BIOSIMILAR BATTLEGROUNDS

and rheumatoid arthritis. Rituximab is a large and why there has not been more action in Canada. complex protein for treatment of a potentially life- There is not a lot of biosimilar development threatening disease, so it can be expected to be activity by Canadian-based companies. It would closely scrutinized by regulators deciding whether be in Canada’s benefit to provide incentives ento grant biosimilar approval. courage local companies to continue to invest in

Merck established Merck BioVentures in De- both innovative biologic and biosimilar biologic cember 2008 for biosimilar development. In 2010, drug development, particularly where Canada has Merck stated that it had two biosimilar candidates developed unique expertise and has a competiin development and anticipated having five bio- tive edge. similars in development by 2012. Merck has also In 2008, Apotex announced a biosimilar departnered with the Korean company Hanwha velopment collaboration with Intas BiopharmaChemical Corporation to develop a biosimilar ceuticals Limited and Kwizda Pharma to produce version of etanercept. a biosimilar GM-CSF (Granulocyte-Macrophage

Teva has four biosimilars in end Phase 2 clini- Colony-Stimulating Factor). cal trials: follitropin alfa, glyco - PEG-G-CSF, and SemBioSys and Plantform Corporation are rituximab. Teva also has two other biosimilars in developing plant-based expression systems for end Phase 3 clinical trials. Teva Pharmaceutical biosimilar production. They each have propriIndustries Ltd. purchased the Ratiopharm Group etary protein-expression systems that are differin 2010 in an effort to expand its generic opera- ent from the expression systems used by many tions in Europe, which at that time had received innovator biologic companies (eg. single cell sysapproval for one biosimilar (filgrastim) in the EU. tems, such as yeast, are most commonly used for

Pfizer partnered with Indian biotechnology biologic drugs). Health Canada’s guidance docucompany Biocon in 2010 to market a biosimilar ment states that differences in the manufacturing version of human insulin worldwide. Pfizer ex- process will be considered in the comparability pects to gain approval for its biosimilar insulin assessment. It is unclear the extent to which a in Europe by 2012 and in the U.S. by 2015. The plant-based product will be able to rely on ininvolvement of Pfizer in the biosimilar space is of interest to industry- novator product data. Companies will be preparing to address these watchers, since Pfizer has a very strong focus on developing its own regulatory issues. innovator products in conventional pharmaceuticals, not second Cangene Corporation (majority owned by Apotex) manufactures entry products. recombinant therapeutic proteins. Cangene has FDA and Health

Another interesting trend is companies well known in other indus- Canada-approved biologics. Cangene has previously developed its tries moving into the biosimilar business, such as Samsung. Samsung own versions of established products using proprietary host systems. has invested between $250 million and $390 million (depending on It has gone through the formal new drug application process but the report) in a partnership with Quintiles Transnational Corp. to could potentially move more towards the biosimilar pathway, for exdevelop biosimilars. ample with its GM-CSF in development. There are a number of other contract development and manufacturing companies with expertise United States in therapeutic protein manufacturing and development that have the Some biosimilars such as somatropin (human growth hormone) potential to partner with other companies. Therapure Biopharma have been approved in the US under ‘old’ laws regulating biolog- Inc. is an example of a biopharmaceutical company with expertise ics. The same pathway has been used by other biosimilars of older in producing therapeutic proteins and biosimilars. biologics. Other examples of subsequent entry biological products It is clear from the above high level view that there is a lot of ongoapproved by the FDA are glucagon, hyaluronidase, and calcitonin ing international biosimilar development. Most of the market leaders salmon recombinant. are based outside Canada. However, there are Canadian companies

The US government approved a new, abbreviated pathway for that are working hard to develop a foothold in biosimilar drug debiosimilar approvals in 2010. The FDA is already willing to accept ap- velopment. As with conventional pharmaceuticals, there is enough plications for approval the pathway. Acceptance is on a confidential space in the international biologic marketplace for both brand name basis so we do not know the extent to which there is activity on the companies and biosimilar companies. Canada would only stand to new pathway. Initial regulatory guidance from the FDA on applying benefit from nurturing its expertise in biologic drug development, for biosimilar approval is imminent. Biosimilar companies are watch- preferably leading to a cluster of companies with different, diverse ing developments in the US with great interest. One interesting pair R&D strength in either innovator biologics or biosimilars. of bedfellows announced in December 2011 is innovator Amgen and generic Watson Pharmaceuticals. They will make oncology antibody Noel Courage is a partner in Bereskin & Parr LLP, intellectual property law biosimilars (no biosimilars of Amgen’s products). and drug regulatory law. Thank you to Jaime Holroyd for helping with research for this article.

