Transcript LifeTrack Biotherapeutics

Advances in drug stability monitoring
Stephen E. Zweig, Ph.D.
CEO, CliniSense Corp.
7/21/06
CliniSense Corporation
1
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!
7/21/06
CliniSense Corporation
2
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
7/21/06
CliniSense Corporation
3
Biotherapeutics are delicate drugs
7/21/06

Much larger and more complex
than traditional
pharmaceuticals

Composed of unstable proteins
with a precise structure

Easily damaged by unfavorable
temperature history during
storage
CliniSense Corporation
4
Even insulin has temperature problems

Insulin Shelf-life
Insulin is a very temperature
stable biotherapeutic
1000

A graph of storage life vs
temperature shows a “saw
tooth” peak
Months
100
10
1

The product dies at both
temperature extremes
0.1
-20
0
20
40
60
Temperature (C)
7/21/06
CliniSense Corporation
5
Effect of temperature storage extremes
< 0o C
> 8o C
Freezing
 Protein denaturation
 Formation of aggregates
 Loss of functional activity
 Formation of potentially
hazardous immunogenic
byproducts

7/21/06
Chemical side reactions
 Protein denaturation
 Formation of aggregates
 Loss of functional activity
 Formation of potentially
hazardous immunogenic
byproducts

CliniSense Corporation
6
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?
7/21/06
CliniSense Corporation
7
An ideal storage monitor:

Accurate and effortless to
read

Show remaining life (gas
gauge-like display)

Outs thermal history
record upon request
7/21/06
CliniSense Corporation
8
Previous time-temperature monitors

Chemical indicators are
not flexible or accurate

Electronic temperature
loggers are accurate, but
don’t show shelf-life.

Chemical
Electronic
Temperature alarms only
show extreme “out of
bounds” conditions
7/21/06
CliniSense Corporation
9
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
7/21/06
LifeTrack RFID
LifeTrack
technology
demonstrator
CliniSense Corporation
10
The stability bank algorithm
Low
temperature
High
temperature
Stability bank "B"
7/21/06
CliniSense Corporation
Small # of
withdrawals per
hour
High # of
withdrawals per
hour
11
Stability calculation example
time
B = 165984 – 0Σ P(temperature)
Stability points per hour
1,000,000
Insulin Shelf-life
1000
100,000
Points
Months
100
10
10,000
1,000
100
1
10
0.1
-20
1
0
20
40
60
Temperature (C)
7/21/06
CliniSense Corporation
-20
0
20
40
60
Temperature (C)
12
Sample LifeTrack profiles

7/21/06
Each different stability profile produces a
different P(temp) function
CliniSense Corporation
13
Evaluating LifeTrack technology

Is our stability data
adequate?

Customers like?

FDA requirements?

How can I do a quick
feasibility test?
7/21/06
CliniSense Corporation
14
LifeTrack Technology Demonstrator
+/good
bad
display
Lifetime
bar
Thermistor
Battery
door
Infrared
LED
7/21/06
Programming
& expansion
Port
CliniSense Corporation
Battery
(3 yr life)
15
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
7/21/06
CliniSense Corporation
16
LifeTrack Demonstrator Display

Shows “+” when
product is good, “-”
when product has
expired

Lifetime indicator bars
decrease as the lifetime
is used up
7/21/06
CliniSense Corporation
17
Programming a unit

Enter the stability data
into an Excel
spreadsheet model

Transfer parameters to
LifeTrack program

Load LifeTrack program
into LifeTrack device
7/21/06
CliniSense Corporation
18
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
7/21/06
CliniSense Corporation
19
Data output example:
The entire relevant history record in only 150 bytes
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
Material: Biotherapeutic ID: 12345678
30
25
Temperature
20
15
10
5
0
-100
Avg. PostExp temp
25 oC
Standard dev
0 oC
7/21/06
-80
-60
-40
-20
0
History before expiration (hours)
CliniSense Corporation
20
Using 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
7/21/06
CliniSense Corporation
21
Smart biotherapeutic packaging
Drug delivery devices

LifeTrack detects
deteriorated product

Can be embedded into
drug delivery devices

Accurate and easily
customized
LifeTrack RFID
LifeTrack
technology
demonstrator
7/21/06
CliniSense Corporation
22
LifeTrackTM Technology
Injection pens
LifeTrack RFID
LifeTrack
technology
demonstrator
Detects all types of improper storage
Recent 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
7/21/06
CliniSense Corporation
24
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
7/21/06
CliniSense Corporation
25
For more information

CliniSense website
(www.clinisense.com)
has many examples

Demo units available

Feel free to call (408)
348-1495 and ask
questions
7/21/06
CliniSense Corporation
26