MAb

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

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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…

April 17, 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

Buffers in Biologics Manufacturing

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Biotechnology has enabled commercialization of protein-based drugs including insulin, growth factors, blood factors, and antibodies. Production and purification of such biologic products require different buffers for pH control and stabilization of reactions in different steps during biomanufacture. These processes include cell culture production (the “upstream” phase), purification (the “downstream” phase), and a final phase in which excipients are introduced to the drug substance to create a drug product (“formulation and storage”). In upstream processes, buffers are primarily used for their…

February 13, 2017

Special Report: A Strategy for Cost-Effective Capture Using Agarose-Based Protein A Resins

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It is well recognized that the cost of Protein A resins is substantial. If a developmental monoclonal antibody (MAb) makes it to marketing approval and manufacturing, the high cost of purification using a Protein A resin is amortized over a large number of purification cycles, and the contribution to cost of goods is reduced to acceptable levels. However, a high percentage of clinical projects will fail, and the Protein A resin will be used only for a small number of…

October 26, 2016

Biosimilar Therapeutic Monoclonal Antibodies: Gaps in Science Limit Development of an Industry Standard for Their Regulatory Approval, Part 1

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Biosimilars are biologically derived pharmaceuticals intended to have clinical similarity to a legally marketed innovator product when that product’s patent or market exclusivity has expired. By contrast with generic small-molecule drugs, clinical performance of a biologic pharmaceutical is a function of its structural complexity and higher-order structure (HOS). Biomanufacturing controls of such complex products cannot fully ensure chemical similarity between an innovator product and putative biosimilar because minor differences in chemical modifications and HOS can significantly alter a product’s safety…

October 14, 2016

Addressing the Challenges of Developing Biopharmaceutical Drugs

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The biopharmaceutical industry is enjoying considerable success. Its products account for about a fifth of world pharmaceutical revenues, which are growing at twice the pace of those generated by most traditional chemically synthesized drugs. Biopharmaceuticals populate the list of best-selling drugs, and a number have achieved blockbuster status. Biotechnology stocks have outperformed the general market as investment has flowed into the industry. As with other highly profitable markets, the market for biopharmaceuticals has become increasingly competitive. Reflecting this fact, in…

September 28, 2016

Standardized Economic Cost Modeling for Next-Generation MAb Production

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Historically, in generating material for clinical testing during antibody process development, emphasis was placed on efficacy, product quality, regulatory compliance, and speed. As the biopharmaceutical industry has matured (and with increasing competition), emphasis has shifted toward cost optimization and manufacturability. Reducing the costs of medicines for patients and payers (thereby broadening access to drugs) is now a key driver during development of new therapies as well as modernizing processes for existing molecules. Cost reduction includes providing robust manufacturing processes that…

September 15, 2016

Quality By Design for Monoclonal Antibodies, Part 2: Process Design Space and Control Strategies

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Process design space and control strategy are two fundamental elements of quality by design (QbD) that must be established as part of biopharmaceutical development and regulatory filings. Like all of QbD, they are interconnected and iterative. Both are based on knowledge gained during product and process development — but both need to be in place (in a potentially very limited form) when a company begins to manufacture drug substance for clinical trials. Part 1 of this discussion appears on pages…

September 15, 2016

Performance Qualification of a Single-Use, Stirred-Tank Bioreactor with CHO-S Cell Culture

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The increasing role and importance of cell culture in biophamaceutical manufacturing has led to considerable research and development (R&D) into bioreactor design and performance in recent years. As a result, a greater understanding of bioreactor fluid dynamics and critical physical parameters is now essential to maximize cell growth and productivity. Stirred-tank bioreactors are especially important in this development process because of their favorable properties in areas such as mixing efficiency and homogeneity, energy transfer, and scalability. The design and manufacture…

September 15, 2016

Optimizing Continuous Monoclonal Antibody Polishing By Using Coupled Unit Operations

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The biopharmaceutical industry is under a great deal of pressure to modernize manufacturing to meet the challenges of production at vastly different scales for niche drugs as well as for expected massive blockbusters, biosimilars, and regional manufacturing. To address these challenges, the biopharmaceutical industry is embracing process intensification through single-use and continuous processing technologies. Implementing these technologies offers increased productivity and manufacturing flexibility and reduces the footprint, capital outlay, and operating costs. Pall Life Sciences has developed several technologies designed…

June 27, 2016