BPC 2008: Science Chairman’s address: resolving challenges for pharmaceutical science

In an article based on his conference address entitled “Adding years tolife and life to years: interfacing pharmaceutical, biomedical andmaterials sciences", Andrew Lloyd discussed future challenges affectingpharmaceutical scientists’ ability to take products from the laboratoryto clinical practice

by Andrew Lloyd

In an article based on his British Pharmaceutical Conference 2008 address entitled “Adding years to life and life to years: interfacing pharmaceutical, biomedical and materials sciences", Andrew Lloyd discussed future challenges affecting pharmaceutical scientists’ ability to take products from the laboratory to clinical practice.

He argued that pharmacy will be able to continue to add years to life and life to years only if pharmaceutical scientists collaborate more closely with biomedical and materials scientists and use knowledge from a broad range of sources to find effective solutions to the challenges of ageing

 

Conference Science Chairman

Andrew Lloyd

Andrew Lloyd is professor of biomedical materials and dean of the faculty of science and engineering at the University of Brighton.

He serves on several UK biomedical materials committees and is a member of the editorial boards of the International Journal of Pharmaceutics, the Journal of Applied Biomaterials and Biomechanics and Expert Review of Medical Devices.

He is also an adviser for a number of pharmaceutical and medical device companies. His multidisciplinary interests in pharmaceutical, chemical, materials and biological sciences are reflected in the 300 articles he has published.

The many awards he has received in recognition of his work include the Society’s BPC science award in 2000 and the Lilly Prize for pharmaceutical excellence in 1999.

Since the 1939–45 war, the pharmaceutical industry has made great advances in combating most major classes of disease.

Such advances include the development of vaccines, antimicrobials, antivirals, cardiovascular drugs and chemotherapeutics, as well as analgesics and anti-inflammatory agents to manage the body’s reaction to trauma and disease.

These have been developed by pharmaceutical scientists and delivered to patients by pharmacists whose training ensures that they have a fundamental understanding of the scientific basis of these medicines.

Over this period our knowledge of fundamental biology and disease processes has enabled the industry to identify more potential therapeutic targets and develop more effective methods of screening potential therapeutic agents — leading to a continuous pipeline of new and improved medicines.

Similarly, advances in our understanding of synthetic and analytical chemistry have led to more effective approaches to the synthesis of drug molecules and improved analytical techniques for the monitoring of chemical reactions and biological systems.

Although the industry has been challenged in some areas, such as the delivery of biopharmaceutical agents and achieving targeted site-specific drug delivery for the treatment of particular diseases, its overall impact on society has contributed significantly to an increase in the average life expectancy of about 10 years between 1950 and 1998.

This increasing life span presented other challenges over this period, in particular the need to replace, or augment, defective or diseased organs and tissues.

Three key innovations were

  • the intraocular lens developed by Harold Ridley in 1951
  • the modern artificial joints arising from the work of John Charnley in the 1970s
  • the cardiovascular stent developed in the late 1980s

As mobility, vision and cardiac function are probably the three key determinants of healthy ageing, these developments have made a major contribution to adding life to years, playing a key role in increasing human health span and ensuring quality of life for our aged population.

Although these devices were originally developed by clinical engineers, developments in cell and developmental biology and polymer chemistry over the past 20 years have led to the birth of the transdisciplinary fields of tissue engineering and regenerative medicine, involving collaborations between clinicians, biologists, chemists, engineers and, more recently, pharmaceutical scientists.

Initial developments in tissue engineering focused on structural reconstruction and more recent innovations have focused on functional tissues.

Examples include cell-based wound dressings for the treatment of diabetic foot ulcers and burns, tissue-engineered corneal epithelial cell sheets for corneal reconstruction, tissue-engineered neurones for neural reconstruction and tissue-engineered heart tissue.

The development of our understanding of the factors controlling tissue growth in vitro provides a platform for the longer term development of approaches to tissue regeneration in vivo — an area in which the controlled delivery of biological agents will play a key role.

Challenges of the future

Despite these major advances in pharmaceutical and biomedical sciences over the past 60 years, the future presents significant challenges.

