Monday, July 6, 2009

Thermal Validation in the Pharmaceutical Industry

:

The pharmaceutical industry is a highly regulated
environment based on research, evidence, recordkeeping,
and validation. The term “thermal
validation” is the process of validating / qualifying
equipment and storage facilities to prove that they
will create and maintain the temperatures they are
designed for.
For those responsible, choosing the right validation
tool is decision #1 - and making that choice requires
a thorough understanding of different sensors types.
This paper will specifi cally focus on two common
sensors: thermocouples and thermistors (see table
below).
With nearly a decade of experience using both
thermocouples and thermistors, Veriteq Instruments
knows the advantages and disadvantages of each
sensor, and will discuss them as they relate to data
logging in the pharmaceutical industry. This paper
will also include specifi c references to Veriteq data
loggers, which utilize internal thermistors. But fi rst,
a brief defi nition of thermocouples and thermistors:
A thermocouple is made of two dissimilar metals in
Thermocouple Thermistor
Temp. Range -270 to 1800°C
(-454°F to 3272°F)
-86 to 150°C
(-123°F to 302°F)
Sensitivity Low High
Stability Low High
*Time-savings Lengthy set-up Minimal set-up
*Sources of Error Many Few
*Accuracy Low High
Ideal Applications High temperature oven profi ling,
Cryogenic freezing
Warehouse monitoring, Stability testing,
Chamber qualifi cation, Cooler and Freezer
Monitoring, Lab monitoring, Cold Chain
monitoring.
* This comparison looks at a total data logging system, and not just the sensor.
contact with each other. The thermocouple works by
generating a small voltage signal proportional to the
temperature difference between the junctions of two
metals.
In contrast, a thermistor is a resistive device made
up of metal oxides that are formed into a bead and
encapsulated in epoxy or glass. As temperature
changes, so does resistance, causing a large voltage
drop.
Both sensors are quite small and normally encased
in a protective shell, stainless probe, or wire
coating, meaning that they may look very similar to
the end-user.
Temperature Range
Thermocouples offer the widest range of
measuring capabilities, which admittedly makes
them a suitable choice for extreme temperature
applications such as oven profi ling and cryogenic
freezing.
However, in the range of –86 to 150°C (-123°F to
302°F), thermistors become an option, and for most
applications they are the better choice. Thermistors
and is an important component of sensor accuracy.
Thermistors are highly sensitive; in fact the name
thermistor evolved from the phrase “thermally
sensitive resistor”. Stuart Ball, an electrical
engineer and author for embedded.com writes that
“of all passive temperature measurement sensors,
thermistors have the highest sensitivity.”
In comparing thermistors with thermocouples,
Stuart goes on to say: “The voltage produced by a
thermocouple is very small, typically only a few
millivolts. A type K thermocouple changes only
about 40 microvolts per 1°C (1.8°F) change in
temperature.”
With such a
small voltage
to measure,
it becomes
difficult to
distinguish
an actual
temperature change from noise. Enercorp
Instruments Ltd., a provider of thermocouples and
thermistors, speaks directly to this issue: “The
voltage produced is very small and amounts to only
a few microvolts per degree Celsius. Thermocouples
are therefore not generally used within the range of
-30 to 50°C (-22 to 122°F).” temp/Thermistors_comparision.html>.
The picture above is a visual representation of the
increased sensitivity that a thermistor based system
are primary sensors, meaning that they operate
independently, without the need for a second
reference sensor. In fact other systems, including
thermocouple systems, often use thermistors as their
reference sensor.
It should be noted that the stated temperature range
of –86 to 150°C (-123°F to 302°F) is just for the
thermistor itself, and not for an enclosed Veriteq
data logger. Veriteq data loggers are designed
to withstand the range of -86 to 85°C (-123°F to
185°F) meaning that the loggers themselves can
be placed in the temperature environment and
left there. This
makes them an
ideal solution
for chamber
qualifications,
stability testing,
warehouse,
cooler and freezer
monitoring.
Veriteq’s solution for the higher range of 85°C
to 150°C (185°F to 302°F) requires an external
thermistor probe that allows the connected data
logger to remains outside the high temperature
environment.
Sensitivity
The term sensitivity refers to the size of signal
received in response to a temperature change,
“The voltage produced is very small and
amounts to only a few microvolts per degree
Celsius. Thermocouples are therefore not
generally used within the range of -30 to 50°C.”
HIGH SENSITIVITY:
A Veriteq thermistor changes 35 mV (35,000
microvolts) in response to the same 1° C change
LOW SENSITIVITY:
A typical thermocouple changes only 40
microvolts in response to a change of 1° C
*Theoretical temperature change at 25° C
0 mV
+50 mV
0 mV
+50 mV
Hard to distinguish a 40
microvolt change from noise
(such as a Veriteq data logger) detects as compared
to a thermocouple system.
Stability
Thermistors are very stable, which makes them ideal
for portable applications such as warehouse and
chamber qualifi cations. For example, Veriteq data
loggers can be moved frequently and still maintain
an accuracy of +/- 0.15°C (+/-.27°F).
