Downstream Development

Accelerating Purification Process Development of an Early Phase MAb with High-Throughput Automation

    Monoclonal antibodies (MAbs) are the fastest growing segment in the biopharmaceutical industry because they are potentially efficacious in the treatment of diseases such as cancer and autoimmune disorders (1,2). With steadily increasing demand for efficient and affordable therapies, speed to clinic/market is important, and biopharmaceutical companies push multiple drugs into development each year to ensure business sustainability (3,4,5,6). Downstream purification process development for therapeutic MAbs is a critical step on their path to reach clinical trials and beyond…

Single-Use Bioreactors and Microcarriers

Cell-based therapies hold promise for treating many acute and chronic diseases (1). Optimism surrounding that therapeutic potential has driven the initiation of multiple clinical trials in pursuit of such treatments. Procedures for preparing these therapeutic agents begin with selective isolation of cells from desired tissues. That is followed by ex vivo expansion of cells of desired phenotype and functionality. Once expanded to acceptable levels, cells are stored to preserve their viability during transportation to treatment facilities. The final step in…

Enabling Technologies

Many technological advancements in recent years have enabled companies to shorten time to market, to better understand their manufacturing processes, and to characterize their products well. In BPI’s December 2013 issue (pages 47–50), I reported on the first half of an informal reader survey about those technologies, with commentary from some survey participants and others. This month concludes with my examination of analytical, formulation/fill–finish, and facilities technologies. Analytical Technologies After writing several installments of our new “BPI Lab” series this…

Innovation in Biopharmaceutical Manufacture

The following is a report from a workshop on innovation in biopharmaceutical manufacturing held at the Annual bioProcessUK Conference in Bristol on 29 November 2012. The aim of the workshop was to access the experience of practitioners in the United Kingdom so as to understand better the challenges and opportunities for innovation in this sector. The workshop addressed the drivers that influence the implementation of process improvements and novel technologies in biopharmaceutical manufacture from the perspective of both manufacturers and…

Emerging Challenges to Protein A

Protein A affinity chromatography has been a target for replacement since its commercial debut, mainly because of its high acquisition cost. The technique became established despite the cost because it was born into an industrial culture that favored speed to market over manufacturing economy (1). Vendors have since strengthened protein A’s position with incremental but worthy improvements such as higher capacity, lower ligand leaching, and modest tolerance of NaOH. Collateral improvements in polishing technologies, such as the high throughput and…

Keeping New Technologies Coming

The biomanufacturing industry is heavily invested in improvements in productivity and efficiency, and innovation is a critical component to ensuring gains in these areas. Yet that is not always the case. Suppliers and innovators in this market face greater challenges, and much longer product evaluation cycles than in other segments, for example the information technology or semiconductor industries. In the highly regulated biomanufacturing environment, changing any aspect of a process can potentially necessitate additional regulatory submissions to the US Food…

Comparability Protocols for Biotechnological Products

Comparability has become a routine exercise throughout the life cycle of biotechnological products. According to ICH Q5E, a comparability exercise should provide analytical evidence that a product has highly similar quality attributes before and after manufacturing process changes, with no adverse impact on safety or efficacy, including immunogenicity (1). Any doubt about data from such studies could translate into unforeseen pharmacological or nonclinical studies — or worse, clinical studies. Selection of analytical methods and acceptance criteria that will be applied…

Purifying Common Light-Chain Bispecific Antibodies

A bispecific antibody can bind two different antigens. Immunoglobulin G (IgG) type antibodies have two binding sites with different variable regions. An IgG variable region is made up of a variable light-chain sequence (VL) and a variable heavy-chain sequence (VH). The light chains (LCs) of common LC antibodies are identical for both variable regions, leaving the heavy chain (HC) for generating different specificities. Thus, recombinant host cells for production of common LC bispecific antibodies carry genes for both HCs, with…

High-Throughput Chromatography Screenings for Modulating Charge-Related Isoform Patterns

Monoclonal antibodies (MAbs) are an important class of biopharmaceuticals and are widely used to treat a variety of diseases such as cardiovascular diseases, cancer, and blood disorders. Antibodies are very complex proteins that show a high degree of microheterogeneities, including charge-, hydrophobicity- and size-related variances (1). Such variants can arise during any stage in a manufacturing process or storage as a result of enzymatic or nonenzymatic processes (2). Particular antibody variants that may affect the in vitro and in vivo…

Liquid or Powdered Media?

For decades, innovations in research and production techniques have been driving forces in the biopharmaceutical industry. But market conditions fueled by the economic downturn over the past five years have increased regulatory burdens in the United States and Europe. Rising costs and risks associated with new drug development now require that biopharmaceutical companies manufacture their products more quickly and cost-effectively than ever before. To this end, companies are looking for new ways to reduce expenditures, increase profitability, speed research, enhance…