OUTSOURcing AnD TEch TRAnSFER in cAnADA’S biOTEch EcOSySTEM

outsourCing and teCh transfer

in Canada’s biotech ecosystem

it’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

Figure 1: outsourcing and tech transfer in Canada’s biotech ecosystem

SME biotech developers

Produce material: GMP

Tests before CTA approval: GLP

Licence or co-develop molecular assets

Contract research organization

Assays and methods

Public research organization

Test in patients

Clinical trial organization

Contract development and manufacturing organization

Expression systems and characterization

University

Basic Research Target ID Hit and Lead Candidate

Preclinical Development

Clinical Phase I/II Clinical Phase III Market

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 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 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.

Innovating together

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/