Risk Assessment of HFAs used as Propellants in Autoinjector systems

We undertook a risk assessment of hydrofluoroalkanes (HFAs) exposed intradermally or subcutaneously during autoinjection in humans using a medical device. As exposure to HFAs via this pathway is uncommon, data from other exposure pathways were considered, taking into account metabolic pathways and local and systemic effects.

The use of hydrofluoroalkanes in many circumstances e.g. propellants and in refrigeration units, is on the increase as a more environmentally acceptable alternative to the use of hydrofluorocarbon species. HFAs have been used as propellants in Metered Dose Inhalers (MDIs) for a number of years, consequently a large body of safety data exists for a range of these chemicals via inhalation exposures. A similar range of HFAs were chosen to provide the controlled propulsion of subcutaneous injections of pharmaceuticals in an automated injector system. Whilst significant data existed to safely assess the risk from potential accidental systemic exposure to HFAs via the subcutaneous injection route, there was a data gap for possible local effects in the subcutaneous tissue. Further literature searches established a clear potential hazard to subcutaneous and intradermal layers of the skin following exposure to compressed gases and to low temperature materials. Therefore, a testing strategy was designed in accordance with international ethical standards and conducted to ICH pharmaceutical and medical device standards in order to complete a risk assessment data set. These data can be used to satisfy producers and users of the safety of the autoinjector device.