Investigational medicinal product logistics encompasses the planning, provision, storage, allocation, return and documentation of investigational medicinal products for a clinical trial. Its objective is to ensure that a suitable, correctly labelled and released investigational medicinal product is available at the trial site at the intended time and under the specified conditions. It thereby protects participants, preserves product quality, and ensures blinding and traceability of every unit.
Planning, labelling and allocation
Planning begins with determining requirements by country, depot and trial site, as well as with the packaging, labelling and release strategy. It takes into account shelf life, delivery times, import requirements, blinding, replacement shipments and recall processes. The delivery plan should also consider limited storage capacity, site closures, seasonal transport obstacles and required safety stocks. Responsible parties and verifiable release points must be clearly defined for every delivery stage. Delegated Regulation (EU) 2017/1569 requires the manufacturer to prevent cross-contamination and unintended mixing through technical or organisational measures and to pay particular attention to the handling of investigational medicinal products during and after the completion of blinding. Labelling and packaging must enable safe use while maintaining the required blinding.
In randomised studies, logistics are linked to the randomisation system. An interactive response system can assign a suitable kit following a rule-based allocation and simultaneously trigger replenishment or transfers. However, the system must not alter the randomisation decision in an uncontrolled manner. The interfaces between randomisation, kit numbers, depot inventory, shipment and dispensing at the trial site must be defined, validated and controlled when changes are made before the study begins. This also includes authorisations for unblinding, replacement kits and emergency procedures. Such processes must protect participant safety but may lift the blind only to the extent intended. Every system-supported allocation must therefore remain reconcilable with the investigational medicinal product actually dispensed.
Temperature chain and storage
The approved storage and transport conditions must be defined for each investigational medicinal product. The temperature chain encompasses not only refrigerated transport, but also the continuous control of the specified conditions from shipment through storage and dispensing. Suitable packaging, qualified shipping routes, temperature monitoring, receipt checks and documented storage areas must be coordinated for this purpose. A temperature log alone is insufficient if the assessment of deviations and the decision on usability are missing.
In the event of a temperature deviation, the affected investigational medicinal product is placed on hold until a qualified assessment is conducted in accordance with a procedure defined in advance. The trial site may not independently release or dispense the unit. The assessment must link the batch, kit, duration and extent of the deviation with the decision on use, return or destruction in a traceable manner. This control is particularly important because quality losses can impair safety and the validity of the trial.
Accountability, return and destruction
Accountability refers to the complete, traceable accounting of the receipt, storage, allocation, dispensing, return, shipment back and final disposition of the investigational medicinal product. At the trial site, deliveries, inventory, dispensing to participants, returns and remaining quantities are documented promptly and reconciled with the source data and system data. Deviations, damaged or expired units and unused kits are controlled separately. Accountability also applies to comparator and placebo products insofar as they are provided for the trial.
After completion of a treatment or study, unused or returned units are shipped back or destroyed in accordance with the defined strategy. Destruction takes place only after the required approval and must be documented with the quantity, identity, date and responsible party. Delegated Regulation (EU) 2017/1569 also governs the retention of reserve samples and requires product specification documents and batch records to be retained for at least five years after completion or discontinuation of the last trial in which the batch was used. The detailed Commission guidelines C(2017) 8179 final further specify that destruction may take place only after prior written authorisation from the sponsor and completion of reconciliation, and that the records, including the certificate of destruction, must remain attributable to the affected batches. Complete accountability makes it possible to assign each unit to the appropriate batch, storage location and, where applicable, allocation.
Relevance for clinical trials
Errors in investigational medicinal product logistics can directly jeopardise treatment safety, blinding, availability at the trial site and the interpretability of results. Particularly critical are delayed deliveries, undetected temperature deviations, unreconciled inventories and discrepancies between kit and participant data. A logistics plan therefore requires clear roles among the sponsor, manufacturer, depot, shipping service provider, trial site and randomisation system, as well as defined escalation pathways.
Full-service CROs such as Mediconomics support needs planning, coordination of depots and trial sites, definition of accountability processes, reconciliation with randomisation data, and monitoring of storage, return and destruction. Clinical Supply, Clinical Operations, Monitoring, Quality Management and Data Management can thereby bring product and participant data together in a traceable manner and address deviations in a timely way.
Frequently Asked Questions (FAQ)
What happens in the event of a temperature deviation?
The affected investigational medicinal product is placed on hold in accordance with the defined procedure. Only a documented expert assessment can decide whether it may be used, returned or destroyed.
Why is there a connection to randomisation?
In blinded randomised studies, the dispensing of a kit must correspond to the intended allocation without revealing the treatment. Randomisation and supply systems must therefore work together in a controlled manner.
What does investigational medicinal product accountability cover?
It documents the complete disposition of every supplied unit, including receipt, storage, dispensing, return, shipment back, destruction and justified deviations.
Regulatory references
- Delegated Regulation (EU) 2017/1569 – lays down the GMP principles for the manufacture, handling and documentation of investigational medicinal products.
- Detailed Commission guidelines C(2017) 8179 final – specify packaging, relabelling, reserve samples and destruction.
- Regulation (EU) No 536/2014 – establishes the EU legal framework for clinical trials and investigational medicinal products.
- ICH E6(R3) Good Clinical Practice – requires controlled processes for investigational medicinal products and relevant records.
- EudraLex Volume 10 – contains guidelines on the application of Regulation (EU) No 536/2014 in study operations.