Biotechnology Focus December 2016/January 2017

INSIGHTS FOR THE LIFE SCIENCE INDUSTRY

DECEMBER 2016/JANUARY 2017 VOLUME 19, NUMBER 6

Offshoring vs. Domestic

outsourcing INSIDE:

Special ROUNDTABLE Report:

What does CETA mean for Canada’s life science industry?

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FEATURES

contents

9

Offshoring vs. Domestic Outsourcing Looking at the pros and cons of choosing between an offshore or domestic outsourcing partner (By Anthony Grenier)

December 2016/January 2017 – VOLUME 19 – NUMBER 6

12 Creative Collaboration

Agreements that work; Fostering Innovation through partnerships (By Noel Courage)

21

Outsourcing and tech transfer in Canada’s biotech ecosystem A rundown of the many types of organizations that Canadian biotech SMEs turn to for their outsourcing and tech transfer needs (By Lynne Lesauteur, Alexandre Serrano, April Luong, Donald Paquette and Sonia Thomson)

23 Innovations in Biopreservation of therapeutics cells and tissues Cold chain logistics is becoming more and more important to determining success or failure for biotech companies in the biologics and cell therapies spaces (By Mike Rice)

13

Special Report: Industry stakeholders weigh in on what the Canadian-European Union Comprehensive Economic and Trade Agreement (CETA) means for Canada’s life science industry

26 How Scientists can help corporate Canada foster tech innovation We all know the stereotype of the scientist: white coat, intelligent, highly detail-oriented and very much at peace in the sanctity off their lab.

However, more and more, we’re seeing another side to scientists – many actually make great business people (By Paul Smith)

(Compiled by Shawn Lawrence)

DEPARTMENTS 6

Research news

8

Business corner

27

New Products

in every issue

30

The Last Word Perspective on trade agreements (By Peter Pekos)

29 Calendar of events www.biotechnologyfocus.ca

1:59 PM

December 2016/January 2017 BIOTECHNOLOGY FOCUS 3

PUBLISHER’S note PUBLISHER/ EDITOR-IN-CHIEF SENIOR WRITER CONTRIBUTING WRITERS

Terri Pavelic Shawn Lawrence Alexandre Serrano

Anthony Grenier April Luong Donald Paquette Lynne Lesauteur Mike Rice Noel Courage Paul Smith Peter Pekos

A small but significant step towards addressing Canada’s intellectual property regime shortcomings Flip through the pages of this issue and you’ll see there are two themes to this edition of Biotechnology Focus. The first is of course outsourcing, and its importance to small and medium sized Canadian biotech firms. The second is Free Trade Agreements, specifically the recent official signing off on the Canadian-European Union Comprehensive Economic and Trade Agreement (CETA).

With respect to the outsourcing theme, we have two feature stories for you. The first is a contributed piece by independent pharmaceutical technology transfer and outsourcing consultant Anthony Grenier. Anthony takes a look at the pros and cons of offshoring outsourcing activities versus maintaining production locally. He weighs which is the right path for innovative and generic products, discusses steps to take when offshoring, and finally, makes his recommendations to ensuring a successful sponsor/client relationship.

Our second outsourcing article comes to us via members of the National Research Council of Canada. It runs down many types of organizations that Canadian biotech SMEs turn to domestically for their outsourcing and tech transfer needs, especially in the growing subsector of biologic drug development.

On the topic of CETA, senior writer Shawn Lawrence has compiled a special Q&A roundtable report to discuss this new trade agreement and its impact on the Canadian life science and biotech sectors. Offering their insights are representatives from three of Canada’s leading industry associations: Andrew Casey of BIOTECanada, Declan Hamill of Innovative Medicines Canada and Dr. Jason Field of Life Sciences Ontario. Additionally, Noel Courage of Bereskin & Parr addresses the legal implications of the agreement.

Dalton Pharma Services president and CEO Peter Pekos continues the CETA discussion via his Last Word column, and does his part to play devil’s advocate to the positives outlined in our Special Report. He makes the case that while Free Trade agreements propose to open up new markets in theory, quite often they are not “fair” to both sides and often come at a cost to one side.

We hope you enjoy this edition and look forward to receiving your comments.

Happy New Year!

4 BIOTECHNOLOGY FOCUS December 2016/January 2017

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Elena Pankova John R. Jones Mary Malofy

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EDITORIAL ADVISORY BOARD Christine Beyaert, Roche Canada; Pierre Bourassa, IRAP, Montréal; Murray McLaughlin, Sustainable Chemistry Alliance; Ulli Krull, UTM; John Kelly, KeliRo Company Inc.; Peter Pekos, Dalton Pharma Services; Robert Foldes, Viteava Pharmaceuticals Inc.; Gail Garland, OBIO; Barry Gee, CDRD; Bonnie Kuehl, Scientific Insights Consulting Group Inc.; Raphael Hofstein, MaRS Innovation; Roberto Bellini, Bellus Health; Peter van der Velden, Lumira Capital; Albert Friesen, Medicure Inc.; Ali Tehrani, Zymeworks Inc.

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R&D news Bayer teams up with Versant to launch new stem cell company in Toronto

Bayer AG and Versant Ventures are joined by Federal Minister of Innovation, Science and Economic Development Navdeep Bains and Ontario Premier Kathleen Wynne, to launch USD $225m BlueRock Therapeutics. (L to R: Dr. Jerel Davis, Dr. Axel Bouchon, Hon. Navdeep Bains, Hon. Kathleen Wynne, Dr. Bradly Wouters, Dr. Gordon Keller, Alok Kanti)

TORONTO, ON – Bayer AG and venture capital firm Versant Ventures are dedicating $295 million ($225 million USD) to the creation BlueRock Therapeutics, a stem cell company that will work in collaboration with institutions from Canada, the U.S., and Japan.

The new company, which will be based in Toronto’s MaRS Discovery District, as well as in New York and Boston, will focus on the development of induced pluripotent stem cell (iPSC) therapies to cure a range of diseases, including heart and degenerative brain diseases. Among its assets is the iPSC intellectual property (IP) invented by Nobel Prize winner Dr. Shinya Yamanaka of Kyoto University and licensed from iPS Academia Japan Inc. One of BlueRock’s initial programs is to regenerate heart muscle in patients who have had a heart attack (myocard infarction, MI), or are suffering from chronic heart failure. The program is being advanced in collaboration with the Toronto-based McEwen Centre for Regenerative Medicine and University Health Network (UHN) and includes Dr. Gordon Keller, who is a world leader in stem cell biology and a scientific co-founder of BlueRock Therapeutics, and Dr. Michael A. Laflamme, who is a cardiac cell therapy pioneer and founding investigator of the new company.

Also integral to BlueRock Therapeutics’ formation is a wide-ranging strategic partnership with Memorial Sloan Kettering, Dr.

Lorenz Studer, a scientific co-founder of BlueRock Therapeutics and 2015 MacArthur Genius Award winner, and Viviane Tabar, neuro surgeon and founding investigator of BlueRock Therapeutics, to advance stem cell therapy programs that address various neurological diseases. Dr. Studer, a world leader in the field of developing neurons from stem cells has pioneered large scale production of dopamine neurons and his research has led to important breakthroughs that show the potential to directly treat PD through replacement therapy with functional, stem cell-derived, dopamineproducing neurons.

The manufacturing platform at BlueRock Therapeutics will be enabled by a partnership with the Toronto-based CCRM. CCRM has developed technologies and expertise to support robust and scalable GMP production of various stem cell types for cellular therapeutics.

Bayer and Versant’s financial commitments represent one of the largest-ever series A financings for a biotech company. The funds are projected to give BlueRock Therapeutics at least four years of runway and will allow the new company to advance a number of programs into the clinic.

To see this story online visit http://biotechnologyfocus.ca/bayer-andversant-team-to-launch-new-stem-cellstartup-in-toronto/

6 BIOTECHNOLOGY FOCUS December 2016/January 2017

Stem cell-based test may help tailor therapies for Leukemia TORONTO, ON – Leukemia researchers at the Princess Margaret Cancer Centre have developed a 17-gene signature derived from leukemia stem cells that can predict at diagnosis within a day or two whether a patient with acute myeloid leukemia (AML) will respond to standard treatment.

The findings, published online in Nature, could potentially transform patient care in AML says co-principal investigator Dr. Jean Wang, affiliate scientist at the Princess Margaret, University Health Network (UHN) and a Hematologist at Toronto General Hospital, UHN. According to Dr. Wang, the new biomarker is named the LSC17 score as it comes from the leukemia stem cells that drive disease and relapse. These dormant stem cells have properties that allow them to resist standard chemotherapy, which is designed to defeat rapidly dividing cancer cells. The persistence of these stem cells is the reason the cancer comes back in patients despite being in remission following treatment.

The study authors write that using the LSC17 score to single out high-risk patients predicted to have resistant disease “provides clinicians with a rapid and powerful tool to identify AML patients who are less likely to be cured by standard therapy and who could be enrolled in trials evaluating novel upfront or post-remission strategies.”

The researchers identified the LSC17 score by sampling the leukemia stem cell properties of blood or bone marrow samples from 78 AML patients from the cancer centre combined with molecular profiling technology that measures gene expression. Stanley W. K. Ng, a senior PhD candidate in the lab of Dr. Peter Zandstra at the Institute for Biomaterials and Biomedical Engineering, University of Toronto and co-lead author of the paper, used rigorous statistical approaches to develop and test the new “stemness score”, using AML patient data provided by the Princess

Dr. Jean Wang, Affiliate Scientist at the Princess Margaret Cancer Centre. (Photo: TPMCF​​​)

Margaret leukemia clinic and collaborators in the U.S. and Europe.

“We identified the minimal set of genes that were most critical for predicting survival in these other groups of AML patients, regardless of where they were treated,” says Dr. Wang. “With this core 17-gene score, we have shown we can rapidly measure risk in newly diagnosed AML patients.”

The test to measure the LSC17 score has been adapted to a technology platform called NanoString. As the research team and international collaborators continue to validate the stemness risk score, plans are

under way to test the score in a clinical trial at the Princess Margaret, which now has the NanoString system in its molecular diagnostic laboratory.

Dr. Wang adds that the fast turnaround time to measure the LSC17 score on the NanoString system will be key to moving the test into the clinic.

Feds back study of bacterial cell genes to find targets for new antibiotics

To see this story online visit http://biotechnologyfocus.ca/stem-cellbased-test-predicts-leukemia-patientsr e s p onse-to-therapy-to-help-tai lortreatment/

UniQuest and CCRM to co-develop treatment for chemotherapy-induced neutropenia TORONTO, ON & BRISBANE, AUSTRALIA – Patients at risk of life-threatening infections following chemotherapy could benefit from a new cell-based treatment developed from University of Queensland research.

In the weeks following chemotherapy, a patient’s immune system is depleted as a result of neutropenia – a decrease in the number of circulating white blood cells or neutrophils – which leaves the patient vulnerable to potentially fatal infection. UQ’s Australian Institute for Bioengineering and Nanotechnology’s (AIBN) professor Lars Nielsen and his team have developed a method of producing a therapeutic dose of white blood cells in a typical transfusion bag which can be administered to patients immediately after chemotherapy.

Professor Nielsen explains that chemotherapy-induced neutropenia (CIN) is a life-threatening risk to cancer patients.

“It exposes them to infection and fever, which can lead to delays in treatment and reductions in chemo dose intensity.” he says.

The treatment most commonly used for neutropenia involves an injection of granulocyte colony-stimulating factor (G-CSF) which stimulates the patient’s own stem cells to expand and differentiate into neutrophils. According to Nielsen, G-CSF’s effectiveness relies on the number of stem cells in the patient’s bone marrow, which is significantly reduced after chemotherapy, and it takes time for the stem cells to recover and mature into white blood cells.

