The importance of cross sector collaboration to advancing the 3Rs

On its pages (https://en.wikipedia.org/wiki/Collaboration) collaboration is defined as “working with each other to do a task and to achieve shared goals”.  It is a bit of an oversimplification, as with any collaborative enterprise it is also closely coupled to an implicit acceptance of risk sharing.

The most productive collaborations are the ones where all parties bring something to the table, shared vision, resources and intellectual contribution.  Medical research is highly complex, expertise has become more specialised and costs have spiraled so greatly that no one organisation can burden all the expense and uncertainty. This is why Pharma are joining forces across all stages of drug development, to shoulder the tremendous risks and costs associated with bringing new medicines through development, regulatory approval and ultimately to patients. Industries are having to evolve, no longer is it the strongest that survive, or the most intelligent, but the ones that are most responsive to change.  There has never been a more important time for collaboration.

In March 2006, I attended a kick-off meeting organised by the NC3Rs,­ an open debate on the exploration of 3Rs opportunities in the use of non-human primates (NHPs) in the discovery and development of therapeutic monoclonal antibodies (mAbs) and recombinant proteins.  It was the same day the ill-fated TGN1412 was tested for the first time in humans (six taken ill after drug trials), and a salutary and poignant reminder of the confidence we place in animal-derived data.

The meeting was the trigger for a cross functional group from academia, industry and regulators to share data on internal experience and perspective in a pre-competitve manner. Are there opportunities for replacement, refinement and reduction of NHPs in mAb development? Could we refine existing regulatory guidance (ICH Guidance) based on the collective evidence of many rather than the internal experience of one?

Each group had a different perspective and motive for wanting to participate: 3Rs, ethics, cost containment, study power improvement, etc. Lead by Kathryn Chapman from the NC3Rs, its findings and recommendations have been widely published (Chapman et al 2007, 2009, 2010, 2012). The observations are transformational: apply the guidance and there will be a measurable impact on NHP use in therapeutic mAb development. That is not just good for 3Rs principles, but massively impacts R&D costs as well. Win-win for all, but it is just the start.

Many organisations are still apprehensive regarding the use of alternatives to NHPs in safety and efficacy testing of mAbs, despite precedence. There are few incentives for this sort of boldness and risk-taking, however, with time and more evidence, confidence in strategies for further NHP replacement and reduction will hopefully become more accepted.  Perhaps there are other ways to achieve this objective too.

The natural interactions that bring collaborators together, either by shared scientific experience or through the formal structures of scientific meetings are essential to the identification and execution of new ideas.  However, additional mechanisms, including the increasing use of novel crowd sourcing paradigms, such as TopCoder, and specific funding calls (e.g. NIH RFA, NIH NCATS, Kickstarter, etc), are bringing experts together with a vested interest in contributing to an outcome from a wider group of perspectives than can be conceived by one individual alone.  With CRACK-IT, the NC3Rs have taken a significant step to bringing the scientific community closer together to resolving a specific challenge.

CRACK IT opens doors between academic institutions and industry in ways not conceived by conventional research proposals.  It is an exciting concept and I am involved in one of the challenges, which asks whether it is possible to model and predict renal tubular injury using state-of-the-art multi-compartmental, microfluidic tissue systems.

Nephrotoxicity is a considerable drug development and clinical issue, and while there has been tremendous advancement in our ability to identify tubular toxicity with biomarkers, predicting its occurrence has been very challenging.  The CRACK IT ‘NephroTube’ Challenge has a grand objective, and its success hinges on the cross-sector collaboration that CRACK IT provides.  It needs input from industry to provide data and compounds, to set some expectations around how the technology would be used and qualified.  It needs the experts with access and knowledge of complex cellular systems, technologies and sophisticated biochemical and biophysical assays.  It is not mainstream science, it is risky and from the academic perspective conventional funding mechanisms are limited.  It would be difficult for either group to do this alone.  The 3Rs imperatives of the initiative are clear, but there is also a strong expectation that success will deliver a legacy that has a huge potential to reduce cost, cycle times and importantly risk.  As we move towards the readout of Phase I of NephroTube, I am excited by the prospect of what Phase II will bring – partnership with individuals and on technologies in ways not envisioned, as well as data that will lay the foundation for future innovation.

The statements or opinions expressed in this article are the author’s and do not necessarily represent those of Pfizer.