Drug Evaluation Committee 2012-46 How to record temperature control of investigational drug
Related classification: Other
First published: March 2013
Question
In order to meet the various requirements for temperature control by each sponsor, we introduced a clinical trial temperature logger that meets the following requirements.
- Calibration of instruments once a year and issuance of a calibration certificate
- Data loggers that can record as well as measure temperature
- Backup function in case of power failure
- Measurement at 10-minute intervals
- Immediate alarm in case of temperature deviation or equipment failure
- Sends an e-mail if the alarm is not cleared after a few minutes (for nighttime, weekends, and holidays)
- Logs can be viewed on the screen, but are printed out once a month for CRA's review and provision of copies.
- Several times a month to confirm that the equipment is working properly
After introduction, several sponsors requested the following, given that they are described in the investigational new drug handling procedures
- Print out logs more frequently than monthly
- Once a day, temperature deviations need to be checked by a person
- Need to record the date, time, and signature of the check as collateral for daily checks
- Since the daily minimum and maximum values cannot be seen at a glance and do not meet the requirements of the handling procedure manual, only the form described in the procedure manual is acceptable.
- The handling procedure manual includes a temperature record (Form ○), and other forms are not acceptable.
Although Article 39 of the GCP guidance (formerly "Notice of Operation") states "in accordance with the procedure manual," our hospital considers this to be an excessive response that goes far beyond the principles of investigational drug management. As the Pharmaceutical Cooperative Drug Evaluation Committee, we would like to hear your opinion on the above request. Also, do you have any plans to unify the views of the Pharmaceutical Cooperative Association regarding temperature control at the facility side in the future?
Opinion of the Pharmaceutical Manufacturers Association of Japan (PMAJ)
There are no clear standards in GCP regarding the method of checking and recording the temperature of investigational drug storage areas. However, considering that the purpose of GCP is to appropriately manage investigational drugs in accordance with the storage conditions described in the investigational drug management protocol and to be able to explain this fact to third parties, the following points* are considered to be important.
- It must be possible to detect deviations from storage conditions when they occur.
- The degree (maximum temperature difference) and duration (time, days) of the deviation must be ascertainable.
- The investigational drug manager should be able to know the occurrence of deviations promptly and respond to the deviations.
- If alarm and e-mail systems are used, the equipment and systems must be regularly tested and maintained.
In general, we believe that the temperature control system introduced at your hospital covers the above points, but the detailed control method, such as the level of accuracy for detecting deviations, depends largely on the provisions of the study protocol (administration schedule, etc.) and the characteristics of the investigational drug. Therefore, we would like to ask your hospital to set the temperature of the drug at your hospital. Therefore, we recommend that you confirm the reason for the inadequacy of the temperature check and its record in your hospital with the sponsor and discuss how to respond to the inadequacy.
For the reasons stated above, the Pharmaceutical Manufacturers Association of Japan (PMAJ) cannot provide uniform standards for temperature checks of investigational drug storage areas and their recording methods, but we would like to raise awareness by presenting the approach described in our response so that member companies will not be required to take excessive measures.
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As of December 2023Although the points mentioned above are important points to keep in mind regarding temperature control of investigational drug storage locations and recording methods, we do not believe that temperature control records are mandatory in all cases. For example, some sponsors may not require temperature records if the investigational drug is stored at room temperature in a place where the risk to the quality of the investigational drug is significantly low, such as a place where the temperature is controlled 24 hours a day, including weekends and at night (air conditioning is in operation).