Source: Montreal Gazette

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Biotechnology

Canada Ahead of the Curve

Canada’s position as a biotechnology leader-one of the top five countries in the world-is a reflection of the country’s world-class credentials.

The biotech industry also benefits from powerful partnerships that strengthen government research dollars through collaboration with universities and industry, as well as progressive financing and venture capital programs for Canadian biotech enterprises.

Proven Research Strengths in:

• Genomics
• Proteomics
• Bio-informatics
• Immuno-therapies
• Protein engineering
• New drug delivery systems
• Vaccines
• Regenerative medicine (stem cells)
• Neuroscience
• Cardiovascular

Toronto has the largest faculty of medicine in North America and the output of peer-reviewed publications from this area is greater than any other medical centre in the world.

University of Toronto biomedical scientists have pioneered the genetic mechanisms for several diseases and discovered a way to increase the yield of stem calls from umbilical cord blood by removing unwanted cells that inhibit stem cell growth.

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Life Sciences

From the identification of the muscular dystrophy gene, to discovering new ways of creating stem cells, Canada’s life sciences innovators are at the very forefront of discovery. Industry leaders are carving out global niches in biopharmaceuticals, medical devices and contract services-all thanks to Canada’s world-renowned research institutes and biotechnology clusters. Add on Canada’s 20-year patent protection, alongside its large pool of post-graduate and post-doctoral researchers, and the potential for innovation is limited only by our imagination.

With a significant and profitable healthcare market, Canada has become very attractive to life sciences companies. It is home to more than 390 pharmaceutical and 400 biotech companies that employed nearly 29,000 highly-skilled workers in 2007, making Canada the country with the third-largest number of biopharma firms in the world.

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Biopharmaceuticals

Human health represents over half of all life science companies, 70 percent of all revenues and close to 90 percent of all R&D. Canada is globally recognized for: discovery and characterization of therapeutic molecules; genomics and proteomics platforms; vaccines and immunotherapeutics, regenerative medicine; and, stem cell research and drug formulation & delivery systems.

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Contract Services

Canada is home to high-quality contract research and manufacturing services utilized by the world’s top pharmaceutical companies. As a result, we have become recognized for: advanced services in drug formulation and delivery systems; clinical trials; manufacturing and packaging; design and manufacture of high-value medical devices; and, analytical services.

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Medical Devices

Some 1,000 small and medium-sized firms employ 26,000 people in this sector in Canada. In 2007, Canadian medical devices companies generated total revenues of $4 billion and exports of $2.4 billion. Canadian firms benefit from our strengths in related sectors such as advanced materials, microelectronics, and telecommunications, among others.

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Pharmaceuticals

With an 9% annual growth rate, Canada is the third fastest growing market in the world for pharmaceuticals. The sector benefits from Canada’s thriving biotechnology industry, which also fuels pharmaceutical companies’ growth. Add to these advantages a well-educated workforce with highly-trained scientists and technicians, as well as business-friendly government policies, and it’s not surprising that nearly every major pharmaceutical company has manufacturing and/or R&D operations in Canada.

Why Canada provides a great business environment for all aspects of the pharmaceutical industry:

• Globally-recognized industry
• A vital, proactive approach to R&D
• Facilitated access to export markets

Companies in the Know Choose Canada

• Abbott Point of Care
• AstraZeneca
• Amgen
• Apotex
• Bristol-Myers Squibb
• GlaxoSmithKline
• Johnson & Johnson
• Merck Frosst
• Novartis
• Novopharm
• Pfizer
• Roche
• Sanofi-Aventis
• Schering-Plough

“Increasing numbers of people are seeing the strong, direct link between a college education and a meaningful career,” said Linda Franklin, president and CEO of Colleges Ontario. “People understand the importance of exploring their options in higher education and choosing the programs that best prepare them for their career goals. In many cases, those programs are offered at Ontario’s colleges.”

In total, 100,495 people have applied to Ontario college programs for this year.

Each year, about 40 per cent of applicants apply directly from high school. These applications increased by 8.6 per cent over last year. Non-direct applicants (people who do not apply directly from high school) increased by 20.2 per cent this year.

