Laboratory Focus February/March 2015

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Pharmaceutical

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Tips, Tricks and Information for the ergonomic design of your laboratory Page 7

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February/March 2015 Volume 19, Number 1

Exploiting Macrocycle Space for Drug Discovery Page 10

R&D News.......................... 1 Pharma Notes..................... 5 Appointments..................... 6 New Products................... 15 Calendar........................... 17 App Reviews...................... 18

Merck joins Structural Genomics Consortium (SGC) makes $7.5 million contribution filling the unmet medical needs of patients, who are at the core of everything we do,” he said. “In Canada, Merck is very pleased to be able to encourage innovation and research across an established SGC collaborative network of more than 250 academic laboratories at leading institutions.”

Developing an “open source” public-private partnership

(From left to right) Dr. Ronan O’Hagan, Dr. Aled Edwards, The Honourable Reza Moridi, Mr. Chirfi Guindo and Ms. Jennifer Chan. (CNW Group/Merck)

The Structural Genomics Consortium (SCC) Toronto announces it has added global pharma giant Merck as its newest member . In addition to joining the consortium as a partner, Merck is contributing $7.5 million to the network. The money will go towards sup-

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porting projects with a focus on pre-competitive research. One of the projects will see the partners developing small inhibitory molecules called chemical probes to study epigenetic mechanisms of regulation. In collaboration with leading clinical institutions in On-

tario and around the world, use of the probes will expand the understanding of biology in multiple disease areas, particularly cancer and inflammatory diseases. According to Merck Canada Inc. president and managing director Chirfi Guindo, the SGC’s track record for delivering high-quality science, along with Toronto’s ecosystem of world-class hospitals and research labs as well as a strong commitment of collaboration between government and industry, make the SGC an ideal research partner. “At Merck, we strive to identify and support research areas that will have the most impact on ful-

The SGC is creating an “open source” public-private partnership that generates knowledge, technologies, and research tools to discover and characterize “pioneer” drug discovery targets. The partnership will leverage past and future investments made into the SGC by its public and private sector funders, and its large network of collaborators based at leading academic institutions worldwide. The overarching aim of the partnership is to enable private sector funders to advance a significant number of pioneer targets into proprietary drug discovery programs. “At the heart of our partnership is a commitment to transparency and quality,” said Dr. Aled Edwards, founding and current CEO of the Structural Genomics Consortium (SGC). The SGC is funded by Abbvie, Bayer, Boehringer Ingelheim, the Canada Foundation for Innovation, Eli Lilly Canada, Genome Canada, GlaxoSmithKline, Janssen, Merck Canada, Novartis, the Ontario Ministry of Research & Innovation, Pfizer, Takeda, and the Wellcome Trust. To see this story online visit http://www.laboratoryfocus. ca/?p=2841


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feds suPPort new metabolomics technoloGy demonstration centre The federal government through Western Economic Diversification is investing just less than $3 million towards new state-of-the-art metabolomics assessment equipment that will enable Genome Alberta together with the Uni-

versity of Alberta to establish a new Metabolomics Technology Demonstration Centre. Other investors in the new centre include the National Institute of Nanotechnology, Alberta Innovates Health Solutions, Metabolomics Technol-

ogies Inc. (MTI), and Genome Canada. Metabolomics is a growing field of research that examines the comprehensive, qualitative and quantitative cellular-level activities in cells, tissues and organisms. Me-

tabolites provide scientists with a powerful route to measure gene-environment interactions, which is helpful in generating health solutions in human and animal health, continued on page 3

PUBLISHER/EDITOR-IN-CHIEF Terri Pavelic SENIOR WRITER Shawn Lawrence CONTRIBUTING WRITERS Mark Peterson Steven Klein Stuart Ray ACCOUNT MANAGER Laskey Hart GRAPHIC DESIGNER Elena Pankova CONTROLLER John R. Jones MARKETING MANAGER Mary Malofy CIRCULATION DIRECTOR Mary Labao circulation@promotive.net Tel: 289-879-4272

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agriculture and nutrition. One-third of all metabolomics companies in the world are located in Alberta. The equipment, a 700 MHz Nuclear Magnetic Resonance machine and a Quadrupole-Time of Flight Mass Spectrometer, will assist companies in the metabolomics sector in moving biomarkers from the research lab to the medical testing facility. Companies will test, validate, and assemble prototype kits using existing research from the University’s Metabolomics Innovation Centre’s biomarker panels, to cost-effectively create more accurate and less invasive medical tests. To see this story online visit

http://www.laboratoryfocus. ca/?p=2843

news GSK partners with NEOMED to create new biologics and vaccine centre of excellence In a proposed partnership with NEOMED, GSK is re-engineering its research and development facility in Laval to create a unique Biological Products and Vaccine Centre of Excellence. GSK expects to contribute $47 million over the next five years to support the creation of the new centre of excellence. It is expected that of GSK Laval’s 122 permanent employees,approximately half will be transferred to the new Centre of Excellence. For those facing job loss, the transition is expected to be complete by late 2015. “GSK is acting responsibly by ensuring the continued presence of crucial research expertise in Québec, and NEOMED will be able to build on what GSK developed for the last nine years in Laval,” NEOMED president and CEO Max Fehlmann said. “We are very pleased to partner with NEOMED to create a unique Biologics and Vaccine Centre of Excellence,” said Paul Lirette, president, GSK Canada Pharmaceuticals. “It enables GSK to look externally and develop collaborative partnerships to optimize R&D,

and represents the dawn of a new and promising era for pharmaceutical research in the Montréal region.” The new NEOMED biologics and vaccines division is structured around three distinct integrated pillars: • The transformation of the GSK research facility, and its high-tech laboratories and equipment, into a multi-tenant hub of small and medium-sized enterprises specialized in this important area of expertise; • The creation of a specialized contract research organization (CRO) that will market its biology and clinical immunology services to the business community and to GSK for at least three years; • The creation of an exclusive partnership between GSK and NEOMED in order to share risks and benefits on existing biologic and vaccine projects. As part of the new partnership, GSK and NEOMED say they will each invest $10 million to fund up to five product research and development projects transferred from GSK. GSK will continue to pay the entire cost for leasing the facility for-five years, representing

NEOMED president and CEO Max Fehlmann

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February/March 2015

an investment of $10 million. Additionally, GSK will buy clinical testing services from the Contract Research Institute (CRO) which will be part of the Centre of Excellence, for at least three years representing an additional investment of $27 million. To see this story online visit http://www.laboratoryfocus. ca/?p=2845

SFU lab creates potentially life saving heart cells A group of Simon Fraser University researchers’ cultivation of dozens of beating heart cells in Petrie dishes could one day save or improve the lives of patients with inherited heart arrhythmias. Elham Afshinmanesh and Sanam Shafaattalab, graduate students in SFU’s molecular cardiac physiology lab, have created the heart cells, also known as cardiomyocytes, beating in unison. They’ve been crafted from the skin of heart arrhythmia patients. Because the beating heart cells share the same genomes as the patients, these cells also mimic the patients’ diseases, permitting scientists to experiment with potential drug therapies and interventions. The students are working under the supervision of Glen Tibbits, a SFU professor and Canada Research chair in Molecular Cardiac Physiology. They are collaborating with cardiologists, who specialize in inherited cardiac arrhythmias, at B.C. Children’s and St. Paul’s hospitals. Their research is key to developing one of the first laboratories capable of testing cardiomyocytes

in vitro and then recommending customized treatment for individuals who have these inherited heart diseases. “It’s often very challenging for clinicians to assess risk in these patients,” explains Tibbits. He adds, “It is frequently difficult to determine whether a patient has a high likelihood of suffering from cardiac arrest or will be okay by simply taking a beta blocker and/or other medications. The idea behind our work is to test, with the patient’s own cells, what therapies might work, or not.” The research is new and complex, and according to Tibbits, they are optimizing the methods by which a patient’s blood cells can be reprogrammed into induced pluripotent stem cells, which can then become any kind of cell. They have already mastered the ability to turn skin cells into this type of stem cell (iPSC), but would prefer to work with the patient’s blood, since this is more efficient and less invasive than using skin biopsies. Says Afshinmanesh, “When we convert the blood and skin cells to stem cells not all of them can be further differentiated into heart cells. So we’re looking for markers that will predict which stem cells are good prospects

SFU molecular biology and biochemistry students Sanam Shaffaattalab (front) and Elham Afshinmanesh, and their doctoral thesis supervisor Professor Glen Tibbits view manufactured beating heart cells. Photo: Simon Fraser University for becoming heart cells.” Tibbits expects that within the next few months his lab will be ready to begin testing the beating heart cells with therapeutic interventions to determine the efficacy of individual treatments. “We have grants to support our work right now, but eventually we hope that these tests will become part of the Medical Services Program,” explains

