Biotechnology Focus April/May 2015 - industry report

Special Report:

THE CLINICAL TRIAL LANDSCAPE

IN CANADA

By Michelle Hampson

C

CLINICAL TRIALS ARE A KEY ASPECT OF HEALTH INNOVATION, driving the translation of basic research to products on the market. The benefits of clinical trials for patients, institutions and economies are numerous, including better access to care and quality of life, increased knowledge and understanding of diseases, attraction of highly qualified clinicians, job creation and economic growth.

Canada has long been known internationally for its high quality of research, which has been a significant attribute for attracting clinical trials in the past. However, over the last decade Canada has fallen behind in the global race for clinical trial investment. According to a HealthCareCan report, Canada’s share of pharma-sponsored trial sites dropped from five per cent of the global total in 2005 to four per cent in 2010; additionally, the number of Canadian sites participating in clinical trials had declined by 16 per cent, researchers had enrolled fewer Canadians in those trials, and the cost of recruiting patients was among the highest in the world at over $17,000 per patient.1 Several different factors are driving this decline for Canada. Examples include the emergence of low cost clinical research competitors from emerging markets and their improving quality, combined with increasing hospital and academic overhead charges in Canada. With time being of the essence for conducting clinical trials, a large part of Canada’s decline on the global market can also be attributed to more efficient trial processes in other countries.

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“I am more concerned in making certain that an institution’s review process is going to be done quickly, so that I can get my trial going, with the set of patients I need. It’s important to work with institutions that aren’t overloaded or backed up and can work on a schedule – because in industry, time is money.” — David Dodd, president and CEO of Aeterna Zentaris “Canada is increasingly less competitive and less often one of the sites chosen for clinical trials,” says John Soloninka, president and CEO of the Health Technology Exchange.

“It’s just not about quality only anymore; there are other jurisdictions in the world that are just eating our lunch.”

In 2011, Canadian government, institutions and industry recognized the crisis and came together at the National Clinical Trials Summit to identify problems and to undertake initiatives to reverse the trend. Nine key action steps were outlined and many of these steps have since been taken on at both the provincial and national levels.

Provincially, there have been a number of initiatives to make each jurisdiction more appealing. What will likely have the most significant impact, at least in respect to getting trials in Canada running more quickly, are streamlined research ethics review processes. Most provinces have recently introduced initiatives to make the ethics approval process more efficient. Other factors that are coming into play include model Clinical Trials Agreements (mCTAs), quality of research and infrastructure, patient recruitment and tax incentives.

Each sponsor has its own priorities when choosing trial sites, but ultimately, time is money. The provinces pursuing initiatives that get the first patient through the door quicker will likely attract more trials than others, and those jurisdictions that work collaboratively to make the clinical trials process as smooth as possible across borders will be where the major sponsors and decision makers focus their attention.

Streamlined Review Ethics Boards

With multicentre clinical trials, the ethics review process has often been complicated and inefficient with independent reviews required at each site. The Action Plan that followed the National Clinical Trials Summit in 2011 identified the issue of multiple ethics reviews at each site, which result in “different requirements, results, and inconsistent turnaround times,” as one of four factors affecting clinical trial start up times. This inefficient process is believed to discourage clinical trials investment in Canada and is “costing Canada substantially in lost opportunity.”

From the industry perspective, David Dodd, president and CEO of Aeterna Zentaris, explains, “It really comes down to how quickly we can get the first patient into the BIOTECHNOLOGY FOCUS April/May 2015

program. And that is driven by the ethical review board.”

Prior to the summit, many provinces recognized the need for more efficient systems and endeavoured to restructure their processes.

However, there is some variation in the types of models and uptake by each. For example, in some provinces the harmonization only applies to handful of institutions through reciprocity agreements, rather than systematically throughout the entire province. Perhaps the most useful approaches that provinces are taking are those that work inter-provincially, which may be most appealing to companies looking to do large, multi-site trials – the most significant source of investments and most likely to be beneficial for Canada as a whole.

Each province has a slightly different approach, each with its own benefits and limitations.

Alberta was one of the first provinces to form a reciprocity agreement between its six designated review ethics boards (REBs) in February 2011. Since then, the six respective REBs have merged into three and a full reciprocity agreement became effective in November 2013, which allows approval from one of the three REBs to apply to all health research locations in the province. Additionally, to coordinate the ethics review process, Alberta has been using an online system (REMO).

