The phrase “supply chain” conjures images of something rigid, straightforward. Rarely, however, is this impression accurate, and it’s certainly never true in the field of clinical logistics, where challenges for complying with handling and shipping regulations for different countries are many and diverse: Investigational Medicinal Products (IMPs), biological samples, medical devices, point-of-care devices, bedside diagnostics and study-specific documents.
Managing IMPs and ancillary supplies is a complex and delicate process — one that’s subject to change at every stage. There’s also much at stake, from maintaining IMPs that represent millions of dollars in investment to the health of volunteers and patients involved in the trials and eventual treatments. It’s never just a simple matter of crating drugs and making sure the delivery label is correct.
The IMP supply chain involves demand calculation, supply forecast, customs clearance, global sourcing, inventory management and a host of other variables. If any are mismanaged or imprecision occurs, it could harm the outcome of the clinical trial or, worse, place the safety of patients at risk. Avoiding costly trial delays, reducing patient risk and maximizing the opportunity for a successful clinical trial requires a holistic plan, rapid adoption, and the formation of a reliable ecosystem of expert partners.
PLAN EVERY PART
Just as one weak link can break a chain, in this case it’s a chain that supplies the demand for complex, multinational, multi-center studies. A range of variables needs to be addressed for each study, including the quantity of drugs required throughout; shipping regulations of the country where the study is being conducted; optimum packaging configurations and conditions; the cost; and important considerations such as randomized trials, which impact how drugs are packaged, delivered and tracked.
In simple terms, planning starts with a bill of materials. This bill of materials is very important in the planning phase for developing a global distribution strategy. Creating and streamlining the supply chain processes in a study’s early stages improves communication, reduces the supply risk, ensures increased protocol compliance and increases quality/patient safety. An insufficient supply of medication and ancillary supplies available for patients at sites across the globe represents a huge risk to the entire clinical study/program, even if all other clinical operations are under control.
IMPs themselves demand a special type of handling. After all, they’re precious cargo. These experimental drugs represent years of discovery and analysis costing millions of dollars. Overproduction and oversupply can be as costly as underproduction and undersupply. IMPs are also extremely sensitive with expiration dates and, often, cold-storage needs. From an inventory log-in to a disabled delivery truck — errors result in a staggering loss of product and a significant increase in expense.
However, before any medication can be distributed, it must be labeled as per clinical trial and local regulatory agency requirements. Regulatory requirements can be particularly stringent, and include stipulations such as paper type, font, format and language style that. In fact, a study label often turns into a booklet.
Of course, there’s more than one market and set of regulations to navigate. Each country has its own regulations. Failure to follow them will delay clinical trial supplies because they will be held up by border officials requiring correct documentation. Completion of import/export documentation requires expert knowledge that must be constantly updated as regulations continuously change.
Some countries even ban certain materials used in clinical trials, particularly in the area of gene therapy. When developing a patient recruitment strategy, experts in clinical logistics can provide invaluable advice on country selection to avoid these situations.
While protecting and delivering IMPs is the core job of clinical logistics, other facets of the IMP supply chain are equally important. A set of components too often overlooked is ancillary supplies. For every vital IMP that must be distributed there is a bevy of non-drug materials that need to accompany it and remain replenished. This includes printing material, patient diaries, lab instruments, medical equipment and incentives for volunteers and staff.
Trials are becoming more complex, so the amount of ancillary supplies and the number of vendors providing those supplies has greatly increased. As a result, ancillary supplies are traditionally managed in a way that results in their arrival from different places at different times. Unfortunately, this approach increases project management time and costs, leads to higher material and shipping costs, and creates complex, suboptimal processes that result in higher failure rates.
A better approach is to consolidate as many non-drug-related outbound activities as possible. In other words, institute a material flow that can be centrally managed. This approach yields significant shipping cost savings, time and process efficiency, and inventory transparency.
PLAN TO BE FLEXIBLE
However, having every component mapped, tracked and organized is not enough. Moving them becomes the next concern. Demand isn’t stable in clinical trials. It’s based on the original operational plan of a clinical study, which changes over the course of planning and execution.
Demand impacts everything from the number of patients needed for the trial to IMP shelf life to depot management. Adequate flexibility has to be planned in advance so that when the components change, demand can be addressed quickly and appropriately.
However, it’s not only demand. At any stage, all elements and environments that have been so carefully coordinated could change, threatening the integrity of the entire supply chain. Clinical logistics is a discipline of surprises, requiring careful distinction between following SOPs and being flexible enough to accommodate changes. Of course, that flexibility should never come at the expense of control. Without control, the supply chain falls apart.
The recent political unrest in the Ukraine is a timely example. Often, such major disruptions cannot be specifically predicted, but there should be a contingency plan in place. To minimize the impact of such disruptions, a business continuity plan has to be in place to get the staff, patients and materials in an ongoing study in that region in as safe a position as possible. When managing unanticipated changes, there’s no substitute for experience. A clinical logistics team needs solution-oriented expertise culled from years of hands-on experience in both clinical logistics and clinical trials themselves.
However, expertise alone isn’t enough. These experts must be equipped with tools to adapt to changes in a timely and compliant manner. These tools should include a library of successful lessons learned, IP tracking systems, inventory management and shipment management systems, and a global network of depots prepared to provide full services.
In addition to materials, clinical logistics is also about the people in the system. These contributors range from staff at the investigational site to the clinical team to couriers to depot staff, all entrusted with these important, delicate, and often irreplaceable IMPs. When adjusting to the unexpected, you will have to rely on people adapting, not systems, although a clinical supply chain outsourcing strategy is most effective when tasks and technologies are seamlessly integrated to reduce risk.
Close collaboration with the investigational site is a must. These professionals are the primary partners because they are executing the clinical study and treating patients. It is essential to receive feedback from them on a regular basis to make sure they are content, address areas for improvement and maintain communication throughout any study changes.
From a clinical supply chain perspective, key factors to consider with the investigational site are:
• The geographic location of sites and patients (based on feasibility, recruitment rate and country selection)
• Requirement of ancillary supplies to allow smooth execution of site activities
Close collaboration with the internal clinical team, whether it’s your own team, a sponsor’s team, or a team from another CRO. This team can only complete its timelines when clinical logistics delivers accordingly.
Other important links in the supply chain are shipping partners, including couriers and depot staff, especially when the latter represent third-party depots in other countries. The supply chain moves because of those who take materials from Point A to Point B. These partners must be trained to handle fragile and highly regulated IMPs. They must undergo thorough qualification process and be monitored and audited on an ongoing basis to ensure they are fulfilling the highest industry standards, whether they involve temperature-sensitive storage, which most IMPs need, or regulations of different countries.
Even though every clinical trial is different, they all have one characteristic in common: Every aspect can change and change quickly. Being flexible enough to adapt without risking supply chains and the trials they serve requires a holistic view of the entire process, from operational plans to ancillary supplies to the training of couriers who deliver IMPs. Adopting a holistic view enables one to foresee deviations before they occur and institute strategies to properly react well to those that are unexpected. This can ensure that the right personnel, partners and training are in place to carry out that plan and address those changes. Most importantly, this will create the best opportunity for clinical trial success.