Continuous Bioprocessing

Continuous Processes: Disposables Enable the Integration of Upstream and Downstream Processing

Despite decades of advancement in characterization analytics, biotherapeutics still are largely defined by the manufacturing processes used to make them. This linking of process to clinical results (and thus to commercial success) has made the biopharmaceutical industry somewhat risk-averse when it comes to the adoption of new technologies. That desire to “derisk” biomanufacturing through better process understanding — as well as the need to adapt to uncertainties in patient population size through process flexibility — in turn drives the need…

The Value of Single-Use and Other Flexible Technologies

The biopharmaceutical industry is adding mammalian cell culture capacity at rates that we haven’t seen in over a decade. Over the past five years (2012–2016), we estimate that industry-wide capacity has increased from 3.4 ML to 4.0 ML, an increase of 18% (1). We estimate that industry-wide capacity will increase over the coming five years (2016–2020) to 5.7 ML, an increase of >40%. Clearly, this growth is a response to the continued increase in demand for biopharmaceutical products and to…

Difficult-to-Express Proteins: Resolving Bioprocessing Challenges with a Scalable Perfusion Bioreactor

Recent advances in protein engineering have identified new classes of complex biotherapeutics that challenge existing manufacturing platforms. These products have unique cell culture requirements that make them difficult to manufacture cost effectively. Industry standard bioprocessing platforms include large-scale (1,000–5,000 L) batch and fed-batch stirred-tank bioreactors. Historically, the powerhouse molecule of the biologics industry has been human IgG, which necessitates those large-scale platforms. Difficult-to-express proteins and other new modalities (including precision medicine and orphan drugs) have increased pressure on manufacturers to…

Is Continuous Downstream Processing Becoming a Reality?

Over the past 30 years, several biopharmaceuticals have been produced by continuous cell culture processes run in a chemostat or perfusion mode. In most cases, no alternative was available to produce certain unstable molecules (1). However, downstream processing is and has remained a step-by-step batch operation. Continuous processing generally requires more process knowledge, equipment, and technological advances than do batch processes. With the maturity of bioprocessing and increasing awareness of manufacturing costs, companies are focusing on developing continuous downstream processing…

The Industry’s Hesitation to Adopt Continuous Bioprocessing: Recommendations for Deciding What, Where, and When to Implement

The US Food and Drug Administration has stated its appreciation of continuous bioprocessing (CBP), and some studies have shown that it can save manufacturers time and money. However, the bioprocessing industry is still reluctant to implement continuous bioprocessing right away. It will be interesting to see which companies will be among the first-movers to harness the competitive benefits. Although few biologics today are made using CBP-enabled equipment (e.g., advanced bioreactors), the industry is changing. For biologics already in production, it…

How to Set Up a Perfusion Process for Higher Productivity and Quality

Biotherapeutic proteins usually are produced by either fed-batch or perfusion processes. Perfusion manufacturing can provide much higher levels of productivity than fed-batch systems can, thereby reducing production costs. A 2013 study showed that perfusion is more cost effective than fed-batch processes for most combinations of titers and production volumes (1). Moreover, because a perfusion process is much closer to steady state than is a fed-batch process, it often produces a more consistent product — especially for molecules that are sensitive…

Drivers, Opportunities, and Limits of Continuous Processing

Biologics represent a significant group of approved drugs, and they are expected to continue their exceptional growth in the foreseeable future. At first glance, innovative monoclonal antibodies (MAbs) and their derivatives seem to dominate the field; however, biobetters, biosimilars, and other therapeutic proteins have gained in relevance lately. This diverse portfolio also is reflected in the range of different biomanufacturing processes used. Most blockbuster antibodies are produced by mammalian cells cultured in large bioreactors (10–20 m³) in fed-batch mode. But…

Multicolumn Chromatography: Facilitating the Commercialization of Monoclonal Antibodies

Since 2001, global contract development and manufacturing organization (CDMO) CMC Biologics has completed more than 120 projects with at least 100 pharmaceutical partners. During that time, the company has taken a holistic approach to helping clients balance manufacturing risks and rewards. The team focuses on evaluating key technologies to deploy a constantly evolving set of capabilities in support of biopharmaceutical clients throughout their product lifecycles. Part of that commitment is continually evaluating what would best benefit customers and where key…

The History of Continuous Processing: Why Has the Biopharmaceutical Industry Been So Late to Adopt?

Continuous and semicontinuous manufacturing systems have been used for many years in numerous sectors — including the automotive, food and beverage, oil refining, chemicals, pulp and paper, electronics, metal smelting, steel making, and waste-water treatment industries. Most of these industries are capital intensive and switched to flow manufacturing to increase productivity and flexibility; reduce cycle times, inventory, waste, and costs; and achieve enhanced product quality. Despite the capital intensive nature of drug manufacturing, the biopharmaceutical industry has lagged behind these…

Moving One Unit Operation At a Time Toward Continuous Biomanufacturing: An Overview of Pall Solutions for Integrated Continuous Biopharmaceutical Production

Numerous industries have demonstrated that continuous manufacturing provides significant benefits and advantages, ranging from reduced capital and operating expenses to greater efficiency and product quality and consistency. The conventional approach to biopharmaceutical manufacturing involves the batch performance of a series of unit operations separated by hold steps requiring additional tanks and/or biocontainers. Such an approach fails to maximize facility use, requires large buffer volumes, and results in overall inefficiencies. An integrated, continuous approach to bioprocessing connects each unit operation, minimizing…