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Assessing In Vitro BE Using Realistic Inhalation Profiles for Regulatory Approval of Generic Inhalers

Sandell D.

Respiratory Drug Delivery 2016. Volume 1, 2016: 133-146.

Abstract:

In vitro bioequivalence (IVBE) evaluations for orally inhaled products (OIPs) are critical and challenging tasks both for product changes and for generic/originator comparisons. One potential area for improvement is the use of more realistic test methods for the comparison; this is expected to make the conclusions more reliable. Equations provided in Delvadia [1] which predict the 10, 50, and 90 percentile values for peak inspiratory flow rate (PIFR) from the resistance of the studied dry powder inhalers (DPIs) were compared to the PIFR results from a wide range of published data for different DPIs and patient groups. Equations for PIFR based on data collected from professionally-trained normal volunteers overestimated the PIFR values from the DPI literature, especially for low resistance devices, while equations for literature-trained subjects generally provided better match. A more general model was introduced and fitted with good results to literature data [2]. When combined with recently published equations to simulate inhalation flow rate versus time profiles, the proposed model enabled simple factorial experimental designs to be proposed for two major purposes: 1) as a development tool to separately assess the effects of the peak inspiratory flow rate (PIFR), the time at which it occurs (TPIFR), and the total inhaled volume (V); and (2) a more realistic comparison between a candidate generic and originator DPI product, as recommended in regulatory guidance by both FDA and EMA.