APR Sept/Oct 2023 - 80

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DRUG DELIVERY
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centric strategy, neither is a one-size-fits-all solution, and both are
easier said than done. Given the ubiquity with which these solutions
are offered, it is worth taking a moment to consider each more fully.
Changing Propellants
Like Kindeva, most CDMOs and other organizations working with
inhaled therapies are continuously engaging in research to improve
what is available and find what is next. This research, however,
is not fast by design, which is something much of the current
legislative processes fail to recognize. The pharmaceutical industry
is highly regulated worldwide in order to ensure proper testing and
appropriate measures are taken to protect patients. Additionally,
were the act of discovery at-will, modern life would likely be much
different. Science, and particularly the science of human health,
simply takes time. From determining the proper compound and
formulation to testing and practical logistics, the pathway to meeting
revised legislation is likely to require six to seven years. And it bears
repeating that this is not a flaw in the system but is, in fact, a feature
meant to safeguard patients.
While both HFC-152a and HFO-1234ze, which respectively have 90%
and 99.9% lower GWP than the current greenest propellant, are both
near commercialization at Kindeva, ensuring research anticipates
legislation introduced years later is an impossibility. In the case of
HFO-1234ze, which has the lowest GWP of the alternative propellants
discussed thus far, it is currently within the scope of the ECHA draft
PFAS legislation, illustrating that even when the discovery process
seems to be on the right path, an unwelcome surprise could wait
around the corner.
While changing propellants in pMDIs is absolutely an integral part
of strategies to lessen the environmental impact of drug-delivery
combination products, it is simply not something that can happen
on demand. Patient safety must be at the fore of every decision we
make as providers of needed therapies, so creating the safest, most
effective product should always be the end goal. This means there is
no wiggle room in adherence to timelines and procedures that ensure
responsible formulation, development, and testing.
A Different Device
Given the necessary delay between the start of the discovery process
and commercialization, the tactic of just switching patients to DPIs
seems logical. As with the change in propellants though, it misses
the fundamental necessity of putting the patient at the center of the
discussion. While DPIs are accessible for many people, they are not
suitable for all patients, including those who lack the capacity to create
adequate inspiratory flow. The medical community also has ethical
concerns around switching already stable patients, given the potential
for short- and long-term harm.
If changing to a DPI were to adversely impact the effectiveness of
the therapy or otherwise impair the ability of the patient to properly
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use the device, that can cascade into a sequence of events that will
negatively impact the environment, including transportation to the
doctor and hospitalization. While these may seem like secondary
concerns, they further support the notion that the right device for the
patient is the right device for the planet.
Proponents of a DPI switch are also missing the bigger picture of
crafting a green therapy prior to patient use, overlooking the total
footprint of devices in favor of focusing on a single portion of their
design. While DPIs offer a lower GWP than pMDIs, they fail to exceed
many of those same devices in other environmental measures, as will
be discussed in the next section.
A Wide-Lens Look at
Environmental Threats
With these two options in mind, it is important to determine how the
needs of the patient and the needs of the planet can best align within
the drug-delivery combination product marketplace. While there is a
purpose within the industry to acting incrementally, in part to allow
for responsible timelines, there is also an opportunity to map out at
least a partial path forward that would allow organizations to more
accurately begin transitions prior to the proposal of requirements. This
sort of preparation also provides a clearer view of the road toward
truly greener therapies, ensuring the focus on individual compounds
and components is not missing the bigger picture of a combination
product's environmental impact.
The pushes to change propellants and switch to DPIs both limit the
ability of the industry to truly reach the goal. While there is value to
transitioning in stages, an understanding of the overall challenges
is the only way to responsibly pivot in the short term. Along with
ensuring patients have access to devices that work for them, it is
vital to make sure the device to which you are pivoting is not doing
equal or greater damage in another area of environmental concern. To
exemplify the holistic evaluation that must be performed, we will use
data from a 2019 University of Manchester, U.K., evaluation of the life
cycle impact to the environment of DPIs and pMDIs using HFC-134a,
HFC-227ea, and HFC-152a.3
This study examined a range of environmental impacts, including GWP,
fossil and metal depletion, and freshwater and marine eutrophication.
While the DPI lived up to its promise in GWP measurement, coming
in 2.4 times lower than the HFC-152a pMDI, it stumbled in other
evaluations. In fossil depletion, for instance, the DPI was the worst
option, with 75% higher depletion than the HFC-152a inhaler. Similarly,
the DPI proved the worst choice based on impacts to both freshwater
and marine eutrophication. In fact, for 10 out of 14 categories, the HFC152a
pMDI proved to have the least environmental impact, whereas
the DPI had the most damaging impact in eight categories, in large
part due to its componentry.
So, briefly removing patient use concerns from the discussion, the
researchers found that switching entirely from pMDIs to DPIs would
reduce the climate change impact of inhalers in the U.K. by 96%,
but the environmental trade-off is a significant increase in human
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