Franklin said career-focused higher education is particularly important in this economy, when people are looking for education, training and retraining opportunities.

“About 90 per cent of college graduates find work within six months of graduation,” Franklin said. “This is a very attractive outcome in any economy, but particularly in the current one.”

Many applicants are people seeking retraining through the Ontario government’s Second Career programs. Students in Second Career programs are funded separately from students and colleges are able to deliver programs to these students while continuing to serve high school graduates and other applicants.

However, Franklin said colleges do face pressure to find the capacity to address the huge demand in Ontario for college education.

“The popularity of our colleges speaks to their success, but also emphasizes the need to fund our colleges sufficiently to deliver the education our communities need,” Franklin said.

“We must partner with the government to fund enrolment growth so that all qualified applicants can get the education they need to find good jobs.”

Clinical research is a fast paced world full of scientific events, an exciting atmosphere where you learn how to handle research projects in an active networking with academic people. You will find yourself actively learning and producing knowledge rather than just using it. This program updated me with different aspects of clinical research specifically in North America and the 13 weeks placement put me in a workplace full of opportunity to use this knowledge and to participate directly in research projects.

My thanks to Dr. Nicholas who’s been always more than a teacher for students in this program.

Mitra M.

I am a graduate from Oxford College’s Clinical Research Program and would like to recommend it to all the new IMG’s who would like to get back into the Canadian health care profession.

The CRA program designed by Dr. Nicholas is one of the best. He is not only a teacher but a friend, philosopher and guide, and is willing to help us students anytime and in any situation.

The program prepared me to face the fast paced research field and also increased my knowledge about the Canadian healthcare system. The best parts of the program for me were the presentations and placement. During the program we were taught how to give presentations, which I had never done before. I was very nervous during my first presentation, but by the end of the program, I could present my topic without being nervous. The other best part of the course is the placement, and for me it was at The Hospital for Sick Children. It is one of the best hospitals in Canada. During my placement I got the opportunity to recruit subjects for study, conduct interviews with subjects, attend grand medical rounds, help with REB application, help in writing grants, and attend the National Institute of Health (NIH) conference.

All of this was possible as a result of attending the Clinical Research program at Oxford College.

I thank Oxford College and especially Dr. Nicholas for helping me get ready for the research field.

Vikas B.

Sponsors should submit increasingly detailed information as their clinical trials move through the various phases, according to Health Canada’s final guidance on preparing clinical trial applications (CTAs).

The new guidance addresses both chemistry and manufacturing technical requirements for Phase I, II and III clinical trials. The guidance includes a set of three quality overall summary (QOS) templates to assist sponsors in meeting specifications in each phase. Submissions for combination protocols — Phase I/II or II/III — should satisfy the quality requirements of the higher phase, the guidance says.

The QOS templates follow a common format, which includes the following:

* Introduction;

* Drug substance (general information, manufacture, characterization, control of drug substance, container closure system and stability); and

* Drug product (description and composition of the drug product, pharmaceutical development, manufacture, control of excipients, control of drug product, container closure system and stability).

Sponsors “may cross-reference all quality information to previously approved CTAs provided they are of the same or higher phase (e.g. Phase III CTAs cannot be fully cross-referenced to Phase II CTAs but may be cross-referenced to approved Phase III CTAs), with the exception of the drug product batch analysis for Phase I and Phase II clinical trial applications,” the guidance says.

A revised draft version of the guidance issued in April 2008 elicited 135 comments. Stakeholders commented on topics from good manufacturing practice requirements in Phase I trials to clarification about the type of information requested in the new templates, Health Canada says.

Changes to the final document include removal of a section on manufacturing process development in the Phase III template and the use of more consistent language across all three templates, the agency says. The Phase III template was revised to eliminate duplicate reporting of information and simplify the submission process.

The guidance takes effect June 1. However, companies are encouraged to begin using the new “Quality Summary — Chemical Entities” templates now. After June 1, the agency will notify potential sponsors that use of other formats may lead to comments and requests for clarification when the submission is reviewed.

