Article of the month Feb 08 - Thermal Validation & Thermal Mapping

For thermal validation and thermal mapping in the pharmaceutical, bio-medical and healthcare industries an accurate, reliable measurement system is necessary to meet the requirements of the relevant guidelines of HTM0101, HTM2010, HTM2030, EN285, EN554 and FDA21 CFR part11.

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Thank you

The temperatures stated for thermocouples calibration in the article are 40ºC, 150ºC and 121-134ºC, for low, high, and set point. However, these temperatures are suitable for autoclaves validation, but not for other equipment, such as ovens, depyrogenation tunnels or freezers.

I think that should be more accurate to say that calibration of thermocouples should take into account the working range of temperatures of the equipment to be qualified, and the needs of the process. In my opinion, it is senseless to calibrate a thermocouple set at 150ºC, if your autoclave reaches 122ºC-123ºC as a maximum (and it is set to regulate temperature among those limits). With 130ºC as high point would be enough. The same for the low point. If the autoclave reaches higher temperatures, then the problem is not that we used the wrong temperatures for calibration, but an equipment malfunction.

That´s my personal opinion. Hope it will help



Thanks Marco for the great information

What has measurement uncertainties got to do with HTM2010? Nowhere in any HTM document does it mention measurement uncertainties.

Also Kaye and Fluke dataloggers which are “multi-purpose” dataloggers according to the author of this document, have served this industry very well for many years, and now we are told that you have to use a specific Type T datalogger?

What poppycock!

For Steriliser and Washer Disinfection, an accurate, repeatable measuring system is necessary. HTM2010 produces guidelines to help us achieve this.

HTM2010 states that “6.16c. For all the types of sterilizer covered by this HTM, the repeatability of the recorder should be ± 0.25ºC or better, and the limit of error of the complete measurement system (including sensors) should be no more than 0.5ºC”. This should in no way be confused with this document which misleads this statement to mean that the combined measurement uncertainties of the complete measurement system should not exceed +/-0.5ºC. These are two completely different meanings. To limit the error of the complete measurement system (including sensors) to 0.5ºC is a quantified measurement. This is the measurement after calibration where the combined systematic errors of the Datalogger and the errors of the thermocouple are calibrated out as a “system loop” (i.e. at the same time) against an Independent Reference Probe. Uncertainties are measurements, which cannot be quantified in a Calibration, and cannot be calibrated out. These are often known as Random errors.

HTM2010 does not state how we should measure or take into account uncertainties however HTM2010 does go on to say in the Calibration and sources of Error section that there should be good practices followed to reduce measurement uncertainty.

6.4 The errors produced in temperature and pressure measurement will arise from a number of factors. Some are inherent in the design, age and condition of the measuring equipment, and others are due to loose terminals, imperfect plug and socket connections, and the change of environmental temperature around the instrument. Variations in thermocouple alloys, preparation of thermocouple hot junctions, the method of introducing sensors into the chamber, and their location within the load will add to the error in temperature measurement. Temperature fluctuations within pressure-sensing elements will lead to errors in pressure measurement.

Therefore datalogger selection should represent a number of factors. However good practices such as using singular wired thermocouples to the datalogger and welding the hot junctions on thermocouples decreases uncertainties in the measurement.

6.5 Every effort should be made to eliminate or minimise these errors by attention to detail, location of instruments, effective maintenance, and skill in the application, handling and use of the instruments. Systematic errors can be reduced by careful calibration.

6.6 Instruments should be maintained and calibrated as recommended by the manufacturer as part of a planned maintenance programme. Each instrument should be labelled with the calibration date and a reference to its certificate. The calibration of all test instruments should be verified yearly by using reference instruments with a valid certificate of calibration traceable to a national standard. A history record should be kept for each instrument.

These two are self-explanatory

6.7 All electronic test instruments should be allowed a period of time to stabilize within the test site environment. They should be located in a position protected from draughts, and should not be subjected to rapid temperature variations. The manufacturer instructions should be followed.

By allowing the datalogger to stabilize in the ambient conditions, which ideally should be the same environment that the test person is to do his testing, this dramatically reduces other random errors. Errors, such as Thermal Scattering is a function of the ability of the input terminals to maintain a uniform temperature across all input connection under changing ambient conditions. The difference in temperatures at the terminals to which thermocouples are attached can be caused by external sources such as the radiant heat from the wall of the autoclave. The temperatures at the different terminals can also change at a different rate to the cold junction sensor. This error exists only when there are changes in ambient conditions. By stabilizing a data logger in a room for a period of time before use and connecting the thermocouple at a terminal inside the data logger near the Cold Junction Sensor can reduce these errors significantly. This is important because in HTM2010 it states “6.14 The intrinsic accuracies quoted by recorder manufacturers are measured under controlled reference conditions and do not include errors from temperature, pressure or humidity sensors. Temperature measurement errors due to ambient temperature changes should not exceed 0.04”C per ”C rise.”

