ARTICLE

Prepping for commercialization
through supply chain logistics
Cell and gene therapies (CGT) are bringing new hope to patients experiencing rare and serious
diseases. And they are disrupting the biopharma market in new and challenging ways.
Patients experiencing rare and serious diseases have seen a steady increase in possibilities fortreatment as nearly 1,308 developers (as of 2021) were investigating regenerative medicine andadvanced therapies (RMAT) in over 2,400 clinical trials globally. The RMAT sector included $22.7
billion of investments in 2021, a 14% increase from its $19.9 billion record in 2020.1
US regulators are responding to this growth and the tremendous patient need by establishing new
guidance and procedures including expedited programs for regenerative medicines.2 Because
there is no reason to believe that demand and market growth will slow any time soon, the CGT
space must recognize and prepare to mitigate supply chain challenges that result from and further
limit current capacity. Here we discuss several industry challenges and pain points as clients
prepare for commercialization of CGT products.

Challenges with cell and gene therapy supply chain logistics
Ultra-low temperature control
CGTs require ultra-low temperature control, a difficult and sometimes
risky requirement. Product integrity typically requires that theproduct be maintained at frozen and cryogenic temperatures withan aim at eliminating time out of environment. Maintaining this strict
temperature control creates challenges not only during storage,
but also during other aspects of the value chain from pick andpack to secondary labeling to shipping. As such, CGT developers
may choose to outsource their ultracold storage and sample
management to a reliable service provider that offers flexibility andscale-up capacity.
Aggressive and changing timelines
Successful logistics for any product requires adherence tocarefully planned timelines—when to pack an item to have it readyfor pickup and when to have it at the airport or other means oftransportation in order to ensure timely delivery to a patient inneed. With standard therapies, this can generally be accomplishedusing standard forecasting and logistics planning methods, butwith CGTs, the timeline is often dependent upon patient readinessand need, which can be unpredictable. Specifically, autologous
cell therapy includes a very limited window of manufacturing anddistribution (“vein-to-vein” time). Allogeneic cell therapy and genetherapy may be similar to biopharma production (e.g., they canbe made in bulk), but they still require late-stage customization.
Working with tight and sometimes moving timelines can befrustrating if processes are not in place to facilitate quick response
and flexibility. Similarly, accommodating and planning for just-intime processes (e.g., manufacturing, packaging, labeling, andshipping) is a crucial capability in CGT supply chain management.

Scale-up requirements
Another challenge for CGT developers and manufacturers centersaround the need to scale up product manufacturing. Simply
adding resources is not sufficient to appropriately expand CGTs
to commercialization. Instead, technological enablement should
be a focus. Commercial scale for CGTs often includes many smalllots, which increases documentation, tracking, and shipping
requirements as well. Innovative approaches to supply chain
logistics are required to manage the full spectrum of challenges
associated with scale-up. Some experts suggest that the industry
may move toward closed manufacturing systems, which would
likely enable decentralization of manufacturing, affecting related
storage and distribution services as well.
Communication challenges
In any complicated process, communication is key to successand avoidance of major hurdles. Many different stakeholders
and service providers work together to ensure that each stepalong the path from clinical to commercialization of a CGT isplanned, performed, and documented appropriately. Tight andshifting timelines make communication even more difficult,but that much more important. A delay in one point of thevalue chain could result in delays in many other areas. Careful,flexible, responsive coordination and communication of activities
is a critical component and a huge challenge of CGT supply
chain management.

Documentation and tracking requirements
Further challenges in CGT supply chain logistics center aroundmaintaining the chain of identity, chain of custody, and chain ofcontrol/condition. These types of documentation and tracking are
critical to the integrity of the materials and the process and should
be kept top of mind among CGT supply chain managers. Chainof identity is particularly important for personalized medicine
where the drug product is made with the patients’ own biologicalmaterial. It is absolutely critical that chain of identity is maintained
during the entire process from clinical to commercial.
In addition, the US Drug Supply Chain and Security Act (DSCSA)3and EU Falsified Medicines Directive (FMD)4 require serialization
for secondary packaging. This requirement increases the securityof the drug distribution supply chain but requires specialized
equipment and software to enable global distribution.
Maintaining chain of control/condition is especially important
for temperature sensitive shipments, requiring temperature andshipment monitoring devices.

