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In this section, discover why the calibration of temperature sensors is necessary within the pharmaceutical industry. You will also find some valuable audit tips below, along with information about certification and accreditation.
What is temperature calibration?
Calibration is a comparison test between a reference device and a device under test.
The accuracy and uncertainty of the reference device is known and traceable back to the national physical laboratory (NPL) through calibration.
The device under test is checked multiple times for accuracy within a predefined tolerance during the calibration process. The device under test passes calibration if it reads within the tolerance. Typically, calibration is carried out over more than one temperature point to ensure linearity.
The calibration standard operating procedures (SOP) can be accredited to ISO 17025 standards. Regular audits and intercompany tests are hosted to ensure reliability.
Temperature calibration involves the reliable, reproducible, and documented comparison of a sensor or data logger being tested with reference equipment. The referenced instrument is exact and undergoes regular checks in an accredited laboratory.
Sensor calibration takes place at defined measurement points. Firstly, a device or machine maintains stable conditions using a small bath or a dry block. Next, the hardware adjusts for a set interval, usually thirty minutes, to reach the same temperature.
Then, technicians compare the temperatures displayed by the devices being tested and the reference. If the readings do not match, the usual action is to adjust the device under examination to display correctly. Once within specification, a calibration certificate records the result.
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Why Temperature Calibration is Necessary From a Regulatory Perspective
In effect, regulations require calibrated thermometers and data loggers in good distribution practice (GDP) environments involving the packaging, storage, and distribution of pharmaceutical products. In addition, most GDP guidance documents, e.g., U.S. Food & Drug Administration (FDA), EU, and WHO, call for calibrated sensors. Some interpretations even insist on an ISO 17025 calibration for every cold chain shipment.
Often, FDA auditors request calibration certificates and reference documents. An example might be to produce a copy of the data from a specific temperature data logger used for a product release shipment two years ago.
Similarly, an auditor might also ask to see the then valid calibration certificate for that same data logger. Ideally, digital copies of certificates should be available from anywhere with internet access and at any reasonable time. It is prudent, therefore, to store files securely in a reliable cloud database.
The Swiss Accreditation Service (SAS) and the Swiss Calibration Service (SCS) are the relevant national authorities in Switzerland. Similarly, DaaKs (Deutsche Akkreditierungsstelle GmbH) is Germany's exclusive accreditation agency for sensor calibration and testing.
In Great Britain, the United Kingdom Accreditation Service or UKAS is the relevant accreditation body. Its experts assess organizations that provide calibration, testing, inspection and certification services.
In contrast, the US National Institute of Standards and Technology (NIST) is now part of the Department of Commerce. Its authority is to ensure excellence in measurement infrastructure to support economic and scientific capability.
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Why Temperature Calibration is Necessary From a Technical Perspective
At the core of every data logger is a sensor with a defined measurement range and stated level of accuracy. Before installation, it is essential to confirm sensor accuracy, calibrate the unit, and document the completed procedure.
Some sensing and measurement devices are subject to drift, i.e., change over time. After one year, a repeat calibration is recommendable to certify that the sensor's accuracy is still within specification.
What is "In-Process" Calibration?
In-process calibration is a quick and relatively inexpensive method, typically used on-site or in-situ with thermometers. However, it tends not to be as precise as the complete procedure in stabilized conditions.
Essentially, the in-process approach involves comparing the readings of devices under examination with reference devices. By definition, these comparisons take place only at current process temperatures.
Nonetheless, even though the theoretical risk of error is higher than with the fuller procedure, in-process results are usually accurate enough.
What Causes Drift?
As components age, the risk of drift varies according to the sensor type, the measuring principle used, and the degree of physical protection. Nonetheless, suitable quality sensors tend to be stable for many years, whether used in fixed positions or portable applications.
In contrast, the risk for drift in humidity sensors depends on the usage and the sensing technology. As a general rule:
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Use capacitive humidity sensors at room temperature and in transport vehicles.
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Use electrolytic humidity sensors for high-precision or demanding applications, e.g., in cleanrooms, hot cabinets, and incubators.
If we run a PT100 at its most resistant environmental temperature of +150ºC continually, it’s tested to produce a maximum drift of 0.03% for every 1000 hours. So essentially, at the harshest possible temperature and worst case scenario, the calibration integrity will only ever drift to a maximum of 0.045ºC over 41 days (maximum of 0.4ºC per 365 days). In most cases, this will still be within tolerance at the annual service interval. Considering that typical ambient, refrigerator, and freezer conditions are much less resistant, the accuracy drift reduces substantially.
