Position Paper

EBE Position Paper ” A Risk-based Approach to Setting Sterile Filtration Bioburden Limits”

12 Oct 2016

As part of the submission supporting the request for a marketing authorisation, medicines must demonstrate that they are of appropriate quality, which often includes a demonstration of sterility.  Biotechnology-derived medicinal products are typically sensitive to common methods of terminal sterilisation (sterilisation once the product has been filled into the final container) such as steam sterilisation and irradiation. They are therefore manufactured through aseptic processes where microbial contaminants are typically removed through sterile filtration. If the medicinal product contains a high level of microbial contaminants (so-called bioburden) before sterile filtration, the chance of breaching the sterilising filter is higher, which may lead to high amounts of contaminants, that might cause product safety and quality issues.

As a result, pre-filtration bioburden testing is required by regulatory guidelines.

The present EBE position paper proposes a novel, risk-based approach to setting bioburden limits before sterile filtration. This novel approach is in accordance with the quality by design principles in ICH Q8  and provides a scientific methodology for justifying smaller bioburden test volumes and alternate specifications for bioburden test limits to current requirements.

Read the position paper here