In commercial-scale biopharmaceutical manufacturing, downstream chromatography steps are still a bottleneck and contribute to significant operational costs (1, 2). Some of those costs are inherent (e.g., resins, large buffer quantities, and cleaning) whereas others are avoidable (e.g., product loss due to rejected lots or deviations that result in production downtime). Maintaining efficient and robust chromatography process performance is therefore critical for minimizing operating costs. To do so, we introduce a simple and one-point multiparameter technique (SOP-MPT) for monitoring chromatographic process performance.
Traditionally, chromatography process performance has been monitored by analytical assays (e.g., those measuring yield, impurities, and molecular integrity) along with visual review of chromatographic profiles by trained personnel. However, such techniques have limitations. Analytical assays are performed for each production lot but not necessarily at each process step, thus creating gaps in process monitoring. Assay results may be unavailable for one to two weeks after a lot is processed. Therefore, a production process is run at risk during the assay testing period, and the sole mitigation for that is visual review, which captures only gross column failures (not emerging process issues).
There is a gap between what traditional process monitoring can detect and how events unfold in real time. Recent efforts to close that gap have driven development of advanced and complex models such as transition and multivariate analyses (3, 4). However, those models require long lead times to develop and can be cost prohibitive. Skilled personnel also are required to extract and compile data and to execute those models in monitoring routine processes. Furthermore, complex models are limited by computational factors such as data collection frequency, high signal-to-noise ratio, and extensive processing requirements (5).
To overcome those limitations, a novel SOP-MPT was developed to enhance routine process monitoring. It has the following salient features:
- Evaluates performance of any chromatography step immediately after a process has completed (near real-time)
- Identifies emerging process performance issues
- Requires no capital outlay and works with current production software capabilities
- Improves process understanding and identifies potential opportunities to improve process robustness and yields, reducing quality issues and enhancing process efficiency
- Gives production personnel ownership of process monitoring
- Acts as a communication tool between management and operators.
Bayer personnel have used SOP-MPT to monitor more than 1,000 commercial-scale lots and detected significant process performance issues such as compromised column packing integrity, column underperformance, and chromatographic skid failures. In addition, the SOP-MPT enhances production efficiency by providing product quality insights and process-improvement opportunities.
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