1. Precious Cargo
Monitoring New Parameters With Today’s SMART
Shippers - Potential Impacts to Your Therapy
Heidi Crawford, M.B.A., B.S.M.E.
BioLife Solutions
October 6, 2016
2. Agenda
• Current regenerative medicine and cell therapy cold chain challenges
• Current industry solutions and challenges
• Best practices and emergence of SMART shippers
• BioLife Solutions and Brooks Life Sciences scientific study
• Conclusions
1
3. 2
Current Biologistics Reality
All vaccines
and 70% of
biologics are
temperature
sensitive.
Stability of
traditional
containers is
limited.
Cell viability
declines.
Lost and
unusable doses
result.
Regenerative
medicine
therapies
require precise
thermal
protection in
shipment.
Use of real-
time
temperature
monitoring and
reporting
during
shipment is
limited.
TIME
4. 3
Biologistics Risks
EconomicClinical
Administering a thermally
sensitive biologic dose that:
• was exposed to unknown
temperature excursions
• was exposed to pack out
errors
• has exceeded its stability
period
Cost of scrapping biologic
source material or manufactured
cell products
Clinical trial impact from poor
biologistics management:
• lost dose
• poor shipping container
performance
• temperature excursions
Rx $
6. Common Shipping Options
• Old technology
• Poor performance
• Single use
5
Foam Coolers
Data Loggers
Vacuum Panel Shippers
Liquid Nitrogen Dry Shippers
• Records container, not
payload temperature
• Data reviewed after
clinical product is used
• Overly complex
• Heavy, expensive to ship
• Prone to pack out errors
• Significant variations can
occur among shippers
• Heavy, expensive to ship
• Some difficulty or delay in
shipper returns
7. Regenerative Medicine Biologistics Needs
Regenerative medicine ships a
variety of products…
• Apheresis units
• Tissues
• Cell-based Products
• Other
… at a variety of temperatures
• Controlled Room
Temperature
• 2-8 degrees C
• Dry Ice
• LN2
6
“Erin Cross begins lifesaving therapy in Seattle.“
-- Chester and Cheshire News, July 28, 2016
8. Regenerative Medicine Cold Chain Challenges
Dry Ice Example
• Temperatures vary across
payload areas
• High value payloads can move as
dry ice sublimates, making cells
vulnerable to temperature
excursions
• May need to chisel out sample
• Forgotten or inactive data logger
produces no data
• No chain of custody, tilt or location
tracking
• No alerts to stakeholders for
active shipments
• Risk of loss or of reduced cell
viability
7
9. Industry SMART Shipper Solutions
Benefits
• Precious payload secured in stable position
• Integrated sensors and electronics
• No temperature stratification across payload.
All within 1 degree C.
• Temperature, chain of custody, tilt and
location tracking
• Tracks shipment data both en route and
historically through software
• Real-time SMS and email alerts sent to any
stakeholder
8
11. Question
• There is generally accepted knowledge on temperature effects when
shipping small molecules.
• There is generally accepted knowledge of temperature effects for
pharmaceuticals and biologics.
– ex: Humira, Enbrel, etc.
• We know intuitively that cells, in general, are more susceptible to
temperature and temperature excursions.
• BUT: There are limited defining studies on temperature variations in
the cold chain and effects on cells.
BioLife and Brooks commenced a small study to observe temperature
variations and potential effects on cells shipped via cold chain.
10
13. Objective
The quality of procedures and products used for preparing, transporting
and storing cells at cryogenic temperatures have a direct impact on the
post-thaw viability and functionality of the cells. Sub-standard
preparation, handling, storage, and products may subject cells to
improper cryoprotectant exposure. Inadequate transport packaging and
negligent shipping practices can cause variability in product
temperatures and unknown transient warming events throughout the
handling, storage and logistics chain. This can negatively impact the
viability, recovery and functionality of sensitive cells and therapies.
The objective of this study is to compare two methods of preparing,
transporting and storing living cells (Cold Chain) to achieve the highest
post-thaw viability. One method is intended to show an optimized cold
chain and improved best practice, the other is considered current
common practice. The outcome of this study recommends best practices
for procedures and products to ensure consistency, visibility, and
documented control of the cold chain.
12
15. Ambient Payload Temperature
in BioLife to Brooks Outbound Route
• Events such as “shipper opened” recorded for customer.
• Full ambient temperature profile available throughout shipment to
correlate with events.
14
16. Internal Payload Temperature in
BioLife to Brooks Outbound Route
• Temperature held well below – 70 degree C cell health threshold, at
-76 to -81 degrees C for 2 days.
• Events such as “shipper opened” tracked for correlation with effect
on payload temperature.
15
18. BioLife/Brooks Study Results for
Jurkat T-Cells (1 of 2)
• There was similar recovery in
all samples.
% Recovery % Viability
• Cells in the DMSO/EPS group
experienced significant decline in
viability post thaw (membrane integrity
as determined by Trypan Blue
Exclusion.)
• Cells in CryoStor/evo group did not
lose viability during transport and were
statistically similar to non-shipped
controls.
17
19. Brooks/BioLife Study Results
for Jurkat T-Cells (2 of 2)
• Cells in the DMSO/EPS group experienced a significant delay in
functional recovery at 48 hours.
• Cells in the CryoStor/evo group experienced a more rapid rise in
metabolic function, identical to non-shipped controls at all time
points.
alamarBlue Fluorescence
18
20. • Jurkat T-cells frozen in CryoStor CS5 were similar to, but exhibited
less baseline variability, than reference ‘home-brew’ cryomedia.
• Jurkat T-cells frozen in traditional 95/5% cryomedia and shipped in
an EPS container experienced a significant decline in viability
immediately post thaw and a delayed return to function 48 hours
post-thaw.
• The combination of CryoStor CS5 and the CRYO evo smart shipper
afforded superior protection from cryopreservation and transportation
stress with no measurable decline in structural and functional viability
as a result of freezing, thawing and two cross-country transit events.
Conclusions (1 of 2)
19
21. • The CRYO evo smart shipper and biologistexTM cloud-based
shipment application allow real-time status, tracking and event
alarms throughout the entire shipping process, permitting enhanced
tracking and knowledge of any environmental excursions as they
happen.
• The design of the CRYO evo smart shipper prevented warming from
dry ice sublimation and maintained the Jurkat T-cells within the
desired temperature range throughout transit.
Conclusions (2 of 2)
20
This shows air travel from Seattle to Louisville KY to Boston. The ambient temperature fell well below -15 degrees C with gas escaping inside of the shipping box.
Aboard the aircraft the pressure and temperature decreased.
