Issue link: https://www.e-digitaleditions.com/i/1524818
Inhalation August 2024 27 Likewise, generic products may simply be withdrawn (or forced out); and waiting for NDA exclusivity to expire requires three years for a 505B2 NDA or five years for a 505B1 NDA. Such a situation could cre- ate a gap of three to five years at minimum, (plus at least another six months for an ANDA review) before the next cohort of NDA-based MDIs with new pro- pellants could be introduced and cause further delays for registration of any generics related to them. Even if the likely and predictable drug shortage issues do not occur with a new (A)NDA require- ment approach, the loss of current generic MDIs for at least three to five years post-approval of new NDAs, and/or the lack of availability of currently approved MDI products under NDAs, would likely result in fewer therapeutic options available to clini- cians, as well as the loss of lower-cost MDI options, thereby affecting payor reimbursement. I believe that the MDI propellant switch scenarios need not occur with such severity, hardship and cost (in time and money) to asthma and COPD patients. Requiring new NDAs for already approved MDIs for the transition to HFA-152a or HFO-1234ze(E) is a more cumbersome and higher cost (in devel- opment and user fees) and is overall a less feasible and longer process, which may be inconsistent with modern science and regulatory options. Under con- temporary methods for MDI design, the develop- ment, characterization, manufacture, control and make the upcoming propellant transition as feasi- ble and unencumbered as possible, consistent with modern science. It is foreseeable that the impending loss of existing NDA and ANDA MDI drug products under a man- date for new NDAs could lead (with high predict- ability) to drug shortages as manufacturers struggle with respect to resources in developing new NDAs, while supporting existing NDAs, and while already approved ANDAs also come under threat. ere are numerous complexities that may impact approved ANDA MDI products as a result of an RLD MDI being withdrawn or and/or replaced by another NDA [23]. An RLD MDI product is the anchor upon which an ANDA MDI is approved. If the RLD MDI is with- drawn (or otherwise not available for reference test- ing), the approved ANDA MDI is caught in limbo. Another approved MDI may be designated as the listed drug [22] (if one is suitable and available), but this is an uncertain and time-consuming pro- cess for all parties concerned. Further, if an existing, approved NDA is withdrawn for reasons related to safety or effectiveness, that requires any correspond- ing ANDA(s) to be immediately withdrawn. Some NDAs and ANDAs may simply drop out of the market altogether for the particular MDI pro- duct(s), rather than face full NDA development.