HFO-1234ze(E) has a global warming potential (GWP) close to 1 whereas other propellants have GWPs that range from 138 to 3350 as per the IPCC’s Assessment Report 5. It is estimated that the average inhaler using HFO-1234ze(E) would have carbon emissions of 5-9 g CO2 equivalents per dose, compared to 9 g, 20 g, 263 g, and 697 g CO2 equivalents per dose for DPIs, HFA-152a, HFA-134a, and HFA-227ea inhalers, respectively [Jeswani and Azapagic].
HFO-1234ze(E) is non-flammable at 23°C per ASTM E 681, EC A11, and ISO 10156 testing methods. Under standard conditions of 23°C and 50% relative humidity (RH), HFO-1234ze(E) does not exhibit a flame limit. It is nonflammable per the ASTM D3605 flame projection test, the ignition distance test, and the enclosed space ignition test (closed drum test, GHS Rev. 8). That said, under specific, nonstandard conditions (≥30° C AND ≥50% relative humidity AND a high energy ignition source) HFO-1234ze(E) can exhibit a very narrow flammable range. Typically, in a pharmaceutical manufacturing environment the temperature and humidity are controlled.
In a 2011 study, HFO-1234ze(E) was shown to have comparable effects on valve components as the currently used HFA propellants. EPDM, nitrile, chloroprene, butyl, and TPE gaskets were fully immersed in HFO-1234ze(E), HFA-134a, and HFA-227ea for 4 weeks at room temperature and 40°C / 75% RH. The swelling and mechanical resistance were measured for all samples. The swell of elastomers immersed in HFO-1234ze(E), HFA-134a, and HFA-227ea were all acceptable (<5%) and mechanical resistance were all similar.
Yes, extensive preclinical toxicological studies have been conducted to characterize the safety of HFO-1234ze(E) in MDI applications. Toxicological data is available upon request. Additionally, safety and tolerability of HFO-1234ze(E) in humans is well established through a phase 1 clinical trial.
Yes, there is a DMF filed with the US FDA that can be referenced for IND, ANDA, and NDA filings. There are also DMFs filed in Japan and China.
Commercial quantities of HFO-1234ze(E), cGMP, are available from Solstice’s Baton Rouge, LA facility, and sample quantities of cGMP materials, such as 1/2 ton and 50lbs, are available from the Buffalo, NY facility for research and development purposes.
