Archives for the month of: February, 2013

The European Clinical Trials Regulation is reaching another milestone in its progress to the statute book. This week sees the deadline for amendments in the European Parliament’s Committee on the Environment, Public Health and Food Safety (ENVI) before a series of votes takes place on the European Commission’s proposals from last summer.

It was great to be able to participate in a European Parliament event on “what to expect from the revised legislation” at its London office last Friday. At a well attended and high powered meeting Stefano Soro of the Commission explained the purpose of the Regulation, and Glenis Willmott the MEP appointed rapporteur on the dossier spoke to her planned amendments.

There was a useful and practical discussion with the voices of non-commercial, academic and clinical perspective and I was glad that the BIA was able to give our members expert perspective, as the only industry body to contribute to the debate.

As such it was great to be able to highlight just how welcome this revision of the clinical trials directive is, because under the existing rules disproportionate regulatory requirements, high costs, and a lack of harmonisation has led to the number of clinical trials conducted in the EU falling by 25% between 2007 and 2011.

I was also able to highlight the fact that this proposal should make things simpler, easier, quicker and safer through the single submission via the EU portal, the single assessment report and a single outcome.
I was reassured that the rapporteur is supportive of the regulation and in particular understands the importance of the timeline for assessment.

However, I was able to voice the fact that some of the proposed amendments seemed to be viewed solely from what I’d call a “Phase III clinical trial” perspective by requiring clinical trial sponsors to publish a full clinical study report on the EU database. It is worth pointing out that these reports are prepared for submission to the regulatory authorities when applying for marketing authorisation. I think they miss the fragility of the current early clinical development process. The changing nature of drug development increasingly means many are now collaborations and partnerships between academia, medical research charities, SMEs and multinational biopharmaceutical companies.

Protection of know-how provides a key factor underpinning the funding of such partnerships. The detailed requirements for open publication set out in these amendments as the work goes along makes getting funding for such risky work even harder. This view was echoed by others from the non-commercial sector. The challenge of being able to obtain patent protection later in the product lifecycle after publication was also voiced, but Glenis Willmott surprised me by saying said she had heard from pharma that this was not a big concern. On the contrary the life sciences industry urged that a balanced approach is taken with regard to public access to information held on the European database concerning on-going clinical trials in the EU.

I fear the loss of such protection would dramatically impact upon investment into the sector, which cannot be made up by government funding alone, thus removing a key pillar for collaborative research and development of medicines designed to improve patient outcomes and care.

When Glenis Willmott was appointed rapporteur last October she said “There couldn’t be a better time to change these rules. If we get them right they could create many skilled jobs in the UK and Europe, as well as leading to new life saving treatments and drugs.” I agree – if we get them wrong by imposing new onerous rules that disincentive investors we will do the opposite.

So the upcoming debate on the amendments in the European Parliament is one to watch closely.

Malcolm_Skingle_220_330The Diamond Light Source synchrotron has a wide number of applications to the pharma and biotech industries. GlaxoSmithKline’s Malcolm Skingle, Chair of Diamond Industrial Science Committee (DISCo), explains more.

Since November 2004 I have had the pleasure of being Chair of the Diamond Industrial Science Committee (DISCo). During that time Diamond has grown from being a construction site to a thriving science facility, helping hundreds of researchers a year deliver world-leading science.

Diamond Light Source is the UK national synchrotron facility, one of the biggest public science investments in the UK in the last 40 years. A synchrotron accelerator produces infrared, ultraviolet and X-ray beams of exceptional quality and brightness to scientific end-stations, referred to as beamlines. These beams are of high intensity, extremely well collimated and tuneable. This allows researchers to collect data substantially faster, on smaller samples and using different wavelengths than they can in their home laboratories.

Diamond Light Source synchrotron

Diamond Light Source synchrotron

The applications of synchrotrons to the pharma and biotech industries are widespread and we here at GSK are making extensive use of Diamond.

Structural characterisation using X-rays forms a major proportion of the research done by GSK at synchrotrons, with applications ranging from protein crystallography, through small molecule crystallography to high resolution powder diffraction.

Macromolecular crystallography is used to study complex macromolecules and their binding to ligands with potential inhibitor effects. This is one of the most important steps in the rational drug design process. Diamond has invested heavily in automation and detector technology to make it possible to go from crystal to electron density map in a matter of minutes.

For colleagues in drug development, the synchrotron is ideal for supplementing home laboratory equipment. Small molecule crystallography is the gold standard technique for determining crystal structure of drug candidates but unfortunately, not all samples co-operate during crystallisation and chemists are left with crystals that are too small to be studied using standard X-ray diffractometers. In addition, with samples that do diffract well, the benefits of the synchrotron are significantly higher resolution and very fast data collection. Because of the higher intensity of the X-rays generated, smaller crystals can be used for structural studies, with samples of a few cubic microns routinely measured. Additional facilities allow samples to be studied at high temperature, low temperature, high pressure and under controlled humidity conditions.

The solution of more complex structures from powder diffraction data is a newer technique. While it is possible to solve structures using standard laboratory based diffractometers, the low symmetry of most organic materials can make analysis of the patterns troublesome due to severe peak overlap. The high resolution data obtainable using the synchrotron light can usually overcome this problem. With the incorporation of robotic sample changers on beamlines, along with state-of-the-art detector systems, high quality diffraction patterns can be collected in a fraction of the time that it would take using a standard laboratory diffractometer; this also makes the technique ideal for polymorph screening.

