TRANSPORTATIONSOLUTIONSFOR CELL AND
GENE THERAPY
SUPPLY CHAINS• API• BIOLOGICS• VIRAL VECTORSERVICES• EARLY & LATE PHASE
DEVELOPMENT• CLINICAL TRIAL
SOLUTIONS• LOGISTICSSERVICES• COMMERCIAL

MANUFACTURING

Angie West
Global Relationship Director,
Pharma Services
Allentown, PA

The number one priority with cell and gene therapies
during transportation is maintaining the integrity ofthe drug, as well as ensuring it arrives on time to its
destination and within temperature specification.
The task of maintaining speed, temperature, and integrity becomes much more complicatedwith these drugs. Many gene therapies are moved at a minimum of minus 80 degrees Celsius,
while many cell therapies are moved at cryogenic temperatures, which can be as low as
minus 196 degrees Celsius.
In addition to these strict temperature and timing requirements, cell and gene therapy supply
chains are more complicated than traditional life science supply chains. Coordination
challenges exist in the manufacturing process, especially for autologous therapies, given thehighly personalized nature of the medicine itself. It is essential to quickly and efficiently movematerial to meet the needs of often extremely ill patient populations. This includes ensuring
sufficient supply and storage conditions for raw materials, collection and transportation ofapheresis or other patient-derived starting material, and final distribution back to patient.
Maintaining temperatures for cold chain drugs requires strict coordination of the supply chain
to ensure the material arrives on time to its destination and within specification. Therefore,
developing a strong supply chain both in terms of the raw material up front and the ultimate
distribution of your cell and gene therapy, can make your company a more attractive target
for acquisition as well as a more competitive player in the commercial environment.

3

Key considerations for evaluatingtransportation partners
Before evaluating transportation partners, you should thoroughly define your logistics
requirements and evaluate partners against them, even if you are planning to use your default
transportation option. The result is a customized solution tailored to meet your product’sneeds. Some questions to ask that can help define your requirements include:
What is the scope and scale of your trial? Are you delivering to 10 patients at a single clinicalsite or 100 patients across multiple countries? What are your patient enrollment goals for later
phases of your clinical activity? Consider how the decision you make now will impact yourcost of goods sold as you approach commercialization.
What is the temperature and time sensitivity of your product? This helps determine what typeof shipper you use, how and where the carrier positions the shipper in their network, and the
speed and service level that are required to move the product.
How much control and visibility do you want into the movement of your product? Do you needjust in time (JIT) pickups or deliveries within a specific time window? How much lead time doyou have to move the product? Will you require GPS monitoring?
What are the geographic requirements? Crossing borders is going to increase the complexityof the move, and there may be country-specific requirements for importation, especially forclinical versus commercial product. You may also need intermediate storage while the productclears customs. Regarding control and visibility, if your product will be shipped to othercountries, you will need access to global trade compliance expertise.

Evaluating potential partner capabilities based onservice level expectations
Risk mitigation should be at the forefront of any process,but you should choose a partner who will lower risks while
also remaining cognizant of any cost pressures that you
may be facing. One of the most important factors inselecting the right partner for your project’s needs is a clear
understanding of the difference in service level expectations
for integrators versus those of specialty carriers. This is anarea where there are common misconceptions, and it iscritical you understand the differences in not only how they
deliver your product, but also how they measure up against
your business needs. Below are a few critical questions youshould ask to explore where your potential partner stands.

AN INTEGRATOR VERSUS A SPECIALTY
COURIER: WHICH IS A BETTER FIT FOR
YOUR NEEDS?
The biggest difference between integrators and specialty
carriers is that an integrator is an asset-based provider,whereas specialty couriers generally are not. Integrators
have their own planes, trucks, and a global network ofdistribution facilities. Conversely, specialty couriers dohave their own global network of distribution facilities, ordepots, but they likely have very few owned assets thatphysically move the material. Instead, they rely on an agent
network, which is made up of qualified companies that a
specialty courier will contract to move your material within a
specific region. Whether a partner is asset-based or not
impacts how materials are moved through your supply
chain and the amount of flexibility that exists while doing so.
A specialty courier functions like a taxi. If there are anydisruptions in a route, they can choose an alternate pathand still arrive on time. However, an integrator functions likea public bus system, where there are predetermined routes
with regular stops from which they cannot deviate.

