Sterilisation of the medicinal product, active substance, excipient and primary container - Scientific guideline

Guidance is provided on the selection of appropriate methods of sterilisation for sterile products. Although, terminal sterilisation using a reference condition of the European Pharmacopoeia (Ph. Eur.) is the method of choice whenever possible, this guideline provides information on when other terminal sterilisation processes, sterilising filtration or aseptic processing, (either alone or when combined with an additional post-aseptic processing terminal heat treatment), could be accepted as an alternative. Guidance is provided on the documentation expected for sterile finished products, sterile active substances, sterile excipients and sterile primary containers in a new marketing authorisation application or a variation application for a medicinal product.

This guideline replaces the previous annexes to Pharmaceutical development Decision trees for the selection of sterilisation methods, (human and veterinary). It also revises the information on methods of sterilisation previously described in the note for guidance on manufacture of the finished dosage form (human and veterinary).

This guideline applies to human and veterinary medicines.

Keywords: Active substance, aseptic processing, container, decision trees, excipients, filtration, finished dosage form, sterilisation, sterilisation assurance level, terminal sterilisation, post-aseptic processing terminal heat treatment

Current version

Guideline on the sterilisation of the medicinal product, active substance, excipient and primary container

AdoptedLegal effective date: 01/10/2019Reference Number: EMA/CHMP/CVMP/QWP/850374/2015

Document history

Guideline on the sterilisation of the medicinal product, active substance, excipient and primary container

AdoptedLegal effective date: 01/10/2019Reference Number: EMA/CHMP/CVMP/QWP/850374/2015

Overview of comments received on the ‘Draft guideline on the sterilisation of the medicinal product, active substance, excipients and primary container'

Reference Number: EMA/CHMP/CVMP/QWP/366428/2018 (v.3.11)

Draft guideline on the sterilisation of the medicinal product, active substance, excipient and primary container

Consultation dates: 13/04/2016 to 13/10/2016Draft: consultation closedReference Number: EMA/CHMP/CVMP/QWP/BWP/850374/2015Summary:

This guideline provides guidance on the documentation expected for sterile products in the quality dossier for a marketing authorisation application or a variation application for a medicinal product, (called quality dossier throughout the guideline), and the selection of appropriate methods of sterilisation for sterile products. Although, terminal sterilisation using a reference condition of the European Pharmacopoeia (Ph. Eur) is the method of choice whenever possible, this guideline provides information on when other terminal sterilisation processes, sterilising filtration or aseptic processing, (either alone or when combined with an additional terminal microbial reduction process), could be accepted as an alternative to a reference terminal sterilisation process.

Draft concept paper on the establishment of a guideline on the selection of sterilisation processes for drug products

Consultation dates: 09/04/2014 to 09/07/2014Draft: consultation closedReference Number: EMA/CHMP/CVMP/QWP/128000/2014Summary:

This concept paper addresses the need for a revision of the guidance on the selection of sterilisation methods currently provided for in the annexes to the (separate) human and veterinary development pharmaceutics guidelines, that is, CPMP/QWP/054/98 “Annex to development pharmaceutics: Decision trees for selection of sterilisation methods” adopted in 1999 (1), and EMEA/CVMP/065/99-FINAL “Annex to note for guidance: Development pharmaceutics for veterinary medicinal products: Decision trees for the selection of sterilisation methods” (2) adopted in 2000.

Superseded annex to note for guidance on development pharmaceutics: Decision trees for the selection of sterilisation methods

AdoptedReference Number: CPMP/QWP/054/98

Effective from 01/08/1999 – 01/10/2019

Superseded annex to note for guidance on development pharmaceutics for veterinary products: Decision trees for the selection of sterilisation methods

AdoptedReference Number: EMEA/CVMP/065/99 - Final

Effective from 01/09/2000 – 01/10/2019

Revised note for guidance on limitations to the use of ethylene oxide in the manufacture of medicinal products - Superseded

AdoptedReference Number: EMEA/CVMP/271/01 Rev. 1Summary:

This Rev.1 revision revises the coverpage (only) of the Note for guidance on limitations to the use of ethylene oxide in the manufacture of medicinal products (CPMP/QWP/159/01 & EMEA/CVMP/271/01 Rev.1). None of the text of the note for guidance (guideline) has been changed, only the cover page and the format.

Effective from 01/04/2001 – 01/10/2019

Note for guidance on limitations to the use of ethylene oxide in the manufacture of medicinal products

AdoptedLegal effective date: 01/04/2001Reference Number: CPMP/QWP/159/01

Concept paper on a proposal to limit the applicability of the CPMP/CVMP Note for guidance on limitations to the use of ethylene oxide in the manufacture of medicinal products to veterinary medicinal products - Superseded

AdoptedReference Number: EMA/CHMP/SWP/211900/2015Summary:

The proposed guideline will replace 'Note for Guidance on Limitations to the Use of Ethylene Oxide in the Manufacture of Medicinal Products’ (CPMP/QWP/159/01).