Tibbits. “Then we will isolate the skin or blood cells, convert them, determine the appropriate patient therapy and then be reimbursed.” The Canadian Institutes for Health Research is funding the research. To see this story online visit http://www.laboratoryfocus. ca/?p=2848


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Breaking down the (cell) wall: making fuels and chemicals from bio-inspired sources Living cells are a hive of activity, full of tiny structures making proteins, breaking down junk and creating energy. All of this happens through a series of chemical reactions made possible largely because of the humble cell wall. “If you remove the cell wall, keeping exactly the same molecules that were inside the cell, then the same reactions will not occur or will occur very, very, slowly,” says Cecile MalardierJugroot, assistant professor in chemistry and chemical engineering at the Royal Military College of Canada. Inspired by the reactive power of cells, her team and collaborators are working to develop nanoreactors that mimic natural biosystems and their very high efficiency within a confined space. Their hope is to produce something more stable than biosystems offer, harnessing their advantages and using their structure and function as a model. By introducing confinement to nanosystems, researchers mimic the effect of the cell wall on reactions. Suddenly, reactions that would not occur normally in bulk materials start to form. They’re fairly slow reactions, but they are special because no heat, pressure, nor catalysts need to be added to the mix to get the activity going. Biosystems are inherently efficient in both thermodynamic and kinetic terms, but how best to maximize their nanoreactor cousins will take a great deal of study. The goal is to make

more efficient fuel cells than anything currently on the market, working with carbon nanotubes and sheets, on the scale of individual atoms. One of the first variables to test is the introduction of platinum crystals within their nanoreactor templates — a design also inspired by nature, since many cells use a metal centre as a reactive site. This first nanoreactor provided a three fold increase in the reaction rate within the template in the presence of the metal center compare to the empty nanoreactor. The researchers also plan to test gold and gold-platinum alloys to open up more potential applications. The function of these metal-reactive site systems is still relatively new territory, and called for new research methods. To achieve the fine detail needed to analyze these systems, the team used the Canadian Light Source synchrotron, transmission electron microscopy and the Canadian Centre for Electron Microscopy. “When we started this four years ago, we did the characterization using transmission electron microscopy, however with this technique, the samples have to be in the dry state and you get only the sense of one part of the sample, not the average of the sample which we needed to find out if we had the same number of clusters distributed everywhere in our sample,” explains Malardier-Jugroot. The Malardier-Jugroot team is most specialized in modelling, so they were

Artificial nanoreactors with 1D and 2D confined environment, the Pt metal center observed by transmission electron microscopy is shown on the left (a) with an average diameter of 1.89 nm. The X-Ray spectra of the system presented in blue (b) shows the Pt nanoparticle peaks at 2q of 17.49 and 20.22o Cite: Groves, Michael N., Cecile Malardier-Jugroot, and Manish Jugroot.

grateful to work with the CLS crystallography scientists, who performed the X-Ray Diffraction analysis for the researchers. “We’re trying to understand at a the atomic level what’s happening inside the nanoreactor templates, so having a link with experimentalists at that level, and being able to send them our models and trying to understand the interactions going on — that was very very helpful.” There were surprises in store. For one thing, the templates, which were normally only stable at pH 7, remained stable from pH 3-13 with the addition of platinum. How and why that occurs is a major question. In fact, the field remains full of mysteries: the nanoreactors can be light sensitive, so how

can that be harnessed? What creates specific crystal structures? How do these structures affect function? Fuel cells are only one potential application for these mimic of biosystems — more wait to be uncovered. The research was supported by the National Science and Engineering Research Council of Canada (NSERC), the Canadian Centre for Electron Microscopy (McMaster University), the NIST-CNR in part by the National Science Foundation and the Canadian Macromolecular Crystallography Facility at the Canadian Light Source. To see this story online visit http://www.laboratoryfocus. ca/?p=2851

NRC, Lilly Creek and AMRIC join forces on vaccine to prevent gastritis, ulcers and gastric cancer

(L to R) Sean Thompson, President and CEO of Lilly Creek Vaccines, Francisco Diaz-Mitoma, CEO & Scientific Director of AMRIC and Jim Richards and Eleonora Altman from NRC visit Lilly Creek Vaccines in Sudbury to announce an agreement to develop a new vaccine to combat Helicobacter pylori infection in Canada (Photo credit: NRC)

Vaccines have the power to prevent infections that cause cancer – familiar examples include Gardasil and Cervarix to prevent HPV infections that cause cervical cancer. Researchers at the National Research Council of Canada (NRC), the Advanced Medical Research Institute of Canada (AMRIC) and Lilly Creek Vaccines are harnessing this principle to develop a new vaccine to combat and eradicate Helicobacter pylori (H. pylori) infection in Canada. As part of this two-year, $575,000 agreement, NRC’s Vaccine Program will design a candidate vaccine using glycoconjugate antigens that stimulate the immune system. NRC will also carry out preclinical testing to determine its efficacy. H. pylori infection affects about 50 percent of the world’s population – 70 per cent in developing countries and 20 to 30 per cent in industrialized countries, with most infections occurring in childhood. The

infection causes gastritis in almost all cases, peptic ulcers in 10 to 15 per cent of cases, and gastric cancer in about one per cent of cases. A class 1 carcinogen, H. pylori increases the risk of gastric cancer six-fold. Particularly at risk for H. pylori infections are Canada’s northern communities, where infection rates range from 50 to 60 per cent compared to about 20 to 30 per cent nationally. If results from the new program are positive, preclinical research and clinical trials in high-risk populations in northern Canada will be conducted by Lilly Creek Vaccines, a new venture created by AMRIC a Health Sciences North hospital affiliated research institute that aims to improve health care outcomes in Northern communities and across Canada. To see this story online visit http://www.laboratoryfocus. ca/?p=2854


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Laboratory Focus February/March 2015

Pharma Notes ProNAi Therapeutics Inc. (Vancouver, BC) reports that the first patient with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) has enrolled in the company’s “Wolverine” Phase 2 study and has been treated with PNT2258. The patient was treated by Dr. Wael Harb, founder of the Horizon Oncology Center in Lafayette, Ind. The multi-center, single-agent, open-label, Phase 2 investigation of PNT2258 will characterize anti-tumour activity and collect safety data on approximately 60 patients with relapsed or refractory DLBCL. The primary endpoint is overall response rate, assessed by FDG-Positron Emission Tomography (PET) scan and compared to relevant historical controls. Secondary outcome measures include disease control rate, progression-free survival, overall survival, and exploratory predictors of outcome assessed by tumour biopsy and pharmacodynamics sample analysis. OncoGenex Pharmaceuticals, Inc. (Vancouver, BC) reports it has executed an initial agreement with Teva Pharmaceutical Industries Ltd. to regain the rights to custirsen, an investigational compound. The compound is currently being evaluated in a Phase 3 clinical trial as a treatment for prostate and lung cancers. The transfer of rights is connected with the termination of the collaboration agreement between OncoGenex and Teva executed in 2009. The initial agreement reached by OncoGenex and Teva provides that, following execution of the final agreement to terminate the collaboration between the parties, OncoGenex will receive a $27 million payment from Teva, subject to certain adjustments. In addition, OncoGenex will take over responsibility for all custirsen related expenses, including those related to the ENSPIRIT trial, as well as manufacturing and regulatory activities for custirsen programs, which are currently being managed by Teva. Cipher Pharmaceuticals Inc. (Mississauga, ON) reports it is expanding its dermatology product portfolio licensing the Canadian rights to Ozenoxacin, a topical treatment for adult and paediatric patients with impetigo, from Ferrer, a privately-held Spanish pharmaceutical company. In 2013, Ferrer successfully completed a first Phase 3 clinical trial of Ozenoxacin in adult and paediatric patients aged two years and older with impetigo.The study demonstrated the superiority of Ozenoxacin one per cent cream versus a placebo, applied topically twice daily

