Keeping Cool Under Increasing Pressure

Geraint Thomas, Technical Director of Laminar Medica, explains how the latest temperature controlled packaging technology is helping pharmaceutical companies to meet the growing challenge of shipping temperature sensitive products around the globe.

In this time of global economic slowdown, with operating margins being squeezed, pharmaceutical companies are under pressure to cut costs while at the same time ensuring they comply with ever tougher legislation. This is especially true in the area of temperature controlled shipping, where rising freight costs are set against a background of complex standards that vary from country to country and region to region.

While stringent laws and guidelines relating to the transportation of pharmaceuticals are necessary to protect the health of patients, complying with the regulations requires sophisticated and dependable transportation solutions. The extended distances and durations now being travelled by pharmaceutical products has led to the development of temperature controlled packaging technology that is capable of protecting its contents in a wide range of ambient temperatures, so that temperature critical drugs can be shipped safely and cost effectively whatever their destination.

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New regulations

In recent years, the number of laws and regulations that drugs manufacturers and distributors must meet when shipping temperature sensitive products has increased considerably. In Europe a number of EU Directives are now stringently enforced, detailing the measures that must be taken to ship pharmaceuticals safely. For example, EU Directive 2005/28/EC outlines the legal requirements that now apply to the manufacturing or importation of clinical trial materials, while EU Directives 2003/94/EC and 2001/83/EC lay down further principles and guidelines for good manufacturing and distribution of pharmaceuticals.

In addition to the laws and regulations that must now be met, there are also an increasing number of guidelines and best practice documents available, which attempt to help standardise global shipping practices. These include the PDA’s (Parenteral Drug Association) Technical Report No.39 on protecting temperature sensitive products, which has been put together by its Cold Chain Management Interest Group and reviewed by technical experts from the industry, and the Irish Medicines Board’s Guide to Control and Monitoring of Storage and Transportation Temperature Conditions for Medicinal Products and Active Substances.

With so many laws, regulations and guidelines now applicable to the distribution of temperature sensitive pharmaceuticals, ensuring you distribute products in a lawful and responsible way can be complex and time consuming. One of the best ways to reduce the time, money and resources needed is to work closely with a temperature controlled packaging specialist that can offer advice and guidance as to the relevant legal requirements and best practices.

Increasing demands

The increasingly global nature of the pharmaceuticals industry is resulting in the need to transport drugs over extended distances and durations, increasing the challenges facing the manufacturers of temperature controlled packaging solutions. Products are often required to pass through a number of different climates on various modes of transport, making it essential that packaging is chosen that can continue to protect its contents as the ambient temperatures change.

In response to these increasing demands, recommendations have been published for classifying countries into four zones, ranging from Zone I: temperate, less than +20ºC (e.g. Germany, Russia and Canada), to Zone IV: hot and humid, more than +24ºC (e.g. Taiwan, Singapore, India and South America). While these guidelines go some way to enabling appropriate storage measures to be taken, there remains a degree of ambiguity due to national variations in climate.

Additionally, there are a number of logistical issues that can add to this complexity. For example, many of the less developed countries that products must pass through have limited infrastructures and storage facilities, making it difficult to ensure that the pharmaceuticals being shipped are handled in the correct manner and within the expected timeframe.

The need for temperature sensitive drugs to be protected against more extreme temperatures and for longer durations has led to the development of more effective and dependable packing solutions that are able to guarantee the integrity of the pharmaceuticals being shipped, while keeping costs to a minimum by maintaining compact and lightweight designs.

Dependable control

This new generation of temperature controlled packaging offers considerably higher levels of protection than the solutions suitable for less demanding shipments, which typically incorporate frozen or chilled pouches of water combined with insulating liners in cardboard outer cartons.

More sophisticated protection is achieved through the use Phase Change Materials, or PCM’s, which offer a proven, versatile and cost effective method of protecting valuable products for both cold and temperate chain distribution. PCM’s maintain a desired temperature range by absorbing or releasing large amounts of heat energy (Latent Heat Capacity) as they move from one physical state, or phase, to another; for example, from a solid to a liquid.

