March 17, 2021

The journey to a successful transport validation study

By Peter Black, Cytiva

Many steps and obstacles exist in bringing a drug to market, and each needs to be carefully navigated. One that can easily be overlooked is the safe transportation of drug substances between the manufacturing site and the fill-finish provider.

Preparing for the journey ahead

There are many steps and obstacles on the metaphorical road to bring a drug to market, and each of these must be carefully navigated to arrive safely. One that can easily be overlooked, until it is encountered, involves a physical road, and that is the safe transportation of drug substances between the manufacturing site and the fill-finish provider.

Such a journey may involve many miles and could include several handling steps and different forms of transport. Each of these adds risk to the process and to the precious cargo within. Throughout the duration of the journey, and during the storage steps both before and after the transport, the safety, efficacy, and potency of the bulk drug needs to be maintained. For biologic drugs this almost always involves reduced temperatures and a carefully controlled and monitored cold chain. Stability of the drug substance and shelf life are often maximized using freezing as low as –80°C. We have discussed the increasing awareness of the challenges associated with these freeze/thaw processes for bottles and biocontainer bags in this blog.

At these low temperatures, all polymeric containers become brittle, and this change in their mechanical properties makes them more susceptible to damage. A risk assessment of the process quickly identifies this transportation as a step that needs control and mitigation to prevent failure of the containers used to hold the bulk drug substance. This is especially true for biocontainer bags that, when combined with plate freezing, enable this control during the freeze and thaw processes.

The need for transportation data to support process validation and risk mitigation is also mirrored by bodies such as the International Air Transport Association (IATA) to ensure compliance with the dangerous goods regulations as recognized by the International Civil Aviation Organization (ICAO). These protect the environment and personnel. For biological substances (UN3373), these simply state “a leak-proof primary container with sufficient absorbent material to absorb the entire contents if the container should break must be placed in a secondary leak-proof container surrounded by an outer rigid packaging material with a strength and size suitable for the contents.” While these ensure adequate management should leakage occur, given the valuable and precious contents, confidence that such an event will not occur is preferable. Here International Safe Transit Association (ISTA) procedures (3E and 3H) are generally performed to demonstrate that the packaging is adequate for shipment.

Taking the next step

As you may know, we have collaborated with Single Use Support GmbH to provide a simple, yet robust combination of Allegro™ biocontainer bags and single-use systems and RoSS storage and shipping solutions. Together these form the heart of our Freeze and Go Solutions, but the question remains. Together, will they withstand the rigors of transportation?

To answer the question, shipping containers and biocontainer bags from 1 L to 10 L in size were tested. Biocontainer bags were filled to the maximum and partial fill levels of each size and frozen to –70°C. Each was tested for shock, vibration, and horizontal robustness according to ISTA procedures after being shipped from Single Use Support in Austria to an ISTA certified laboratory in France using a Full Truckload (FTL) delivery service. This is approximately a distance of 800 km, and such a journey was chosen to simulate a long-haul road freight shipment including a truck and air shipment.

Before shipment, each Allegro™ biocontainer bag was contained within an appropriate RoSS shell and installed in a ROSS.SHIP container with the space filled with tailor-made, expanded polypropylene spacers to guarantee immobilization of the biocontainers but with sufficient space to allow cold air circulation when packed with dry ice.

After shipment, robustness testing was completed, and the shipping containers returned.

Are we there yet?

  • All robustness testing was successful.

  • Thermal data logging confirmed that target temperature was maintained throughout the journey.

  • After thawing, visual inspection of the biocontainers confirmed no visual damage to the biocontainers, tubing, or sterile connectors.

  • Helium leak testing confirmed the integrity of the systems after transportation, thawing, and emptying including all tubing and junctions.

Our results confirm that the systems maintained their integrity throughout the freezing, transportation, and thawing process, and we know they will do the same when they carry your precious cargo.

Learn more about our solutions.

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