The FDA draft guidance on albuterol sulfate MDIs published April 8, 2013 includes recommendations for a total of 7 studies, including 5 in vitro studies, 1 PK study, and 1 PD study to establish bioequivalence.
The recommendations for in vitro testing cover single actuation content, aerodynamic particle size distribution (APSD), spray pattern, plume geometry, and priming/repriming. The recommended PK study is a single dose, two-way crossover study measuring albuterol in plasma, and the recommendation for the PD study is for either bronchoprovocation or bronchodilation with equivalence based on dose-scale analysis of the PD data.
The guidance also suggests that the test product be “similar in size and shape” to the reference product and notes that the sponsor “is encouraged to submit a working model of the MDI to the Office of Generic Drugs prior to the ANDA submission, in order to ensure the eligibility of a T device under the 505(j) pathway.”
According to the document, the recommendations are non-binding, and an alternate approach is acceptable “if the approach satisfies the requirements of the applicable statutes and regulations.”
The notice of publication in the Federal Register states that comments on the draft guidance should be submitted by June 7, 2013.
View the draft guidance.
View the notice in the Federal Register.