Active and Passive Shipping Systems and Transport Equipment

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Thursday, 8 September 2022 9 .00 - 17.15 h

Stability Studies to Support Shipping/Distribution of Pharmaceuticals and Biopharmaceuticals - Live Online Training

In this article, we will provide some information and examples of active and passive shipping systems and equipment used for the transport of time and temperature sensitive pharma products.

Note: The following text is an abridged excerpt from a newly developed pre-reading material exclusively for participants of the ECA Live Online Training "GDP for Beginners" on 02/03 March 2022. The package was developed and written by Dr Zvonimir Majic from Teva Pharmaceutical Industries Ltd.

Passive Shipping Systems

Storage and transportation (handling) temperature vs. pharma product temperature is probably the single most important aspect of transporting and distribution of time and temperature sensitive pharma products. In other words, the product label storage claim might not necessarily correspond to a transport temperature range defined for particular transport solution. The actual product temperature is maintained through specifically engineered and qualified shipping system composing of insulation materials designed to capacitate certain amount of pharma product, packed together with the temperature stabilizers or refrigerators.

A specific internal temperature can be maintained for a defined period of time subject of preanticipated maximum and minimum external temperatures used during shipping system qualification. For some types of passive shipping system a contributing factor for maintaining internal (in the passive equipment) temperature at required level is storage of the equipment – shipment at different, stabile temperature range.

It is therefore important to distinguish product temperature requirement for transport vs. transport temperature range.

Standard transport ranges common for all transport modes are:

• +2°C to +8°C, Cold
• +15°C to +25°C, Controlled room temperature
• +2°C to +25°C, Extended room temperature
• -20°C to -10°C, Frozen

Additional handling instructions on transport documents, such as, “Do not Freeze” can be used depending on a transport mode. Such instructions are however optional since the most relevant is the one of the transport ranges above.

Most conclusive advantages of passive transport equipment can be summarized in following points:

• No risk of failure of any mechanical or power unit components.
• Equipment can be used for multiple shipments or disposed after single use.
• Passive shipping systems typically have low tare weight thus adding less cost on transport.
• Insulation materials have improved over years providing more protection with same weight of packaging and being more environmental friendly.

The disadvantages of passive transport equipment can be summarized in following:

• Some types of passive transport packaging requires prior temperature preconditioning to ensure thermal stability over predefined time.
• Some refrigerants are restricted in airfreights, such as dry ice – Carbon dioxide – UN1845 and might require replenishing during transit.
• Passive transport packaging assembly requires training and might be time consuming. Components require storage capacity in amounts sufficient to ensure supply.
• Multiple components require stock control and operability inspections in case of multiple use.
• Passive transport equipment using refrigerants is limited in efficiency of maintaining temperature range and depends on external environmental conditions.
• Qualifications of passive transport equipment is showing limited durability and largely dependent on external temperature conditions. The higher are temperature extremes – the less durability during transit.

Requirements for more effective passive transport equipment with more effective insulation materials and temperature stabilizers, have urged packaging industry to develop high performing passive containers. These containers are proven to have good performance results with less sensitivity to extreme external conditions. It is however important to remember all of those are qualified only for the limited duration and require specific storage temperature range in transit to ensure maximum efficiency. Regardless of the how good the insulation is or ability to maintain certain temperature range, all passive and active shipping systems require defined handling and transport processes with risks identified, analyzed and mitigated on all critical control points. It is thus important to perform documented risk assessment on intended use prior any use of passive or active shipping system for time and temperature sensitive pharma products.

In this respect, and as a part of a route definition and risk analysis, following simple activities on reducing risk of temperature excursion are important for temperature management:

• Minimize exposure to external temperature conditions during loading, transit an offloading beyond predefined transport temperature range
• Avoid sudden or prolonged exposure to heat sources like direct sunlight 
• Reduce operational time in ocean ports where containers are not plugged in to a power source
• Reduce time on airport tarmac known to be a source of extreme high and low temperatures as well as air circulations
• Reduce time during handling and shipment / documents preparation in uncontrolled temperature environment
• Avoid use of waterproof coverings in direct sunlight to avoid creation of greenhouse effect
• Select direct routings wherever possible

Active Shipping Systems

The latest generation of active shipping systems mainly falls under airfreight Unit Loading Devices (ULDs) which are containers designed and approved long distance aircraft types. Such containers all operate on same principles thus organization can rationalize their use by performing risk assessment on the interchangeability. This means that units from different manufacturers having a same design, approvals and intended use can be used without prior qualification or approval. This may come useful especially in times of frequent demand for active containers on the market and their reduced availability.

