1. Temperature Indicators for Vaccines

2. ShockWatch Cold Chain Solutions
Increasing Value to Customer
Intelligent Monitoring System
TrekView
ColdMark2
WarmMark2
Real-time Monitoring
Performance
Multi-use recorder
Single use
Low cost
Go – No/Go
Data Recorders
ColdMark
WarmMark
Chemical Indicators
Price

3. Complexity of the Vaccine Supply Chain

4. Extreme Temperatures in the Supply Chain
AIR CARGO
-20oC
OVER THE ROAD
43oC
WAITING ON THE TARMAC
32oC
OCEAN FREIGHT

5. Vaccine Supply Chain
Manufacturers are focused on the production of safe and effective vaccines
When product leaves the manufacturer, there is a loss of visibility and control over its safety and efficacy
Quality agreements are required for the hand-off points in the supply chain
Manufacturer’s name is on the line even after product leaves their facility
Wholesalers must abide by quality agreements established with manufacturers but not governed by the FDA
Frequently reuse packaging materials
Work on very low margins

6. Critical Control Points
Manufacturing Site
Short-term storage
Packaging design
Transportation modes
Third-Party Logistics
Vehicle qualification
Handling
Wholesaler
Storage Coolers
Effects of opening and closing the refrigerator door
Repackaging / Reuse of packaging

7. Critical Control Points
Last mile transportation
Vehicle qualification
Transportation modes
Packaging
Handling
Doctor’s office / Hospital
Storage coolers

8. Vaccine Last Mile Last mile is the most challenging
Not always known if temperature control has been maintained in the previous supply chain segments
Vaccine clinics, doctors offices are not always equipped to maintain appropriate temperature control
US Department of Health & Human Services’ Office of the Inspector General reported that approximately 44,000 doctors offices and clinics participating in the Vaccines for Children Program (VFC) did not store vaccines at suitable temperatures

9. Last Mile Concerns
3 in 5 surveyed physicians are "very concerned" that cold chain breaches will compromise the efficacy of the drugs they prescribe
More than 50% cite concerns about serious adverse effects due to poor cold chain management
Harris Interactive survey finds that more than 83% of primary care doctors report experiencing a cold chain break
Specialist doctors report more cold chain breaks during product delivery as products reach their offices
Primary care doctors and pediatricians, on the other hand, report more storage-related cold chain breaks for products stored in their offices
Source:

10. Solutions to Cold Chain Concerns

11. Validation vs. Monitoring
Validation is used to demonstrate that the appropriate equipment and processes are in place to maintain temperature control
What happens in the real world?
People are in a rush
Handing errors occur
Packaging / coolers are damaged
Equipment failures occur
Validation is a great starting point, but it does not eliminate the need to monitor

12. Why Use Temperature Indicators?
Vaccine shipments can exceed 1000 shipments per day
Packaging usually validated for large quantities
Low cost temperature indicators used as back up in validated packaging
Low volume shipments from bio-techs & clinical trials
Recorders / indicators in shipments for non-validated shippers
Recorders / indicators for temperature-controlled transport vehicles
Provides the ability to make important decisions on whether to use or discard vaccines
Provides the ability to make important decisions on which vaccines should be used first

13. Benefits Quality Control Cost Savings Easy Decision Making
Temperature-damaged vaccines unknowingly delivered to patients
Allows developing country users to safely administer vaccines, despite potential cold chain interruption
Cost Savings
Good vaccines thrown out due to lack of knowledge about actual exposure (or lack of exposure)
Helps to facilitate the creation of new policies on handling of multi-dose vaccines
WHO estimates that the use of temperature indicators could reduce wastage rates by up to 30%
Source: Frost, Laura J., and Michael R. Reich. Access: How do good health technologies get to poor people in poor countries?. Harvard Center for Population and Development Studies, 2008.
Easy Decision Making
Users can quickly tell which vaccines are safe for use

14. WarmMark2 and ColdMark2

15. WarmMark2 & ColdMark2
Single-use, single temperature threshold indicators
Field-armable
Easy-to-read with a definitive color change
Accurate & affordable
Identifies out-of-tolerance temperature conditions

16. How WarmMark2 Works
Patented process diffuses a blue liquid across the window in the label in a controlled and repeatable way - which means it can be used to measure the length of time since activation.
Inactive: liquid in blister, awaiting activation
Armed: blister squeezed, ON in Indication window lets you know the WarmMark®2 is now active
Activated: after exposure to temperatures above the threshold, the blue dye will progress over time through the indication window and can be read against the printed time scale
Stopped: progression of dye will stop when temperature drops below threshold

