fda行业指南中英对照待完成

F D A行业指南中英对
照待完成
-CAL-FENGHAI.-(YICAI)-Company One1
Guidance for Industry
Container Closure Systems for Packaging Human Drugs and
BiologicsChemistry, Manufacturing and Controls Documentation
行业指南
人用药品及生物制品的包装容器和封装系统：化学，生产和控制文件
指南发布者：美国FDA下属的CDER及CBER
发布日期：May 1999
TABLE OF CONTENTS目录
I.INTRODUCTION介绍
II.BACKGROUND 背景
A.Definitions 定义
B.CGMP, CPSC and USP Requirements on Containers and Closures. CGMP, CPSC和USP对容器
和密封的要求
C.Additional Considerations 其他需要考虑的事项
III.QUALIFICATION AND QUALITY CONTROL OF PACKAGING COMPONENTS包装组件的合格要求以及质量控制
A.Introduction 介绍
B.General Considerations 通常要求
rmation That Should Be Submitted in Support of an Original Application for Any Drug
Product 为支持任何药品的原始申请所必须提供的信息
D.Inhalation Drug Products 吸入性药品
E.Drug Products for Injection and Ophthalmic Drug Products 注射剂和眼科用药
F.Liquid-Based Oral and Topical Drug Products and Topical Delivery Systems 液体口服和外用药
品和外用给药系统
G.Solid Oral Dosage Forms and Powders for Reconstitution 口服固体剂型和待重新溶解的粉末
H.Other Dosage Forms 其他剂型
IV.POSTAPPROVAL PACKAGING CHANGES 批准后的包装变更
V.TYPE III DRUG MASTER FILES 药品主文件第III类
A.General Comments 总体评述
rmation in a Type III DMF 第III类DMF中包括的信息
VI.BULK CONTAINERS 大包装容器
A.Containers for Bulk Drug Substances 用于原料药的容器
B.Containers for Bulk Drug Products 用于散装药品的容器
ATTACHMENT A 附件A
REGULATORY REQUIREMENTS 药政要求
ATTACHMENT B 附件B
COMPLIANCE POLICY GUIDES THAT CONCERN PACKAGING 关于包装，所适用的政策指南ATTACHMENT C 附件C
EXTRACTION STUDIES “提取性”研究
ATTACHMENT D 附件D
ABBREVIATIONS 缩略语
ATTACHMENT E 附件E
REFERENCES 参考文献
GUIDANCE FOR INDUSTRY1
Container Closure Systems for Packaging Human Drugs and BiologicsChemistry,
Manufacturing and Controls Documentation
I．INTRODUCTION介绍
This document is intended to provide guidance on general principles2 for submitting information on
packaging materials used for human drugs and biologics.3 This guidance supersedes the FDA Guideline for Submitting Documentation for Packaging for Human Drugs and Biologics , issued in February 1987 and the packaging policy statement issued in a letter to industry dated June 30, 1995 from the Office of Generic Drugs.4 This guidance is not intended to describe the information that should be provided
about packaging operations associated with drug product manufacture. 本文件目的是为递交人用药品和生物制品的包装信息提供总体原则指南。

本文件替代了FDA在1987年2月发布的另一份指南，以及替代了仿制药办公室在1995年6月30日向行业内发布的包装政策声明信。

本指南不描述药品的包装操作。

Approaches which differ from those described in this guidance may be followed, but the applicant is encouraged to discuss significant variations in advance with the appropriate CDER chemistry review staff or CBER review staff. This is to prevent applicants or sponsors from spending unnecessary time and effort in preparing a submission that the FDA may later determine to be unacceptable. 可以采取与本指南的内容不一致的措施，但是我们建议申请人就明显的差异预先与CDER或CBER的审核人员进行讨论。