An ageing population

The proportion of the UK population aged over 60 is expected to increase by over 52 per cent over the next 40 years, with those aged over 80 predicted to increase from 2.8 to 6.2 million by 2048. This will place an increasing financial burden on the UK healthcare services.

Although improvements in life style through exercise and diet will undoubtedly contribute to increasing health span, reduce morbidity and limit the requirements for long-term healthcare support, the economic impact of the growing population on funding for healthcare could potentially limit the commercial viability of novel products for the treatment of some diseases, particularly disease with relatively low incidence within the population.

Increasing development costs

Under the present UK system, pharmaceutical companies will increasingly be required to demonstrate that the immediate clinical benefit justifies the provision of high cost medicines for small populations when governments can more effectively spend healthcare resources on low cost medicines which offer a greater clinical benefit to a larger population.

This will be compounded by the increasing costs of the development and clinical evaluation of new medicines and devices to meet the demands of regulatory authorities.

Under these conditions the medicines and devices most likely to reach the market will be those that can be developed at lowest cost and offer the greatest clinical benefit to the maximum number of potential patients over existing technologies.

Worldwide poverty

On a worldwide scale the population is expected to increase from 6.7 to 9.4 billion over the next 40 years, with the proportion of people over 60 expected to increase from 10.8 per cent to 21.5 per cent and much of the growth in population being in the developing world.

This growth in world population will only be sustainable if we can combat poverty and disease in these developing countries. Of particular importance is the link between health, productivity and the economic prosperity of a country.

Although environmental advances, such as providing effective sanitation and safe drinking water, are essential components of sustainable development, the rapid and effective treatment of disease by either pharmaceutical or surgical interventions will be important if we are to provide sustainable improvements in the health of the population in these countries.

As the world population increases it is unlikely that the substantial investment made by the pharmaceutical industry in the developing world will be sufficient to meet world demand. Other pressures on the industry could potentially reduce their ability to contribute as they have done in recent years in some key areas.

If we are to address these issues on a worldwide scale, affordable healthcare solutions will be required and it is important to recognise the major role, outside the minimisation of environmental waste, that pharmaceutical scientists and pharmacists can make to sustainable development through their contribution to combating world poverty.

Infection problems

Finally, it is important to highlight the challenges arising from the unintended consequences of pharmaceutical and biomedical developments over the past half century, which must be addressed if we are to continue to add years to life and life to years.

In the medical device field, although indwelling devices such as catheters have had a marked impact on the quality of life for particular groups of patients, such as those requiring ambulatory dialysis, these have led to the added complication of device-related infections in a significant number of patients.

This, combined with the increasing incidence of antimicrobial resistance within the clinical environment, could have catastrophic consequences worldwide. Although some of the solutions will rely in limiting transmission by improving infection control within hospitals, we need to find alternative solutions as more organisms develop resistance to antibiotics.

Effect on pharmaceutical scientists

Over recent years pharmaceutical scientists have increasingly been required to work across disciplinary boundaries of chemistry, biology and engineering as the pharmaceutical industry has sought to bring novel biopharmaceutical agents to the market and develop more effective ways of achieving site-specific targeted drug delivery to reduce clinical complications and improve patient compliance.

Developing broader skills

In this era of tissue engineering, regenerative medicine and combination devices there will be an increasing requirement to broaden the pharmaceutical scientist knowledge base through continuing professional development. This does not necessarily require the broadening of the basic knowledge base of the graduate pharmaceutical scientist but it means providing opportunity to gain specialist knowledge and skills through postgraduate training.

This is already being being addressed by some universities by providing research and taught master’s programmes to prepare individuals to undertake higher research degrees in these fields. Similarly many institutions are now seeking to offer master’s level modules, arising from these programmes, as part of continuing professional development programmes for those already within the industry.

In particular there will be an increasing need for all pharmaceutical scientists to understand the “language” of these emerging “disciplines” in order to work effectively with biomedical and materials scientists and bioengineers. The proposed professional body for pharmacy should have a key role in supporting such developments.

