Cirrus - recently acquired by India-headquartered Kemwell Biopharma - was selected by the US Food and Drug Administration (FDA) to undertake the study, entitled ‘Comprehensive Evaluation of Formulation Effects on Metered Dose Inhaler Performance’ which is set to last a year.
“It is well known that excipient concentrations have an impact on the aerosol performance of MDIs,” Dr. Jay Holt, Sr. Director for Inhalation & Analytical Testing at Cirrus, told in-Pharmatechnologist.com, citing, as an example, “inclusion of a component - such as ethanol - that is less volatile than the hydrofluoroalkane (HFA) propellant may result in a coarser particle size distribution.”
However, for a generic approval the FDA requires that “the inactive ingredient levels must match the reference listed product to within 5%,” but “what has not been systematically studied for MDIs is how changes of excipient levels within and outside of that range may impact performance.”
Though excipients are a key goal of the research, Cirrus will also evaluate the impact of changes in the active pharmaceutical ingredient (API) particle size on aerosol performance, Holt added.
Furthermore, “another aspect of the studies is that aerosol performance tests (e.g. aerodynamic particle size distribution by inertial impaction and dose content uniformity) can have significant inherent variability,” he told us.
“It will be of interest to see if these standard performance tests can detect small, intentional changes to the MDI formulation.”
According to Holt, the FDA selected Cirrus based on the company’s experience in MDI development, an example being the formulation and CMC work for Sunovion Pharmaceuticals’ Xopenex MDI. Cirrus did not divulge any financial details.
The study is also set to enhance the FDA’s reviewing process under the Quality by Design (QbD) model.
As one of the underlying goals of QbD, understanding how product attributes relate to product performance will help the Agency frame their review of MDI submissions under this paradigm, Holt said.
It is important to understand “how excipient concentrations and API primary particle size impact MDI performance” and understand “the limits of current analytical metohdologies to detect those changes.”
As well as regulatory review, the results should help pharma companies in developing a QbD plan for developing MDIs, he added.