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Temperature Indicators for Vaccines

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

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Complexity of the Vaccine Supply Chain

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

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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 Manufacturers 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

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

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Critical Control Points Last mile transportation Vehicle qualification Transportation modes Packaging Handling Doctors office / Hospital Storage coolers Handling

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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

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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: http://www.fiercepharmamanufacturing.com/story/mds-voice-concerns-over-cold-chain-breaches-effects-drugs/2010-06-22#ixzz2ZAogxvjKhttp://www.fiercepharmamanufacturing.com/story/mds-voice-concerns-over-cold-chain-breaches-effects-drugs/2010-06-22#ixzz2ZAogxvjK

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Solutions to Cold Chain Concerns

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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

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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

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Benefits Quality Control 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

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WarmMark 2 and ColdMark 2

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WarmMark 2 & ColdMark 2 Single-use, single temperature threshold indicators Field-armable Easy-to-read with a definitive color change Accurate & affordable Identifies out-of-tolerance temperature conditions

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How WarmMark 2 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

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How ColdMark 2 Works Patented activation allows ColdMark 2 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

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Cold Chain Complete Combines WarmMark 2 and ColdMark 2 products into a single package Monitors for out-of- refrigeration conditions Available in four variations: 0C 8 C 0C 10 C 2C 8 C 2C 10 C

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Return on Investment Example Costs not captured that may be reduced with monitoring program: Administration feesAudits / Regulatory Fines Replacement logisticsPotential Litigation

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Quality and the Validation Process

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Quality Product WarmMark 2 and ColdMark 2 are subjected to rigid quality processes Certificate of conformance sent with every shipment Release documents available upon request Internal validation processes in place 3 rd -party validation conducted

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How to Use

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Product Demos

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WarmMark2 Demo

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ColdMark2 Demo

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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.

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Vaccine Cold Chain Overview

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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 +2C to + 8C, 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 elses responsibility

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Drivers for Ensuring an Effective Cold Chain Source: http://coolchain.org/cool-logistics-for-pharma-healthcare-surveyhttp://coolchain.org/cool-logistics-for-pharma-healthcare-survey Over 300 pharmaceutical executives responded to a survey in September 2012 and prioritized their cold chain drivers

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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

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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

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Vaccine Values Polio / Measles (1980) 4000 doses @ $500 Rotavirus (2010) 600 doses @ $3500

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

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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?

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Unit Level Or Case Level Monitoring WM 2 measures the cumulative time exposure above a selected threshold Need to develop some guidance on monitoring on the unit or case level

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WarmMark 2 Benefits Accuracy Temperature accuracy of +1C 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

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ColdMark 2 Benefits Accuracy Temperature accuracy of +1C 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

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Sources http://www.logisticsmgmt.com/view/3pl_manage ment_conquering_the_cold_chain/3pl http://www.logisticsmgmt.com/view/3pl_manage ment_conquering_the_cold_chain/3pl http://coolchain.org/cool-logistics-for-pharma- healthcare-survey http://coolchain.org/cool-logistics-for-pharma- healthcare-survey