Pulse - June 2021 - 20

MEDICAL LEEWAY
MYVETZONE@GMAIL.COM
When Patience Is Not a Virtue
Christopher A. Lee, DVM, MPH, DACVPM
D
oes Plato's
COVID-19.
aphorism,
" necessity is the mother of
invention, " hold true today?
development. QED.
2020. New vaccine
the
Despite
necessity of invention, many people
wonder if vaccine production has
been rushed. Understanding how
vaccines are brought to market provides
important background when
considering vaccines for ourselves,
our family, and our patients.
Once measles became nationally reportable,
the US documented 6,000 deaths per
year and recognized that almost all children
became infected. In 1954, John F. Enders
and Dr. Thomas C. Peebles
isolated the
measles virus from a young, 13-year-old
boy named David.
A short nine years later, voila! A licensed
vaccine in the United States. Even today,
the measles strain in many commercial vaccines
bears David's last name of Edmonston.
With the Morbillivirus genus boasting
the most infectious pathogen on our planet,
nine years must have felt like a very long
time. Imagine if we had another eight years
to wait for a COVID-19 vaccine! So how
did we get our vaccine so fast?
From concept to customer, the average
vaccine requires 15 years to make. Background
studies can take years, even decades,
before an Investigational New Drug (IND)
application is submitted to the government.
All drugs work through the FDA. Human
biologics continue to travel through the
FDA, while animal vaccines move through
the USDA.
Luckily for COVID-19, much of the
groundwork had already been completed.
WebMD reports that other coronaviruses
cause roughly 20 percent of common
colds. Due to this prevalence, laboratory
studies had been underway long before
2019. When a novel and deadly coronavirus
erupted onto the world scene, this
previous work provided some necessary
20
background.
Then genetic sequencing
filled in the RNA coding blanks by
January 2020. Together with additional
COVID-19 specific
studies, companies
moved into Phase trials.
Phase I revolves around safety and also
determines tolerability, delivery route, and
dosage. Roughly 30 percent of vaccines
fail here. For human vaccines, these trials
include hundreds of volunteers.
Phase II looks at efficacy and expands
safety to evaluate longer-term effects.
Thousands of volunteers magnify the data
collection and stop two-thirds of vaccine
concepts here. For human vaccines,
30 to 60 thousand enrollees enable Phase
III testing, which compares to existing
options and covers more safety, efficacy,
and transmission. When ethically appropriate,
challenge studies are included. With
COVID-19, only healthy adults between
18 and 30 years of age were challenged.
Typically, three-fourths of potential vaccines
successfully move past this phase.
Roughly one out of 5,000 products
makes it through the decade of background
studies and phase trials to submit an application
for licensure with the FDA. Some
estimates place drug chances closer to one
out of 10,000 submissions. This means that
companies invest money behind 4,999 to
9,999 formulas that go nowhere.
Some suggest that pharmaceutical companies
should sell all new drugs at cost, for
the benefit of all. With a minimum of 800
million dollars of investment, to billions for
human products, and at least 100 million
dollars for veterinary products, companies
require profit to invest in future medical
innovations. Unless we have no interest in
advancing our current state of medicine,
we need to accept an appropriate profit
level for pharmaceutical and biologic companies.
This profit allows companies to
donate to charities and support countries
or areas of dire medical need.
Our government responds to pandemics
by working with companies to streamline
regulation. Do we skip background
JUNE 2021
PULSE
and phase trials? Not at all. Luckily for
us, the coronavirus background studies
had largely been completed by 2019.
New technology in nucleic acid vaccines
(Pfizer and Moderna) and viral vectored
vaccines (Janssen and AstraZeneca)
avoided many safety pitfalls seen with
modified-live or attenuated vaccines.
Also, companies overlapped phase trials.
Instead of waiting until Phase I concluded
to start Phase II, intelligent use of biostatistics
assists Phase II's safe institution during
the latter half of Phase I. Then Phase
III overlapped Phase II.
To shorten the wait, instead of submitting
a biologics license application (BLA)
that takes years to review, the FDA allowed
the use of an emergency use application
(EUA). Currently, there is not a standardized
licensed COVID-19 vaccine.
A benefit of vaccines over pharmaceuticals
remains that the active ingredient is an
antibody. This means that unless the antibody
binds to a self-antigen, a safeguard
precaution avoided by normal immune
systems, vaccines remain fairly safe. Continued
animal studies on various pathogens
allow the prework to phase trials to
be largely completed before other pandemics.
Advanced statistic methodology
and preplanned government protocols help
stack phase trials when emergencies arise.
Regardless, the FDA and USDA work to
ensure that even when patience is not a
luxurious virtue, safety and efficacy characterize
any pharmaceutical or biological
product delivered to the general public. I
want to thank the FDA for both COVID19
vaccines that I was lucky to receive. P
References, supplemental reading, and
podcasts available at www.MyVetZone.com
or search " vetzone " on Spotify.
http://www.MyVetZone.com
Pulse - June 2021

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