“Our method instead avoids that ‘at risk’ period following treatment by extracting and separating stem cells from umbilical cord blood to produce a transfusion-ready therapeutic dose of white blood cells, which can be administered to patients immedi-

R&D news

ately after chemotherapy,” says Nielsen.

The technology is based on research

by UQ’s professor Nielsen and Dr. Emma Palfreyman, and Dr. Nick Timmins, formerly of UQ and now based at CCRM – a Canadian organization that develops and commercializes regenerative medicine technologies and cell and gene therapies.

The technology will now progress towards the clinic following a licensing deal with CCRM, negotiated by UQ commercialization company UniQuest.

UniQuest CEO Dr. Dean Moss said CCRM was the ideal partner to take the neutrophil technology towards the market.

“CCRM has demonstrated experience in fundamental stem cell science and the commercialization of regenerative medicine and we are delighted that they will take UQ’s research towards the clinic so that it can benefit patients,” Dr. Moss says.

CCRM president and CEO, Dr. Michael May, adds that the centre is excited about the agreement with UQ and UniQuest.

“By combining the technology licensed from UQ with CCRM’s expertise and capabilities in the commercialization of stem cell therapies, we believe we can provide a solution to this unmet clinical need and make a real difference to chemotherapy patients,” says May. The neutrophil research at UQ has been supported since 2003 by Stem Cells Australia and its forerunner, the Australian Stem Cell Centre, as well as the Australian Red Cross Blood Service and the Australian Research Council.

To see this story online visit http://biotechnologyfocus.ca/uniquest-and-ccrm-sign-deal-to-developtreatment-for-chemotherapy-inducedneutropenia/

REGINA, SK – A research project at the University of Regina that hopes to overcome the challengse of antibiotic resistance facing health care professionals and patients is getting new funding from the Federal Government.

As part of his research project, Dr. Mohan Babu, an assistant professor at the University of Regina, plans to use the latest in proteomics and genomics technologies to screen the genes of the bacterium Escherichia coli to understand how the interaction between genes contributes to drug resistance. The hope, he says, is that this work will produce knowledge to guide the development of new therapeutic strategies to address the challenge of antibiotic resistance.

Antibiotic resistance happens when bacteria that cause illness become resistant to the antibiotic drugs used to treat them. The threat of antibiotic resistance is that infections such as pneumonia become untreatable. This situation has created an urgent demand for new treatments for bacterial infections.

The project will be supported by a grant of $1,123,815 over five years from the Canadian Institutes of Health Research (CIHR).

The project is one of 491 projects funded in CIHR’s 2016 Project Grant competition.

“This award has come at the right moment,” says Dr. Babu, while adding that his team has accomplished a lot in the area of bacterial genetics and systems biology. “We now have the financial capability and innovative strategies to take the next steps toward identifying new drug targets. This means we are closer to coming up with new broad spectrum drugs that will kill bacterial infections, such as E. coli,” he said.

To see this story online visit http://biotechnologyfocus.ca/feds-backstudy-bacterial-cell-genes-find-targetsnew-antibiotics/ December 2016/January 2017 BIOTECHNOLOGY FOCUS 7

BUSINESS corner MaRS Innovation-backed Triphase to sell compound to Celgene TORONTO, ON – One of MaRS Innovation’s leading portfolio companies, Triphase Accelerator Corporation (Triphase), is selling assets related to its first investigational compound, marizomib (MRZ) to U.S.-based Celgene Corporation.

Triphase was first established by MaRS Innovation in partnership with the Ontario Institute for Cancer Research (OICR) and MaRS Discovery District in January, 2014. The company’s clinical asset marizomib (MRZ), a novel brain-penetrant proteasome inhibitor, was identified as showing promise in the fight against glioblastoma — a common and aggressive malignant brain tumour.

Marizomib is currently in development for patients with glioblastoma and relapsed and/or refractory multiple myeloma. It is being evaluated in clinical studies in combination with bevacizumab (Avastin®) and as monotherapy in patients with glioblastoma.

Marizomib is the first major divestiture of a compound developed inside a MaRS Innovation portfolio company.

As part of its mission, MaRS Innovation was instrumental in building the leadership team inside Triphase, providing seed funding as well as facilitating discussions with external investors. After two years of development,

Celgene was introduced to Triphase.

“This engagement between Celgene and Triphase reinforces MaRS Innovation’s commitment to Triphase as a company dedicated to advancing novel compounds through Phase 2 proof-of-concept clinical studies,” said Dr. Rafi Hofstein, president and CEO, MaRS Innovation. “Companies like Celgene recognize the importance of pursuing avenues of medical innovation to advance the science more quickly and address unmet needs.”

The Celgene deal marks the first major exit for MaRS Innovation. MaRS Innovation plans on reinvesting the proceeds from this transaction back into its portfolio of companies, fostering new opportunities and setting itself on a path of becoming a self-sustaining centre of innovation.

“This is not only good for our portfolio but it’s also good for our 15 Member Institutions and for the greater Canadian innovation community,” commented Dr. Hofstein.

Some of the more notable companies in the the MaRS Innovation portfolio include: • Encycle Therapeutics: a spin-off from the University of Toronto is developing novel enhanced cyclic peptides, which are being developed for treatment of inflammatory

bowel disease (among other inflammatory diseases) as well as novel cyclic peptidebased treatment for a variety of cancer diseases; • XOR Labs: a spin-off from University Health Network is changing the face of organ transplantation by exponentially increasing the number of donated lungs available for transplantation around the world; • ScarX Therapeutics: a spin-off from SickKids Hospital is a biotechnology company that discovers and develops innovative treatments for dermal scarring (fibrosis).

ScarX’s lead candidate, SCX-001, shows promise as the first prescription cream for the reduction of post-surgical scarring; and • Flybits: a Ryerson spin-off is the world’s only context-as-a-service product providing instant cloud access to everything needed to transform the mobile experience from generic and static to personalized and dynamic. The technology offers a unique approach to understanding where the user is currently located.

To see this story online visit http://biotechnologyfocus.ca/marsinnovation-backed-triphase-sellcompound-celgene/

AmorChem sells cystic fibrosis assets to Vertex Pharmaceuticals

Montréal, QC – AmorChem L.P. reports that it has sold its cystic fibrosis (CF) assets to Amercian pharmaceutical company Vertex Pharmaceuticals.

According to both parties, the molecules acquired interact with the cystic fibrosis transmembrane conductance regulator (CFTR) protein, known to be defective in

people with CF, and will be used in research to help advance Vertex’s CF program.

“Vertex’s expertise and dedication to CF uniquely positions the company to progress these molecules,” said Inès Holzbaur, managing partner at AmorChem. “We are gratified to know that our assets are now on a path to eventually help cystic fibrosis patients.”

8 BIOTECHNOLOGY FOCUS December 2016/January 2017

AmorChem financially supported the development of the molecules through a successful collaboration between professors David Thomas and John Hanrahan at McGill University and Traffick Therapeutics Inc., and also NuChem Therapeutics inc., AmorChem’s medicinal chemistry contract research organization.

“Our venture capital fund was launched on the premise that there is valuable research being achieved in Québec-based institutions,” said Elizabeth Douville, managing partner at AmorChem. “This agreement continues to prove that we can indeed deliver highly attractive assets to biotech companies interested by innovative, early-stage research.”

To see this story online visit http://biotechnologyfocus.ca/ amorchem-sells-cystic-fibrosis-assetsvertex-pharmaceuticals/

| By Anthony Grenier

outsourcing

Offshoring vs. Domestic

outsourcing W

ith the cost burden on healthcare budgets increasing in Western countries, the pharmaceutical and biotech industries were not exempt from the growing offshoring trend that has been observed over the past ten years in most industries. Generic companies especially have massively outsourced their manufacturing needs to India and Eastern Asia. Innovating companies too, but to a lesser extent. This article will look into the pros and cons of offshoring versus maintaining production locally.

Innovative vs. Generic products The first distinction to be made is between the highly cost competitive generic and low margin over-the-counter (OTC) products, and the innovative pharmaceutical products. From when the generic industry soared in the 80s and 90s, China and India have always been powerhouses when it comes to manufacturing non-patented or off-patented pharmaceutical ingredients.

Driven by cost reduction initiatives by Western governments, the 2000s saw an exponential increase in the number of fully integrated companies flourishing in India and in Eastern Asian countries like China, South Korea and Singapore. These companies have developed generic dossiers and offered them to Western generic companies willing to penetrate their own market. These same Western generic companies have simply outsourced their domestic manufacturing to emerging countries too. India and China were obviously the big beneficiaries of this major industry trend, while OTC and private labels products have followed the same trend.

Driven by cost reduction initiatives in sourcing, but much more conservative in its approach due to intellectual property protection, innovation companies also came to these emerging countries progressively. First, the Big Pharma companies launched jointventures in jurisdictions like China, dealing

with Contract Manufacturing Organizations (CMOs) especially, while maintaining a strong oversight over them. Typically, the “man-inthe-plant” model was the most successful, meaning that after due diligence, including compliance acceptance from corporate auditors, CMOs were welcoming on site temporary employees from the sponsor company.

This approach is still widely used even today by medium and large biotech companies as well as by Big Pharma companies, especially those that have biosimilars or biological products manufactured abroad.

stage. It is more advisable to invest money to better develop and optimize your process upfront and locally. Moreover, sponsors should avoid relying on their offshore CMO to do it for them and as it likely won’t bring the anticipated savings and in the end take longer.

Secondly, one should think twice about offshoring some legacy products, as older products are often more equipment and process dependent, therefore even harder to replicate in non-Western countries where machinery brands defer on top of having to revamp the process.

Offshoring

Attractiveness of offshoring

For specialty and small pharma companies, the narrative is quite different. Despite the fact that offshoring is an attractive strategy for lowering technology transfer costs and decreasing the cost of goods (COGs), there are multiple aspects to take into consideration before making the big jump into these markets.

First of all, transferring an early stage drug like one in Phase 1 or 2 clinical trials, or a product that is non-optimized, not sufficiently characterized, or with a lack of process understanding to an offshore supplier, will certainly worsen all the challenges typically observed during this critical manufacturing scale-up

The four key opportunities for offshoring include high volume products, technology transfers with a significant Capital Expenditure (CapEx), joint-ventures and when internal resources are internally available.

High volume products are particularly suited for offshoring, as savings will cumulate and provide a better return on investment.

Likewise, offshoring is a good outsourcing choice when there is a need to invest significantly in equipment and infrastructure. Building up a plant from scratch will be financially much more advantageous for the sponsor willing to accept the risk of offshoring.

December 2016/January 2017 BIOTECHNOLOGY FOCUS 9

outsourcing

While manufacturing locally is often a preference, it is not always possible because of the lack of local innovation, higher cost of goods and also a lack of manufacturing capacity.

Multinational pharma companies have already adopted the joint-venture model, doing so a couple of decades ago. Availability of internal resources is a strong asset to ease offshoring too, as it allows to support strong local oversight like a “man-in-the-plant” model, when possible. It also helps diligently in managing suppliers of offshored products, especially with the sponsor’s technology transfer team members and documentation compliance personnel.

The downside of offshoring On the opposite side of the ledger, offshoring comes with its own distinct challenges.

Amongst them, we can mention communication, cultural differences, the underestimated oversight costs, the difficulty to source some materials in emerging countries and compliance issues, a hot topic these days.

Project managers will tell you that teleconference calls with contract manufacturers in India and China often end with the sentence “Could you please send me an email to confirm,” which between the lines often means “The line was not good or we could not hear you properly and we would like to have the request written to make sure we understand the ask.” The efficacy of project calls is very low in such cases. Another point to add is that the rapidity at which the email exchanges are executed in North America is not the norm elsewhere in the world.

