Strategy for scaling semi-continuous downstream and integration of process analytical tools for monoclonal antibody toxicology

Currently, continuous processing for biologics is being pursued from a technology perspective in order to increase productivity and decrease cost of manufacture. Disruptive technologies, such as PCC (Periodic Counter-current Chromatography), have been researched extensively in order to reduce the bottleneck for the downstream capture chromatography step. However, there is extremely limited knowledge in how to scale these disruptive technologies for clinical and commercial manufacturing. In this presentation, we demonstrate a strategy for scaling and integration of a PCC capture step into a semi-continuous downstream process (Protein A chromatography-Viral inactivation-Filtration-Anion exchange chromatography). Harvest cell culture fluid (HCCF) feed streams ranging from 0.5 – 1 kg of various subclasses of IgG antibodies was purified using this integration process to generate material for toxicology studies. The process parameters on PCC for each mAb is matched to the process parameters in batch mode except for loading. The productivity (g/L-1 hr-1), product quality and yield are compared to the small scale semi-continuous operations and traditional batch mode operation. The use of PAT (Process Analytical Tools) for monitoring real time product quality and processing is also described

Pushing the closed and continuous boundary: End-to-end ICB at the pilot scale

Encouragingly, the biomanufacturing field continues to move towards GMP implementation of integrated and continuous processes. To our knowledge, all implemented ICB processes – including those at Sanofi – do not extend the ICB boundary to drug substance. In fact, questions remain not just as to whether fully continuous is necessary but whether the required process and engineering technologies yet exist to enable fully continuous at a commercially relevant scale. At Sanofi, we have built on our experience developing and implementing ICB technology to achieve an industry-first demonstration of a fully continuous process, including all typical downstream purification steps, to produce kilograms of drug substance. We will present our vision for end-to-end integrated and continuous biomanufacturing including design goals related to closed processing, automation, and continuous unit operations (not fast batch). Operation at the pilot scale, integrated to an intensified 100L perfusion bioreactor, required creative solutions in many aspects of the run design and execution while allowing for identification of true failure modes and, therefore, identification of areas for future development. Overall, we believe that currently available technology may allow for the realization of an end-to-end closed continuous commercial process. Moreover, our results suggest investment in pushing the continuous boundary may inspire disruptive innovation across bioprocessing to meet long-held aspirations for a truly disruptive facility of the future

Prediction of Protein Retention Times in Anion-Exchange Chromatography Systems

INTRODUCTION Ion-Exchange Chromatography (IEC) is a widely accepted standard bioseparation technique that has been growing in importance during the past decade in keeping with current rapid developments in biotechnology. To date, there are two main kinds of IEC: cation-exchange and anion-exchange chromatography, determined by whether a negative charge (cation-exchange) or a positive charge (anion-exchange) is carried by the functional groups on the surface of the IEC stationary phase. The ionic biopolymers, such as proteins, are separated primarily through the electrostatics interactions between the charged surface of the ion-exchange resin and the ionic solutes bearing the opposite charge. In the case of anion-exchange chromatography, negatively charged proteins bind in a transient fashion to the positively charged stationary phase sites, as long as the salt concentration is kept low. Proteins bound with different degrees of interaction can be separated with the aid of an increasin

COVID-19 infection in children with cancer and stem cell transplant recipients in Turkey: A nationwide study

To the Editor: Adults with cancer are reported to have a higher risk for coronavirus disease (COVID-19) infection and more severe disease and mortality than the general population.1, 2 Although children seem to be at a lower risk for COVID-19 than adults,3-5 data specifically addressing children with cancer are limited

Central Nervous System Fungal Infections in Children With Leukemia and Undergoing Hematopoietic Stem Cell Transplantation: A Retrospective Multicenter Study

Background: Central nervous system fungal infections (CNSFI) are seen in patients with hematologic malignancies and have high morbidity and mortality. Because of their rarity, there is limited data on CNSFI in children with no established treatment protocols or guidelines