这样做的目的是为了避免申请人或发起人花费不必要的时间和努力准备申报资料，而这种申报资料经FDA认定是不可接受的。

II． BACKGROUND背景
The Federal Food, Drug, and Cosmetic Act (the Act) mandates the need for adequate information
related to packaging materials. Section 501(a)(3) of the Act states that a drug is deemed to be
adulterated "if its container is composed, in whole or in part, of any poisonous or deleterious substance which may render the contents injurious to health...." In addition, section 502 of the Act states that a drug is considered misbranded if there are packaging omissions. Also, section 505 of the Act requires a full description of the methods used in, and the facilities and controls used for, the packaging of drugs (see Attachment A). 联邦食品、药品和化妆品法案（简称“法案”）要求必须提供包装材料的充分信息。

法案的第501(a)(3)部分规定，如果某个药品的包装材料含有有毒、有害的物质，导致药品损坏健康，那么该药品为劣药。

另外，法案的第502部分规定，如果某药品在包装方面有缺失，则被认为是贴错标签。

还有，法案第505部分要求详细描述包装药品时所用的方法，所用的设施和控制措施（见附件A）。

Section 505(b)(1)(D) of the Act states that an application shall include a full description of the methods used in, the manufacturing, processing and packing of such drug. This includes facilities and controls used in the packaging a drug product. 法案的第505(b)(1)(D)部分规定，申请人必须完整描述该药品的生产、加工和包装。

其中包括包装药品时的设施和控制措施。

A.Definitions5定义
Materials of construction6 refer to the substances ., glass, high density polyethylene (HDPE)
resin, metal) used to manufacture a packaging component. 组成材料是指用来生产包装组件
的物质（例如玻璃，HDPE树脂，金属）
A packaging component means any single part of a container closure system. Typical
components are containers ., ampules, vials, bottles), container liners ., tube liners), closures .,
screw caps, stoppers), closure liners, stopper overseals, container inner seals, administration
ports ., on large-volume parenterals (LVPs)), overwraps, administration accessories, and
container labels. A primary packaging component means a packaging component that is or
may be in direct contact with the dosage form. A secondary packaging component means a
packaging component that is not and will not be in direct contact with the dosage form. 包装
组件是指一个容器/封装系统的任何单独部分。

通常的组件有容器（例如安瓿，西林瓶，
瓶子），容器垫，封装，封装垫…….等，包括给药附件和容器标签。

一级包装组件是指与
制剂直接接触的组件，或者可能会直接接触的组件。

二级包装组件是指不会与制剂直接
接触的组件。

A container closure system refers to the sum of packaging components that together contain
and protect the dosage form. This includes primary packaging components and secondary
packaging components, if the latter are intended to provide additional protection to the drug product. A packaging system is equivalent to a container closure system. 容器/封装系统是指包装组件的组合，在一起盛装和保护制剂。

这包括一级包装组件和二级包装组件，后者的目的是为药品提供额外保护。

包装系统就等同于容器/封装系统。

A package or market package7 refers to the container closure system and labeling, associated
components ., dosing cups, droppers, spoons), and external packaging ., cartons or shrink
wrap). A market package is the article provided to a pharmacist or retail customer upon
purchase and does not include packaging used solely for the purpose of shipping such articles.
包装或上市包装是指容器/封装系统，以及标签，相关组件（例如量杯，滴管，药匙
等），以及外包装（例如纸箱或收缩包装）。

上市包装是指提供给药剂师或零售消费者的包装物件，不包括仅仅用于运输目的的包装物件。

Quality refers to the physical, chemical, microbiological, biological, bioavailability, and stability attributes that a drug product should maintain if it is to be deemed suitable for therapeutic or diagnostic use. In this guidance, the term is also understood to convey the properties of safety, identity, strength, quality, and purity (see 21 CFR (a)). 质量是指：一种药品可被看做具有治疗或诊断用途时，它所具有的理化、微生物、生物、生物利用度以及稳定性方面的品
质。