There is no intent here to list all the possible cultural differences between the sponsor and the vendor in such off-shoring relationships, but to name a few, such as suppliers in Asia, for example, will rarely argue and say “no” to your requests, leaving you with the under-

standing that all will be executed as discussed.

Unfortunately, that is not always the case.

Also, auditing a site during a pre-arranged visit won’t necessarily give you the day-to-day portrait of the way the site is operated the majority of the time.

Despite the fact that anticipated savings might not always be there, it is important to account for the cost of the oversight either from the beginning during the technology transfer or during routine production with documentation review.

In the case of transferring products developed and/or launched domestically, the sourcing of the ingredients and components may unexpectedly be complicated if, for example, a high proportion of North American suppliers are involved. This is especially true for narcotics, active ingredients requiring permits and some packaging components with proprietary molds.

Last, but not the least, from a compliance point of view, Health Canada is relying on the European agency’s (EMEA) and the FDA’s site inspection reports. And over the past few years, there have been an unprecedented number of warning letters and import alerts issued by the FDA from manufacturing sites located in India and China.

Compliance has constantly been driven upwards over the years and the regulatory space more and more stringent. A CMO successfully passing a Pre-Approval Inspection or an EMEA first approval inspection, but subsequently not maintaining sufficient quality standards for the next inspection, could be the source of product disruption for the sponsor. In these circumstances, more resources for periodic site inspections will have to be considered.

10 BIOTECHNOLOGY FOCUS December 2016/January 2017

Opportunities for domestic outsourcing Domestic outsourcing offers many benefits to sponsors, such as better site and information access, an advantageous exchange rate, easier agreement execution and the ability to closely manage the project. First, easy accessibility to the facility and the possibility to reach sponsor’s counterparts to discuss technical or supply challenges is essential particularly in the early phases of the product transfer where multiple challenges can occur right up to validation.

In terms of currency, with the history of the exchange rate in Canada, for outsourcing needs Canada remains competitive with Europe and the U.S. That could weigh in the balance on top of reducing transportation costs and risks associated with it, like temperature excursions for example.

Regarding agreements, supply agreements are typically quicker to execute domestically, and it helps that by being in the same jurisdiction, you are more likely to share the same business practices. Lastly, on the project management front, all project managers will tell you that working within the same timezone and speaking the same language will ease the communication flow between the sponsor and the CMO, especially during technical and project discussions. Communication is key during site change and technology transfer projects.

Limitations to the made in Canada model While manufacturing locally is often a preference, it is not always possible because of the lack of local innovation, higher cost of goods

outsourcing

and also a lack of manufacturing capacity.

The lack of available technology or infrastructure for new projects is particularly true for biologics and specialized dosage forms like inhalants or injectors, to name a few. Depending on the type of product, its complexity and volumes, the Canadian CMO marketplace being relatively small, domestic outsourcing might simply be impossible to achieve, and expected price targets impossible to meet due to higher COGs. The Canadian contract manufacturing market is also limited by the number of true players in this space, and it is likely that many kinds of products cannot be outsourced domestically given the projected sales.

Recommendations for offshoring What drives the decision to offshore may vary from one company to another. However, once preliminary discussions have been completed, including technical assessment and quotes, compliance of the site will have to be confirmed by a state-of-the-art quality audit from the sponsor. It is highly recommended to target the shortest return visit possible as per spon-

sor’s Standard Operating Procedures (SOPs).

I’d also advise that no firm orders should be placed before the audit report has been issued and observations / recommendations have all been addressed.

There have been multiple projects working successfully in the context of offshoring, but I would suggest having one or several local employees trained by the sponsor, or, for which compliance and audit skills were already confirmed by the sponsor.

Also, a local project manager proficient in english and with extensive international experience is a “must” to keep moving the technology transfer forward, on budget and in a timely fashion. Moreover, time differences can and should be used to the sponsor’s advantage.

I personally have always loved to have our investors or upper management witness the production of their product at any time. For troubleshooting, coordinating a manufacturing schedule is sometimes challenging and, domestically, it remains feasible, otherwise, with the distance, offshored products will require the presence of the sponsor for several weeks.

Conclusion In summary, there are many factors to take into account when making the decision to offshore the manufacturing of a product and for outsourcing domestically. Companies should carefully weigh all available options knowing that offshoring is most of the time the solution to reduce costs and address a lack of capacity, but it also requires enough internal resources from the sponsor to keep a proper oversight on the execution of the outsourced activities.

Anthony Grenier is an Independent Pharmaceutical Consultant at Technology Transfer & Outsourcing Solutions.

Previously he was Manager, Technology Transfer and Sourcing at Paladin Labs.

In his current role he assists small and virtual pharma companies in finding the right CMO for their clinical or commercial manufacturing needs. He can be reached at agrenier.ag@gmail.com.

To see this story online visit www.biotechnologyfocus.ca/offshoring-vsdomestic-outsourcing/

December 2016/January 2017 BIOTECHNOLOGY FOCUS 11

Special Report | By Noel Courage, Partner at Bereskin & Parr LLP

Creative Collaboration Agreements that Work Fostering Innovation Through Partnerships

M

cCartney & Lennon, Jobs & Wozniak, Watson & Crick.

We are all looking for synergistic collaborations. In life sciences, some of those collaborations may be with your employees, independent contractors or corporate research partners. This article will look at a few key IP issues to tie up in your research with others on patentable inventions.

Being prepared for any outcome is important – not all the collaborations mentioned above had happy endings!

Identifying Inventors

Going into a research project, there is an

end goal and you may have a sense of who the likely inventors will be. However, there are usually a few unexpected problems to resolve, plans change, and perhaps there will be a touch of serendipity. Inventors may be owners by default so you need to control everyone’s potential IP. It is also important to properly identify all inventors on a patent filing.

As an example, in a case that went to the Supreme Court of Canada, two NIH scientists tested samples of GSK’s AZT drug in a human HIV assay on a blinded basis. GSK controlled the scientists’ input for scientific integrity and to try to maintain sole inventorship. The NIH scientists were ultimately not considered inventors. So those doing outsourced work to verify efficacy, even with a complex assay, may not be inventors (the NIH invention was its assay, not use of AZT for treating HIV). Consider whether inventorship may have differed if the NIH scientists had been involved earlier in the project, and in more detail, knowing the drug they were assessing going in, interpreting results, and advis-

ing GSK on efficacy for treating HIV. Involve your research partners as much as you wish, but know the potential IP consequences on inventorship.

Tying Up Ownership with Assignments

Your employees and independent contractors should sign an agreement transferring IP to your company. If you are outsourcing research or clinical work on a fee-for-service basis, those partners should also agree that your company owns the IP. If your company is in need of a partner for complex analysis, solving problems, making an invention and commercializing it, then both organizations may expect to share in the ownership. Nonetheless, companies can make whatever ownership arrangements they wish, for example, having ownership follow inventorship or basing it on the subject matter of the particular invention made. As well, depending on the country, there may be restrictions on how each co-owner can commercialize or transfer their own rights to an outsider owner, so an agreement helps manage this activity.

In a recent case in Alberta, a disgruntled former employee tried to deny transferring his IP ownership to his company, for a sonic tool to improve oil well production. However, he had signed a broad agreement transferring IP, and the inventions he made fell within the clause, so the company owned his IP. The IP assignment stood up even though the inventor had never been fully paid.

Agreements

The terms of a commercial collaboration should be in writing to ensure

12 BIOTECHNOLOGY FOCUS December 2016/January 2017

that expectations are managed, and everyone feels they are treated fairly going in. Agreements between companies collaborating on research projects are a rulebook, setting out the research milestones, commercial plan and sharing of proceeds. It is good to have agreements in place early on before revenue starts to flow, so that parties’ entitlements and obligations are clear before there is money on the table. These agreements will deal with IP in inventions, but may also deal with other types of IP ownership, for example, in written manuals, graphic design, software code and other work product.

This ensures that the IP is transferred to the appropriate owner, regardless of who is the author or inventor. It is important to have clear financial terms, and to make sure everyone is on the same page with respect to when payment is due.

In a case in Ontario, an inventor sold his invention (a cold air draft-blocker for a window) to a company that manufactured and distributed the product. The agreement was a bit ambiguous on when the royalty obligation ended, so the two companies ended up in litigation. The court fairly picked an earlier date to end royalties, and the inventor was cut off earlier than he liked. A clear agreement would have avoided litigation.

Use IP agreements early on and wisely in all your collaborations. Get good legal advice to make sure you dot all the i’s and cross the t’s. This expression sounds overly cautious, but there was a case just a few years ago where Rogers and Aliant litigated over the positioning of a comma in a contract clause, which affected liability for millions of dollars in royalties!

| Compiled by Shawn Lawrence

CETA REPORT

Special Report

CETA and opportunities for Canada’s life science industry

O

n October 30, 2016, after seven years of negotiations, Canada and the European Union (EU) officially signed off on the Comprehensive Economic and Trade Agreement (CETA). With the ink barely dry, the Canadian government tabled Bill C-30 (First Reading) the following day. Its intent is to implement CETA into Canadian law sometime this year.

Experts have already weighed in on the CETA, saying on a broad scale it has the potential to open up a huge market for Canadian companies by giving them advantages in exporting their products to Europe. But the question is: what does it mean for Canada’s life sciences industry? After all, it is an industry where most companies are either of the small and medium variety and often are years away from actually having products to export.

Many of Canada’s leading life sciences and biopharma industry organizations have since put forth statements of support for CETA, not for opening up new markets to Canadian companies, but rather because calling it a step forward in leveling the playing field when it comes to comparing our intellectual property regime with those of other countries. Life Sciences Ontario’s Jason Field got the ball rolling with his Op-Ed piece: “CETA opens new pathways for Canadian in-

novation -- now we need to build on it.” In his piece he outlined that the agreement “continues provisions directly impacting Canada’s life sciences sector and the protection of Canadian innovation,” most notably through first, Patent Term Restoration which offers research-based pharmaceutical companies the potential to recover up to two years of time lost on their patent as a result of lengthy regulatory and government approval; and second with the Right of Appeal that will allow research-based pharmaceutical companies to more effectively appeal court decisions where a patent is ruled invalid, a process that has been available to challengers but not to patent-owners to date. And yet while most would say this is positive news, how substantial these steps are and the changes these amendments bring, is still up for debate.

As such, this month, we’ve put together a special Q&A roundtable report to further discuss the implications of the CETA to Canada’s life science and biotech sectors. Taking part are representatives from three of Canada’s leading industry associations: Andrew Casey of BIOTECanada, Declan Hamill of Innovative Medicines Canada and Dr. Jason Field of Life Sciences Ontario. Rounding out our participants is Bereskin & Parr LLP’s Noel Courage to address the legal implications of the agreement.

December 2016/January 2017 BIOTECHNOLOGY FOCUS 13

CETA REPORT

Jason Field President and CEO, Life Sciences Ontario

Q: Jason, you got the ball rolling on our coverage of CETA with your Op-Ed piece, ”CETA opens new pathways for Canadian innovation -- now we need to build on it.” Can you outline for us some of the positives you see in this trade agreement, and what these new pathways for Canadian innovation are?

First, we have to look at the overarching context of intellectual property in Canada, and as Canadians we need to be realistic about how we’re viewed externally. I think for the most part, Canada and Canadians have a very good international reputation but we shouldn’t take for granted that it applies to all areas. Intellectual property is one of those areas where Canada has lagged behind other nations globally.

We’re really not seen as competitive when it comes to protecting innovation. CETA is a small step toward addressing that bigger issue, but it is still a very important step in the right direction; that’s why in my op-ed piece I said we need to build on this. We still have a long way to go in terms of being competitive in our IP policy environment.

