How packaging design can affect material need and complexity of the IVR

Almac can help you manage your supply chain for the flawless delivery to market of drugs.

In today's rapidly growing global drug development market, pharmaceutical and biotech companies are constantly faced with the challenge of delivering drugs to market faster. With tight timelines and limited study budgets, the sponsor organisations are reaching out to experts like Almac to manage their supply chain and flawlessly deliver their drug to market.

Pharmaceutical and biotech companies are always looking for ways to expedite the drug-delivery process while still maintaining a reputation for delivering high-quality products. For example, a phase II, multicentre, double-blind, randomised, comparator-controlled study was investigating the use of a new treatment for a disease affecting a large population of middle-aged adults. Developing and testing the drug while quickly bringing it to market was top priority for the sponsor. An aggressive study start timeline (seven weeks from time of initial discussions to first patient screened (FPS)), limited drug supply, and a proposed kit design further complicated their ability to enrol and meet patient needs. Additionally, they expected to manage the drug supply challenges with a customised IVR/ IWR system that required complex programming that could not be completed prior to the expected FPS date.

Supply chain management
Realising the clinical trial material challenges, the sponsor reached out to supply chain management experts to develop an understanding of the clinical protocol requirements and drug supply variables. Based on these components, the Almac supply chain team formulated a kit design and drug assignment schedule that would overcome the drug supply vs demand challenges.

They were also able to recommend a new patient kit design that decreased supply requirements, reduced 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 less than ten staff members and limited internal

clinical supply expertise. They had outlined a manufacturing, packaging and labelling schedule for clinical trial material that was closely aligned with the study start date and site ramp-up period with full release of 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 randomised 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 a day for six weeks. The sponsor?s patient kit contained six weeks of treatment (42 single-use containers) plus seven additional doses to replace damaged or lost containers.

Due to limited availability of drugs throughout the start-up phase, the sponsor did not plan to seed investigator sites with clinical trial materials. The strategy was to delay site supply shipment until a patient was screened and then send one kit based on the predicted treatment group in which the patient was randomised. If the patient were not randomised, the site would keep the kit until a new patient was screened. When a new patient was screened, the treatment group assignment would again be predicted and a new kit of the appropriate treatment type would be shipped if necessary.
This scenario presented multiple risks:

• The study used a centralised randomisation 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 randomisation.
• The potential for un-blinding increased due to the fact that a new kit shipped to the site (whether due to the inability to assign a kit on site or the kit being inappropriate for the next assignment) could differ in design from existing kits on site.
• The supply forecasted at the initial stages was not sufficient to satisfy the projected patient demand due to the plan to provide patients with supply needed for the treatment duration at randomisation.

In addition, the proposal to make predicted shipments off of the randomisation scheme required the development of a customised 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 maximise 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 composed of seven weekly kits that were to be consolidated into one large patient kit and assigned at randomisation (day zero). Upon review of the clinical trial material packaging, kit design, protocol and patient visit schedule, the supply chain manager quickly realised that 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 randomisation visit. Instead of assigning seven weekly kits at randomisation, kits would be assigned over a 21-day period with two kits assigned at day zero (one kit for the first seven days of treatment and one kit for replacement purposes), two kits assigned at day seven, 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 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 randomisation was an advantage as only sites that screened patients would be seeded
• eliminated need for a customised 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 the set-up of a more efficient and simplified drug shipment strategy.
This strategy, developed by Almac, 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 maximise the flexibility of available clinical trial material during start-up, on-hand site inventories were minimised by reducing values for trigger/resupply and projection windows. Once the depot inventory levels reached a comfortable surplus, the trigger/resupply and projection windows were adjusted to reduce the number of shipments and optimise shipment efficiency.

The supply chain management team assisted the sponsor partner in developing solutions to multiple clinical trial material concerns while meeting an aggressive study start date.

As a result of the supply chain manager's recommendations, the sponsor was able to make more efficient use of available clinical trial materials, preventing potential stock-outs and un-blinding scenarios and providing an efficient drug shipment strategy. The recommendations allowed for the use of a configurable IVR/IWR system enabling the client to meet study timelines and stay within budget guidelines.