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The business of Monoclonal antiBody Production
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MabNet ran a course on the Business of Monoclonal Antibody Production at the Biotech Research Institute, Montréal. Pictured above are the 65 participants.
MabNet, the national Monoclonal Antibody Network sponsored an advanced course: “The Business of Monoclonal Antibody Production” at the NRC-Biotechnology Research Institute, Montréal September 10-11, 2012. The advanced course was designed to provide education and training on industrial and business aspects of monoclonal antibody production. There were approximately 65 delegates in attendance that included 30 experts from industry and government and 35 MabNet trainees. The Natural Sciences and Engineering Research Council of Canada (NSERC) provided support for the course, including travel for MabNet trainees, through a grant under the Strategic Network Enhancement Initiative.
The objective was to ensure that all participants gained a grasp of the implementation of state-of-the-art Monoclonal Antibody (Mab) technologies in an industrial setting. Business, fi nancial and intellectual property issues were also covered, providing a comprehensive review aimed at current and future business executives and industry managers. The course was organized as a series of lectures delivered by invited speakers from the bio-industry and included discussion following formal presentations at the end of each day. Opening the meeting were Michael Butler, MabNet Scientifi c director, who emphasised the important role of a national network like MabNet in enhancing the biotechnology industry in Canada and David Shindler, chair of MabNet’s board of directors, who noted that during the very early development of monoclonal antibodies, the technology was dismissed as of no commercial value when fi rst assessed for patent protection!
The fi rst speaker, Marcel Mongeon gave an exceptionally lively opening lecture on patent law and practice. Describing himself as an “Intellectual Property Coach,” Mongeon elucidated the basic requirements to establish a patent. Using relevant examples he demonstrated the necessity to establish novelty and utility of an invention but cautioned on the complexity and cost of establishing patents worldwide. Only a small proportion of all patents (probably < one per cent) recover the costs of fi ling and become money earners. Nevertheless, industry executives and managers must establish patent portfolios and protect inventions in order to be world-competitive.
There followed a series of lectures on the business basis of contract manufacturing in biotechnology. Jason Dowd of Apotex described the challenges that can exist between client and provider. The client can often be a virtual company that may well underestimate the full fi nancial cost of development of a novel product. Bioprocess scale-up often comes the competing challenges of maintaining high productivity and product quality assessed by for example the degree of sialylation of a glycoprotein. Challenges of developing a biosimilar can be associated with misinformation of the correct amino acid sequence because of discrepancies in available databases. Gregor Awang of Cangene developed these points by emphasising the need to establish realistic end-points at each stage of scale-up. There are various choices to be made in developing a potential glycoprotein product including the choice of cell line and the control of the defi ned serum-free media. Strategies that avoid intellectual property issues are important. The quality profi le of the fi nal product needs to be monitored closely to ensure consistency as scale-up is developed from cell banks, shake fl asks and to larger multiple liter bioreactors. Devender Sandhu of Therapure then explained the business strategy associated with custom manufacturing organizations (CMOs). The number of licensed biologicals is increasing rapidly. This includes an explosion of interest in drug conjugates with the ability to bind to two separate receptors. This increase in products has enhanced the importance and need for CMOs. The growth of the client base of Therapure in Toronto was described as an example of a rapidly expanding CMO. Richard Mateles, an independent biotechnology consultant from Chicago expanded this theme by explaining that contracting out specifi c tasks for bioproduction is a common industry practice, as there are only a few stand-alone CMOs globally.
Ziawei Fung of GE Healthcare gave a description of the importance of downstream processing as a stage in bioprocessing. High throughput methods have been developed by GE and designated as Fasttrack technology. This offers possibilities for rapid and
adaptable turn-key 2-column chromatographic methods for purifying monoclonal antibodies.
The first day was concluded by a presentation from Bernard Massie, program director at the National Research Council (NRC). He described in detail the new strategic plan of the NRC that includes “pillars” which are scientific themes that allow interaction between the different national sites of the NRC. Course organizers expressed appreciation to NRC for providing the ideal venue for the course.
