WO2022079118A1

WO2022079118A1 - Monitoring the core temperature of products

Info

Publication number: WO2022079118A1
Application number: PCT/EP2021/078352
Authority: WO
Inventors: Dieter Süss
Original assignee: Suess Dieter
Priority date: 2020-10-14
Filing date: 2021-10-13
Publication date: 2022-04-21
Also published as: AT524272A1; EP4229375A1

Abstract

The invention relates to a method for monitoring the core temperature of pharmaceutical products. A temperature sensor system is attached to the pharmaceutical product, said temperature sensor system comprising a storage device, an antenna for a wireless data transmission, a microchip, a battery, and a temperature sensor, and at least one barcode of the pharmaceutical product is read by a reading device and is written into the storage device by means of a wireless data transmission. Temperature measurements are taken in time intervals ti by means of the temperature sensor, and the measured data points are written into the storage device. The storage device is read by a reading device at a later point in time, said reading device displaying the cold chain compliance by means of a binary response, wherein the response is calculated using an algorithm, and the recorded temperature data is used. In order to determine the binary response, the stored temperature data is used where the temperature T exceeded or fell below a critical temperature Tc. All of the time intervals where the temperature is greater than the critical temperature Tc are cumulatively added together (ZMeasurement), and the magnitude of ZMeasurement is compared with the magnitude of Zlimit, the binary response being based on whether ZMeasurement is greater than or equal to Zlimit, or the area (TZMeasurement) between the current temperature and the critical temperature Tc in the temperature-as-a-function-of-time curve is determined for all the points in time where the temperature is greater than the critical temperature Tc.

Description

Monitoring the core temperature of products

The invention relates to the measurement of temperature and in particular to a method suitable therefor to demonstrate compliance with the cold chain, according to the preamble of claim 1 and a device according to the preamble of claim 15.

The measurement of temperatures, in particular the detection of exceeding or falling below a critical temperature, is of great importance for many areas. For product liability issues and process monitoring, if you know about critical temperatures that have been exceeded or fallen below, a statement can be made as to whether limit values have been complied with.

For example, temperature measurement is essential when transporting food and medicines, where compliance with the prescribed temperature tolerances must be logged. If not only the current temperature is of interest for monitoring the cold chain, but also the question of whether the temperature of the product has exceeded a permissible maximum or minimum value during the entire logistics process, various methods have been proposed.

DE 196 22 671 A1 describes a device for irreversibly displaying that the permissible temperature has been temporarily exceeded. This sensor contains a medium with a melting point just above the permissible storage temperature. In contrast to this device, a digital system is used in the invention, which offers significant advantages in terms of both accuracy and handling.

In (B. Bergmair, J. Liu, T. Huber, O. Gutfleisch, D. Suess "Wireless and passive temperature indicator utilizing the large hysteresis of magnetic shape memory alloys." Applied Physics Letters, vol 101.4, 2012, p. 042412 ) describes a system in which the resonant frequency of a magneto-acoustic platelet is changed by changing the properties of "shape memory" alloys. This sensor can only be read using a special reader. In particular, a signal with a frequency of approx. 58 kHz is emitted. Due to the low frequency, the reading/transmitting unit requires relatively large lateral dimensions. Furthermore, in this system it is not possible to send an ID with the sensor signal, which is necessary for many applications. Another application is checking whether the core temperature of a blood unit is still within the guidelines when it is subjected to a transport process or when it is being stored. A large number of studies examine the optimum storage temperature for donated blood. Thus, in (Parpart, Arthur K., et al. "Whole blood preservation; a problem in general physiology. An in vitro analysis of the problem of blood storage." The Journal of clinical investigation 26.4 (1947): 641-654. ) investigated the influence of storage temperatures on spontaneous hemolysis and the loss of potassium from red blood cells. A range of 4 °C to 10 °C can be taken from this work as optimal storage. It is therefore essential that a refrigerated stored red blood cell concentrate does not exceed 10 °C after removal. In (Pick, P., and J. Fabijanic. "Temperature changes in donor blood under different storage conditions." Transfusion 11.4 (1971): 213-215.) it was found that an erythrocyte concentrate stored at 1°C after removal had a core temperature of 10°C when exposed to room temperature for between 45 minutes and one hour. From this it is concluded in (Wagner et al, Federal Ministry of Health (BMG), "Handbook on blood management in hospitals" March 2016) that a cooled erythrocyte concentrate stored in a range of +2 to +6 °C will cool down after approx 30 minutes at room temperature (20-25°C) to over 10°C. In (Wagner 2016) it is stated that an erythrocyte concentrate heated in this way may still be administered within 6 hours, but under no circumstances may it be cooled again.