GSK uses many of the techniques available at Diamond and also accesses the facilities in a variety of ways including:

  • Full Service – GSK scientists send samples, Diamond staff collect the data, perform the appropriate analysis and report back;
  • Mail-in Service – GSK scientists send samples, Diamond staff collect the data and then return it for data analysis;
  • Remote access – this route allows our scientists to ship their samples to Diamond and then collect the data from home. This minimises our travel costs and also allows the whole team to be involved in the experiments;
  • Beamtime only – used by our experienced users when they prefer to collect their own data.

The industrial use of Diamond has, to date, been dominated by the life sciences sector, with around 80% of proprietary use by pharmaceutical and biotech users. The crystallography techniques mentioned above make up the majority of this use. However, for industry to get the maximum benefit from investment in synchrotron facilities then we need to broaden our usage to other synchrotron techniques. Structural biologists are starting to explore the use of complementary techniques such as Small Angle X-ray Scattering (SAXS) and Circular Dichroism (CD) alongside their traditional use of macromolecular crystallography. Other new developments at Diamond include the introduction of facilities for X-ray pair distribution function measurements. This technique, while in its infancy relating to use by the pharmaceutical sector, allows characterisation of amorphous drug candidates. Powerful imaging techniques are also now available. The figure shown illustrates how synchrotrons can support the entire scope of the drug development process.

Technique areas where synchrotrons can support the drug discovery process.

Technique areas where synchrotrons can support the drug discovery process.

While Diamond engaged with industry early on in the construction phase, in order to facilitate the use of Diamond by industrial scientists and engineers, a dedicated team of industrial liaison scientists was later established in 2007.

The Industrial Liaison team (L-R): Anna Kroner, Leigh Connor, Alex Dias, Elizabeth Shotton, Jitka Waterman and Claire Pizzey

The Industrial Liaison team (L-R): Anna Kroner, Leigh Connor, Alex Dias, Elizabeth Shotton, Jitka Waterman and Claire Pizzey

These Industrial Liaison scientists assist our in-house scientists, helping with experiment design, collecting data and, in some cases, analysing the data and reporting back. The establishment of this dedicated support group recognises the fact that the customer profile has altered dramatically since the early industrial usage of synchrotrons more than 25 years ago. At that stage, only large, multinational companies such as GSK had the resources to either partly fund beamlines or have the in-house staff capability to run beamtime. Now, with flexible access and support from synchrotron staff, large science facilities are accessible to all researchers from industry from the traditional large users through to start-up companies of only a few staff. I would encourage you to contact the Diamond team if you believe that synchrotron science may help you drive your research projects forward. They are professional, helpful and like me, they want UK Industry to benefit from this world-leading facility.

At the BIA’s 13th annual Parliament Day on 31 January 2013, during our members meeting with the Technology Strategy Board, a number of questions were asked about the new TSB funding rules applied to projects in partnerships with universities. David Bott, Director of Innovation Platforms at the TSB, has addressed this point on the TSB’s blog and provides an overview of the new funding rules companies need to be aware of. The blog post is a must read for all companies interested in applying for such funding streams.

David Willetts, Minister of State for Universities and Science, was the guest speaker at the BIA’s Gala Dinner on 31 January.

Dr Colin MilesLast week’s announcement that £40 million of funding will become available to invest in Industrial Biotechnology and Bioenergy will help the UK become a world leader in this exciting sector, says Dr Colin Miles the Head of Strategy Industrial Biotechnology and Bioenergy at BBSRC.

The industrial biotechnology and bioenergy sector (including biopharmaceuticals and biorenewables, IBBE) represents an area of huge potential for UK science and the economy with the IB market worth between £4 and £12 billion by 2025.

The £15 million funding, from the Biotechnology and Biological Sciences Research Council (BBSRC) will establish up to 10 networks between academia and industry and additional support from the Technology Strategy Board (TSB), will contribute to a £25 million IB Catalyst to make the most of research projects stemming from these networks.

The networks mechanisms will attract new researchers into the area of IBBE with specific skills that will be useful to the IBBE community. We have highlighted genomics, systems and synthetic biology as key areas to be adopted and used in research projects. The networks will also be multidisciplinary working across the boundaries of biology, chemistry and engineering and encouraging the participation of mathematics, computational modelling, environmental science, economics and social science.

This investment will grow the UK’s IBBE research community, supporting the translation of new ideas into commercial applications by providing fora to promote academic-business interactions, which will lead to new collaborative research projects. The networks idea aims to join up the small and fragmented industrial community that is made up of many small companies and only a few large multinationals by providing a mechanism enabling them to link up with the research community and each other.

The networks will also provide a vehicle for proof-of-concept funding, giving emerging projects a bit of a boost through the support for preliminary data: the peer review process often looks for preliminary data before a grant is considered and this may well give projects the edge they need to get funded.

The proposal to develop an Industrial Biotechnology Catalyst springs from the recognition that the Catalyst model is effective at driving translation of research towards outcome, and therefore delivering impact from the research investment.

The IB Catalyst is modelled on the MRC/TSB Biomedical Catalyst and will encourage major challenge-led research projects derived from the networking activities. Launching in 2014 it will be designed to provide the support for the best proposals from the UK, speeding up the process of turning research into commercial applications.

The initial call will allocate funds up to a value of £25 million, £20 million from BBSRC and £5 million from the Technology Strategy Board allowing industry to receive funding for more applied research. The aim will be to build this investment to a scale comparable to the £180 million Biomedical Catalyst already in existence.

The schemes are now live at the BBSRC website.