As the bioprocessing industry has shifted away from traditional stainless steel bioreactors and vessels toward single-use technology, a new breed of manufacturing facilities has arisen. Flexible facilities take full advantage of traditional multiuse technologies and combine them with increasingly popular single-use technologies, offering an ability to mitigate risk and decrease manufacturing timelines. Although some companies have made the choice to remain strictly traditional (multiple use) and others have moved fully into single use, the flexible hybrid format gives…
Manufacturing
Establishing Strategic Supplier Partnerships to Facilitate Manufacturing Success
In November 2009, Talecris Biotherapeutics announced an ambitious US$269 million expansion of its Clayton, NC, manufacturing facility. The company was subsequently purchased by Grifols, Inc. in 2011. Constructing a new facility with a state-of-the-art manufacturing process intended to generate clinical products involves top-notch project management, exceptional fortitude, and numerous supply chain decisions. Suppliers are often relied on to provide standard product support. When used effectively, they can be an invaluable resource beyond basic services. Additional support may include…
Understanding the Patient Journey
The biopharmaceutical industry is abuzz with talk regarding a 2011 US Food and Drug Administration (FDA) guidance on human factors and the mitigation of user-based risk in the development of medical devices (1). As expected, his talk is often accompanied by a sense of anxiety. Device developers and the growing number of biomanufacturers developing combination drug–device products now need answers to usability questions they are hardly familiar with. Wrong answers may have direct (and troubling) implications from a…
Lean Six Sigma
About 10 years ago as a vice president of Avecia Biologics, I wrote an article for an early issue of BioProcess International looking ahead at likely changes in biomanufacturing (1,2,3). For the best part of the intervening period, Avecia Biologics and Diosynth slugged it out in the marketplace, each trying to grow its contract manufacturing business at the expense of the other. But in a life-altering two-year period between 2009 and 2011, both companies saw their realities and…
Biopharmaceuticals On Demand
By 2016, five of the top 10 biopharmaceuticals are expected to be monoclonal antibodies (MAbs). Follow-on (biosimilar) versions of those blockbusters will most likely become available in later years due to patent expiry and the introduction of legislation for biosimilars around the world. Personalized therapies will drive the fractionation of the biopharmaceutical market, trending biomanufacturing toward smaller batch sizes and campaign-based production schemes. A growing need for flexible, multipurpose, and cost-effective manufacturing will significantly affect the design of…
Culture of Normal Human Dermal Fibroblast Cells in a Functionally Closed Automated Cell Expansion System
The Quantum Cell Expansion System is a functionally closed and automated hollow-fiber bioreactor system that is designed to expand both adherent and suspension cells in a reproducible manner. The hollow-fiber membrane requires a coating agent to help facilitate cellular adherence when culturing an adherent cell type such as MSCs. Pooled human cryoprecipitate (CPPT, Bonfils Blood Center) was examined as an alternative to FN because it is a rich source of extracellular matrix components, including fibrinogen (Freedman, 2010), and also because…
The Dinosaurs Can Evolve
Barring fire, major earthquakes, or volcanic catastrophe, concrete is good for centuries — the Pantheon has been in continuous use since 126 AD. The long expected life and high initial cost of biomanufacturing buildings and equipment builds legacy into the system from the start. And the imperatives of launching a new biotechnology industry in the 1980s led to the building of many facilities within a few years to produce the first wave of recombinant DNA products. I spoke…
Participating in the Rx-360 Pilot Joint Audit Program
The Rx-360 consortium has had a profoundly positive impact on pharmaceutical manufacturers and their suppliers. As an international, nonprofit, pharmaceutical supply chain group (established in 2009), its mission is to “create and monitor a global quality system that meets the expectations of industry and regulators that assures patient safety by enhancing product quality and authenticity throughout the supply chain†(1). The list of consortium members (www.rx-360.org/Membership/ListofMembers/tabid/71/Default.aspx) is diverse and presently includes both pharmaceutical manufacturers and suppliers (24 and…
Toward Nonantibody Platforms
Monoclonal antibodies (MAbs) remain the largest segment of the biopharmaceutical market, but they are not the only recombinant proteins in development. Remember that the first biopharmaceutical approved for sale was recombinant insulin — a hormone — back in the 1980s. And proteins aren’t the only recombinant biologics. The sector has expanded since then to include gene therapies and viral vectors, vaccines, and even cells and tissues. Companies around the world are developing such products for cancer, neurological, infectious disease, metabolic,…
Polysorbates, Immunogenicity, and the Totality of the Evidence
Protein aggregation underlies many deleterious effects for biotherapeutics. Principal among those are loss of efficacy, induction of unwanted immunogenicity, altered pharmacokinetics, and reduced shelf life. Consequently, aggregation-preventing surfactants are essential components of many protein formulations. They facilitate the development, manufacture, and stability of dosage forms by helping formulators manage protein aggregation and reduce interactions with container and delivery device surfaces. Monoclonal antibodies (MAbs) present difficulties with respect to aggregation because they usually require relatively high doses for therapeutic…