In order to ensure that the valuable and scarce resource of blood, which has been withdrawn from the cold chain but not administered, can be brought back to the blood bank for later use, it is necessary to determine whether the core temperature has remained below 10°C.

Although approaches existed for temperature monitoring, such as chemical indicators (US Pat. No. 8,671,871), these systems could not gain acceptance because these systems are not individually calibrated and thus lead to inaccurate results. Furthermore, the activation is unwieldy and no digital or automatic documentation is possible.

There are also a large number of temperature data loggers (US20040212509, AT A605/2015), but these methods are inappropriate and unsuitable for blood monitoring, for example. There is no method that estimates the core temperature of a blood unit, provides a clear yes/no decision about reuse, and wirelessly reads out the data and stores it in a database. EP 3 702 969 A1 discloses a method for monitoring the handling of medical and biological products. The method relates to labeling containers with labels to identify the contents. The labels are also provided with a monitoring device. A reader is configured to enable wireless reading of the monitoring device. The monitoring device is provided with a memory in which data for identifying the material are stored. Furthermore, the monitoring device is configured to record in the memory the handling conditions affecting the quality of the material, in particular the storage temperature. In addition, the reader is configured in such a way that it issues a warning signal if a threshold value is exceeded or not reached.

The object of the invention is to solve the aforementioned problems and proposes to detect the current temperature with high accuracy and to store it in an internal EPROM memory. This data is read out using RFID, for example. From the temporal development of the measured surface temperature, the core temperature of the pharmaceutical product is estimated using methods described later and a yes/no (binary) answer is given as to whether the product can be used further. Furthermore, the data can be stored in a database.

According to the invention, this is achieved in a method for monitoring the core temperature of pharmaceutical products, with a temperature sensor system being attached to the pharmaceutical product, which system comprises a memory, an antenna for wireless data transmission, a microchip, a battery and a temperature sensor, with at least one code or barcode of the pharmaceutical product is read in by means of a reading device and is written into the memory by means of wireless data transmission, and temperature measurements are carried out by means of the temperature sensor in the time intervals ft and the measured data points are written into the memory and this memory is read out by a reading device at a later point in time , which indicates compliance with the cold chain with a binary response, the response being calculated with an algorithm and using the recorded temperature data, and for the determination of the binary response d The stored temperature data are used where the temperature T has exceeded or fallen below a critical temperature T _c , achieved in that all time intervals are cumulatively summed up (Zmeasurement) at which the temperature is greater than a critical temperature T _c and this variable Zmeasurement is compared with a variable Ziimit and the binary response depends on whether Zmeasurement is greater than or greater than or equal to Ziimit (variant I), or that in the temperature-as-function-of-time curve the area (TZ measurement) between the current and the critical temperature Tc is determined for all times at which the temperature is greater than a critical temperature Tc (variant II) .

In the device according to the invention for monitoring the core temperature of pharmaceutical products, a temperature data logger is attached to the pharmaceutical product, which contains a memory, an antenna for wireless data transmission, a microchip, a battery and a temperature sensor, and this temperature data logger is introduced into a double-walled adhesive label and this adhesive label is attached to the pharmaceutical product, the object of the invention is achieved in that the adhesive label is double-walled according to the invention, and that the double-walled adhesive label can be opened after use in order to be able to remove the temperature data logger again.

