodology which will be used to test a new product - a complete assessment of laboratorys conformance with GMPs - a specific aspect of laboratory operations 3. INSPECTION PREPARATION FDA Inspection Guides are based on the team inspection approach and our inspection of a laborato

7、ry is consistent with this concept. As part of our effort to achieve uniformity and consistency in laboratory inspections, we expect that complex, highly technical and specialized testing equipment, procedures and data manipulations, as well as scientific laboratory operations will be evaluated by a

8、n experienced laboratory analyst with specialized knowledge in such matters. District management makes the final decision regarding the assignment of personnel to inspections. Nevertheless, we expect investigators, analysts and others to work as teams and to advise management when additional experti

9、se is required to complete a meaningful inspection. Team members participating in a pre-approval inspection must read and be familiar with Compliance Program 7346.832, Pre-Approval Inspections/Investigations. Relevant sections of the NDA or ANDA should be reviewed prior to the inspection; but if the

10、 application is not available from any other source, this review will have to be conducted using the companys copy of the application. Team members should meet, if possible, prior to the inspection to discuss the approach to the inspection, to define the roles of the team members, and to establish g

11、oals for completion of the assignment. Responsibilities for development of all reports should also be established prior to the inspection. This includes the preparation of the FDA 483. The Center for Drug Evaluation and Research (CDER) may have issued deficiency letters listing problems that the spo

12、nsor must correct prior to the approval of NDA/ANDAs and supplements. The inspection team is expected to review such letters on file at the district office, and they are expected to ask the plant for access to such letters. The team should evaluate the replies to these letters to assure that the dat

13、a are accurate and authentic. Complete the inspection even though there has been no response to these letters or when the response is judged inadequate. 4. INSPECTION APPROACH A. General In addition to the general approach utilized in a drug CGMP inspection, the inspection of a laboratory requires t

14、he use of observations of the laboratory in operation and of the raw laboratory data to evaluate compliance with CGMPs and to specifically carry out the commitments in an application or DMF. When conducting a comprehensive inspection of a laboratory, all aspects of the laboratory operations will be

15、evaluated. Laboratory records and logs represent a vital source of information that allows a complete overview of the technical ability of the staff and of overall quality control procedures. SOPs should be complete and adequate and the operations of the laboratories should conform to the written procedures. Specifications and analytical procedures should be suitable and, as applicable, in conformance with application commitments and compendial requirements. Evaluate raw laboratory data, laboratory procedures and methods, laboratory equipment,including maintenance and ca