HOW DO THEY ENSURE GLOBAL TRADECOMPLIANCE?
All logistics companies should possess a quality andcompliance program that drives their services. Somecompanies are more compliance and quality driven thanothers, so ensure you ask providers to review theircompliance program when evaluating different options.
Product classification is not typically a service that isoffered by an integrator or a specialty courier. However,couriers do work with brokers within their network to review
and approve required documentation prior to a shipment
departing its origin. This pre-approval ensures timely
customs clearance and delivery. Integrators, in most cases,
rely on a consolidated manifest that is sent to customs inthe destination country. Understanding how this works isimportant, as it could affect the timing of delivery dependingon the urgency and complexity of your shipment.

HOW DO THEY TRACK QUALITY?
For any shipments within the life sciences industry, andspecifically shipments within the cell and gene therapy
space, you want to be mindful of how the company istracking deviations, complaints, and corrective andpreventive actions (CAPAs). There are several specialty
couriers that have built their businesses around the life
sciences industry, which means they are not only familiar
with the industry’s specific requirements but also that theirquality assurance or quality management systems havebeen developed to support the level of rigor required bythese companies. Integrators are primarily trying tomaximize the efficiency of packages moving within theirown networks, so they may not have this expertise. You willlearn more as you evaluate any company in further detail,but early indications of a robust quality management system
and an experienced quality team are an important start.

5

HOW DO THEY COMPARE IN COST?
You may be able to leverage better rates with an integrator,
but you must also evaluate the risk trade-offs required tomove your product. It is not uncommon for clients to initiallyselect an integrator based primarily on price but then faceissues with the level of service provided. For example,
clearing customs can be far simpler using a courier that canwork closely with the in-country broker. Oftentimes,
specialty couriers can help with other supply chain functions
that integrators may be slower to adapt to due to their
existing networks, which may limit overall flexibility insupporting your therapy.

WHAT ARE THEIR PERFORMANCE DRIVERS?
Specialty couriers all leverage the same commercial airlinesthat you use for personal travel every day to move somethingfrom point A to point B. What impacts performance here,
though, is the relationship the courier has with the airline, its
personnel, and the ground handlers. All specialty couriers
leverage network providers. Remember, most specialty
couriers are not asset-based. When they need to leverageboots on the ground, this is largely provided by their agent
networks. Developing a strong agent network requires
robust training on standard operating procedures. With somany similarities between specialty couriers, customer
service can be a key differentiator to help you decide which
is best for your business needs. A partner with good
customer service will have a plan in place to proactively
notify you if there is a delay or change to your plan as wellas if there are any unexpected excursions or deviations.

How couriers build your proposal
Once you have established your requirements and are ready to seek proposals, you will needto develop a transportation proposal. First, you must define the following:࡟ lead time
࡟ product shelf life࡟ pack-out assistance࡟ temperature requirements
࡟ origin/destination pairs࡟ consignee (receiver) of product if shipping to international locations
࡟ shipper technology and temperature monitoring devices
The courier will begin by reviewing this information and should work backward from thedestination to determine the best optimal path for on-time delivery, all while taking into
account the lead time, shelf life, and temperature requirements. As you might expect, theorigin and destination pairs drive the strategy. The shippers must be positioned in a way thatallows them to reach the origin site as quickly as possible, making the services of an integratoror specialty courier crucial. Using a specialty courier can significantly reduce risk, due to thelevel of customization and high-touch customer service, which may not always be necessary
if you have enough lead and hold time with your shippers. For example, shippers with a shorthold time with extremely critical material inside will still likely move via a specialty courier,even if there is sufficient lead time based on scheduling the patient for a subsequent
manufacturing run. Depending on the geography, you may have more flexibility, given that theshipper has a longer hold time and you could potentially do all three legs via an integrator.