Now when comparing “apples with apples” some manufacturers do not quote these figures and they do not in the Manufacturers Specification declare what this error is. They only give the accuracy of the cold junction sensor, and not how the logger behaves during different ambient conditions. Also be aware that alot of the Manufacture Specifications “are out of the box” accuracy claims and are often quoted to different specification standards and for different period of time and temperature ranges. It is how the Datalogger performs after Calibration that is most important, for example how long the Datalogger stays within Calibration, and how accurate and repeatable the temperature measurements are in stable and changing ambient conditions.

When choosing the datalogger, other aspects apart from repeatable accuracy need to be considered and that is scanning speeds and the number of channels available. If many types of HTM2010 testing such a porous loads and fluids are required as well as other applications such as HTM2030 testing then 12 thermocouple measurement as a minimum are required. HTM2010 states “6.9 Twelve temperature channels are sufficient for all the tests on each type of sterilizer in this HTM, though more may be convenient for determining chamber temperature profiles (see paragraph 7.21). One pressure channel is required for all sterilizers except fluid sterilizers which require up to three.”

However scanning speeds are also important as HTM2010 also states “6.16a for digital recorders, the sampling interval should be short enough for the holding time to contain at least 180 independent measurements in each recording channel. This corresponds to a sampling interval of one second for the shortest holding time (3 minute, high-temperature steam sterilizers) and 40 seconds for the longest (120 minute, dry-heat sterilizers)”. Therefore the datalogger required should not only be repeatable to +/-0.25ºC and accurate to within +/- 0.5ºC (including sensors), but it also has to be able to scan extremely quickly as well, which makes Dataloggers selection even more difficult. Not only this, but HTM2010 also states “6.16b the integration time of the recorder (the response time) should be short enough to enable the output to follow significant fluctuations in the cycle variables and to ensure that successive measurements are independent of each other, It should not be longer than the sampling interval;” Therefore not only should we get a scan in every second, but every channel on each scan has to be able to record a different value from the previous scan and this has to happen every second!

To get the accuracy, repeatability as well as scanning speed, thermocouple selection is also important. HTM2010 states “6.21 Thermocouples should conform to BS4937: Part 4 (nickel-chromium/ nickel-aluminium) or Part 5 (copper/constantan). The calibration accuracy should be Tolerance Class 1 as specified in EN 60584: Part 2 formerly BS4937: Part 20). The tolerance on Part 4 thermocouples (± 1.5 º C) is high when compared with that allowed for those in Part 5 (± 0.5 º C), and for this reason copper/constantan thermocouples are usually preferred for the test recording system.” Therefore Class I thermocouples which has an accuracy of 0.5C should be used, and this will also reduces other errors into the system such as thermocouple drift.

However other factors within HTM2010 should be considered when choosing Calibration equipment as well as the Datalogger. In HTM2010, a section on Verification of Calibration gives us a good guide on what type of equipment is required.
For the Datalogger HTM2010 states “6.32 The recorder should incorporate mechanical or electrical calibration facilities. The manufacturer of the recorder will normally calibrate it without the use of temperature sensors or transducers”.
For every datalogger manufactured, there will be a calibration certificate with the datalogger. However when we calibrate thermocouples, we are also calibrating out the systematic errors of the Datalogger. Therefore we will be calibrating out the combined error of the datalogger and the thermocouples against the Independent Reference Probe at the same time. With good calibration techniques, such as, one continuous length of thermocouple wire from the inside of the vessel to the datalogger itself, leaving the Datalogger to stand before use for a period of time to stabilize in its ambient conditions (with no draughts etc) and to calibrate in the same ambient conditions (or as close to it) that we are going to perform our testing in are all good practices to minimise the random errors. However these days the calibration factors are corrected automatically by the Validation Software and stored in the PC and not in the datalogger itself, and is perfectly acceptable for HTM2010 as long as the software can be seen to calibrate these factors correctly.

When selecting the correct Heat Source or Dry Block Calibration Bath, as well as selecting it’s operating temperature, we must also consider what HTM2010 states "6.33 An independent temperature reference source (a hot source ) is required, with a pocket to accommodate up to 12 temperature sensors. The temperature gradient within the pocket should not exceed 0.2 º C and the control accuracy should be within ±0.1 º C over the relevant sterilization temperature band."
The temperature gradient is often know as Uniformity. Uniformity is made up in two parts. Axial Uniformity and Radial Uniformity. The Calibration bath’s “Axial Uniformity” is how the sensor’s temperature reading differs depending on the depth inside the hole within the dry well. The Radial Uniformity takes into account the difference between the sensor’s temperatures in the different holes within the dry well. Also to consider is the quality of the Stem Conduction particularly in small Calibration Baths. If for example you have 12 thermocouples in one hole and 3 in another hole, within the dry well, often the hole with 12 thermocouples is at a lower temperature due to the increase in thermal mass. Also we must consider the Control Accuracy of the Calibration bath. The Control Accuracy is not the accuracy of the reading on the Calibration Bath itself, but the stability of the bath over time and needs to be able to fluctuate less than +/-0.1ºC to give a stable reading. However we do not need to know the accuracy of the value of the Calibration Bath as we can greatly increase the accuracy of measurement by using an Independent Reference Probe. Therefore we use the Probe to give us an accurate measure of the Bath, however the Bath gives us an extremely stable measurement to calibrate the Datalogger and thermocouples.