In Saskatchewan, a reciprocity agreement between the University of Saskatchewan, the University of Regina and the Regina Qu’Appelle Health Region came into effect in June 2012, covering all human research. Under this agreement investigators complete a single application/submission package, which is submitted simultaneously to the institutions. REBs collaborate on a unified Notice of Ethical Review (NER) issued by the initial REB and researchers respond to a single set of revisions/requests for clarification that has been agreed upon by each REB. As well, the University of Saskatchewan has been established as the Board of Record to the provinces’ regional health authorities, which has been accomplished through MOUs with three of the Regional Health Authorities and the Saskatchewan Cancer Agency.

British Columbia was the next in line to adopt a harmonized REB system. With oversight from the Michael Smith

Special Report:

The CliniCal Trial landsCape in Canada

Health Research Foundation, eight institutions in British Columbia signed a reciprocity agreement in April 2013. Using an electronic system, one REB is selected and once the ethics are approved, the approval applies to all sites that fall under this agreement.

Explaining the benefits to this system, Laurel Evans, director of Research Ethics at the University of British Columbia, says, “What that does is really allow us, on an institutional level, to try out various models so that we don’t have to go back and get contracts or proper authorization from senior leadership, from the institutional management, every time we want to try to do something a little bit different. That has been a huge benefit for us.”

There are currently three models that are in place for the eight institutions involved in the BC reciprocity agreement: minimal risk, above minimal risk and sponsor clinical trial models. However, Evans notes, that often industry is not interested in intra-BC trials, but rather trials with sites across different provinces. One initiative that may help in this respect is a tripartite agreement between the University of British Columbia, the University of Alberta and the University of Saskatchewan, that allows a sponsor to have a single harmonized ethics process across all three of these institutions.

Nova Scotia has also been a leader in optimizing its review ethics boards. In January 2014, stakeholders in the province created a Multisite Review Ethics Board, which does a single review of multiple sites within the province using an online system. This applies to all trials involving adults in the province, while the IWK Health Centre maintains its own review ethics board for trials involving children.

In February of 2015, Québec launched its new Multicentre Framework, which applies only to public institutions and covers any research that is being done at multiple sites, not just clinical trials. The framework will be in a transition period until March 31, 2016, where during this period stakeholders can offer input for improvement.

With this framework, one designated REB does the ethics review, while at the same time site-specific assessments are underway, local institutions have the option to submit comments. A downside to this model is that it only applies to public institutions, which all fall under the same insurance policy, and excludes private and university-affiliated REBs.

In March of 2015, Clinical Trials Ontario (CTO) officially launched its new Streamlined Research Ethics Review System within the province of Ontario. With this system, REBs of various institutions become CTO Qualified. When a trial application is submitted, CTO will select a “REB of Record” from one of its qualified REBs, which does a single review for all sites and is responsible for continuing ethics oversight of the trial. The review process is managed using an online system. At the time of launch, eight REBs were CTO Qualified, with more REBs in the process of becoming qualified.

One benefit of CTO’s model is that the qualification process is a means of quality assurance, which in some cases may address trust issues between institutions.2 The Council of Academic Hospitals of Ontario (CAHO), which represents Ontario’s 24 research hospitals, has said it is the intent of its member hospitals to use CTO’s new system.

To increase its appeal for multicentre trials across Canada, the University of British Columbia has indicated its interest in becoming CTO qualified and it is encouraging other institutions in British Columbia to do the same. Although the CTO streamlined system is in its early stages, should it be adopted by more out-of-province institutions, it could be a significant step towards a more connected network of streamlined REBs across Canada.

For Canada as a whole, the increasing emergence of specialized REBs such as the HIV REB or the Ontario Cancer Research Ethics Board (OCREB) may be helpful in attracting more trials internationally. An assessment of new REB systems by SPOR-SHRER found that, “For the specialized REBs, quality of review was seen as a benefit with the review questions from the specialized board (both scientific and community members) considered more germane to the REB application than some of the local REB review questions. They had been told it was “a lot less work to submit to (the specialized REB) than to their local REB.” The higher level of expertise on the specialized REB was also noted as a benefit for researchers.”2 The same report found that personnel in the jurisdictions using online systems found the electronic approach helpful.

