High throughput screening of ultrafiltration and diafiltration processing of monoclonal antibodies via the ambr® crossflow system

Abstract As the biopharmaceutical industry moves toward high concentration of monoclonal antibody drug substance, additional development is required early on when material is still limited. A key constraint is the availability of predictive high‐throughput low‐volume filtration screening systems for bioprocess development. This particularly impacts final stages such as ultrafiltration/diafiltration steps where traditional scale‐down systems need hundreds of milliliters of material per run. Recently, the ambr® crossflow system has been commercialized by Sartorius Stedim Biotech (SSB) to meet this need. It enables parallel high throughput experimentation by only using a fraction of typical material requirements. Critical parameters for predictive filtration systems include loading, mean transmembrane pressure (Δ TMP ), and crossflow rate ( Q F ). While axial pressure drop (Δ P axial ) across the cartridge is a function of these parameters, it plays a key role and similar values should result across scales. The ambr® crossflow system is first presented describing typical screening experiments. Its performance is then compared to a traditional pilot‐scale tangential flow filtration (TFF) at defined conditions. The original ambr® crossflow (CF) cartridge underperformed resulting in ~20x lower Δ P axial than the pilot‐scale TFF flat‐sheet cassette. With an objective to improve the scalability of the system, efforts were made to understand this scale difference. The ambr® CF cartridge was successfully modified by restricting the flow of the feed channel, and thus increasing its Δ P axial . Additional studies across a range of loading (100–823 gm −2 ); Δ TMP (12–18 psi); and Q F (4–8 L/min/m 2 ) were conducted in both scales. Comparable flux and aggregate levels were achieved.