Alternate approaches may be acceptable, the guidance says, provided they are backed by adequate scientific justification. Sponsors should discuss plans to use an alternate approach with the agency before submitting an application.

“Quality (Chemistry and Manufacturing) Guidance: Clinical Trial Applications (CTAs) for Pharmaceuticals” can be accessed at www.hc-sc.gc.ca/dhp-mps/alt_formats/hpfb-dgpsa/pdf/prodpharma/qual_cta_dec-eng.pdf.

Canadian researchers studying the effects of a heart drug two years ago tried to expedite the experiment by farming out much of their clinical-trial work to developing countries, where suitable human subjects are easy to find and costs rock-bottom low.

But when they looked into some suspicious data coming out of a trial site in Iran, the scientists made a startling discovery. The study results there turned out to be largely fraudulent, to the point where one patient listed by the Iranian researchers as dead was still very much alive.

“It was bad, so bad we thought the data was not salvageable,” said Dr. Gordon Guyatt, part of the research group at McMaster University in Hamilton. “It’s a different culture, a culture with a lack, perhaps, of a long-standing research tradition dedicated to high standards and integrity.”

The incident underlined the little-discussed pitfalls of a dramatically new era in human drug research. Clinical trials –as studies on people are called–are crucial to determining whether medicines or medical devices are licensed for widespread use or not, and an important way to gauge the safety or efficacy of products already on the market.

Yet statistics show increasing numbers of trials are being outsourced to emerging economies such as India, China and Eastern Europe to limit expense and avoid what some researchers call stifling red tape in Canada and other jurisdictions with highly sophisticated medical systems. The trend is sparking debate about the quality and applicability of some of the research, and the treatment of vulnerable subjects in poor nations.

Health Canada said recently it had unearthed problems in a number of developing-world trials submitted by companies trying to get drugs approved here. Key information on side effects and other potential shortcomings had been left out, either deliberately or because of misunderstanding.

The problems “bring into question the reliability of the data and whether or not the trials were conducted to acceptable … standards,” a Health Canada official is quoted as saying within minutes of a January meeting with a pharmaceutical trade group.

The regulator is drafting a warning to pharmaceutical companies to ensure that quality is maintained in clinical trials in lower-income countries, and has launched a study to determine if more action is required, said Alastair Sinclair, a Health Canada spokesman. It is also offering direct guidance to India, which has experienced a boom in clinical research lately.

“Clinical trials have always been global to some extent. What we have seen is a huge expansion … to a whole set of new countries: Easternbloc countries, India and China,” said Kevin Schulman, a medical professor at Duke University in North Carolina, who co-authored a commentary on the topic published recently in the New England Journal of Medicine. “There’s no reason not to take advantage of lower costs … but I don’t think what we want is lower ethical standards.”

There is also concern that Canadian scientists will have fewer opportunities for clinical research as the trend progresses, and Canadian patients less access to investigational drugs. Still, Dr. Guyatt and other scientists who run clinical trials say outsourcing to emerging-economy countries is a fact of life and has clear benefits, such as improving research expertise and availability of medicine in poorer countries. What is needed, some say, is to step up monitoring of outsourced trials and bring regulators in those places up to Western standards.

There is no question that a dramatic shift is underway. Canada still had the fourth-largest number of trial sites in the world in 2007, but its relative number had dropped 12% from the year before, according to a paper published last year in the journal Nature Reviews Drug Discovery. Meanwhile, India’s total had jumped 20%, China’s 47% and Argentina’s 27%.

Money is a key factor influencing the shift: One report said the cost per trial patient at a respected Indian site was $1,500 to $2,000, a tenth of the price tag in the United States. Large numbers of patients also make such countries attractive.

Ironically, though, one of the chief reasons trials are moving to jurisdictions with questionable regulatory oversight is that the process here has become bogged down, according to critics, by an overly restrictive ethics system.

