Upstream Processing

Advocating an Evolution

In a 2006 report, the US Department of Health and Human Services hailed regenerative medicine as “the vanguard of 21st century healthcare” and “the first truly interdisciplinary field that utilizes and brings together nearly every field in science” (1). To fuel support for regulatory, legislative, and reimbursement initiatives in this new therapeutic class, a small group of scientists, life science business executives, patient advocates, and other experts formed the Alliance for Regenerative Medicine (ARM, http://alliancerm.org). Starting with 17 charter members,…

2012 in Review

As children growing up, we could barely contain our anticipation for those banner, milestone years: entering first grade, becoming a teenager, turning 16 and then 18, high-school graduation. But even the most innocuous “in-between” years saw notable change and maturation, and 2012 was just such a year for the growing cell therapy sector. Although it is not likely to be noted as a pivotal or breakthrough year, 2012 nonetheless delivered some significant and welcome signposts of continued sector maturation. Here…

Single-Use Technologies in Cell Therapy

Single-use technologies (SUTs) are tools that can be used in producing cell therapies and personalized medicines. Such products must meet specific requirements because of the way they are used. To meet those criteria, the cell therapy industry simply has no alternatives to single-use systems. SUT applications are rapidly changing. Traditional uses for single-use systems in cell therapy include processing in clinical settings (e.g., blood bags, transfer sets) and research and development (e.g., T-flasks, pipettes). Although such applications continue, the commercialization…

Automation of Cell Therapy Biomanufacturing

Biomanufacturing automation is an established mission-critical step in the commercialization pathway for conventional therapeutics, including small molecules and monoclonal antibodies (MAbs) (1). The prospect of a potential biologic progressing into late-stage clinical trials without a robust biomanufacturing strategy to support at least pilot-plant scale bioprocessing is simply unthinkable. Conversely, the cell therapy industry (or at least a significant proportion of it) regard this as a trend that is unlikely to be mirrored as the industry develops. The aim of this…

PEGylation of Biologics

In the 1970s, life-science researchers envisioned protein therapeutics as the ultimate targeted therapy. Companies could use them to address genetic deficiencies and cancer, among other disease classes, as well as to nudge the immune system for treating autoimmune disorders. The first therapeutic proteins were derived from animal or microbial cells, so patients launched immune responses to them that could curtail their activity and produce dangerous side effects. PEGylation was initially used to prevent immune responses with such drugs. PEG is…

Managing Contamination Risk While Maintaining Quality in Cell-Therapy Manufacturing

With an increasing number of cell therapies becoming available for patient use, the need for controlled and consistent manufacturing and delivery of cell products is increasingly important. A closed cell culture process not only offers control and consistency, but may also relieve labor demands. Single-use components within a closed process also can reduce contamination risk. Closed systems with single-use platforms may reduce the risk of biological contamination and cross-contamination that could inadvertently be introduced into cell-culture processes. Such contaminants use…

Implementation of Quality By Design in Vaccine Development

At the IBC Third Annual International Forum on Vaccine Production, I presented an outline of “Best Practices for Quality by Design (QbD) in Biological Products and How to Implement in Vaccines.” It covered process development and QbD principles, best practices used in biologics, how QbD fits in with process validation, how it applies to vaccines, and some thoughts on the potential for seasonal vaccines. Shifts in Process Development Classic process development (as practiced in the early days) generally involved rudimentary…

Antibodies, Bioassays, and Cells

It’s no surprise that immunochemistry forms a broad and solid basis of biopharmaceutical analytical laboratory work. Immunochemicals include antibiotics and antigens, nucleic acids and nucleotides, enzymes, lipids, antioxidants, probes and dyes, and proteins and peptides. Available from companies such as Advanced Immunochemical, Immundiagnostik, Lampire Biological Laboratories, and Rockland Antibodies and Assays, their many uses include antibody isotyping and fragmentation. Adjuvants, buffers, assay kits, target biomolecules, and phage-display systems support those applications. Because background and off-target effects complicate the study of…

Protein Scaffolds

The recent success of monoclonal antibodies (MAbs) as therapeutic agents to treat cancer, multiple sclerosis, rheumatoid arthritis, and other chronic inflammatory and autoimmune disorders (Table 1) has catapulted these once difficult-to-develop molecules to the forefront of modern molecular medicine (1, 2). The size of the global MAb market in 2008 was valued at almost US$28 billion. Industry analysts predict that the size of the MAb market will grow to almost $68 billion by 2015, with the largest growth occurring in…

Evaluation of a New Single-Use UV Sensor for Protein A Capture

As the adoption of single-use systems continues to expand beyond bags and tubing to complete process steps, a full range of sensing technologies will be needed to complement the resulting varied single-use applications. Single-use sensors must meet or exceed the performance of traditional sensing technologies in areas such as accuracy, response time, ease of use, control system integration, process compatibility, regulatory requirements, and cost. Single-use flow-through process sensors are currently available for pressure, temperature, flow, and conductivity. Here, we report…