The increasing number of new biological entities and biosimilars in development means that new strategies are needed to safeguard product integrity during clinical studies. Efficient management of complex biologic/biosimilar studies requires a keen understanding of the clinical supply challenges associated with handling these highly sensitive products, as well as the development of a solid plan to mitigate the risk of delays due to compromised product integrity.

Sensitive issue

Not only could an interruption or delay in clinical supply have a detrimental effect on the study timeline and budget, but it can also potentially prevent patients from receiving timely treatment. Failure to preserve the integrity of highly sensitive cold chain investigational medicinal products (IMPs) and high-value and/or limited supply reference products can lead to expensive replacement costs, long lead times, or both. One of the first steps sponsors should take in their efforts to maintain product integrity is to understand common cold chain shipping challenges.

Beyond maintaining a global cold chain, common difficulties encountered when obtaining reference products can also threaten to derail a study. For example, some innovators may request upfront information about the study and the intended use of the drug before even considering a sale.

Sponsors may also face marketplace shortages, high costs and long lead times, and even if the product is readily accessible, it may not be available in the desired packaging, quantity or format, such as single or multiple lots. Stability data, while vital for ensuring stringent end-to-end cold chain management and evaluating the impact of any temperature excursions, can be difficult to obtain, or very short-dated.

Maintain integrity

As well as ensuring a sufficient supply of the reference and innovator product, cold biologic and biosimilar studies require the use of temperature-controlled packaging systems that use materials with specific thermal characteristics in order to ensure that the thermal integrity of clinical supply shipments are maintained for defined durations.

Conventional, single-use systems use expanded polystyrene (EPS) and water-based coolants. The former are relatively inexpensive and are commonly used for durations of 72 or 120 hours. However, they are vulnerable when external temperatures are above 25 or below 2°C.

The newest cold chain shipping technology uses vacuum-insulated panels (VIPs) and phase-change materials (PCMs). VIPs have insulation values ten times greater than EPS and are also spatially efficient; this thinner insulation leaves more room within the shipping container for the product. PCM works by absorbing and then releasing thermal energy to maintain a regulated temperature and mirrors the external temperature until the PCM melting point is reached, allowing the product to stay at a designated temperature for much longer periods of time than is possible with an EPS system.

One of the first steps sponsors should take in their efforts to maintain product integrity is to understand common cold chain shipping challenges.

The benefits of new VIP/PCM systems include reduced physical storage requirements because the assembled shippers and components take up less space than EPS products. The amount of required coolants and components is also reduced, and year-round pack-outs are available, eliminating the need to change the ratio of coolant materials seasonally – more ice and less water in summer, for example.

The newer materials are also quicker to pack, reducing cycle time and increasing the number of shipments that can be packed in any given day or shift, while the likelihood of human error also decreases.

Quick turnaround

VIP/PCM systems are more expensive than conventional EPS/water systems, but based on volumetric weight, it can be more economical to ship products using VIP/PCM components. Furthermore, some VIP/PCM systems are reusable and some of the components are more recyclable than traditional EPS systems.Reusable systems also enable the recipient to remove the product from the packaging immediately, put it under the correct storage conditions and then give the reusable shipper box back to the waiting courier, thereby reducing the cost of disposal for the facility.

Catalent’s specialised expertise in cold chain shipping and logistics can enable sponsors to avoid problems while products are in transit, avoid unnecessary and costly delays, and maintain the integrity of their valuable products. Using new technology such as VIP/PCM, systems can assist in mitigating distribution risks and safeguarding product integrity of valuable materials.