January 2010
Validation professionals spend extensive time validating temperature to ensure the integrity of controlled environments and to fulfill compliance requirements.
Pre- and post-calibrations—a necessary part of the process of thermal validation—typically take up 50-80% of the time it takes to map a given area. Carefully distributing and re-distributing thermocouple wires (after re-calibrating with each placement) is not only time consuming, it entails cessation of normal operations and—as this article will show—actually degrades measurement accuracy.
Despite a move toward ever leaner operations in regulated industries, thermal validation is one area that has eluded the cost and time savings associated with improving measurement technologies. In part, this is because of the imperative that cost-saving measures do not increase the risk of inaccuracy; especially when the application involves temperature-sensitive product and requires complete documentation.1 This may explain why validation is still performed using thermocouples that require time-consuming preand post-calibrations.
The following article will discuss the major differences between thermistors and thermocouples, their appropriate measurement ranges, and give some real-world calibration statistics for thermistorequipped data recorders. These statistics provide evidence that the stability of thermistors supports their use in multiple validations with the benefit of time saved by fast deployment and the reduction of nonessential pre- and post-calibrations.
THERMOCOUPLES: A BRIEF HISTORY
Thermocouple systems have long been used for thermal validation. Their function is based on the thermoelectric effect discovered in 1821 by Thomas Seebeck, who found that when two dissimilar metals were joined and a temperature difference was present, a voltage was produced. Known as the Seebeck effect, this forms the basis of all thermocouples.
The modern thermocouple is composed of two high purity wires welded at the tip. Available in a variety of standard materials, Type T (Copper and Constantan) is used most often for thermal validation. However, a common source of error with thermocouples is separation at the junction point, which often occurs with repeated use. While most validation professionals have dealt with common problems like a break at the junction (J1, Figure 1), there are some lesser known subtleties in thermocouple function that have a large impact on their accuracy and usability in certain applications.
Any imperfections along the length of the wire also increase error. This is because the entire length of a thermocouple is a sensor. Thus, voltage is not only generated at the junction, but over the entire length of thermocouple.
Many applications (warehouses or walk-in chambers), require long thermocouple lengths. Unfortunately, the longer the wire length, the greater likelihood of degradation in the wire; the more imperfections in the wire, the greater the sources of measurement error in the sensor. Each imperfection in the thermocouple wire, created either at the time of manufacture or during handling, will cause “micro-thermocouples” to be formed along its length. This is because each of these micro-thermocouples produces a slightly different voltage per °C and thus introduces measurement errors.2
Thermocouples produce a small output signal; 40uV (microvolts) per °C of temperature difference.3 Such a small output requires a high amount of signal amplification (gain) in the measuring system, which often introduces measurement drift. These very small signals are also susceptible to external noise sources, a particular problem with long wires; therefore, the longer the wire, the greater the potential noise pickup.
Every junction of dissimilar metals produces a Seebeck- voltage when a temperature difference is present. For example, a copper to copper junction that has formed an oxide will produce a voltage 10 times greater (>500uV per °C) than the intended (thermocouple) junction (See Figure 2). This can produce one of the largest sources of error, swamping the measurement of the intended junction.
Another source of error comes from the secondary cold junction temperature measurement system, which is a necessity with thermocouples. Thermocouples do not respond to an absolute temperature, but rather, to the difference in temperature across the length; no difference will result in no output voltage.4 As a result, each thermocouple measuring system must have this secondary measurement system, with its own sources of error.
With so much potential for error, it is understandable why thermocouple systems need continual re-calibration during mapping. Potentially unstable when shifted from one application to the next, thermocouples must be calibrated before and after every single test run.5
Many QA/QC and validation professionals have realized that, within certain temperature ranges, mapping with thermistor-equipped recorders can result in accurate test results in a significantly reduced time.
