Understanding the Essentialities in Establishing the Bioequivalence of Oral Inhalation Drug Products to be Marketed in the USA.

Abstract

Oral inhalation drug products (OIDPs) are combination products comprising two components, i.e., a device and the corresponding formulation, and are manufactured with 'patient use' being the key consideration. The formulation is designed to be compatible with the device, as the device and formulation have to work in tandem for the intended effect of the drug to be imparted to the patient. OIDPs are generally categorized into three sections: pressurized metered dose inhalers (pMDIs or MDIs), dry powder inhalers (DPIs), and nebulizers. As OIDPs are most convenient in the treatment of asthma and COPD, it makes these drugs all the more vital in terms of inhalational therapy. The introduction and sustenance of a generic market for these drugs is extremely essential as prices of innovator OIDPs have always been a point of contention with respect to ensuring adequate patient care. Since generic drug approvals require the conduct of bioequivalence studies, it becomes imperative for regulatory authorities to establish strict guidelines for the same. For a long time now, the lack of an appropriate approach for the conduct of bioequivalence studies for OIDPs has proven to be a major obstacle. With the publication of individual guidance documents for OIDPs, the US FDA has paved a path for future approvals of generic OIDPs guided by the ideology that "no one-size-fits-all." This approach, known as the "weight-of-evidence" approach, requires manufacturers to submit in vitro studies, pharmacokinetic studies, and pharmacodynamic studies, in order to seek authorization for marketing generic OIDPs.