Analytical

Aggregation from Shear Stress and Surface Interaction: Molecule-Specific or Universal Phenomenon?

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Exposure to solid–liquid and air–water interfaces during production, freezing and thawing, shipment and storage of protein therapeutics may be a contributing factor in their degradation (e.g., aggregation, fragmentation) (1, 2). Surface exposure, particularly during manufacturing processes, often is accompanied by various degrees and durations of shear stresses originating from fluid flow and acting on proteins at interfaces. The magnitude and duration of shear rates depends on velocity gradients within each solution and varies significantly among manufacturing steps. On the low…

April 17, 2017

Strategies for Successful Sample Transfer

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Nadine Ritter is president and senior analytical advisor of Global Biotech Experts, LLC and a long-time member of BioProcess International’s editorial advisory board. At a recent CASSS North American CMC Strategy Forum called “Methods on the Move: Addressing Method Transfer Challenges,†she discussed the biopharmaceutical industry’s logistical challenges of analytical test samples for drug substances and products. At the conference, BPI’s editor in chief Anne Montgomery met with her to discuss some key points of this topic. Logistics Challenges Montgomery:…

April 17, 2017

Enabling Faster Workflows with Protein Purification Technologies: Improvements in Chromatography and Electrophoresis

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Purification of recombinant proteins is a critical step during protein therapeutics development. Protein therapeutics have a number of classifications based on their potential applications, including use as vaccines and diagnostics as well as for enzymatic, regulatory, or targeting activities (1). For all such applications, identifying and verifying protein purity is most important. Whether proteins themselves are therapeutics or the target proteins of interest, effective purification is essential in drug development. Since the introduction of recombinant proteins in the early 1980s,…

April 13, 2017

Evolving Bioassay Strategies for Therapeutic Antibodies: Essential Information for Proving Biosimilarity

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The modern age of biologics began 35 years ago with the approval of Lilly’s Humulin product — a biosynthetic form of human insulin derived from recombinant DNA and microbial cell culture (1). Today, about a quarter (27%) of the drugs approved yearly by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) are biopharmaceuticals: primarily monoclonal antibodies (MAbs), but also vaccines, blood products, and (recently), advanced therapies based on genes and cells. A decade ago, the average…

April 11, 2017

Extractables and Leachables: Standardizing Approaches to Manage the Risk

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The implementation, maturation, and benefits of single-use technologies in biopharmaceutical development and manufacturing are well documented and understood. As analytical methods and testing services also rapidly improve, it is clear that management of risk associated with extractables and leachables also must evolve. Standardization is universally accepted as a goal; how to define, implement, and educate the industry is where debate resides. The container–closure segment has had more experience dealing with leachables and extractables than those implementing single-use process components do…

March 29, 2017

Biological Characterization Using Protein Crystal Measurements

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Monoclonal antibodies (MAbs) have become important therapies and are projected to generate US$125 billion in sales by 2020 (1). Given that potential revenue, biopharmaceutical companies are highly motivated to find novel ways to deliver their drug products and extend patent lifetimes. Many such therapies are administered intravenously at low concentration and large volumes (2). Althea’s Crystalomics technology facilitates delivery of traditional biotherapeutics with high concentration, low viscosity, and low volume by arranging a drug’s individual molecules in an ordered crystal…

March 20, 2017

Comparing Culture Methods in Monoclonal Antibody Production: Batch, Fed-Batch, and Perfusion

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Recombinant protein manufacturing with Chinese hamster ovary (CHO) cells represents over 70% of the entire biopharmaceutical industry (1). In fact, human monoclonal antibodies (hMAbs) produced by CHO cells have played a major role in both the diagnostic and therapeutic markets for decades. One of the first human–mouse chimeric MAbs to obtain FDA approval was Roche’s rituximab treatment for non-Hodgkin’s lymphoma, chronic lymphocytic leukemia, and rheumatoid arthritis. Since that approval in 1997, scores of chimeric, humanized, and human MAbs have gained…

March 20, 2017

Conditional/Inducible Gene-Expression Mouse Models Using Advanced Gene Editing

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Transgenic mouse models have been an essential part of biomedical research for many decades. They have provided valuable insights in developmental biology, gene regulation, and our understanding of the genetic basis of human disease. And they play a critical role in drug discovery and development. Traditional methods to generate these mouse models entailed a milieu of disadvantages: e.g., low efficiency, high incidence of undesirable recombination outcomes, randomly and multiply inserted genes of interest, ectopic expression, gene silencing, and insertional mutations…

March 20, 2017

Accelerated Development Through Strategic Analytical Partnerships

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The analytical field for biologics has evolved greatly over the past 30 years, and the underlying growth has shifted from biopharmaceutical companies to contract research organizations (CROs). The global biopharmaceutical market is growing annually at >15%, making it the largest and consistently fastest growing segment of the healthcare industry with annual sales in excess of US$200 billion. Contract manufacturing organizations (CMOs) are expanding capacity by building new cost-efficient facilities, reflecting market demand. Many product sponsors are outsourcing, some even increasing…

March 14, 2017

Outsourcing Biosimilar Development

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As the debate continues over the high cost of pharmaceutical treatment options, the development of biosimilars continues to play a dominant role in that discussion and will be an important part of the solution. Biosimilar companies are working at a feverish pace to develop the next generation of follow-on products. Outsourcing to a growing group of contract development and manufacturing organizations (CDMOs) is a key strategy for savvy developers to accelerate their products’ launch. Finding the right CDMO isn’t an…

March 14, 2017