Academia-industry partnerships

Academic pharmaceutical scientists have always been effective at seeking to transfer knowledge from the laboratory to the industry. The increasing role of universities in the transfer and translation of knowledge for economic and social benefit will further support this activity and there will be a greater requirement for stronger partnerships between academia and industry.

In particular small and medium-sized enterprises (SMEs) are gaining substantial benefits from their academic partnerships. These provide companies with access to both a broader knowledge base and physical resources not available within the companies and they provide academics with an opportunity to gain experience of the challenges of undertaking research and developing products in a commercial environment.

Transdisciplinary collaboration

The increasing requirements not only to develop new technologies but also to focus on those that can most readily be translated from the laboratory to the clinic will require pharmaceutical scientists to be more innovative and creative in their application of knowledge.

I believe that the greatest innovations will come from the application of knowledge across disciplinary boundaries.

To capitalise fully on these opportunities, pharmaceutical scientists need to be able to identify areas of new knowledge and be willing to transfer this into their own discipline through transdisciplinary networks and collaborations.

Support should be provided for this by any future professional body for pharmacy and collaborations with other professional bodies such as the Royal Society of Chemistry and the British Pharmacological Society.

Our research at Brighton into biomedical materials over the past 15 years provides some examples of the innovative opportunities that arise from the transfer of knowledge across traditional subject boundaries and the challenges of translating these development from laboratory to patient.

Our research into the properties of zwitterionic betaine polymers and their use as biocompatible materials for medical device and drug delivery applications originally arose from a desire to find a new coating to improve the biocompatibility of intraocular lenses.

The basis of this work was the development of the phosphorylcholine (PC) technology by Biocompatibles UK Ltd, a company established by the biomaterials scientist Dennis Chapman in the 1980s to exploit the low thrombogenicity of PC-based materials. These PC-materials are designed to mimic the key component of the surface of phospholipids bilayer — the phosphorylcholine head group.

These PC-based monomers were co-polymerised with a range of other methacrylate monomers to produce a range of polymers with a wide range of mechanical and adhesive properties to allow the optimisation of costings for different medical substrates.

In partnership with the company we were able to develop a range of polymer coatings for various medical device applications and demonstrate that these biomimetic materials also had minimal inflammatory response and reduced cellular adhesion.

The publication of a series of papers by Steve Armes at the University of Sussex into the synthesis of sulfobetaine polymers initially led to the establishment of a further collaboration leading to the first comparative evaluation of the biocompatibility of sulfobetaine and phosphobetaine polymers.

As Professor Armes developed ways of producing polymers with novel molecular architectures, we recognised the possibilities of using PC-based polymers for drug delivery and cell-based therapeutics.

However, despite the advantages offered by the PC-polymers over other materials in biomedical applications, the commercialisation of these technologies has to date been limited, primarily because the risks of being unable to recover the costs of commercialisation outweigh the clinical benefit that may be offered by the technology.

In another area of research at Brighton, recognising the important role that phosphatidylserine plays within bone matrix vesicles in the mineralisation of bone led to a novel coating for orthopaedic implants which encouraged the nucleation of hydroxyapatite and had the potential to improve bone fixation.

The phosphorylserine coating overcomes the requirement for high temperature to produce hydroxyapatite coatings on medical implants and has been shown in preliminary studies to perform as well as traditional hydroxyapatite coatings in a rabbit model.

However, despite the potential advantages of this process, the clinical performance was not deemed to be sufficient to justify investment in the further development of the technology.

Some would raise issues regarding the value of embarking on applied research of this nature in areas where there is likely to be limited commercial potential.

However, the benefit of such research is difficult to quantify at an early stage and the value may not be in the immediate exploitation of the technology but in the knowledge that it provides to others in the future.

Re-evaluating old technologies

In the light of the above, it is important that pharmaceutical scientists do not just look across disciplines but continue to reflect back on the huge body of scientific knowledge that has been generated over the past century.

The re-emergence of post-war technologies in the battle against antimicrobial resistance provides good examples of the potential to exploit previously abandoned technologies in a modern era.

The first of these technologies is the development of photodynamic disinfection. The use of photoactivated antimicrobials against various micro-organisms was reported in the early 20th century, but the work in this field was discontinued with the introduction of penicillin and sulphonamides.

