Overview In many clinical trial scenarios, there may only be one chance to collect, ship, test and analyze a patient's specimen. These often time-sensitive snapshots into a patient's progression in a study are critical not only to the overall study results, but ultimately the safety of patients undergoing treatment. The lifecycle of a specimen, which starts at collection and ends at database lock, can be prone to human error along each step of the testing process, particularly when conducting global clinical trials in more remote ends of the world. Sponsors need to ensure the integrity of the specimen throughout this process, while balancing the relative cost of logistics. Based on lessons learned from managing global clinical trials testing, ACM Global Lab and its partners will share their insights on monitoring and oversight on patient safety, safeguarding sample integrity, and good business sense.

1. 1

2. An Innovative Approach to Handling Cold
Chain Clinical Trial Material in the
Transportation Channels
Larry G. Stambaugh
Chairman & CEO
CryoPort, Inc.
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3. Today – Frozen Shipping for the New Global
Requirements in Clinical Trial Specimens
• Frozen shipping is dominated by dry ice and the
paradigms established by its limitations
• Specialty couriers have been widely used to globally
transport dry ice
• Freight forwarders have not been willing to provide re-
icing services
• Most trials have been run in the U.S. and Western
Europe
• Biologicals have played a smaller role in products and
drug development in the past
• Moving products and samples has gotten more
difficult in today’s new norm for global
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4. New Forces Working on Global
Cold Chain
• Globalization of products and clinical trial markets are
stretching the current standard options and raising new
concerns
• Growing regulatory concern about proving cold chain
integrity and security
• More biologicals in development today than ever before
• Emphasis on improving security and sustainability in
cold chain processes
4