It would be in Canada’s benefit to provide incentives encourage local companies to continue to invest in both innovative biologic and biosimilar biologic drug development, particularly where Canada has developed unique expertise and has a competitive edge.

Canada

Canada published a SEB guidance document in 2010. About the same time, Sandoz received approval for its human growth hormone (Omnitrope). Canada has approved of the general approach taken by the EMEA guidelines. It is fair to say that Canada is open for business to biosimilars. The small Canadian market is of secondary interest to many multinational pharmaceutical companies, which may explain For more ACROSS CANADA information visit our COMMERCIALIZATION Web Portal at

www.bioscienceworld.ca

Ultracentrifuges New Optima X

Series preparative ultracentrifuges from Beckman Coulter, Inc. incorporate an array of contemporary technical features to enhance the user experience and increase productivity. With a large touchscreen display, the Optima X Series product offers a selection of nine languages while real-time graphing plots speed and temperature over time as a run progresses. Enhanced remote control capabilities allow the ultracentrifuges to be monitored from a personal computer or a smart phone. When powered on but not running, the unit requires the same energy as a 60-watt incandescent bulb, further increasing energy efficiency. Optima X Series ultracentrifuges reach a maximum speed of 100,000 rpm and generate forces up to 802,000 x g. Optima X Series instruments are available in two models – the XE, which delivers all of the basic features required to quickly set up and complete a run, and the XPN, which includes all features of the XE plus networking capability, on-board simulation tools and a variety of customizable security and tracking features. The XE is available in 90,000 and 100,000 rpm configurations, while the XPN is offered in 80,000, 90,000 and 100,000 rpm configurations.

www.beckmancoulter.com

MILLIPLEX® MAP Kits EMD Millipore

launches three MILLIPLEX® MAP kits for cellular metabolism. Based on the Luminex® xMAP® assay technology platform and cellular metabolism antibodies from MitoSciences®, the MILLIPLEX® MAP kits enable fast, sensitive, simultaneous quantification of multiple cellular metabolism biomarkers involved in fatty acid oxidation and the pyruvate dehydrogenase complex. Each kit provides highly validated and characterized cellular metabolism immunoassay antibodies, all necessary reagents, and optimized protocols. www.emdmillipore.com

DispoEquilibrium DIALYZER™

The Harvard Apparatus 96-Well DispoEquilibrium DIALYZER™ provides simple and

reliable techniques to analyze up to 96 equilibrium dialysis chambers simultaneously on disposable dialysis plates. These ready to use equilibrium dialysis plates are convenient and cost effective tools for ligand binding experiments including serum protein binding, protein-drug binding, protein-protein binding and proteinDNA binding assays. Each test well in the plate consists of two chambers separated by a regenerated cellulose membrane with a molecular weight cut off of either 5,000 or 10,000 Daltons. Each chamber holds up to 300µl of sample or buffer. To decrease the dialysis time, the plate needs to be rotated through 360° in a vertical position. Harvard Apparatus can also supply a one or two plate rotator or an eight plate rotator with temperature control. www.harvardapparatus.com

Wireless Logger T&D Corporation introduces its new RTR-505V Wireless Logger. The RTR-505V can measure DC voltages from 0 to 22VDC with accuracy of ±0.5mv and can measure voltage directly or from the output of a wide variety of sensors and instruments. The RTR-505V features a large LCD display, capacity for 16,000 readings, IP64 water resistance and up to four years battery life with the “L” version. Compatible with all TandD RTR-500 Series Wireless Data Collectors, the RTR-505V can be seamlessly integrated into a wireless network with other logger types. They can be monitored locally, through a cellular phone system, or anywhere in the world over the Internet. Advanced features include real-time monitoring and warning notifications. The communication range is up to 500 ft. which can be extended with the use of a repeater. www.tandd.com

Titrator JM Science’s AQUACOUNTER® Volumetric Karl Fischer Titrator (AQV-300) is reliable, easy-to-use and has performance features which allows measure of moisture content from low to high concentrations quickly and accurately. Measurements are simple and routine with unsurpassed precision. The AQV-300 has six built-in calculation modes to accommodate solid, liquid and gas samples. It includes a statistics package with one-touch calculations. Four files with preset conditions can be stored in memory and allows instant recall of data for up to 20 samples. A built-in detector monitors titration status and a direct key access allows entry of titration parameters. This compact unit with a very small footprint has balance and computer interfaces for GLP and ISO documentation and it is CE approved. The titrator comes with DVD training movie, plasticized Quick-Start guide for use in the lab, paper and pdf manual. Also included,

complete accessories, download software for transferring results to a laptop or PC, RS-232 cable, and AQUACOUNTER® KF Reagent starter kit. www.jmscience.com

