Cooling the cold chain

John Pring and Prof Geoff Tovey discuss the problems associated with transporting drugs around the world, while ensuring they arrive in the same condition as they departed

The value of sensitive drug materials shipped yearly has been put at £300bn, and the value of these shipments is growing at approximately 9% annually. Yet ensuring that product reaches the destination in useable condition is at the mercy of problems of transport delays, bank holidays, acts of god and more crucially the human interface.

Unacceptable levels of failure occur in the systems by which these sensitive medical materials are distributed. Published data on this is difficult to find but figures in the range 5-9% have been acknowledged by industry.

The World Health Organisation (WHO) suggests 40% for the vaccine cold chain in the field. Inspectors are examining critically at audit, records of temperatures experienced by pharmaceutical materials in storage and transit with a view to stricter enforcement.

Many companies are now reviewing and updating their arrangements for collecting and archiving such data. Each company has its own non-standard procedures for testing of containers. They use particular quality system methodologies for specific applications.

It has hitherto been difficult to obtain definitive data that each package has arrived in compliance with the temperature regulations. However gradual development of container and logger technology has led to a major leap forward in the control of these variables.

This is achieved by reusable containers, typically such as those provided by Kryotrans, which are highly durable. They benefit from design experience gained in the food industry, with separately accessible refrigerant reservoirs so that the contents are not accessed during replenishment of the refrigerant, where this is required. Refrigerant can be in the form of dry ice, eutectic plates or locally produced wet ice. Dry ice is typically used for summer distribution and eutectic plates in winter mode. The various temperature ranges available are shown in table 1.

Reusable containers can have improved insulation without significantly increasing the per trip cost. They have integral loggers which provide complete accurate audit trails for each trip monitoring core temperature, ambient temperature and tampering. This gives the capability for particular handling events to be attributed to a particular limb of a multimodal journey. This trip record is a powerful analytical tool.

The reusable container system is complemented with a software package which controls downloading and handles shipping documentation for sending, receiving and optional archiving via the internet. Calibration [three point ISO 45001] is valid for 50 trips after which containers are repurchased.

Most importantly, costs for using this system are competitive with those for disposable systems. Cost analysis includes that of containers and electronics amortised over the life of the reusable container. For disposable containers, indirect costs including calibrations and validations should be taken into account.

For licenced products, complex packaging configurations are often defined in cGMP quality systems. The mediscience industries currently utilise approximately 50bn litres of disposable plastics and cardboard per year in packaging materials ending in landfill. In virtually all cases, materials used are disposable and on arrival at destination, these materials are an environmental blight. Extensive legislation now covers their disposal. This is a time-consuming and expensive business. It is also a strong indication for the introduction of reusable containers.

logging conditions

Validation of containers for cold chain use is time consuming and expensive. It is also a quality system requirement. Each 'purpose' i.e. each combination of destination and package type requires to be validated. Loggers, which must also be validated, are included within the container on a sample basis or more rarely as routine. They are often not returned to the sender, causing further expense. If, however, reusable containers are employed, the electronics can be of high quality while adding little expense to the project. Furthermore, the need for validation of the combination of the logger with each disposable box is avoided and the container can be validated in ways closer to those used for validation of refrigerators. This validation is considerably less onerous.

Logging of conditions in transit enables the attribution of responsibility for failure to a particular leg of a multimodal distribution chain. This will facilitate a new, financially viable system of insurance for sensitive medical materials in transit.

In addition to product temperature, ambient temperature and tampering, which are provided as standard, the client company can choose from pressure, orientation, shock, humidity, pH, and light data options. There is also a prolonged inertia option. This will log periods during which the container fails to move. This is often indicative of a failure in transit. Kryotrans is also producing containers capable of being tracked by barcoding and technology based on satellites and telephony.