More specifically: “Access to these (online) systems was credited by researchers with streamlining applications submissions, saving time and money by not having to photocopy, resulting in a noticeable improvement in timelines, the convenience for researchers of being able to access the system

“I think that we need to continue with our efforts to harmonize contracts and harmonize ethics, making the administrative processes more efficient so that it fades into the background and allows our researchers to really shine. We need to promote the great assets that we have for clinical research, and that’s where the Canadian Clinical Trials Asset Map comes into play.”

— Heather Harris, director of the British Columbia Clinical Research Infrastructure Network (BCCRIN) April/May 2015 BIOTECHNOLOGY FOCUS

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“My view is that it’s really through the principal investigator and through the infrastructure that’s put around that investigator. And I think if you ask most CROs or companies doing trials, that’s the number one issue. And Canada continues to avoid that issue. The Canadian government thinks they can do education, they think they can provide incentives, but you’ve got to get the right PI and (dedicate) money for the infrastructure… That’s where the focus should be.” — Dr. Albert Friesen, president and CEO of Medicure

at any time, having all documents in one place and being able to track and automatically record correspondence.”3 In summary, much progress has been made to improve the REB process, including: • Reciprocity agreements among multiple institutions within a province (e.g., BC, Alberta, Saskatchewan); • Reciprocity agreements between institutions, but across multiple provinces (e.g., UBC, U of S and U of A); • Province-wide harmonization (Quebec and Nova Scotia); • A single designated REB among a group of qualified REBs through the CTO model (Ontario, but with the potential to connect REBs across provinces); • The adoption of online platforms, which appears to be increasing efficiency; and • Specialized REBs, which can offer a higher quality of review.

The key question going forward is how closely provinces can work together to make the REB process seamless across Canada.

Clinical Trials Agreements

The second major time constraint when initiating trials is negotiating the Clinical Trials Agreement. Since the Clinical Trial Summit of 2011, there has been a national initiative underway led by the Canadian Institute of Health Research (CIHR), the Association of Canadian Academic Healthcare Organizations (ACAHO), HealthCareCAN and Rx&D to create a model Clinical Trials Agreement (mCTA) that could be used as a national template for contract negotiations.

The national model is still being piloted and the feasibility of this mCTA is still in question. Many pharmaceutical companies, and especially larger ones, will have their own legal concerns and dedicated legal teams.

Dodd explains, “(A model contract) can be helpful… but the company is going to decide what’s important to them and their legal team is going to drive the modifications. Any model contract that I look at, I assure you my clinical and legal team are going to review and send back a redlined version.”

However, he does note that taking initiative to create a model contract indicates that the given jurisdiction is dedicated to meeting the sponsor’s needs.

BIOTECHNOLOGY FOCUS April/May 2015

“In any selling situation where you’re going to sign a contract, that’s what your targeted customer always wants to hear,” he says.

Likewise, Jeff Bacha, president and CEO of Del Mar Pharmaceuticals, feels that in principle model CTAs are great, but industry input is crucial. He cites a situation in the U.S. where a model CTA has been negotiated, with input from 39 industry institutions.

“We are a party to that agreement with one of our sites, and as we extend our trial it will make things very easy because there is no (further) contract negotiation,” says Bacha.

The national mCTA, which is open to industry input, is still being piloted with no published revisions since 2012. While this ongoing mCTA is being fine-tuned, some provinces have endeavoured to create their own.

British Columbia (BC) was the first to create a provincial mCTA in June of 2013. The BC mCTA is in place at eight of the province’s research intensive institutions and may be used when a pharmaceutical industry sponsor is interested in initiating a Phase 2 or 3 clinical trial.

Heather Harris, director of the British Columbia Clinical Research Infrastructure Network (BCCRIN), says, “We’re finding that most of the uptake is with smaller, more virtual biotech companies that may not have an extensive legal department to do their contracting. We’re finding that the major pharma companies may already have master service agreements in place with our institutions and their preference is to use those. Definitely, it would be a faster process for people who don’t have a legal group to use the model agreement.”

With its Streamlined System for research ethics reviews in place, Clinical Trials Ontario is now also looking into creating a streamlined contracts review process for the province of Ontario.

While provincial efforts to increase the efficiency of the contract process are underway, it is still important for independent Canadian institutions to be as flexible as possible.

