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Pooling Resources

Clinical trials help bring new and innovative drugs to market to improve the health and wellbeing of patients across the globe. To safely and efficiently conduct these trials, drug sponsors rely on highly specialised, complex supply and logistics services for studies that can span dozens of countries and hundreds of sites around the world. Implementing interactive response technology (IRT) can provide seamless supply chain management, shorter timelines and a lower cost of product development.

A common challenge that can arise during the course of a trial – resulting in lengthy delays and potential financial loss – is ensuring that clinical supplies are available when needed. Maintaining maximum supply chain flexibility to mitigate risk of future stock-outs and control costs associated with the manufacturing, labelling and shipping of clinical supplies is critical.

What is IRT?

An IRT system – also known as an interactive voice and web response system – is used to manage the logistics involved in conducting clinical trials. Hosted online, it can be accessed at any point, from anywhere, to more effectively control trial processes.

In the not so distant past, sponsors used manual tools and spreadsheets to manage the supply chain. As trials and studies have become increasingly complex – with more patients, sites, regions and variables – they now also have distinct supply chain requirements. For example, the correct product must be collected from, and delivered to, the right locations according to exacting schedules, keeping batches within their expiration date for use. Without an IRT, the margin for error and potential for financial loss is too great.

IRTs have a marked impact on supply chain management by helping sponsors to control drug supply and shipments, dispensing drugs to trial patients and handling returns. They can also be used to create forecasting reports or supply chain simulations.

The benefits offered by IRT systems go even further. They include: ordering algorithms that can reduce waste and overall shipping costs; the ability to adjust supply strategy ceiling and floor levels as the trial reaches full enrolment; and real-time product release expiry updating and status management for rapid product updates. Another advantage is just-in-time (JIT) ordering where supported by protocol design. This involves placing initial orders based on the commencement of site enrolment or screening, rather than on-site activation – particularly if the minimum window between screening and randomisation is longer than the lead time required to order, dispatch and deliver a shipment.

Supply Pooling

To keep a tight rein on costs, and reduce waste and the overall quantity of supplies required to conduct trials, supply pooling can often be an effective strategy (1). IRT can be used to manage the supplies manufactured for pooling.

Supply pooling uses the same product batch across multiple protocols or development programmes. In this scenario, a product is manufactured and labelled for a programme of studies, instead of for a single trial. It is not assigned to a specific study until ordering to site (for depot pooling) or at the site from the point of allocation (for site pooling). Pooling techniques can be used with investigational medicinal products, as well as with concomitant or comparator medications and devices. One of the greatest benefits of supply pooling is that it maintains flexibility in the clinical supply chain and can be conducted at the depot or site.

Depot-Level Pooling
At the depot level, supplies are released for multiple protocols. The consignment generator runs against these protocols, identifying supply needs for new and existing subjects within a prediction window, and matching identified product needs with the appropriate product batches to meet those requirements. Using this method, sponsors can significantly cut down on manufacturing needs required to support a clinical development programme covering multiple trials.

Another element that pooling has an impact on is labelling requirements. At the depot level, pooling does not require sites to be approved for multiple protocols within a programme; instead, orders are placed independently for each study. The IRT then assigns a protocol to the product at the point of ordering. This typically requires a JIT over-labelling capability, as the protocol is added to the product label at the point of picking for dispatch to the receiving location. Expiry may also be added to the label – this is useful given there could be different expiry dates for each country release, or when storing and shipping product that is stored frozen and then thawed prior to shipment.

A further approach involves adding multiple protocols to the product label, though they must be individually approved for each destination country (2). This method necessitates careful planning and does not account for any unknown protocols at the point of label creation.

Site-Level Pooling

With site-level pooling, product is ordered to sites that could fill requirements for multiple protocols. Although the product is available for multiple protocols, it is assigned to a single one at the point of subject allocation. Depending on the label language, additional content may be required – for example, over-labelling with the protocol, where the base label includes only a programme or product identifier. Sponsors may also add multiple protocols to the label.