在本指南中，此术语还被理解为安全性，等效性，规格，质量和纯度等性质（见21 CFR (a)）。

An extraction profile refers to the analysis (usually by chromatographic means) of extracts
obtained from a packaging component. A quantitative extraction profile is one in which the amount of each detected substance is determined. 提取性特征是指对从包装组件中所得提取物的分析（通常用色谱的方法）。

定量提取性特征是指所提取的每种成分的测得量。

B.CGMP, CPSC and USP Requirements on Containers and Closures CGMP, CPSC和USP对容器
和密封的要求
Current good manufacturing practice (CGMP) requirements for the control of drug product
containers and closures are included in 21 CFR Parts 210 and 211. A listing of the relevant
sections is provided in Attachment A. In addition, a listing of Compliance Policy Guides that
deal with packaging issues is provided in Attachment B. References in this guidance to CGMP regulations are provided for completeness. For additional information, refer to the FDA
Compliance Program Guidance Manual for Pre-Approval Inspections/Investigations which
describes specific responsibilities for CDER scientists and for field investigators. 现行良好生产规范（CGMP）关于“药品容器/封装的控制”的要求在21 CFR的第210和211部分。

相关部分的清单请见附件A。

另外，关于包装方面的“Compliance Policy Guides达标政策指南”清单请见附件B。

本指南关于CGMP的参考文献对本指南有补充作用。

更多的信
息，请参考“FDA达标项目指南手册”，以指导“批准前检查/调查”，里面描述了
CDER科学家和现场检查的具体职责。

The FDA requirement for tamper-resistant closures is included in 21 CFR and the Consumer Product Safety Commission (CPSC) requirements for child-resistant closures are included in 16 CFR 1700. An outline of these and other applicable regulatory requirements is provided in
Attachment A. FDA关于防篡改封装的要求请见21 CFR ，消费者产品安全委员会（CPSC）对“儿童防护封装”的要求请见16 CFR 1700。

附件A提供了这些法规要求和其他相应法规要求的要点。

The United States Pharmacopeial Convention has established requirements for containers
which are described in many of the drug product monographs in The United States
Pharmacopeia/National Formulary (USP/NF). For capsules and tablets, these requirements
generally relate to the design characteristics of the container ., tight, well-closed or light-
resistant). For injectable products, materials of construction are also addressed ., "Preserve in single-dose or in multiple-dose containers, preferably of Type I glass, protected from light").
These requirements are defined in the "General Notices and Requirements" (Preservation,
Packaging, Storage, and Labeling) section of the USP. The requirements for materials of
construction are defined in the "General Chapters" of the USP (see Attachment A). 美国药典委员会建立了对容器的要求，这在“美国药典/国家处方集（USP/NF）”的各药品专论中进行了描述。

