EMA 의 [Q&A on quality]에서 다음과 같은 내용이 새롭게 올라왔습니다.

Q : What data is required for sterilisation processes of primary packaging materials subsequently used in an aseptic manufacturing process? H+V April 2016

A : 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.

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:

1. I.S. EN ISO 20857:2013Sterilization of Health Care Products - dry Heat - Requirements for the Development, Validation and Routine Control of a Sterilization Process for Medical Devices (ISO 20857:2010);
2. I.S. EN ISO 11135:2014Sterilization of Health-care Products - Ethylene Oxide - Requirements for the Development, Validation and Routine Control of a Sterilization Process for Medical Devices (ISO 11135:2014);
3. I.S. EN ISO 17665-1:2006Sterilization 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;
4. I.S. EN ISO 11137-1:2015Sterilization 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);
5. I.S. EN ISO 11137-2:2015Sterilization of Health Care Products - Radiation - Part 2: Establishing the Sterilization Dose (ISO 11137-2:2013);
6. I.S. EN ISO 11137-3:2006Sterilization of Health Care Products - Radiation - Part 3: Guidance on Dosimetric Aspects.

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.

Dossier requirements

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

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

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.

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.