Pharmaceutical Package Integrity
药物包装完整性
Technical Report No. 27
技术报告第27号
PDA
April 1998
1998年4月
1. Preface  前言
This report reviews issues of pharmaceutical product package integrity and provides guidance for evaluating the barrier qualities of a pharmaceutical package. It supersedes the previously issued "PDA Technical Information Bulletin No. 4, Aspects of Container/Closure Int
egrity." In this updated guideline, the term "product package" is used, rather than the term "container/closure system," as it encompasses any nonporous barrier system that protects a pharmaceutical product from the environment. Similarly, the term "package seal" is used generically to mean all types of seals or closure systems. Although it is written to reflect the complexity of all pharmaceutical products and packages, the emphasis throughout the document is clearly on packaging intended for sterile products.
该报告审核了药物产品包装完整性的主题，为评价药物包装的屏障质量的评价提供了指南。它代替了先前发布的“PDA技术信息通告第4号：包装容器/密封完整性方面”。在该升级的指南中，使用术语“产品包装”，而不是术语“包装容器/密封系统”，因为它包含了任何用于保护药物产品隔绝于环境的无孔屏障系统。同样，一般也使用术语“包装密封”，意味着所有类型的密封或密闭系统。虽然，书面上是反映所有药物产品和包装的复杂性，整个文件强调的重点明显是意图用于无菌产品的包装。
This report was written by the following members of the PDA Task Force on Container/Closure Integrity:
该报告由PDA关于容器/密封完整性的特别工作组的下列成员撰写：
Michael C. Carroll, The Liposome Company, Inc.
Vivian F. Denny, Peak to Peak Pharmaceutical Associates
Dana M. Guazzo, Ph.D., The R. W. Johnson Pharmaceutical Research Institute
Mark W. Kaiser, Lancaster Laboratories
Lee E. Kirsch, Ph.D., The University of Iowa
John D. Ludwig, Ph.D., G. D. Searle and Company
Gerald K. Masover, Genentech, Inc.
Jeri L. May, DuPont Merck Pharmaceutical Co.
Jeanne E. Moldenhauer, Ph.D., Fujisawa USA, Inc.
Jean I. Olsen, SmithKline Beecham Pharmaceuticalsreactive翻译
Terri M. Poison, Glaxo Wellcome Inc.
Glenn E. Wright, Eli Lilly & Co.
In addition, the Task Force acknowledges the immense help and support of Michael S. Korczynski, Ph.D. and Russell E. Madsen of PDA. Their editorial assistance and their insight into many of the key issues of package integrity were invaluable contributions to this effort.
另外，特别工作组感谢PDA成员Michael S. Korczynski, Ph.D. 和Russell E. Madsen的很大帮助。他们的编辑辅助和他们对包装完整性很多关键关键观点的洞察，对该成就作了非常大的贡献。
This document should be considered as a guide; it is not intended to establish any mandatory or implied standard.
该文件仅作为指南，不意图设立任何强制或潜在的标准。
2. Introduction  介绍
Product quality can be defined in terms of the ability of a product to perform its desired functions despite the stresses to which it has been exposed before and during its intended use. Pharmaceutical container systems may have a variety of functions including facilitation of product use, prevention of improper use, light protection, containment of the product, maintenance of a microbial barrier, and maintenance of a rarefied product environment. Assurance of package integrity is primarily concerned with product containment and the maintenance of an effective barrier against ingress of microorganisms or potentially reactive gases such as oxygen or water vapor, and sometimes, the maintenance of a vacuum. The information provided in this guideline is intended to assist users in developing integrity assessment strategies for use during the phases of product life.
产品质量可定义为产品保持期望功能的能力，无论在使用前或使用期间暴露于怎样的外界苛刻条件。药物包装系统可以有各种各样的功能，包括使产品容易使用，防止不正确的使用，光照防护，产品的密闭，生物屏障的维持和维持纯净的产品环境。保证包装完整性主要是有关产品密闭和维持有效屏障以防止微生物或潜在反应气体例如氧气或水汽的侵入，有时也用于保持真空。该指南提供的信息是意图帮助用户在产品生命期间的使用时开发出完整性评价
策略。
3.  Integrity Assurance Through Product Development And Product Life
  贯穿产品开发和生命周期的完整性保证
Product package integrity assessment begins during a product's development phase and continues throughout its life cycle, encompassing routine manufacturing and shelf-life stability assessments.
产品包装完整性的评价开始于产品的开发阶段，并持续贯穿整个生命周期，包含日常的生产和保存期间的稳定性评价。
The phases of a product's life cycle include:  产品的生命周期阶段包括：
3.1 Package design, process development, and durability assessment
      包装设计，工艺开发和耐久力评价。
3.2 In-process control
      在线控制
3.3 Product testing
        产品检测
Further reconfirmation of product package integrity should occur when there are major changes in the package system that may affect its integrity, including package design, package materials, and/or when changes occur in the manufacturing processing conditions, including sterilization.
当包装系统包括包装设计、包装材料和/或生产工艺条件包括灭菌出现变更，可能影响包装的完整性时，应进行产品包装完整性的进一步确认。
  The following subsections contain information on the critical factors for assessing a product's  package integrity over its life cycle.
下列分章节包含了整个生命周期内评价产品包装完整性的关键因素信息。
During the package design/process development phase, a thorough knowledge and understanding of the package seal is critical for designing an appropriate package system. Subsection 3.1 describes the nature of these requirements, including a knowledge of the seal location, the sealing mechanism, and the critical factors of design, assembly, and processing that may impact seal quality. The importance of testing the package and processing parameters at extremes is stressed to ensure that the package will be able to withstand the rigors of processing, distribution, and usage.