The device according to the invention thus has a double-walled adhesive label. A temperature logger system is inserted between this double wall, e.g. two foils. These two foils of the adhesive label can be pulled apart after use in order to use the temperature logger again. The temperature recording of the logger is activated upon delivery and during this process the barcode of the erythrocyte concentrate is also saved on the logger. In a further expansion stage, a unique patient ID can also be saved on the logger. Before the canned food is administered, the canned food ID, the patient ID stored on the logger and the patient ID on the patient wristband can be clearly checked. This increases patient safety when administering the red blood cell concentrate through digital verification.

If the erythrocyte concentrate is not administered and the blood product is sent back to the blood bank, a "red/green traffic light system" can be used to immediately and clearly identify whether the temperature has exceeded or fallen below the set temperature limit. The temperature limits can be determined in accordance with the guidelines from (Wagner et al, Federal Ministry of Health (BMG), "Handbook on blood management in hospitals" March 2016).

The methods described make it possible to assess whether the blood product has been exposed to room temperature for more than 30 minutes and the core temperature has therefore exceeded 10°C. the Compliance with the core temperature can be checked when taking over using a handheld device with a red/green traffic light system. The reading device reliably indicates whether the blood reserves have remained within the permissible temperature range during transport and saves the temperature data as a function of time in a database. In this way, immediate proof that the cold chain has been maintained, a reduction in the discard rate of blood products and digitization for more patient safety can be implemented.

The invention is explained in more detail below with reference to the exemplary embodiments illustrated in the drawings. It shows:

1: Top view of an embodiment of the device according to the invention with the attachment of the temperature logger with double-walled adhesive film

Fig. 2: Another representation of the attachment

Fig. 3: Closed foil

Fig. 4: Representation of the adhesive and non-adhesive areas

Fig. 5: Representation of a punching in order to be able to remove the film more easily

Figure 6: Flow chart of a possible process for using the system

Fig. 7: Binary output after temperature recording

Fig. 8: Representation to detect a temperature excess

Fig. 9: Alternative algorithm for detection of excess temperature

Fig. 10: Typical components of the temperature logger system

In Fig. 1 an embodiment of the invention is shown, wherein the double-walled adhesive label is shown. One of the two films 4, 5, here film 5, is attached to a pharmaceutical product, a blood bag 1, with an adhesive that is certified for blood bags. Another foil 4 can be detached from this foil in order to insert a sensor. In this example, the sensor is a temperature logger 10. In some forms, it is advantageous if the entire surface is not adhesive either on the film 4 or on the film 5, but rather no adhesive 66 is applied in one part. Alternatively, the adhesive can be neutralized in the area 66 . This allows easy removal of the Sensors 10. This sensor can then be reused. In some instances, it may be beneficial to make the adhesive label and sensor significantly smaller than the blood bag so that there is enough free area of the blood bag. This area can be used to determine the surface temperature using an infrared measuring system. This may be necessary if the blood bag is warmed in an air conditioning system prior to administration.

2 shows the double-walled adhesive label 4.5, the sensor 10 and the blood unit 1 in a different representation.

In Fig. 3 the double-walled adhesive label is shown in the closed state. In this state, the pharmaceutical product and the temperature monitoring system are transported.

Adhesive 5 and non-adhesive areas of the adhesive label are shown in detail in FIG. These can be realized, for example, by not applying any adhesive or by neutralizing the adhesive. The non-adhesive area 66 is advantageous so that the sensor 10 can be removed again. The non-adhesive area 67 is advantageous in order to be able to pull the film 4 off the film 5 easily. The non-adhesive surfaces are not necessarily realized on the film 5. If the adhesive is not on foil 5 but on foil 4, the non-adhesive surfaces are on foil 4.

In Fig. 5 a punching of the film 4 is shown. This punching divides the area of the film 4 into two parts. As a result, the foil 4 can be pulled off the foil 5 more easily. For this purpose, for example, the foils can be bent around the area of the punching when being pulled off.

6 shows the flow chart of a possible process. In step 1, the label, for example the double-walled adhesive label, is applied. If the label does not yet contain the sensor system when it is applied, the sensor system is applied in step 2.

