The CFC to HFA transition and its impact on pulmonary drug development

The terms of the Montreal Protocol have eliminated chlorofluorocarbons (CFCs) and other ozone-depleting agents from commercial use, with the exemption of their use as propellants in metered-dose inhalers. Two new propellants have been approved for CFC substitutes: hydrofluoroalkane (HFA)-134a and HFA-227. An extensive safety program was conducted by the International Pharmaceutical Aerosol Consortium for Toxicity Testing (IPACT studies I and II), which found that the HFAs were as safe as or safer than the CFCs. The change from CFCs to HFAs in metered-dose inhalers was not a straightforward exchange. Indeed, substantial new technology had to be developed to make the HFAs suitable for use in metered-dose inhalers. Fortunately, with new understandings of respiratory diseases and the areas of the lungs that need to be targeted by medications, the new HFAs provided the opportunity to improve the performance of the beta-agonist products and created some entirely new ability for inhaled steroids to reach all the airways, both large and small, where asthma pathology resides. The transition from CFCs also spurred novel new drug-delivery technologies, improved dry powder inhalers, and highly dispersible engineered powders.