When a clinical trial crosses national borders, study teams typically must weigh a longer list of factors than if they were tackling a regional trial. For example, one country has different regulatory requirements than the next; another might have hard-to-navigate infrastructure. Dealing with these complexities calls for thoughtful planning, and connecting with resources within a country’s border can make a difference.
Leon Dzivinsky, vice president of global logistics with ICON, connected with Outsourcing-Pharma and shared a wealth of information on what it takes to make a global trial work.
OSP: What are some of the added challenges associated with a global trial, compared to a regional trial, when it comes to logistics?
LD: To clarify the definitions, under a global trial we mean a trial that is conducted in multiple countries while a regional trial is limited by the borders of one country or a specific region.
Conducting trials around the world is becoming more complex due to a wide range of challenges; from changing regulations to planning for uncertainties. The complexity increases as sponsors are looking to add new sites in new regions, implement adaptive trials and provide direct-to-patient deliveries.
Regulatory challenges
Country-specific regulatory guidance and local legislation need to be taken into account and considered at the earliest planning stage of the trial and closely monitored throughout the study duration. These include the following:
- Customs regulations (to include requirements to IOR/EOR, import and export licenses and permits, local certifications, and custom clearance timelines)
- Requirements for a local depot for storage, distribution, and local sourcing activities (a necessity of having a local depot in-country, pharmaceutical license for sourcing activities, licensed local couriers for effective distribution plan)
- Regulations for clinical trial approvals and reporting to regulatory authorities
- Quality standards
- Local data privacy regulations
- Patient protection standards.
Operational challenges
Global clinical trials involve more complicated coordination and planning efforts. Logistics for a global trial is a multistep process that requires coordination across multiple functions, geographies, and activities; import & export, storage, distribution, sourcing, returns, destruction – in the correct order to create a smooth and uninterrupted supply chain that conforms to international and local quality standards. Moreover, these activities need to be synchronized to ensure that the supply flow taking is streamlined. Challenges include:
- Managing vendor selection and management: including lack of vendors and limited infrastructure in some countries, efficient use of vendors, and mitigating risk
- Time constraints: import and export issues (e.g. goods stuck at customs and either delayed or not permitted for entry), shipping delays, extended transit duration, tight enrolment timelines are some of the issues that can add complexity to logistics
- Cost containment: it’s important to manage increased use of resources, delivery strategies (DTS vs via depot) to avoid fines and sanctions due to improperly planned import and export activities, oversupply of investigational products at the depot, and expiration of the useful life of the drugs
- Quality management: temperature excursion risks, damages (during import, storage, and transportation)
- Language and cultural barriers: variance and multiple time zones, local supply availability can add another layer of complexity
- Evolving regulatory environment
While multiple challenges exist, none of these are insurmountable. Navigating them successfully requires well-defined and sustainable processes capable of mitigating risks from the beginning to the end of the supply chain process. It also requires knowledge and expertise of those assigned with logistics tasks and local presence in the countries where such tasks need to be performed.
OSP: Could you please talk about some of the most complicated aspects of planning and coordinating logistics for an international trial?
LD: Differences in country-specific regulatory requirements and the fact they are constantly changing and regulations related to local logistics need to be constantly monitored. Unexpected changes in the global environment (BREXIT, COVID, etc.) - may lead to the need to take urgent measures to comply with the new realities while avoiding critical delays and unnecessary costs (preparing alternative strategies, responding to change with quick and effective solutions, ensuring quality standards in a new environment).
Depending on the country-specific environment, it may be necessary to concentrate on a particular supply chain aspect, such as the engagement of local vendors with certain expertise in regional logistics, use of appropriate shipping solutions and packing materials (e.g., in large countries with multiple climate and time zones more attention should be paid to planning the cold chain management strategy to ensure product quality during prolonged transfers).
You also need to consider development of a cost-effective budget that balances both cost and performance with ongoing assessment throughout the study duration. Supply chain management for global trials requires flexibility and capability to adapt to the changing environment, quickly and efficiently.
OSP: Please talk about some of the expertise and services your company offers regarding importing and exporting equipment and supplies.
LD: ICON’s Global Logistics business is capable of managing all logistics-related study activities, providing warehousing and distribution services to the clinical trial industry. By expanding the reach to new geographies and adding the associated capabilities of import and export management and logistic coordination services, it also provides integrated logistical solutions for all types of clinical trial supplies.
Services include:
- Logistics coordination: countries supported include Argentina, Belarus, Brazil, Chile, Colombia, Costa Rico, Georgia, Guatemala, Israel, Mexico, Peru, Russia, Taiwan, Turkey, and Ukraine.
- Import and export services: countries supported include Argentina, Belarus, Brazil, Chile, Colombia, Costa Rico, Georgia, Guatemala, Israel, Mexico, Moldova, Peru, Russia, Serbia, Taiwan, Turkey, UK, Ukraine.
- Depot and distribution services:
- Countries supported with their own depots include Russia, Ukraine, and Belarus
- Partner depot network: Bosnia, Croatia, Georgia, Israel, Moldova, Serbia, Taiwan, Turkey, Philippines, South Africa, and South Korea.
Import and export services
Our experts manage import and export processes, beginning at the study start-up stage and continuing through the end of a study in Eastern and Western Europe, Latin America, and Asia Pacific. They oversee management of all necessary import and export permissions, review and approval of shipping documents, shipment tracking during international transfer, import customs clearance in the country of destination with subsequent export, and return of supplies back to their owner.
We achieve streamlined import and export processes on the global and local level, reduce regulatory risks and apply cost- and time-efficient solutions for import and export activities.