17. How ColdMark2 Works
Patented activation allows ColdMark2 to be armed prior to use. With a below-temperature threshold event, the indicator will turn red allowing you to know you had a cold chain breach.
Inactive: liquid in blister, awaiting activation
Armed: blister squeezed, RED in Indication window lets you know the ColdMark®2 is armed
Activated: after exposure to temperatures below the threshold temperature for 30 minutes or less, red dye will appear in indication window

18. Cold Chain Complete
Combines WarmMark2 and ColdMark2 products into a single package
Monitors for out-of-refrigeration conditions
Available in four variations:
0°C – 8° C
0°C – 10° C
2°C – 8° C
2°C – 10° C

19. Return on Investment Example
Costs not captured that may be reduced with monitoring program:
Administration fees
Audits / Regulatory Fines
Replacement logistics
Potential Litigation

20. Quality and the Validation Process

21. Quality Product
WarmMark2 and ColdMark2 are subjected to rigid quality processes
Certificate of conformance sent with every shipment
Release documents available upon request
Internal validation processes in place
3rd-party validation conducted

22. How to Use

26. Product Demos

27. WarmMark2 Demo

28. ColdMark2 Demo

29. Internal Training Note: These slides are to help Sales and distributors better understand the market. They can be integrated into a customer presentation where appropriate.

30. Vaccine Cold Chain Overview

31. Misconceptions About the Vaccine Cold Chain
The following statements are NOT accurate:
Vaccines are robust products that can tolerate heat and cold
Vaccines are free or inexpensive
Warming vaccines is more harmful than freezing them
Vaccines that have been frozen always look frozen, solid or changed
Vaccine refrigerators look after themselves
Refrigerators storing vaccines require a low level of maintenance
During refrigerated transit or storage, if the thermometer shows a temperature outside +2°C to + 8°C, there must be something wrong with the thermometer
The temperature throughout a refrigerator is the same
Refrigerators cannot reach freezing temperatures
Cold chain management is someone else’s responsibility

32. Drivers for Ensuring an Effective Cold Chain
Over 300 pharmaceutical executives responded to a survey in September 2012 and prioritized their cold chain drivers
Source:

33. Regulations
United States Pharmacopeia (USP) 1079 sets the standards for storage and distribution practices of healthcare products in the United States and is recognized by many countries around the world
World Health Organization (WHO) issued QAS/4.068 on Good Distribution Practices in order to ensure the integrity of pharmaceutical products during the distribution process
Parenteral Drug Association (PDA) published cold chain guidance reports
Technical Report 39 – Guidance for Temperature-Controlled Medicinal Products, Maintaining the Quality of Temperature-Sensitive Medicinal Products through the Transportation Environment
Technical Report 46 – Last Mile: Guidance for Good Distribution Practices for Pharmaceutical Products to the End User
Country-Specific Regulations
Many countries have specific regulations / guidelines that govern maintenance of the cold chain

34. Vaccine Development
335 new infectious diseases emerged between 1940 and 2005
Typical development time for new therapy is 10 – 15 years with an average development cost of more than $1.2B

35. Vaccine Values Polio / Measles (1980) 4000 doses @ $500 Rotavirus

36. Temperature Control of Vaccines
By 2015, 8 of 10 global pharmaceutical products will require 2° – 8°C storage & handling
Effective cold chain practices are needed to maintain the efficacy of vaccines

37. Is there a need for monitoring?
Is the product temperature-sensitive?
What are the thresholds?
Will multiple temperature products be shipped together?
How many indicators are needed?
How long will the indicator need to work?
What is the ambient temperature at the time the indicator / recorder is installed?
Will the package be opened / repackaged?
What is the ambient temperature when the indicator is read?
What else needs to be considered?

38. Unit Level Or Case Level Monitoring
WM2 measures the cumulative time exposure above a selected threshold
Need to develop some guidance on monitoring on the unit or case level

39. WarmMark2 Benefits Field-armable The word ON appears when device armed
Accuracy
Temperature accuracy of +1°C
No false activations from human handling
Quality
Certificate of conformance with every shipment
Heat-sealed to prevent bleeding
Tamperproof
Release documents available upon request
Easy to Read and Use
Field-armable
The word ON appears when device armed
Traceability
Unique identifiers assist tracking
Product is lot-traceable

40. ColdMark2 Benefits Accuracy Temperature accuracy of +1°C
Accurate response time
Quality
Certificate of conformance with every shipment
Tamperproof
Release documents available upon request
Easy to Read and Use
Field-armable - requires no special packaging or overnight shipping
Window on device shows it has been armed
Traceability
Unique identifiers assist tracking
Product is lot-traceable

41. Sources