for five days, on both the clinical and bacteriological endpoints by end of therapy visit. Ferrer commenced a second Phase 3 trial of Ozenoxacin in June 2014. The multicenter, randomized, double-blinded, clinical study comparing Ozenoxacin one per cent cream versus placebo will be conducted in approximately 412 patients aged two months and older with a clinical diagnosis of non-bullous or bullous impetigo. Ferrer anticipates that the second Phase 3 trial will be completed by the end of Q1 2015. Under the terms of the agreement, Ferrer will receive an upfront payment and is eligible for development milestones and revenues from product sales in Canada. Ferrer will manufacture Ozenoxacin and deliver the finished product to Cipher. Cipher Pharmaceuticals Inc. (Mississauga, ON) reports it has acquired the assets of Hershey, PA-based life science company Melanovus Oncology Inc.. The assets include seven pre-clinical compounds for the treatment of melanoma and other cancers. Founded in 2012, Melanovus acquired an exclusive global license to a library of compounds and related intellectual property from the Penn State Research Foundation. The compounds originate from work done by Dr. Gavin Robertson, professor of pharmacology, pathology, dermatology and surgery at Penn State University, and director of the Penn State Hershey Melanoma Center. The transaction includes an upfront payment to Melanovus of US$500,000, as well as the payment of certain IP expenses related to patent prosecution and maintenance. Clinical stage company Aptose Biosciences Inc. (Toronto, ON) reports it has dosed the first patient in its Phase 1b clinical study of APTO-253 in patients with relapsed or refractory hematologic malignancies. APTO-253 is a first-in-class inducer of the Krüppel-like factor 4 (KLF4) tumour suppressor gene, and the only clinical-stage compound targeted for patients with suppressed KLF4 levels. The Phase 1b trial is a multicenter, open-label, doseescalation clinical trial. It is designed to assess the safety, tolerability, pharmacokinetics and pharmacodynamic responses and efficacy of APTO-253 as a single agent. During the trial, APTO-253 will be administered twice weekly, over a 28-day cycle. The study is expected to enroll up to 30 patients with relapsed or refractory hematologic malignancies across two separate dose-escalation arms: (a) up to 15 patients with acute myeloid leukemia (AML) and

high-risk myelodysplastic syndromes (MDS) patients, and (b) up to 15 patients with lymphomas (Hodgkin and non- Hodgkin lymphoma) and multiple myeloma. ProMetic Life Sciences Inc. (Laval, QC) orally active anti-fibrotic lead drug candidate, PBI-4050, has been approved to commence a clinical trial in patients suffering from idiopathic pulmonary fibrosis (IPF), following the CTA clearance by Health Canada. The objectives of the 12 weeks open-label, single-arm, exploratory Phase 2 study are to evaluate the safety and tolerability of PBI-4050 in 40 patients suffering from IPF and to gather data on the effects of PBI-4050 on pulmonary function, disease progression and inflammatory/fibrotic markers. ProMetic successfully completed its PBI-4050 Phase 1 clinical trial in 40 healthy volunteers, in which it was found to be safe and well tolerated, with no serious adverse events. The company has also started enrolling patients with diabetic kidney disease (DKD) in the multi-dose part of the Phase 1b trial and is expected to report results thereon by the end of the first quarter of 2015.

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Canadian biotech company Zymeworks Inc. (Vancouver, BC) has inked another deal with a biotech giant, this time teaming up with Celgene. Under the terms of the agreement, Zymeworks and Celgene will collaborate on the research and development of multiple bi-specific antibodies based on the Azymetric™ platform. The deal gives Celgene the right to develop and market an undisclosed number of antibody drug candidates that are designed to hit two biological targets instead of just one. Celgene will also have the option to advance the resulting bi-specific candidates through clinical development and subsequent commercialization. Zymeworks will receive an initial upfront payment, as well as an equity investment of $10 million from Celgene. Zymeworks is eligible to receive clinical, regulatory, and commercial milestones on successful candidates totaling up to US $164M per therapeutic candidate. Additionally, if any of the experimental drugs make it all the way to the market, Zymeworks will collect royalties on worldwide net sales. Further financial details are not disclosed.

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February/March 2015 Laboratory Focus www.laboratoryfocus.ca

aPPointments

Northern Lipids Inc. announces the appointment of Dr. Norbert Maurer as director of R&D. Dr. Maurer brings to NLI over 20 years of experience in the development of delivery technologies for conventional chemotherapeutic agents and biopharmaceuticals such as therapeutic antibodies and nucleic acid-based drugs. Most recently as head of formulations at CDRD, Dr. Maurer focused on the formulation of drugs, from novel small molecule therapeutics to the new macromolecular therapeutics coming from proteomics and genomics research. Previously, he was involved with a number of Vancouver-based pharmaceutical companies that tended to focus on delivery platforms. Dr. Maurer obtained his PhD in Physical Chemistry while living in Austria followed by post-doctoral training in the Biochemistry Department (The Liposome Research Unit) of the University of British Columbia. He has authored 27 peer-reviewed papers, review articles and book chapters and is named on six patents/patent applications. Sirona Biochem Corp. has added Dr. Martin Gleave to its board of directors. Dr. Gleave is a clinicianscientist and urologic surgeon and holds numerous leadership positions in research and academia. He is currently a distinguished professor and vice chair of the department of urologic sciences at UBC and director at the Vancouver Prostate Centre (VPC). His major research focus involves the study of cellular and molecular mechanisms mediating progression of prostate cancer to its lethal stage of androgen independence, and use of this information to develop integrated multimodality therapies that specifically target these mechanisms. Dr. Gleave established a role for clusterin as a cancer-related cell survival protein involved in treatment resistance and developed an inhibitor, designated OGX011, which improved efficacy of hormone- and chemo-therapies in prostate and other cancer models. He is also the scientific founder of OncoGenex Pharmaceuticals Inc. The TVN Network has elected Russell Williams, president, Canada’s Research-Based Pharmaceutical Companies (Rx&D), as its new chair of its board of directors.

ness director of oncology, global strategic marketing and therapeutic area head of oncology at Roche, Basel, where he also served as medical director in oncology and global development project leader.

Russell Williams

Mr. Williams assumed the role at the board’s first meeting held in Toronto on January 22, 2015. TVN is a not-for-profit research network aimed at improving the care of seriously ill elderly patients, and supporting their families and caregivers. Prior to joining Rx&D, he successfully represented the Montréal riding of Nelligan for 15 years as a Liberal MNA in the National Assembly of Québec, and is well known for his advocacy for individual rights and government services focused on the needs of citizens. He continues active volunteer involvement in palliative care and, in January 2014, received the Quality End-of-Life Care Coalition of Canada (QELCCC) second annual Award of Excellence in Advocacy for his tireless advocacy for hospice palliative care. He is also well known for his championship of Canadian health research, and this commitment was honoured in November of 2014 when he received the inaugural Research Canada Leadership Award. Aptose Biosciences Inc. has added oncology industry veteran and venture investor Dr. Erich M. Platzer to its board of directors. He brings considerable product development, clinical trial management, licensing and commercialization expertise from his career in the pharmaceutical industry. He also has a rich background in oncology and hematology from both the clinical and business perspectives. Dr. Platzer is a board certified physician in internal medicine, hematology and medical oncology. Previously, Dr. Platzer was busi-

BriaCell Therapeutics Corp has engaged Dr. Steven J. O’Day as principal investigator for its upcoming BriaVax™ vaccine clinical trial. Dr. O’Day is a highly specialized oncologist with a history of leading successful clinical trials, having been educated and trained at Johns Hopkins, Harvard, and Oxford. Dr. O’Day has acted as the principal investigator on over 100 clinical trials including several large, international Phase 3 clinical trials. He served as the principal investigator in BristolMyers Squibb’s Phase 3 clinical trial for its Yervoy, which included 676 patients, and saw a significant improvement in overall survival for late-stage melanoma patients. Lynne Bulger will be joining Cipher Pharmaceuticals Inc. in the role of vice president, medical and clinical affairs where she will lead the company’s clinical development and medical affairs efforts for current and new pipeline products. Ms. Bulger has 27 years of experience in drug development in the pharmaceutical industry, conducting clinical research and providing strategic medical marketing support in dermatology, rheumatology, osteoporosis and CNS. Most recently, she held the position of director medical affairs at Stiefel, a GSK company. In this role, she was responsible for medical affairs activities for Stiefel Global and Canada for 35 dermatology products. Previous to that, she was director medical and regulatory affairs at Barrier Therapeutics and director medical affairs at Hoffman-La Roche. She also served as president of the Canadian Dermatology Industry Association from 2005 to 2008. In addition to this appointment, Cipher promoted Peter Weiler to the position of vice president, business development and Linda Angaritis to the position of vice president, global regulatory compliance and quality. The Public Health Agency of Canada announces the appointment of Dr. Matthew Gilmour as its new scientific director general

National Public Health Laboratories, responsible for the National Microbiology Laboratory (NML) in Winnipeg, MB and the Laboratory for Foodborne Zoonoses (LFZ) in Guelph, ON. Dr. Gilmour is currently a clinical microbiologist with diagnostic services of Manitoba and an assistant professor in the department of medical microbiology at the University of Manitoba.

Dr. Matthew Gilmour

He is also a past employee of the Agency where he held the positions of director of bacteriology and enteric diseases and the chief of enteric diseases at the NML. As scientific director general, he will be responsible for managing the delivery of laboratory public health and emergency preparedness programs, providing strategic scientific advice to senior officials and representing Canada’s top human health laboratories nationally and internationally. The position is being filled following the retirement of Dr. Frank Plummer. Xite Bio welcomes Bob Reekie to its team. Reekie was named the company’s new business and product manager. He will be based out of Regina, SK. Reekie has a long history of excellence in sales, marketing, and business development with Bayer CropScience (BCS), and most recently as a BCS consultant. His roles at Bayer CropScience have included director of cereal crops marketing Canada, director of marketing Western Canada, director of InterAg, and cereal portfolio manager.