Capabilities include:
- Set-up of import and export processes on the country level and ensuring safe and efficient fulfillment of functions of Importer and Exporter of Record either by the local ICON office or through a contracted vendor
- Expert assistance with import and export processes during the whole term of the study
- Coordination of import and export shipments, obtaining all necessary non-regulatory import and export permissions, creation and update of trackers, comprehensive support of the Study Team
Coordinating logistics for global trials
The logistics coordination department serves as the central communication hub between project teams and logistics service providers and coordinates all study logistics activities for supplies of any type intended for a clinical trial. It streamlines all logistical processes to ensure smooth, timely, and cost-efficient fulfillment of tasks associated with start-up, maintenance, and close-out of a study. The overall result of coordination is increased transparency, manageability, and efficiency of logistics activities taken by ICON.
Capabilities include coordination of all study-related logistics activities, including:
- Depot set-up
- Clinical trial supplies sourcing
- Shipments and distribution
- Destruction and return of clinical trial supplies
- Coordination of relevant activities
Key activities:
- Single contact point for all logistics related study-specific inquiries
- Execution of logistics processes in accordance with study needs
- Management of logistics vendors
Depot and distribution services
We also provide high-quality, reliable, and cost-effective depot and distribution services for clinical trials in Russia, Ukraine, and Belarus. We possess a full scope of logistics and warehousing services while ensuring the highest industry operation standards.
The department was set up on the basis of IMP Logistics – a logistics and warehousing division of ICON. IMP Logistics’ head office is located in the UK, with its first operational facility launched in Russia (Moscow region) in 2004. Locations in Ukraine (Kiev) opened in 2007 and Belarus (Minsk) opened in 2009.
As of today, IMP Logistics is one of the leading providers of clinical trial supply services in its region. Its logistics facilities are ISO 9001:2015 certified, have strategic locations close to the main airports, and provide storage in all temperature zones. All services are provided in accordance with Good Distribution Practice (GDP) and Good Manufacturing Practice (GMP). All elements of operations are controlled by detailed SOPs.
Through depot location and depot partner network, ICON supports clinical trials with a full scope of logistics and warehousing services and ensures the highest industry operational standards. Our depots are in Russia, Ukraine, and Belarus.
Services include:
- Storage in all temperature zones (+15+25° C, +2+8° C, -25-15° C, -60-80° C)
- Handling and distribution of investigational medical products and clinical materials
- Courier
- Sourcing of comparators and other materials for clinical trials
- Equipment purchase
- Labeling
- Return and disposal of unused drugs
We have an existing partner depot network in:
- Georgia
- Serbia
- Moldova
- Turkey
- Israel
- Taiwan
- Philippines
- South Africa
- South Korea
Keeping track of regulatory matters
At ICON we have internally assigned staff whose task is to collect and maintain the database on logistics requirements and relevant legislation per country and consult team members on an ongoing basis to ensure compliance.
Contingency planning
Ensuring continuity of service is a priority and the following have been set up to reduce and manage risk:
- Risk mitigation plans per each scenario where we might face potential risks connected with IE, depot, and distribution activities.
- Vendor backup network
- Business continuity plans per each facility.
OSP: How has COVID-19 impacted the job of coordinating global trial logistics?
LD: The COVID-19 pandemic introduced new logistical problems that had to be confronted and resolved rapidly. The COVID-19 pandemic was an opportunity to showcase our adaptability in terms of carrying on business as usual. We constantly monitored coronavirus restrictions per each country of operations (including flights, transportation service availability, lockdowns, etc.) which allowed for timely decision making, the adoption of alternative options and helped to avoid any disruptions.
Quickly reacting to clients’ requests following local restrictions and sites closeouts due to the virus, we have added direct-to-patient (site-to-patient) supply capabilities to our services offerings in a number of countries we cover. With the increase of vaccine trials, we can offer ready-to-plug-in infrastructure and expedited timelines for gaining access into particular countries under our coverage.
When it came to our internal operations (in particular, Depot and Distribution Services department) - we knew that some staff (logistics coordinators, drivers, and warehouse workers) are unable to perform their services virtually and had to be on-site for the uninterrupted logistics activities.
With the dual goal in mind of efficiently managing the studies without delays and ensuring the safety of our employees, we developed and implemented a shift-based work schedule, adding transportation coverage for our staff, providing protective materials and equipment, and continue to monitor the health and safety of our employees for the duration of the pandemic.
OSP: Do you have any key pieces of advice for trial teams looking to make logistics aspects of a global trial as smooth as possible?
LD: Early involvement of logistics experts in the clinical trial planning process and development of a supply strategy is a critical step to ensure a global trial runs smoothly. Communication is the key and involving logistics experts in study design planning would be beneficial to ensure a smooth and efficient supply chain process.
Collection of detailed information on the supply chain needs of the sponsor and study at the earliest possible stage will contribute to early understanding of the scale, cost, and timelines of the logistics project.
Important aspects to be considered:
- Putting in place duly documented agreements between all parties involved into the project (Sponsor, vendors, logistics, and other study teams)
- Constant communication throughout the project between study teams and logistics parties involved regarding changes, issues, and potential requests.
OSP: Do you have anything to add?
LD: A core supply planning structure must be in place and carefully evaluated to ensure clinical trial success:
- Availability of documented global processes that regulate each aspect of logistics for clinical trials: extensive global standard operation procedures (SOPs) to ensure compliance and harmonization, detailed processes and defined process maps should be in place.
- Development and use of appropriate technology that connects the clinical trial supply chain stages and facilities globally and provides the supply chain better visibility.
- Appointment of a single source of logistics project information for study team members.
- Constant analysis of risks, search for opportunities, and introduction of improvement actions.
