EMA发布无菌生产工艺用无菌内包材所需数据问答

EMA publishes Q&A on data required for sterilized primary packaging materials used in aseptic manufacturing processes

EMA发布无菌生产工艺用无菌内包材所需数据问答

The European Medicines Agency, EMA, recently published questions and answers on quality of packaging materials (H+V April 2016):

EMA最近发布了关于包材质量的问答（H+V 2016年4月）。

"3. What data is required for sterilisation processes of primary packaging materials subsequently used in an aseptic manufacturing process? 用于无菌生产工艺中的内包材的无菌工艺需要什么数据？

Terminal sterilisation of the primary packaging, used subsequently during aseptic processing of the finished product, is a critical process and the sterility of the primary container is a critical quality attribute to ensure the sterility of the finished product. Both need to be assured for compliance with relevant Pharmacopoeial requirements for the finished product and product approval.

用于制剂成品无菌工艺的内包材的最终灭菌是一个关键工艺，内包装容器的无菌是关键质量属性，用以确保制剂成品的无菌性。要确保两者都符合制剂成品药典要求，和产品批准。

The site where sterilisation of the packaging materials takes place may not have undergone inspection by an EU authority and consequently may not hold an EU GMP certificate in relation to this activity1. When GMP certification is not available, certification that the sterilisation has been conducted and validated in accordance with the following ISO standards would be considered to provide an acceptable level of sterility assurance for the empty primary container:

包材灭菌的场所可能没有接受过EU官方检查，因此也就不会持有与此活动相关的EU GMP证书。没有GMP证书时，实施和验证无菌操作符合下列ISO标准的证书将被认为可以证明空内包装容器的无菌保证达到可接受水平。

I.S. EN ISO 20857:2013 Sterilization of Health Care Products - dry Heat - Requirements for the Development, Validation and Routine Control of a Sterilization Process for Medical Devices (ISO 20857:2010);
I.S. EN ISO 20857:2013，卫生产品灭菌—干热---医疗器械无菌工艺研发、验证和常规控制的要求（ISO 20857:2010）
I.S. EN ISO 11135:2014 Sterilization of Health-care Products - Ethylene Oxide - Requirements for the Development, Validation and Routine Control of a Sterilization Process for Medical Devices (ISO 11135:2014);
I.S. EN ISO 11135:2014 卫生产品灭菌—环氧乙烷---医疗器械无菌工艺研发、验证和常规控制的要求（ISO 11135:2014）
I.S. EN ISO 17665-1:2006 Sterilization of Health Care Products - Moist Heat - Part 1: Requirements for the Development, Validation and Routine Control of a Sterilization Process for Medical Devices, and, ISO/TS 17665-2:2009 Sterilization of health care products -- Moist heat -- Part 2: Guidance on the application of ISO 17665-1;
I.S. EN ISO 17665-1:2006 卫生产品灭菌—湿热---第1部分：医疗器械无菌工艺研发、验证和常规控制的要求，以及，ISO/TS 17665-2:2009 卫生产品灭菌—湿热---第2部分：ISO 17665-1应用指南
I.S. EN ISO 11137-1:2015 Sterilization of Health Care Products - Radiation - Part 1: Requirements for Development, Validation and Routine Control of a Sterilization Process for Medical Devices (ISO 11137-1:2006, Including 1:2013);
I.S. EN ISO 11137-1:2015 卫生产品灭菌—辐射---第1部分：医疗器械无菌工艺研发、验证和常规控制的要求 (ISO 11137-1:2006, 包括1:2013)
I.S. EN ISO 11137-2:2015 Sterilization of Health Care Products - Radiation - Part 2: Establishing the Sterilization Dose (ISO 11137-2:2013);
I.S. EN ISO 11137-2:2015 卫生产品灭菌—辐射---第2部分：灭菌剂量设定 (ISO 11137-2:2013)
I.S. EN ISO 11137-3:2006 Sterilization of Health Care Products - Radiation - Part 3: Guidance on Dosimetric Aspects.
I.S. EN ISO 11137-3:2006 卫生产品灭菌—辐射---第2部分：剂量测定法指南
It is the responsibility of the user of the manufacturer of the medicinal product, to ensure the quality, including sterility assurance, of packaging materials. The site where QP certification of the finished product takes place, and other manufacturing sites which are responsible for outsourcing this sterilisation activity, should have access to the necessary information to demonstrate the ongoing qualification status of suppliers of this sterilisation service. This should be checked during inspections. The Competent Authorities may also decide, based on risk, to carry out their own inspections at the sites where such sterilisation activities take place.

药品生产商的用户有责任确保包材质量，包括无菌保证。对外包此类无菌活动负责的QP认证制剂成品的场所，和其它生产场所，应具备有权限获得必要的信息用以证明此无菌操作服务供应商的确认状态。在检查中应对此进行检查。官方机构也可以基于风险来决定对进行无菌操作的工厂自行进行检查。

Dossier requirements: 文档要求

The following details regarding the sterilisation of the packaging components should be included in the dossier:

以下关于包装部件的无菌操作应包括在文档中：

1. The sterilisation method and sterilisation cycle;

无菌处理方法和无菌工艺周期

2. Validation of the sterilisation cycle if the sterilisation cycle does not use the reference conditions stated in the Ph. Eur.;

如果无菌工艺没有使用EP里声明的参考条件，则需要提交无菌工艺验证

3. The name and address of the site of sterilisation and, where available details of GMP certification of the site. Where the component is a CE-marked Class Is sterile device (e.g. sterile syringe), confirmation from the manufacturer that the component is a Class Is sterile device, together with a copy of the declaration of conformity from the Notified Body will suffice.

无菌操作工厂的名称和地址，如果有GMP证书则要提交证书详情。如果部件是CE标识Is无菌装置（例如，无菌注射器），从生产商处确认部件是无菌装置Is级别，同时提交发证明机构的确认声明复印件就足够了。

In the absence of GMP certification or confirmation that the component is a CE-marked Class Is medical device, certification that the sterilisation process has been conducted and validated in accordance with the relevant ISO standards should be provided.

如果没有GMP证书，也没有CE Is级医疗器械部件证明，则要提供所实施和验证的无菌工艺符合相关ISO标准的证明。

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1Sites located in the EU which perform sterilisation of primary packaging components only are not required to hold a Manufacturer's/Importer's Authorisation (MIA). Sites located in the EU, which carry out sterilisation of medicinal products, are required to hold a MIA in relation to these activities."

注：在EU境内实施内包材无菌操作的工厂不需要持有生产许可或进口许可（MIA）。在EU以境内实施医疗器械无菌操作的工厂，需要持有此类活动的MIA。

Source: European Medicines Agency - Quality of medicines Q&A: Part 2 - Packaging.

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