HTM2010 states that “6.34 The temperature of the hot source should be measured either by a mercury-in-glass laboratory thermometer conforming to BS593 or other temperature measurement system of similar or greater accuracy. The supplier should be asked to provide a certified calibration curve traceable to the national primary standard. Note that all the thermometric measurements required by this HTM will ultimately depend upon the accuracy of this calibration; an uncertified laboratory thermometer will not be accurate enough to ensure that the sterilizer is working correctly and may give dangerously misleading results.” Most Reference Thermometers on the market are better than +/- 0.1ºC, which will give excellent Calibration results, but a Certified Calibration Certificate must be provided. The better the accuracy of the Reference Probe the better your overall Calibration will be. These days PT100’s are used instead of Thermometers.

With all this in mind, when we do a Calibration before testing and a Verification of Calibration thereafter, we have to take in mind the accuracy and repeatability of the Datalogger with Class I thermocouples attached, the Uniformity and Stability of the Calibration Bath, the accuracy of the Reference Probe, and all the good techniques described in HTM2010 to reduce Random Errors. How can we quantify this? Again HTM2010 help us. It states “6.36 Before a recorder is taken to site, verify the calibration of the system by inserting the test sensors into the hot source at a temperature within the sterilization temperature band. Adjust the recorder in accordance with the manufacturer instructions until the mean temperature measured by the sensors is the same as the temperature indicated on the thermometer. The calibration is satisfactory if the temperatures measured by individual sensors do not differ from the mean by more than 0.5 º C. This test should be carried out at an ambient temperature as close as practicable to that expected at site”.

In Conclusion.

To Select a Datalogger. If you can prove that in similar conditions (or ideally at the testing site) we can prove that the difference between the Datalogger’s measurements provided before and after testing is less then 0.5ºC from our Independent Reference Thermometer (“the mean”), and the measurements are repeatable to less than +/- 0.25C for a minimum period of time, then we have passed our Calibration and Verification of Calibration.
The Dataloggers temperature measurement errors due to ambient temperature changes should not exceed 0.04ºC per ºC rise.
During testing for Porous Load Sterilises in particular, we need to be able to get 180 scans in the hold time period (i.e. every second), but every scan provided is independent from the previous scan.
Ideally, the Datalogger should accommodate at least 12 thermocouples. If the Dataloggers can pass all this criteria, then the Datalogger selected is fit for purpose. However some dataloggers are more repeatable and accurate than others, and do significantly give better performances than others in changing ambient conditions.

However, more information can be found out about what contributes to Datalogger Inaccuracies, and how we can calibration out Systematic errors and reduce our Random errors from reputable sources

Thermocouples need to be Class I type. However again, to see how we can improve our measurement when using thermocouple in Sterilisers again can be found at many reputable sources.

When selecting the Calibration Bath, if the temperature gradient does not exceed 0.2ºC, can accommodate 12 thermocouples and the control accuracy is within ±0.1ºC then the Calibration Bath is fit for purpose.
Again some Calibration Baths are more accurate, have smaller uniformities errors and are quicker to get to the control temperatures than others, but most have similar operating ranges, and some do come with an Independent Reference Probe provided.

If however, we need an Independent Reference Probe, this will dramatically improve the accuracy of the calibration overall. However the more accurate they become, the more expensive they become. Often to get an accuracy of +/-0.02ºC can be twice as much as +/-0.05ºC. However the Independent Reference Probe is vital to the calibration as there are extremely accurate devices to use, and can quite easily improve you Calibration by 10 fold quite cheaply against the accuracy of the Calibration bath. With all this in mind HTM2010 asks to provide a Calibration against an Independent Reference Probe.

Hi Crunchie,

That maybe the greatest (certainly the longest post ever on this site)

I applaud you sir!

[quote=gokeeffe]Hi Crunchie,

That maybe the greatest (certainly the longest post ever on this site)

I applaud you sir![/quote]

Why thank you.

Its just nothing annoys me more when companies promoting their own products, cannot seem to quote HTM2010 correctly to suit their own needs :wink:

Agree with Marcos and Chrunchie one of our calibration:

1.6.1. Minimum Temperature: 90 °C
1.6.2. Maximum Temperature: 130 °C.
1.6.3. Check Temperature: 121 °C
1.6.4. Sensor Stability: 0.20 °C for 3 minutes.
1.6.5. IRTD Stability: 0.012 °C for 2 minutes.
1.6.6. Deviation Criteria, Uncalibrated Sensor: 1.00 °C.
1.6.7. Deviation Criteria, Calibrated Sensor: 0.50 °C.
1.6.8. Log Corrected Results: 3 minutes.