对于胶囊和片剂，这些要求通常与容器的设计特征有关（例如牢固，密闭良好，或者避光）。

对于注射剂产品，还有生产材料的要求（例如，“保存在单次给药或多次给药容器中，最好采用I型玻璃，避光”）。

这些要求在美国药典的“通则和要求”（保存，包装，贮存和标签）部分。

关于生产材料的要求在美国药典的“总章”
（请见附件A）。

C.Additional Considerations 其他需要考虑的事项
1.Submissions of INDs
The packaging information in the chemistry, manufacturing, and controls section of an
IND usually includes a brief description of the components, the assembled packaging
system and any precautions needed to ensure the protection and preservation of the
drug substance and drug product during their use in the clinical trials.
For general guidance regarding the container closure system information to be
submitted for phase 1 studies, refer to the FDA guidance for industry Content and
Format of investigational New Drug Applications(INDs) for Phase 1 Studies of Drugs,
Including Well-Characterized, Therapeutic, Biotechnology-derived Products (November
1995).
General guidance regarding the container closure system information to be submitted
for phase 2 or phase 3 studies will be provided in the FDA guidance for industry INDs
for Phase 2 and 3 Studies of Drugs, Including Specified Therapeutic Biotechnology-
Derived Products, Chemistry, Manufacturing, and Controls Content and Format, when
finalized (draft guidance published April 21, 1999).
2.Submissions on Packaging of a Drug Product by Another Firm
a.Contract Packager
A contract packager is a firm retained by the applicant to package a drug
product. The applicant remains responsible for the quality of the drug
product during shipping, storage, and packaging.
The information regarding the container closure system used by a contract
packager that should be submitted in the CMC section of an application (NDA,
ANDA, or BLA), or in a DMF which is referenced in the application, is no
different from that which would be submitted if the applicant performed its
own packaging operations. If the information is provided in a DMF, then a
copy of the letter of authorization (LOA) for the DMF should be provided in
the application (see section .
b.Repackager8
A repackager is a firm that buys drug product from the drug product
manufacturer or distributor and repackages it for sale under a label different
from that of the manufacturer. The repackager is responsible for ensuring
the quality and stability of the repackaged drug prpoduct. The repackaging
operation is required to e in compliance with CGMPs (21 CFR Part 211), and
there are limits to the expiration period that may be used with the
repackaged product unless the repackager conducts stability studies.9
Packaging qualification information is not required if the repackager uses the
same container closure system approved in the original application.
All significant phases of the manufacturing and processing of a drug product
(including packaging) should be described as part of the CMC section of an
application (NDA, ANDA or BLA), or in a DMF referenced in the application.
The only exception is the repackaging of solid oral drug products for which an
approved application already exists.10 For biologics, repackaging is
considered a step in the manufacturing process for which licensing is
required (21 CFR (u) and 601)
III.QUALIFICATION AND QUALITY CONTROL OF PACKAGING COMPONENTS包装组件的合格要求以及质量控制
a)Introduction介绍
CDER and CBER approve a container closure system to be used in the packaging of a human
drug or biologic as part of the application (NDA, ANDA or BLA) for the drug or biologic. A
packaging system found acceptable for one drug product is not automatically assumed to be
appropriate for another. Each application should contain enough information to show that
each proposed container closure system and its components are suitable for its intended use.
药品或生物制品的（NDA, ANDA或BLA）申请时，作为其中一部分的容器/封装系统也由
CDER或CBER批准。

某个容器/封装系统被批准用于一个药品，并不自动被认定为适用于
其他药品。

在申请资料中应有充分的信息显示所采用的容器/封装系统和其组件适应这个
用途。

The type and extent of information that should be provided in an application will depend on the dosage form and the route of administration. For example, the kind of information that should be provided about a packaging system for an injectable dosage form or a drug product for inhalation is often more detailed than that which should be provided about a packaging system for a solid oral dosage form. More detailed information usually should be provided for a liquid-based dosage form than for a powder or a solid, since a liquid-based dosage form is more likely to interact with the packaging components. 申请资料中要提供信息的类型和程度取决于剂型和给药途径。

例如，为注射或吸入剂型的包装系统提供的资料往往比固体口服剂型的包装系统所提供的资料要详细。

为液体类制剂的包装系统提供的资料要比粉末或固体制剂要多，因为液体类制剂更容易与包装组件相互作用。

Table 1 illustrates the correlation between the degree of concern regarding the route of administration with the likelihood of packaging component-dosage form interactions for different classes of drug products. 表1说明了“给药途径的受关注程度”与“各类药品的包装组件-制剂相互作用”之间的关系。

