Multifunctional Chromatography materials for improved downstream processing

It's only really during the last century that we have been able to exert any positive influence over our own mortality. Up until 1900 whether we lived or died was governed by a combination of genetics and luck! Just what a difference we've been able to make is illustrated by this amazing fact. Of all the people who have ever lived on this planet past the age of 65 nearly 70% are still alive today! So what are the primary reasons for the dramatic improvements in our circumstances? Improved socioeconomic factors of course - better santitation, lifestyle, diet, improved wealth, conditions in the work place and at home, etc. But there's also the phenomenal progress in health care, drug discovery and development especially over the last 30-40 years. Indeed disease related mortality in Europe has dropped by 40% over the last 30 years, and thanks to antibiotics and vaccines the six major diseases of the 1920's i.e. influenza/pneumonia, syphilis, diptheria, whooping cough, tuberculosis and measles, have all but been erradicated. But hang on a minute! Infectious diseases still account for more than a quarter of deaths worldwide and of the 30,000 or so diseases we know of we only have effective treatments for a quarter of them. Hundreds of millions of people are afflicted by uncured diseases, such as heart disease which is the major killer in Europe accounting for 49% of all deaths, and the global cost not to mention the pain and suffering, runs into trillions of dollars. So what about our future prospects for health? Most of today's medicines are solely used to treat the symptoms of individual maladies, but in the near future it should be possible, through the use of so called 'biological therapies' based on modified genes, cells and organs, to address the cause, onset and progression of uncured conditions. Gene therapy is one of these new kinds of biological therapies by turning genes into drugs that fight life threatening diseases. When gene therapy and genetic vaccination become success stories, it's clear that very large amounts of different therapeutic genes will be needed to treat very many different diseases. For example, nearly seven million people die of cancer per year, whereas AIDS and malaria account for one and two million deaths p.a. respectively. Until now little attention has been paid to how we might be able mass-produce these precious medicines cost effectively. Today when the biopharmaceutical companies make biological drugs they insert human genes into bacterial or animal cells, and then get these cells to produce large quantities of the drug by growing them very rapidly in a rich soup packed full of nutrients by a process known as fermentation. Once the cells have consumed all the nutrients and have stopped growing, it's time to extract the drug. This is not an easy task .The technology for separating drugs like insulin (used to treat diabetes) out of the complex fermentation broth which contains many thousands of other ingredients in addition to the drug, has taken the pharmaceutical industry very many years to master. Unfortunately this separation technology cannot be employed efficiently for much newer, very much larger and very 'sticky' gene medicines. The end result is that these new wonder drugs will be very expensive and made available in very small supply. Researchers at Birmingham University may have found a breakthrough. They are developing tiny porous polymeric beads which are able to discriminate between genes and smaller contaminating molecules. These beads have two regions, a thin outer non-stick layer that prevents the genes from binding to the bead, and an active inner core that effectively 'hoovers' all of the small contaminating biomolecules into it . These new bilayered beads should improve the efficiency of processes for purifying these specialised medicinal products, and in doing so make genetic therapies much cheaper and therefore more widely available to patients in need of treatment.

The manufacture of many of today's biopharmaceuticals already stretches technical/economic acceptability to breaking point, and the move towards ever more sophisticated biologics and therapies is expected to compound these issues yet further. The explosion in new high-level expression systems for the production of recombinant proteins has reduced upstream processing costs to the point where concentration and purification operations, i.e. downstream processing (DSP), now dominates the overall manufacturing cost for many protein therapeutics. The success of future medicines, especially those characterized by very large physical size and referred to as nanoplexes, will to a great extent hang on our ability to introduce radical and prompt changes to current biomanufacturing thinking and practice. In light of the above, and given the dominant role that chromatography has played over the past forty years and is no doubt expected to play long into the future, shouldn't we now expect much more from 'next generation' chromatography matrices? The objective of this project proposal, which targets 'Improved Downstream Processing' of the BRIC initiative is to advance new 'multifunctional' chromatography materials that enable efficient separation of future nanoplex bioproducts from smaller, but chemically very similar 'problem' contaminants in a 'one column-one bead' process that combines size exclusion with ion exchange principles. The above responds expressly to the identified challenges of improved downstream processing, as well as to areas the BIG-T report considers vitally important, i.e. novel manufacturing and bioseparation technologies.