EU regulation 536/2014: Key Considerations When Planning for the Return and Destruction of Your Product.

Since the transition period for EU regulation 536/2014 started this year, the focus has returned to meeting all of the demands that will change from the Directive that everyone has been accustomed to following.

One commonly overlooked detail listed in the protocol requirement described in Annex I, states that the clinical protocol shall include “a description of the arrangements for tracing, storing, destroying and returning the investigational medicinal product and unauthorized auxiliary medicilinnal product…” This highlights an aspect of clinical supply management that is typically not a main consideration during the trial planning phase.

Aspects of accountability, reconciliation, return, and destruction should be part of the drug supply planning process. Unfortunately, however, this is often overlooked and significant effort is required to compile historical data. This difficulty can be avoided with a little up-front planning that in itself does not need to be extensive or detailed, but can remove many future complications.

Key Considerations

1. Where will destruction happen?
Will the clinical sites be able to coordinate destruction, or will a central return location be required? This information should be a required part of the clinical site evaluation. It is common to allow sites that are able to complete destructions to do so, however, not all sites will have that capability. In which case, both local and central destruction locations can be established. Identifying the reverse logistics supply flow may seem like a basic activity but is it a fundamental step in planning the process.

2. What level of accountability will be needed?
Does the drug need to be accounted for at the dosage level or dispensable unit? There may be additional drug attributes to consider, for example, whether it is a controlled substance and so a risk-based approach should be taken to establish the level of detail needed for accountability.

3. Vendor considerations for central returns
The default position is for the vendor responsible for packaging and distribution activities to be the location where the loop is closed for return and destruction. Once again, this capability is typically not considered when evaluating a clinical supply partner. Focus is usually on the ability of the selected partner to produce the clinical supply materials and get them to the patient, without considering the need for reconciliation and disposal of remaining investigational medicinal products. Knowing the answers to questions 1 and 2 above will allow you to include the requirements for return and destruction as part of a vendor evaluation process.

Key Questions to Ask Your Clinical Supplies Vendor

1. What is the vendor’s process for dealing with returned materials?
Ask about how returned materials are handled in the same way that you would for the release and distribution of clinical kits.

2. How are returns and destructions documented?
These activities are governed by GMP requirements. Discuss the systems used for initiating and maintaining all documentation and how the records can be obtained for audit requirements. Sponsors need to be
able to account for investigational products from time of production until they receive a certification of destruction.

3. What activities will you need the vendor to perform?
Will the vendor simply receive the shipment from the site and log the return, or will the carton need to be opened and the contents verified against site accountability? Ensuring the vendor is able to open packaging and document at the dosage level is a critical capability.

Taking the time to answer these simple questions will provide a solid foundation for creating a complete reverse logistics plan. Including reverse logistics in your clinical supply plan will help mitigate unexpected increased costs, delays in study close-out, inaccurate reporting from missing information, and potential audit findings from incomplete data. A holistic and end-to-end approach to clinical supply planning will ensure clinical trial integrity and help you achieve your clinical program goals.
At PCI, we engage with clients to develop a flexible and dedicated service to meet the needs of every clinical trial, from drug product manufacture to clinical packaging, labeling, and distribution, including developing study-specific return processes. Our global logistics experts ensure complete accountability and supply chain integrity throughout the clinical lifecycle.

Planning for the Return and Destruction of Your Product when Establishing your Clinical Supply Strategy.
As seen in World Pharma – Clinical Trial Insight 2022 Vol 1

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