Trends and Challenges in Sterile Filtration of High Concentration Drugs

Drug formulations are changing, and the share of subcutaneous administration over intravenous infusion is increasing. Subcutaneous administration is seen to be the preferred approach both by patient and healthcare providers.

Careful consideration is required when selecting a sterilizing grade filter for drug product filtration. With the development and manufacture of subcutaneous biologics come challenges in the sterilizing or bioburden reduction filtration of drug substance that is both highly concentrated (>100 g/L) and viscous (10-30 cP). Two significant problems are:

• The use of larger filters because of the high fouling properties of the feeds. This results in the loss of high value drug substance in hold-up volumes in both the filtration assembly and system.

• The relative scarcity of product during process development. This results in limited opportunities for meaningful filter benchmarking studies and can lead to sub-optimal filter selection.

The relative value and availability of high concentration drug formulations limits the practicality of performing extensive evaluations of a range of sterile filters to identify the optimal selection. In this presentation we will share the approach we took, allowing us to undertake extensive filterability trials without the need to generate a high quantity of expensive product.