Biosimilars are ready to make a breakthrough on the global pharmaceutical scene. Jane Ellis visited the Sandoz biopharmaceuticals production site at Kundl in Austria to look at progress
Developing a biosimilar, or follow-on biological product, is an altogether more complex process than producing a standard generic drug. It is therefore not surprising that the market has been slower to develop with just six biosimilars approved to date in the EU under the EMEA biosimilar pathway.
However, the recent launch by Sandoz, the generics division of Swiss drugmaker Novartis, of its recombinant human growth hormone somatropin in Japan suggests that biosimilars are now beginning to establish a place on the global scene. The drug is already sold under the name Omnitrope in the EU, the US and Australia, among others, but the fact that it is the first biosimilar to be given market authorisation in the second largest pharmaceutical market in the world signifies something of a breakthrough.
A significant number of biosimilar companies in the West have developed or acquired proprietary technologies for producing improved biologics, and an increasing number of manufacturers, including Sandoz, are making biosimilars part of their strategy for the future. For example, Teva Pharmaceutical Industries, of Israel, and Swiss-based Lonza Group have established a joint venture to develop, manufacture and market a portfolio of affordable, efficacious and safe generic equivalents of a selected portfolio of biologic pharmaceuticals.
But while Japan's Ministry of Health, Labour and Wealth (MHLW) has set out guidelines that pave the way for a national biosimilar regulatory pathway, based on similar scientific principles to the approval pathway already in place in the EU, progress in the production of biosimilars seems to have hit a brick wall in the US. US legislators are considering a bill that would give the manufacturers of biologics a data exclusivity period of between five and seven years, similar to that applied to generic versions of small molecule drugs.
Biologic companies in the US are lobbying hard for a data exclusivity period of 12 to 14 years, claiming that a period of five to seven years would make it nearly impossible for them to be globally competitive. Manufacturers in the EU enjoy 10 years of exclusivity with the option of an additional year if a biologic shows particular promise.
The European Medicines Agency (EMEA) established the first pathway for biosimilars in 2004, putting it five years ahead of the US in terms of legislation. Australia adopted the EU guidance in 2008, and World Health Organisation finalisation is expected imminently. Numerous other countries have produced draft or final guidelines on biosimilars, including Canada, Malaysia, Turkey, Taiwan, Korea, Singapore, Argentina and Saudi Arabia.
One of the perceived issues with giving biosimilars market authorisation is that manufacturers of biosimilars do not have access to the originator's molecular clone and original cell bank, nor to the exact fermentation and purification process. Therefore they need to show the regulators that their versions are just as safe and effective.
Undetectable differences in impurities and/or breakdown products could have serious health implications, leading to concerns that copies of biologics might perform differently from the original branded version of the drug.
"To develop biosimilars you need to know what you're doing," says Joerg Windisch, head of global technical development of biopharmaceuticals at Sandoz in Kundl, Austria. The Kundl plant claims to be the largest microbial site in the world, producing 40,000L from four lines.
Sandoz has a long history in biopharmaceuticals and is a pioneer in the biosimilars market. It manufactures three of the biosimilars approved in the EU - Somatropin (Omnitrope), Binocrit (Epoetin) and Filgrastim (Zarzio) - and claims to be market leader.
Biosimilars are produced using modern biotechnology. The process involves modifying bacterial, yeast and mammalian host cells to produce recombinant proteins. The proteins are grown under controlled conditions in steel fermentation tanks, triggering product accumulation inside or outside the cells.
The proteins are then extracted, refolded and purified to generate the drug substance, which is frozen in aqueous solution. There are multiple purification steps. The next stage is to formulate the drug substance into a stable, sellable, finished drug product (vial, syringe, cartridge) with a convenient device such as a pen or autoinjector.
Biosimilars take much more work to develop than small molecule generics. There are multiple biological functions involved: physicochemical characterisation; biological characterisation; pre clinical studies, PK (pharmacokinetics)/PD (pharmacodynamics); clinical safety/efficacy and Phase III clinical trials.
According to Windisch, the clinical safety/efficacy part of the process takes the longest and costs the most. "Biosimilars will never go down to the prices of generics because development and manufacturing is expensive, depending on the complexity of the product," he says.
But in spite of the cost and complexity of the products, Sandoz believes that biosimilars could offer major savings to patients and healthcare systems as they are around 25-30% cheaper than small molecule drugs. In a study in 2008, German r&d institute for healthcare, IGES, identified potential savings of more than Euro 8bn by 2020 in Germany if biosimilars were prescribed. In the US, savings in the high double-digit billions range are expected over a 10-year period.
"Biopharmaceuticals offer real therapeutic hope to those suffering from the most complex diseases of modern society," said Jeff George, chief executive of Sandoz. "Biosimilars, pioneered by Sandoz, increase access to these essential drugs, lowering treatment costs and saving money for the healthcare system."