When patients are recruited at several universities and hospitals across Canada, for instance, researchers must apply to ethics committees at each institution, and the panels typically have different rules and can take months to decide, scientists say. “There is a huge amount of bureaucracy,” said Dr. Ian Tannock, a cancer researcher at the University of Toronto. “I think it’s gone overboard.”

The result is a prolonged process that is convincing many pharmaceutical CEOs, amongst others, to send trials elsewhere, said Russell Williams, head of Canada’s Researchbased Pharmaceutical Companies, the main industry association.

As trials started moving to developing countries, one of the first issues to emerge was the treatment of the patients recruited as subjects. A 1996 trial by Pfizer of an antibiotic in Nigeria, for instance, was allegedly conducted without the patients’ consent and resulted in the deaths of 11 children. Pfizer has denied wrongdoing and said the subjects died from a meningitis outbreak.

But less light has been shone on the quality and nature of data coming out of the trials in such countries. One problem is that factors on the ground in those jurisdictions, such as higher rates of infectious disease and less-developed health-care systems, can skew how a drug affects someone.

There is also evidence that genetic differences sometimes alter results. Dr. Schulman said researchers told him recently about an Alzheimer’s drug they were testing in China, only to discover that no one there had the specific genetic makeup that responds to the medication.

“Someone of southeast Asian ancestry may react one way to a drug, versus someone who is of African American or European background,” said Dr. David Klein of St. Michael’s Hospital in Toronto. “Just because you can prove something in a large population in south Asia, that doesn’t necessarily mean you’re learning all the lessons you need to learn about how the drug might act in a North American population.”

Dr. Guyatt, though, downplays the issue, saying drugs that work differently on different ethnic groups are extremely rare. Then there is the question of research quality. In a January meeting with the Canadian Generic Pharmaceutical Association, Health Canada outlined problems it discovered in out-sourced trial results submitted with applications for various generic versions of medicines.

Some showed fewer adverse reactions than would be anticipated, given evidence that has already been published on the same drugs. Some reports also failed to note deviations in both the trial’s protocol and the timing of blood and urine sampling, anomolies the regulators would expect to see, according to the minutes.

Dr. Guyatt maintains that the standard of research is adequate in most of the lower-income countries he has dealt with, but says particular care is needed to pick the right colleagues in those nations. His team’s trial initially involved 10,000 patients in 21 countries, both industrialized and lower-income.

Called POISE and headed by Dr. P. J. Devereaux, a McMaster colleague, the study was published in the journal Lancet last year, suggesting that patients given beta-blocker heart drugs before undergoing noncardiac surgery are at increased risk of stroke or death. The final results did not include those from Iran, or from one research assistant in Colombia whose data was also considered fraudulent.

The Iranian team was enrolling people not eligible for the trial and it was unclear if any patients were even getting the study drug, said Dr. Guyatt. When perceived problems first arose, Dr. Devereaux flew to the middle-eastern country to get to the bottom of things, earning the nickname Sherlock from his colleagues. “He was brilliant,” recalls Dr. Guyatt with a laugh. “He got there and says, ‘I’m going to find out what really happened’ and he picks out a chart. ‘It says this person is dead. I want to call the relatives and find out.’ So, lo and behold, the person is alive.”

Pfizer Canada recently announced it is providing $1.25 million to support the establishment of the Quebec - Clinical Research Organization in Cancer (Q-CROC) network. Made in partnership with the Fonds de la recherche en santé du Québec (FRSQ) and its Cancer Research Network, the funding will lay the groundwork for a province-wide consortium on clinical research in oncology. The Q-CROC has brought together 100 experts from hospitals and research centres affiliated with the four universities that have a medical school: McGill University, Laval University, the Université de Sherbrooke and the Université de Montréal.

The Q-CROC represents a concrete response to the concerted research approach called for by the États généraux sur le cancer, organized in 2007 by the Coalition Priorité Cancer au Québec. The need for joint action was also echoed by researchers, the medical community and industry.

“This clinical research infrastructure in oncology will facilitate the development of new therapies to help cancer patients,” said Raymond Bachand, minister of finance and minister of economic development, innovation and export trade. “It is an innovative partnership between Pfizer Canada, the Q-CROC and FRSQ that is in keeping with the policies and guidelines enunciated in the Stratégie québécoise de la recherche et de l’innovation.”

