Before we can diagnose and solve these challenges, we need to agree on what we mean by accountability and reconciliation in simple terms.
Accountability is documenting the activities at each stage of the journey of IMP at the site. These activities include (but are not limited to) receipt, dispensation, quantities dispensed/returned, sent for destruction, etc..
Reconciliation is the act of comparing accountability records with the physical reality to ensure the documentation can be supported, to identify any discrepancies, and to ensure the records are corrected if needed.
Now that we know the "what" we need to know the "who", the primary challengers in this struggle, Investigational Site sand Sponsors. They both have a role to play and skin in the game.
Let us then turn to the regulations to get a baseline of responsibility as outlined in The ICH Guideline for Good Clinical Practice E6 (R3) (Final Version Adopted 06 January 2025).
For the Investigator it seems very clear.
2.10.1 Responsibility for investigational product(s) management, including accountability, handling, dispensing, administration and return, rests with the investigator/institution. The sponsor may facilitate aspects of investigational product management (e.g., by providing forms and technical solutions, such as computerised systems, and arranging distribution of investigational product to trial participants).2.10.2 When the investigator/institution delegates some or all of their activities for investigational product(s) management to a pharmacist or another individual in accordance with local regulatory requirements, the delegated individual should be under the oversight of the investigator/institution.
But then 2.10.3 introduces delegation to the Sponsor clouding this slightly.
2.10.3 Where the investigator has delegated activities related to investigational product management or aspects of these activities have been facilitated by the sponsor, the level of investigator oversight will depend on a number of factors, including the characteristics of the investigational product, route and complexity of administration, level of existing knowledge about the investigational product's safety and marketing status.
For the Sponsor ICH also contains responsibilities around the records to be maintained regarding IMP.3.15.3 (c)
(ii) Maintain records that document the identity, shipment, receipt, return and destruction or alternative disposition of the investigational product(s) (see Appendix C);
Appendix C Essential records for the conduct of a clinical trial.
C.1.3
The investigator/institution should have access to and the ability to maintain the essential records generated by the investigator/institution before and during the conduct of the trial and retain them in accordance with applicable regulatory requirements.
C.3.1
(v) Provides information about the shipment, storage, packaging, dispensing, randomisation and blinding of the investigational product;
(w) Provides, where appropriate, traceability and accountability information about the investigational product from release from the manufacturer to dispensation, administration to trial participants, return and destruction or alternative disposition;
So here you have it, two responsible parties who want to manage that responsibility in their own way.
Sites are responsible for what happens in their facility and consequently they want to use their systems. Even if they conducted no clinical trials they would manage and track medications under their control. Large institutions have built or purchased sophisticated internal systems to accomplish this goal. They have created SOPs and processes based on these systems. They don't want to do things twice.
Sponsors also have responsibility for knowing the disposition of the IMP in their studies. Not only do they need access to these records they want a reliable record for themselves. They want a single source They are focused on a data set of a particular trial, not all the medications coming in and out of a particular facility. They want a clean data set akin to EDC with all this data in one location.
While integrations between commercial and bespoke pharmacy management systems at sites are technically possible there is little appetite from sponsors or sites to pay for these integrations. A primary reason for this is there are so many of these systems in use that the outcome would not justify the resources required.
IRT companies have developed good tools (Taikun Pharma Services' is particularly great) but the tension between sponsors and sites leads to underutilization of these products/features.
Is this the immovable object against an irresistible force? Maybe, but hopefully not. In my experience this is an area where understanding must be the first building blocks of a solution. Only when both sides of the equation have a mutual understanding of the challenges faced by the other can we have true collaboration and solution. In the short term a risk-based approach that respects all constituencies and is flexible to the situation of each is a path forward.
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