Table 1
Examples of packaging Concerns for Common Classes of Drug Products
a For the purposes of this table, the term suspension is used to mean a mixture of two immiscible phases ., solid in liquid or
liquid in liquid). As such, it encompasses a wide variety of dosage forms such as creams, ointments, gels, and emulsions, as
well as suspensions in the pharmaceutical sense.
For the purpose of this guidance, container closure systems for the most common types of
dosage forms will be discussed in terms of five general categories: Inhalation Drug Products
(section ; Drug Products for Injection and Ophthalmic Drug Products (Section ; Liquid-based
Oral and Topical Drug Products and Topical Delivery Systems (section ; Solid Oral Dosage Forms and Powders for Reconstitution (section ; and Other Dosage Forms (section 在本指南中，绝大多数类型的制剂的容器/封装系统将按照5种类型讨论，即：吸入性药品（第部分）；
注射性药品和眼用药品（第部分）；液体口服和外用药品以及外用给药系统（第部
分）；固体口服制剂和待重新溶解的粉末（第部分）；以及其他剂型（第部分）。

b)General Considerations 通常要求
Suitability refers to the tests and studies used and accepted for the initial qualification of a component or a container closure system for its intended use. Quality control (QC) refers to the tests typically used and accepted to establish that, after the application is approved, the components and the container closure system continue to possess the characteristics
established in the suitability studies. The subsections on associated components and secondary components describe the tests and studies for establishing suitability and quality control for these types of components. However, the ultimate proof of the suitability of the container closure system and the packaging process is established by full shelf life stability studies. 适应性是指：为最初确定一个组件或容器/封装系统是否适用于其用途，所采用和接受的试验和研究。

质量控制（QC）是指常规使用的试验和被接受的试验，用来证明（申请被批准后）组件和容器/封装系统继续具有在适应性研究中所建立的特征。

“相关组件”和“二级组件”两个部分描述了为建立这种类型的组件的适应性和质量控制而进行的试验和研究。

但是，容器/封装系统和包装工艺的适应性的最终证据要靠完整的有效期试验研究来建立。

i.Suitability for the Intended Use 关于目的用途的适应性
Every proposed packaging system should be shown to be suitable for its intended use:
it should adequately protect the dosage form; it should be compatible with the
dosage form; and it should be composed of materials that are considered safe for use
with the dosage form and the route of administration. If the packaging system has a
performance feature in addition to containing the product, the assembled container
closure system should be shown to function properly. 每一个拟采用的包装系统都应
能显示其目的用途的适应性：它必须充分的保护制剂；必须能与制剂相容；在特
定的制剂和给药途径下，其组成材料必须安全。

如果包装系统除了能盛装产品，
还有其功能特征，那么组装后的容器/封装系统应能显示其功能正常发挥。

Information intended to establish suitability may be generated by the applicant, by
the supplier of the material of construction or the component, or by a laboratory
under contract to either the applicant or the firm. An adequately detailed description
of the tests, methods, acceptance criteria, reference standards, and validation
information for the studies should be provided. The information may be submitted
directly in the application or indirectly by reference to a DMF. If a DMF is used, a
letter authorizing reference ., letter of authorization (LOA)) to the DMF must be
included in the application (see section . 用来证明适应性的信息可以由（药品）申
请人提供，也可以由材料或组件的供应商提供，或者由他们的外协实验室提供。

必须提供以下详细描述资料：试验，方法，接受标准，标准品，以及验证。

这些
信息可直接放入申请资料递交，也可以用非直接的方法即DMF，然后由FDA审
核DMF。

如果使用了DMF，那么必须在申请资料中附一份授权书（LOA），请见
部分。

General issues concerning protection, compatibility, safety and performance of
packaging components and/or systems are discussed below. In this guidance,
component functionality and drug delivery will also be addressed in connection with
specific dosage forms and routes of administration (see sections , , , , and . 下面讨论
了包装组件和/或系统的一些问题，有：保护，相容性，安全以及功能。

本指南中，组件功能和给药系统将与特定剂型和给药途径一并阐述（请见, , , , and 部
分）。

1.Protection 保护
A container closure system should provide the dosage form with adequate
protection from factors ., temperature, light) that can cause a degradation in
the quality of that dosage form over its shelf life. Common causes of such
degradation are: exposure to light, loss of solvent, exposure to reactive
gases ., oxygen), absorption of water vapor, and microbial contamination. A
drug product can also suffer an unacceptable loss in quality if it is
contaminated by filth. 容器/封装系统应能为制剂提供充足的保护，保证
在有效期内能避免一些因素（例如温度，光线）造成此制剂的品质降
级。