While thermocouples are the only way to validate extreme temperatures, in environments from -90°C to 130°C, thermistor sensors are far more accurate and stable. This is because they sense temperature by significantly changing their electrical resistance. In a thermistor-based system, a signal of 35 mV (millivolts) per °C is typical; nearly 1,000 times greater than a thermocouple- based system. The large signal results in a far more stable measurement. Also, the high resistivity of the thermistor allows a measurement lead resistance that produces a typical error of 0.05°C.6
A major difference in the measurement accuracy of thermocouples and thermistors is that the latter has no other dependencies. Thermistors produce an output which is proportional to the absolute temperature. This is why they are ideal for thermal mapping when placed inside a small data recorder that is equipped with a wrapping memory, a long life battery, a clock, and a microprocessor.
Although designed for more limited temperature ranges than thermocouples, thermistor-equipped data recorders offer numerous advantages such as faster setup, greater accuracy, long-term in-calibration performance, and data redundancy. Data recorders can provide temperature accuracies to 0.1°C and some models are tamperproof and 21 CFR Part 11 compliant.
WHAT THE CALIBRATION SHOWS: (ONE YEAR LATER)
One manufacturer of thermistor-equipped data recorders reported that of the 2,427 routine service calibrations they performed on temperature recorders that had been in the field for at least one year, 99.7% of the devices were still within published specifications. Of the failed calibrations (0.3%), none were out-of-specification by more than 0.12ºC; the average out-of-specification value being 0.036ºC.7 This performance is well within acceptable limits for most pharmaceutical validations.
These statistics show that the recorder/thermistor combination is a safe substitute for difficult and errorprone thermocouple systems in validation. Post-calibrations are normally performed to avert product implication should the thermocouple system reveal a future calibration error. However, when a more stable thermistor-based device is used, the need for post-calibration is eliminated, which is a substantial savings in time, personnel, and costs.
CHOOSING THERMAL MAPPING EQUIPMENT: KNOW THY TEMPERATURE RANGE
In any regulated environment, calibration is not optional. However, there is also no requirement for excessive calibration. The ultimate goal is to use a method that provides the highest degree of accuracy, at the lowest possible cost.
When choosing thermal validation equipment, buyers must obtain statistical data from the manufacturer that details recommended calibration intervals, product test specifications, and performance. Evaluating performance specifications on validation equipment will mitigate doubts over new equipment and protocols and justify the effort of changing over from an inefficient validation method.
As economic necessity forces regulated industries to periodically optimize their processes, eliminating waste is a constant challenge. Using data recorders equipped with thermistors for temperature mapping offers higher accuracy in temperatures from -90°C to 85°C,8 simple setup and operation, faster test completion, improved quality of data, and minimization of site disruptions.
The autonomy of thermistor-equipped data recorders (when they also have a self-contained power source and redundant recording), make them the ideal tool for large- and small-scale thermal validation projects. In addition, long-term stability of thermistors allow validation professionals to use the device for multiple validations, without spending excessive time on pre- and post-calibrations; the result being more efficient validations and significant savings in time and money.
References
- GAMP® Good Practice Guide: Calibration Management ISPE (2001)
- Kerlin, T.W. (1999). Practical Thermocouple Thermometry USA: Instrument Society of America
- Temperature Measurement Thermocouples ISA-MC96.1 Instrument Society of America (ISA): (1982)
- Manual on the use of Thermocouples in Temperature Measurement—4th Edition, (1993) ASTM Committee E20 on Temperature Measurement.
- Daneman, H.L. Thermocouple Calibration – The Do’s and Don’ts of Good Practice (1991), NCSL Workshop & Symposium USA
- Practical Temperature Measurements: Application Note 290: (2000) Reynolds, Geoff Aglient. Retrieved January 27, 2008, from
http://cp.literature.agilent.com/litweb/pdf/5965-7822E.pdf - One-year statistics from the calibration database of Veriteq Instruments showed that 99.7% of 2,427 data recorders, having been used in a variety of environments over a period of 10 to 14 months, were still within published accuracy specifications to 0.15°C.
- Veriteq Instruments’ temperature accuracy specifications for thermistorbased data recorders are 0.15°C between the range of 20 to 30°C and 0.25°C between the ranges of -20 to 70°C.
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