Q: What input did LSO have on CETA? We actively collaborated with our counterparts in Québec, Montréal InVivo and the other BiopolisQuébec partners, as part of the Ontario and Québec life sciences corridor. We wrote several joint letters to the Federal ministers of industry, encouraging them to adopt the recommendations around intellectual property as it relates to the pharmaceutical industry as part of the CETA regime. But this was more than just about protection of pharma; we spoke to the overarching intellectual property regime and the protection and value of innovation in Canada. If we want to be competitive as a nation in a global innovation economy, we need to build a strong intellectual property protection regime across the board. And there’s definitely a direct link between strong IP and having a favourable environment to attract foreign direct investment, as well.

Q: How do your members feel about CETA? We have a very diverse membership, and CETA itself is a comprehensive agreement that touches on many areas of trade. We focused our efforts on the intellectual property piece, so it’s hard for me to say that yes, every member of LSO supports everything about the agreement, but what I can say is that IP is an important element for all of our members and I think in regard to that specific part of CETA, they’re pleased that there was progress made. But again, we feel that it’s a small step forward and there’s still a lot more to be done in terms of bringing the Canadian 14 BIOTECHNOLOGY FOCUS December 2016/January 2017

intellectual property regime into the realm of competiveness.

Q: My understanding is that CETA increases the intellectual property rights of EU and US pharmaceutical companies. Indirectly, what does Canada’s life science industry stand to gain from the agreement?

I don’t think that’s entirely accurate that it just supports EU and US pharmaceutical companies because the changes are to the Canadian IP regime regardless of where a company’s head offices are located.

If they hold a Canadian patent and are dealing with Canadian intellectual property rights, then these new rules apply to the Canadian IP. Put simply, it benefits Canadian patent holders. As for the second part of the question, I think any trade agreement opens markets for Canadian firms and life science companies in Ontario and Canada.

Also, Canadian companies have been somewhat criticized for not being externally focused enough, and not being as aggressive in terms of tapping into export markets. I think in order to do that, we need to make sure that we have the right environment here at home to enable companies to succeed in our local markets. Ontario needs to be a first adopter of made in Ontario innovations, we need to buy into Canadian innovations here at home to help them launch sales into new markets. While CETA opens doors, I think we still have a lot of work to do domestically to take full advantage of these global opportunities.

Q: You also highlighted in your op-ed piece and in some of your previous answers that the two key points from the agreement are patent term restoration, and reducing multiplicity in litigation. Can you explain how this agreement helps to solve issues in these two key areas?

The easy one is patent term restoration. The pathway to developing a drug product from discovery all the way through to commercialization, including clinical work and regulatory approval, is a long process and a very expensive one. The numbers typically cited are an average of 12 years and a billion dollars, and it’s probably more than that now. And that’s just for small molecules; biologics are even more complicated. These products are also some of the most strictly regulated in any industry because they’re being given to sick people, and of course you want them to be safe and effective, so they are very heavily and carefully regulated – rightly so. Those strict regulatory processes often times cause delays in terms of reaching the market.

So, for an innovative company developing a drug product, going through all of these regulatory approvals and investing huge amounts of time and capital, they’re losing time that they would have in terms of their patent protection to recoup their costs by selling the product while it’s still under patent. Patent term restoration is really a minimal acknowledgement that for regulators, which are often government bodies, there is a cost to companies in terms of delaying or using time that their intellectual property is under patent protection. It really is a restoration of that regulatory review time lost. Mind you, in the CETA agreement, Canada has only agreed to up to two years of patent term restoration which again is well below what other nations are providing. In terms of the right of appeal, this is uniquely Canadian because our Notice of Compliance regulations are very different from both the U.S. and the EU, but it is closing a loophole that I think generics firms utilized. It essentially brings a sense of fairness to the NOC process

CETA REPORT whereby innovators can appeal decisions that are made, and it was a right previously that was only extended to the generics firms and not the innovators. Again, I think there’s still work to be done on the NOC system; it’s still one of the few environments where generics products can go to market while still under a valid patent. In the EU, they have something called a interlocutory injunction to delay that while patent validity is battled out in the courts.

Q: Could CETA indirectly increase the price of drugs in Canada?

Brace yourself, I’ve got a strong view on this one. Intellectual property policy should never be a tool to manage healthcare costs. If you do that, you will absolutely undermine Canada’s competiveness in the global innovation economy. Just the concept that as a nation we can control drug costs by weakening the patent protection that we afford innovators is absolutely shortsighted. I’m a former chemist and researcher who has worked in the pharma industry, and to be honest, this concept at its basis is offensive because it shows a complete ignorance of the intense knowledge, work, and skills, and the risk and capital requirement to bring an innovative pharmaceutical product to market. So, I think the question itself is problematic: intellectual property protection has nothing at all to do with pricing. What we should be looking at is how do we protect innovators so that we can encourage innovation as

we transition into a knowledge economy and become competitive in a global environment. Managing healthcare costs is a separate issue, and there are separate mechanisms with which to address that.

Q: Finally, was there anything missing in the agreement that Life Sciences Ontario would’ve liked to have seen?

Certainly things like how Canada handles patent utility compared to other nations, or how do we deal with orphan drugs or rare diseases in relation to intellectual property protection comparative to other nations such as the U.S. and within the European Union. On patent utility, that’s becoming more and more important – where patents have been invalidated based on judgements of utility in Canada, and they don’t seem to be aligning with internationally or globally agreedupon definitions. Canada has to be very careful there. But again, we’re already seen as uncompetitive when it comes to intellectual property for innovators, and that’s another example where globally we’re getting a bad reputation. Then of course there is the data exclusivity piece, which was missing from CETA as well. In many regards, even the areas that were addressed in the agreement, like Patent Term restoration, that gives innovators an additional two years, and it’s five years in other major markets. So, while CETA made some headway, we’re still lagging behind on many of these areas.

Declan Hamill

Q: What prompted the CETA agreement?

VP, Legal, Regulatory and Policy at Innovative Medicines Canada

Q: Tell us a bit about who your members are?

We have approximately 50 members and they are located across Canada. Some of them are small biopharmaceutical companies, others are very large multinational companies. We have a very diverse membership, but all are on the research-based side of the pharmaceutical spectrum.

Q: Does Innovative Medicines Canada agree that CETA opens up new pathway for innovation in Canada?

We see it as being a step in the right direction, sending a positive signal with some of the legal and regulatory changes, that Canada is upping its game in terms of life sciences innovation.

CETA has been an idea which has been around for decades. Since the 1970s, Canada has been interested in a more integrated trading relationship with the European Union, or originally as it was known as the Common Market. One of policy drivers has always been given Canada has had a tremendous trade dependence on the United States for its exports, so there has been a desire to diversify export markets and to increase ties with other jurisdictions. That to my understanding is the historic driver of this. The origins of the most recent round of negotiations, which are finally seeming to be coming to a conclusion, was in 2009 when there was a joint study done by the European Union and Canada which supported the idea of having an enhanced trading relationship and set out some of the benefits of it. This current round of negotiations started with that study in 2009, but the idea of having some sort of free trade agreement between Canada and Europe has been around for decades.

Q: How does Canada’s life science industry benefit from this trade agreement?

There are several benefits arising from the agreement. One is the European Union generally speaking has higher intellectual property standards than Canada, and as part of this agreement with the E.U., Canada is moving to more closely harmonize its IP standards. Why is that good for Canadian innovative life science companies? It’s because their inventions also need to be protected by patents and data protection, so it is a benefit in that sense. There are also other beneficial chapters in the agreement. There’s a chapter that is supposed to promote increased regulatory cooperation, and of course, more December 2016/January 2017 BIOTECHNOLOGY FOCUS 15

CETA REPORT regulatory harmonization with jurisdictions like Europe and the U.S. would also benefit life science innovators in Canada. There’s another chapter that deals with labour mobility, and in many cases companies seek to bring people from one jurisdiction to another because they’re specialists or senior management, and the chapter aims to support or improve the flow of people between Europe and Canada. I think that’s also a benefit to the Canadian life science sector in a sense that we have very talented people and they want to work elsewhere, or alternatively, there are such people who can come here and help our industry, and other sectors as well.

Q: What input did Innovative Medicines Canada provide during the CETA negotiations?

We participated in the Government of Canada’s consultation processes. Throughout the long negotiation of the agreement, that Government of Canada kept the business community and other societal stakeholders as well informed as it could throughout the negotiations.

With respect to Europe, the European industry also inputted into the European Commission with its ideas of what should be in the agreement. So I think the industry did provide input, like other stakeholders, both here and in the E.U.

Q: Our understanding is that CETA increases the intellectual property rights of EU and U.S. pharmaceutical companies, but what does it do for Canadian companies and innovators?

We would see it as being good for innovators irrespective of where their corporate headquarters might be. Our view of it would be that because IP is important to protect innovation and because other developed nations have generally speaking higher standards of IP protection than Canada, and that greater harmonization with respect to these developed world standards is desirable for innovation in Canada.

We certainly don’t look at it as a win-lose dynamic, rather, we actually saw it as being a benefit for innovation in Canada.

Q: But isn’t the increase to IP rights more about creating a friendly IP environment for foreign companies in Canada, or is there more to it than that?

It’s to encourage companies to do business in Canada, but importantly it’s also to encourage them to bring innovations to Canada. Because innovative companies have only a time limited opportunity to get a return on investment in the Canadian market, which is constrained by the life of the patent and by the duration of data protection, and to the extent that there is an ability to bring more product to Canada, that’s a good thing for our system. Companies have to make decisions on where they launch products, and they have to consider what possible -returns they might get on their investments and therefore having a suitable period to recover R&D expenses that are incurred while making innovative drugs is important.

Q: What does Canada’s life science industry stand to gain from the agreement, particularly in terms of Right of Appeal and Patent Term restoration?

There are two different issues here. The first is what we would call patent term restoration, which helps to restore some of the patent life lost in the development and regulatory approval process. With respect to that particular issue, the up to an additional two years is beneficial for innovators because currently Canada has no such system in place, making it one of the very few OECD countries with no form of patent 16 BIOTECHNOLOGY FOCUS December 2016/January 2017

term restoration whatsoever. The maximum time in other jurisdictions like Europe, the U.S., Japan and Switzerland is five years, so two years is of course a step in the right direction, but it’s still not equivalent to what is available to innovators in some other jurisdictions. So, it’s a good thing and a step in the right direction. It is not a complete harmonization with the standards of other developed nations.

On the issue of the changes to pharma patent litigation, that really is very complicated. What the treaty requires is actually very simple, it says that to the extent that one or the other party to the treaty has a system of a patent linkage, as Canada does, you have to ensure that both parties in the litigation have equivalent rights of appeal. That’s what the treaty says, however the government of Canada has also signaled that it intends to do a much more comprehensive change to the patent linkage system under which most pharma patent litigation is done in Canada, and therefore they’re going to try to create a one track system. Currently there is the possibility that you can sue or be sued under the patent linkage system, but there’s also the infringement action under the Patent Act. What the government has stated is that, in addition including the right or appeal, it also wants to simplify patent litigation in Canada by having the one track system. For this issue, the devil really is in the details. While an effective right of appeal for innovators should be a positive development, the overall impact of these changes and whether they’re positive or negative remains to be seen. We are significantly concerned that more broad changes to the system could have unintended consequences, including the possibility of an increase in patent litigation in Canada because an entirely new system will be in place, and people will test that system, contrary to the stated policy intent to reduce patent litigation.

Q: Has there been any other concerns raised or protest to the agreement?

I don’t think there’s been protest per se, however there is concern about the overall impact of these patent linkage reforms. That patent term restoration component it is a positive thing for innovators, but whether the patent linkage changes are positive remains to be seen. You cannot discern much from Bill C-30 about this because this is a matter that will be largely dealt with the regulations which follow the Bill.

Q: Do you believe that beyond Patent Term Restoration and The Right of Appeal, that CETA is an example of desperately needed progressive public policy that supports innovation here at home?

