October 2022

Overcoming the Productivity Bottleneck in MAb Capture

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It is no secret that progress toward intensifying monoclonal antibody (MAb) production processes has focused on upstream steps. Although the industry welcomed increased production, that also created bottlenecks in downstream processing, including during capture chromatography steps. Technologies that are intended to alleviate such bottlenecks must meet four important criteria to increase productivity and profitability. They must • improve productivity of the MAb capture process, such as by purifying more MAbs, using less media, and/or reducing timelines. • perform as well…

October 20, 2022

Applying Quality By Design Principles to AAV Manufacturing

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The expectation to apply quality by design (QbD) principles to new manufacturing processes has been voiced by regulatory authorities for over a decade (1, 2). They recognize that because of the generally low patient populations for emerging therapies, such as adeno-associated virus (AAV)-based therapeutics, available chemistry, manufacturing, and controls (CMC) information might not be as exhaustive as for other biologicals such as monoclonal antibodies (3, 4). Other challenges include the need for rapid development to address currently unmet medical needs…

October 20, 2022

A Plug-and-Produce GMP Plant for Cell and Gene Therapies Part 2: Rapid Deployment of a Commercial-Scale Facility

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Extending the use of approved advanced-therapy medicinal products (ATMPs) to the tens of thousands of patients who could benefit from such treatment requires a 10- to 100-fold production scale-up. Given that each autologous ATMP batch yields one dose for one patient, expanding production throughput is not a question of boosting volume, but rather of amplifying single manufacturing runs. That is, scale-up is actually scale-out, and the dimensions of the ensuing endeavor extend beyond what occurs in the cleanroom. Coupled with…

October 20, 2022

Two-Step Monoclonal Antibody Purification Using a Multicolumn Continuous Chromatography Platform

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Biomanufacturers typically have relied on multistep processes for optimal removal of impurities such as host-cell proteins (HCPs), DNA, adventitious viruses, and aggregates. However, additional purification steps increase downstream expenses significantly, including costs of supplementary resin, hardware, and buffers. The substantial footprint required at a processing site and additional time needed to perform a complete multistep purification process also increase production costs and complicate process execution. Thus, it is imperative to design and test effective purification procedures for high-quality biotherapeutics, but…

October 20, 2022

Investigation of HCP Enrichment During CGMP Scale-Up

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On paper, scaling a bioprocess from a 10-L to a 100-L to a 2,000-L bioreactor may seem like a straightforward math problem that could be solved by software. In practice, however, the exercise relies on a complex set of biological, chemical, and engineering assumptions; on maintenance of healthy cell cultures; and on management of equipment and analytics while adjusting to each increase in scale (1). Process development and quality control groups need to monitor how scale-up might affect critical quality…

October 20, 2022

Bridging Anti-CHO HCP Antibodies: From Two Third-Generation Cygnus CHO HCP ELISA Kits By AAE-MS

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A well-developed, broadly reactive, and qualified enzyme-linked immunosorbent assay (ELISA) is the gold-standard method for ensuring removal of host cell proteins (HCPs) and demonstrating process consistency and final drug substance (DS) purity. Regulatory guidelines require sponsors to use orthogonal methods for demonstrating antibody coverage of individual HCPs and provide a comprehensive assay qualification package to ensure that the ELISA is fit for purpose. In a June 2022 webinar, Eric Bishop (head of R&D and custom development services at Cygnus Technologies)…

October 20, 2022

From Immigrant to Entrepreneur: Lessons Learned in Building an Innovative Business

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As an entrepreneur, I stepped away from a fulfilling position in a large and established company to go out on my own and build something new. My decision to leave the advanced research department at Illumina, Inc. to create a start-up might seem like an extreme leap, but I am very familiar with the risks of starting over. After earning my bachelor of science degree in biotechnology from the University of Tehran, I immigrated to the United States. I left…

October 20, 2022