Continuous Bioprocessing

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…

Preparing for Continuous Bioprocessing: An Interview with Pall Corporation’s Chief Technology Officer Martin Smith

Martin Smith, PhD, has been with Pall for about nine years and assumed the role of chief technology officer at Pall about 18 months ago. He spoke with Cynthia Challener, PhD, about Pall’s biopharmaceutical business unit and how the company is positioning its technology suite for a continuous process paradigm. Smith: There is no doubt in our minds that we see movement toward continuous bioprocessing. When you look across an array of different industries, the move to continuous or parallel…

Regulating Quality in Continuous Processing

Regardless of the industry and product being manufactured, continuous processing has demonstrated numerous benefits. In addition to smaller manufacturing footprints, reduced material consumption and waste generation, increased efficiencies, and lower capital and operating costs continuous manufacturing typically leads to more consistent processes and product quality. In the pharmaceutical industry, the latter two attributes align perfectly with FDA’s Quality by Design (QbD) and process analytical technology (PAT) initiatives. The challenge is determining how to apply these concepts in practice. Applying the…

Moving Toward a Continuous Future

During the March 2016 BPI West conference in Oakland, CA, BPI publisher Brian Caine and I had an opportunity to meet with Michael Egholm, PhD, Vice President and General manager of Biopharmaceuticals at Pall Life Sciences. We are pleased to be able to share his thoughts about Pall’s support of continuous processing — and the company’s current offerings. Montgomery: Not everyone seems to be defining continuous processing in the same way. What is your general concept of it? Egholm: At…

Using Technology to Overcome Bioprocessing Complexity: Advanced Concentration and Analytical Technologies Accelerate Development and Manufacture of mAbs, Vaccines, and Biosimilars

Unlike chemically synthesized drugs, whose structure is known and reproducible, biological drugs are derived from living cells and are sensitive, complex mixtures requiring cutting-edge biological technologies for their production. The growing importance of biosimilars in recent years is reflected in a corresponding rise in market value. The value of the global biologic therapeutic drug market reached approximately US$230 billion in 2014 and, according to BCC Research, will increase to nearly $390 billion by the end of 2019. This corresponds to…

Continuous Chromatography Is Now Possible for Clinical Manufacturing

Intensified and integrated bioprocess technologies are creating a paradigm shift toward more efficient, higher flexibility facilities for biopharmaceutical manufacturing. Continuous technologies that are designed as single-use systems help to greatly facilitate process intensification, delivering further efficiencies with reduced set-up times and elimination of the need for cleaning and cleaning validation. Chromatography is often considered to be a challenging bioprocess step, which has caused great interest in a simplified, safer solution. Continuous multicolumn chromatography using a single-use flow path is an…