行业指南药品检测结果OOS调查指南

Guidance for Industry， Investigating Out of Specification

(OOS) Test Results for Pharmaceutical Production

行业指南：

药品检验结果OOS的调查

DRAFT GUIDANCE

指南草案

U.S. Department of Health and Human Services

Food and Drug Administration

Center for Drug Evaluation and Research (CDER)

September 1998

CP #

TABLE OF CONTENTS目录

I. INTRODUCTION 序言. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . .. . . . .. . . .. . . 1 II. BACKGROUND . 背景. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ... . . . . . . 1 III. IDENTIFYING AND ASSESSING OOS TEST RESULTS OOS检验结果的判断和评估. . .. 2 A. Responsibility of the Analyst 检验员的责任. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 2 B. Responsibilities of the Supervisor主管的责任. . . . . . . . . . . . . . . .. . . . . .. . . . . . . . . . . . . . . .. . . . .3

IV. INVESTIGATING OOS TEST RESULTS OOS 检验结果的调查. . . . . . . . . . . . . . . . . . . .. 5 A. General Investigational Principles . . 一般调查原则. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 B. Laboratory Phase of an Investigation . 实验室的调查阶段 . . . . . . . . . . . . . . . .. . . .. . . . . . . . . . . . 6 V. CONCLUDING THE INVESTIGATION . .调查结论 . . . . . . . . . . . . . . . . . . . . . . . . .. . .. . . . . . . 10 A. Interpretation of Investigation Results . 调查结果的解释 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10 B. Reporting . . .报告 . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11

This guidance has been prepared by the Office of Compliance/Division of Manufacturing and Product

Quality, Center for Drug Evaluation and Research (CDER) at the Food and Drug Administration. This guidance document represents the Agency’s current thinking on evaluating OOS test results. It does not create or confer any rights for or on any person and does not operate to bind FDA or the public. An alternative approach may be used if such approach satisfies the requirements of the applicable statute, regulations, or both.

本指南由FDA的CDER的达标办公室/制造、产品、质量分部起草，本指南阐明了机构关于评估OOS检验结果的现行的想法。它不会创造或赠与任何人任何权力，也不会约束FDA或公众。如果其他可选择的相接近的指南能满足适用的法令和法规的要求，也可以使用。

GUIDANCE FOR INDUSTRY1

Investigating Out of Specification (OOS) Test Results

for Pharmaceutical Production 行业指南：药品检验结果OOS的调查

I. INTRODUCTION 序言

This guidance for industry provides the Agency’s current thinking on how to evaluate suspect, or out of specification (OOS), test results. For purposes of this document, the term OOS results includes all suspect results that fall outside the specifications or acceptance criteria established in new drug applications, official compendia, or by the manufacturer.

本行业指南反应了FDA关于如何评估怀疑的或OOS检验结果的现行想法，本指南的目的，OOS结果包括超出了新药申请材料、

法定标准、生产商建立的可接受标准或规格的所有可疑的结果。

This guidance applies to laboratory testing during the manufacture of active pharmaceutical ingredients, excipients, and other

components and the testing of finished products to the extent that current good manufacturing practices (CGMP) regulations apply (21 CFR parts 210 and 211). Specifically, the guidance discusses how to investigate suspect, or OOS test results, including the responsibilities of laboratory personnel, the laboratory phase of the investigation, additional testing that may be necessary, when to expand the investigation outside the laboratory, and the final evaluation of all test results.

本指南适用于API、赋形剂和其它组分生产的实验室检验和CGMP法规应用的成品检验。特别的，指南讨论了如何调查可疑的或OOS检验结果，包括了实验室人员的责任、实验室阶段调查、必须的额外试验，何时进行实验室范围外的调查和对所有检验结果的最终评估。 II. BACKGROUND 背景

FDA considers the integrity of laboratory testing and documentation records to be of fundamental importance during drug

manufacturing. Laboratory testing, which is required by the CGMP regulations (§ 211.165), is necessary to confirm that components, containers and closures, inprocess materials, and finished products conform to specifications, including stability. Testing Specifications must be scientifically sound and appropriate (21 CFR 211.160(b)), and test procedures must be validated as to their accuracy, reliability, and suitability under actual conditions of use (21 CFR 211.194(a)(2)). For products that are the subjects of NDAs, ANDAs, or INDs, specifications are contained in the application. Specifications for non-application products may be found in official compendia, or established by the manufacturer.

FDA认为在药品生产中实验室检验和文件记录的完整性是基本重要的。CGMP要求的实验室检验，必须确定成分、容器和封口材料、生产用辅料、成品符合标准要求，包括稳定性。检验标准必须是科学正确和适当的（1 CFR 211.160(b)，检验方法必须验证现行使用条件下的正确性、线性和适应性(21 CFR 211.194(a)(2))，如果是用于NDAs, ANDAs, 或 INDs申请的产品，申请材料中应包括标准。 如果是非申请产品的质量标准，可以在法定标准中找到或由企业自已建立。

Although the subject of this document is OOS results, much of the guidance may be useful for examining results that are out of trend. also supports analytical and process validation efforts. General CGMP regulations covering laboratory operations can be found in part 211, subparts I (Laboratory Controls) and J (Records and Reports). These regulations provide for the establishment of scientifically sound and appropriate specifications, standards, and test procedures that are designed to ensure that components and containers of drug products conform to the established standards. Section 211.165(f) of the CGMP regulations specifies that products that fail to meet established standards and other relevant quality control criteria will be rejected.

尽管本指南的目的是OOS结果，其中许多部分对于调查超出趋势以外的结果也是有用的，对分析和工艺验证也有用。有关实验室操作一般性CGMP法规可以在211部分，分目I (实验室控制)和分目 J (报告和记录)找到。这些法规规定了科学正确和适当的用于保证制剂的成分和容器符合建立标准的规格、标准和检验方法的建立。CGMP的211.165(f)章节规定不符合既定标准和其它相关质量控制标准的产品不得放行。

III. IDENTIFYING AND ASSESSING OOS TEST RESULTS OOS检验结果的判断和评估

FDA regulations require that an investigation be conducted whenever an OOS test result is obtained. The purpose of the investigation is to determine the cause of the OOS. Even if a batch is rejected based on an OOS result, the investigation is necessary to determine if the result is associated with other batches of the same drug product or other products. Batch rejection does not negate the need to perform the investigation. The regulations require that a written record of the investigation be made including the conclusions of the investigation and follow-up (211.192).

FDA法规要求当OOS检验结果出现时应该进行调查，调查的目的是确定引起OOS的原因。即使因OOS结果判断了不合格批，