“In Quebec, as elsewhere in the country, Pfizer is looking to promote collaborative projects that support innovation in conjunction with the scientific community, governments, patients and industry. Support of the new consortium is a cogent example because it serves as a rallying point for our best and brightest researchers and offers people with cancer improved access to clinical trials, thereby paving the way to more treatment options for patients. This is crucial to the development of therapeutic solutions that adopt an increasingly targeted and personalized approach to fighting cancer,” says Paul Lévesque, president of Pfizer Canada.

“This year,” states Dr. Beaudet, ”CIHR plans to spend approximately $917 million on peer-reviewed health research projects conducted at universities, hospitals and research centres across Canada.”

They do note that a couple of programs, the Intellectual Property Mobilization (IPM), and the Open Team Grant, are being discontinued.

A multimillion-dollar construction project is underway at the I.H. Asper Clinical Research Institute. Tucked in behind St. Boniface General Hospital Research Centre, the 100,000-square-foot building is more visible from the other side of the Red River, as if it is trying to shy away from more immediate inspection.

The province’s newly formed Manitoba Innovation Council does not have public relations as one its mandates. But it is not hard to imagine that in its stated intention to come up with a more co-ordinated approach to technology commercialization for the province — and accessing the capital needed to fund that work — it will probably mean there will be greater public awareness of the assets that are already in place.

The construction work at the Asper Clinical Research Institute is part of a large cardiac development project at St. Boniface General Hospital and will include construction of patient care as well as research facilities on the first, fourth and fifth floors of the building.

Although the new facilities are surely going to fulfil important patient-care responsibilities, the research was the institute’s original concept. It was built during a brief flurry of spending in life sciences research earlier this decade. There is still plenty going on, but the sustainability and ultimate competitiveness of the research and development enterprise in the province could use some high-level planning.

That is just was the Manitoba Innovation Council is charged with doing. The council is more than a year in the making — its creation was disclosed in the 2008 provincial budget — but it’s not like there has been a hue and cry because it was so long in coming.

“Its test for success will be not whether it makes more recommendations for action but whether it can provide advice that will actually deliver action,” said Brian Kelcey, executive director of the Life Sciences Association of Manitoba.

The fact the council has been put together just as the current work on the Asper Clinical Research Institute is beginning might be seen as the start of the next round of development in the city’s life sciences and technology sector.

The institute’s $25-million construction price tag in 2002 was part of about $100 million of capital that was in play at the time that included the cost of the Richardson Centre for Functional Foods and Nutraceuticals at the University of Manitoba and $30 million that the Western Life Sciences venture capital fund had just raised.

That fund is fully subscribed and there is no obvious source of replacement capital. But seven years later, there is arguably a more mature infrastructure in place. Albert Friesen, CEO of Medicure Inc. and the city’s most experienced scientist/entrepreneur, is the co-chair of the council along with Joanne Keselman, interim vice-president academic at the U of M and its former head of research. “Some might say it’s just another committee, but I’m quite excited about it,” Friesen said.

He figures the idea that a group of senior professionals from diverse backgrounds stepping back to consider the best way to grow the province’s innovation sector could yield good new ideas on how to take the province’s strengths in research into the commercial realm.

Among the council’s resources is a consultant’s report — Towards an Integrated Technology Commercialization System for Manitoba — produced for the province and Destination Winnipeg last year. Its 36 recommendations require about $80 million over three years.

But even if you ignore the technicalities that it details as well as the wish list of new money, it does pose some addressable cultural issues.

For instance: “Manitoba’s technology commercialization stakeholders, including the province’s academic and research institutions, are not well integrated into a broader technology commercialization. The constrained funding environment and scale disparities between the individual organizations contribute to this situation.”

Jeff Zabudsky, president of Red River College, another member of the council, said it is too early to say what the group will accomplish. “But,” he said, “we do know we want to do this in a collaborative way.”