High Consistency Rubber Shin-

Etsu Silicones of America’s newest HCR (High Consistency Rubber) product line – Sil-X-Shin™ Silicone Elastomers are specifically engineered for extruded tubing and profiles. Sil-X-Shin Silicone Elastomers are available in a wide range of Shore A Hardness–from 30–80−and come in a convenient 10:1 ratio of base compound to catalyst. The most unique advantage of the Sil-X-Shin product line is that one universal catalyst can be used with each of the six bases, providing ultimate flexibility. The Sil-X-Shin series has a single, universal catalyst that cures any of the six bases with less than 10 per cent of the composition. Sil-X-Shin Silicone Elastomers are USP Class VI compliant, and their platinum, additioncure chemistry produces a tight surface finish with few residual by-products.

www.shinetsusilicones.com

Batch Controller The new Mettler Toledo IND780 stand-alone batch controller combines advanced batching control technology while adhering to the ISA SP-88 Batch Standard. The IND780batch optimizes batch processes with consistent, accurate material transfers, to minimize material waste and improve batch quality. The flexible stand-alone terminal can be used for single or multi-scale batching applications. With the IND780batch, users can take control of manual processes with dependable recipe management and the ability to handle 999 materials. Tolerance checking, material identification via bar-code input, and operator prompting all help to ensure the operator is guided through each batch. Multi-material automatic batching control handles up to 28 automatic materials with recipe-specific control, including conditional control tasks, go-to commands, recipe re-scaling, timing functions, and control of discrete inputs and outputs to allow the controller to interact with other equipment in the process. www.mt.com

Slide Imaging System PerkinElmer

Inc. launches the VectraTM 2 automated slide imaging system, a turnkey platform that allows true walk-away batch processing of up to 200 tissue sections at a time. Additionally, the Vectra™ 2 addresses the need of scientists focused on biomarker research, pharmaceutical development, clinical research and tissue application test development for validated tissue labeling and automated scoring methodology. The new platform adds HistoRX’s AQUA® technology to Vectra’s unique multispectral and image analysis capabilities. Its unique multispectral capabilities, coupled with the powerful image analysis tool inFormTM, can be used to explore even the most demanding of today’s tissue analysis problems, from multi-analyte in situ cytometric analysis and cell phenotyping to stereology-like analyses of tissue disease states. The technology provides >97 per cent inter- and intra-assay coefficient of variation, giving researchers assurance in the quality of their results. The system supports both tissue sections and tissue microarrays (TMAs) with ease and offers a slide hotel for batch scanning of up to 200 slides. The Vectra platform is empow-

ered by the same multispectral imaging technology that drives over 400 NuanceTM cameras sold to date, giving researchers the ability to analyze multiple fluors/ chromagens in a sample, quantifying each separately and accurately. www.perkinelmer.com

Vessels The Thermo Scientific CryoExtra™ vacuum-insulated, stainless steel vessels are available in four different sizes, from 407 litres to 1,630 litres, accommodating both vapour and liquid-phase storage. These containers minimize top-tobottom temperature variation, preserving the integrity of critical cryogenically frozen samples. Its innovative lid and neck design, combined with advanced temperature monitoring, reduce temperature fluctuations that occur due to lid openings. Furthermore, the microprocessor-based LN2 level control ensures that liquid nitrogen levels are tightly controlled, and the de-fog function allows easy, push-button sample identification.With the ability to store up to 90,000 1.2 – 2.0 mL vials, the largest of the four CryoExtra models (1,630 liter) has the same external footprint as the 1,350 liter unit. All four CryoExtra containers can accommodate both vertical and horizontal racks, and the Thermo Scientific racking solutions are specifically designed for this vessel configuration, further maximizing capacity. www.thermoscientific.com

Fume Hoods Air Science introduces its new Purair ECO™ line of Energy-Saving Ductless Fume Hoods designed for both chemical and particulate protection over a broad range of laboratory and industrial applications. The Purair ECO is available with a choice of controllers including the company’s new ECOair™ touchpad control with color display interface. An optional BACnet network interface connects all cabinet control, monitoring and alarm functions to an open-source facility monitoring system. The system is based on an industry-wide, non-proprietary ASHRAE compliant protocol for green building management. The Purair ECO is available in five standard sizes from 30” wide to 69” wide. www.airscience.com

