Operating clinical studies with a silo mentality with undoubtedly yield poor results. With various risks associated at each stage of the clinical supply chain Adrian Collins, production manager, Almac Clinical Services, explores the hidden challenges of clinical packaging and how they may be overcome…
bigger picture
From small, single-arm trials to large, complex studies involving a range of research centres, in multiple countries, the last 25 years has seen a dramatic evolution in clinical trials and the processes that support them. As a result, the development and delivery of IMP (Investigational Medicinal Product) to clinical sites and the patient is changing continually.
Despite these changes, one thing that remains unaffected is the objective to supply clinical trial patients and sponsors with safe, flexible packaging to meet the varying needs of individual clinical trial protocols without impacting the stability of the IMP. Safety and flexibility are two vital ingredients within the planning of a study which are often overlooked, or not given the consideration they deserve early in the process. Indeed, failing to consider potential packaging challenges at the study’s planning phase, has the potential to compromise the timing, safety and success of a trial.
The hidden challenges
There are risks associated at all stages within the clinical supply chain, but those hidden challenges at the planning stage can mean the difference between a successful study and no study at all. Special considerations in clinical packaging include:
- Visibility — clinical supply is a vital, but often unseen timeline factor. Ensuring this element isn’t overlooked in the planning stage of a study is essential for delivery.
- Unstandardised — product, protocol and patient needs differ based on the unique nature of each study, which in turn demand a specialised solution.
- Change — study size, scope, clinical direction, patient demand and regulatory compliance is variable for each study and is particularly evident in multi-country studies, there is, therefore, a need for continual monitoring of the entire supply chain in order to accurately meet study demand.
- Institutional learning — historical product and/or programme learnings can be lost when personnel move or company structure changes. Strong relationships and succession planning are essential to ensure knowledge retention.
It is never too early to begin planning your clinical trial packaging and distribution strategy and questions must be asked at the outset of any study regarding the quantity required, stability and expiry date of the IMP, if blinding is necessary and, ultimately, if material and timelines could impact production. To ensure success, and overcome the hurdles posed by the above challenges, these questions may seem obvious but are fundamental to developing effective packaging strategies and ensuring appropriate resource capacity is available.
Overcome the challenges
There are many factors that, if addressed early enough and approached in an integrated manner, can help to create an optimised operation.
Firstly, ensuring full visibility of kit design during the initial planning stage is critical as this influences the materials, quantities and specific tooling requirements needed. Additionally, the lead-times associated with the specific kit design will impact durations and deliverables, it is important that this is agreed as part of a wider project. The stability and dose form of the drug is also a key consideration and can often restrict the choice of packaging for the kit.
Blinding — and the complication it can introduce to packaging — should be explored at the earliest opportunity. Without knowing that the samples of both IMP and comparator products are available, or if blinding is even possible (and if so, that there is a process for it), timelines and more critically, study design, could be jeopardised.
Planning for the unpredictable is essential. As we know, change, often unforeseen, is inevitable. A flexible study design is vital to enable modification if there was a change to elements such as: study size, visit schedules, clinical site, patient demand or regulatory compliance. In these cases, applying scrutiny to plans means that alternative packaging scenarios can be considered. In one sponsor’s case, early planning of the packaging design resulted in a switch from a visit kit to multiple weekly dosing in a compact wallet design.
This not only made patients’ lives easier but resulted in the reduction of overall clinical supply units from 300K to 108K, saving an estimated six weeks and approximately £600K.
Finally, one must consider the challenges presented when demand surpasses supply in active studies. This is a serious consequence of disjointed supply chain planning that fails to align site activity with production processes, leading to a risk of stock outs. Similarly having slower than expected demand can also pose challenges. Patient recruitment and retention is one of the most important aspects of a trial. Having measures in place to protect against stock outs and being able to react quickly and accurately needs to be a priority during the planning phase of a study; not left as a costly knee jerk reaction when the problem unexpectedly occurs.
Conclusion
Ultimately, to properly understand clinical packaging and achieve efficiency and compliance, it needs to be viewed as part of the bigger picture. Operating with a silo mentality will yield poor — potentially catastrophic — results. Clinical packaging not only needs to be part of the conversation at the outset of trial planning, but its role within the drug development process properly scrutinised and pro-actively managed to overcome any challenges posed mid-trial. Managing an integrated supply chain means preparing for every eventuality with effective forecasting, maintaining clear dialogue with third parties and embracing innovative ways of identifying and solving problems.
Clinical packaging strategy isn’t something you can buy off the shelf. It is something that requires both considerable effort and expertise. If approached correctly and early, it can safeguard patient safety, reduce significant cost, ensure regulatory compliance and champion successful studies that will no doubt contribute to future leaps forward in drug discovery and advancements in human health.