Pharmacopeia Europe and Helvetica: This is the Status Quo
The primary purpose of this quality standard on therapeutic products is to make sure that all the products that go into the market are effective, safe, and are of high quality through adequate temperature monitoring.
For some time now, ELPRO has noticed an upsurge in the support request numbers from its customers relating to the methods of calibration used. This can be attributed to the steady increase in complaints during inspections done by competent cantonal monitoring authority or Swissmedic and the inspection agency of the region.
Almost all of these complaints arise from the new set of rules in the Swiss Pharmacopeia, otherwise referred to as Pharmacopeia Helvetica, which are prone to improper interpretation.
As highlighted in the Pharmacopoeia Europe and Helvetica, these rules were initially put into place to liberalize the regulations that were there earlier in relation to thermometer calibration. Prior to implementing the new regulations, all the stakeholders in the whole value chain that produces and distributes medication, active substances, and medical devices were forced to have a thermometer from Pharmacopeia Europe.
These stakeholders can currently use any available instrument that measures temperature as long as it has been calibrated in the approved range.
In relation to the support cases that ELPRO has received, it is recommended that you put huge importance on the requirements on the monitoring of transportation and environmental conditions to avoid any variations during inspections.
Pharmacopoeia Helvetica Requirements for Temperature Measuring Instruments
The Pharmacopeia Europe and Helvetica state that when measuring temperature, only temperature- measuring devices that have been calibrated should be used and should be suitable for the temperature range that is currently being measured.
Additionally, these temperature measuring devices should be able to display the temperature information as mentioned in the Pharmacopeia Europe to the nearest decimal place.
Pharmacopeia Europe Helvetica further states that these instruments that measure temperature ought to be calibrated at uniform intervals. The manner in which these intervals are decided should be based on the amount of risk that is involved.
Furthermore, calibration of these temperature measuring devices should be traceable to the nationally recognized standards that are in accordance with the CIPM-MRA (International Committee for Weights and Measures Mutual Recognition Arrangement, which is under BIPM (International Bureau of Weights and Measures).
However, the internal calibrations of these devices that measure temperature should only be done using a suitable temperature measuring device that has been calibrated in an approved testing lab and only using the approved predefined procedures.
Finally, a two-point calibration that encompasses the whole operating range is slowly but surely becoming a requirement by cantonal inspection agencies. This sort of calibration ought to be repeated from time to time.
The Selection of Calibration Points
When selecting calibration points, you should do so in relation to the desired range of applications. For example, at the request of a two-point calibration method, one point should be set just above the application range, and the other point should be set just below.
If a refrigerator has an application range of between 2˚ and 8˚, it should be calibrated at 0˚ and 10˚. ELPRO further recommends the implementation of a 3 point calibration, which can be used for the process of demonstration and also equipment robustness.
Compliant Calibration Certificate According to Pharmacopoeia Helvetica
First, a compliant calibration certificate should have an accreditation logo and an accreditation number that are clearly indicated. The laboratory that did the calibration should also leave their address on the certificate, and if the calibration was done on-site, evidence of where it was done should also be present.
If by any chance, the calibration was done in a foreign laboratory, the ILAC logo together with the local accreditation mark ought to be specified to ensure that it is the equivalent of SCS.
Next, the calibration certificate should be identified clearly without much strain. Additionally, the measuring chain should be visibly clear and be identified with a serial number.
Adding onto that, it is a standard requirement that the contact information and the customer’s name be shown on the document. If by any chance that this information is not there, ELPRO recommends that this decision is documented in a risk assessment.
The proof of the traceability to the standards of calibration by the lab that did the calibration should also be included in the certificate. If the calibration certificate is an ISO 17025, traceability is also ensured by the accreditation authority.
A compliant calibration certificate should also include the environmental conditions prevailing at the time the calibration was done.
A minimum of a two-point calibration system as recommended and viewed as being state of the art is required to be on the certificate. According to Pharmacopoeia Helvetica, the calibration of the measuring equipment should be done at regular intervals by taking multipoint measurements across the whole workspace.
The method used in calibration should be available on the calibration certificate to ensure that the calibration can be repeated under the same conditions as the initial calibration if need be.
If, in any case, any repair or adjustments have been made, it should be clearly noted down at the time the measurements were done. In each certificate, ELPRO indicates the calibration type. ELPRO can be noted as having made no measuring system changes if the output and input calibration have been checked.
ELPRO always provides its customers with two certificates. One is the input certificate, which has the values before any repair or adjustment has been done. The other one is the output certificate, which has the values after any replacement, repairs, or adjustments have been done.
A compliant calibration certificate should also provide the decision rules under which this was done if the statement of conformity has been provided.
Additionally, the person who approved the certificate, the day the calibration process was done, and the day the certificate was prepared should also be clearly indicated on the certificate.
Finally, the calibration certificate ought to indicate the identified measurement uncertainty and also include a note that indicates what this measurement uncertainty is and the coverage factor that was used.
K=2 is the industry standard coverage factor. The test specimen and the measurement uncertainty should be both indicated in the same unit.
By following the above-mentioned practices and procedures concerning temperature calibration, Pharmacopeia Europe and Helvetica's high standards will always be met by offering drugs in the best possible condition.