A New Year for biotech

Biotechnology companies face some interesting technical and regulatory challenges in 2007, and beyond, in the race to bring patients a wide range of innovative products. According to a recent study from the Tufts Center for the Study of Drug Development (CSDD), the average cost of developing a new biopharmaceutical drug is around $1.2 billion. And biotech products take almost 98 months, on average, to get through clinical development and regulatory review — about 8% longer than for traditional molecule therapeutics. Therefore, there is mounting pressure on manufacturers to cut costs and speed up the production cycle.

On the plus side, the CSDD report states that biologics have a higher clinical approval rate than conventional pharmaceuticals — 30.2%, compared with 21.5%. There are currently several hundred biotech-based drugs in clinical trials, representing around a quarter of all drugs in development — a proportion that looks set to increase.

Besides recombinant proteins and monoclonal antibodies, there are now cell and tissue therapies, DNA vaccines, and RNAi-based products requiring GMP manufacture in clinical trial quantities. There is also increasing interest in the development of biosimilar products, following the EMEA's eventual approval of Sandoz's Omnitrop (a 'follow-on' version of recombinant human growth hormone) and Biopartners' Valtropin, a recombinant somatropin in 2006. An increasing number of biotech drugs come off patent in the next few years, so manufacturers must start thinking about producing biosimilars now.

A couple of years ago, the prospect of this heavy and diverse 'workload' precipitated panic within the industry over cell culture capacity. Was there enough fermentation capacity to produce the hundreds of kilograms of product to serve clinical trial and commercial demand?

The capacity crisis never really materialized, according to Avinoam Kadouri, chairman of the European Animal Cell Technology Industrial Platform. Today, the emphasis has shifted towards smarter upstream and downstream technologies, which can decrease both cost of goods and manufacturing times. "Required fermenter size will shrink, as high producing clones and cheap, simple media are developed," he predicts. "And more investment in downstream processing will mean greater recovery of product."

For example, there is increasing emphasis upon selecting high-producing clones using technologies such as Cyntellect's LEAP (laser enabled analysis and processing), marketed by SAFC Biosciences, which allows rapid screening of millions of cells for the rare high protein producers. In the downstream area, Pall's Process Proteomics uses a microarray-based approach to optimize chromatography conditions for purification in hours, rather than the days that would be required by conventional column experiments. Such technical developments, while not yet universally adopted, can help companies achieve their goals of reducing costs and timelines.

Manufacturers will also have to deal with the increasing shift away from bovine serum and other animal component-containing media, replacing these with synthetic media that give equivalent — or even higher — productivity in cell culture. Regulatory authorities now require companies to justify any continuing use of animal components in production processes. Companies also need to consider whether to replace some, or even all, of their stainless steel plant with plastic disposable components. Disposables score on flexibility and save on cleaning and sterilization costs, but can be a costly investment.

Of course, the availability of manufacturing capacity is still important — whether it is based upon stainless steel or disposables — especially for academic groups and small biotechs trying to produce sufficient of their therapeutic to GMP standard to progress to proof of principle.

There is no shortage of contract manufacturing organizations, both in Europe and, increasingly, in the Far East and India — should a company decide to outsource. And this month (January 2007) sees the opening of the UK's National Biomanufacturing Centre in Liverpool, which will help academic groups and SMEs get a foot on the manufacturing ladder. There is also a £3 million access fund, which allows for purchase of development and clinical manufacturing services at the Centre.

Small companies need other help too and this should be forthcoming from the EMEA's new SME office, which will offer a range of incentives, including fee reductions for scientific advice and inspections and deferral of fees for an application for a marketing authorization. And on 1 January 2007, the EU introduced new state aid rules that allow Member States to provide tax breaks and other help to young innovative companies (YICs), such as small biotechs, without breaking European competition rules (at the time of publishing, it was anticipated that the EU would introduce these new state rules). The YIC status was first introduced in France and Belgium and EuropaBio has been campaigning for it to be widened to the whole of Europe for some time, according to Dr Andrea Rappagliosi, chairman of its healthcare council.

Another top priority for EuropaBio this year is the implementation of the EU's Regulation on Advanced Therapies, which is to cover gene, cell and tissue-based therapies already on the market, or coming onto the market in the future. "This will provide a centralized European platform for regulation for the new therapies that will be developed over the next 5–10 years," says Dr Rappagliosi. The regulation will cover manufacturing and technology issues, such as risk management and traceability, although decisions on the use or nonuse of stem cells, including those from embryonic sources, will remain the responsibility of Member States. It will also include a mandatory centralized procedure for obtaining marketing approval through EMEA, and it is hoped this will support companies in developing cell and tissue therapies.

EMEA is also developing guidelines on clinical and non-clinical aspects of biosimilar medicinal products containing a biotech-derived protein as an active substance. This is an important opportunity for companies to place greater emphasis upon process analytical technology to show to the regulatory authorities that their 'generic' version of a recombinant protein is safe, pure and effective in comparison with the original product.

As far as the biotech business scene is concerned, Dr Kadouri predicts more competition — with a further increase in the number of companies. All the big pharmas are interested in biotech now, so watch for more developments, such as AstraZeneca's acquisition of Cambridge Antibody Technology, Novartis' purchase of NeuTec Pharma and, on the other side of the pond, Merck's acquisition of RNAi company Sirna. "In the last few years, biotechs have participated in lots of deals — collaborations, licensing, codevelopment, spin-offs and acquisitions," says Dr Rappagliosi. "These deals can only benefit biotech by helping build a critical mass and it is an integral part of how the industry is evolving. We are expecting many more such deals in 2007."