Dr. Albert Friesen, president and CEO of Medicure, notes that often the contract negotiations can take much longer than necessary, especially when inexperienced lawyers become involved.

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“I think in a lot indications, Canada does have a leadership role in terms of the quality of its investigators. From a clinical perspective, if you look at the number of publications that come out of that little area around the university and college corner in Toronto, it’s staggering on a per capita basis.”

— Jeff Bacha, President and CEO of Del Mar Pharmaceuticals “Some sites do these agreements every day and they don’t need to spend nine months going back and forth to contracting sites,” he says.

How well Canada can speed up the contract process largely depends on how receptive companies are to the new model CTAs, as well as flexibility among independent institutions in negotiating contracts.

Quality of Research

Quality of the research, which has always been a strong point in Canada, is still a priority to most sponsors. Quality of research is often related to the experience and expertise of investigators and the infrastructure to support clinical research. These factors, plus a means for Canada to advertise its quality assets through the new Canadian Clinical Trials Asset Map, are described in the following subsections.

Experienced and Knowledgeable Investigators

One of the most important factors contributing to the quality of research is the experience and expertise of the principal investigator. Jan-Ake Westin, VP of Clinical Research at Medicure, says that for sponsors choosing sites, “It boils down to, in reality, where the best investigators are. That comes from their medical and scientific skills, and the staff they have.”

“I think in a lot indications, Canada does have a leadership role in terms of the quality of its investigators,” says Bacha.

“From a clinical perspective, if you look at the number of publications that come out of that little area around the university and college corner in Toronto, it’s staggering on a per capita basis.”

While Canada tends to have high quality researchers, it’s important to keep them engaged in the clinical trials sphere. A common problem internationally is the high turnover rate of PIs. A Tufts Center for the Study of Drug Development study states: “While the number of investigators globally now stands at nearly 40,000, a record, half of them were new to the job in 2013, the most recent year for which data is available.” In addition, although the highest turnover rates are observed among the least

active investigators, turnover rates have been getting progressively worse among more active investigators.4 Susan Marlin, president and CEO of CTO, believes that supporting new PIs and retaining our experienced ones is vital.

“We’re not going to have the investigators to do the trials years from now if we don’t continue to engage them in the process…and really have the environment such that they think it’s a good thing to do clinical research,” she says.

If Canada wants to increase its ability to attract clinical trials, creating incentives to retain principal investigators, as well as providing training and infrastructure to support principal investigators, should be key priorities.

Infrastructure

Infrastructure is the means to facilitating Canada’s high quality work, however, there are different types of infrastructure to consider. In regards to infrastructure in the clinical setting, many Canadian sites are lacking enough staff and resources.

Some provincial governments, such as Ontario’s, have been particularly supportive of R&D research, which helps to cultivate high quality research. The Québec government, which has dedicated a lot of funds to biomedical research, is also supportive of R&D research. Perhaps the most effective way to attract sponsors is through highly specialized research institutions and well-established networks; overall, Canada is strong in this sense.

“I think one of the things that Canada has done that has (been beneficial) is the centres of excellence and networks that have been established, which was really somewhat of a government driven initiative to create pools of money that could allow for collaboration,” Bacha comments.

For sponsors, established networks are a reliable resource to find qualified investigators that offer streamlined clinical trials and higher levels of patient recruitment. Québec, which already has a high volume of research institutions, may become more appealing in the near future in this respect. The McGill University Health Centre has undergone a massive overhaul with the formation of a mega-facility that replaces the existing facilities of the Royal Victoria Hospital, the Montréal Children’s Hospital, the Montréal Neurological Hospital and the Montréal Chest Institute. After much planning, the megacentre will be fully functioning this April.

Similarly, another massive merge is underway with the Centre hospitalier de l’Université de Montréal, and is expected to be completed by 2016.

“These are to be two major poles of attraction for research…. from a logistics and a cost perspective, having these mega upcoming research centres will provide tremendous opportunities and benefits,” says Gilles Gagnon, president and CEO of Ceapro Inc. He notes that while Canada has successfully attracted April/May 2015 BIOTECHNOLOGY FOCUS

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late stage clinical trials, new megacentres such as the ones in Québec will increase the potential to attract clinical trials at earlier stages as well.

