Alarms and excursions

The risks of exceeding parameters in cold chain distribution are well known, but pharma and biotech products in the warm chain are also vulnerable, says Geraint Thomas, of Laminar Medica

Breaches of GDP (good distribution practice) do not happen, as received wisdom would have it, just in the cold chain. According to Geraint Thomas, technical director of Laminar Medica, a leading European manufacturer of TCPs (temperature controlled packaging) for the pharmaceutical and biotechnology industries, no less than 23% of serious GDP deficiencies recorded in the sector during 2003/04 were not related to the cold chain and the figure included a large number of TCD (temperate chain distribution) failures.

TCD is the term for ambient shipping or the 'warm chain' coined by John Taylor, quality and standard manager of the Inspection and Enforcement Division of the MHRA. It involves the storage and transportation of products that are chemically and physically stable between 15 and 30°C (with the occasional excursion to 35°C being permitted for some products). Due to a vastly increased global traffic in infectious substances, diagnostic specimens, cell cultures, vaccines and blood products as well, as the growing number of controlled temperature pharmaceutical products, TCD activity has expanded vastly in recent years.

unfamiliar effects

While most people in the industry are aware of the results of cold chain excursions not so many are familiar with the effects of their TCD equivalents. They can lead, says Thomas, to both physical and chemical changes in products being shipped.

The effects of a 30°C excursion on products in the 15-25°C range, for instance, could lead - depending on the item - to separation of emulsion systems, sedimentation of active ingredients in suspensions and semi-solids, and loss of volatile components such as chloroform and flavouring agents from oral liquids. Chemical changes as the result of this level of temperature excursion can include accelerated degradation leading to loss of shelf life, as well as the possible production of toxic substances. Excursions can also bring about undesirable interactions with packaging materials as well as an increased risk of interaction between components in aqueous solutions.

The requirements for warm product shipping are entirely different from those for frozen or chilled shipping. Conventional packaging for TCD requires shippers of highly complex configuration that take up a lot of expensive payload space and whose assembly requires considerable training to be undertaken. This is because changes in ambient temperatures during transit demand packaging designs that must cope with positive and negative ambient temperature stresses.

Conventionally this means the incorporation of solid and liquid PCMs (phase change materials). The former prevents the payload from getting too warm and the latter stops it from getting too cold. These conventional systems achieve the necessary stability, but assembling the package is complex and costly - and complexity almost inevitably entails more things that can go wrong.

new development

Now Laminar Medica has developed a new PCM that will, says Thomas, change the way we think about TCD. Designated Medisorb, it is a salt-based inorganic PCM that offers multiple individual phase changes over a range of temperatures.

This is different from the traditional organic PCM that offers only a single-phase change over a small temperature range. It also means that there is just one preparation instruction for the shipper and the payload is optimised while performance is greatly enhanced and extended.

A further benefit is that Laminar's new PCM can, given reasonable handling, offer almost indefinite re-use and can also be recycled.

In a recent test against the equivalent water-based system, the new PCM held a 20-30°C temperature for 102 hours, whereas the conventional system managed only 12 hours. Medisorb is already in action successfully shipping skin cells all over the world for an Australian company.

Laminar believes that its salt-based inorganic PCM is the way forward for TCD and that the knowledge that a cost effective and highly efficient TCD shipper now exists will further stimulate the growth of warm chain activity.