MAb

Characterization of Human Mesenchymal Stem Cells

Human mesenchymal stem cells (hMSCs) are a self-renewing population of adherent, multipotent progenitor cells that can differentiate into several lineages. The current definition of MSCs includes adherence to standard tissue culture plastic ware, expression of various surface antigens, and multilineage in vitro differentiation potential (osteogenic, chondrogenic, and adipogenic). hMSCs hold great promise as therapeutic agents because of their potential ability to replace damaged tissue and their immunomodulatory properties. Consequently, many clinical trials using hMSCs are currently under way in a…

A Statistical Approach to Expanding Production Capacity

Contract manufacturer DSM Biologics — at its current good manufacturing practices (CGMP) facility in Groningen, The Netherlands — provides services for clinical development and commercial production based on mammalian cell culture technology (Photo 1). During the 2011–2012 year, the facility went through a major expansion project to enlarge its capacity and fulfill a growing customer demand. From a business point of view, the project had a well-defined target for future production capacity as well as investment volume. Photo 1: Photo…

Tunable Half-Life Technology

While a constantly developing market puts increasing pressure on pharmaceutical companies to provide advanced and personalized therapies, the industry is investing heavily in the development of targeted biologics. The aim is often to take new therapeutics through clinical trials and to market as quickly as possible and to develop more novel, tailored drugs. One common challenge for many biologics is their short plasma half-life. That often leads to reduced bioavailability, meaning that an administered drug will clear from a patient’s…

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,…

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…

Performance of a Salt-Tolerant Membrane Adsorber in Flow-Through Mode

Monoclonal antibodies (MAbs) have become the most prevalent therapeutics in the biopharmaceutical industry. Their downstream purification typically involves protein A chromatography as a capture step followed by one or two additional chromatographic polishing steps. Additional unit operations dedicated specifically for viral clearance (e.g., viral inactivation and filtration) are added to ensure product safety. According to a survey of Amgen processes, after processing through a protein A column, only trace amounts of impurities such as Chinese hamster ovary cell protein (CHOP)…

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…

Analysis of Bacterial Biomass Growth and Metabolite Accumulation

Mathematical modeling has been widely used in microbiology and biotechnology for several decades. The main objective of modeling is to find optimal conditions for microbial growth and biosynthesis of useful metabolites. We modified the well-known equation of Perth–Marr (1) — proposed to calculate the energy consumption of a substrate— to analyze the energy consumption by cells for growth and viability maintenance. Our study includes that theory along with our own development. Our initial modeling work was carried out with Yersinia,…