5. Globalization of transportation of frozen
biologicals and products
There are 110,965 clinical trials listed in 174 countries today *
As of July 2011 the global trials breakdown as follows:*
• United States 55,548
• Western Europe 28,408
• China 8,352
}
• Canada 8,471
• Latin America 6,522
• Southeast Asia / Australia 5,238
• Middle East 41,008 4,318
• Africa 2,381
• Japan 1,917
• Eastern Europe 1,920
• India 1,889
*clinicaltrials.gov
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6. Explosive Growth in Cold Chain
Segment of Clinical Trials
Growth projected 2012 - 2015 in cold chain*
– US 15%
– Europe 18%
– Asia 43%
– Rest of world 59% (Brazil, Eastern Europe, Middle East)
*Biopharma cold chain Sourcebook 2011
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7. Significant Trends in Pharmaceutical Development
• More biologicals in development today than ever before –
more than 400 *
• Of 15 drug approvals in the U.S. for new molecular entities during
2010, 11 were biologicals**
• Unprecedented trend toward outsource clinical development to CROs,
Central Labs and others
• First time that regulatory approvals of new drugs in Europe exceeded
the U.S.
• Companies starting to look at first approvals in China and Middle East
*BioPharma Cold Chain Source Book
** Pharma.org – new drug approvals in 2010
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8. More Challenges for Frozen Shipping
• Increase in stem cells, cell lines, cell banks, in-vitro
fertilization, vaccines, etc.
Biologists report up to 40% loss of cells during transportation
• High value and volatile biologicals
Values can range from $1,000 to $5,000 for many of the biological shipments
today
• Pressure on costs of product distribution and clinical
development
Overnight shipping expensive and increased global shipping is raising costs
• Data monitoring needed to prove integrity and security
Temperature excursions hard on biologicals
Constant track and trace often ineffective today
Regulatory scrutiny of temperatures a new focus
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9. The New Norm
• Terrorists alerts and grounded planes
• Volcano disruptions
• Suspicious packages delays
• Custom increased scrutiny
• Sophisticated counterfeiting of drug products
• Changing regulations and permits required
• More limited routes by carriers
• Limiting dry ice volume per plane
• Outsourcing of non core processes required
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10. The Future of Frozen Shipping for the
New Global Requirements in Clinical Trial Materials
and Pharmaceutical Products
Longer holding times for packaging alternatives and new
technologies needed for global shipments:
Dry Ice sublimates daily – requires specialty carriers
LN2 dry vapor provides longer holding times up to 10+ days
Gel Packs and phase change materials provide longer holding
times
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11. The Future of Frozen Shipping for the New Global
Requirements in Clinical Trial Materials and
Pharmaceutical Products, cont.
Stable temperatures, eliminating temperature excursions are
necessary for most biologicals
Dry ice (-70 C) fluctuates with re-icing and other conditions
LN2 dry vapor provides a stable constant temperature
(-150 C - below the glass point)
Phase change materials provide variable temperature ranges
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12. The Future of Frozen Shipping for the New Global
Requirements in Clinical Trial Materials and
Pharmaceutical Products, cont.
Temperature monitoring that verifies integrity and security of
samples and products
Specimen or product temperature monitoring is difficult with dry
ice – probes used to monitor box not samples
Specimen chamber temperature monitoring is possible with LN2
dry vapor and some phase change materials
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13. The Future of Frozen Shipping for the New Global
Requirements in Clinical Trial Materials and
Pharmaceutical Products, cont.
Temperature monitoring that verifies integrity and security of
samples and products, continued
Data monitors generally track temperature only
New monitors will track:
• Temperature
• Humidity
• Shock and vibration
• Pressure
Monitors may be used to manage security by detecting tampering
during shipment.
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14. The Future of Frozen Shipping for the New Global
Requirements in Clinical Trial Materials and
Pharmaceutical Products, cont.
Shipping solutions will better utilize “green” sustainable
materials and processes
Dry Ice is considered dangerous goods shipping and it is shipped in
Styrofoam / EPS boxes that are excluded from landfills
New technologies such as LN2 dry vapor and phase change
materials introduce non hazardous shipping and recyclable
materials
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15. The Future of Frozen Shipping for the New Global
Requirements in Clinical Trial Materials and
Pharmaceutical Products, cont.
Business models that facilitate full outsourcing of the frozen
shipping solution desirable
Solutions that provide outsourced capabilities to manage frozen
shipping in connection with Good Distribution Processes
Expertise in complying with country by country rapidly changing
custom and permit requirements in global shipping
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16. Other Possibilities Through Innovation
Rethinking Frozen Supply Chain
• Shipping products and collecting clinical samples five days a
week
• Two day shipping rather than overnight
• Using shipping container as temporary storage device
• Wireless temperature monitoring
• More cost effective outsourcing of cold chain transportation
• Eliminate risk of loss of sample viability due to degradation
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17. The Future of Frozen Shipping for the New Global
Requirements in Clinical Trial Materials and
Pharmaceutical Products
• Longer holding times for packaging alternatives
• Stable temperatures, eliminating temperature excursions
• Improved processes to address customs, permits and
increasing regulations
• Temperature and data monitoring that verifies integrity and
security of samples and products
• Compliance with good distribution practices by outsourced
partners
• Sustainable processes that eliminate hazardous materials and
non recyclable materials
• Shipping five days a week and two day shipping
• Cost effective outsourcing of shipping process
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18. CryoPort Express® – Setting a New Standard
Enter order through CryoPort’s CryoPort Express® proprietary Package received and
Express® Portal which manages container arrives ready to ship unloaded; simply flip box flaps,
complexities of all required legs with all required docs and no and send to CryoPort for reuse
of transit hazmat handling
Preparation In-Transit Post-Shipment
 Technology-rich web portal  10 day holding time allows much greater  Data logger tracks temperature
streamlines ordering and flexibility and no re-icing throughout shipment, ensuring integrity
ensures successful shipment  Stable -150 degree celsius ensures of sample and detection of tampering
 Easy to use dry vapor LN2 condition of specimen throughout transit  Simply return shipper to CryoPort - no
shipper arrives charged with  Integrated carrier solution allows for environmentally unfriendly packaging to
required documentation greater control of shipment progress dispose of
 Non-hazardous shipping and – In transit updates and alerts available  CryoPort dry vapor LN2 shipper is tested,
handling through portal and sterilized for next shipping cycle
 Reliable, outsources frozen shipping
solution
CryoPort’s Express® Offers a Simpler Method with More Reliability for Less Cost
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19. Questions?
Thank you
• Larry G. Stambaugh
• Chairman & CEO
• CryoPort, Inc.