Continuous Bioprocessing

Run Rules with Autocorrelated Data for Continued Process Verification

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Control charts can be used to assist in monitoring of biopharmaceutical product quality attributes as part of continued process verification activities. A number of tests known as run rules have been developed to assess whether biomanufacturing processes remain in statistical control. In practice, results for such attributes can be positively autocorrelated. Simulated data are used to assess the performance of run rules with autocorrelated data to assist in determining risk–reward profiles for process monitoring. Autocorrelated Data The tendency for data…

October 29, 2020

Developing Process Control Strategies for Continuous Bioprocesses

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Process control enables biomanufacturers to ensure that operating parameters are within defined specifications. A control strategy should be established during early stages of process development while process and product performance are being defined using risk-based methods such as quality by design (QbD) and process analytical technologies (PATs). Confirming process control as an essential part of product development creates greater process knowledge and understanding and provides the first steps toward process optimization. By understanding how process performance relates to product quality,…

May 15, 2020

eBook: Continuous Bioprocessing — Promises and Challenges

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Biotechnological productions are commonly executed as batch processes, especially during downstream processing. Higher titers in fermentations, reductions in operating scale, and the quest for improving product quality all have led to an intensified effort for developing continuous processing. It is forecasted that within the next 10 years, about 50% of all drugs under development will be biopharmaceuticals, making it worthwhile to develop more efficient processes. In this BPI eBook, Babu Halan (project engineer) and Wolfgang Minas (global lead of the…

February 18, 2020

Bioprocess Intensification – Fast, Flexible, and Efficient Solutions

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Propelled by single-use systems (SUSs), biopharmaceutical companies are approaching the ideal of continuous bioprocessing. In addition to improving process integrity and decreasing production costs, SUSs have enabled exciting ways to configure, operate, and evaluate manufacturing steps. Sensitive process analytical technologies (PATs) and discriminating data analysis platforms are supplementing those developments, helping process engineers and operators to study and modify workflows in unprecedented ways. The goal now is to intensify: to apply increasingly nuanced process knowledge and growing technological capability in…

November 21, 2019

Flow Monitoring in Continuous Processing and Single-Use Systems

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Flow sensors placed at critical points in both upstream and downstream processes fulfill the regulatory goals of the process analytical technology (PAT) framework. PAT has been defined as a mechanism for design, analysis, and control of biotechnical and pharmaceutical manufacturing processes through measurement of critical process parameters (CPP). Constant flow monitoring can support its overall targets fundamentally to reduce production cycling time prevent rejection of batches enable real-time release increase automation and control improve energy and material use facilitate continuous…

October 23, 2019

Control of Protein A Column Loading During Continuous Antibody Production: A Technology Overview of Real-Time Titer Measurement Methods

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During production of therapeutic antibodies, harvest titer is measured to monitor product mass loaded onto the protein A capture column. This prevents both column underloading (underusing expensive resin) and overloading (wasting product as flow-through (FT)) while allowing for column yield calculations. Batch production yields a single homogenous harvest pool, thus only one titer measurement (along with volume loaded) is sufficient to determine the mass loaded. During continuous production, however, cell-free harvest (permeate) continuously exits a perfusion reactor and loads a…

September 21, 2019

Advances and Challenges in Vaccine Development and Manufacture

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Scientists have made significant breakthroughs in bioprocess and analytical technologies for supporting vaccine development. Such technologies have helped vaccine manufacturers achieve consistent product purity and quality rapidly and cost effectively. Although interest in vaccine development and manufacture continues to increase because of the rapid growth of the global vaccine market, this area of the bioprocess industry remains challenging and complex. Here we review the current constraints and complexities in the vaccine industry, specifically related to product development and manufacture. We…

September 21, 2019

Continuous Biomanufacturing: A New Approach to Process Scale

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The BioPhorum first-edition Technology Roadmap outlined a 10-year vision for therapeutic protein production in the biopharmaceutical industry (1). The roadmap describes multiple manufacturing scenarios ranging from large-scale (~20,000-L production) to small and agile, portable production facilities. It includes detailed analyses of the needs for the future in each of the following areas: Process technologies (2) Inline monitoring and real-time release (3) Automated facilities (4) Modular and mobile (5) Knowledge management (6) Supply partnership management (7). Since the 2017 publication of…

June 20, 2019

From Interest in Intensification to a Factory of the Future

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Much has been published on improvements and advances in many individual technologies for biomanufacturing. If you take a comprehensive look at the field, however, you find overlap, muddling, and even contradiction about which particular processes or aspects of technological development should be designated properly as process intensification. Although the industry is addressing such distinct goals as improved manufacturing yield, product quality, and cost-effectiveness, the names of initiatives commonly applied to accomplish those goals overlap at best. Such ambiguity and lack…

June 12, 2019

An Integrated Bioprocess for Antibodies: From Harvest to Purified Bulk in Six Hours

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Antibody production platform processes have been widely adopted in biomanufacturing, but many unit operations are not suitable for integration and automation. Here we describe the work of integrating unit operations by transforming a column operation to a more robust cassette format. We have selected a biomolecule-friendly buffer (phosphate) to eliminate, or delay, the performance of a circulating tangential flow ultrafiltration/diafiltration (UF/DF) operation, so the harvest-to-purified-bulk process can be integrated, resulting in a single, direct-flow operation, that reduces the batch process…

June 12, 2019