Accuracy by Design
In itself, calibration does not make sensors more accurate. Instead, accuracy is inbuilt by design. So first, manufacturers pair robust calibrated sensors with a compatible algorithm. Next, technicians conduct sample tests to verify that the resulting measuring equipment is accurate and meets the specification(s).
Often, a validation certificate accompanies the production calibration certificate supplied with new equipment.
Recalibration Requirement
From a technical point of view, repeat calibration of these sensors might appear unnecessary. The risk of drift is minimal, and they are usually stable for long periods. So why replace or recalibrate them every year?
The answer is because GxP guidance documents such as those of the FDA, EU, and WHO refer to calibrated sensors. While some publications make a general reference, others insist on regular calibration – typically annually.
Additionally, some auditors insist on what might appear to be an extreme interpretation of the regulations requiring ISO/IEC 17025 calibrated single-use sensors for transportation. Fortunately, most audits adopt a risk-based approach, taking into account the measurement range of the application and the sensors.
How to Calibrate Temperature Sensors
During production, temperature sensor readings are documented as as-found calibration. Next, staff adjust the sensors to show the expected value. They repeat the test and record the results, termed as as-left calibration.
Resistance thermometers in digital sensors have low drift, so they do not usually require further adjustment. However, if sensor readings are outside tolerance, the equipment will likely have sustained damage and is due for replacement.
Similar procedures and terminology apply to the calibration of humidity sensors. In comparison to temperature sensors, humidity sensors have a higher risk of drift—in particular when they are used in extreme wet or extreme dry environments. Therefore, they are typically adjusted during re-calibration. The first calibration is called “as-found calibration” and documents the status before adjustment. The sensor is then adjusted by the measured deviation. Afterwards, the so-called “as-left calibration” is performed to check if the adjustment has been successful. If a temperature sensor is outside tolerance, it is likely that it has been polluted too much and/or is physically damaged. Therefore, it is typically exchanged.
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What are the correct temperature points to calibrate cold chain data loggers?
Regulations do not specify the number of points and their values. Nonetheless, it is best to calibrate data loggers at three temperatures – unless there is a persuasive argument and clear evidence for fewer points.
Sensors must be stable within their specified operating conditions. Therefore, calibration points should cover the anticipated range. For instance, -30 °C, 0 °C and 50 °C would correctly monitor typical frozen, refrigerated, and room temperature environments.
Finally, it is acceptable to calibrate single-use and low-cost electronic indicators at only one temperature point.
What is ISO 17025?
ISO 17025 standards apply to calibrations. In addition, to issue certificates under its auspices, the laboratory concerned must have received accreditation from the relevant national authority, as described above.
What is the difference between factory and ISO 17025 calibrations?
Though both are similar, ISO 17025 has two additional criteria. Firstly, four-eye (not two-eye) approval is necessary, i.e., a second person to check and countersign. Secondly, the entire process is not just GAMP 5 validated but also approved by national accreditation bodies.
I can rely on this certificate, since the process has been approved by an official regulatory body.
Although the processes, devices used, and the tolerance parameters applied are the same, auditors often favor ISO/IEC 17025 certificates. Not least, they consider the process as approved by an official regulatory body.
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Beware of Third-Party Supplier Certificate Descriptions
While certain suppliers might use the word calibration, their processes do not always fulfill the accepted requirements.
Let us consider three examples:
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A new batch monitoring system functions correctly but does not store every test result from each sensing element. Staff takes a sample and tests it. Based on the acceptance of this sample, the company releases the complete batch with a certificate. This action is validation, not calibration.
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Technicians test a sensor against a reference device but do not document the result. Instead, they give the customer a copy of the reference device certificate. This malpractice constitutes mistaken in-process calibration.
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Various devices warm to different temperatures in an oven with known operating tolerances. Towards the end of this process, technicians test whether all the devices have functioned within tolerance. If so, they issue a certificate to this effect without recording the exact deviation measured in each device. This certificate proves testing and validation, but not calibration.
ISO 9001 vs ISO 17025 Calibration
Standards and Requirements
Conclusion
Above, you have seen the essentials of sensor calibration and its importance in the pharmaceutical sector. If you are a decision-maker in logistics, storage services, or quality management and wish to discuss your temperature monitoring and calibration requirements, please contact us. ELPRO is a global leader in environmental monitoring hardware, intelligent software solutions, and GxP services.