The second day was opened by a presentation from Jean-Francois Marier of Pharsight Consulting Services on modeling and simulation to support clinical development of monoclonal antibodies. Dr. Marier discussed the historical 50 per cent failure rate of drugs in Phase 3 clinical studies and how modelling and simulation of clinical trials may have prevented these failures based on a priori knowledge available in Phase 1 to 2 studies. Modelling of pharmacokinetics (PK) and pharmacodynamics (PD) of monoclonal antibodies and simulation of clinical trials were discussed as a tool to support decision making in drug development. These considerations are such that clinical trials involving monoclonal antibodies need to be designed differently than small molecule therapeutics in order to ensure successful outcomes in late stage clinical development.
Pranav Desai of GE Healthcare continued with a presentation on the trends in monoclonal antibody process economics. Early decisions are critical in the development of a novel product connected with the predicted quantity of the material that will be required. The specific productivity of the producer cell, length of culture and down-stream processing protocols are all major parameters of early decision making. Such decisions have a bearing on the size of bioreactor and whether to employ single-use bioreactor components. Although disposable bioreactors have been popular lately, there may be distinct advantages of using stainless steel bioreactors at larger volumes (>10,000 litres).
Jennifer Maynard from the University of Texas then discussed the clinical basis of antibody therapy. She emphasised the importance of studying the binding capacity of therapeutic Mabs and pointed to past examples of the use of polyclonal antibodies in the treatment of conditions including diphtheria and snake bites. These examples point to the value of targeting multiple epitopes of the clinical target. A mimic of the older therapies might be considered with a cocktail of Mabs for the same target. This can be a better strategy than improving the binding capacity of a single Mab, a strategy which has been shown to not always improve the clinical outcome. Carlos Bosques of Momenta Pharmaceuticals gave a presentation on the potential immunogenicity and potential side effects of therapeutic Mabs. Emphasising that a Mab formulation may well contain a mixture of isoforms based upon variations in the source material, cells and the control of the bioprocess. As recently as the late 1990s it was maintained that CHO cells, typically used for industrial Mab production, did not have the capacity to produce the well-known immunogen, gal-α1,3 gal. However in a recent paper Carlos and others showed that indeed the genetic capacity for producing this unwanted immunogen is present in the CHO cell lines commonly used in large-scale biopharmaceutical production. Donald Gerson continued with a description of his experiences of building a large-scale production plant for protein biopharmaceuticals in a newly developed area of Incheon, South Korea. Initial funding of $200 million ensured that the plant was state-of-the-art with an enormous potential for rapid development of novel biological entities. Donald has now returned to Canada taking up the challenge with PnuVax Inc of building a biomanufacturing facility in adjoining ground to the NRC building in Montréal.
The meeting was concluded with a presentation by John Babcook from the Centre for Drug Research and Development in Vancouver with an overview of current trends in antibody-based therapeutics. Many of his examples were taken from the so-called SLAM technology using a xenomouse program that led to multiple examples of FDA approved Mabs.
In conclusion, it was felt that the two-day meeting provided a unique opportunity for attendees to gain new insights into a dimension of the commercial production and clinical aspects of monoclonal antibodies For trainees, the course complemented their experiences in their laboratory-based projects. This meeting provided a platform that helped participants to understand various critical aspects of the Monoclonal Antibody sector, that is gaining an enormous global importance.
Michael Butler is a Distinguished Professor at the Department of Microbiology, University of Manitoba, Winnipeg, Manitoba and Scientific Director of MabNet. He can be reached at butler@ cc.umanitoba.ca.
To see this story online visit http://biotechnologyfocus. ca/?p=2192
Continued from page 23
needs of the private sector partner, and the demand from global healthcare markets provides an industry-friendly atmosphere.
Co-development and licensing deals are already enriching Techna’s track record. Since its launch in November 2011, Techna has been actively commercializing products through the UHN TDC, four of which are generating revenue. Revenues are reinvested into the projects for further development, creating a self-sustaining model that is rare amongst public and academic institutions. Almost all these products have a close industry partner to help manufacture, sell, and distribute the technology.
As an institute of UHN, Techna has access to over 500 hospital researchers, 13,000 clinical staff, and 1300 technical staff. Through its partnership with UofT, Techna has access to thousands of faculty and researchers in the fields of medicine, applied sciences and engineering, business, and the physical sciences. Techna is the gateway for industry and private inventors to utilize these human resources. Techna helps with evaluating the clinical need of new technologies developed internally and externally. It can advise on the value proposition, and commercial viability prior to further development of the product.