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Tips, Tricks and Information for the ergonomic design of your laboratory

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he advantages of an orderly work situation are obvious. It allows one to keep all required instruments in view and within reach, therefore generating smooth work flow. Instruments and devices do not have to be found and brought to the bench first. Even leaning forward and stretching the upper body in order to reach something violates the ergonomic concept of an orderly workplace. The more chaotic and untidy a workspace, the more unnecessary or even harmful additional movements are required. Finally, an untidy work area can lead to increased mental strain, since constant searching interferes with the concentration required for the actual task at hand. One solution for lack of order stems from the principles of Kaizen (from the Japanese: “change for the better”) which is often employed in production. This Japanese term stands for a stepwise approach, with the help of which increasingly higher standards in the improvement of quality and

reduction of waste can be achieved. Thus, Kaizen implies small but nevertheless steady improvements. According to Kaizen, there are seven forms of waste which are to be kept to a minimum: overproduction, waiting times, preventable transports, complex and useless processes, large stock, superfluous movements, as well as mistakes and useless fixes. These forms of waste are universal. They can be identified equally well in a global pharmaceutical or biotech company, in the molecular lab at a University, or in a private home. In order to reduce these forms of waste, Kaizen offers four different sets of rules: Best Point – workplace design, One Piece Flow (flow principle), 5 S-rule and Poka Yoke. The 5 S-rule prescribes five simple rules which are to be followed: first, those things which are useless and superfluous are removed from the workplace (Seiri). Those items which are then part of the work area are organized (Seiton). The thus defined

workspace should from then on be kept clean and organized (Seiso). In order to put these points into practice, a personal desire for cleanliness and order needs to be developed and cultivated (Seiketsu). Finally, standards must be defined and implemented for these five rules to become habit (Shitsuke). The rules of Seiton and Seiso imply that means and ways must be found to organize items and, furthermore, maintain that order long term. To this end, deviations should be noticed quickly and rectified immediately and in an uncomplicated fashion. No strictly defined rules apply, as each workplace and each laboratory have their own expectations with respect to order. As such, individual creativity is essential. For example, a diagonal line drawn across the front of a row of binders in sequence will help keep these binders in the correct order. It is easy to spot missing binders immediately. In order to guarantee efficiency in the workplace/laboratory

it is further necessary to avoid large stocks of gloves, tips, etc. (Seiri and Seiton). Large stocks are one of the seven types of waste which are to be avoided. However, this does not imply the complete elimination of stocks; on the contrary, the availability of a certain minimum stock is a prerequisite for efficient work. A simple solution must be found for keeping the necessary stock without over stocking or under stocking. One such solution could be the traffic light system, where the colors green, yellow and red, in that order, represent a decreasing minimum stock. Shelves, drawers, etc. are easily and economically equipped with such a system. Most laboratories, however, present an entirely different picture: drawers are filled to the maximum with boxes of gloves, tips, etc., in a disorganized fashion. This, however, is a false assumption. It would be much better to note the threat of low supply of various items in drawers, cupboards and shelves via their “traffic lights” and to prevent this occurrence with one trip. When organizing a core workstation (Seiton) with consideration for physical-ergonomic requirements, in addition to the 5-S rules, the Best Point Principle should be consulted


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February/March 2015 Laboratory Focus www.laboratoryfocus.ca

Feature as well. This principle of workplace design states that items which are a part of a core work space should be kept in locations which are easiest to reach by the user. Ideally, all items would be within arm’s reach. Even in a simple office, this would be difficult to implement, and it sounds like utopia when considering the work space at hand – the laboratory. Therefore, in order to be able to implement the Best Point Principle in the laboratory, it is crucial to sort items into three different areas of reach, according to their frequency of use. The optimum area of reach is equivalent to a radius of the length of a person’s lower arm, including the hand, without stretching. This radius is the actual work area. For a range of body heights between 1500 and 1900 mm (4’11” to 6’3”), this radius is approximately 35 cm (13 ¾”). However, the maximum physiological reach comprises a radius of the length of the outstretched arm without severe leaning forward of the upper body (approx. 50 cm or 19 ½” for body heights between 1500 and 1900 mm or 4’11” to 6’3”). This is the ideal area in which items for daily use should be kept. The anatomical area of reach for persons of heights between 1500 and 1900 mm (or 4’11” to 6’3”) is up to 60 cm (23 ½”) and thus requires leaning forward in order to reach items located within this radius. It is suitable for items used in the long term. It is recommended that one get up in order to retrieve or use them, rather than leaning over to reach. Leaning forward should generally be avoided. Within the entire work area, both hands should be used. This supports coordination and distributes strain between two hands. Following the successful sorting of items, the ergonomic requirements during sitting and standing need to be considered. This is a part of orientation along the Best Point Principle. Mainly the task and the furniture in the laboratory determine whether one is sitting or standing while working. In fact, a German study of laboratory personnel revealed that approximately half the people sit while pipetting while the other half stands.1 If one stands exclusively, a chair with a high seat should be used as a sitting-standing support, and ergonomic workplace mats should be used. If one sits without exception, care should be taken to adjust the chair to the individual body height. The height is to be adjusted to allow the knees to form a 90 degree angle and the lower back to lean against a back rest. To the disadvantage of lab personnel, laboratory benches are often equipped with countless under-desk cupboards which preclude sitting altogether, or allow it only at an angle. From an ergonomic perspective, a combination of standing, walking and sitting

is superior, as in this case all stabilizing muscles are in turn activated and relaxed, depending on the state of activity. Hence, it makes sense that following a pipetting task which has been performed while standing one would move to an office area, sit down at a table and record the data into the lab book. This combines ergonomics with responsible laboratory work. In addition, the introduction of organization is subject to cognitiveergonomic requirements. These are extensively considered within the Poka Yoke rules of Kaizen. Poka Yoke desires to uncover mistakes in all possible areas of work as early as possible, thus helping prevent them. This is rooted in a form of process visualization, which allows one to recognize the flow and therefore “missteps.” Error reduction saves cost, energy and time. Productivity increases. Inevitably, products of higher quality are produced. With regard to the laboratory work space, colour coding of pipettes and tips takes center stage. While many manufacturers are now colour-coding their tips, not all of these color codes actually help prevent errors. Colour codes only make sense if they are visible unequivocally from all work positions. The advantage of intelligent color coding is rooted in minimizing pipetting errors and unnecessary actions, which result from searching for the correct pipette. Apart from colour coding, there exist many other aides in the sense of Poka Yoke. A calibration warning device installed in some electronic pipettes acts as an automatic reminder for calibrations due. Some pipettes are equipped with special mechanisms which protect the volume setting from being changed accidentally. Some electronic dispensers automatically recognize the volume of the tip fitted. The requirement for order in accordance with the rules of Seiri and Seiton extend beyond the individual workplace and are applied to the structure of the laboratory as a whole. The flow of movement in a laboratory may be compared, in a

simplified view, to those in a kitchen. In 1922, the American Christine Fredericks conducted a study to analyze the organization of kitchens. To this end, she pinpointed the paths she took in her kitchen during the preparation of an evening meal with the help of a thread. The result was a chaotic structure. Based on this observation, she re-organized all utensils and appliances according to the flow during cooking and repeated the experiment. The result was considerable reduction of distance covered and faster preparation of the evening meal. Employing similar studies of the optimization of flow in the kitchen, the German architect Margarete Schütte-Lihotzky designed the “Frankfurt kitchen” in the 1920s. Parallels to the laboratory abound. Apart from over stock, many drawers and shelves contain items (single pieces, etc), the designation of which may be difficult even for a long term member of the laboratory team. Furthermore, products (e.g. samples) are often distributed among several refrigerators. The location of instruments often does not represent the work flow. It is generally advisable to keep products and instruments which are always used together in close proximity to one another. The same is true for the storage of parts and items which are functionally related. Samples which are to be measured or processed together should be stored in the same refrigerator. A waterbath/ thermomixer should be in the vicinity of a photometer if enzyme activity is to be analyzed. As a positive side effect, the risk of contamination will be reduced. Furthermore, if possible, all work stations within a laboratory are to be organized. This will not only reduce the need for detours, but it also improves safety (toxic substances no longer need to be transported between individual laboratories, etc.). However, his type of laboratory restructuring does not aim to eliminate walking altogether. Walking should always be a part of the daily routine in the laboratory, as it provides natural breaks from repetitive tasks, and it relaxes