2

Potential solutions to cell and gene therapy supply chain
challenges
As technologies evolve, and new challenges emerge, innovative
solutions must be developed to address them. One of themost important strategies to keep in mind when preparing forcommercialization of CGTs is to find an experienced partner who
can support many different aspects of the value chain. Together,you and your supply chain partner should ensure you understandregulatory guidelines associated with CGTs and keep an eye
on the evolving regulatory environments of all geographies ofinterest. Work with a partner who can grow with you, who shares
your focus on patient-centricity, and who has the appetite forthe investment needed to grow with a nascent industry and theflexibility to adjust as new challenges develop.
A successful partnership will also include the provision of or support
to build flexible solutions and just-in-time processes. Additionally, aservice provider should be prepared to offer global solutions whenclients expand globally.

Thermo Fisher’s Advanced Therapy solutions
In addition to Advanced Therapy development and manufacturing,
Thermo Fisher offers a unique and comprehensive approach tosolving current industry challenges in CGT supply chains withmultiple service offerings and a broad team of highly knowledgeable
experts. A thorough understanding of the complexities of these
innovative therapies and the challenges of bringing them to patientsdrives the development of well-defined and carefully managed
processes and services. Below are a few ways Thermo Fisher canhelp address the common pain points listed above.
Ensure product integrity through cold chain logistics expertise
Thermo Fisher Scientific’s Bioservices & Specialty Logistics
business brings 35+ years of experience managing critical biologicalmaterial at ultracold and cryogenic temperatures. The organization
offers more than 400,000 sq. ft. of GMP space for ultracold storage
and distribution, completes more than 400,000 global shipments
annually (36% of which are cold or refrigerated shipments), andhas a proven record of offering logistics solutions for all aspects ofthe cold chain. They operate with a “Zero Temperature Excursion
Mindset” for packaging, labeling, storing, and distributing clinicalsupplies. As such, more than 99% of all their controlled shipments
arrive without temperature excursion. Click here for more informationon cold chain management and mindset at Thermo Fisher.

Adhere and manage timelines with specialized services
Thermo Fisher services help clients minimize risks through perfectly
timed studies, just-in-time processes (e.g., manufacturing, packaging,labeling, and shipping), and dedicated project management support.
Additional time (and cost) savings comes through the Direct-toPatient offering, which includes Direct-to-Clinical Site and Directto-Pharmacy, and through their specialized courier service (with a99%+ on-time pick-up and delivery record). These offerings may
become even more important in the future if technology innovations
lead to a shift toward a decentralized manufacturing and clinical trial
model for CGTs.
Maintain chain of custody/identity with end-to-end solutions
Thermo Fisher has implemented comprehensive processes andverification steps throughout the entire product journey to minimize
the risk of mix-ups and ensure product integrity. Serialization
services in particular create a unique product identity that can betracked from the packaging site through distribution to the hospitalor point of care, and enable compliance with the Drug Supply
Chain and Security Act and Falsified Medicines Directive.
Scale-up with minimized risk through collaboration withexperienced partners
In addition to the above services, Thermo Fisher supports scale-upof CGTs in a manner that centers on optimizing quality, adhering
to regulatory requirements, understanding industry best practices,and leveraging the expertise of highly trained personnel.
All of these offerings, when viewed together, form a comprehensive
solution to many of the industry challenges associated with CGT
supply chains. Finding a partner with end-to-end capabilities(rather than multiple service providers) enables more efficient
movement through each component of the supply chain process,higher confidence in the integrity of the materials being developed
and transported, and easier communication between process
stakeholders. Most importantly, a successful CGT supply chain
allows for better, faster, and more reliable delivery of potentiallylife-changing cell and gene therapies to patients who need them.

References
1. Alliance for Regenerative Medicine. 2021: Regenerative Medicine: Disrupting the Status Quo Annual Report. Available at: http://alliancerm.org/wp-content/uploads/2022/03/ARM_AR2021_FINAL-singles.pdf. Last accessed March 24, 2022.
2. Food & Drug Administration. Expedited Programs for Regenerative Medicine Therapies for Serious Conditions: Guidance for Industry. Available at: https://www.fda.
gov/media/120267/download. Last accessed March 24, 2022.
3. FDA. Drug Supply Chain Security Act (DSCSA). 2022. FDA Website. Available at https://www.fda.gov/drugs/drug-supply-chain-integrity/drug-supply-chain-securityact-dscsa. Last accessed March 24, 2022.
4. European Commission. Falsified Medicines. European Commission Website. https://ec.europa.eu/health/medicinal-products/falsified-medicines_en. Last accessed
March 24, 2022.

3

+1 919 226 3200

• thermofisher.com/patheon • pharmaservices@thermofisher.com© 2022 Thermo Fisher Scientific Inc. All rights reserved.
Published 05/22