Following numerous manufacturing failures, Discovery Laboratories believes it has resolved the stability issues that have plagued Surfaxin, its experimental respiratory treatment for infants, and is now seeking a meeting with the US Food and Drug Administration (FDA) to address its concerns.
The Pennsylvania-based drugmaker has put together a briefing package covering certain key chemistry, manufacturing and controls (CMC) matters contained in an approvable letter sent by the FDA last April about Surfaxin, as well as detailing Discovery's investigation and remediation of a process validation failure.
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 New Drug Application (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 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 Discovery has been carrying out an investigation to identify the faults before the FDA allows new stability testing, while the company 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.
To address the process validation stability failure, Discovery says it has conducted a comprehensive review of its manufacturing processes, equipment and process validation, manufacturing components, drug substances, review and assessment of out-of-specification and deviation reports, method validation and change control documentation.
The company claims it has successfully manufactured numerous lots of Surfaxin that achieved a desired stability profile and anticipates that the meeting with the FDA will occur in the fourth quarter of 2006.
Since it will take six months to carry out the stability testing and another six months before Discovery gets another PDUFA date, it will be in early 2008 or late 2007 at the earliest when Surfaxin reaches the US market.
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.