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 with several industry experts regarding legacy technologies in bioprocessing for a special report in the September issue of BPI (
1
). The discussions herein delve deeper into some examples among upstream production and downstream processing unit operations.
Concrete and Steel
Andrew Skibo (executive vice president of operations at MedImmune) pointed out some key factors that produced that clutch of concrete and steel dinosaurs. Most plants built in the 1980s were “designed by no more than three or four engineering firms — Jacobs Life Sci...
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 30 companies, respectively, as of June 2012). Auditors, regulatory agencies, and professional trade organizations may participate as observers. Rx-360 actively engages with global regulatory agencies such as the European Medicines Agency (EMA), the US Food and Drug Administration (FDA), the World Health Organization (WHO), the European Directorate for the Quality of Medicines & Healthcare (EDQM), and t...
In biopharmaceutical development, ancillary business operations such as logistics and supply chain management are frequently perceived as secondary objectives to the ultimate goal of discovering treatments and cures for devastating diseases. However, in the hypercompetitive world of drug development, forward-thinking companies have found that optimizing their clinical-trial supply chain can provide a strategic advantage to accelerating drug development.
The globalization of clinical research has made the safe, punctual, and compliant transport of study drugs and other temperature-sensitive materials increasingly complex. Two other trends are also increasing the demand for transporting sensitive materials: Biotech companies are creating more large-molecule drugs, which are much less stable than most small-molecule drugs. Furthermore, although blood, urine, and microbiological and viral sampling has always been common, increasing numbers of tissue samples are being collected to support biomarker research.
C...
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, autoimmune, and cardiovascular disorders, to name just the most prominent. And although MAbs are finally fulfilling their “magic bullet” promise, many other approaches are becoming available to drug developers targeting those markets — and others.
Meanwhile, funding challenges are increasing emphasis on manufacturing and development efficiencies. Even though total funding of the biotechnology industry has rebounded since the 2008 recession — from about US$13 billi...
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 efficacy (1–2 mg/kg). So they need to be concentrated sufficiently to allow for reasonable administration volumes by intravenous infusion or subcutaneous injection. But MAbs are not unique with regard to potential aggregation–related problems. The need for formulation with surfactants transcends many classes and types of biotherapeutics.
PRODUCT FOCUS:
PROTEINS, AN...
Vaccines represent a significant, increasing area of product development within the biopharmaceutical industry. The segment includes several blockbuster commercial products, nearly 300 vaccines currently in development, and many more candidates in various stages of research and preclinical development (
1
). The 2010 worldwide vaccine market was ~US$20 billion and is projected to approach $30 billion by 2015 (
2
). Conjugate vaccines sales currently exceed $7 billion and are expected to increase substantially. Conjugate vaccines (covalently linked polysaccharide and protein) have shown to be effective against several bacterial pathogens such as
Haemophilus influenzae
type b (Hib),
Streptococcus pneumoniae, Neisseria meningitidis
, and
Salmonella enterica serovar Typhi
(
3
).
The Role of Carrier Proteins
Carrier proteins increase the immunogenicity of peptides, oligosaccharides, polysaccharides, and haptens. Polysaccharides, which are T cell–independent antigens, are poor immunogens unless they are ch...
+2Taking full advantage of high cell-specific productivity of recombinant proteins requires use of robust fed-batch processes involving addition of one or more concentrated nutrient solutions. Proportionately large amounts of concentrated nutrient supplements are often needed to support the stoichiometrically balanced metabolic requirements of high-density cell cultures. Large feed additions ultimately dilute the final product at harvest, but attempts to minimize feed volumes often lead to multiple concentrated acidic and basic subgroups. Those impart additional complexity to manufacturing processes.
When optimizing basal media and feeds, increasing key component concentrations (fortification) can help increase product titers. However, alternative methods must ensure maintenance of specific productivity later in culture. Considering the difficulties intrinsic to providing desired concentrations of key nutrients in fed-batch culture, an ideal additive would be highly concentrated, single-part, pH-neutral, an...
+6 Single-Use Technology
Product:
inSITE inflation and integrity testing system
Applications:
Media/buffer preparation, filtration, separations, seed/culture harvest, ultrafiltration, final filling
Features:
ASI’s inSITE system applies a final integrity test at the point of use to eliminate concerns for gross and fine leaks that can come from handling and loading procedures. The unit will inflate to a specified pressure to limit errors from pinching and creasing. It can be used with any container ≤3,000 L and is completely mobile with cleanroom-grade wheels and a light-weight design. An on-board printer documents test results, and a scanner provides access to product details.
Contact ASI Life Sciences
www.asius.com
Electroporation
Product:
AgilePulse In Vivo electroporation system
Applications:
Vaccines and gene therapies
Features:
The AgilePulse In Vivo electroporation system uses variable pulse-amplitude technology with patented waveforms consisting of multiple, varying low- to high-pulses. This pr...
This is the only event in Japan with coverage of all oligonucleotide classes: RNAi, peptide therapeutics, and vaccines. AsiaTIDES continues to be the premier forum where attendees get a comprehensive update, meet key players, and increase their knowledge of the oligonucleotide- and peptide-based therapeutics fields.
Hear the latest reports from RXi, Tekmira, Santaris, miRagen, Arrowhead, REPLICor, Noxxon, Silence, PeptiDream, Pfizer, Immunovaccine, OncoTherapy Science, Zealand, Radius, Aileron, and more. Learn manufacturing capabilities of all the major oligonucleotide and peptide contract manufacturing organizations (CMOs). For updates on science, business developments, and regulatory changes — as well as practical tutorials — this event is your best conference choice to update your knowledge in all the relevant areas in just three days.
Many presentations throughout the program will include unpublished data first heard at AsiaTIDES. Gain a competitive edge by hearing first-hand unpublished data from our...
Increased activation of cell survival signaling cascades helps tumor cells grow and makes cancer cells difficult to kill. Inhibiting proteins involved in those survival pathways is a useful strategy for selectively destroying such cells. The mitogen-activated protein kinase (MAPK) pathway is one such signaling cascade. Preclinical research finds that it is activated in most melanomas. One key kinase involved has become the focus of some targeted melanoma therapies. MAPK/ERK kinase (MEK), also known as MAPKK, has several known isoforms that play different roles. Two of those (collectively “MEK1/2”) are associated with MEK’s ability to promote cell survival.
Another oncogenic perturbation to cellular signaling cascades is hyperactivation of BRAF kinase. Genetic mutations causing the BRAF protein to be unusually active are found in 60% of melanomas.
Roche/Genentech and Plexxikon
(part of Daiichi Sankyo) have together developed and commercialized a targeted therapy (vemurafenib) for metastatic melanoma with...