造成这种降级的因素通常有：暴露在光线中，溶剂的减失，暴露在
活泼性气体中（例如氧气），吸收水蒸气，微生物污染。

药品还可能因
为被污物污染而造成无法接受的品质降低。

Not every drug product is susceptible to degradation by all of these factors.
Not all drug products are light sensitive. Not all tablets are subject to loss of
quality due to absorption of moisture. Sensitivity to oxygen is most
commonly found with liquid-based dosage forms. Laboratory studies can be
used to determine which of these factors actually have an influence on a
particular drug product. 并非所有药品都易于受上述因素影响而品质降
级。

不是所有的药品都对光线敏感。

不是所有的片剂会因吸收水蒸气而
品质降低。

对氧气的敏感最常见于液体制剂。

对于某个特定药品，可以
用实验室研究的方法确定哪种因素真正会造成影响。

Light protection11 is typically provided by an opaque or amber-colored
container or by an opaque secondary packaging component ., cartons or
overwrap). The USP test for light transmission (USP <661>) is an accepted
standard for evaluating the light transmission properties of a container.
Situations exist in which solid and liquid-based oral drug products have been
exposed to light during storage because the opaque secondary packaging
component was removed, contrary to the approved labeling and the USP
monograph recommendation. A firm, therefore, may want to consider using
additional or alternate measures to provide light protection to these drug
products when necessary. 避光保护通常采用不透明或棕色容器，或采用
不透明的二级包装组件（例如纸箱或外包装纸）。

美国药典中的光透过
试验（请见USP<661>）是一个被认可的标准，用来评价一个容器的光透
过性质。

有些情况下，贮藏中的固体和液体口服制剂会暴露在光线中，
原因是不透明的二级包装组件被去掉了，导致与已经批准的标签不符，
与美国药典的专论推荐不符。

Loss of solvent can occur through a permeable barrier ., a polyethylene
container wall), through an inadequate seal, or through leakage. Leaks can
develop through rough handling or from inadequate contact between the
container and the closure ., due to the buildup of pressure during storage).
Leaks can also occur in tubes due to a failure of the crimp seal. 溶剂减失会
发生于可透过性屏障（例如聚乙烯容器壁），密封不严，或者泄露。

泄
露可能是因为粗暴的操作或者容器与封装部分结合不紧密（例如贮藏期
间的压力积累）。

泄露还可能发生于瓶子，原因是卷曲密封没有做好。

Water vapor or reactive gases ., oxygen) may penetrate a container closure
system either by passing through a permeable container surface ., the wall of
a low density polyethylene (LDPE) bottle) or by diffusing past a seal. Plastic
containers are susceptible to both routes. Although glass containers would
seem to offer better protection, because glass is relatively impermeable,
glass containers are more effective only if there is a good seal between the
container and the closure. 水蒸气或者活泼性气体（例如氧气）可能穿过
容器的封装系统，途径可能是穿过透过性容器表面（例如LDPE瓶
壁），或者通过密封口散播。

塑料容器易于发生上两种情况。

虽然玻璃
容器看起来能提供更好的保护，因为玻璃是相对非透过性的，但是玻璃
容器只能在容器和封装密封严密的情况下才更为有效。

Protection from microbial contamination is provided by maintaining
adequate container integrity after the packaging system has been sealed. An
adequate and validated procedure should be used for drug product
manufacture and packaging. 避免微生物污染，在于包装系统密封后保持
容器的完整不被破坏。

药品生产和包装中必须使用恰当的、经过验证的
方法。

patibility 相容性
Packaging components that are compatible with a dosage form will not
interact sufficiently to cause unacceptable changes in the quality of either
the dosage form or the packaging component. 与某制剂相容的包装组件不
会与制剂发生过多的作用，以导致制剂或包装组件的质量发生不可接受
的改变。

