1. 7/21/06CliniSense Corporation1 Stephen E. Zweig, Ph.D. CEO, CliniSense Corp. Advances in drug stability monitoring

2. 7/21/06CliniSense Corporation2 A chain is as strong as the weakest link Problems can potentially occur at any time during storage, causing “hidden damage” Manufacturer’s responsibility doesn’t just stop on initial delivery – it continues until the product is actually used!

3. 7/21/06CliniSense Corporation3 Where hidden problems can occur Initial shipment: between different storage sites, each with separate temperature recorders In the health care facility – Receiving – Transport to one or more storage sites – Transport to point of care site – Transport to patient – Time delay before administration – Patient mishandling of drug delivery devices

4. 7/21/06CliniSense Corporation4 Biotherapeutics are delicate drugs Much larger and more complex than traditional pharmaceuticals Composed of unstable proteins with a precise structure Easily damaged by unfavorable temperature history during storage

5. 7/21/06CliniSense Corporation5 Even insulin has temperature problems Insulin is a very temperature stable biotherapeutic A graph of storage life vs temperature shows a “saw tooth” peak The product dies at both temperature extremes Insulin Shelf-life 0.1 1 10 100 1000 -200204060 Temperature (C) Months

6. 7/21/06CliniSense Corporation6 Effect of temperature storage extremes < 0 o C Freezing Protein denaturation Formation of aggregates Loss of functional activity Formation of potentially hazardous immunogenic byproducts > 8 o C Chemical side reactions Protein denaturation Formation of aggregates Loss of functional activity Formation of potentially hazardous immunogenic byproducts

7. 7/21/06CliniSense Corporation7 Smart packaging vs dumb packaging Smart packaging can guard against human errors in handling, and accidental temperature abuse. Is traditional dumb packaging simply a relic from an earlier era? Does it pass modern failure modes analysis?

8. 7/21/06CliniSense Corporation8 An ideal storage monitor: Accurate and effortless to read Show remaining life (gas gauge-like display) Outs thermal history record upon request

9. 7/21/06CliniSense Corporation9 Previous time-temperature monitors Chemical indicators are not flexible or accurate Electronic temperature loggers are accurate, but don’t show shelf-life. Temperature alarms only show extreme “out of bounds” conditions Chemical Electronic

10. 7/21/06CliniSense Corporation10 LifeTrack™ Technology Monitors and analyzes temperature history Custom programmed to exactly match the sensitivity curve of any pharmaceutical Instantly shows all types of temperature abuse LifeTrack RFID LifeTrack technology demonstrator

11. 7/21/06CliniSense Corporation11 The stability bank algorithm Small # of withdrawals per hour High # of withdrawals per hour Stability bank "B" Low temperature High temperature

12. 7/21/06CliniSense Corporation12 Stability calculation example B = 165984 – Σ P(temperature) 0 time

13. 7/21/06CliniSense Corporation13 Sample LifeTrack profiles Each different stability profile produces a different P(temp) function

14. 7/21/06CliniSense Corporation14 Evaluating LifeTrack technology Is our stability data adequate? Customers like? FDA requirements? How can I do a quick feasibility test?

15. 7/21/06CliniSense Corporation15 LifeTrack Technology Demonstrator +/- good bad display Lifetime bar Infrared LED Battery door Programming & expansion Port Battery (3 yr life) Thermistor

16. 7/21/06CliniSense Corporation16 Inside the unit Low-cost electronics Simple construction Designed for high production volumes Digital watch example – Modules cost < $1.00 – Ultimate costs in $2.00 to $3.00 range

17. 7/21/06CliniSense Corporation17 LifeTrack Demonstrator Display Shows “+” when product is good, “-” when product has expired Lifetime indicator bars decrease as the lifetime is used up

18. 7/21/06CliniSense Corporation18 Programming a unit Enter the stability data into an Excel spreadsheet model Transfer parameters to LifeTrack program Load LifeTrack program into LifeTrack device

19. 7/21/06CliniSense Corporation19 Demonstrator Data Output Downloads temperature statistical data via IR cable to an RS232 port Only one bit needed to tell good/not good, additional bits tell you how and why Highly compatible with the limited data transmitted by RFID tags

20. 7/21/06CliniSense Corporation20 Data output example: The entire relevant history record in only 150 bytes Statistics Product NameGeneric Biotherapeutic name Product IDABCDE123456789 StatusExpired Security code OK Hours elapsed130 Hours since expired30 Avg. PreExp temp5.85 o C Standard deviation4.72 o C Avg. PostExp temp25 o C Standard dev0 o C Material: Biotherapeutic ID: 12345678

21. 7/21/06CliniSense Corporation21 Using LifeTrack Technology Provide biotherapeutic stability data for multiple temperatures (e.g < 0, 4-8 o C, 25 o C, etc.) CliniSense will generate one or more provisional algorithms, request approval, and return flash programmed LifeTrack technology demonstrator units for evaluation within a few days CliniSense will work with you to embed this technology into your preferred drug delivery device or other type platform, license as needed

22. 7/21/06CliniSense Corporation22 Smart biotherapeutic packaging LifeTrack detects deteriorated product Can be embedded into drug delivery devices Accurate and easily customized LifeTrack RFID LifeTrack technology demonstrator Drug delivery devices

23. LifeTrack TM Technology Detects all types of improper storage LifeTrack RFID LifeTrack technology demonstrator Injection pens

24. 7/21/06CliniSense Corporation24 Recent publications Zweig SE: Advances in vaccine stability monitoring technology, Vaccine, 2006 (in press) Zweig SE: 21 st century electronics for 21 st century drugs, Drug Delivery Reports, Spring/Summer 2006 Zweig SE: From Smart Tags to Brilliant Tags: Advances in Drug Stability Monitoring, BioPharm International, November 2005, 36-44. Zweig SE: Technologies for monitoring IVD stability, IVD Technology 10(5) 59-63, June 2004

25. 7/21/06CliniSense Corporation25 Recent patents Patent 6,950,028, Electronic Time-Temperature Indicator Patent 7,096,090, Electronic time-temperature indicator and logger (basis for PCT filings) Patent application 10/747,926 (pending) Method and device to reduce therapeutic protein immunogenicity

26. 7/21/06CliniSense Corporation26 For more information CliniSense website (www.clinisense.com) has many exampleswww.clinisense.com Demo units available Feel free to call (408) 348-1495 and ask questions