We would indeed agree with that. It’s symbolically important because there’s been a lot of concern within the industry about intellectual property in Canada. You may have heard of some of the issues with respect to what’s known as patent utility and the promise doctrine. There’s been some attention been placed on Canada by the international industry and candidly not all of it has been positive. So therefore, to the extent that CETA can send a positive signal about life sciences intellectual property in Canada, that would be helpful for innovation in Canada.

Q: Could CETA increase the price of drugs in Canada?

That’s a good question and the answer is no. When critics and commentators look at intellectual property and say IP is driving drug costs, they do so while ignoring examples from around the world. For example, although IP standards are higher in the European Union or Japan, those jurisdictions do not, on average, pay more for innovative drugs, and they don’t pay more for generic drugs. Clearly IP cannot be the cost driver for the pharmaceutical products in those jurisdictions. What’s missing from

CETA REPORT analyses focusing exclusively on IP is the access regime in the country.

Countries take measures through listing agreements and negotiations with the industry to control prices in accordance with their drug processes, and nothing in CETA will impede that in Canada, either public or private payers. In our view, comparisons or suggestions that the IP changes in CETA are going to drive prices up are really off the mark and they ignore the international experience of other developed nations.

Q: Was there anything missing in the agreement that Innova-

tive Medicines Canada would’ve liked to have seen?

Oh yes, of course. We would have preferred if the harmonization in the form of the introduction of patent term restoration was equivalent to the system that is in place elsewhere. We would have preferred it to be at the maximum five-year level which is in place in the 28 nations of the European Union, the U.S., Japan and other jurisdictions. We would also have preferred to see Canada change its current level of data protection from a base period of eight years to the EU level of 10 years. However, while there are other measures which could have been undertaken

in the context of the agreement, the negotiation of the agreement is now closed. I don’t think it’s in anyone’s interest either in Europe or in Canada to reopen substantive negotiations at this stage.

Q: Wasn’t data exclusivity protection another ask by the industry in CETA consultations?

It is correct that during the negotiations, the EU encouraged Canada to move from its current base level of eight years of data protection to the EU based level of 10 years. Our industry supported this position.

However, and for reasons that we are not privy to, the final CETA text sets out that each party to the agreement must have a minimum period of eight years of data protection in place. While it is true that CETA did not modify the current data protection period, it is important to note that this period is set out in regulations that could potentially be changed in the future without the treaty. CETA has an important role because it enshrines the current minimum level of eight years of data protection in the treaty, meaning that this level of protection will be stable and well protected for the future.

Canada. Those larger companies represent potential investors, or ultimately potential partners for whatever the innovation is. And it is important for those other larger companies that are doing business President and CEO, BIOTECanada here that their products are treated as they would be in other key jurisdictions, that they are provided the same protections they’re afforded in other jurisdictions. And that’s where it becomes really important for our members. It’s an indirect benefit to our smaller members. And when you look at those big companies, and you use JLABS @ Toronto as an example, there were a number of other countries saying, “we need a JLABS here,” whether it be in Brazil or wherever else Johnson & Johnson (J&J) is operating, and you’re sitting at those global tables and making decisions, then you have to say here’s the other reasons why we should bring it to Canada. Of course, other people in the company would ask why would J&J put it in Canada, they don’t treat our IP with the same respect we get in Europe, and so it’s important for companies like that to be able to make the case that Canada is a Q: As the national industry association for Canada’s health, good place to invest, and to do business. As such, this agreement is industrial and agricultural biotechnology sectors, what is BIOjust one part of a much broader suite of incentives that would make TECanada’s stance on CETA and does it open new pathways Canada an attractive place to do business. for Canadian innovation?

Andrew Casey

The creation of a trade agreement like CETA is certainly about keeping pace with other key jurisdictions with whom we must remain competitive. This agreement is absolutely vital to ensuring Canada remains a destination for investment and partnerships in this space.

In terms of input, Innovative Medicines Canada (IMC) took the lead, but we were supportive of the CETA negotiations and certainly what IMC was advocating for, at least from a Canadian position in terms of patent protection and extension, and right of appeal. We would certainly also echo any sentiments that came from Innovative Medicines Canada, but for slightly different reasons. If you look at our membership, BIOTECanada has all the major pharma players, but the vast majority of our members are the smaller pre-commercial companies.

And those companies, as they’re taking a wonderful innovation forward, really require the larger companies to be present and active in

Q: What prompted CETA to exist?

CETA in a macro sense is a recognition that Canada is a trading nation and that we will only survive as an economy if we have trading partners. If you look to the markets that we do most of our trading with, the U.S. is the primary one, but you don’t want to be beholden to one market because then you are subject to the ebbs and flows of that marketplace. As such, it is important to diversify and international trade agreements like CETA are good start. It comes down to the fact that Canada is too small of a marketplace on its own to survive, so you have to take a global view with your products and take them to marketplaces all over the world, and international trade agreements are a good way to do that. It helps also that Europe has some significant ties to Canada, both historically and economically.

December 2016/January 2017 BIOTECHNOLOGY FOCUS 17

CETA REPORT

I think that’s been raised often by the critics of CETA, but I think it’s a red herring. When you look at Canada, there’s a whole bunch of ways that governments are able to manage costs and prices and so I don’t think that patents are the way that you manage prices. — Andrew Casey Canadian courts are treating patent utility and usefulness. That’s an area that needs to be addressed in Canada as well, and while obviously CETA doesn’t tackle that issue, it is still an important step to making sure that the rest of the world knows that Canada is trying to stay competitive. As far as the courts go, I think Parliament would have to intervene there, obviously you can’t lobby the courts for different decisions so it really requires the government to step in and do something to reestablish the rules of patents in Canada and that would require some sort of political movement to actually change anything on that front in a more significant way.

Q: What input did BIOTECanada have on CETA as it was drafted?

As mentioned, Innovative Medicines Canada took the lead because they have the expertise and bandwidth to really handle these things.

We played a supportive role in what they were doing. Participating in several meetings, we added our voice representing small innovative companies that are in the Canadian biotech ecosystem. For us, this is not just a way of giving something to big pharma outside of Canada, as there are also implications for smaller biotech companies in this country. There’s no doubt that in any trade agreement, there’s give and take. Canada has a very vibrant biotech ecosystem here, and to keep it competitive we have to keep up with other jurisdictions especially in relation to measures that protect intellectual property rights.

Recognizing that and the importance of the IP itself, this agreement does stress from Europe’s point of view that Canada needs to keep up with other jurisdictions.

Q: Why is IP protection so important to our industry?

Every jurisdiction wants to have innovation industries in their country because they are either going to create jobs directly, or indirectly by making other sectors more competitive. With biotech specifically, Canada is in a global fight with other jurisdictions to attract innovation as well as the investment that’s going to make that innovation thrive.

In those other jurisdictions, they’re already putting in place blueprints and policy measures to attract the major players. The treatment of intellectual property is one such major policy measure, because for this sector, the IP is the asset. If you compare biotech to forestry, mining, oil and gas, those other industries also have to attract investment, but unlike biotech, if they’re not attracting investment they can’t just pick up and move to the U.S. or South America where investors are willing to invest. In our sector, if you’re not attracting investment here, you can take your idea or IP and move it to where the investment is and continue to commercialize from that place. This is what we’re facing, this threat of losing our innovation to other jurisdictions. For Canada essentially to keep pace, IP treatment must become a priority. In terms of the benefits of patent term extension, I think the biggest thing is the message it sends that Canada wants to remain competitive with other markets. If you have an extension on data protection or right of appeal, I think it sends a signal that the government in Canada is willing to take it more seriously. Another emerging challenge is how 18 BIOTECHNOLOGY FOCUS December 2016/January 2017

Q: Multinational brand name pharma companies operating in Canada often say patients come first. On this front could CETA increase the price of drugs in Canada?

I think that’s been raised often by the critics of CETA, but I think it’s a red herring. When you look at Canada, governments have a number of tools to manage costs and prices. Restricting patent life is not the way to manage prices.

Q: Was there anything missing in the agreement that BIOTECanada would’ve liked to have seen? And what more work needs to be done to strengthen IP protection in Canada?

Data exclusivity was one of the three asks from the industry, along with Right of Appeal and Patent Term restoration, but unfortunately it was dropped from CETA. That to me was the one area we would have liked to have seen provisions put in place. That’s really important from the biologics standpoint, because they (biologics) are so much more complex to develop than small molecule drugs, and most of our companies are in the biologics space, and rare diseases, where the data sets are a bit smaller. It can take a lot more time to get to the marketplace with both these types of products. The fact is when it comes to protection of data exclusivity, we aren’t competitive. As an example, Canada is at eight years exclusivity, while other major jurisdictions like Europe and the U.S. are at 10 and 12 years respectively. It would have been nice to see that disadvantage addressed in the CETA agreement.

Q: Are there any other comments you want to make on the agreement?

The CETA is an important trade deal for Canada. Canada needs to remain as competitive as possible with other jurisdictions, otherwise we’ll lose these investments and innovations. We’ll eventually get the innovation back, but we’ll have lost out on all the benefits that come with commercializing it here, so any way we can remain competitive, and IP protection is certainly one of the ways particularly in the biologics space because it does require such specific kinds of investors, it is more complex, the regulatory process can take longer because the data sets are smaller for some of them and can take longer to get through the approval process, all of that recognizes the importance. If we’ve got patent protection and intellectual property policies in place that really reward investment and recognize its importance, I think that sends a strong signal outside the country where we’re going to have to find those investors and partners.

CETA REPORT

Q: Who are the big winners in this agreement?

Noel Courage Partner with Bereskin & Parr LLP and member of the Life Sciences practice group

Unanimous decision - big pharma wins with the extra patent term.

Keep in mind that there is no gift of patent term - there will only be a patent term extension to compensate for regulatory delays in Health Canada reviewing and approving a drug. This extension represents time that the brand name could have otherwise been on the market, selling under its patent. Health Canada should take the time it needs to do proper reviews of safety and efficacy, but this prevents it from being lightning fast in its approvals. Both brand names and generics should benefit from the provisions of the Bill designed to reduce the multiplicity of litigation around pharma patents.

Q: Who doesn’t fare as well as a result of this agreement?

Q:

Where are we in the process of CETA becoming official?

It is happening. The federal government introduced a bill in the House of Parliament in October to implement the IP provisions of CETA as well as other portions of the treaty.

Q: Why do you think this agreement took so long to be ironed out?

There is a lot of bureaucracy, many country approvals and the occasional recalcitrant region (Wallonia, Belgium) required for final approval of the treaty. I don’t think three years from first announcement to final signatures and a draft Bill in the House is too far off of realistic expectations.

Q: Can you outline for us some of the positives you see in this agreement from a legal perspective for the Canadian life science, pharma and biotech industries?

Pharma and biotech are finally happy to get a patent term extension in Canada through the Supplementary Protection Certificate system.

The extension could be up to two years, only if there are regulatory delays by Health Canada in approving the drug. This is significant because most of the money is made on the back end of the patent term.

Generic companies may have to wait longer for patents to expire before they can get on the market in Canada with a copycat product. However, they have not spent the big money, or taken the risk, on R&D that the brand name companies have. — Noel Courage

Generic companies may have to wait longer for patents to expire before they can get on the market in Canada with a copycat product.

However, they have not spent the big money, or taken the risk, on R&D that the brand name companies have. Since generics are riding the coat tails of the brand name company, it’s fair if their windfall is pushed back a bit. The patent term extension won’t prevent generics from manufacturing and exporting drugs for international markets, so this is a big concession since that activity would typically be a patent infringement.

Q: Multinational pharma companies with operations in Canada often say patients come first. On this front could CETA increase the price of drugs in Canada?

CETA should not increase the prices of brand name drugs. We have government price regulations on the price of patented drugs. However, the brand name drug will be the only option on the market for a longer period of time if there is a patent term extension in effect.

