Supply chain management and packaging design in clinical trial efficiencies

Almac is a leading provider of global supply chain management services to the pharmaceutical industry. Here, it explains how superior supply chain management can lead to enhanced efficiencies.

Clinical trial supplies are now seen as a necessary element in strategic planning, and a key component of ensuring the successful start and completion of a clinical programme. Sponsors are seeking supply chain stakeholders (internal and external) who not only offer the standard provision of clinical supplies, but are also able to provide additional value through proactive supply chain management services. From small companies with limited internal resources to handle each stage of the trial to large firms managing multiple projects, effective management of the clinical supply chain is critical.

Sponsors seeking to run complex, multicentre global trials are now considering expertise as a tangible asset as each trial consists of unique variables that intertwine and careful consideration needs to be taken to ensure compliance at every stage. A vendor or partner in the process must have the ability to not only offer a strategic portfolio of trial support services such as clinical packaging, global distribution, IVRS expertise, but also be able to proactively advise on the best approaches and solutions to challenges to allow for flexible production and delivery of investigational products worldwide.

One of the most important but overlooked areas of trial design lies within the design of clinical trial material and the method in which it is presented to the patient. Requests from sponsors can be tactical, such as a comprehensive scope of work providing details on all material and methods required. In other cases, the supply provider must deploy effective supply chain management strategies to determine the best inventory levels and kit design to make optimal use of inventory available and site stock level strategies. Supply chain managers leverage their expertise to provide the most optimal packaging solutions to the most challenging clinical supply scenarios, saving time and costs for the sponsor without compromising compliance and quality.

Clinical packaging is typically 'one of a kind' and unlike commercial packaging is very variable. Factors such as blinding requirements (of both IMP and potential comparator product), randomisation, and specific label requirements necessitate skill and expertise to ensure total compliance in the study. Decisions made in isolation have wider implications, which is why the role of clinical supply teams (internal, external, or both) is of vital importance.

Project and protocol timelines, and patient compliance
Timelines are crucial and trials are often designed based on very tight and regimented schedules. Packaging must be designed to make the best use of automation where possible and a strategy to permit just-in-time packaging and flexibility so that the supply chain is robust and responsive, especially important considering adaptive trials or those on which dosing and group allocation can vary during the study.

One misstep has the ability to cause a ripple effect throughout the remainder of the supply chain and hence affect the trial. The patient must receive and administer the drug product as directed to ensure study compliance and accuracy, so the packaging must be designed with the sites and the final users in mind.

Product stability
Typically, packaging must be consistent with the immediate materials used to conduct product stability trials and will dictate the specification that immediately comes into contact with the investigational product. This may have a bearing on the size and presentation format offered to the patient during the actual clinical trial.

Maintaining study blindness
Blinding trial material is a specific area of expertise and stretches beyond just the product itself. Packaging considerations weigh heavily on maintaining blindness since any distinguishable differences between packaging run the same risk of unblinding a study. This also includes labelling and presentation cartons used for monthly dosing and so forth. Seemingly simple factors, such as the placement of a label or colour variation in a bottle, can have a major impact on receiving unbiased results from the trial. Each packaging operation and label printing job must be indistinguishable from any others, hence the need for robust GMP-compliant solutions and effective quality systems to maintain blindness.

Maintaining efficiency and flexibility in supply
Choosing the correct packaging method can drastically impact your budget, and affect the supply to sites and patients. For example, the design of a kit may be compliant with study design, but not optimal for distribution because it only allows for a small number of kits per shipping unit. This is typically illustrated in the weekly and monthly visit kit scenario. An effective supply chain manager will illustrate not only the effect of kit decisions on the packaging supply chain, but also the crucial impact of site inventory and distribution models for the trial. Identifying an alternative solution early allows for study compliance and distribution optimisation.

Accurate supply chain forecasting and simulation is also helpful when assessing manufacturing strategies. A forecast can determine quantities of stock needed up front based on recruitment, usage or expiry dating, and direct the strategy of production for the trial itself.

Key factors to consider in clinical packaging design
When evaluating packaging design, there are many key considerations. Choosing the best option for a study can be a tedious task if you're not familiar with all options available. Packaging configurations typically involve bottles, blisters, wallet cards and patient kits. Each of these options is briefly discussed below.

Bottling: good for simple studies or those with longer term fixed dosing. Consider automation and automated labelling for cost effectiveness and rapid supply.

Blistering: varies significantly on the fill and stability requirements. Stability will dictate materials, and size and shape used. Dosing will also need to be considered and how this will be presented to the patient. Consideration should also be given to mixed blister filling for more complex dosing requirements. Mixed fill is technically more difficult but is offset by efficiencies and use of automation.

Carding: consider the size of the blisters required. Dosing instructions can be printed on cards and on study labels, with labels being the majority considering global requirements. Full automation should be used for larger phase III projects since it is faster and has more efficient output to supply global sites. It is important to evaluate these options up front, again relating to the importance of effective supply chain management.

Kitting: thought must be given to the IMP format: cards, vials, bottles, syringes, patient compliance and accessibility. This also affects the supply chain in terms of the units actually given to the patient at each site visit, IMP availability, and how the IVRS may be set up in terms of medication allocation at site.

Case study
One of Almac's clients, a leading pharmaceutical company, provided an initial pack design for a complex clinical study involving over 10,000 patients in 40 countries. Supply chain mangers within Almac quickly recognised the opportunity for alternative design options that would result in significant cost savings. Almac proposed this new kit design to the client, which incorporated automated packaging and labelling services, and allowed for reduced timelines. The innovative approach to kit design not only greatly reduced operational costs, but also provided further savings across label printing, translations, and distribution ultimately saving the client more than £1 million when compared with the original design.