Breaking the biotech barriers

Dr Derek Ellison, business development director of Eden Biodesign, reviews how a new UK centre plans to meet demand for biotech materials for early phase clinical trials.

While often viewed by sceptical investors as a 'jam tomorrow' industry, biotech is increasingly delivering on promises to patients. Globally, revenues from successfully approved products are in excess of $40bn and in 2005 there were more than 1,700 biopharmaceuticals in development worldwide, according to Pharmaprojects.Biopharma was also the fastest growing segment of the global pharma market over the previous five years, recording compound annual growth of an impressive 20% or more.¹

In terms of numbers of public biotech companies and the volume of products in clinical development, the UK is the clear leader in European biotech. In 2005 some 58 companies were responsible for the ongoing development of more than 200 biopharmaceuticals. In particular, the UK is strong in late stage clinical development within Europe, with four products in pre registration, nine in phase III and 38 in phase II trials.

However, its position is vulnerable. While obtaining venture funding is still possible, UK investors are increasingly insisting on a well developed late phase portfolio or, better still, actual product revenues, before committing to fund the development of innovative new medicines. In short, cash is increasingly hard to come by for small companies, even those with promising technology.

In addition to sufficient funding, successful clinical development of products by UK biotechs requires access to specialised manufacturing facilities. Biomanufacturing is without doubt one of the major technical challenges in development. The complex molecular structures of biological drugs are highly sensitive to the manufacturing processes used to produce them. These require exacting control of living production systems, making the manufacture of biological drugs far more challenging than for traditional small molecule pharmaceuticals. As a result, biomanufacturing processes require both state- of-the-art facilities and a great deal of technical expertise.

There has long been a mantra within the biopharma industry that 'the manufacturing process is the product'. This is more than simply a flip concept; when seeking marketing approval for a new biopharmaceutical, great emphasis is placed on the submission and subsequent review of the manufacturing process and the site of manufacture.

Small biotechs moving research candidates into early clinical development face a dilemma over whether to: spend investors' precious money on pilot scale facilities and recruit a manufacturing development team; license product very early in development to big pharma, thereby accepting a reduced product valuation; or outsource clinical production.

For small companies the problem became larger in 2004 with the EU Clinical Trials Directive, which necessitates manufacture of investigational medical product in GMP-compliant, licensed facilities. The capital outlay required to build, equip and validate manufacturing facilities for cGMP manufacture of clinical trial material is beyond the vast majority of European biotech companies. The facilities available for commercial contract manufacturing vary in quality and the services come at a high cost.The question is, how can small companies or new start-ups realise the commercialisation of fantastic technology and delivery of potential blockbuster products without the necessary funding, expertise and facilities to help them?

In 2003 the UK government announced that the UK National Biomanufacturing Centre (NBC) was to be built in Speke, Liverpool. This programme is led by the Northwest Regional Development Agency (NWDA) through its biotech sector development group, BioNow, and is also funded by the UK DTI and European Regional Development Fund, to a total cost of £34.25m. Eden Biodesign is the commercial operator of the National Biomanufacturing Centre and was appointed through an open, Europe-wide tendering process.

regional strength

North West England is already home to major manufacturing facilities for top tier US biopharma companies such as Eli Lilly, Chiron and Medimmune. This biomanufacturing concentration has developed out of the region's historical base of pharmaceutical and chemical manufacture, which includes Astra-Zeneca, GlaxoSmithKline, Aventis Pharma and Bristol Myers Squibb.

The purpose of the NBC is to provide the expertise and facilities to develop production processes and manufacture biopharmaceutical medicines for early phase clinical trials. Its role is to support new and existing biotech companies, providing product development services designed to fill skills and resources gaps that exist within these organisations.

In a nutshell, its goal is to be an engine for growth, propelling early stage biotech companies up the value chain by rapidly moving products into clinical development. By adding clinical and commercial value to products through the application of best product development practices, biotech companies will be better placed to raise funding and achieve satisfactory out-licensing agreements with big pharma.

The project also includes an access fund of just under £3m that will provide assistance to UK-based SMEs, particularly in the Merseyside region, helping them to purchase services from the NBC. The fund, which will be administered by an independent steering group set up by the NWDA, is important as many small biotech companies face a chicken and egg situation: without significant funding they can't afford to move into human clinical trials, but they struggle to raise venture funding without proof of principle data from products actually in the clinic. The access fund is open to applicants from April 2005 in order to allow sufficient time for UK biotech companies to receive notification of successful funding well before the Centre opens. With construction of the NBC completed and validation underway, the Centre is officially due to open early in 2006. This will create a worldclass biomanufacturing and development facility of approximately 4,100m².

The operational services of the NBC will be aimed at the production of pre-clinical and clinical material, including cell banking, API manufacture (fermentation and purification) and supply to clinical centres. Such technologies will help the NBC to become Europe's leading biopharmaceutical design centre, capable of producing a variety of novel therapies and vaccines.

It has been designed to be as flexible as possible, allowing projects to be undertaken on almost every major biopharmaceutical product technology. In practice this was achieved by taking 10 diverse candidate production processes and carefully modelling the required manufacturing operations for each process through the facility at every stage of design.

Three segregated cGMP production suites will allow mammalian, bacterial and viral products to be manufactured simultaneously. The facility is aimed at rapid small-scale production with GMP capacity of up to 100 litres for microbial products, 200 litres for mammalian and 20 litres for viral, and has been designed to take maximum advantage of the latest disposable bioprocessing technologies. The suites are designed to biocontainment category 2 (as specified by The UK Health and Safety Executive's 'Advisory Committee on Dangerous Pathogens' and the 'Advisory Committee on Genetic Modification') and will be compliant with the latest EU and US GMP guidelines.

The GMP clinical trial manufacturing facilities are supported by three dedicated non-GMP product development suites, fitted with scaled down versions of the same bioprocessing equipment present in the GMP suites to allow rapid transfer and scale-up. Quality control testing, analytical development and product characterisation will be performed in well-equipped analytical laboratories.

Prior to the NBC becoming operational, the project has already provided limited amounts of free consultancy to UK biotech start-ups. To date about 20 companies have been assisted in this manner, including Edinburgh-based Amoebics, Cambridge-based Immunobiology and businesses based in local biotech incubators, such as Merseybio (Liverpool) and UMIP (Manchester).

skills base

Once the Centre is operational there will be a graduate training programme focused on developing bioprocessing operational skills. The NBC will seek to work closely with local training initiatives, one of which is a National Vocational Qualification for Biomanufacturing, provided by The Partnership for Learning, also based in Speke. The goal is to provide a skilled work force to support the growing local and national biomanufacturing industry.

Biopharmaceutical manufacturing is recognised by many governments as critical to grow and sustain a prosperous biotech industry. The NBC is a unique public-private partnership seeking to capitalise on the biomanufacturing history and skill base of North West England. The project should strengthen the position of the North West and the UK as a whole in attracting inward investment. The project will not only provide support for UK and international biotech companies, but will encourage development of UK bioprocessing expertise, dovetailing with other national initiatives to help keep the UK at the front of the European biotech industry.