There is no lower-priced generic product available during that time.

Q: Was there anything missing in the agreement that stakeholders in Canada’s life science industry would have liked to have included? Ie. As an example, we’ve been told that data exclusivity protection was a third ask by the industry in CETA consultations, but this wasn’t included in the final draft.

You are correct that many brand name companies would have liked to have a longer data exclusivity period. Canada currently provides a basic eight year data exclusivity term. In this period, generics cannot rely on a brand name company’s data as a shortcut to get their generic approval. The basic corresponding term in Europe is 10 years.

However, it wasn’t even a decade ago when Canada raised its data exclusivity from five years to eight and strengthened the protection. I think it was overly optimistic to think Canadian data exclusivity would increase shortly afterward to a 10-year term.

To see this story online visit www.biotechnologyfocus.ca/ ceta-and-opportunities-for-canadaslife-science-industry/ December 2016/January 2017 BIOTECHNOLOGY FOCUS 19

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| By Lynne LeSauteur, Alexandre Serrano, April Luong, Donald Paquette, and Sonia Thomson (National Research Council of Canada)

outsourcing

Outsourcing and tech transfer in Canada’s biotech ecosystem

I

t’s evident that outsourcing has become a leading mode of drug development for both large pharma and biotechs: in 2014, 21 per cent of global R&D spending was outsourced, and the trend is expected to grow to 32 per cent by 2019.1 In Canada, drug development is led by small and medium enterprises (SMEs) focused on biologics for oncology and central nervous system diseases.2 Our SME developers leverage many types of organizations to help drive innovation, and each player fulfills a necessary and unique role in advancing new biologics toward patients.

Outsourcing along the biologics development pathway During biologics discovery, biotechs can leverage assets from universities and publicly funded research organizations: promising targets or early-stage molecules to licence from or co-develop with these organizations. When biotechs identify hits and lead candidates, they contract private sector preclinical contract research organizations (CROs) that provide indispensable screening, chemistry, analytical, and animal research services under GLP conditions, to progress promising leads to clinical trials. Contract manufacturing organizations (CMOs) are also hired at the preclinical stage, as they produce and characterize the material needed for toxicology studies under GMP conditions. If they are involved in developing the manufacturing process, they are called CDMOs. Regulatory consultants help biotechs prepare clinical trial applications to test their molecules in patients; when biologics receive approval, clinical trial organizations (CTOs) pick up the baton. CMOs or CDMOs continue to be involved, producing clinical-grade batches for testing and later, the market. To finance clinical trials, SME biotechs are increasingly entering into strategic partnerships with biopharma to share cost and future revenue.

Regulatory and marketing consultants are contracted when the biologic approaches and is granted approval, and post-market surveillance may be contracted to a CTO.

Vibrant preclinical CROs underpin Canadian success Biotechs make up 80 per cent of all drug developers in Canada.3 As small developers increasingly go virtual, forgoing lab space and large research teams, the quality and range of services they can access at CROs becomes critical. Canada has a wealth of world-class CROs who play a major role in helping biotechs advance their products, while generating positive economic impacts such as creating high quality jobs and attracting foreign R&D spending.

To illustrate what CROs contribute scientifically, a Canadian developer could for example: • discover and generate antibodies against a promising target with ImmunoPrecise Antibodies; • tap into flow cytometry and mass spectrometry expertise for immune monitoring, biophysical characterization and biomarker quantification at MRM Proteomics, Caprion, ImmuniT, or inVentiv Health; • characterize drug substance and drug product for chemistry, manufacturing, and controls (CMC) at SGS Pharma Services or Dalton Pharma Service;

• validate the safety and efficacy of biologics at specialized in vivo preclinical testing facilities such as Charles River, ITR Labs, or CiToxLAB; • conduct predictive pharmacokinetic and pharmacodynamic (PK/PD) modelling in preparation for clinical trials with ImmuniT, Algorithme Pharma or inVentiv Health.

This is but a snapshot of CRO capabilities in Canada. To better understand the landscape, we conducted an analysis of Canada’s three main clusters: Ontario, Québec, and British Columbia.4 We determined that 117 private sector CROs offer preclinical biologics services: 54 in Québec, 44 in Ontario, and 19 in BC. At least 75 can support discovery (hit and/or lead identification), more than 99 offer preclinical services (pharmacology, toxicology, PK/PD), and at least 68 can provide chemistry, manufacturing, and control (CMC) analytics in preparation for GMP biomanufacturing and clinical trials. Our analysis suggests that British Columbia demonstrates strength in discovery, while Québec and Ontario’s strengths are spread evenly across discovery, preclinical, and analytic capabilities – which may reflect the emerging and established

December 2016/January 2017 BIOTECHNOLOGY FOCUS 21

10:54 AM

outsourcing answer complex questions developers have about their large molecules, and define PK/ PD parameters. With CMOs, NRC can develop and transfer custom expression platforms in mammalian cells to produce biologics, as well as new analytical methods to characterize the biologic’s critical quality attributes. Technology transfer of material, documentation, and procedures is accompanied by support from NRC experts, enabling CROs, CMOs, and CDMOs to offer new services to a large scope of clients, at higher volumes, with profit in mind.

Figure 1: Outsourcing and tech transfer in Canada’s biotech ecosystem SME biotech developers Test in patients

Clinical trial organization

Produce material: GMP

Contract development and manufacturing organization

Tests before CTA approval: GLP Licence or co-develop molecular assets

Innovating together

Contract research organization Expression systems and characterization

Assays and methods

Public research organization

University

Basic Research

Target ID

Hit and Lead Candidate

Preclinical Development

nature of these clusters, respectively.

Economically, the impact of preclinical CROs is substantial. Innovation, Science, and Economic Development (ISED) measures revenue, SR&ED expenditures, and employment using three categories: preclinical contract research, clinical contract research, and contract manufacturing. According to their data, Canadian preclinical CROs generate about $350 million in revenues per year and employ about 3,100 people in high quality jobs.5 Because CROs are a major scientific and economic contributor to the industry, their success underpins the Canadian ecosystem, and is crucial to continued growth in the biotech sector.

Fostering continued growth through co-development and technology transfer Many Canadian CROs are seeing their business grow each year. The advantages of working with Canadian CROs can include accelerated paperwork for regulatory submissions, faster regulatory approval, faster service, better communication, ease of access geographically, being able to supervise studies more closely, greater transparency, high quality of work, and unique offerings.

However, SME developers are also driven by price, so they may select CROs abroad to save costs. Canadian CROs can continue to distinguish themselves by offering cuttingedge expertise in testing biologics, in-depth knowledge of what regulators expect, and optimal client interface.

The National Research Council of Canada’s (NRC) Human Health Therapeutics (HHT) expertise can help foster the continued

Clinical Phase I/II

Clinical Phase III

Market

growth of CROs, CMOs, and CDMOs in Canada who operate in the biologics space. Unlike CROs, CMOs, and CDMOs, NRC is a publicly funded, not-for-profit research organization.

NRC’s mandate is to conduct research and provide innovative scientific expertise that is unique, to strategically catalyse the sector’s success. With the advent of different types of biologics (eg. bi-specific antibodies, antibody-drug conjugates, gene therapy, CAR-T cells) and production methods (eg. biomanufacturing using viral vectors), there is a clear role for NRC to develop innovative approaches that meet regulatory expectations, reduce the cost of biologics development, and effectively monitor safety and efficacy.

What do NRC’s interactions look like? First, Canadian biotechs can collaborate with NRC to co-develop complex molecules. Developers see value in tapping into over 25 years of biologics experience: 350 experts dedicated to identifying targets and hits, selecting and developing lead candidates, and conducting early preclinical testing that de-risk and add value to biotech products. NRC offers flexible quality assurance levels based on the stage of development, and is aligned with downstream requirements so that molecules and processes can be smoothly handed off to CROs and CMOs who specialize in GLP and GMP environments.

Second, the National Research Council of Canada aims to transfer its innovative biologics development and biomanufacturing platforms to CROs, CMOs, and CDMOs focused on conducting tests required for CTA/IND approval. NRC can also collaborate with CROs to develop new assays that

22 BIOTECHNOLOGY FOCUS December 2016/January 2017

Preclinical contract research is thriving in Canada, with close to 120 private sector CROs active in the biologics space. This is a trend we should seek to maintain because it is generating positive impacts on product development and the economy. Public organizations also have a role to play: our strategies should foster scientific excellence, better health outcomes, economic impact, international competitiveness, and sectorial growth.

A sound strategy to coordinate what each brings to the table is best arrived at through ongoing dialogue with the players involved in innovation. We welcome discussions with CROs, CMOs, CDMOs, and others about how the National Research Council of Canada can help maximize synergies, expand their offerings, and contribute to value creation.

Each organization has a unique role to play, and together, we can provide some of the best, most innovative support available to Canadian biotech developers. This helps them advance one of the world’s richest pipelines bursting with next-generation therapies that have the potential to revolutionize cancer, CNS, and infectious disease treatment. Innovating together in Canada’s biotech ecosystem is something we should aim for, and will lead to breakthroughs we can collectively feel proud of.

References: 1. Forst & Sullivan, Global CRO market, 2015.

2. http://www.ic.gc.ca/eic/site/lsg-pdsv.nsf/ eng/h_hn01728.html 3. Medtrack, 2016 complemented by NRC analysis and knowledge of biotech client pipelines.

4. We consulted Medtrack, One Source, BiotechGate, Contact Canada, Contract Research Map, Outsourced Pharma, Top 1000 Bio, Pharmaceutical Industry Project, and company web sites.

5. Innovation, Science and Economic Development (formerly Industry Canada), 2012.

To see this story online visit www.biotechnologyfocus.ca/outsourcingand-tech-transfer-in-canadas-biotechecosystem/

Biopreservation

| By Mike Rice

Cold Chain Logistics: Innovation in Biopreservation of Cell Therapies and Tissues

C

old chain logistics can determine success or failure for any biotech company shipping time and/or temperature-sensitive products, many of which have the potential to save lives. These include traditional solid organs intended for transplantation into a recipient, and also a new and growing class of novel cellular therapies and engineered tissue products.

In the high-profile and promising personalized medicine arena, a circular process is used with cold chain logistics playing a

critical part in two steps. For autologous cell therapies using chimeric antigen receptor and other types of T cells targeting various cancers, the process involves removing source material such as bone marrow, peripheral blood, or adipose tissue from a patient, shipping these to a processing and manufacturing facility, manufacturing a dose of therapeutic cells, and then shipping the cells back to the original clinical site for reinfusion into the same patient. Due to their fragile nature and limited shelf life outside the body, cold chain technologies are used

to maintain a reduced temperature of these biologic materials, to slow or stop metabolic activity during transport.

Challenging the status quo in cold chain Until recently, there has been minimal innovation in the design of insulated packaging systems used for the transport of time and temperature sensitive drugs, vaccines, biologics and other delicate life-saving materials. Traditionally, the industry has been rife with a lack of control, including gaping holes, interruptions and blind spots in processes, and the unavailability of temperature and other data to support the quality of a drug or cell sample. For example, the most commonly used insulated container in the healthcare industry is made from polystyrene (a beer cooler!); ice packs or some other temperature stabilizers are wedged inside to keep the product at a predetermined temperature but with no external monitoring capability. An aviation analogy can be used to illustrate critical assumptions and process limitations that exist in current distribution practices leading to suboptimal conditions and potential disaster for patients. In retrospective investigations of aircraft disasters, typically a series of pilot errors are discovered; not a single decision, but a series of incorrect assumptions that build upon what preceded, leading to loss of life.