The Techna Network research infrastructure is integrated throughout the campuses of UHN, MaRS Discovery District, UofT, and through other affiliated partner facilities. The infrastructure includes hardware and software laboratories, MR scanners, x-ray CT suites, multimodality PET-CT suite, preclinical laboratories at the STTARR facility (http://www.sttarr.com/), Healthcare Human Factors laboratory (http://humanfactors.ca/), and machine shops. Additional infrastructure will become operational in 2012 and 2013 – MR-PET, MR-guided radiotherapy (MRgRT) suite, cyclotron and radiochemistry laboratory, magnetoencephalography (MEG) facility, NanoMedFab facility, Guided Therapeutics (GTx) laboratory, and TRIGOR-A x-ray and optically guided operating room. Techna also helps its investigators and partner institutions secure lab and office space.
Techna is expanding and is hiring fully funded faculty and accepting applications for cross-faculty appointments. Techna management works with UHN and UofT leadership to offer an exciting environment that will attract the best talent and scientific, clinical, and engineering trainees.
References:
1. Advanced Medical Devices in Ontario –
Healthcare Solutions for Global Markets (08/2008) 2. Clinical Trial in Ontario (05,2009) 3. Oncology (05/2009) 4. Research and Development in Ontario –
Incentives for Innovation (11/2010) 5. eROI – Report on Ontario Investment,
Spring 2012
For more information regarding Techna, please visit the website or email at Techna@rmp.uhn.on.ca
Luke Brzozowski Ph.D. is a Director of Operations and Engineering at the Techna Institute for the Advancement of Technology for Health University Health Network
To see this story online visit http://biotechnologyfocus. ca/?p=2209
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Data Logger: Omega introduces its new series of precision RTD temperature data loggers. The OM-CP-RTDTEMP101A accepts 2-, 3- or 4-wire 100 pt RTD input and features a long battery life of 10 years, multiple start/stop function, ultra high speed download, 670,000 reading storage capacity, memory wrap and programmable
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Pipettes: Eppendorf presents its new electronic pipette Eppendorf Xplorer plus®. The intuitive operating concept and ergonomic display of the Xplorer set new standards in simplicity, precision and reproducibility. The Eppendorf Xplorer is specially designed for users working with complex or long pipetting series requiring the utmost in exact setting of parameters, maximum reproducibility and low operating force. Now with the release of the Xplorer plus there are additional intelligent applications, adjustable fixed-volumes and individual programming tasks are performed much faster and easier. The Xplorer plus also includes a history function that automatically saves the last parameters for faster handling! A password can be entered to guarantee the highest degree of protection for personal programming and settings. These features mean no more delays due to complicated programming or inflexible processes. Instead, get precisely adjustable parameters, maximum reproducible results, fatigue-free work and consistent, full control over the pipetting processes. Web: www.eppendorf.com/xplorer
Measuring: The new Eppendorf µCuvette G1.0 is designed for the accurate and reliable measurement of small volumes of highly concentrated biomolecules, such as proteins and nucleic acids. Users can work easily with samples as small as 1.5 µL without the need for a time-consuming dilution step. The µCuvette G1.0 expands the measuring range of the Eppendorf BioPhotometer and the Eppendorf BioSpectrometer. Synchronized apertures mean that a closed system is created when used alongside Eppendorf detection instruments, for optimum results and reliable operation.
