The US Food and Drug Administration has failed to reach a decision on approving a growth hormone (hGH) product developed by Novartis' generics subsidiary Sandoz in what is emerging as a test case for the development of generic copies of biological drugs.
Sandoz said it had received notice from the FDA that it is unable to reach a decision on whether to approve an application for the marketing of its recombinant DNA human growth hormone Omnitrope.
In a statement acknowledging the FDA's action, Sandoz acknowledged that the approval of most follow-on biologics in the US would require new legislation to ensure that the FDA has the authority to fulfil its mission of ensuring the safety and efficacy of every approved medicine.
Some of the biggest-selling biological drugs developed during the first phase of the biotechnology revolution in the 1980s - including human growth hormone (hGH) and insulin - are set to lose patent protection in the US in 2005 and beyond. This opens up a market currently worth $30 billion and growing at 10 per cent a year - but only if a regulatory route to market can be teased out.
Governments and insurers are keen to get biogenerics approved to reduce the cost burden of these drugs, which tend to be very expensive compared to small-molecule agents, but the complexity of their manufacture means that it can be difficult to ensure that changes in production will not lead to alterations in the final resulting medicine.
Sandoz said that it "supports a transparent public process to help identify an appropriate regulatory pathway for follow-on biologics with an emphasis on ensuring patient safety while protecting the legitimate intellectual property rights of innovator companies."
According to the FDA letter issued to Sandoz, the agency has completed its review of Omnitrope and did not identify any deficiencies in the application, but 'uncertainty regarding scientific and legal issues' meant it had been unable to reach a final decision on the application.
Last December, former FDA commissioner Mark McClellan said that the agency was looking into the legality of approving biogenerics under federal law, and would be publishing initial proposals on this issue 'in the next few months'.
And last year saw Europe move forward as well on this issue, after the European Parliament approved new pharmaceutical legislation which, among other things, set out a legal framework for the registration of so-called 'biosimilar' drugs. But the European Medicines Agency (EMEA) must still set out guidelines on the practical implementation of the initiative.
Omnitrop, as Sandoz' product is known in Europe, received a positive recommendation for approval from the EMEA's Committee for Proprietary Medicinal Products last June but was rejected by the European Commission in April 2004.
"We … believe we have submitted complete and thorough data to support marketing approval for Omnitrope," said Alexander Berghout, head of clinical development and regulatory affairs, biopharmaceuticals, at Sandoz.
It is important for patients and healthcare providers, he added, that that 'cost-effective follow-on biologics like Omnitrope become available as safe and effective therapeutic alternatives'.
To date approval of biogenerics has been patchy to say the least. Last year, SICOR (now part of Teva) gained approval in Lithuania for a generic version of granulocyte colony stimulating factor (G-CSF), the active principle in Genentech's Neupogen (filgrastim) drug for treating neutropenia in patients undergoing cytotoxic cancer chemotherapy.
Other companies, for example Wockhardt (with erythropoietin) and GeneMedix (with granulocyte macrophage colony stimulating factor or GM-CSF), have concentrated on Asian markets until such time as a route to market for these drugs in the US and Europe opens up.