In the burgeoning regenerative medicine industry, when validating shipping lanes for prospective shipments of starting/source material and manufactured cell products, startup companies typically make three test shipments with temperature data loggers inside the shipping container. Upon receipt at the destination, the temp data is reviewed. If no temperature excursions occur during the test shipments, an assumption is made that none will ever occur during high volume commercial production, so often, no temperature data logger is included in every shipment—this is the first process deficiency—relying on a “validate then assume” mentality about the condition of transported biologic materials.

December 2016/January 2017 BIOTECHNOLOGY FOCUS 23

Biopreservation The evo Smart Shipper product line represents the next generation of cold chain packaging and logistics, empowering shippers to document the physical condition of their time-critical and temperature-sensitive shipments by incorporating multiple technologies.

Next, even if a temperature monitor is included in each shipment, the data are not reviewed before the cells are administered to the patient. This is often completed days or weeks after infusion/injection, so the clinician is unaware of any temperature excursions that may have rendered the cells dead and useless. This is the second process deficiency. Lastly, since manufactured cells have limited shelf life, there is not enough time to aliquot a sample of cells from the received shipment to complete cell viability assays before dosing the patient. There is an assumption that the cells are viable. This is the third process deficiency. These process deficiencies create tremendous risk for patients, clinicians and providers since current distribution practices do not assure all stakeholders that time and temperature sensitive cells arrive alive and viable to provide their intended therapeutic benefit. The bottom line on this is that dead cells don’t cure cancer!

biologistex™ and evo™ To overcome these cold chain issues, BioLife Solutions and SAVSU Technologies formed the joint venture biologistex™ CCM. This is also the brand name of a cloud-hosted cold chain management Software as a Service (SaaS) that is integrated with evo™, a new generation of Smart Shippers designed by SAVSU and marketed by BioLife. The evo Smart Shipper product line perfectly complements BioLife’s family of proprietary clinical-grade cell and tissue hypothermic storage and cryopreservation freeze media products. To date, BioLife’s CryoStor® and HypoThermosol® are embedded into more than 230 customer validations and clinical trials of cell therapies targeting cancer, heart disease, vision loss, stroke, and other leading causes of disability and death. The combination of optimized, best-in-class biopreservation media and high-performance insulated shipping containers offer the cell therapy market a greatly improved chance for success in clinical trials, and hence regulatory approval to commence large-scale commercial production.

24 BIOTECHNOLOGY FOCUS December 2016/January 2017

The evo Smart Shipper product line represents the next generation of cold chain packaging and logistics, empowering shippers to document the physical condition of their time-critical and temperature-sensitive shipments by incorporating multiple technologies.

Weighing significantly less than comparably sized passive shippers, evo seamlessly integrates cellular communications with an onboard multi-parameter environmental, anti-pilfering, theft-deterrent monitoring system, a geo-location/geo-fencing feature and a secure, webbased app.

User-appointed designees anywhere in the world can monitor a package in near real time throughout its journey. The components are shaped so that they can’t be packed out incorrectly. A NIST-traceable thermocouple is embedded within the payload cavity, providing accurate payload temperature and eliminating the need for a separate data logger that can be accidentally discarded at the destination.

The biologistex Cold Chain Management Software as a Service (SaaS) app enables users to monitor high-value shipments during transit and configure actionable alerts for downstream recipients for location, approaching destination, delivery, package open, and remaining shelf life or ability via a countdown timer. These actionable alerts enable clinicians to improve patient logistics and ensure manufactured cell products are administered within their required shelf life.

Industry embracing new cold chain solutions The benefits of using evo and biologistex for transporting a variety of temperature-sensitive products for research and clinical use is starting to gain recognition in the regenerative medicine and broader life sciences markets.

Vancouver, BC-based STEMCELL Technologies is currently testing the evo Smart Shipper and biologistex cold chain SaaS for potential adoption of these technologies into its distribution practices. Many of STEMCELL Technologies’ products, such as primary cells and cell lines are time and temperature sensitive, requiring cold chain logistics to ensure biologic stability and usability by end users. STEMCELL Technologies has been a strategic distributor of BioLife Solutions’ biopreservation media products since 2008.

Brooks Automation collaborated with BioLife Solutions and presented a poster on a shipping and storage study to support best distribution practices for T cells at the International Society for Cellular Therapy (ISCT) 2016 Annual Meeting.

In the study, current practices for cell freezing using a serumcontaining home-brew freeze media and a common foam dry ice shipping container were compared to using serum-free, clinical-grade CryoStor freeze media and the CRYO evo dry ice Smart Shipper.

Cells were frozen, shipped from BioLife to Brooks, transferred to liquid nitrogen storage for 45 days, then shipped back from Brooks to BioLife and assessed for viability and functional recovery. Significant improvement in total cell survival (viability) and faster regrowth

Biopreservation

Life Sciences Ontario Annual Awards Gala Dinner

Recognizing our 2017 Award Recipients Reserve your table or ticket today March 1st, 2017 at Liberty Grand, Exhibition Place, Toronto Lifetime Achievement Award: Dr. Mickey Milner, Past President & CEO, HTX (recovery) post-thaw were observed in the cells frozen in CryoStor and shipped in the CRYO evo Smart Shipper.

Among the specific findings of the study, Jurkat T-cells frozen in traditional 95/5% cryomedia and shipped in an EPS container experienced a significant decline in viability immediately post-thaw and a delayed return to function post-thaw. The combination of CryoStor and the evo Smart Shipper was observed to provide superior protection from cryopreservation and transportation stress with no measurable decline in functional viability as a result of freezing, thawing and two cross-country transit events.

Furthermore, the CRYO evo Smart Shipper and biologistex cloudbased shipment application allowed real-time status, tracking and event alarms to be sent throughout the entire shipping process, permitting enhanced tracking. The design of the CRYO evo Smart Shipper prevent payload warming from dry ice sublimation and maintained the Jurkat T-cells within the desired temperature range throughout transit.

Innovation in the design of the evo Smart Shipper and an IoT approach in the design of the biologistex Cold Chain SaaS have resulted in a complementary solution that enables shippers of time and temperature sensitive biologic materials to have better visibility of in-transit shipments, leading to better informed clinical decisions on the use of these materials with patients.

Mike Rice is President and Chief Executive Officer of BioLife Solutions, a developer, manufacturer and marketer of biopreservation media products and smart shipping containers connected to a cloud hosted cold chain management app designed to improve the quality of delivery logistics for cells, tissues, and organs.

To see this story online visit www.biotechnologyfocus.ca/cold-chain-logistics-innovation-inbiopreservation-of-cell-therapies-and-tissues/

Community Service Award: Dr. Raphael Hofstein, President & CEO, MaRS Innovation

LSO Volunteer Award: Dr. Alison Symington, Principal, Life Science Strategic Consulting

LSO Leadership Award: Russell Williams, Vice President Government Relations and Public Policy, Canadian Diabetes Association

Life Sciences Company of the Year: Synaptive Medical, represented by Cameron Piron, President and Co-founder

For more information on registration and sponsorship phone: 416-426-7293 or email: admin@lifesciencesontario.ca.

For more details, please visit: www.lifesciencesontario.ca December 2016/January 2017 BIOTECHNOLOGY FOCUS 25

innovation

| By Dr. Paul Smith

Scientists can help corporate Canada

foster tech innovation

We all know the stereotype of the scientist: White coat, intelligent, highly detail-oriented and very much at peace in the sanctity off their lab.

H

owever, more and more, we’re seeing another side to scientists – many actually make great business people. The focus and problem-solving skills that make them terrific chemists, physicists or engineers are among the same ingredients that shape great business minds.

And, as Canada embarks on an innovation agenda under the Trudeau government, scientists can play a crucial role helping startups and corporate leaders bridge the cycle of doom that often crushes promising ideas before they can be brought to market and commercialized.

Canada has a long track record of innovation. We are one of the heaviest funders of discovery research in the world. We’re fortunate to have a highly trained and educated workforce. We also have a wealth of budding entrepreneurs with no shortage of bright ideas for new technologies.

But where we often falter is in the critical stages of moving from research to scale-up and commercialization. That’s where many start-ups fall into the gap and fail to get their ideas off the ground. And that’s where sci-

entists who are as comfortable in corporate board rooms as they are in research labs can lend their expertise, guiding start-ups past the risks threatening to take them down before they really begin.

Consider what Michael Schulhof, the former president and CEO of Sony Corporation of America, had to say on the subject in a column in Scientific American.

“Scientists understand the process of critical thinking. They know how to analyze problems by concentrating on the important elements and filtering out the irrelevant,” he wrote. “… They are willing to admit there are things they do not understand and then take the time to find out what it is they don’t know.

Business needs that kind of vision and that kind of intellectual courage.”

As a former physicist himself, Schulhof was speaking from firsthand experience of someone who had traded his lab coat for a business suit as a leader of one of the world’s most popular technology brands.

And while Schulhof penned that column more than 20 years ago, it’s as true today as it ever was.

At the Xerox Research Centre of Canada (XRCC) we see the power of fusing the worlds of science and business together on a daily basis.

For more than 40 years, Xerox engineered new materials like inks, toners and photoreceptors for the company’s own purposes at the research lab. As the primary advanced materials research and development centre for Xerox’s operations around the globe, virtually every Xerox product in market today

26 BIOTECHNOLOGY FOCUS December 2016/January 2017

has been influenced in some way by the research team in Mississauga.

But over the past four years, we have opened the doors to our lab so we can put our experience and expertise to work for other companies, collaborating with them to research and develop hightech products and bring them to market.

Members of our team have been able to draw on the problem-solving skills they developed in the lab to help start-ups identify risks, demonstrate the value-proposition of their technologies and guide them through the steps to commercialization.

As much as Canada would benefit from bringing more scientists with deep research and technical experience into the boardroom, we have to also acknowledge that not everyone is cut out for making the move out of the lab.

Mixing science and business requires individuals who can look beyond solving the pure science problems tied to a new product or technology. They have to be able to see the larger picture, where they have to take commercial problems and the challenges of a global market as well.

As Canada tries to reach its innovation potential and improve the country’s overall competitiveness on the world stage, it would do well to tap into the business acumen of the men and women solving problems in labs across the country.

Dr. Paul Smith is the Vice President and Centre Manager of the Mississauga-based Xerox Research Centre of Canada (XRCC), home to a world-class team of scientists and engineers with broad expertise in materials chemistry, formulation design, prototyping, testing, and chemical process engineering.

To see this story online visit www.biotechnologyfocus.ca/scientistscan-help-corporate-canada-foster-techinnovation/

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Protein Purification Biotage® SNAP Bio C18 and Biotage® SNAP Bio C4 cartridges represent a new range of high

assay is the first 384-well kit for use with the Luminex FLEXMAP 3D® platform. Researchers can now simultaneously measure multiple protein biomarkers in a single sample, collecting up to 366 data points per plate in the same time it would take to run a 96-well plate.

Web: www.emdmillipore.com Hoods Air Science’s Purair FLOW series laminar flow cabinets are designed to protect the work surface, products and materials from particulate contamination. The

performance flash cartridges with wide pore media (300 Å) for reversed phase purification of peptides and other larger molecules.

The cartridges have an increased loading capability compared to prep RP-HPLC, enabling more peptide to be processed in a single injection and hence faster, more efficient peptide purification. Flash purification also facilitates a reduction in solvent usage and therefore waste compared to RP-HPLC. Biotage® SNAP Bio columns are available in 10 g, 25 g, 50 g and 100 g sized cartridges and contain either Biotage® HP-Biosphere C18 or Biotage® HP-Biosphere C4 silica.

Developed with a small particle size (20 µm) and large pore size (300 Å) they provide increased resolution and the effective separation of complex peptide mixtures; making flash chromatography an efficient technique for peptide purification.

Web: www.biotage.com Assays MilliporeSigma has launched its MILLIPLEX® MAP Human High Sensitivity cytokine panel for human cytokine assays.