Examples of interactions include loss of potency due to absorption or
adsorption of the active drug substance, or degradation of the active drug
substance induced by a chemical entity leached from a packaging component;
reduction in the concentration of an excipient due to absorption, adsorption
or leachable-induced degradation; precipitation; changes in drug product pH;
discoloration of either the dosage form or the packaging component; or
increase in brittleness of the packaging component. 相互作用的例子包括：
吸收或者吸附活性药品成分造成的含量降低，或者从包装组件上脱落的
化学成分引起活性药品成分的分解；由于吸收，吸附，或者脱落物引起
的辅料浓度降低；产品pH值的改变；制剂或者包装组件的变色；或者
包装组件脆性增加。

Some interactions between a packaging component and dosage form will be
detected during qualification studies on the container closure system and its
components. Others may not show up except in the stability studies.
Therefore, any change noted during a stability study that may be attributable
to interaction between the dosage form and a packaging component should
be investigated and appropriate action taken, regardless of whether the
stability study is being conducted for an original application, a supplemental
application, or as fulfillment of a commitment to conduct postapproval
stability studies. 有些包装组件和制剂之间的相互作用可在容器/封装系统
及其组件的合格性研究中发现。

有些则显示不出来，除非是稳定性试
验。

因此，任何在稳定性试验中发现的改变如果是由于制剂和包装组件
的相互作用引起的，那么就必须展开调查，并采取合适的措施，不论这
个稳定性试验是为了一个原始申请而正在进行的，或者是补充申请，或
者是履行“批准后的稳定性试验”。

3.Safety 安全性
Packaging components should be constructed of materials that will not leach
harmful or undesirable amounts of substances to which a patient will be
exposed when being treated with the drug product. This consideration is
especially important for those packaging components which may be in direct
contact with the dosage form, but it is also applicable to any component
from which substances may migrate into the dosage form ., an ink or
adhesive). 包装组件的组成材料应该是不脱落有害物质或过量的物质，而
使接受这个药品治疗的患者暴露于这些物质。

这一点对于那些直接与制
剂接触的包装组件尤其重要，不过，任何有可能释放物质进入到制剂中
的组件也适用于此要求（例如墨水或粘合剂）。

Making the determination that a material of construction used in the
manufacture of a packaging component is safe for its intended use is not a
simple process, and a standardized approach has not been established. There
is, however, a body of experience which supports the use of certain
approaches that depend on the route of administration and the likelihood of
interactions between the component and the dosage form (see Table 1). 判
定生产包装组件的材料相对于其用途是否安全并不是一个简单的过程，
现在还没有建立一个标准化的方法。

不过，根据给药途径和组件与制剂
相互作用的可能性，有大量的经验可以支持某些方法的应用（见表
1）。

For a drug product such as an injection, inhalation, ophthalmic, or
transdermal, a comprehensive study is appropriate. This involves two parts:
first, an extraction study12 on the packaging component to determine which
chemical species may migrate into the dosage form (and at what concentration); and, second, a toxicological evaluation of those substances which are extracted to determine the safe level of exposure via the label specified route of administration. This technique is used by the Center for Food Safety and Applied Nutrition (CFSAN) to evaluate the safety of substances that are proposed as indirect food additives ., polymers or additives that may be used in for packaging foods).13对于一些药品，例如注射液、吸入性药品、眼科用药或透皮药品，需要做全面的研究。

包括两个部分：首先，进行包装组件的提取性试验，以确定哪些类型的化学物质会混入制剂（以及混入的数量）；其次，对提取出的物质进行毒理学评价，确定：按照标签指定的给药途径，安全的暴露水平。

