A modular and multi‐functional purification strategy that enables a common framework for manufacturing scale integrated and continuous biomanufacturing

Abstract

AbstractBiopharmaceutical manufacture is transitioning from batch to integrated and continuous biomanufacturing (ICB). The common framework for most ICB, potentially enables a global biomanufacturing ecosystem utilizing modular and multi‐function manufacturing equipment. Integrating unit operation hardware and software from multiple suppliers, complex supply chains enabled by multiple customized single‐use flow paths, and large volume buffer production/storage make this ICB vision difficult to achieve with commercially available manufacturing equipment. Thus, we developed SymphonX™, a downstream processing skid with advanced buffer management capabilities, a single disposable generic flow path design that provides plug‐and‐play flexibility across all downstream unit operations and a single interface to reduce operational risk. Designed for multi‐product and multi‐process cGMP facilities, SymphonX™ can perform stand‐alone batch processing or ICB. This study utilized an Apollo™ X CHO‐DG44 mAb‐expressing cell line in a steady‐state perfusion bioreactor, harvesting product continuously with a cell retention device and connected SymphonX™ purification skids. The downstream process used the same chemistry (resins, buffer composition, membrane composition) as our historical batch processing platform, with SymphonX™ in‐line conditioning and buffer concentrates. We used surge vessels between unit operations, single‐column chromatography (protein A, cation and anion exchange) and two‐tank batch virus inactivation. After the first polishing step (cation exchange), we continuously pooled product for 6 days. These 6 day pools were processed in batch‐mode from anion exchange to bulk drug substance. This manufacturing scale proof‐of‐concept ICB produced 0.54 kg/day of drug substance with consistent product quality attributes and demonstrated successful bioburden control for unit‐operations undergoing continuous operation.