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Considerations for Robust Clinical and Commercial Manufacturing of Next Generation Sustainable Metered Dose Inhalers

Atkinson N.

Respiratory Drug Delivery 2022. Volume , 2022: 75-86.

Abstract:

Existing F-gas propellants used for pressurized metered dose inhalers (pMDIs) have a high global warming potential (GWP). Notwithstanding the impact on the environment, tightening legislation governing the use of these propellants is already impacting their availability and cost. Suitable low GWP propellant alternatives have been identified and the industry must ensure that pMDIs continue to meet patient needs while minimizing their environmental impact.

However, this transition may not be straightforward. Next generation low GWP propellants are likely to impact formulation, container closure systems and manufacturing equipment. Successful pMDI production with low GWP propellants will not only require these challenges to be overcome but may also require one further consideration: flammability. One promising next generation propellant is HFA-152a, which is classified as a flammable gas. HFO-1234ze(E), another next generation propellant, has a narrow flammability band at specific environmental conditions. Production of pMDIs using these next generation propellants requires our industry to develop a deep understanding and appreciation of the controls needed to manufacture pMDIs safely. Lessons can be learnt from other industries already using next generation propellants, including adopting existing standards which define best practices. However, the existing guidance is not applicable to some nuances of pMDI manufacturing and therefore companies need to undertake their own process safety risk assessments to identify appropriate controls.