The FDA has issued a 483 to Exemplar citing observations regarding problems with MDI filling from its March 21, 2012 inspection of the company’s Massachusetts facility. Exemplar is referring inquiries about the issue to MAP Pharmaceuticals, which recently met with the FDA to address manufacturing problems with its Levadex inhaled dihydroergotamine cited in a Complete Response Letter in March 2012.
The 483 cites two observations: 1) “The in process control procedures were deficient in that they did not include an examination of the adequacy of mixing to assure uniformity and homogeneity” and 2) “There are no written procedures for production and process controls designed to assure that the drug products have the identity, strength, quality, and purity they purport or are represented to possess.”
More specifically, the inspectors noted that the pressurized filling system lacked controls to prevent changes in drug concentration due to propellant evaporation and no way to assure that canisters are filled to specifications in the event that pressure fluctuates and/or flow is disrupted. Among other problems, they cited “a catastophic failure perturbing product flow resulting in canisters meeting fill weight specification with total content below specification.”
A MAP press release states that, “The FDA provided clarity on the steps necessary for the Company’s third party manufacturer to address observations related to the implementation and documentation of manufacturing process controls cited during a facility inspection. The Company is working closely with its third party manufacturer. The third party manufacturer provided responses to the observations to the FDA, and the Company believes the observations cited by the FDA either have been resolved or will be addressed in conjunction with the resubmission.”
MAP Pharmaceuticals President and CEO Timothy S. Nelson commented, “Based on our meeting with the FDA, we believe that we have clarity on what is needed to address the issues in the Complete Response letter, and we are encouraged by the FDA’s collaborative dialogue in providing guidance that will help us move forward with our resubmission process. We plan to resubmit to the FDA in the late third quarter/early fourth quarter 2012 timeframe.”
View the FDA Form 483.
Read the MAP Pharmaceuticals press release.