Like passive, the manufacturer qualifies all active shipping systems. This comprises of Design Qualification (DQ), Installation qualification (IQ) and Operational Qualification (OQ). Pharma manufacturers – Shippers are often conducting Performance Qualification (PQ) by deploying
such units over a risks assessed and mitigated airfreight route.

Main operational principles of active containers can be summarized in following points:

• Unit is equipped with electric heating and compressor cooling system.
• Units are using internal rechargeable (nickel metal hydride) batteries to operate heating/cooling system.
• Units have ability to quickly re-charge by plugging the unit to standard grid power source with the enclosed cable.
• Set temperature ranges are from 0¢XC to +25¢XC thus making them suitable for both cold chain and controlled room temperature product.
• These units are most frequently used for refrigeration or +2¢XC to +8¢XC products.
• Door can be locked and seal applied for enhanced security. This feature is also depending on airfreight security regulations. Unit has capability of recording the events of door opening to verify security integrity.
• Unit has capability and capacity of recording internal, external ¡V exposure and set temperature during entire trip.
• Units are well constructed to sustain standard airfreight handling and manipulation processes with sufficient amount of polyurethane foam as an insulator.

For the airfreight most common active unit loading device units are coming in three sizes:

• Capacity of one euro or US pallet ¡V size code RKN
• Capacity of three euro pallets or two US pallets ¡V size code RLP
• Capacity of 5 euro pallets or 4 US pallets ¡V size code RKN

Most conclusive advantages of active shipping transport equipment in airfreight can be summarized in following points:

• Active units do not require specific constant, temperature-controlled storage during usage. They can be stored in general, non-temperature controlled warehouse, plugged in to a power source.
• In some circumstances pharma manufacturers – Shippers can load active units by themselves and seal them. Additional consideration in risk assessment is made on security requirements and screening of the payload when required.
• Active units can typically be leased anywhere in the world. However, their availability for pickup and delivery (to end the lease) needs to be considered in risk assessment on intended use. Those containers can be leased globally
• The RKN and RLP size active units can be forklifted thus additionally convenient for handling.
• Loading and offloading of active containers is a simple activity as well as operation of control panel for temperature setting.

The most common disadvantages in using active airfreight units can be summarized as follows:

• Despite the global operations model there are limitations related to network and aircraft types for these containers.
• The tare weight ¡V one that is additionally payed for by the Shipper is high. Tare weight of an RKN is 880kg, tare weight of RKN is 635kg and tare weight of a largest RAP is 1.100kg.
• Active units cannot be purchased, only leased for which there are pickup and return charges.
• To ensure their safe and efficient operation, active units require plug-in to grid during transit at the airport to recharge the batteries.

Besides the airfreight, active temperature-controlled transport vehicles, equipment and containers are also used in two other, main transport modes for pharma, road and ocean.

Principle of temperature-controlled ocean container (TCU) is similar to this of a temperaturecontrolled truck with exception of T-bars positioned on the floor of the ocean container. The air in ocean TCU is drawn from below the ceiling of the container into the refrigeration unit where it is cooled or heated to the predefined temperature range, i.e. set point and then sent across the container through T-bars grid on the floor of the container. When prepared for transport, these containers are plugged in to an electricity or genset (power generator for trucking from the loading point to the ocean port of origin).

Like in airfreight route planning, in ocean transport a risk assessment is required to determine the suitability of the transport mode and shipping system vs. product planned for shipping. Conclusion might be that not all products are suitable for ocean transport mode and as such, an alternative transport solution is required.

Predisposition for selection of any passive or active shipping system is a successful qualification and documented risk assessment on intended use.