EC Updates Guidelines for Sterile Drug Manufacturing

The European Commission (EC) is detailing its expectations for manufacturers running media fills to assess aseptic processing operations.

Under revisions to the GMP guidelines for sterile drug products, no contamination should be detected when firms fill fewer than 5,000 units. When filling 5,000­–10,000 units, manufacturers need to consider revalidating the sterilization process. If only one unit is contaminated, an investigation needs to occur and the process may need to be repeated.

Media fills, used to gauge contamination levels, simulate the aseptic sterilization process by using culture media in place of the actual drug.

For fills of more than 10,000 units, one contamination needs to result in an investigation, the new guideline states. Two contaminations need to prompt firms to consider revalidating their aseptic process.

The current guideline states that a contamination rate of less than 0.01 percent, with a 95 percent confidence interval, is acceptable. The revised guideline takes effect next March.

The guideline, “EudraLex: Volume 4 EU Guidelines to GMP Medicinal Products for Human and Veterinary Use, Annex 1, Manufacture of Sterile Medicinal Products,” can be accessed at ec.europa.eu/enterprise/pharmaceuticals/eudralex/vol-4/pdfs-en/2008_02_12_gmp_annex1.pdf.