To prove the point Veriteq recently checked the
calibration of 106 data loggers after a year of use in
the fi eld. Each logger was checked at the following
calibration points: -20°C, 25°C, and 70°C. The
results were impressive, showing less than 1% of
the points to have any excess drift. Still, Veriteq
recommends that data loggers are re-calibrated on a
yearly basis.
Thermocouples, on the other hand, are known for
low stability, which is why a pre-cal / post-cal is
required with every use.
Time-savings
A veriteq data logger is a system in itself, and one
that is easy to use. Each data logger, containing a
thermistor, is simply set to the desired sampling frequency
and then placed in the monitoring location.
Following the test period, the data is downloaded
via a PC or PDA. The system is very straightforward
and doesn’t require any stringing of wires - the
result is a signifi cant time savings.
In contrast, a thermocouple based set-up can be
quite time consuming, especially for high-accuracy
applications requiring a pre and post-calibration.
For example, qualifying a chamber with a thermocouple
system involves fi rst putting all sensor ends
(i.e. the hot junctions) inside a calibration unit and
going through the pre-calibration process. Following
a successful calibration, the thermocouples
are strung from the central data logging unit, to the
Sources of Error
Thermocouple System Veriteq Thermistor System
Physical damage to sensor
‘Cold working’ degrades
thermocouple wires as they are
repeatedly bent, stepped on, or
shut in chamber doors.
There is minimal risk because the
sensor is protected inside the data
logger.
Non homogeneity (consistency of thermocouple
wire and the environment it
runs through)
Always present to some extent N/A
Cold Junction reference error
• Temperature deviation between cold
junction reference point and the actual
cold junction
• Accuracy of cold junction sensor
The single largest source of
error
N/A
Pre & post calibration errors
• Reference transfer calibration error
• Traceable temperature standard
• Environmental stability
• Movement of sensors
In fi eld calibration introduces
many sources of error
Pre & post calibration is not
required
Operator Error
High level of knowledge required
to minimize errors
Less risk as the system is relatively
simple
Analog to Digital conversion Minor Minor
chamber, through a door seal, and then taped into
various positions. Care must be taken to keep a
good seal on the door while minimizing damage
to the thermocouple wire. Only then can the data
collection begin. And when that is complete, all
thermocouple sensors must still be moved to the
calibration unit for post-calibration. Finally, it is
not uncommon for thermocouples to fail the postcalibration,
meaning that the whole process may
need to be repeated.
Sources of Error
Being a self-contained
unit means
that Veriteq data
loggers have less
error sources to
deal with - there
are no wiring errors,
no cold junction
errors, and no
errors associated
with in-fi eld calibration
(see table on previous page).
In contrast, thermocouple systems have numerous
sources of error, the most signifi cant being the
cold junction
reference error.
Goran Bringert,
of Kaye Instruments,
states the
following: “A
change in ambient
temperature
is the most signifi cant source of error in thermocouple
measuring systems, particularly multi-channel
systems with internal cold junction references”
validation.pdf>.
Accuracy
High accuracy is critical for temperature validations
because of the 4:1 rule, which recommends
that instruments be at least 4 times as accurate as
“A change in ambient temperature is the most
signifi cant source of error in thermocouple
measuring systems, particularly multi-channel
systems with internal cold junction references.”
the parameter being measured/validated. Therefore,
Veriteq data loggers, with their accuracy of
+/- 0.15°C (+/-.27°F), can be used to monitor/
validate parameters as tight as
+/- 0.60°C (+/-1.1°F).
As for thermocouple based systems, a leading
provider claims to have a total system accuracy of
+/- 0.28°C (+/- 0.5°F). While this may be true from
a theoretical point of view, it would require having
optimal conditions available. Others in the industry
believe that +/- 1-2°C (+/- 1.8-3.6°F) is a more
realistic accuracy for such a system, meaning that it
could be used to validate parameter specifi cations of
+/- 4-8°C (+/- 7.2-14.4°F), applying the
4:1 rule. In any event, very few people dispute the
fact that thermistors are more accurate than thermocouples.
Conclusion
When choosing a system for performing thermal
validations the fi rst question asked should be “what
kind of sensor is being used?”
Thermocouple sensors should be avoided because
they involve a lengthy set-up, numerous error
sources, and marginal accuracy. It would be best to
restrict thermocouple
systems
to applications
involving very
high or very low
temperatures,
simply because
there are no other
choices available at those extremes.
In contrast, thermistor sensors are ideally suited to
high accuracy monitoring in the range of -86° to
150°C (-123°F to 302°F). The Veriteq thermistor
based system is highly sensitive, stable, accurate
and easy to use. In addition it eliminates the many
error sources associated with thermocouple systems,
and allows for a much quicker set-up time. In short,
you save time, experience less hassle, and obtain
high-accuracy results.
Veriteq Instruments Inc. 2002
www.veriteq.com
1-800-683-8374
info@veriteq.com

No comments: