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Nearly all solid dosage forms contain drugs in crystalline form; and all crystals have the potential to `morph', suddenly, into different forms which can affect the safety and efficacy of the medicinal product. A number of high-profile cases in which marketed medicines had to be withdrawn [Lee, et al., Annu. Rev. Chem. Biomol. Eng. 2011, 2, 259-280] led multinational drug company Pfizer to conclude that a greater understanding of polymorphism was required to enable drug product design for the 21st Century. The University of Greenwich pioneered methods to predict crystal behaviour on the shelf and during manufacture that were affordable, timely and effective. It enabled Pfizer to select the optimal polymorphic drug form and manage risk associated with uncontrolled solid-state transformations, thereby safeguarding patients and avoiding huge costs.
The Abraham solvation parameter approach developed at UCL has become integral to the work carried out by drug discovery teams at [text removed for publication] and other major pharmaceutical companies, as well as research and development groups at international chemical companies including Syngenta and [text removed for publication]. It enables chemists to predict physicochemical and biochemical properties of chemicals, including drugs and agrochemicals, rapidly and efficiently, without the need to conduct time-consuming experiments. The method helps drug discovery teams to identify and optimise the most promising compounds, and often results in fewer compounds being made before a candidate is selected, saving time and resources. The approach has been integrated into software used for drug discovery [text removed for publication].
Since 2008, pioneering contributions to the field of computational chemistry for drug discovery have been made by InhibOx Ltd., a spin-out company based on the research of Graham Richards and co-workers at the University of Oxford. InhibOx launched Scopius, the world's largest searchable virtual database of small-molecules (>112 million compounds) and pioneered the use of cloud computing for large-scale molecular modelling. The key impact for customers of InhibOx has been the reduced costs in identifying molecular leads for new drugs. InhibOx's work has helped to open up early stages of drug development to smaller companies; 75% of InhibOx's clients are SMEs. Since 2008, InhibOx has received £ 2.8M in income and investment.
Novel vapour sorption experimental methods for the characterisation of complex particulate materials have been developed in the Department of Chemical Engineering. This research and expertise resulted in the creation of Surface Measurement Systems Limited (SMS), whose Dynamic Vapour Sorption (DVS) and Inverse Gas Chromatography (IGC) instruments are now found in >500 laboratories around the world. They are recognised standard research and development tools in the global pharmaceutical industry (DIN 66138). SMS has contributed >270 man-years of employment and generated £27M of turnover, whilst SMS instruments have generated over £300M of economic value, over the REF period.
The cost of goods is an especially important issue in developing commercially available agrochemicals, which must be manufactured on a large scale. Richard Compton's research at the University of Oxford has led to a step change in the understanding of heterogeneous reaction mechanisms for liquid — organic solid or liquid — inorganic solid processes involved in large-scale manufacturing processes. Compton's work has had particular impact on optimising the processes used by Syngenta AG in its manufacturing of agrochemicals. Since 2008 the insights gained on inorganic-base dissolution have been of great benefit to Syngenta in its development of scalable robust manufacturing processes, particularly in relation to production of its fungicide Amistar and insecticide Actara, which are two of the world's largest selling products of this type. In 2012 Syngenta achieved total sales of over $ 14 billion, $ 4.8 billion of this from fungicide and insecticide revenues.
Research by the School of Pharmacy played a key role in the 2008 regulatory approval of Janssen Pharmaceutica's HIV drug Intelence®. As a poorly soluble drug, Intelence® required specialist formulation and was the first formulation of its type to be approved by the FDA and EMA. Intelence® offers significantly improved clinical outcomes due to its efficacy in patients with HIV resistance. Global Intelence® sales in 2012 were $349M, with additional not-for-profit supplies to resource-limited countries. As a result of this landmark regulatory approval formulation development strategies at Janssen were adapted enabling a further poorly soluble drug to reach the market. Telaprevir, a second-generation Hepatitis C treatment (marketed as Incivek®, Incivo® & Telavic®), gained global regulatory approval in 2011. 2012 sales exceeded $1bn in the US alone.
The unique application of combinatorial chemistry in materials science at Southampton has directly underpinned the success of University spin-out, Ilika Technologies. Since 2008, the breadth of applications of the research has allowed Ilika:
Between 2008 and 2012, Ilika enjoyed considerable growth, doubling employment to 35 staff, increasing turnover by approximately 25% annually, and floating on the AIM with a market capitalisation of £18.7 million.
University of Huddersfield research in physical organic chemistry has delivered economic, industrial and societal benefits. It has led to process improvements in chemical manufacturing, most notably in the optimisation of the synthesis of antisense oligonucleotides and in the use of liquid ammonia as a solvent. It has also led to the development of new inhibitors of bacterial β-lactamases for use as antibacterials. The research team's expertise has been reflected in the success of IPOS (Innovative Physical Organic Solutions), a unit established in 2006 to carry out research in process and other areas of chemistry for the chemical industry. IPOS expanded significantly from 2009 to 2013 and has now collaborated with more than 150 companies, many of them based in Yorkshire/Humberside where regeneration is critically dependent on the success of new, non-traditional, high-technology firms and industries. Through these collaborative projects, IPOS has contributed to the growth and prosperity of both regional and national industry.
The activities of the Organic Materials Innovation Centre (OMIC) at the University of Manchester generate impact from its research activities through knowledge transfer to industry. This is exemplified by:
Provision of research-based training in the field of printed electronics and sensors to over 250 people from 2008 onwards.
Labelled compounds form an essential part of drug discovery and development within the pharmaceutical industry. Novel iridium catalysts, developed by Kerr at WestCHEM since 2008, have introduced a step-change in the ability to label pharmaceutical candidate compounds with radioactive (tritium) or non-radioactive (deuterium) isotopes.
The catalysts are applicable to specific types of compounds that comprise approximately one-third of all drug candidates. Advantages of the catalysts include greater efficacy (less catalyst needed and higher yield of labelled product, giving cost savings), greater speed (efficiency savings), and a significant decrease in radioactive waste compared with previous methods (environmental and safety benefits).
Even since 2008, their adoption within the pharmaceutical industry has been extremely rapid; e.g., the multinational pharmaceutical company AstraZeneca now applies the Kerr methodology to 90% of their relevant candidate compounds. Additional impact has been achieved by Strem Chemicals who have been manufacturing and marketing the catalysts worldwide since October 2012. Even in that very short period, multiple sales have been made on three continents providing economic benefit to the company.