the stabilizing muscles. The organization described above can only be maintained over time if a long-term desire for order is created (Seiketsu). Therefore, the introduction of a new ergonomic organizational system requires the participation of all employees involved.2 Despite the participation-based approach, the realization just how effective a new organizational system can be does not appear by itself. In the beginning phase of the new organization, this realization needs to be supported by the implementation of standards and rules (Shitsuke). During the early phase, clear delegation of responsibilities for the maintenance and reinstatement of order is essential. The introduction of a schedule for order and cleanliness is helpful. However, the guarantee of cleanliness is subject to large variation according to the understanding and expectations of the individual. Thus, checklists are still required, which need to be adhered to by the person in charge according to the schedule. For example, this person makes a trip to the storage room as soon as he or she notices the need during regular check of the traffic light system. Further, the location of all individual items must be available to everyone (location of instruments, devices, consumables, chemicals, etc.). Attitude is the readiness to react to certain environmental stimuli in either a consistently positive or a consistently negative manner. In this case, the affective component plays a major role. It represents the emotional evaluation of an object. In the case where the object to be evaluated is a task or the work in its entirety, the affective component is strongly influenced by the environment. Mainly light, noise and climate play critical roles. Especially during precision tasks such as pipetting, light which is too dim places a strain on the eye muscle (focusing). Therefore, illumination between 500 and 1000 Lux is recommended for office areas and 750 to 1500 Lux for older employees.3 The higher the demand for precision during the performance of a task, the stronger the illumination required.3 When working with electronic instruments (e.g. electronic pipettes), the illumination of the display should be adjusted to ambient light conditions. A screen which is too bright irritates the eyes in dark or dimmed rooms. As a rule, natural daylight is the best and most healthy illumination. With its unique spectrum, it regulates many physiological processes; it is a well-known fact that the circadian rhythms of humans and animals are dependent on daylight. Therefore, a laboratory should have a sufficient number of windows. Furthermore, these windows need to be equipped with blinds against direct sunshine. Nevertheless, artificial light may be necessary from time to time, depending on the time


www.laboratoryfocus.ca of year and time of day. In addition, rooms without daylight are consciously chosen for certain research projects and the experiments involved therein. Loud background noise interferes with concentration. If one is subjected to it long term, it may, in extreme cases, lead to cardiovascular disease.4 For these reasons, the noise level should be kept as low as possible in order to facilitate stress-free and concentrated work. The noise level can be expressed in decibels. The decibel is a relative value, where an increase in 10 decibels is felt to be twice as loud. Normal breathing has a noise intensity of 10 decibels, whispering is already 20 decibels, and speaking in a low voice is 40 decibels. Hence, quiet speech is perceived to be eight times louder than normal breathing. The stress or tolerance level, respectively, is at 60 decibels and is equivalent to loud speech. During highly concentrated work, an average daily noise level of 35 to 40 decibels should not be exceeded.3 For tasks which require less concentration, 55 decibels are not to be exceeded.3 In terms of climate, a temperature between 21 and 22 °C (but not higher than 26 °C), relative humidity of 40 to 60 per cent and air current of 0.1 to 0.15 m/s (at 21 °C) are considered optimal.3 Furthermore, air should be free of toxic gases and low in carbon dioxide. Chemical aerosols and dust are also to be avoided. In order to achieve this, opening of windows for 10 minutes every day is recommended.3

References 1. Bruder R, Richter M, Müller J, Heppener A, 2006: [Development of a basic ergonomic concept for different types of pipettes, internal report to Eppendorf AG, Darmstadt: Institute for Labor Science] [German] Entwicklung eines ergonomischen Grundkonzeptes für unterschiedliche Varianten von Pipetten, Interner Bericht an die Eppendorf AG, Darmstadt: Institut für Arbeitswissenschaft. 2. Duell, W., 1983: [Participation-based work design. Conditions of successful intervention]

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Laboratory Focus February/March 2015 [German] Partizipative Arbeitsgestaltung. Bedingungen erfolgreicher Intervention. Psychosozial 20:71-90 3. Wittig-Goetz U, 2011: http://www.ergoonline. de/site.aspxurl=html/arbeitsplatz/arbeitsumgebung_beleuchtung/ laerm.htm http://www.ergoonline.

de/site.aspxurl=html/arbeitsplatz/arbeitsumgebung_beleuchtung/beleuchtung.htm http://www.ergo-online. de/site.aspxurl=html/arbeitsplatz/arbeitsumgebung_beleuchtung/klima_im_buero.htm 4. [Government agency for workplace protection and workplace medicine,

2003: Labor science research #124: Monitor work – noise reduction in multi-user offices] [German] Bundesanstalt für Arbeitsschutz und Arbeitsmedizin, 2003: Arbeitswissenschaftliche Erkenntnisse Nr. 124: Bildschirmarbeit – Lärmminderung in Mehrpersonenbüros.

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feature by mark Peterson and steven klein

Exploiting Macrocycle Space for Drug Discovery

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n the never-ending search for new pharmaceutical agents, significant attention has been focused on the advances enabled by the “omics” technologies, such as genomics, proteomics and metabolomics. These innovations have led to the identification and characterization of an increasing number of promising pathways and targets for therapeutic intervention. Associated with this resurgence of novel targets, a dramatic shift in drug discovery approaches to biomolecular entities has contributed to a greater number of antibody and protein drug products appearing and advancing in the pipelines of pharmaceutical and biotech companies. Unfortunately, the chemical strategies employed to attempt to modulate these pathways and targets have not experienced a similar transformation. Indeed, many of the targets being investigated are proving intractable to the traditional small molecule structures that dominate historical corporate compound collections. To address this dilemma, one area that has attracted considerable interest over the last few years is that of macrocycles.1,2 Macrocycles are chemical structures containing one or more rings of at least 12 atoms and, as such, are typically larg-

figure 1

macrocycles span the gap between small molecules and biological drugs

Target Classes ProteinProtein Interactions

Biomolecular Drugs Antibodies

Protein-DNA Interactions

Peptides

Phosphatases

Macrocycles

Proteases Ion Channels Nuclear Receptors

Proteins

Small Molecule Drugs (MW <500)

Antisense

RNAi

(MW 500-2000)

Kinases GPCRs

Molecular Weight

Figure 1. Macrocycles span the gap between small molecules and biological drugs


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Laboratory Focus February/March 2015

FEATURE

Figure 2

Cyclenium CMRT macrocycles adopt diverse topologies

er than the 500 Da molecular weight limit imposed to traditional small molecules by the well-known Lipinski “rules of five.” Importantly, this compound class effectively fills the gap between conventional small molecules and biomolecules (Figure 1), and can offer attractive features of each, the high potency and selectivity of biomolecules combined with favorable pharmacokinetic properties, including oral bioavailability, as well as the ease and lower cost of development of small molecules. Further, a wide assortment of natural products are macrocyclic in nature and have already proven to be a fruitful source of interesting bioactivity with a number of marketed drugs arising from this class. Detrimentally, preparation of analogues of natural products to modulate the properties or circumvent unfavorable aspects of the initial compounds is usually not possible due to their limited quantity, significant complexity, and poor synthetic accessibility. Nonetheless, macrocyclic compounds represent a potential wellspring for novel pharmacological activity and offer a number of attractive features: • Dense, complex functionality • Conformational rigidity • Structural preorganization • Display of diverse interacting groups in extended regions of three-dimensional space • Viable approach to protein-protein interaction (PPI) modulators and other difficult targets • Underexplored intellectual property space To date, however, difficulties in the de novo synthesis of macrocyclic structures, particularly in the library format required for the high throughput screening (HTS) campaigns that are a common starting point for most

modern drug discovery efforts, have hampered their exploration. Recently, this situation has changed and an array of innovative technologies have been developed that provide access to macrocyclic compounds of varying size and composition.3 These approaches range from purely chemical in nature to hybrid strategies that combine biological methods such as phage or mRNA display and directed translation systems with one or more chemical steps.4,5 The latter in particular can generate very large numbers of compounds, but tend to also be in the higher MW range, bringing concerns regarding their ability to possess drug-like properties. In contrast, pure chemical strategies often provide structures on the lower MW side of the macrocycle continuum with their concomitant higher potential for favorable physicochemical and pharmacokinetic profiles. Intending to exploit the advantages provided by this region of macrocycle space, a research collaboration between Cyclenium Pharma, a Québec-based pharmaceutical company specializing in the discovery and development of novel drug candidates based on proprietary macrocyclic chemistry, and the Institute for Research in Immunology and Cancer — Commercialization of Research (IRICoR) along with Université de Montréal and its Institute for Research in Immunology and Cancer (IRIC) was announced in January. This collaboration will utilize Cyclenium’s proprietary QUEST Library™ of next generation macrocyclic molecules and associated hit-to-clinical candidate optimization expertise in concert with IRIC’s state-of the-art capabilities in biological target identification, characterization and screening, as well as medicinal chemistry. The objective of the col-