Maurice

and the snow storm

Maurice, our Front Desk Agent, isn’t exactly a huge fan of the snow. And driving in the stuff? He dislikes that even more. But one cold, grey December evening, our intrepid Maurice ventured out into one of the biggest storms of the season. What could have driven him to drive into this tempest? His sense of duty. You see, one of our guests had left an important item behind. Knowing that a cab wouldn’t make it to the airport in time to reunite our guest with his property, Maurice took matters, as well as a frigid steering wheel, into his own hands. Arriving at the airport with mere minutes to spare, Maurice personally handed the item to our surprised, and extremely relieved, traveller. Proof once again that, even after you’ve left our hotel, you’re still a VIP.

We don’t go home happy until you do.

Downtown Ottawa 377 O’Connor St. 800.465.7275 victoriapark.com

Really, ReallyBig

Hotel Suites.

The moment.You know it. It happens any time you stayat a new hotel,right after you swipe your room key.The moment before you open the door.Will the room be big,or small? Light,or dark? Nice,or not?

Here’s what you’ll find the moment you open your door at Albert at Bay—space,and lots of it.Our suitesare the biggest in Ottawa and feature real bedrooms,real kitchens and real living rooms.And they don’t costany more than those of our competitors.Really, why would you stay any place else?

JANUARY 2-12

January 9–11

Biotech Showcase™ 2012 Venue: San Francisco, CA Email: update@ebdgroup.com Web: www.ebdgroup.com/bts/index.php

January 30-31

Bio Manufacturing Summit Venue: San Diego, CA Tel: (416) 214-1144 Fax (416) 214 3403 E-mail: melissa.youngsing@wtgevents.com Web: www.biomansummit.com

FEBRUARY 2012

February 4-8

Society for Laboratory Automation and Screening 2012 Venue: San Diego, CA Tel: 630-256-7527 Fax: 630-741-7527 Email: slas@slas.org Web: www.slas.org

February 13-14

Bio CEO & Investor Conference 2012 Venue: New York, NY Email: bd_registration@bio.org Web: www.bio.org/events/conferences/ bio-ceo-and-investor-conference/700-0

February 16-20

AAAS Annual Meeting Venue: Vancouver, BC Tel: 202-326-6400 Fax: 202-842-1065 Email: meetings@aaas.org Web: www.aaas.org

February 25

BIOTECanada CEO Whistler Summit Venue: Whistler BC Email: kira.pejemsky@biotech.ca Web: www.biotech.ca/en/default.aspx

February 26-28

BioPartnering North America Venue: Vancouver, BC Tel: 1-831-464-4230 Fax: 1-831-464-4240 Web: www.techvision.com/bpn/

MARCH 2012

March 11-16

PITTCON 2012 Venue: Orlando, FL Tel: 412-825-3220 Fax: 412-825-3224 Email: info@pittcon.org Web: www.pittcon.org

March 19-21

BIO-Europe Spring® 2012 Venue: Amsterdam, The Netherlands Tel: 760-930-0500 Email: chundschell@ebdgroup.com Web: www.ebdgroup.com/bes/index.php

MAY 2012

May 29-30

Biofinance 2012 Venue: Toronto Tel: 1-866-342-4933 Fax: 1-866-342-4934 Email: kvanvogt@biofinance.ca Web: www.biofinance.ca

