As a result, alternative apparatus may be required for certain products or markets. For example, the British Pharmacopoeia requires use of an MDI content uniformity apparatus that is unique to the BP, likely having been retained for historical reasons.
Q: Why do we need guidances and pharmacopoeial monographs that cover inhaled product testing for specific products?
A: A product-specific FDA guidance, or a product-specific monograph, is designed to streamline the process of demonstrating bioequivalence (BE) for a certain active ingredient — usually a popular subject of Abbreviated New Drug Applications (ANDAs) — delivered via a specific route.
Levels of generic activity have increased exponentially over the last decade or so, substantially increasing the number of ANDAs presented to the FDA. Figures for Jan – July 2013 show that in this period alone the FDA approved 235 ANDAs and the generics sector continues to grow strongly, most especially in India where annual growth rates are running at around 27%. Targeted guidance for the most popular generics may enhance productivity by providing ANDA sponsors with the testing methods most likely to result in successful submissions.
The success of a generic submission relies on the robust demonstration of BE to the reference labeled drug (RLD), which normally involves presentation of in vitro test data to demonstrate that the generic will perform in a clinically identical way to the RLD. Arguably the easiest and least risky way to demonstrate BE is to present equivalent results using directly comparable in vitro test methods and identical test equipment.
The expected results and/or acceptance criteria for delivered dose, impactor drug mass-per-stage, fine particle dose or mass balance testing could be specific to, or influenced by, the equipment type and test method used, so duplicating the original equipment and test methods as closely as possible eliminates uncertainty about test results that might result from such sensitivities.
For many of the popular targets of inhaled drug ANDAs, early research work may pre-date generic development by a period of close to 20 years, and over the last two decades, inhaled product testing has marked a period of considerable evolution. As a result, many of the analytical approaches used in the development of originator products that form the basis of today’s most popular generic targets differ from our current testing methods.
