The Increasing Demand For Sterile Filtration Of High Concentration Drugs

Drug formulations are changing, and the share of subcutaneous administration over intravenous infusion is increasing. The subcutaneous administration trend has gained traction and is seen to be the preferred approach both by patients and healthcare providers due to the potential benefits of reduced infusion time and enhanced patient convenience.

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 as a consequence 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.

Biotech companies are increasingly targeting the production of drugs at a high concentration as part of their formulation strategy for their next-generation therapies. The relative value and availability of high-concentration drug formulations therefore 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 current trends and challenges with the manufacture of high-concentration drug products, and we will provide an overview of the approach we took to perform extensive filterability trials without the need to generate a high quantity of expensive product.