Downstream Development

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

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…

Accelerated Development Through Strategic Analytical Partnerships

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…

Outsourcing Biosimilar Development

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…

Introduction: Process Issues in Cell, Gene, and Tissue Therapies

It’s hard to believe that just six years ago, BioProcess International published its first cell therapy supplement, which included just one article on “cell therapy bioprocessing” (1). At the time, most such processing was conducted in special clinical laboratories and academic institutions. As BPI continued to cover this relatively new segment of the biopharmaceutical industry, we heard more about “the product is the process” and “scale out instead of scaling up.” After many trials, errors, and milestones, regenerative medicine has…

Buffers in Biologics Manufacturing

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…

Reducing Clinical-Phase Manufacturing Costs: Collaborating for Savings without Compromising Quality or Performance

In downstream purification of monoclonal antibodies (MAbs), the single greatest contributor to manufacturing costs is the expensive capture step typically based on protein A affinity chromatography. Almost since its introduction to bioprocessing, efforts have been made to reduce the cost of this step. Several alternative ligands have been promulgated as potential replacements for protein A, but they have proven difficult to adopt and scale up. Supplier companies have pushed for increases in capacity and economics, but those are always accompanied…

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

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…

Emerging Technology Trends in Biologics Development: A Contract Development and Manufacturing Perspective

For a contract development and manufacturing organization (CDMO), process development and manufacturing of recombinant proteins must be linked because of tight timelines driven by client expectations. Those are in turn driven by a need for rapid progression to clinical testing. Early in process development, the choice of raw materials needs to reflect existing supply chain and manufacturing infrastructure, but remain suitable for scaling up to meet future needs. One approach is to establish platform processes for a class of molecules…

Selective and Flexible Chromatography Media: Improving Biopharmaceutical Operational Efficiencies

Continuing development in protein and peptide engineering have produced a broad range of new biological products with improved therapeutic and diagnostic potential. In the development pipeline, more than 900 biologic products target more than 100 diseases (1). Increased manufacturing complexities caused by closely related impurities and requirements to improve process efficiencies and reduce operating costs highlight the need for new approaches in protein purification. Platform-based chromatographic approaches have been successfully applied in separating and purifying monoclonal antibody (MAb) products. But…

Viral Clearance in Antibody Purification Using Tentacle Ion Exchangers

Manufacturers strive toward cost-effective purification of target molecules and a high level of confidence that their biologics are safe and not compromised by the presence of endogenous retrovirus-like particles or adventitious viruses (1). Reliable reduction of viral particles throughout downstream purification processes must be ensured through different techniques such as chemical treatment, filtration, and chromatography. Common monoclonal antibody (MAb) purification schemes use both cation- and anion-exchange chromatography steps (CEX, AEX). Although CEX (to remove product- and process-related impurities) is not…