laborators is to discover and develop new pharmaceutical agents for the treatment of cancer and immunological disorders. “As a chemistry-focused company, it is critical for Cyclenium to find appropriate partners, such as IRICoR, with complementary biological and pharmacological expertise, to provide a robust engine for generating new pharmaceutical agents,” commented Dr. Helmut Thomas, president & CEO of Cyclenium Pharma. “The combination of our unique CMRT™ Technology, together with the significant biology, pharmacology and medicinal chemistry expertise of IRIC provides strong synergy for the development of novel therapeutics against cutting-edge targets in oncology and immunology.” In a similar vein, Cyclenium established a collaboration with Southern Research Institute (Birmingham, Alabama, USA) in April 2014 and has indicated that additional such partnerships in their therapeutic focus areas of oncology, infectious diseases and inflammation/pain will be announced in early 2015. Although Cyclenium is a relatively young organization, its founders originate from one of the pioneers in the macrocycle field, Tranzyme Pharma, which shuttered its Sherbrooke R&D facility in November 2013 following the merger of its parent company with Ocera Therapeutics. The Cyclenium team has capitalized on its over 15 years’ experience with a significant knowledge base regarding macrocyclic drug discovery in creating its proprietary CMRT (pronounced “smart”) Technology that addresses the deficiencies of the initial efforts in this area, which often fail to deliver compounds with properties appropriate for further development as pharmaceuticals. Indeed, the focus for Cyclenium on the low-

er end of macrocycle space (MW < 800) is due to the better pharmacokinetic and physicochemical profiles that can be attained with such structures. More specifically, CMRT macrocycles combine variable linker components with bifunctional building blocks, many derived from amino acids, to permit simultaneous investigation of a diverse chemical and topological space (Figure 2). The QUEST Library contains a representative sampling of the compounds occupying this space and enables a rapid survey of it for novel bioactivity. Once initial hits are attained, the modular construction of Cyclenium’s macrocycles simplifies and accelerates hit-to-lead-to-clinic optimization through systematic variation of the linker and building block components. “With CMRT, we have maintained certain key characteristics from earlier work, but took advantage of the lessons we learned through a myriad of internal and collaborative drug discovery projects to incorporate a number of new aspects that overcome the limitations of the first generation macrocycle technologies,” explained Dr. Thomas. “As such, our strategy combines the best from the past with several novel fundamental design concepts to make CMRT a powerful and versatile approach with definite advantages for macrocyclic drug discovery.” Previous research from the Cyclenium team, while at Tranzyme, was highly successful resulting in the first two synthetic small molecule macrocycles to progress into late stage clinical trials: ulimorelin, an intravenous ghrelin agonist for postoperative gastrointestinal (GI)

“Our strategy combines the best from the past with several novel fundamental design concepts to make CMRT a powerful and versatile approach with definite advantages for macrocyclic drug discovery.”


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February/March 2015 Laboratory Focus www.laboratoryfocus.ca

feature figure 3a

figure 3b

macrocycles span the gap between small molecules and biological drugs

peutics, IRICoR has numerous active drug discovery partnerships with a number of companies, including Bristol-Myers Squibb, Merck, Pfizer, Pharmascience, and Domain Therapeutics. “In addition, we have several ongoing drug discovery and development projects with the Centre for Drug Research and Development, MaRS Innovation, and Amorchem,” continued Dr. Klein. “We look forward to a long and productive collaboration with Cyclenium.” Given the exciting potential and largely unexplored nature of the macrocycle space, it can be expected that additional collaborative efforts to take advantage of the particular expertise of organizations with an established presence in this research area, like Cyclenium and IRICoR, will continue to appear over the next couple of years.

References

recovery, which completed Phase 3 investigation, and TZP-102, an oral ghrelin agonist for GI motility disorders such as diabetic gastroparesis, which reached the end of Phase 2b. For IRICoR, this latest collaboration is an extension of its interest in the growing macrocycle area, as it is already involved in a partnership, funded by Merck Canada, with Encycle Therapeutics, a biotechnology start-up founded by Dr. Andrei Yudin of the University of Toronto and MaRS Innovation, to develop an orally-bioavailable macrocycle drug to target integrinα4β7 which is involved in the inflammatory process

in a number of diseases, most notably for inflammatory bowel disease. “Collaborating with Cyclenium is a natural fit for our business model,” according to Steven J. Klein, Ph.D., vice-president, business development at IRICoR. “We had a previous successful collaboration with Helmut and his team while they were at Tranzyme. We plan to initiate our new research effort together by including the Cyclenium QUEST Library™ in a number of upcoming HTS campaigns for novel targets in oncology and immunology, and in particular for PPI-based screens.” IRICoR’s main objective is to rap-

idly translate highly innovative scientific projects from IRIC, UdeM and various centres into high value novel therapies in oncology, immunology and related indications through strong partnerships with the private sector, thereby efficiently bridging the innovation translation gap between early stage academic research and industry (Figure 3). IRICoR is a fully-integrated drug discovery and commercialization centre, with one of the largest industry-experienced academia-based medicinal chemistry groups in Canada. In addition to the collaborations with Cyclenium and Encycle Thera-

1. Diggers, E.M.; Hale, S.P.; Lee, J.; Terrett, N.K. Nat. Rev. Drug Disc. 2008, 7, 608-624. 2. Marsault, E.; Peterson, M.L. J. Med. Chem. 2011, 54, 19612004. 3. Terrett, N.K. Drug Disc. Today Tech. 2010, 7, e97-e104. 4. Bionda, N.; Cryan, A.L.; Fasan, R. ACS Chem. Biol. 2014, 9, 20082013. 5. Bashiruddin, N.K.; Suga, H. Curr. Opin. Chem. Biol. 2015, 24, 131– 138.

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Laboratory Focus February/March 2015

Feature

By Stuart Ray, Technical Director, Seward Ltd

Preparing for Food Safety In the latter part of the 20th century, the food industry has evolved in response to the consumer demand for even greater convenience and utility.

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rozen foods, chilled foods and a variety of other manufacturing techniques were further developed to deliver to consumers’ requirements. This was all accompanied by an increase in the risk posed by microbial contaminants to consumer safety and to the survival of food manufacturers. Food poisoning and spoilage in the 21st century can now lead to food manufacturers’ bankruptcy and the destruction of hard fought for reputations of quality and safety. Unfortunately, the solution will not be the elimination of risk as the variables and possibilities of contamination from “farm to fork” are so myriad. The fact remains that a single breach can be catastrophic. Instead, the food industry as meticulously as it can, both economically and technically, continues to strive to reduce the risk with the microbiological monitoring of products and processes.

Consequences Reports posted by the Canadian Food Inspection Agency in Ottawa for the first month of this year alone highlight the pressure the food industry is under to guarantee the safety of food. Two of the most virulent and deadly species, Salmonella and Listeria have already made an appearance in vegetables and health food products, showing that it is not just eggs, soft cheeses and chicken that present a potential threat to human health. New threats and old threats appear to defy our efforts to get ahead.

An international issue Food safety is an international issue facing methods and testing regimes

across international borders. However, farming practices and permissible interventions in the food chain such as the use of antibiotics vary enormously. As a result food safety practices can affect international trade and reduce access to international markets because these practices are not harmonized. The trade agreement between the European Union (EU) and the U.S., The Transatlantic Trade and Investment Partnership (TTIP), has raised a number of contentious issues including the use of antibiotics. The public is, so far, reassured by statements made by the Food Standards Agency that antibiotic and growth hormone treated meat products will not be forced onto the plates of EU citizens. The Canada-European Union Comprehensive Economic and Trade Agreement (CETA) adopts a more harmonized approach with existing EU standards. The EU rules on food safety are designed to protect human life and health, as are the current Canadian standards. Broadly, imports of foodstuffs must comply with general conditions including traceability, hygiene and microbiological criteria. Specific rules apply on genetically modified food and feed, bio proteins and novel foods and the use of antibiotics and pesticides. Countries in the Far East keen to access western markets have found that applying accepted western testing and hygiene practices to export food products have made EU and North American markets easier to access. That all said, the key focus of food hygienists still remains on protecting consumers at home where new and unpleasant surprises often fill the headlines.


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February/March 2015 Laboratory Focus www.laboratoryfocus.ca

feature The traditional techniques of horizontal isolation of campylobacter are reliable but slow. New real time PCR techniques require shorter preenrichment following Stomaching.

If elimination of campylobacter is proving a struggle, then close monitoring and epidemiological studies will be keeping microbiologists busy for the foreseeable future.

