The Technical Challenges of the Developing Existing Inhalation Drug Products into New Metered Dose Inhaler Designs

The Technical Challenges of the Developing Existing Inhalation Drug Products into New Metered Dose Inhaler Designs

Neha Patel, ¹ Alex Slowey¹ & Lester Harrison²

¹3M Drug Delivery Systems Division (DDSD), Charnwood Campus, 10 Bakewell Road, Loughborough, Leicestershire, LE11 5RB, UK.

²3M Drug Delivery Systems Division (DDSD), 3M Center, St. Paul, MN 55144-1000, USA.

Summary

Many of the best-selling inhaler products currently on the market deliver drugs that have been around for decades, yet the complex regulatory pathway required to develop generic inhalers has resulted in few generic inhalers being available on the market.  In general, companies have chosen to develop ‘branded generic’ products using the same drug substances and inhaler design as the reference product on the market using the 505(b)(2) regulatory pathway in the US or Article 10.3 submission in the EU. 

An alternative approach is to develop existing drug substances into new inhaler designs that contain the same drug substances currently in the reference inhaler product, but within an entirely new delivery system (e.g. developing a new metered dose inhaler (MDI) that delivers drugs which are currently delivered via a dry powder or soft mist inhaler (SMI)).  This approach may be chosen due to intellectual property considerations, as a product lifecycle management strategy or to provide market differentiation (e.g. using improved inhaler technologies). This abstract will illustrate some of the technical challenges associated with developing existing drug substances into new inhaler designs, with the consideration of more complex in-vitro and in-vivo relationships.

An approach for establishing in-vitro-in-vivo relationships for different delivery formats, through the careful design of an early proof of concept (POC) pharmacokinetic (PK) study, is demonstrated in the form of a case study.  POC PK data are presented alongside in-vitro data sets, thus emphasizing the importance of clinically relevant in-vitro testing and the role that this has in determining the viability of developing existing drug substances in the MDI format.