7Next, the courier determines how far the origin is from thedestination point. For example, if the product is going
between Boston and New York, it may make more sense todrive the four hours to reduce the numerous handovers
when tendering to airlines and recovering the product at thedestination airport. The fewer the touches on the product,
the more you can control the risk. While this is not always anoption due to cost considerations, it is certainly something
to consider when possible. Onboard carry - where a courier
physically carries the material on the plane - is the mostextreme example of how to reduce touches. However, thisis very expensive and largely not necessary, due to theinfrastructure that exists today to support cold chain
logistics, both domestically and internationally. If thedestination is too far to drive, the courier will look at how
many nonstop flights depart for the destination on any givenday. The more nonstop flights going from your origin and to
your different destination points, the more likely a delivery
will be on time should the product not make it onto the firstflight out. This can sometimes happen since passenger
baggage typically takes priority over other packages oncommercial airlines. Therefore, if one of your flight legs is aregional flight to a busy destination, your material could
potentially get bumped.
If you are still considering your manufacturing strategy,
location can be an important factor, as it can have longterm cost implications. Ideally, your manufacturing sites
should be in close proximity to several major airports sothat you have more flexibility within your supply chain.
Manufacturing locations or collection points that are more
remote require some form of a dedicated drive (again,consider how to mix in a ground strategy that can reduceturnover of the product). Depending on your position in
between major airports, the courier may suggest using one

airport over another, even if one seems to be further fromthe origin site. Some factors that drive decisions like theseinclude a better relationship with an airline and its groundpersonnel at a particular airport; or perhaps one airport haslarger volumes of cargo shipments, making it is easier toget space on the plane.
Based on your destination, the courier may choose to send
the material to a major hub airport that requires a longer
drive to your destination versus a regional airport that
requires a connecting flight. This can occur if the recoveryof the product is easier at one airport versus another, if you
are sending palletized materials that require use of widebodied planes that are too large to land at small regional
airports, or if there is a potentially better interim storage orreplenishment infrastructure at one airport versus another.
Finally, the courier will consider which agents to use at thedestination as well as what the relationships are withbrokers in that country (if you are shipping internationally).
Regardless of whether the destination is domestic orinternational, couriers will want to obtain approval to ship
the product prior to even leaving the airport. If there is amajor integrator hub near the origin or destination points,
then a hybrid strategy is certainly an option. This reduces
costs while providing a higher level of visibility andassurance via specialty carrier for the recovery and final
mile delivery. Once the courier has considered all thenuances of the geography and the product itself, they willthen determine the primary, secondary, and tertiary next
flight out options, assessing on-time performance, recovery
times, and developing storage replenishment plans at thedestination airport. These are all risk mitigation techniques toprotect the product in the event of any unanticipated delays.

