Author Archives: Lakshmi Prasad Pathange

Product Quality Attribute Shifts in Perfusion Systems, Part 2: Elucidating Cellular Mechanisms

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Part 1 of this two-part report describes an investigation into the potential cause(s) and ways to control a product quality attribute (PQA) of a protein expressed in perfusion cell culture (1). The presence of low–molecular-weight (LMW) species following size-exclusion high-performance liquid chromatography (SEC-HPLC) is a protein quality attribute that can indicate an increase in truncated forms of the expressed protein and/or other LMW moieties. The expressed protein in this study is a heavily glycosylated recombinant glycoprotein (rGP) comprising two subunits:…

December 17, 2020

Product Quality Attribute Shifts in Perfusion Systems, Part 1: Identifying Shifts When They Occur

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Perfusion cell culture processes are continuous, with fresh media continuously added and spent media (harvest) removed simultaneously through a cell-retention device (Figure 1). To maintain specific bioreactor cell density, cells are removed periodically as cell bleed or discard. Perfusion systems offer a number of advantages over batch and fed-batch culture modes such as lower capital costs and an ability to support higher cell densities with better viability over longer manufacturing campaigns requiring shorter turn-around times. However, perfusion systems require complex…

September 22, 2020

Developing an End-to-End Scale-Down Model for a Commercial-Scale Downstream Process: Enhancing Technology Transfer Efficiency

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Large and complex protein molecules used as therapeutic agents are manufactured in a series of process steps that start with thawing of cell-bank vials and finish with filling and packaging (Figure 1). The cost and complexity of commercial-scale biomanufacturing processes make them prohibitive to troubleshoot or experiment at full commercial scale. Biopharmaceutical companies routinely use scale-down models (SDMs) of licensed commercial-scale processes to evaluate raw material changes, process improvements, and deviations (1) (Figure 2). Here, we outline some considerations in…

March 14, 2019

Development and Application of a Simple and One-Point Multiparameter Technique: Monitoring Commercial-Scale Chromatography Process Performance

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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…

December 14, 2018

eBook: Development and Application of a Simple and One-Point Multiparameter Technique — Monitoring Commercial-Scale Chromatography Process Performance

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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…

May 14, 2018

eBook: Development of a Representative Scale-Down UF/DF Model: Overcoming Equipment Limitations and Associated Process Challenges

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Scale-down models (SDM) are physical, small-scale models of commercial-scale unit operations or processes that are used throughout the biopharmaceutical industry for validation studies, commercial deviation investigations, and postapproval process improvements. To support these studies, regulatory guidelines state that SDMs should be representative of the commercial process. For some downstream unit operations such as column chromatography, developing a representative SDM is straightforward because a linear scale-down approach can be used. However, developing a representative SDM for other downstream unit operations such…

February 27, 2018