The emergence of antibiotic resistance and the development of laser technology led to the re-evaluation of this technology and the development of a laser-based photo-activated disinfection system for the treatment of root canal disinfection in dentistry by Denfotex Ltd.

The second example is bacteriophage therapy, which was used therapeutically to treat bacterial infection in the early part of the 20th century. Although research was discontinued in the West, the technology continued to be developed in the Soviet Union.

In recent years the rebirth of the use of bacterial viruses as an antimicrobial therapy has led to numerous studies across the world to evaluate the use of the technology to combat hospital-associated infections.

The highly selective and efficient ability of bacteriophage to lyse specific bacteria provides the possibility of using these systems to combat antibiotic resistant bacteria such as meticillin-resistant Staphylococcus aureus.

This is one of many relatively low-tech technologies that have arisen from states of the former Soviet Union in recent years. It illustrates the potential to find technologies in use in other parts of the world that have been developed in often less economically favourable environments but provide effective solutions to clinical problems.

The Biomedical Materials Research Group at the University of Brighton has been working with another of these technologies, in the form of polymer pyrrolysed carbon adsorbents. Although activated carbon-adsorbent technologies were evaluated in the UK in the 1950s and 1960s, there was limited commercialisation of the technology because of a lack of uniformity and the friability of the materials.

The development of activated carbons from polymer beads provides a material of uniform size with improved mechanical properties, which we are evaluating for a number of medical applications, including the treatment of sepsis.

Developing combination devices

In recent years, there has also been increasing interest in combination devices, such as drug-eluting stents, chemoembolisation agents and antimicrobial bone cements, as the medical device industry has sought to reduce the various clinical complications associated with medical device implantation and reduce the requirements for revision surgery.

Increasingly, pharmaceutical scientists are working more closely with biomedical and materials scientists to improve the performance of existing medical devices through the local delivery of anti-inflammatory, antimicrobial and chemotherapeutic agents.

As the simple combination of regulatory approved therapeutic agents and devices often offers a marked clinical advantage, the regulatory hurdles are often less challenging than in the development of entirely new devices or therapeutic agents, which can, in many cases, reduce time and cost to market.

As a consequence there is an increasing demand for pharmaceutical formulation scientists to support medical devices companies with the development of this generation of products.

Furthermore, as chemoregulation has such a key role in tissue regeneration, there will be an increasing requirement for formulation scientists to work alongside tissue engineers if these cell-based products are to be successfully translated from the laboratory to the clinic.

Engaging with end-users

Finally, engagement with end-users and stakeholders is essential if pharmaceutical scientists are to focus on the development of technologies that meet patient and health service demands and have significant clinical impact.

The establishment of a new professional body for pharmacy provides the opportunity to strengthen the dialogue between practice pharmacists in both the community and hospitals and pharmaceutical scientists in academia and industry.

However, the full benefits of this will only be realised if the professional body encourages membership from all pharmaceutical scientists and those working in other disciplines that directly impact the development of pharmacy and pharmaceutical technology in the UK.

Of equal importance is the need to ensure that pharmacy continues to embrace both science and practice, because the pharmacist is one of the few health professionals whose contribution to the healthcare team provides an underpinning scientific knowledge to support patient care.

From the perspective of pharmaceutical scientists, it is the ability to capitalise on our colleagues’ knowledge of science in practice that will enable us to continue to contribute to the development of healthcare technologies that will have the greatest clinical impact.

Conclusion

In summary, despite the increasing challenges of bringing products from the laboratory to the clinic, the opportunities for pharmaceutical scientists to collaborate more closely with biomedical and materials scientists and use knowledge from a broad range of sources to find effective solutions to the challenges of ageing will ensure that pharmacy in the 21st century continues to add years to life and life to years across the world.

I believe that our ability to capitalise fully on this in the UK will depend on the decisions that are made regarding the new professional body for pharmacy and a willingness for a commitment to science to remain at the heart of the profession of pharmacy in the future.

We need to ensure that pharmacists have a full understanding of science underpinning new and emerging technologies as a consequence of the impact they may have on pharmacy practice.

Citation: The Salvadore URI: 10035503

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