In step 3, a unique barcode of the blood product is scanned with a reading device 77 and a unique ID matching this barcode is stored on the sensor system. Specifically on the memory of the sensor system. This can be done, for example, using NFC or some other wireless communication. The storage of a unique ID of the pharmaceutical product (such as the barcode found on the label of a blood bag) is of great importance as the sensor can be reused and thus could also be removed or mixed up during transport. It is therefore important to check before use, reuse or storage that the Sensor system was not exchanged and the ID stored in the sensor system and the ID on the pharmaceutical product match.

In step 4, the temperature recording of the sensor system is started. Here, the current temperatures Ti measured by the sensor system are written to a memory at specific intervals ft. Step 4 and step 3 can also be swapped over in time. In step 5, the blood product is delivered.

Thereafter, the blood product is either administered or not administered. If it is administered, the sensor is removed in step 6b and reused if necessary. If it is not administered, the blood product is checked for reuse in step 6a. Here, the temperature recording is optionally stopped first and the temperature data is read out. It can also be checked whether the ID stored on the sensor still matches the ID of the pharmaceutical product. If not, the sensor has been replaced or tampered with and the blood product is discarded. If these IDs still match, the cold chain is checked. If the criteria for maintaining the cold chain are met, the blood product including the sensor is prepared for further storage. If the cold chain is not maintained, the blood product is discarded and the sensor is reused.

In Fig. 7 the binary output of the system is shown, which decides whether the cold chain is maintained. If the cold chain is maintained, a message appears on the reading device 77 stating that the blood product can be used further. This can be represented in a green color, for example. If the cold chain is not maintained, a warning message appears on the reading device 77 stating that the blood product must be discarded. This can be represented in a red color, for example.

Various algorithms can be used to decide compliance or non-compliance with the cold chain with a binary output. In FIG. 8, the area in the temperature-time curve is determined for points in time at which the temperature is above a critical temperature T _c . At the time ti the critical temperature T _c is exceeded and at the time punt

falls below the critical temperature T _c again. This area can also be determined approximately if the temperature T is recorded in the time intervals A/.

All those areas where the temperature is above the critical temperature are summed. In order to check compliance with the cold chain, the determined variable TZ measurement is compared with a tolerable variable rZiimit. If TZmeasurement > TZnt, the pharmaceutical product must be discarded. A possible size for TZiimit is, for example, TZiimit = 7200 Ks, i.e. 7200 Kelvin times seconds. A possible value for T _c is 6°C. Of course, an equivalent algorithm for falling below a critical temperature can be used.

Another algorithm for maintaining the cold chain is shown in FIG. The point in time ti is also determined here when the critical temperature T _c is exceeded and the point in time /2 when the temperature falls below the critical temperature T _c again. Measurement ~ E “h (0-2)

All Zmeasurement intervals where the critical temperature is exceeded can be added. In order to check compliance with the cold chain, the determined variable Zmeasurement is compared with a tolerable variable Zimit. If Zmeasurement > Zlimit, the pharmaceutical product must be discarded. A possible size for Ziimit is, for example, Ziimit = 3600 s, ie 3600 seconds. A possible value for T _c is 6°C. Of course, an equivalent algorithm for falling below a critical temperature can be used.

In

10 shows the typical components of an RFID temperature sensor system (10). This includes the memory, such as EEPROM ("electrically erasable programmable read-only memory"), a battery, an antenna for wireless data transmission (examples are coil antennas, rod antennas and any other antenna for electromagnetic waves or for picking up electromagnetic induction from magnetic alternating fields), an electronic product code (EPC), a temperature sensor, a multiplexer and a real-time clock (RTL). The transmission frequency can be UHF (0.3 to 3 GHz) or HF (3 to 30 MHz), or any other common operating frequency. The battery is preferably mechanically flexible.

Different combinations of the elements shown and described are also possible, and it goes without saying that in the future new elements can also be used that have the listed elements Possess properties are used, even if their naming may not correspond to what is currently customary. Of course, the features described above are not limited to blood products and can be used for other pharmaceutical products, food or all other temperature-critical goods such as paints, varnishes, plants, electronic components, etc.