The new panel is an essential tool for aca-

Purair FLOW series product line employs the Air Science exclusive Multiplex™ HEPA filtration technology to sustain the contamination-free environment. Room air first passes through a HEPA filter then uniformly through the cabinet interior by laminar flow to protect work from unfiltered air. The cabinets are able to maintain a 0.45 m/s (90 fpm) airflow velocity, measured 6” (150 mm) from the filter face, with a uniformity of +/- 20% across the filter face. Airflow is oriented to exhaust airborne particulate introduced by the user. These cabinets are intended for use in non-hazardous applications where biological or biohazard byproducts are not generated and user protection is not required. They come in three model sizes with various options.

play back, and many more. This series is ideal for a wide range of applications including R&D and industrial labs, chemical, water treatment or HVAC process monitoring and strain measurement during physical testing of materials.

Web: www.omega.ca/pptst/ OM-DAQXL.html Microscopes The ZEISS Axio Observer family consists of three stable and modular microscope stands for flexible and efficient imaging. Among its features is Autocorr, a technology that allows adaption of immersion objectives to varying sample carriers and imaging conditions. The correction of spherical aberrations results in improved image contrast, higher resolution and more efficient fluorescence detection. The new Autoimmersion option that builds up and maintains stable water immersion without traditional problems such as evaporation or air bubbles is compatible with multiple water immersion objectives in the nose piece.

Definite Focus.2 is a novel hardware focus that automatically compensates for focus drift and enables long-term time-lapse imaging and demanding multi-position experiments. The ZEISS Axio Observer can be combined with the new multicolor LED light source Colibri 7 that delivers up to seven excitation wavelengths. In combination with the new Virtual Filter technology users can perform ultrafast fluorescence imaging with high spectral flexibility. Among

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demic centers, contract research organizations and biotech/pharma companies. It allows researchers to achieve four times higher throughput than traditional assays while using smaller sample sizes. The new

Data Logger The OM-DAQXL Series is OMEGA’s new exclusive portable handheld data logger that delivers high performance and functionality. This series offers 8 or 16 universal analog inputs, fast sampling rates, large data storage, and a 7-inch TFT color touch screen display offering advantages such as an intuitive user interface, easy channel configuration, data logging and

its other features are wealth of interfaces for imaging technologies, ranging from widefield transmitted light to 3D sectioning with Apotome.2, fast and sensitive confocal superresolution imaging with ZEISS LSM 880 and Airyscan, and structured illumination as well as photoactivated localization microscopy with Elyra PS.1.

Web: www.zeiss.com/axioobserver

December 2016/January 2017 BIOTECHNOLOGY FOCUS 27

new PRODUCTS

Fumes & Hoods The new Air Science Safefume™ Cyanoacrylate Fuming

precise volume settings, and is always visible during pipetting.

Web: www.BrandTech.com.

DNA Sequencing Fluidigm Corporation’s Juno™ Targeted DNA Sequencing Library Preparation System is a scalable automated library preparation solution for medium-to-high-throughput next-generation sequencing (NGS). The system brings the Fluidigm® Juno microfluidic automation platform together with the benefits of multiplexed target amplification allowing laboratories to accurately sequence more samples faster and more affordably than ever before. Optimized for use with Illumina sequencers, the Juno Targeted DNA Sequencing Library Preparation System also

Chamber is designed to safely develop latent fingerprints using ethyl cyanoacrylate (CNA) vapour in controlled environments. The chamber’s stamper resistant compartment ensures chain of custody is maintained, while its unique Multiplex™ filtration system, together with professional design and unique construction features offers personnel protection during use. Its ductless filtration system requires no connection to an outside exhaust system, while its automatic control system programs the fuming cycle. A versatile system of hanging rods and shelves allows proper positioning of items of evidence in the chamber. The Safefume is available in 24”, 30”, 48”, 60”and 72” models.

Web: www.airscience.com/ safefume-fuming-chambers.

Pipettes BrandTech introduces the Transferpette® S Adjustable Volume, single channel pipette, now in 0.1-2.5µL and 5-50µL sizes.

Constructed with innovative composite materials, Transferpette® S pipettes are lightweight and fully autoclavable, and accept tips from most manufacturers. True one-handed selection, along with light weight and short pipetting stroke reduce the risk of repetitive strain injury. Its 4-digit display is easy to read for

tion to over 2.3 million spectra. With the update, users can save time by automatically importing structures and properties directly from PubChem to enhance user-built databases. The improvements also help to streamline Bio-Rad’s Enterprise Server software for management of spectral and chemical data throughout an organization.

Bio-Rad’s KnowItAll® ID Expert software application for spectral identification also supports all techniques in the KnowItAll software (Infrared (IR), Raman, NIR, NMR, MS, UV-Vis).

Web: www.knowitall.com/ whatsnew Mixers MilliporeSigma’s Mobius® Power MIX 2000 single-use mixing system is engineered with advanced technology to effectively handle difficult-to-mix buffers, culture media powders and other pharmaceu-

redefines the library preparation workflow from extracted DNA to NGS-ready amplicon libraries. Supporting a range of panel designs from targeted multiplexed panels covering a few user defined genes to more comprehensive panels of up to 4,800 amplicons from hundreds of genes, the system can help laboratories achieve new sequencing efficiencies with consistent performance.

Web: www.fluidigm.com Software Bio-Rad Laboratories, Inc. announces the release of its KnowItAll® 2017 spectroscopy software and databases. The new version offers an additional 976,000 reference spectra in the KnowItAll Spectral Library including Bio-Rad’s Sadtler™ spectra as well as spectra from John Wiley & Sons, Inc., bringing the spectral database collec-

28 BIOTECHNOLOGY FOCUS December 2016/January 2017

tical ingredients. The Mobius® Power MIX achieves a strong vortex using an impeller design and motor based on magneticallycoupled NovAseptic® technology, a proven mixing technology in stainless steel tanks.

The system provides accessible, sterile zero deadleg sampling directly from the mixing container. A probe port allows for insertion of either a reusable probe for non-aseptic processes or a pre-sterilized, single-use sensor for in-process pH measurement of aseptic processes. Other design features make the mixing system easy to use, enabling loading of bags by one person and offering an optional integrated hoist for powder delivery.

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new PRODUCTS

X-ray Analysis SPECTRO Analytical Instruments has released a new generation of SPECTRO MIDEX small-spot energy-dispersive x-ray fluorescence (ED-XRF) analyzers for elemental analysis of precious metals.

The new SPECTRO MIDEX analyzer represents a smart alternative to fire assay testing that not only approaches fire assay in terms of precision, but greatly surpasses it in both speed and ease of use. A midrange laboratory XRF benchtop analyzer, it incorporates the latest developments in ED-XRF detector technology to deliver both an increased accuracy of elemental analysis — critical in the refining of precious metals — and substantially accelerated testing times for higher sample throughput — a priority for highvolume hallmarking centers. It is easier to operate and features helpful software and the easy transfer of results into a laboratory network. Other specific features include high precision and accuracy for a wide range of concentration levels — plus short testing times (often 30 to 40 seconds). An integrated video system aids in accurate positioning of the sample and also can help document the testing spot. Display, print-out, and transfer of analysis results supports later data use and/or proof of compliance. Its compact design with a spacious measurement chamber is able to handle samples from tiny jewelry pins to large silver pieces.

Samples are placed onto a laboratory jack, and a turn of a knob moves it precisely into optimum measurement position. Close the analyzer door and a single screen click begins the analysis.

Web: http://www.spectro.com/midex Custom Panels The SureSeq myPanel™ NGS Custom Cancer Panels from Oxford Gene Technology provides scientists with completely customized, pre-optimiszed NGS probe panels relevant to their research. Its comprehensive library of gene content covers key cancer types including, myeloid, chronic lymphocytic leukaemia, ovarian and breast. Utilizing hybridisation-based capture, the panels deliver complete coverage and uniformity, and are regularly updated for maximum relevance to current research. Moreover, the panels provide uniform coverage through all target regions including intronic and splice sites and reduce the need for fill-in Sanger sequencing which differentiates it from amplicon-based panels.

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December 2016/January 2017 BIOTECHNOLOGY FOCUS 29

LAST word

| By Peter Pekos, President and CEO, Dalton Pharma Services

Perspective On Trade Agreements “I love trade. I’m a free trader, 100 per cent. But we need smart people making the deals, and we don’t have smart people making the deals.”

— Donald Trump, US President Elect

T

he recent U.S. Presidential campaign, which was followed more closely worldwide than any in history, provided one very important benefit. For both Americans and Canadians, it elevated awareness of the North American Free Trade Agreement (NAFTA), and pending agreements such as the Canadian-European Union Comprehensive Economic and Trade Agreement (CETA), and the TransPacific Partnership (TPP).

The main justification given for pursuing a major open trade deal is that “it will provide access to a market with hundreds of millions of people.” The reality for U.S. and Canadian companies is that in practice, significant access is seldom realized.

We should have learned this lesson forty years ago from trade relations with Japan. Although they were very successful in selling to us, North American products were kept out of Japan even though we had free trade. A corporate leader back then said “they are plucking us like chickens.” Today, China quite effectively avoids buying innovative North American goods and services, even if they are made in China.

Freer trade agreements Canada and the U.S. may have in the future with China are doomed to be even more one way. In the case of EU countries, my experience is that they prefer to use EU vendors. A deal like CETA won’t change that, but it will make it easier for EU vendors to sell their competing products and services in Canada.

In past and present negotiations of trade deals, I often wonder whether government officials rationally assessed the value of these agreements in terms of effect on the national economy and employment levels? They appear to be driven by ideology or a desire to “do something” on trade rather than focus on what really happens when we agree to “open borders on trade” It is not at all surprising that trade agreements accelerated the massive closure and shift of North American manufacturing plants to countries with lower labour costs. What has happened since is the quite predictable, business-driven, flow and evolution in the job market. China is no longer interested in the low skill jobs transferred to them. Those jobs now flow to lower cost countries such as Vietnam and Cambodia.

For sound business and economic reasons, Chinese companies are actually moving some of these jobs back to the U.S. In 2013, Chinese companies invested over $14 billion to set up new manufacturing operations in the U.S., creating almost 80,000 jobs. These new plants are going into areas with a low cost labour force, often where high 30 BIOTECHNOLOGY FOCUS December 2016/January 2017

unemployment was created when U.S. companies shifted production to China. The new jobs created by Chinese investment do not begin to replace the millions of lost low skill, middle class, NA manufacturing jobs. U.S. manufacturing output, on the other hand, driven by innovation, has increased in volume and dollar value despite the smaller work force.

Innovation is a preferred driver for export, because products and technology-based services that people want to buy have natural and legal barriers to competition, and do not require assistance from free trade agreements. This is particularly true in the health care economy, which thrives on breakthrough inventions. Canada has a history of encouraging and supporting innovation. We also have an enviable level of global trust. If we focus on the development of innovative products, we will be rewarded with high value economic growth and new jobs.

The U.S. and Canada make great partners in a broad free trade agreement. We share common values, language, and culture. We have business environments free of corruption. We believe international trade is built on trust and true reciprocity, and we have a history of innovation creating products we want and need. While free trade with Mexico has been good for global businesses and for Mexican workers, NAFTA has been disastrous for millions of American and Canadian workers. In the TPP, more than half of the countries involved have different values, and they will gain manufacturing jobs at our expense.

Our current trade deals provide great benefit to developing countries and global enterprises, but adversely affect our workers. Critics suggest we should seek “fair trade” rather than “free trade”. Either we seek practical agreements that serve the best interests of all Canadians, or declare that our trade deals support global businesses and that the transfer of jobs out of Canada is proof of our desire to help raise the standard of living for everyone else.

“There are downsides to everything; there are unintended consequences to everything.” — Steve Jobs, Co-founder of Apple Inc. Got something to say?

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