Rapid methods The traditional techniques of horizontal isolation of campylobacter are reliable but slow. New real time PCR techniques require shorter pre-enrichment following Stomaching. The possibility of reducing the time to 24 hours allows the possibility of processors being able to clear products before shipping. However, the reliability of the final result still depends entirely on the quality of the sample provided, whatever the speed or sophistication of the method. A study of this technique applied to salmonella in chicken demonstrates the advantages of a rapid and reliable method.3

Unpleasant surprises A recent survey of chicken meat purchased from major UK retailers has demonstrated the ubiquitous presence of campylobacter species awaiting the unwary or poorly skilled cook. The project was undertaken by the Food Standards Agency (UK) and used both public and private microbiology laboratories to produce the data. The samples processed were chicken skin and sponge swabs taken from chicken carcasses. The FSA is working with government and industry to try to reduce the incidence of campylobacter in chicken meat by 2015, a target the report suggests they will struggle to achieve.1 In order to process swabs and skin prior to microbiological analysis within the FSA campylobacter project, it was necessary to maximize microor-

ganism recovery at the pre-enrichment phase to obtain reliable and reproducible analytical results within given limits and tolerances. The protocol adopted also stressed the need for preventing cross contamination between samples. The homogenisation technique used therefore needed to address both issues. This was achieved by using the Stomacher® laboratory paddle blender which ensured efficient circulation of the sample and buffer within the Stomacher® bag to maximise organism recovery and enable smaller subsamples to be taken for fully representative analysis of the whole. The sponge swab technique followed by extraction in the Stomacher® has been shown to be a superior method to traditional swab sticks generating a more representative result.2

Sample size matters An approach recently adopted by the FDA in the U.S. has addressed the statistical disadvantage the microbiologist has to work with by increasing the sample size to up to 375g. These methods, which can be found in the Bacteriological Analytical Manual , have gained favour beyond the U.S. jurisdiction and have been adopted in Australia and South Korea.4 The largest sample volumes apply to meat products and not only applied to poultry but also red meat and in particular for the analysis for e. coli 0157.

The problem Microbiology as a science has a problem. The techniques used whether they be the latest DNA probe technology or the traditional techniques,

which Pasteur himself would not be unfamiliar with, are dealing with the detection of life. Food materials are inherently variable and microorganisms unpredictable. Therefore, it is essential that this variability, both within and between samples, is minimized as far as possible prior to microbiological analyses with proper sampling and also sample preparation techniques.

The solution Sample preparation is a critical step in all food microbiology globally. High quality sample preparation delivering subsamples that are fully representative of the whole is vital to the ultimate delivery of good quality, accurate results and is a key consideration in food microbiology. To borrow a phrase from the computer industry, “garbage in, garbage out.” No matter how sophisticated your analytical technique, without a good quality sample the result will be meaningless.

References: 1. https://www.food.gov.uk/sites/ default/files/campylobacter-survey-q2-report.pdf 2. Thom K.A. et al.. Comparison of swab and sponge methodologies for identification of Acinetobacter baumannii from the hospital environment. Journal of Clinical Microbiology 2012, 50(6):2140. 3. http://tools.lifetechnologies.com/ content/sfs/manuals/4476867A. pdf 4. http://www.fda.gov/Food/FoodScienceResearch/LaboratoryMethods/ucm072616.htm

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Laboratory Focus February/March 2015

Liquid Handling Diba Industries Inc., a provider of precision fluid handling solutions for diagnostic, analytical and medical device manufacturers is launching its 10-32 cone-tip ClickN-SealTM Ultra at Pittcon 2015. The 10-32 cone-tip Click-N-SealTM Ultra connects 1/16’’ OD semirigid tubing, such as PTFE, ETF, FEP and PEEK, in to 10-32 conical ports. The fitting is suitable for pressure ratings up to 2000psi (140 bar) and is constructed from PEEK for enhanced chemical resistance. The Click-N-SealTM Ultra has a space saving compact head design and ensures leak free connections. The fitting is hand-tightened until the correct torque is reached, at which point the cap clicks, preventing both over- and under-tightening of the fitting. The fitting can be unscrewed and re-used making it suitable for multi-use applications.

web: www.dibaind.com

Microscopes ZEISS introduces its new scanning electron microscope, the MultiSEM 505. The new system features 61 beams working in parallel, making it possible to acquire 61 images in parallel. Additionally, the MultiSEM 505 offers a capture speed of 1,220 megapixels per second at a pixel size of 4 nm. This high acquisition speed is used for imaging neural tissue in brain research where it is now possible to observe much bigger samples than before. The SEM is designed for continual operation and fitted with the intuitive ZEN Software.

web: www.zeiss.com

Sample Handling Omega’s new TCL-10 series is simple to operate and can keep your sample at a low temperature for long periods. Cooling causes no mess or contamination. 20 sample compartments are in each block, sizes 0.2 ml to 2 ml and the compartments can easily be changed when different sizes are needed. The unit can also use the ceramiccoated aluminum beads to accommodate various sample vials at the same time. There are two different models: TCL-11 the analog device and TCL-12 the digital device.The TCL-10 is ideal for both the laboratory and pharmaceutical development. Simply plug it in, turn it on, and put the sample in.

web: www.omega.com

Chromatography Laboratories characterizing monoclonal antibodies (mAb) now have additional hydrophobic interaction chromatography (HIC) selectivity options, thanks to the expanded family of Thermo Scientific MAbPac HIC HPLC columns. The new MAbPac HIC-20 and MAbPac HIC-Butyl columns offer additional selectivity options for characterizing mAb oxidation variants, intact mAbs, mAb aggregates or fragments and antibody drug conjugates (ADCs). The new columns are also designed for compatibility with organic solvent and aqueous mobile phase, as well as for rugged stability and very low carry-over.

web: www.thermoscientific.com

new Products Genomic Tools

SYGNIS AG launches its TruePrime™ Single Cell WGA kit for whole genome amplification (WGA) from single cells. Single cell analysis has become one of the most exciting applications in next generation sequencing (NGS) today, as it provides accurate analysis of cancer related mutations in cells, taken via biopsies, from different locations in a tumour or characterization of the status of a patient in personalized medicine. Based on the recently discovered primase TthPrimPol, SYGNIS’ TruePrime™ technology stands for a revolutionary way to amplify the amount of DNA or RNA in a sample. While the current gold standard in MDA needs short pieces of DNA (oligonucleotides) to start off whole genome amplification, TruePrime™ does not need any synthetic random primers. The resulting benefits of this innovative approach are enormous and include complete absence of common artifacts linked to the use of oligonucleotides and a reduced amplification bias in genome coverage compared to methods using random synthetic primers. Moreover, TruePrime™ is easy to use and works perfectly well with all commonly used NGS platforms such as Illumina and IonTorrent.

web: www.sygnis.com

comPany & advertiser indeX COMPANY

PAGE

WEBSITE

aMric .............................................. 4 ................................... www.amric.ca aptose biosciences inc. .....................5,6 ............................www. aptose.com briacell therapeutics inc. ................... 6 .............................. www.briacell.com brooks life Science Systems ............. 16 ..............................www.brooks.com canadian society for chemical .................................................................... technology ....................................... 5 ....................www.chem-tech.ca/cct children’s miracle network............ 17 .. www.childrensmiraclenetwork.ca cipher pharmaceuticals inc. ..............5,6 ...................www.cipherpharma.com cole –parmer ................................... 16 .......................... www.coleparmer.ca Diba industries inc. .......................... 15 ..............................www.dibaind.com eppendorf ....................................... 20 .......www.eppendorf.ca/automation GSK ................................................. 3 ...................................... www.gsk.ca Mettler toledo.................................. 16 ........................................ca.mt.com neOMeD........................................... 3 ................................ www.neomed.ca northern lipids inc. ........................... 6 .....................www.northernlipids.com Omega ............................................. 15 .............................. www.omega.com OncoGenex pharmaceuticals inc. ......... 5 ......................... www.oncogenex.com Panasonic ....................................... 19 ....................................................... .............................................................us.panasonic-healthcare.com/twinguard proMetic life Sciences inc. ................. 5 ............................www.prometic.com pronai therapeutics inc. .................... 5 ................................www.pronai.com Simon fraser university ..................... 3 .......................................www.sfu.ca Sirona biochem corp. ........................ 6 .................... www.sironabiochem.com Structural Genomics consortium ........ 1 ................................www.thesgc.org SYGniS aG....................................... 15 ...............................www.sygnis.com thermo Scientific .............................. 15 ................ www.thermoscientific.com vwr ................................................ 2 .............................www.ca.vwr.com wyvern scientific/mandel ................ 9 ...............................www.mandel.ca ZeiSS .............................................. 15 .................................www.zeiss.com Zymeworks inc. ................................ 5 .........................www.zymeworks.com

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New Products

February/March 2015 Laboratory Focus www.laboratoryfocus.ca

Sample Measuring

Sample Collection

The Mettler Toledo MP50 Excellence is a flexible instrument for the automatic determination of melting points and melting ranges up to 300 °C. The instrument allows four samples to be measured simultaneously for higher efficiency. The intuitive one Click® colour touch screen provides fast and secure operation to the user. Accurate measurements are ensured thanks to temperature-accuracy specifications and compliance with current standards including Ph. Eur., USP, and more. Visual camera observation and digital image analysis guarantee that the result values are reliable. The high resolution videos recorded during the measurement can be repeatedly played back on the instrument at any time. This allows you to check unexpected results by visually verifying the measurements.