Claims

Patent Claims:

1. Method for monitoring the core temperature of pharmaceutical products, wherein a temperature sensor system is attached to the pharmaceutical product, which comprises a memory, an antenna for wireless data transmission, a microchip, a battery and a temperature sensor, wherein at least one code, e.g. a barcode of the pharmaceutical product, is read in by means of a reader and is written to the memory by means of wireless data transmission, and temperature measurements are carried out by means of the temperature sensor in the time intervals ü and the measured data points are written to the memory and this memory is read out by a reader at a later point in time , which indicates compliance with the cold chain with a binary response, the response being calculated using an algorithm and the recorded temperature data being used, and the determination of the binary response being based on the stored temperature data en are used where the temperature T has exceeded or fallen below a critical temperature T _c , characterized in that all time intervals are summed up cumulatively Zmeasurement) at which the temperature is greater than a critical temperature T _c and this size Zmeasurement with a size Ziimit is compared and the binary response depends on whether measurement is greater than or equal to Zumit, or that in the temperature-versus-time curve the area (TZmeasurement) between the actual and the critical temperature Tc is determined, for all Times when the temperature is greater than a critical temperature Tc.

2. Method according to claim 1, characterized in that the pharmaceutical product is a blood product which is discarded if Z measurement > 3600 seconds.

3. The method as claimed in claim 1, characterized in that the pharmaceutical product is a blood product which is discarded if the TZ measurement is >7200 Kelvin times seconds.

4. The method according to any one of the preceding claims, characterized in that the critical temperature is greater than 6 °C.

5. The method according to any one of claims 1 to 3, characterized in that the critical temperature is less than 2 ° C.

6. The method according to any one of the preceding claims, characterized in that the memory is read and the code that was written in this memory is compared with the barcode on the pharmaceutical product.

7. A method as claimed in any one of claims 2 to 6, characterized in that it is determined whether the core temperature of the blood product has remained below 10°C during the time that the writing of the data points into the memory was activated.

8. The method according to any one of the preceding claims, characterized in that the pharmaceutical product is a blood bag and that it is determined whether the blood bag was exposed to room temperature for longer than 30 minutes.

9. The method according to any one of claims 1 to 7, characterized in that the pharmaceutical product is a blood bag and that it is determined whether the blood bag has been exposed to room temperature for longer than 15 minutes.

10. The method according to any one of the preceding claims, characterized in that an ID is stored on the EPROM memory, which can be uniquely assigned to a patient ID of a hospital patient.

11. The method according to any one of the preceding claims, characterized in that compliance with the cold chain is represented by a red/green traffic light system.

12. The method according to any one of the preceding claims, characterized in that the UHF transmission frequency is from 0.3 to 3 GHz.

13. The method according to any one of the preceding claims, characterized in that the transmission frequency HF is 3 to 30 MHz.

14. The method according to any one of the preceding claims, characterized in that the temperature data are stored in a database.

15. Device for monitoring the core temperature of pharmaceutical products, wherein a temperature data logger is attached to the pharmaceutical product, which contains a memory, an antenna for wireless data transmission, a microchip, a battery and a temperature sensor, and this temperature data logger is incorporated in a double-walled adhesive label and this adhesive label is attached to the pharmaceutical product, characterized in that the adhesive label (4, 5) is double-walled and that the double-walled adhesive label (4, 5) can be opened after use in order to be able to remove the temperature data logger again.

16. Device according to claim 15, characterized in that the double-walled adhesive label is formed from at least one film, and that one film of the double-walled adhesive label contains a punching which separates this film into two parts.

17. Device according to claim 15 or 16, characterized in that the temperature data logger is mechanically flexible.

18. The device according to claim 16 or 17, characterized in that parts of the adhesive side of the film contain no adhesive.

19. The device according to claim 15 to 18, characterized in that the temperature sensor system includes a flexible battery.

20. The device according to claim 15 to 19, characterized in that the

Temperature sensor system includes a real time clock.

21. The device according to claim 15 to 20, characterized in that the

Temperature sensor system includes an EPROM memory.

22. Device according to claim 21, characterized in that an ID is stored on the EPROM memory which can be uniquely assigned to a patient ID of a hospital patient.