The Clinical Trial Asset Map

To put Canada on the international clinical trials map, a collaborative effort led by the Canadian Clinical Trials Coordinating Centre is underway to better advertise Canadian researchers and their expertise. With the official launch date set for this June, the Canadian Clinical Trials Asset Map will be an interactive database of Canadian clinical research capabilities to help sponsors easily identify clinical research sites and investigators.

In a statement to Biotechnology Focus, Alison Sargent, the executive director of Rx&D’s Health Research Foundation, says, “The overall objective for the CCTAM is to provide a comprehensive picture of the breadth and depth of Canada’s clinical research assets. The CCTAM addresses a gap in the Canadian clinical research resources and mainly, a compressive pan-Canadian one-stop shop tool for all Canadian clinical research resources.”

Patient Engagement and Recruitment

Another critical but often overlooked component of the clinical trials process is patient engagement and recruitment. For Canada, the issue is not so much the time for enrollment, but rather the number of patients enrolled.

“There are a significant number of sites that have one, two, five, 10 patients recruited, which means their cost per patient – when you include the site preparation, the monitoring – is very high,” says Soloninka.

At the Clinical Trials Summit, it was speculated that the reasons for poor recruitment in Canada may be due to: • Access • Universal health coverage and perception of good care • Lack of trust and knowledge • Inefficient infrastructure • Focus on operational improvements The Canadian Clinical Trial Summit...Starting the Conversation report states that, “Canada has yet to develop targeted resources and strategies to market, explain, and attract patients and the public to clinical trials. This can further result in recruitment, retention, and compliance problems.”5 Unfortunately, since the Summit, there has been limited activity at the provincial or national levels to address this

problem. British Columbia has taken the most progressive steps so far, with a clinical trials participation survey underway that looks at the reasons why people are taking part in clinical trials and, even more importantly, why they are not. The survey recently achieved 600 participants and BCCRIN says it will be presenting the interim results of the survey at the ACRP 2015 Global Conference & Exhibition in Salt Lake City this April.

“We’re very excited about this,” Heather Harris of BCCRIN, says. “This is going to give us some really great insights into what’s going on inside clinical trials participants’ heads, so we can better target our engagement strategies, our protocols and consent forms, and things like our behaviour as we’re bringing patients into clinics and welcoming them. It’s really providing some great information.”

Additionally, BCCRIN has signed an MOU with CTO to work on issues that are important to both organizations, which includes patient recruitment. The two organizations say they will be launching a public opinion poll about clinical trials within the next few months.

To this point, CTO has remained focused on its first strategic priority, which is streamlining the ethics review system in Ontario. Going forward, CTO is turning its attention to patient recruitment and retention. Susan Marlin says the results of this joint survey with BCCRIN will help shape CTO’s patient engagement strategy.

Another key development in Canada in terms of patient engagement includes an evolving collection of Permission to Contact (PTC) databases, where patients agree to share personal data and are receptive to being contacted at a later date about relevant trials. The initiation of PTC databases began in some jurisdictions in British Columbia and has since been taken up by other jurisdictions.

“We have over 80,000 participants in a PTC database in Canada, and over half of those are in BC,” says Harris. “It’s a real area of strength for us, and something that we’re hoping to move forward with and become a provincial program in BC. Hopefully we can connect with some of the other provinces on this.”

PTC databases may play a significant role in mobilizing enrollment processes in the future, especially if stakeholders in Canada can continue to build these databases to include more participants in more areas across the country.

Dr. Albert Friesen notes that while recruit-

“(Priorities are) the quality of the researchers and the quality of infrastructure. The upcoming mega centres, SHUN and McGill are really placing Québec at the forefront, I would say, for the next several years, in terms of the potential to attract investments from pharmaceutical companies in Canada.” — Gilles Gagnon, president and CEO of Ceapro Inc. BIOTECHNOLOGY FOCUS April/May 2015

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ment is a significant challenge in Canada, Canadian sites do have their own strengths.

“On average, Canadian sites when selected because of expertise, actually have a higher rate of enrolment than U.S. sites,” he says.

Moving forward, Canada could benefit from emphasizing recruitment through specialized institutions, creating more PTC databases and acting on the feedback from the surveys that are underway. Nationally, there is clearly a deep need for more action on the clinical trials education and participation front.

Tax Incentives

Although tax incentives are not a priority for sponsors when choosing sites, it is still a factor for consideration. Unfortunately, Canada is lacking compared to other countries in this respect.