The latest PCM solutions, from leading manufacturers such as Laminar Medica, use specially developed hydrated salt solutions or paraffin materials. These offer a constant temperature energy storage and release at engineered temperatures, unlike ice, which does so only at 0ºC. Additionally, these PCM’s can store almost as much latent heat energy as frozen water, so that overall pack sizes can remain unchanged. Perhaps most importantly, these new materials offer greatly extended performance durations over considerably wider ambient ranges, making one PCM suitable for use in packages transported through combinations of climatic zones and for use in both winter and summer conditions, in contrast with traditional technology, which requires a separate solution for each.

PCM’s are ideal for international shipments as they are simple to store and prepare for use. In cold-chain applications (+2°C to +8°C) they should be frozen in a -20ºC freezer for up to a day before shipping and then chilled (+5°C) for 24 hours. Packages can maintain stable internal temperature conditions, even when placed in a "chiller" on route to their destination. This solves many of the problems distributors have previously been faced with when their products have been passed to third parties.

Versatile protection

Where pharmaceuticals need to be kept deep frozen, PCM technology is available that allows the products to be kept below -15°C, offering a safer and more effective alternative to traditional dry ice solutions. Dry ice poses a number of problems in shipping, and air transportation in particular. CO2 undergoes massive volume expansion as it sublimes from a solid to a gas; consequently, dry ice (solid CO2) is identified as a Class 9 Miscellaneous Dangerous Good for air transport, requiring packages to be designed to prevent the build up of pressure within them. As such, the quantity allowed on airlines is often restricted, causing considerable problems when a product needs to be air freighted, and freight premiums are applied, escalating operational costs for shippers. CO2 is also recognised as one of the major Ozone depleting gases in the atmosphere.

A further downfall of dry ice is the fact that its Latent Heat energy release is at -80°C, which makes it too cold for direct contact with many delicate products and potentially damaging; for example, cold temperatures can cause shrinkage or perishing of the rubber bungs used to seal many primary packages, while a product can also lose its sterility due to the migration of CO2 into its primary packaging. All of these problems can be avoided using PCM technology.

It is worth noting that the recent developments in PCM’s are not limited to cold chain distribution; a new generation of PCM’s has been specifically developed to provide multiple phase changes over a range of temperatures for temperate distribution. The latest products are designed to provide temperature stability at +15 to +25°C, +15 to +30°C, or +20 to +25°C, and are able to maintain product temperatures commonly referred to as ‘Controlled Room Temperature’, for lengthy service durations in excess of 100hrs.

Monitoring temperature control

With many of the latest guidelines now stressing the importance of recording the temperature inside a packaging system as it is transported, the use of data logging devices is becoming commonplace. These devices can enable detailed information to be collected, such as the average temperature of the inside of the package over the shipping period (including calculations of Mean Kinetic Temperature), the highest and lowest temperature recorded, and any time spent outside of the pre-set high and low limits.

This data logging technology typically consists of small electronic devices that can be placed inside a package with the pharmaceuticals to monitor temperature, humidity, and other conditions for items in-transit or storage. The devices are able to provide an accurate record of the temperature inside a package over the course of its journey to ±0.5°C accuracy, and in ambient temperatures ranging from -30ºC to +70ºC. When the package has reached its destination, information can be downloaded to a PC for detailed temperature history, which can then simply be forwarded electronically for subsequent analysis.

In addition to providing detailed information, these systems can also be programmed to provide a visual alarm if the temperature inside a package exceeds or approaches minimum or maximum tolerances. This can have a significant impact on the safety of a shipment, alerting handlers immediately if there is a problem and allowing remedial action to be taken quickly.

In summary

With increasing pressure on drugs manufacturers and distributors to cut their operating costs, the need to find a cost effective method of protecting temperature sensitive goods is now essential. This requirement, coupled with stringent laws and regulations, has led to the development of a new generation of sophisticated yet affordable temperature controlled packaging technology. By using the latest PCM based solutions, sensitive pharmaceuticals can now be shipped quickly, efficiently and safely.