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Web: ca.mt.com

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Brooks Life Science Systems introduces the SampleStoreTM II SE, an extension of its SampleStore II automated storage solutions portfolio that can manage a wide range of consumable types. The modular SampleStore II SE solution is designed for libraries of 50,000 to 300,000 1.4 ml tubes at temperatures of -20° C to +20° C. It is scalable with expansion modules to meet future needs and can fit through a standard laboratory door. The system’s Strata™ user interface, used across all of Brooks’ automated storage systems, makes it easy to store and retrieve samples. The Strata software also enables comprehensive sample information management, scalability, and integration with laboratory information management systems (LIMS).

Web: www.brooks.com

Peristaltic Pump

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55 Government Laboratories 54 Pharmaceutical Companies including Pharmaceutical Wholesalers 57 Private (Independent) Lab 99 Other:____________________ ____________________________

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Reduce setup time with the Catalyst™ by Masterflex FH Series peristaltic pumps from ColeParmer. The integrated pump and drive systems arrive fully assembled and ready to run. Save additional time when changing tubing—30 seconds is all it takes. Tubing occlusion is automatic when the pump head is closed. The interlock switch powers unit down when pump head is opened while the unit is running. The Catalyst FH100 Precision Peristaltic Pumps offer an intuitive keypad to quickly increase or decrease flow. View RPM on digital display for accurate control and repeatability. Purge tubing before and after use with reversible motor. For automated processes, remote control is standard. Catalyst FH100D Digital Peristaltic Dispensing Pumps display all operational parameters on the LCD for at-aglance monitoring. Programmable dispensing modes include volume, time, or copy, with convenient programmed delay between cycles. These pumps can be programmed in seven languages. Catalyst FH100M Digital Multichannel Peristaltic Pumps provide multiple flow channels in a single pump. Their cartridge design enables quick tubing changes—and eliminates the hardware of other multichannel designs. Select from 4, 8, or 12 channel models.

Web: www.coleparmer.ca


www.laboratoryfocus.ca Laboratory Focus

February/March 2015

Calendar

MARCH 2015 March 8-12 PITTCON 2015 Venue: New Orleans, LS Twitter: @Pittcon Tel: 412-825-3220 Fax: 412-825-3224 Email: info@pittcon.org Web: www.pittcon.org

March 24-27

JUNE 2015 June 13-17 Canadian Chemistry Conference and Exhibition Venue: Ottawa, ON Tel: 613-232-6252 Email: acampbell@cheminst.ca Web: www.csc2015.ca

June 15-18

June 20-24

Bio International Convention Venue: Philadelphia, PA Tel: +1.202.962.6655 Email: convention@bio.org Web: http://convention.bio.org/2015/

Canadian Laboratory Medicine Congress Venue: Montreal, QC Tel: 613-531-9210 Email: info@clmc.ca Web: www.clmc.ca/2015/

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PharmaLink 2015 Venue: Cincinnati, OH Tel: 513-745-3020 Email: toombm@xavier.edu Web: www.pharmalink2015.com

April 16 -18 AMMI Canada-CACMID Annual Conference Venue: Charlottetown, PEI Tel.: (613) 721-7061 Fax: (613) 721-3581 Email: registration@ unconventionalplanning.com Web: http://ammi.ca/ annual-conference/2015/

APRIL 2015 April 16

April 28-30 Food Safety Summit Expo & Conference Venue: Baltimore, MD Tel: 847-405-4124 Email: fisherc@bnpmedia.com Web: www.foodsafetysummit.com

Children’s MiraCle network funds

CritiCal priority needs for

14

Children’s

hospitals

aCross Canada

eaCh day, there are

4,900

Children

17th Annual LifeSciences BC Awards Venue: Vancouver, BC Tel: 604-669-9909 ext. 104 Email: swuertz@lifesciencesbc.ca Web: www.lifesciencesbc.ca/ calendar-events/details/ event04161502.aspx

who rely on the support of Children’s MiraCle network

MeMber hospitals in Canada

MAY 2015 May 4-5 Bloom Burton & Co. Healthcare Investor Conference Venue: Toronto, ON Tel: 416-640-7580 Email: bbloom@bloomburton.com Web: www.bloomburton.com/ conference

May 22-24 Labcon 2015 Venue: Montreal, QC Tel: 905-667-8688 Email: labcon@csmls.org Web: www.csmls.org

What is Children’s Miracle Network? Children’s Miracle Network® raises funds for 170 children’s hospitals in North America, 14 of which are in Canada. These hospitals, in turn, use the money where it’s needed the most. When a donation is given, it stays in the community, ensuring that every dollar is helping local kids. These donations have gone to support critical research and training, purchase life-saving equipment, and ensure excellence in care - all in support of our mission to save and improve the lives of children.

May 26 Vaccine Innovation Conference Venue: Toronto, ON Web: www.biotech.ca

Learn more at: ChildrensMiracleNetwork.ca


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Laboratory Focus February/March 2015 www.laboratoryfocus.ca

app review PCR Essentials

New national hub for glycomics research launched

G

lycoNet, a new national research network based in Edmonton, AB is receiving $27.3 million over five years to develop new drugs and vaccines for conditions such as influenza, genetic diseases and diabetes. The new national hub will unite more than 60 researchers across Canada working in the chemistry, biochemistry, biology and immunology fields. The primary objective of the network is to deliver glycomics-based solutions for key health issues improving Canadians’ quality of life. The network will also try and fulfill the role of a one-stop global destination focused on developing new therapeutics in collaboration with academic and industry organizations to address areas of need through applied glycomics and translational research. Canadian scientists have led the way in this area of research for over 50 years. According to those involved, this new national hub will further build upon these efforts. “The network will build on the activities of the Alberta Glycomics Centre and the tremendous jurisdictional strength Canada has in this important and rapidly evolving field,” said Dr. Todd Lowary, GlycoNet’s scientific director. He adds that GlycoNet will become a crucial driver for novel solutions to unmet medical needs, including vaccines, drugs and devices. As a branch of structural medicine, glycomics is the study of the structure and function of carbohydrates (sugars) in biological systems. It has led to the commercialization of several carbohydrate-based drugs, including ones that fight influenza, blood clots, diabetes, seizures and migraines. GlycoNet researchers will analyze the function of glycomes in the body and find ways to leverage their biological role to fight various diseases. The new hub will also serve a business development function, seeking to form and incubate new spin-out companies from its funded projects. On the training front, GlycoNet will help to develop a Canada-wide curriculum in glycomics for young researchers, industry and international partners who are training in the principles and practice of drug development, intellectual property management and ethical conduct of research. The funding for the new network is a result of the most recent competition in the Networks of Centres of Excellence (NCE) program.

By: Life Technologies Corporation https://itunes.apple.com/ca/app/pcr-essentials/ id606990640?mt=8 https://play.google.com/store/apps/details?id=air.com.lifetech. invitrogen.pcressentials&hl=en PCR Essentials is an app that caters to on-the-go genetic researchers who don’t have constant access to the lab, or who simply wish to work from home. Now, scientists and technicians can monitor instrument performance from home and conduct other tasks like obtaining and reviewing real-time data from Life Technologies’ ProFlex PCR System. The app comes equipped with other tools like the Master Mix Calculator, where recipes can be stored in the cloud for later access via other devices. PCR Essentials also comes laden with interactive and educational videos pertaining to strategies and techniques for using the app. This, in combination with a clear and straightforward interface, make for a noteworthy user experience.

T

E

OTC Guide

By: MDNG https://itunes.apple.com/ca/app/otc-guide/id475326173?mt=8 https://play.google.com/store/apps/details?id=otc.guide For all the pharmacists out there: the OTC Product Guide app will guide users through the most recommended pharmaceutical products as per Pharmacy Time’s prestigious Survey of Pharmacists. With colour coded categorisation and extensive product details, this app is ideal for physicians who want to help their patients make the most informed choice when it comes to drugs and medications. Despite the convenience this free app offers, an unexceptional interface and small bugs and freezes compromise OTC Guide’s reliability.

S

Giv tec ult eas

Le


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96 Well? Done! Eppendorf epMotion® 96—fast and precise 96-channel microplate processing The new Eppendorf epMotion 96 is a semi-automated electronic pipette for high precision pipetting in 96- and 384-well plates. Without changes to the system, a large volume range of 0.5 to 300 µL can be used. Its intuitive handling makes it a great tool for anyone in the lab.

> 0.5 to 300 µL with one system > Auto-detect function for tip size > Intuitive and industry proven software concept and convenient touch screen > Intelligent, preset applications: aspiration, dilution, multi dispense, pipette and mix

www.eppendorf.ca/automation • 800-263-8715 031.A1.0131.A © 2015 Eppendorf AG.

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