Regulating the chill chain

As the majority of new biopharmaceuticals require temperature-controlled distribution, it is vital to receive positive and auditable proof of temperatures from the point of delivery all the way back to the factory.

Many sources suggest that over 50 per cent by value of all new medicines will require temperature-controlled distribution. These new medicines, which cost hundreds of millions of euros to develop and bring to market, are the future of a pharmaceutical industry hard-pressed by patent expiry and government-driven cost reduction programmes.

As new products are launched it is essential to demonstrate clear evidence of increased efficacy over established cheaper alternatives. Since efficacy quickly deteriorates if products are stored and distributed at the wrong temperatures, all manufacturers are acutely concerned to ensure that the fruits of their R&D investments are always delivered in optimal condition. Worse still, products such as vaccines, if incorrectly stored, may actually harm patients by causing adverse reactions, illness and, in extreme circumstances, even death. With this in mind the regulatory authorities across Europe are becoming increasingly stipulative about how medicines are stored and transported in the supply chain.

The majority of the new biopharmaceuticals and vaccines require distribution between 2 and 8°C. Today the industry is developing more advanced techniques to ensure rapid deliveries and full product stability underpinning the requirements of a modern supply chain and patient safety.

Multi-stage and complex journey

There are currently a large number of stages, and therefore stakeholders, within the supply chain for temperature-controlled pharmaceuticals in Europe. The chain, which begins at the factory and ends with a patient, often involves contract bulk transport from the factory to an international shipping agent, international transportation by air, sea and/or road storage in a country warehouse or pre-wholesaler and then local transportation in small quantities to wholesalers, hospitals, doctors, retail pharmacists and even home patients.

For some time the manufacture of these products has been intensively regulated and established arrangements are in place for the international shipment of medicines from country of origin to country of sale. The complexity of the distribution task, however, increases exponentially as the product approaches the user. This is because the number of shipments increases and consignment size becomes smaller.

Isothermic boxes

Historically, for small shipments, isothermic boxes with ice packs or dry ice have been used. These boxes are cheap relative to the value of the product carried and offer the added benefit that non-specialist parcel carriers may be employed to make the deliveries.

With suitable validation it can be reasonably proven these boxes will ensure a suitable temperature is maintained for up to 72 hours after despatch. This validation, however, is limited to the circumstances of the test and cannot deal with the variations of ambient temperature that exist day to day within Europe. During the summer of 2003 temperatures of up to 45°C were recorded in the back of UK parcel carrier vehicles, and isothermic boxes can only provide limited protection in these circumstances. Add too much coolant and the product freezes; add too little and the product will overheat before it reaches its destination. Temperature in isothermic boxes can be monitored by a range of ‘telltale’ devices, but if the product has overheated, or indeed if it remains in transit too long, there is no way for this valuable stock to be returned and suspect stock is usually destroyed.

Chilled and multi-temperature vehicles

With these problems in mind increasingly manufacturers and other stakeholders are specifying that complete and auditable chill chain is maintained for their products’ distribution. This chill chain entails the use of chilled and multi-temperature vehicles which continually measure the transit temperature and a depot infrastructure equipped with validated chill stores monitored on a 24x7 basis. These methods provide customers with positive and auditable proof that suitable temperatures have been maintained from a print out at the point of delivery all the way back to the factory. So far, however, all of these measurements are historic and are only available after the event. The next generation of carriers will use technology to track the temperature from their vehicles using telematics to relay real-time data to their offices. In this way the centre can intervene if the temperature goes outside the agreed range and all stakeholders may gain absolute peace of mind.

Healthcare Logistics is just such a carrier and operates 80 vehicles exclusively engaged in the distribution of chilled medicines and diagnostic products. Healthcare is the UK pre-wholesale subsidiary of Celesio AG, the largest pharmaceutical distribution operator in Europe.