European Union (EU) publishes its final revised EurdraLex Volume 4, Annex 15 guideline

European Union has published its revised EurdraLex Volume 4, Annex 15: Qualification and Validation guidelines. This document is a GMP requirement that manufacturers control the critical aspects of their particular operations through qualification and validation over the life cycle of the product and process.  This Annex describes the principles of qualification and validation which are applicable to the facilities, equipment, utilities and processes used for the manufacture of medicinal products and may also be used as supplementary optional guidance for active substances without introduction of additional requirements to EudraLex, Volume 4, part II.

EurdraLex   Volume 4 gives the rules governing medicinal products in the European Union for the interpretation of the principles and guidelines of good manufacturing practices for medicinal products for human and veterinary use laid down in Commission Directives 91/356/EEC, as amended by Directive 2003/94/EC, and 91/412/EEC respectively. New version of Annex 15 adds four sections which were not including in the previous version of the document. These sections are:

  • Verification of Transportation:

    • Manufacturers are instructed to transport products according to the product's marketing authorization, label or "as justified by the manufacturer."

    • Manufacturers should define routes and take into account "variable factors" such as weather.

    • Manufacturers should conduct a risk assessment for such variable factors and their impact on “controlled or monitored" conditions.

    • For products sensitive to environmental factors, companies should monitor and record conditions inside the vehicle.

  • Validation of Packaging:

    • Companies should qualify all primary and secondary packaging equipment to ensure packaging functions as intended.

    • This qualification should be done at the "minimum and maximum operating ranges" of the equipment.

  • Qualification of Utilities:

    • Manufacturers should confirm the quality of utilities used during manufacturing, e.g. water, air, gas.

    • Seasonal variations should be accounted for if they have the potential to impact the utility.

    • Companies should conduct a risk assessment on utilities’ direct or indirect contact with the product.

  • Validation of Test Methods:

    • Test methods should be validated per EurdraLex Volume 4, Chapter 6.

    • Methods for microbial testing should be validated to ensure the product “does not influence the recovery of microorganisms.

    • Test methods should be validated to ensure that cleaning products do not affect the recovery of microorganisms.

The update to EurdraLex Volume 4, Annex 15: Qualification and Validation goes into effect on 1 October 2015.