PharmaceuticalOutsourcingQ42020 - 39

SUPPLY CHAIN

encounter in transit: temperature, shock, vibration, pressure, and
humidity. Typically, the study is preceded by a risk assessment to
determine which risks are the highest priority for this vaccine or
other drug, which then informs the test design and implementation.
Deep knowledge of the shipping lanes the vaccine will eventually
travel through is also essential to ensuring the test reflects realworld conditions.
With a valid transport test designed, logisticians and engineers can use
simulation technology to test all five hazards on a worst-case scenario
basis, concurrently, in a controlled lab setting, under repeatable
conditions. For instance, various temperature fluctuations can be
tested, varying levels and duration of vibration can be simulated,
and shock events (such as package drops) can be done at different
frequencies. This controlled testing environment yields data that can
help assure pharmaceutical companies and regulators that no matter
what happens in transit in the real world, the integrity, efficacy, and
safety profile of the COVID-19 vaccine will be maintained.
Transport simulation studies also prove useful in situations where the
drug is in short supply (as is the case with the early COVID-19 vaccine
candidates) or is expensive. Given the scale of the pandemic and the
urgency of stemming its spread, every ounce of COVID-19 vaccine
is essential to preserve; there is no room for waste. Conducting a
controlled transport validation in which multiple hazards are tested at
their peak, concurrently, reduces the total amount of vaccine material
needed. Additionally, because COVID-19 vaccine development is in
its early stages there are still knowledge gaps, making it even more
important to obtain as much information about the material as
efficiently as possible.
Beyond meeting the regulatory requirement to demonstrate
product robustness under worst-case hazard conditions, the data
obtained from transport validation helps guide pharmaceutical
companies on how to move forward with their cold chain network.
Ideally, the testing will find that the vaccine maintained its chemical
and physical integrity when subjected to the rigors of worst-case
concurrent hazards.
In the event that transport validation uncovers potential risks in the
operating plan, the company now has the information to develop
risk mitigation measures. Mitigation is especially critical under the
Coronavirus Treatment Acceleration Program (CTAP). There simply
may not be time or resources to change the formulation, so other
measures may be more feasible, such as changes to the packaging
design or materials.
Once the transportation plan is validated and accepted by regulators,
it is important to establish a program of monitoring and controls
to ensure the vaccine reaches the front lines with its safety and
efficacy profile intact. In the early stages of COVID-19 vaccine
distribution, monitoring and controls will prove essential until
additional stability data is available to support a wider acceptable
temperature range. While these early vaccines, and other mRNAbased vaccines, will require deep-frozen temperatures for initial
storage and transportation, they will also require dilution and
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thawing before dosing. After preparation for dosing, the temperature
requirements switch to refrigerated temperatures (2 to 8° C), but the
vaccine can only be kept at this temperature for a maximum of 24
to 48 hours before dosing. These complex temperature requirements
require significant monitoring and controls to confirm the proper
temperature and storage duration.

Looking Ahead
While the earliest COVID-19 vaccine candidates will require the
most restrictive temperature controls, the next generation vaccines
will benefit from a larger body of knowledge about their stability
boundaries, opening the door to some formulations that will be stable
at refrigerated temperatures, which the supply chain has a greater
capacity to handle. For example, viral vector-based vaccines have
less restrictive temperature and duration requirements, making them
stable for months and or even years at refrigerated temperatures.
This temperature range is more suitable to long-term vaccination and
therapy programs, which COVID-19 vaccines will inevitably progress
to over time. The data provided by transport simulation studies
and real-world shipping tests will be integral to providing vaccine
developers with the insights to develop such formulations.
However, challenges still exist when transporting vaccines at
refrigerated temperatures. It will be critical to test that the refrigerated
drug will withstand the hazards of shipment and that the formulation
remains unchanged, through consistent and repeatable transport
validation. When testing is done under the controlled conditions of
a lab environment, it is feasible to repeat the same conditions tested
with an early, deep-frozen formulation and compare the results to
the new refrigerator-stable drug. Such a head-to-head comparison
provides greater assurance to regulators that the proper controls
are in place for safe transport. In turn, the challenges of safely
transporting and distributing COVID-19 vaccines will become more
than surmountable, helping to speed the delivery of these vital
preventive medicines to people globally.

Reference
1. Corum. J., Wee, S., & Zimmer, C. (2020, October 28), Coronavirus Vaccine Tracker, The New
York Times.

Gary Hutchinson, President of Modality Solutions, is an expert
in controlled-environment logistics. He has deep expertise in
understanding the environment and infrastructure, designing
controls, and creating monitoring systems. Gary's background in
the life sciences field includes a focus on biologics, tissue heart
valves, cardiac monitoring equipment, and perfusion systems.
www.modality-solutions.com
Daniel Littlefield, Principal of Modality Solutions, is an expert
in process improvement, risk assessment, safety, and security.
Currently head of the organization's engineering management
activities, he has successfully led clinical trial operations and
assessments worldwide. Daniel's career includes a variety of
technical and supervisory roles in research and operations.
www.modality-solutions.com
| October/November/December 2020

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