这是美国食品安全与应用营养学中心（CFSAN）采用的一种方法，用来评价一些被当作间接食品添加剂的物质的安全性（例如聚合物或者可用来包装食品的添加剂）。

The approach for toxicological evaluation of the safety of extractables should be based on good scientific principles and take into account the specific container closure system, drug product formulation, dosage form, route of administration, and dose regimen (chronic or short-term dosing). 可提取物的毒理性评价方法应基于良好的科学原则，并考虑到具体的容器/封装系统，药品处方，剂型，给药途径以及给药方案（长期或短期给药）。

For many injectable and ophthalmic drug products (see sections and , data from the USP Biological Reactivity Tests and USP Elastomeric Closures for Injections tests will typically be considered sufficient evidence of material safety. 对于许多注射剂和眼科药品（见和部分），USP 生物反应试验和USP 注射用橡胶封装试验所获得的数据通常被看作是材料安全性的充分证据。

For many solid and liquid oral drug products, an appropriate reference to the indirect food additive regulations (21 CFR 174-186) promulgated by CFSAN for the materials of construction used in the packaging component will typically be considered sufficient. Although these regulations do not specifically apply to materials for packaging drug products, they include purity criteria and limitations pertaining to the use of specific materials for packaging foods that may be acceptable for the evaluation of drug product packaging components. Applicants are cautioned that this approach may not be acceptable for liquid oral dosage forms intended for chronic use (see section 对于许多固体和液体口服药品的包装组件生产材料，恰当的参考由CFSAN发布的“间接食品添加剂法规”（21 CFR 174-186）通常被认为是充分的。

虽然这些法规不是专门适用于药品包装材料的，但是它们包括根据特定食品包装材料的用途而制订的洁净标准和限制，可能能被接受用来评价药品的包装组件。

申请人要注意的是：对于长期使用的液体口服制剂（见部分），上面的方法不能被接受。

For drug products that undergo clinical trials, the absence of adverse
reactions traceable to the packaging components is considered supporting
evidence of material safety. 如果是正在进行临床试验的药品，包装组件没
有引起不良反应，即可作为材料安全性的支持证据。

Safety assessments for specific dosage forms are discussed further in section
III of this guidance. 具体剂型的安全性评价将在本指南的第III部分进一步
讨论。

4.Performance 功能
Performance of the container closure system refers to its ability to function
in the manner for which it was designed. A container closure system is often
called upon to do more than simply contain the dosage form. When
evaluating performance, two major considerations are container closure
system functionality and drug delivery. 容器/封装系统的功能是指其按照设
计发挥功能的能力。

容器/包装系统通常不仅仅用来包装制剂。

在评价功
能时，有两个主要方面要考虑：容器/封装系统的功能性和药品输送。

a)Container Closure System Functionality 容器/封装系统的功能性
The container closure system may be designed to improve patient
compliance ., a cap that contains a counter), minimize waste ., a
two-chamber vial or IV bag), improve ease of use ., a prefilled
syringe), or have other functions. 容器/封装系统可被设计成能提
高患者适用性（例如，包括计量装置的瓶盖），减少浪费（例
如，双腔药瓶或静脉输液袋），方便使用（例如，预灌装
针），或者其他功能。

b)Drug Delivery 药品输送
Drug delivery refers to the ability of the packaging system to deliver
the dosage form in the amount or at the rate described in the
package insert. Some examples of a packaging system for which
drug delivery aspects are relevant are a prefilled syringe, a
transdermal patch, a metered tube, a dropper or spray bottle, a dry
powder inhaler, and a metered dose inhaler. 药品输送是指包装系
统按照药品说明书的描述输出一定量制剂或按照一定速度输出
制剂的能力。

一些和药品输送有关的包装系统的例子有：预灌
装针，透皮贴剂，定量管，滴管或喷雾瓶，干粉吸入器，以及
定量吸入器。

Container closure system functionality and/or drug delivery are
compromised when the packaging system fails to operate as
designed. Failure can result from misuse, faulty design,。