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…
Business
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…
Stress-Induced Antibody Aggregates
Biomanufacturing of monoclonal antibodies (MAb) involves a number of unit operations, including cell culture in a bioreactor followed by chromatography and filtration. Purification is intended to remove impurities, such as protein aggregates, but some such operations may actually generate protein aggregation (1). Table 1 summarizes potential sources of aggregate formation during biomanufacturing processes. Aggregates are multimers of native, partially denatured, or fully denatured proteins. Their presence in biological formulations can trigger detrimental immunogenic responses upon administration (2). Moreover, aggregates can…
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,…
Deal-Making in the Biosimilars Market
Driven by significant opportunity and a perceived lower risk strategy for taking a slice of the booming biologics market, companies have been investing heavily in biosimilars to capitalize on a market that’s forecast to be worth US$3.5 billion by 2015. To exploit this opportunity, companies have embarked on a hearty meal of deal-making. Since the biosimilar market’s formal inception in Europe in 2005, deal flow has been solid. Generics companies made early forays, seeking to leverage relationships with payers and…
Manufacturing Culture
Life sciences company leaders need to put the right people, processes, and technologies in place to create evolutionary cultures. Such cultures would embrace advanced manufacturing process intelligence and reap related business benefits. Since the late 1990s, my software company has helped biomanufacturers improve their process understanding. In that time, we’ve seen regulatory drivers such as quality by design (QbD) and process analytical technology (PAT) guidances call for improved manufacturing process performance through better process understanding and optimization. We define process…
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…