It is clear that need for regulatory considerations, special handling and volume shipments of pharmaceutical products require detailed planning. This allows for shipping of pharmaceutical products from the pharmaceutical manufacturer to the healthcare provider in the correct environmental conditions so to ensure that the products are not compromised. Importantly pharmaceutical products must be packed in suitable material, monitored by approved temperature monitoring equipment, and also the method of transit must meet regulatory standards with a high degree of assurance. The term ‘cold chain’ does not only refer to the packaging of pharmaceutical products in insulated containers (including approved quantity of refrigeration) but also include its transport and storage at final destination.
Each component of the cold chain should be measured, analysed, qualified and understood to guarantee the patients safety, quality of product, and preserve the products potency. For this reason there should be documented procedures describing the proper procedures for each step of the cold chain. Staff should be trained in the proper handling, storage and temperature monitoring procedures which must also included the proper use of temperature monitoring equipment. Finally staff should be able to react to emergencies that may result in storage temperature deviation from the recommended temperature range.
Critical to product safety is the equipment used for monitoring storage temperature during transit. Following is two case studies demonstrating the ease by which failures of cold chain management may occur.
Case Study #1
Suppose that the temperature monitor for the pharmaceutical product shipment shows that the storage temperature exceeded 8°C for the entire duration. Inspection determined that the product has been packed in the correct container with the recommended configuration. All previous shipments have been shipped without any problems; that is there was no deviation in the recommended 2°-8°C temperature ranges. Examination of historical transit data shows that the gel pack configuration and insulated container performed to specification during the winter. Temperature ranges for the product shipment was within the recommended range and therefore the configuration was accepted.
However when the pharmaceutical product was shipped during spring time the ambient temperature was much higher resulting in the configuration not having adequate cooling capacity to keep the temperature within the container within range. In addition the container did not have enough insulating material with the effect that the higher external temperature conducted heat more easily into the insulated container. The validation procedures did not take into account all variables that may have effect on the product in transit during the year. Clearly any validation procedure should take into account the worst-case temperature exposure conditions that may occur. Therefore when compiling protocols for the transportation of pharmaceutical products the lowest and highest ambient temperature should be considered.
Case Study #2
A pharmaceutical shipment has been prepared using the recommended configuration from the pharmaceutical manufacturer and a qualified container. However the temperature monitoring device showed that the shipment temperature was higher than the recommended maximum temperature allowed. For this particular product the recommended temperature range should not deviate from the recommended temperature range of 2°- 8°C. Upon inspection it was found that the proper insulated container was used, recommended quantity was not exceeded, correct refrigerants were used, and the product was packed with the proper configuration.
To the packer the refrigerants felt cold therefore no one suspected that the refrigerants were not cooled sufficiently to ensure adequate cooling capacity. It was subsequently found that the refrigerants were not kept at the required temperature during packing.
Consequently by not keeping the refrigerant at the required temperature, cold or frozen, for a sufficient amount of time, the refrigerants outer layer may feel cold but may not internally be at a uniform temperature. When refrigerating refrigerants it is recommended that the refrigerants are refrigerated or frozen for several days prior to use. Protocols should specify the exact procedures for the preparation of refrigerants. Protocols should include information such as the correct storage temperature ranges and the length of time to be stored in refrigeration before used in shipments.
By simply feeling or measuring the external temperature of the refrigerants are not sufficient to guarantee adequate transportation temperatures.
Importance of Temperature Monitoring Equipment to observe the “cold chain”
Temperature monitoring equipment is vital in ensuring that the cold chain is preserved during transport and storage of pharmaceutical products. Deviation from manufacturers recommended storage temperatures may have a detrimental effect on the safety and effectiveness of stored pharmaceutical products. The only effective way of monitoring temperatures within storage units/containers is by way of temperature monitoring equipment. Most providers require records indicating temperature ranges during transportation. For this reason temperature monitoring equipment manufacturers provide an extensive range of continuous monitoring devices, digital data loggers, and temperature alarms.
Following is a broad description of these devices:
Temperature alarms only sound if the cooling/refrigeration unit temperatures exceed the predefined temperature range. Most are programmable but do not record temperatures. Temperature alarms may be fitted to cooling and refrigeration units and also insulated containers. However temperature alarms are only effective when responded to promptly.
Digital data loggers
Digital data loggers continuously records temperature. Data loggers are programmable allowing temperature readings to be recorded at set intervals. These reading may be downloaded to a personal computer for review. Readings may be included in records to ensure that the “cold chain” has not been broken at any stage.
Digital data loggers must have the following features:
- Built in temperature alarm warning that temperatures are out-of-range. Any deviation even for a short time may compromise the integrity of pharmaceutical products.
- Ability to record at least 4000 temperature readings.
- Readings should including maximum, minimum and current temperatures.
- Must be able to interface with a personal computer or preferably tablet.
- Must be VFC complaint.
Continuous monitoring devices
Continuous monitoring devices provide information on when and for how long a pharmaceutical product was stored outside the recommended storage temperature. Although continuous monitoring equipment is similar to digital data loggers they differ in the following important aspects:
- Digital display that allows viewing of temperatures without opening the storage unit.
- Superior accuracy, able to record temperatures to within +/- 0.5°C.
- Capable of recording short and long term temperature readings.
Clearly determining the special requirements for handling cold chain pharmaceutical products are numerous and challenging. Issues such as environmental conditions, proper refrigeration of refrigerants, duration of transit, temperature monitoring equipment, and the correct insulated storage container play a major role in the viability of the delivered product. However these special requirements are manageable by adhering to the proper protocols. With this in mind making use of the proper temperature monitoring equipment will have a positive effect in the management of complex interacting parts.
Temperature monitoring equipment is the only effective method for monitoring and recording temperatures during transport and storage ensuring that the cold chain has not been broken at any stage.