The logistical complexities involved in reconciling and destroying returns of clinical trial supplies should not be underestimated. If a trial is to meet its study closeout timelines, then the handling of returns should be planned at the outset, not addressed at the end.
Given that patient recruitment will inevitably vary from the sponsor’s forecasts, most clinical sites will have unused or even expired products that will need to be properly accounted for and disposed of as part of the study close. Clinical site teams must adhere to good clinical practice, the trial protocol, local policies regarding returned products to safeguard trial participants and comply with the sponsor’s own procedures.
Forward planning
Without a proactive plan in place to account for clinical supplies, sponsors may find they must delay the closure of the study because regulators need to ensure that unused supplies are not left in circulation or diverted. This, in turn, can delay the drug’s regulatory submission and approval.
Returns and reconciliation should, therefore, be an important part of planning conversations between the sponsor and the clinical supply team. The ideal scenario would be to engage in these discussions at the start of the project to allow the supplier to understand where challenges may arise, and then determine the level of service that would be needed to align with the clinical protocol.
There are varying levels of reconciliation possible depending upon the investigational medicinal product (IMP) and applicable regulations. For controlled drug substances, for example, this may involve accounting for every dose distributed and used throughout the trial.
Regulatory differences
There is, therefore, no ‘one-size-fits-all’ approach to returns and destruction, and each study needs to be assessed on a case-by-case basis, depending on the countries in which the clinical sites are located, the nature of the drug(s) involved and the level of reconciliation required. It cannot be assumed that a product can leave a country in the same form as when it arrived.
In some countries, where the export of a clinical product for destruction is not permitted, the destruction must be performed within that country. In others, all unused products must remain within the country for the duration of the study. Recently, some countries have started to classify expired medications as medical waste. This precludes the export of unused product for destruction and requires that the procedure is enacted locally.
Documentation retention remains a regulatory constant and there is an expectation that all study documentation will be stored electronically for seven years after the trial is completed.
Important considerations
Firstly, the natural variances in returns must be understood. It can be difficult for sponsors to predict the levels of returns at each site, given the inherent variances in patient recruitment and drop outs that can impact the level of product consumed, and thus the percentage of waste. It is important to understand how reconciling these unused products will affect the completion of the study.
Next, they should develop a forward-thinking strategy. Sponsors must evaluate the level of accountability required for clinical returns as early as possible in the planning process to ensure it aligns with the clinical protocol. This will allow the clinical supply provider to plan for transport, storage and destruction, and thus be able to give the sponsor a more predictable budget.
Finally, the sponsor should educate the study sites – at clinic and at any clinical research organisations – to have a full understanding of the proposed clinical supply strategy, and the returns and destruction process. Working with the clinical supply provider, this will allow them to ensure the site sets aside sufficient time to complete the returns and create all the associated documentation.
An experienced clinical supply chain specialist will be able to assist in mapping out the end-to-end needs of the trial, enabling it to keep to its planned timeline.