Balancing cost versus risk in your proposal
development process
Risk mitigation is a key focus during transportation, but many of the methods to reduce
unexpected issues and delays and/or temperature excursions also come with added costs. It
is important you understand and consider this balance when defining the requirements foryour transportation proposal. For example, shorter lead times or JIT deliveries can drive costs
up, as can certain types of shipping technologies that are often used to increase reliability
and flexibility, such as shippers using phase change material. The same applies to advanced
shipper technologies or more customized delivery and pickup windows intended to provide
better oversight of your delivery. From a geographical perspective, dedicated groundtransport may be more expensive, but it can decrease turnover risk and the number oftouchpoints the product encounters, which could be a helpful strategy depending on where
you are shipping. While flying may end up being the most expeditious and cost-effective
mechanism, it is worth asking about ground transport so that you understand your options as
they relate to speed, security, and cost.
The EU presents a lot of opportunities for ground trucking, especially since goods can movefreely within the region. In both North America and the EU, you can likely leverage somecombination of integrators and specialty couriers. This is going to allow you a higher level ofcustomer service through the courier and potentially save on cost with the integrator whenyour delivery windows are not time specific. In Asia-Pacific (APAC) areas of the world, youmust be cognizant when using regional flights, as some of these package handlers may not
be familiar with the materials being shipped. Your courier should be in constant communication
with the agents that are going to be handling the shipment on the other side, as well. A dedicateddrive is not much of an option within APAC, and packaging may not be as readily available.
While you want to make sure all shipments are planned well in advance, there are hugevariations in infrastructure across countries, and hybrid solutions can still be an option
depending on how close your manufacturing environment is to a major hub. In all of our
discussions with current and potential customers, Thermo Fisher Scientific stresses theimportance of key performance indicator (KPI) management. Your courier will already be
tracking their on-time performance, but it is important to set up structures early in the processto monitor your own interactions with your partners. For example, depending on your provider,
you may incur additional costs for rush orders, reprocessing, and cancellation. Putting KPIs
in place early in your process helps identify issues quickly and efficiently and subsequently
makes way for root cause analysis that will enable corrective action to take place.

9CASE STUDY

Cell therapy phase III trial
A sponsor was conducting a global phase III trial, enrolling over 1,000 patients at clinical sites in the U.S., aswell as 20 EU and 20 non-EU clinical sites. Thermo Fisher arranged JIT kit distribution to the treatment centers
for collection of tumor cells to be used in the manufacturing process. Once the tumors were biopsied from thepatients, Thermo Fisher arranged the collection of the kits back to its facilities for storage in a validated andclient-dedicated minus 80-degree Celsius storage system for 30 hours.
When the client was ready for a manufacturing run, Thermo Fisher shipped the tumor material on dry ice to theCMO, where it would be processed into 10 to 14 vials of final drug and cryopreserved. Thermo Fisher thencoordinated the return of the 10 to 14 vials of final drug product back to its facilities for storage in a validated
and client-dedicated storage unit. Upon client notification of an order, Thermo Fisher shipped a single dose, or
one vial of drug, for administration to the patient and coordinated the JIT dose distribution and administration
kits to the treatment centers utilizing a validated and dedicated fleet of dry vapor shippers for this client.
Given the scale of patient enrollment across geographies, having detailed work instructions and a robust
training program was extremely important to ensure the timely delivery of materials within specification.
Because Thermo Fisher Scientific’s dry vapor shippers are fully validated at cryotemperatures for 10 days, there
was an option to adjust the shipping schedule. The patient dose was shipped several days in advance via anintegrator using certain EU lanes to make sure it was still available for the patient’s scheduled appointment. If
the shipment arrived early, the shipper could act as a temporary storage device at the clinical site; if it wasdelayed by a day or two, the dose would remain within specification prior to patient dosing due to the 10-day
temperature hold. Because of the number of shipments engaged in this trial, KPI management was essential tomonitor and control costs and complete this phase of the trial under budget for the client.
Overall, the partner you work with for the shipment of your temperature-sensitive drug products must haveextensive experience in this space, in order to manage the complexities of your trial. They must be able toholistically look at your supply chain and leverage their global footprint and network to help you mitigate riskand help you scale your business. Using KPIs, they can drive continuous improvement and ensure any issues
are identified quickly and a corrective action plan is put in place. Investing in your supply chain up front toimprove efficiencies and processes later allows you to protect your materials, your investment, and mostimportantly, patients.

11

+1 919 226 3200 • thermofisher.com/patheon • pharmaservices@thermofisher.com© 2020 Thermo Fisher Scientific Inc. All rights reserved.
Published 05/20 PSG0949