An example scenario of this would be a Phase II, multi-center, double-blind, randomized, comparator controlled study that investigated the use of a new treatment for a disease that was affecting a large population of middle-aged adults. It was a top priority for the sponsor to develop and test the drug and bring it to market as quickly as possible. The study needed to meet an aggressive start timeline (seven weeks from time of initial discussions to First Patient Screened (FPS)) with a limited drug supply and a proposed kit design that further complicated the ability to enroll and meet patient needs. Additionally, the sponsor expected to manage the drug supply challenges with a customized IVR/IWR system that would require complex programming that could not be completed prior to the expected FPS date.
Realizing the clinical trial material challenges, the sponsor organization reached out to various supply chain management experts in the industry to develop an understanding of the clinical protocol requirements and drug supply variables. Based on these components, the supply chain team formulated a kit design and drug assignment schedule that would overcome the drug supply versus demand challenges. The team was also able to recommend a new patient kit design that decreased the supply requirements, reduced the drug supply and distribution complexities, and opened the door for the use of a configurable IVR/IWR solution that could be defined, developed and released in time to meet the FPS target date.
The sponsor of this clinical trial was a small biotechnology company with fewer than 10 staff and limited internal clinical supply expertise. The company had outlined a manufacturing, packaging and labeling schedule for clinical trial material that was closely aligned with the study start date and site ramp-up period, with full release of the initial batches expected just days prior to the FPS target date. Another limiting factor was the sponsor’s manufacturing capacity, which resulted in small batch sizes for both the investigational product and comparator supply. The full clinical trial material need was satisfied through numerous production runs with new batches delivered on a bi-weekly basis throughout the first three months of study conduct. Given this production plan, the ability to satisfy site and patient needs during the first month of study conduct was tenuous.
Patients enrolled into the clinical trial were concurrently randomized to one of two treatments: the sponsor’s investigational product or the comparator control. The investigational product and comparator were supplied in identical, single-use containers that patients could take home and self-administer once daily for six weeks. The sponsor’s patient kit contained six weeks of treatment (42 single-use containers) plus seven additional doses to replace containers damaged or lost. Due to limited availability of drug throughout the start-up phase, the sponsor did not plan to seed investigator sites with clinical trial materials. Instead, the strategy was to delay site supply shipment until a patient was screened and then send one kit based on the predicted treatment group the patient would be randomized to. If the patient was not randomized, the site would keep the kit until a new patient was screened. At the time a new patient was screened, the treatment group assignment would again be predicted and if necessary, a new kit of the appropriate treatment type would be shipped.
This scenario presented multiple risks:
- The study was using a centralized randomization scheme. If more than one subject was in screening at any given time there could be no certainty as to which treatment group would be assigned next, presenting a significant risk that the appropriate treatment type would not be available to assign at randomization.
- The potential for un-blinding was increased due to the fact that a new kit shipped to the site — whether due to the inability to assign a kit onsite or the kit being inappropriate for the next assignment — could differ in design from existing kits onsite.
- The supply forecasted at the initial stages was not sufficient to satisfy the projected patient demand due planning to provide patients with all supply needed for treatment duration at randomization.
In addition to these risks, the proposal to make predicted shipments off of the randomization scheme required the development of a customized IVR/IWR system that was both time- and cost-prohibitive for the sponsor.
After discussing these risks, the sponsor agreed that an alternative approach was needed to maximize the use of the available supply, eliminate the risk of stock outs and un-blinding, and allow for the use of a configurable IVR/IWR system to be able to meet FPS timelines.
The sponsor’s kit design was made up of seven weekly kits that were to be consolidated into one large patient kit and assigned at randomization (Day 0). Upon review of the clinical trial material packaging, kit design, protocol, and patient visit schedule, the Supply Chain Manager quickly realized that the initial demand on supply could be reduced by splitting up the consolidated patient kit, uniquely numbering each weekly kit, and reducing the number of weekly kits assigned at the randomization visit. Instead of assigning seven weekly kits at randomization, kits would be assigned over a 21-day period with two kits assigned at Day 0 (one kit for the first seven days of treatment and one kit for replacement purposes), two kits assigned at Day 7, and three kits assigned at Day 21. This design resulted in a number of benefits:
- Flexibility for the sponsor on the delivery and release of the new batches of clinical trial material and significantly reduced potential for a depot stock out.
- Ability to seed sites with enough supply to eliminate the un-blinding risk and a treatment-specific-site stock out scenario. To further maintain control of clinical supplies, the seven-day period between screening and randomization was used to an advantage as only sites that screened patients would be seeded.
- Eliminated the need for a customized IVR/IWR system due to a simplified design. It became possible to use a configurable system that was able to meet the client timelines and price point.
- Allowed for the set-up of a more efficient and simplified drug shipment strategy.
It is important to note that this strategy did not lead to a greater burden on sites or require any changes to the protocol, as the patient visits already existed in the protocol visit schedule.
Finally, to maximize the flexibility of available clinical trial material during start-up, on-hand site inventories were minimized by reducing values for trigger/re-supply and projection windows. Once the depot inventory levels reached a comfortable surplus, the trigger/re-supply and projection windows were adjusted to reduce the number of shipments and optimize the efficiency of each shipment.
The expertise of the Supply Chain Management team helped assist the sponsor partner in developing solutions to multiple clinical trial material concerns while meeting an aggressive study start date. As a result of the recommendations made by the Supply Chain Manager, the sponsor was able to achieve a more efficient use of the available clinical trial materials which prevented potential stock-outs and unblinding scenarios and provided a more efficient drug shipment strategy. In addition, the recommendations allowed for the use of a configurable IVR/IWR system, which enabled the client to meet study timelines and stay within budget guidelines.
Roger Parlett is Supply Chain Manager, Integrated Services, at Almac Durham. He can be reached at firstname.lastname@example.org.