The US FDA announced its decision in a CRL (complete response letter) issued earlier this week in which it detailed its misgivings about practices at Exempler's canister facility. Manufacturing process issues for the final filled canisters were also noted as a by the agency, although Allergan said it “has already responded to this concern.”
A Form 483 issued to Exemplar last July found the company’s Fall River, Massachusetts plant lacks process controls for its pressurized filling system and did not “prevent propellant loss due to evaporation and concomitant increase in drug substance concentration.”
Exemplar was also cited for failing to have “a mechanism to assure that total content specifications are met when product flow and/or pressure is disturbed.”
But Exemplar is one of only a handful of CMOs with capabilities in aerosol development and Allergan is not likely to move to a different CMO to manufacture the migraine treatment because of these issues.
“We just acquired Exemplar as part of our strategy to secure our supply chain and have appointed Allergan leadership at the site,” Bonnie Jacobs, a spokeswoman for Allergan, told Outsourcing-Pharma.com.
The FDA also acknowledged in the CRL that it has not yet reviewed Allergan's response under the current PDUFA timeline, the company noted.
But this is the second time that the FDA has rejected Levadex over manufacturing issues. The previous decision came last March for MAP Pharmaceuticals, which was acquired by Allergan in late January for about $950M.
Allergan downplayed the impact of this latest CRL, saying that the “main issues cited in the CRL were already identified by the FDA in prior discussions with Allergan” and that even “with an FDA approval under the original timeline, 2013 sales of Levadex would have been minimal.”
The company expects that the FDA will need to re-inspect the facility before it can approve Levadex and that the agency’s next action will come by the end of Q4 2013.
A full update on the course of Allegan’s business and Exemplar’s progress will be included in the company’s earnings call May 1.