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

7/21/06 CliniSense Corporation 1

Stephen E. Zweig, Ph.D.Stephen E. Zweig, Ph.D.

CEO, CliniSense Corp.CEO, CliniSense Corp.

Advances in drug stability Advances in drug stability monitoringmonitoring


A chain is as strong as the weakest A chain is as strong as the weakest linklink

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!


Where hidden problems can Where hidden problems can occuroccur

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


Biotherapeutics are delicate Biotherapeutics are delicate drugsdrugs Much larger and more

complex than traditional pharmaceuticals

Composed of unstable proteins with a precise structure

Easily damaged by unfavorable temperature history during storage


Even insulin has temperature Even insulin has temperature problemsproblems

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

-20 0 20 40 60

Temperature (C)

Mon

ths


Effect of temperature storage Effect of temperature storage extremesextremes

< 0o C

Freezing Protein denaturation Formation of aggregates Loss of functional activity Formation of potentially

hazardous immunogenic byproducts

> 8o C

Chemical side reactions Protein denaturation Formation of aggregates Loss of functional

activity Formation of potentially

hazardous immunogenic byproducts


Smart packaging vs dumb Smart packaging vs dumb packagingpackaging

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?


An ideal storage monitor:An ideal storage monitor:

Accurate and effortless to read

Show remaining life

(gas gauge-like display)

Outs thermal history record upon request


Previous time-temperature Previous time-temperature monitorsmonitors

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


LifeTrack™ TechnologyLifeTrack™ 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


The stability bank algorithmThe stability bank algorithm

Small # of withdrawals per hour

High # of withdrawals per hourStability bank

"B"

Low temperature

High temperature


Stability calculation exampleStability calculation example

B = 165984B = 165984 – – ΣΣ P(temperature) P(temperature)

Stability points per hour

1

10

100

1,000

10,000

100,000

1,000,000

-20 0 20 40 60Temperature (C)

Poi

nts

Insulin Shelf-life

0.1

1

10

100

1000

-20 0 20 40 60

Temperature (C)

Mon

ths

0

time


Sample LifeTrack profilesSample LifeTrack profiles

Each different stability profile produces a different P(temp) function


Evaluating LifeTrack technologyEvaluating LifeTrack technology

Is our stability data adequate?

Customers like?

FDA requirements?

How can I do a quick feasibility test?


LifeTrack Technology LifeTrack Technology DemonstratorDemonstrator

+/- goodbad display

Lifetimebar

InfraredLED

Batterydoor

Programming& expansionPort

Battery(3 yr life)

Thermistor


Inside the unitInside 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


LifeTrack Demonstrator DisplayLifeTrack Demonstrator Display

Shows “+” when product is good, “-” when product has expired

Lifetime indicator bars decrease as the lifetime is used up


Programming a unitProgramming a unit

Enter the stability data into an Excel spreadsheet model

Transfer parameters to LifeTrack program

Load LifeTrack program into LifeTrack device


Demonstrator Data OutputDemonstrator 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


Data output example: Data output example: The entire relevant history record in only 150 The entire relevant history record in only 150

bytesbytes

Statistics

Product Name Generic Biotherapeutic name

Product ID ABCDE123456789

Status Expired

Security code OK

Hours elapsed 130

Hours since expired 30

Avg. PreExp temp 5.85 oC

Standard deviation 4.72 oC

Avg. PostExp temp 25 oC

Standard dev 0 oC

0

5

10

15

20

25

30

-100 -80 -60 -40 -20 0

History before expiration (hours)

Tem

pera

ture

Material: Biotherapeutic ID: 12345678


Using LifeTrack TechnologyUsing LifeTrack Technology

• Provide biotherapeutic stability data for multiple temperatures (e.g < 0, 4-8o C, 25o 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


Smart biotherapeutic packagingSmart biotherapeutic packaging

LifeTrack detects deteriorated product

Can be embedded into drug delivery devices

Accurate and easily customized

LifeTrack RFID


Drug delivery devices

LifeTrackLifeTrackTM TM TechnologyTechnology

Detects all types of improper storage

LifeTrack RFID


Injection pens


Recent publicationsRecent publications

Zweig SE: Advances in vaccine stability monitoring technology, Vaccine, 2006 (in press)

Zweig SE: 21st century electronics for 21st 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


Recent patentsRecent 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


For more informationFor more information

CliniSense website (www.clinisense.com) has many examples

Demo units available

Feel free to call (408) 348-1495 and ask questions

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

Documents

Transcript of 7/21/06CliniSense Corporation1 Stephen E. Zweig, Ph.D. CEO, CliniSense Corp. Advances in drug...