2017

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…

May 2017 – From the Editor

The first half of 2017 has been leading us to next issue’s focus on the state of the industry. Although we are not officially calling it our “15th anniversary issue,” that of course is what prompts our focus on progress and future projections. By the time you read this, that issue will be on its way to the printer. So here are my thanks, in advance, to those of you who took time with our related survey. We editors look…

May Spotlight

Welcome New Editorial Advisor David Rabuka is global head of research and development in chemical biology at Catalent Biologics, with overall responsibility of overseeing continued research and development of SMARTag technology. He also oversees strategy, resource allocation, and scientific oversight of preclinical and clinical studies. David joined Catalent Biologics following Catalent’s acquisition of Redwood Bioscience Inc., where he was founder, president, and chief scientific officer. David’s scientific areas of expertise include chemical synthesis; drug delivery; translational research; chemistry, manufacturing, and…

Innovating in France’s Auvergne-Rhône-Alpes Region

  Lyonbiopole is a French “bio-cluster” based in the Auvergne-Rhône-Alpes region surrounding Lyon (Figure 1). The cluster supports ambitious projects and companies in the broad health industry, counting more than 200 members including Lyonbiopole’s four founders: Sanofi Pasteur (the vaccines division of multinational pharmaceutical company Sanofi), bioMérieux (known worldwide for in vitro diagnostics and microbiological testing), Merial (an animal-health company that merged recently with Boehringer Ingelheim), and Becton Dickinson (supplier of flow cytometers, reagents, tools, and services). The region also is…

An Industry Proposal for Change Notification Practices for Single-Use Biomanufacturing Systems

Current practices for change notification in the biopharmaceutical industry are neither efficient nor conducive to accelerating the adoption of single-use systems (1, 2). Drug manufacturers (end users) often observe that supplier change data packages lack technical content or detail and that the time allowed for change implementation is too short. Occasionally, customers (end users or next tier in supply chain) learn of changes after the fact, possibly even by happenstance. Suppliers, however, can find the potential affect of a change…

Opportunities and Challenges in Biosimilar Development

A biosimilar biotherapeutic product is similar (but not identical) in terms of quality, safety, and efficacy to an already licensed reference product. Unlike generic small molecules, it is difficult to standardize such inherently complex products based on complicated manufacturing processes. Table 1 describes the main differences between biosimilar and generic drug molecules. The global biosimilar market is growing rapidly as patents on blockbuster biologic drugs expire (Table 2) and other healthcare sectors focus on reduction of costs. Biologics are among…

Implementing Quality By Design in Analytical Development: A Case Study on the Development of an Anion-Exchange HPLC Method

The concept of quality by design (QbD) initially was outlined in ICH Q8 guidance for drug-product development and later in Q11 for drug-substance development (1, 2). Since then, the QbD concept was further expanded to the development of analytical methods. FDA issued a 2015 guidance on analytical procedures and method validation for drugs and biologics (3). Although the agency did not explicitly state the requirement for implementation of QbD in analytical method development, the concept is embedded in its section…