JUNE 2012

June 2-4

Labcon 2012 Venue: Gatineau, QC Web: www.csmls.org/labcon2012

June 18-21

BIO 2012 Venue: Boston, MA Web: www.convention.bio.org

COMPANY & ADVERTISER INDEX

COMPANY PAGE WEBSITE

Aeterna Zentaris Inc.................................................................................. 6, 10.....................................................................................www.aezsinc.com Air Science .................................................................................................. 26...................................................................................www.airscience.com AlbertatBay..............................................................................................................27 .........................................................................................www. Albertatbay.com Amorfix Life Sciences................................................................................... 9....................................................................................... www.amorfix.com Bestwestern Victoria Park Suites.........................................................................27 .........................................................................................www.victoriapark.com BioPartnering North America...............................................................................31 ...................................................................................www.techvision.com/bpn BioTalent Canada.....................................................................................................5 ................................................................................................... www.biotalent.ca Caledon Laboratory Chemicals ............................................................................7 ..........................................................................................www.caledonlabs.com Canadian Renewable Fuels Association ....................................................... 7.................................................................................... www.greenfuels.org CNA Canada ..............................................................................................................2 ................................................................................................ www.cnacanada.ca Conference Board of Canada ....................................................................... 7............................................................................www.conferenceboard.ca Eisai Limited................................................................................................. 9.............................................................................................www.eisai.com Eppendorf................................................................................................................32 ........................................................................................... www.eppendorf.com Helix BioPharma..........................................................................................6,9 .........................................................................www.helixbiopharma.com Mettler Toledo ............................................................................................ 26.............................................................................................. www.mt.com Mississauga..............................................................................................................19 ...........................................................................www.mississauga.ca/business Novadaq Technolgies Inc. ........................................................................... 10 ....................................................................................www.novadaq.com Performance Plants Inc............................................................................... 10.................................................................... www.performanceplants.com Perkin Elmer ............................................................................................... 26............................................................................... www.perkinelmer.com SinEtsu........................................................................................................ 26....................................................................... www.shinetsusilicones.com Thermo Scientific........................................................................................ 26.........................................................................www.thermoscientific.com Valeant Pharmaceuticals International Inc. ................................................. 10............................................................................www.valeantcanada.com Verisante Technology Inc............................................................................ 10.................................................................................... www.verisante.com VWR...........................................................................................................................15 ........................................................................................................ www.vwr.com

THE LAST WORD

By Robert Foldes

Robert Foldes is Managing Partner of Cognovie Inc. and can be contacted at robert@ cognovie.com

WANTED:

A champion for home-grown Canadian biopharma

As the often quoted Chinese curse (with unknown origins) goes – “May you live in interesting times” – it is indeed interesting times for the Canadian biopharmaceutical industry.

As a sector dominated by companies engaged in drug discovery and development rather than sales and marketing, its lifeblood requires large and regular infusions of cash. To no one’s surprise, raising capital continues to be the biggest challenge facing the industry and many feel that government can play a significant role in the industry’s success (BIOTECanada/PWC Canadian Life Sciences Industry Forecast 2011). In fact, Ernst & Young highlighted a “funding crisis” facing the industry.

The Expert Panel on Federal Support to R&D (The Jenkins Report) recently released its recommendations addressing many hurdles that apply to the industry. However, this panel’s recommendations relating to the SR&ED tax credit program, may have negative consequences on many biopharmaceutical companies that rely heavily on outsourcing the majority of R&D expenditures. The SR&ED program is of immense importance to the sector. Efforts to improve access to and predictability of the SR&ED program are applauded but efforts to dismantle or reduce its impact could quite easily deliver a death-blow to an already fragile sector.

A recent Mowat Centre Report by Tijs Creutzberg also released several similar messages as the Jenkins Report in improving Canada’s innovation ROI: reduce tax incentives and increase direct support to companies; simplify access to federal and provincial support programs and reduce bureaucratic infrastructure.

In Ontario, the newly re-elected Liberal government has proposed a 35 per cent start-up tax credit to boost investment. However, one thing is clear, the Canadian biopharmaceutical industry needs immediate and targeted action from both levels of government. Its challenges are far more acute and severe than other sectors of the knowledge economy.

Given the current turbulence of global financial markets, biopharmaceutical companies are the “low man on the totem pole” and public financings of non-revenue generating companies have essentially disappeared from a CFO’s arsenal. For a host of reasons, venture capital investment in this sector has also retreated. Again due to the trickledown effect of global financial uncertainty, investors in venture capital funds are not currently favouring the biopharmaceutical sector due to long product development timeframes, large investments required, increased regulatory risks, and poor returns in previous venture capital funds. As a result, many venture capital funds have faced an impossible environment to raise new funds. Some have given up. For those that are still investing (generally nonCanadian funds), desired exits are quite short due to the maturity of the funds - in some cases as little as 3 years. As a result, in the current environment, venture capital – no longer characterized as patient capital – requires validated drug candidates very close to starting human clinical trials or ideally with early clinical data. (A little more than 10 years ago, a drug discovery company with a pending patent application claiming the use of a novel gene would find little trouble in attracting financing.) A new business model has started to emerge in the venture capital community – that of project based financing. This model generally takes the “company” out of the “virtual company” model. In the latter case, a team of experienced executives would be responsible for project management with most R&D activities outsourced to CROs. In the new model being implemented by a few groups (so far), the venture capital team itself is responsible for project management of drug candidates that are in-licensed or acquired and generally advanced to the point of attracting a pharmaceutical company partner. That stage could be attained once human proof-of-principle is obtained, or earlier. The idea is to channel all investment to R&D rather than building overhead in a company. However, underneath the hype, one would assume that the venture capital group would still need to build overhead in-house.