The limitation of this approach applies to both depot and site product pooling. It does not account for unknown protocols or the risk that some may be suspended. A possible solution is to employ JIT over-labelling at the site – a tactic that requires careful control. However, site pooling offers the ability to maintain a common buffer stock at a site for multiple protocols. This can potentially reduce the net quantity of product that is required on site (adjusted for overall site activity), while maintaining adequate stock on hand to prevent stock-outs.

Of course, this approach offers little benefi t if receiving sites are not participating in multiple protocols. Additionally, the product may require a supplemental label on site, at the point of allocation, via IRT. Where and when this method is appropriate, it can reduce overall product quantity requirements.

Planning Ahead

When considering pooled clinical supply manufacturing and management, thorough planning, as well as stakeholder buy-in and readiness, is essential. An index of questions must be developed and answered in order to gain a complete oversight of product, process and organisational readiness. There are, for example, a number of packaging-specific issues to bear in mind: do formulation, packaging and stability data support a pooled approach, and is there a common packaging and global labelling platform (3)? What is the labelling strategy, and what are its capabilities and constraints?

Protocol design and timing must also be taken into account against current product stability data, as well as the implication of variable pack life across protocols. Beyond this, the question of shipping units versus allocation units should be raised, in addition to the potential impact of dose adjustments and titrations.

Before pursuing this method, compliance and regulatory issues must be understood, and all risk management options should be considered.

Additional Features

Careful thought should be given to other IRT configurations that maximise efficient stock utilisation and extend supply chain flexibility. JIT ordering is based on site enrolment activity, rather than approval. Another option is ‘rancode look ahead’ for trials with site-stratified rancode. Here, the consignment generator will select kit quantities and types matching the next available entries in the rancode, instead of using static buffer requirements for every site. A different technique involves implementing allocation substitution rules. For example, a sponsor could allocate 2x20mg packs in lieu of a 40mg pack. Clearly, this approach has practical limitations and must not be used in cases where the study blind could be compromised. Nonetheless, for some protocol designs, it could be a viable option – such as for open label trials.

Further options might include using an e-label smart device application to verify product expiry, status, protocol availability, and usability on site or at the point of allocation during storage. There is also some interest in using such applications to improve compliance. These may rely on a ‘bring your own device’ model, and should work with various operating systems such as iOS, Android or Windows Mobile.

Choosing Tactics

Taking a product pooling approach can have an effect on product manufacturing and labelling, as well as on IRT design. When used correctly for the right product at the right stage of the development lifecycle, this tactic can lead to greater supply chain flexibility when managing large development programmes, through a reduction of required product quantities and product types. But it is important to remember that one size does not fit all; careful planning is required and different tactics should be employed according to the situation. Equally important is that sponsors choose to work with an experienced IRT provider – one that can defi ne programme requirements, guarantee that the system design matches programme goals, and, to the greatest extent possible, mitigate the unknown outcomes through careful planning and risk management.


1. Reige D and Tourtelotte E, Drug pooling: Power and pitfalls, Applied Clinical Trials, 1 April 2008. Visit: www.appliedclinicaltrials drug-pooling-power-and-pitfalls/ articlestandard/article/detail/506849
2. Medicines and Healthcare Products Regulatory Agency, Good Manufacturing Practice: Investigational medicinal products (IMP) FAQs. Visit: medicines/inspectionandstandards/ goodmanufacturingpractice/ faq/imp/#q23
3. Hall C, Clinical supplies: Adapting to supply demand, Pharma Focus Asia, 2008. Visit: clinical_trial_supplies.htm

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Kurt Lumsden is Director, eCDS Client Services, at PAREXEL Informatics, and is responsible for the Randomization and Trial Supply Management Client Services group in Deerfi eld, Illinois, US. He has broad and extensive experience in the industry, spanning 15 years and including sponsor, CRO and site organisation. Prior to this, Kurt served in a number of key roles within healthcare businesses in both the US and Europe. He holds an MBA from City University, Seattle; a BSc in Perfusion Technology from Rush University, Chicago; and a BA in Healthcare Management from National Louis University, Evanston.
Kurt Lumsden
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