Scale-up a stem cell process may be challenging: small variations in physicochemical parameters (surface characteristics, pH and dissolved oxygen) can heavily impact stem cell growth and behavior. The Integrity® Xpansion™ multiplate bioreactors have been designed to enable an easy transfer from multiple-tray stacks process by offering the same cell growth environment: stacked hydrophylized polystyrene plates in a compact and closed system (from 10 to 200 plates per bioreactor equivalent respectively to 6120cm² and 122400cm²). As there is no headspace between…
Manufacturing
Production and Purification of a PER.C6-Expressed IgM Antibody Therapeutic
Immunoglobulin G (IgG) antibodies have been used to treat cancer for many years (1). Another class of antibodies—immunoglobulin M (IgM)—has been overlooked in spite of offering unique advantages that make them highly desirable as cancer therapeutics. Serving a valuable function in our innate immune system, IgM antibodies are the first to be secreted when an abnormal cell is present (2). These antibodies play a critical role in recognition and elimination of infectious particles (3,4), in removal of intracellular…
Glass Delamination and Breakage
Although glass is widely considered to be the most traditional and cost-effective option for a parenteral drug container or delivery system, it may not always be the most economical or the best choice for certain products. With knowledge emerging about the suitability of materials in contact with drug products, it is time to look at alternatives that may offer a more appropriate choice and mitigate the risks associated with glass. As single-use technology finds its way into upstream…
Clinical Development of Biosimilars
Biosimilars require comparative studies that are different from the typical placebo-control clinical trials for first-generation proteins. A typical clinical trial programs must show equivalence of a biosimilar to the originator protein. Hans-Peter Guler, senior vice president of clinical development at INC Research, recently discussed with me the primary objectives and approaches to conducting an equivalence design. By contrast with trials for originator proteins, equivalence trials require a different statistical approach. The biosimilars company needs agreement from the…
Characterization and Performance of the Mobius® CellReady 200 L Bioreactor System: The next Generation of Single-Use Bioreactors
Successful bioprocessing relies on the ability to accurately and effectively monitor and control critical process parameters. The Mobius® CellReady 200 L single-use bioreactor is uniquely designed with the novel Mobius® Mobius® SensorReady technology, an external loop that enables configurable, flexible and functional monitoring and control. Bioreactor characterization properties such as mixing time, volumetric mass transfer capabilities, temperature mapping and power input define the process design space wherein accurate and effective monitoring and control can occur. Each of the aforementioned characterization…
Sustainability in Bioprocessing
The concept of sustainability has evolved over the past few decades to describe conditions for harmonious coexistence of industry and nature while meeting socioeconomic requirements of present and future generations. For this environmentally focused report, I like the simple definition offered by Armstrong International, a provider of steam, air, and hot water systems that improve utility performance, lower energy consumption, and reduce environmental emissions. According to a brochure that in part describes its work with Pfizer, Armstrong defines…
Toward Defined Culture Conditions for Pluripotent Stem Cells, Part 2
At the UK National Stem Cell Network ‘s annual meeting in York, UK on 31 March 2011, a workshop organized by STEMCELL Technologies workshop addressed defined media for human stem cell culture. As illustrated in Part 1 (October 2011), it is critical to understand the pathways that maintain genetic stability during hES self-renewal, which is a prerequisite for all clinical applications. Because physiological DNA damage can take place during normal cellular proliferation, and accumulation of unrepaired DNA could…
Monoclonal Antibody Manufacturing
Continuing the theme of this occasional series, we examine the role of manufacturing in the supply chain in terms of what is required to deliver affordable medicines to patients. The industry has debated the relevance of manufacturing costs in the overall big picture (1). Rising manufacturing costs as a proportion of the overall selling price coupled with increased competitive pressures creates a strong drive to reduce manufacturing costs. However, cost of goods (CoG) is not the only strategic…
Biosimilars in Development
The 2009 Biologics Price Competition and Innovation Act (BPCIA) provided the bioprocessing industry with the legislative pathway toward approval of biosimilars. US Food and Drug Administration information regarding how it will translate that legislation, however, had been limited until an August 2011 article finally provided some insight on how those guidances might actually play out (1). As expected, the agency appears to be implementing a science-driven approach, with sponsor companies needing to apply complementary orthogonal analytical methods to…
Use of Blast Freezers in Vaccine Manufacture
Vaccines are powerful and cost effective prophylactic tools for protecting public health. The Global Alliance for Vaccines and Immunizations (GAVI) estimates that ~5.4 million lives are saved each year by the administration of vaccines for hepatitis B, measles, haemophilus influenza type B (hib), pertussis (whooping cough), yellow fever, and polio (1). According to the World Health Organization, seasonal influenza alone claims 250,000–500,000 lives every year globally, many of which could be prevented by more widespread vaccination with the…