Demand led supply: A novel clinical supply approach tailored to today’s trials
The nature and scope of clinical research has changed significantly over the past decade. Studies are more complex, globalized and patient-centric than ever. Yet, the processes used to package and ship study drugs to trial sites are stuck in an earlier era, depriving sponsors of clinical supply models with the flexibility, speed and efficiency their programs demand. Now, that may be about to change with the advent of demand led supply (DLS), a clinical supply model tailored to today’s trials.
DLS is an attempt to correct a trend that has emerged in recent years, over which period the needs of clinical trials and the capabilities of the models that supply them with drugs have diverged. A host of changes to how clinical trials are run have driven the trend. Many of the changes have made trials more complicated to manage.
The shortcomings of traditional supply models
Between 2002 and 2012, the number of countries involved in a typical Phase III clinical trial increased by more than 200% to 34, according to data from the Tufts Center for the Study of Drug Development (CSDD). The globalisation of late-phase research, which has increased the logistical challenges associated with running clinical trials, has occurred in parallel to an uptick in complexity in other areas. Over the same period, the typical number of sites involved in a trial jumped by 58% to 196, while the number of procedures in the average protocol rose by the same amount.
While many clinical trials are testing supply chains because of their global, sprawling nature, others are posing challenges for quite different reasons. Adaptive study designs are on the rise, as are trials that recruit relatively few participants because the drugs they test are against orphan diseases and subpopulations of cancer patients. Both types of trial pose new challenges to clinical supply models. The situation has been compounded by the emergence of new regulations, notably Annex VI in the European Union, and the predominance of expensive, temperature-sensitive biologics in pipelines.
The upshot of these interwoven trends is that the traditional clinical trial supply model, and variants of it, are seen by some as no longer being fit for purpose.
As it stands, the typical clinical trial supply chain takes the bulk drug, performs primary and secondary packaging on it, adds booklet labels and stores it in one or two central locations. When a site requests trial materials through an interactive response technology (IRT), the booklet-labelled drug is shipped. A variant of this model, just in time, also stockpiles material in secondary packaging, but adds the ability to make last-minute modifications, such as the inclusion of the expiry date or the name of the investigator.
While these models have served the industry for years, their detractors argue they are ill-suited to the needs of today’s trials. In particular, booklet labels are seen as running counter to the prevailing trend for more patient-centric clinical trials.
By enabling sponsors to attach more than 100 pages of content to the packaging of clinical trial materials, booklet labels facilitate the use of one source of information for all of the participants in a study, whatever language they speak. Yet such information overload can prevent patients accessing details of relevance to them quickly and easily. In addition, the pre-printing of all labels means time-consuming later amendments are often unavoidable.
The just-in-time approach partly addresses some of these concerns, but falls short of eliminating all of the waste inherent in the traditional model. As the stock has still mostly been labelled well ahead of shipping, just in time is still a fairly inflexible approach to clinical trial supply.
The flexibility, speed and efficiency of DLS
Recognition of these shortcomings has led to the development of DLS, a model designed to increase supply chain flexibility, speed and efficiency by uncoupling primary and secondary packaging.
When the DLS model is followed, the primary packaging of the bulk drug is performed in a central location, after which the product is shipped to multiple regional facilities. These sites store the drug in just the primary packaging until a request comes in over the IRT, at which point only the relevant country label and patient-specific information are added prior to shipping to the site. The result is a label that quickly and clearly shows a patient only the information they need to know.
This more patient-centric way of displaying information is one of a clutch of benefits linked to the on demand nature of DLS. Another relates to the flexibility of the approach. When using the traditional model of clinical packaging, making changes to expiry dates is an arduous task. Each time data from a stability study forces a change to the date, it is necessary to perform an expiry extension labelling exercise. As some stock may already be at the clinics, this can entail relabeling at the site , destroying the stock and resupplying the site, or as a last resort recalling the materials.
With DLS, such late-stage customisation is built into the model. Expiry dates are applied as the stock is about to leave the warehouse, meaning the packaging always features the most up to date details.
DLS is designed to be less wasteful and more efficient than traditional clinical supply models in other regards, too. One such efficiency is realised when there are multiple programmes of work that use the same primary pack bright stock. Using a DLS model, the bright stock can be pooled across multiple studies and held within each of the regional facilities. Whenever a request for drug supplies comes in over the IRT from any of the studies, the bright stock is labelled for the protocol as required. Pooling materials in this way represents a more efficient way of working.
What it takes to implement DLS
The main downside of DLS is the upfront investment it requires. Creating the decentralised, global continuous GMP packaging, assembly and distribution operation that characterises the DLS model requires significant time, resources and expertise.
Catalent, which is pioneering the approach, has spent two years working to execute DLS. Over that time, an established, functional team has looked at each of the different aspects of DLS — from quality, to operations, to supply chain, to IT — to ensure one standardised solution goes into each of the facilities. Such standardisation is central to DLS.
Each of the regional DLS facilities must have common standard operating practices (SOPs) and lists of equipment. With each of the facilities handling secondary packaging locally, such standardization of the printers, scanners, cameras and ancillary packaging equipment they use and the processes they follow is needed to ensure consistency across sites. Labels are created centrally and printed locally. Similarly, one set of batch records is created and approved. Each site then works to this set of batch records.
The same ethos of standardisation is being applied to IT, notably through the adoption of common technologies for inventory management and scan and trace. For DLS to work effectively, tasks must be performed quickly. As such, there is value in having global IT systems that cut the time it takes to account for materials and create records. Streamlining these tasks ensures the qualified people who monitor quality can perform checks faster, resulting in a DLS system that processes orders within the required timescale without sacrificing safeguards.
Implementing DLS without upfront investment
This work to establish standardised processes and equipment has culminated in Catalent going live with DLS at facilities in China, Germany, Singapore and the US. A site in Japan is scheduled to implement DLS over the summer. Each site houses a local DLS team, which is made up of Catalent employees who have been trained in the SOPs, know the processes and understand the packaging and labelling requirements. Catalent will train up additional teams as it continues to build the DLS facilities it needs to support the global distribution needs of its clients.
In parallel, Catalent intends to continue to further refine its DLS model in response to the evolution of its understanding of the strengths and weaknesses of the approach, and requests and feedback from customers. By responding to such requests, Catalent is aiming to ensure DLS is as tailored to the needs of individual clients as any in-house clinical supply system, while also freeing them from the need to invest the significant amounts of time and resources that are needed to build, maintain and improve the network.
The upshot is that companies now have a relatively straightforward way of accessing a clinical supply model tailored to the evolving needs of their clinical trials.