The drugmaker says it has successfully manufactured two investigational batches of Surfaxin, a liquid instillate, that have passed all of the critical release specification assays, with the remaining release analytical procedures and stability monitoring ongoing.
These investigational batches were in response to the stability failure in April of one of Surfaxin's three process validation batches that were part of the New Drug Application (NDA) with the US Food and Drug Administration (FDA).
The best Discovery can hope for now is to have a meeting with the FDA and agree to manufacture new process validation batches in the fourth quarter of 2006, which means an approval is not on the horizon before the end of 2007.
It is the latest chapter in Discovery's manufacturing saga, which started in February 2005 when the drugmaker was looking forward to a Prescription Drug User Fee Act (PDUFA) date for reviewing Surfaxin's NDA.
Two weeks before the PDUFA date, Laureate Pharma, the contract manufacturer of Surfaxin, received a "483 form" from the FDA alerting it to issues regarding the quality assurance systems, documentation and controls in the manufacturing of the drug.
Then on 14 February 2005, the FDA issued an approvable letter requesting correction of those issues, so after Discovery responded in October 2005 a new PDUFA date was issued of 5 April 2006.
Determined to take the situation in its own hands, Discovery then ended its contract manufacturing agreement with Laureate and bought the Totowa facility in New Jersey where Laureate was producing Surfaxin for $16m (€13.5m).
Laureate was already using Discovery's equipment in the facility so it brought in its own staff, but the change seems to have made little difference.
This is because on 5 April 2006 Discovery received a second approvable letter, this time focusing on the Chemistry, Manufacturing and Controls (CMC) section of the NDA and product labelling.
But the big disappointment for Discovery came on 25 April 2006, when it was announced that one of the process validation batches had failed the six-month stability test required.
Since then an investigation has been ongoing to identify the faults before the FDA allows new stability testing, while Discovery also had to withdraw its application for marketing approval in Europe because of the same manufacturing issues and the European Medicines Agency (EMEA) also asking for additional clinical trials.
"It will take six months to carry out the stability testing and another six months before we reach another PDUFA date so it will be in early 2008 or later 2007 at the earliest when Surfaxin reaches the US market now," Discovery spokeswoman Lisa Caperelli told In-PharmaTechnologist.com.
"We have gone through many changes and we are hopeful we can have the process moving again soon."
Part of the drug's manufacturing challenge is that Surfaxin, unlike its competitors, is not animal-derived; Surfaxin is a surfactant in which the chemically synthesized KL4 peptide is combined with the phospholipids dipalmitoylphosphatidylcholine (DPPC) and palmitoyl-oleoyl phosphatidylglycerol (POPG), as well as palmitic acid, in an isotonic aqueous dispersion.
The drug is designed to closely mimic the function of natural human lung surfactant.
Discovery's current investigation covers analysis of manufacturing processes, equipment and process validation, manufacturing components, drug substances and excipient manufacturers, review and assessment of out-of-specification and deviation reports, analytical methods and method validation and change control documentation.