Downstream Processing

Establishing Effective High-Throughput Contaminant Removal with Membrane Chromatography

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Bharat Serums and Vaccines Limited (BSV) in India conducted a study based on effective removal of host cell proteins (HCPs) from a recombinant hormone with a wide isoform profile in the acidic range imparting drug-product activity. Because the hormone and HCPs have a similar range of active species, the purification process with conventional chromatography resins had difficultly removing those HCPs from the active isoforms of the hormone. To solve that issue, a membrane chromatography technique was implemented. Our initial choice…

February 14, 2018

Streamlined Column-Packing Design for a New Commercial Launch Facility

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To meet network demand for a commercial launch facility, Genentech (Roche) designed a new downstream train and built it within an existing building shell at the company’s Oceanside, CA, site. This downstream train included new technologies to allow for rapid technology transfer of different new products in the company’s drug pipeline. One technology that was pursued was the Axichrom column platform from GE Healthcare and associated column packing equipment to streamline column packing design. Here we focus on how a…

December 13, 2017

Addressing the Challenge of Complex Buffer Management: An In-Line Conditioning Collaboration

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Read this article from scientists at Cytiva (GE Healthcare at the time of publication) to learn more about buffer preparation strategies now. Preparation and storage of buffers is a challenge for biopharmaceutical companies developing protein-based pharmaceuticals. The need for volumes of buffer to purify increasing upstream titers have become a major bottleneck in biopharmaceutical downstream processing. Italian biopharmaceutical company Kedrion Biopharma collects and fractionates blood plasma to produce plasma-derived therapeutic products for treating and preventing serious diseases, disorders, and conditions…

December 13, 2017

µPAC™ Microchip Chromatography: Better By Design

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The boundaries of technology can be pushed significantly when insights from different fields reinforce each other. Based on in silico simulations demonstrating the importance of order on the efficiency of chromatographic separations, PharmaFluidics has combined expertise from the analytical chromatography and semiconductor chip manufacturing industries to create a new type of nanoscale liquid chromatography (LC) column. Conventional LC columns contain randomly packed beads as a stationary phase. By contrast, PharmaFluidics uses a lithographic etching process to create a perfectly ordered…

November 16, 2017

Scaling Considerations to Maximize the High-Area Advantage

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Maximizing filtration-area density is a design strategy to minimize filter footprint and improve filtration process economics. Pleated membrane formats commonly are used to achieve that goal for sterilizing-grade filters operating in dead-end mode (also known as normal-flow filtration). Although high-density pleat geometries increase productivity for a device, such formats can present unique challenges. One of the most common concerns is that pleat formats can introduce flow resistance that impedes a device’s filtration efficiency, particularly for high–pleat-density geometries (1, 2). Filtration…

May 18, 2017

Current Thinking in Viral Safety: Risk Management Protects Patients

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BPI’s editor in chief S. Anne Montgomery recently caught up with long-time editorial advisor Hazel Aranha (purification technologies technology expert for Sartorius Stedim Biotech, North America). They discussed a number of topics related to viral safety. Montgomery: What is the current thinking regarding virus-safety assurance in biopharmaceutical manufacturing? How is the industry preventing viral contamination? Aranha: The “holy grail” of viral safety — absolute freedom from extraneous agents or residual pathogenicity — is a myth. That said, biopharmaceutical products have…

May 18, 2017

Scalable Purification of Viral Vectors for Gene Therapy: An Appraisal of Downstream Processing Approaches

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Gene therapy is the transfer of genetic material to a patient’s cells to achieve a therapeutic effect. Therapeutic DNA is largely delivered using viral vector systems based on adenoviruses (Ad), adenoassociated viruses (AAV), and lentiviruses (LV). With the application of such viral vectors as clinical therapeutics growing, scalable commercial processes (particularly for purification) are being investigated and optimized to best ensure that critical quality attributes (CQAs) are retained. Herein we review viral vector purification techniques and the effect of different…

February 13, 2017

A Statistical Approach to Assess and Justify Potential Product Specifications

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As stated in ICH Q6B, specifications are critical quality standards that are both proposed and justified by drug product manufacturers. Xiaoyu et al. provide information on several statistically based strategies to establish specification acceptance criteria (SAC) (1). Here we address an alternative approach to relate proposed SAC for quantitative data to relevant lot history. In particular, proposed SAC can be derived in part by using calculated limits for which the lower bound of an approximate 95% confidence interval for the…

February 13, 2017

Examining Single-Use Harvest Clarification Options: A Case Study Comparing Depth-Filter Turbidities and Recoveries

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Steadily increasing demand for biopharmaceutical drugs has led the industry to examine its manufacturing scales while pressuring research and development groups to produce high-yielding clones and processes. Improved media, feed supplements, bioreactor designs, and control of process parameters have helped biomanufacturers achieve multifold increases in volumetric productivity from production bioreactors. However, cell culture processes are significantly affected by their bioreactor’s ability to support cells at higher densities and sustain cultures at lower viabilities. With the implementation of a number of…

February 13, 2017

Downstream Disposables: The Latest Single-Use Solutions for Downstream Processing

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Downstream processing has been considered a “bottleneck” in the manufacture of protein biotherapeutics ever since cell culture engineers began dramatically improving production efficiencies around the turn of the century. And as single-use technologies have grown in importance and acceptance, offering more solutions every year, their biggest challenges too have been in the separation, purification, and processing that follows product expression in cell culture. Many of the technologies familiar to process engineers — e.g., centrifugation and chromatography — present technical and…

January 20, 2017