Clinical trial design is getting more complicated, time pressures to deliver on trials are increasing, and sponsors are looking to save costs wherever possible.
Typically, Investigational Drug/IMP is protocol-specific with the protocol added to the label following manufacturing and packaging. If a kit labeled in this usual way does not get used by a patient, it is wasted.
But by sharing medication kits across a suite of protocols/programs, sponsors can minimize the amount of IMP wasted during clinical trials and reduce packing, shipping, and costs. And sponsors recognize an additional benefit of aligning with program-level medication management initiatives.
Here we review additional factors sponsors should consider to fully maximize savings through medication pooling.
Site vs. Depot-level Pooling
In a previous blog, we demonstrated how medication pooling can help reduce wastage with a focus on the options of and considerations for:
- Site-level Pooling: medication is only allocated to a protocol at the time of dispensing to the patient
- Depot-level Pooling: medication is allocated to a specific protocol upon inclusion in a shipment
A recent review of how Calyx customers have leveraged pooling over the years has revealed additional variants and considerations for successful medication pooling strategies. Calyx has experience supporting sponsors with five different variants of depot-level pooling alone.
“When consulted early, Calyx trial supplies experts can present IRT design options to meet the study suite/program needs.”
– Malcolm Morrissey,
Head of Statistics & Product Support Services, Calyx
Additional Considerations for Effective Medication Pooling
The five variants of medication pooling managed by Calyx IRT are governed by responses to the following questions:
- Where is the packaging list held?
- Who manages the pooling: sponsor or IRT?
- When do the kits become protocol-specific?
- What is on the label?
- When are the kits labeled?
Depending on the response to these questions, a combination of approaches can be used.
It is important to note that all these variants impact the sponsor’s processes and labeling plan with regulators.
Does Pooling Affect RTSM Setup?
Pooling may not impact the RTSM setup if handled manually by the sponsor outside of the IRT. If the packaging list for a program of studies is held by the sponsor, they may not share the whole list with the IRT vendor up front.
Medication is packaged and labeled in the usual way; however, it is done using a central list shared across all studies in a program. The next ‘section’ of the program list will be released in an individual IRT study when it needs additional medication.
The pre-planning of the packaging design for the program allows for flexibility and use across studies. But the medication is still released in the normal way and is dedicated to a protocol after labeling.
The impact on IRT is that for each packaging run, the next section of the central list and its medication numbers will need to be added into the individual IRT studies in a timely fashion.
The alternative approach is to hold the whole packaging kit list within each study in the program, but this can increase the risk of error and may affect the speed of some IRT systems for an extremely large list.
When Calyx is consulted early, our trial supplies experts can discuss pooling options and tailor the IRT to the optimal design for the study suite/program needs.
Supporting Depot-level Pooling
Calyx IRT can assist depot-level pooling by:
- Controlling the sharing of packs across protocols for certain common batches
- Facilitating just-in-time labeling of kits, including tailored reports and integrations
This type of depot-level pooling typically has a different label design when compared to the simple form of pooling mentioned previously. In the simple case, the IMP label is protocol specific.
If the medication label can be approved with multiple protocol numbers on it, an IRT can hold the central packaging list for the generic packs in a ‘parent’ study (database which holds the central list) that can talk to the ‘child’ studies (database for each protocol) within the program (See Figure).
These generically labeled kits can be released into the parent study and shipped to a child study as and when required. Within the IRT system, these kits will be used in one protocol, after the point of shipping. An IRT design may use a mixture of generically labeled kits and protocol-specific kits; Calyx IRT can apply a priority to their use if they are of the same type.
In many cases, it is considered difficult to obtain approval for a label with multiple protocols. This may be related to the size of the kit and the confusion for the user handling kits at different points in the supply chain.
A recent trend Calyx has observed is to move to a just-in-time (JIT) labeling approach to assign protocol numbers as they are needed for shipping. So, a generic label is seen initially, but only a protocol-specific kit will leave the depot in a shipment.
Just-in-time labeling therefore also impacts the depot process. As a result, ‘over-labeling feasibility checks’ are important. As part of this process, kit numbers are requested by the IRT for a shipment to a site and an extra physical label is typically added manually to each kit in that shipment to display the protocol number. The size of consignments and the impact on resource hours, as well as lead time, are important considerations.
Calyx IRT can support a JIT labeling approach, so sponsors can realize the benefits of labeling study drug as it’s needed, rather than much earlier/at one time in large batches. The benefits include a reduction of drug wastage and the more efficient use and distribution of study drug.
Follow these Rules for Maximum Benefits
All these methods are exciting and can help to reduce waste when applicable. Much experience has been gained from their use in the industry in recent years. But, in some cases, the experience has not always provided the savings expected.
If these general rules are considered for pooling protocols, the added flexibility and potential waste reduction cannot be ignored:
- The packaging design is suitable for multiple protocols
- The timelines of the protocols overlap to allow the use of the same batch across multiple protocols
- The supply chain storage points (e.g., local depots) overlap for multiple protocols within a program of studies
- A suitable labeling process can be agreed
Many factors can change after initial design choices are made, for example, the study timelines may change, the ability of a depot to over-label kits at the point of shipment may change or increase which impacts the lead time and costs of the process, and protocol amendments can impact the design. But the underlying benefit of flexibility still exists when these tools are utilized.
At Calyx, we believe there is further experience to be shared and gained in this area and that the most efficient use of pooling is yet to come.