KPMG’s 2014 Competitive Alternatives report found: “For research and development operations, many of the countries studied offer significant R&D tax incentives. France, the Netherlands, and Canada offer the lowest effective tax rates in this subsector.”6 In this regard, the Canadian Scientific Research and Experimental Development (SR&ED) tax credit may be helpful for Canadian companies and CROs in attracting clinical trials.

However, the credit is limited and often doesn’t reflect the full scale of a given company’s investment. In terms of attracting foreign investors, the SR&ED credit is often not applicable, unless indirectly through Canadian CROs. However, some provincial credits are fully refundable to all corporations.

Additional tax incentives can vary substantially by province, from 4.5 per cent to 37.5 per cent7 depending on the jurisdiction. Québec is particularly attractive in terms of tax incentives, offering provincial tax breaks of up to 80 per cent for total eligible R&D expenditures that are incurred in connection with a research contract with a university or eligible research centre. Moreover, Québec offers tax incentives to attract foreign researchers, offering them a 100 per cent income tax break for their first two years of living in the province, 75 per cent for the third year, 50 per cent for the fourth year and 25 per cent for the fifth year.

Canada against the International Playing Field: What Needs to Be Done

Since the 2011 Clinical Trials Summit, the federal government has recognized the value and the need to make Canada a leading jurisdiction for attracting clinical trials.

Several initiatives to strengthen the environment for clinical trials in Canada have been undertaken, including the creation of the Canadian Clinical Trials Coordinating Centre. This centre is providing collaborative clinical trials oversight throughout Canada and has generated the Canadian Clinical Trials Asset Map to better advertise Canada’s research strengths. As such, dedicating money to networks

and collaborative efforts has been critical in maintaining Canada’s quality of work and should be continued.

However, further steps to support health research at the clinical trials phase would be helpful in attracting more sponsors, such as making the SR&ED tax credit more accessible to Canadian businesses, and offering more competitive cost incentives to international sponsors.

Jeff Bacha suggests, “If there are incentives provided in terms of grants available to PIs who are involved in international studies, that helps to reduce the costs overall.

Whether that grant comes to the sponsor or the PI as offset, that’s going to be a big driver.”

Canada does have many strengths that make it a desirable location for testing new drugs including a highly trained workforce, experienced investigators, a high standard of medical care and a diverse population. However, the more steps that Canada can take to speed up the time for trials to get started – the number one issue for most sponsors who are holding patents that will expire – will put it in a better position to attract trials.

Model clinical trial agreements that apply to multiple institutions is another area that we could better leverage. The national mCTA being developed by the Canadian Institute of Health Research (CIHR), the Association of Canadian Academic Healthcare Organizations (ACAHO) and Rx&D may be helpful when it is finalized; however, how widely it is accepted by sponsors is yet to be seen.

The provincial initiatives to streamline the REB process will likely make some Canadian sites more appealing to sponsors in terms of increasing the efficiency of the approval process; if Canada aims to improve this process even more, additional inter-provincial collaboration is essential.

To regain traction in the global race for clinical trials, Canada needs to remain flexible and listen to the needs of sponsors. By continuing to improve processes that affect trial start up time and retain our high quality of research, we may become a leader once again.

References 1. http://www.healthcarecan.ca/wp-content/uploads/2014/07/ Trials-and-Tribulations-Clinical-trials-The-national-efforttoattract-more-investments-to-Canada.pdf 2. http://www.healthcarecan.ca/wp-content/uploads/2014/07/ SPOR-SHRER-Report-Appendix-D-Harmonization-Survey.pdf 3. http://www.healthcarecan.ca/wp-content/uploads/2014/07/ SPOR-SHRER-Report-Appendix-D-Harmonization-Survey.pdf 4. http://csdd.tufts.edu/news/complete_story/pr_ir_jan_ feb_2015 5. http://www.healthcarecan.ca/wp-content/uploads/2014/07/ ClinicalTrialsSummit_Background_Final-posting.pdf 6. http://www.competitivealternatives.com/reports/2014_compalt_report_vol1_en.pdf 7. https://www2.deloitte.com/content/dam/Deloitte/global/ Documents/Tax/dttl-tax-global-rd-survey-aug-2014.pdf April/May 2015 BIOTECHNOLOGY FOCUS

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