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Hotplate Stirrers: Undergrad Hot-
plate Stirrers from Stuart® are tailored to fit effortlessly into all kinds of laboratory settings. Undergrad Hotplate Stirrers have a small footprint, and can be stored on their side to reduce the amount of space required for storage even further. A recess underneath the unit accommodates a retort stand, which slides underneath for easy assembly. This removes the need for screwing a retort rod into place, meaning a shorter set-up time and more efficient working practices. The hotplate stirrers also come with a choice of ceramic or coated metal surfaces, and are compatible with the Stuart temperature controller for accurate sample temperature control. Safety is a major priority, with each unit having a unique LED temperature indicator and a power independent hot light, which remains illuminated while the surface temperature is above 50°C even if the unit is unplugged. Web: www.stuart-equipment.com
Particle Characterization: Malvern
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Mills: Retsch Cyclone Mills are ideally suited for temperature-sensitive samples and the grinding of solids depending on the material properties. The rotation of the mill’s rotor or a connected vacuum cleaner produces a rotating air flow inside the cyclone, thus optimizing the air throughput. As a result, sample and grinding tools are cooled and material discharge is improved. These effects are particularly beneficial when grinding temperature-sensitive materials. Further advantages are the complete recovery of the sample material as well as the possibility to process larger sample volumes. Retsch line of laboratory mills includes various models which can be equipped with a cyclone. Whereas the rotor mill TWISTER has an integrated cyclone, the Ultra Centrifugal Mill ZM 200 can be optionally equipped with a cyclone and collecting vessels of various sizes. Web: www.retsch.com
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November 26-30
2012 Materials Research Society Fall Meeting Venue: Boston, MA Tel: 724-779-3003 Fax: 724-779-8313 Email: hastings@mrs.org Web: www.mrs.org
November 27-28
Genomics: the Power & the Promise Venue: Ottawa, ON Tel: 613-563-1984 Web: http://genomicspowerandpromise. cvent.com
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December 2-4
4th Annual BioPartnering China Venue: Shanghai, China Web: http://www.techvision.com/bpc/
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Canadian Renewable Fuels Summit Venue: Ottawa, ON Tel: 613-594-5528, ext 223 Email: d.elson@greenfuels.org Web: http://greenfuels.org/en/ industry-information/summit.aspx
December 10-11
FDA/CMS Summit Venue: Washington, DC Tel: (800) 332-2181 Email: custcare@elsevier.com Web: http://www.elsevierbi.com/mkt/Conf/ FDA-CMS/2012
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ASCB 52nd Annual Meeting Venue: San Francisco, CA Tel: 301-347-9300 Fax: 301-347-9310 Email: ascbinfo@ascb.org Web: www.ascb.org
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2013 Annual Meeting of the ORS Venue: San Antonio, TX Tel: 847-823-5770 Fax: 847-823-5772 Email: ors@ors.org Web: www.ors.org/
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Experimental Biology 2013 Venue: Boston, MA Phone: 301-634-7075 Fax: 301-634-7008 Email: eb@faseb.org
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AlbertatBay..............................................................................................................25 ..........................................................................................www.albertatbay.com Canadian Science Policy Conference..................................................................11 .................................................................................................. www.cspc2012.ca Children’s Miracle Network ...................................................................................9 ......................................................................www.childrensmiraclenetwork.ca CO2 Solutions Inc......................................................................................... 6............................................................................... www.co2solutions.com Critical Outcome Technologies .................................................................... 6...........................................................................www.criticaloutcome.com Eppendorf................................................................................................................32 ........................................................................................... www.eppendorf.com Gairdner Foundation .............................................................................................21 ................................................www.genomicspowerandpromise.cvent.com GE Healthcare ............................................................................................. 10..............................................................................www.gehealthcare.com Genome Canada .....................................................................................................21 ................................................www.genomicspowerandpromise.cvent.com KPMG .......................................................................................................... 10.................................................................................... www.kpmg.com/ca Life Sciences Ontario ..............................................................................................7 ................................................................................. www.lifesciencesontario.ca MaRS Innovation ....................................................................................... 8, 30....................................................................... www.marsinnovation.com MedMira Inc. ................................................................................................ 9..................................................................................... www.medmira.com Mitomics Inc. .............................................................................................. 10...............................................................................www.mitomicsinc.com Novartis Pharmaceuticals Canada Inc. ......................................................... 9.......................................................................................... www.novartis.ca OptumInsight...........................................................................................................2 ................................................................................ www.optuminsight.com/pv POI Business Interiors............................................................................................31 ............................................................................................................. www.poi.ca RX&D........................................................................................................... 10.............................................................................www.canadapharma.org Sanofi........................................................................................................... 6..................................................................................www.sanofipasteur.ca VWR............................................................................................................................5 ......................................................................................................... www.vwr.com
