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International Clinical Trials

Return to Sender

In recent years, the pharmaceutical industry has witnessed tremendous change in the way it is expected to deliver new drugs to market. This has been driven by several factors. The industry has faced head-on the prospect of 'the patent cliff', losing about $290 billion in revenue as a result of branded prescription medications going off-patent. At the same time, drug development timelines are under constant attack, with speed to market paramount to success.

As such, innovation and cost-efficiency is crucial; R&D costs are continuing to grow aggressively, with an average investment of $1.3 billion required to successfully initiate a new drug to market and an average of 12 years to bring a new molecule from laboratory to approval (1). Furthermore, the attrition rate of drugs advancing through clinical trials has suffered greatly; only about 1 in 5,000 candidates that enter preclinical testing make it to market (2).

Due to these continued pressures, the industry’s focus is on developing quality drug candidates and getting them through clinical development as quickly, effi ciently and cost-effectively as possible. As a result, most attention is paid to upfront study planning and ensuring the onset of clinical studies are executed in a timely fashion, while the end of the trial and final milestones are often not given as much consideration.

Neglecting Unused Product

Today's investigational clinical studies have evolved and become more complex. Modern-day trials involve a substantial amount of logistical demands: sourcing developmental drug product; the development and interpretation of study protocol; coordinating language translations; labelling and executing packaging; sourcing comparator drug product; and executing monitored logistics in getting the investigational medicinal product (IMP) to investigational sites around the globe. These activities are best left to clinical supply experts and, even then, there can be unforeseen and unanticipated issues.

Increasingly, clinical trials are carried out with a multinational remit, and often in emerging markets such as Russia and Eastern Europe, Asia-Pacifi c countries, China and South America – giving rise to further cultural and regulatory challenges. However, the complex nature of preparing and delivering these studies often means that planning for the return of unused drug product at the completion of the study is neglected.

IMP regulations mandate that all unused trial medication must be returned and accounted for at the completion of each study. This process of reverse logistics back to the sponsor or designated returns vendor may involve hundreds or thousands of packages needing to be returned and checked off. For the scope of some studies, this may involve accountability down to the individual dose level. Controlled substances, for example, require meticulous reconciliation to the tablet level. Detailed records must be maintained and returned drugs must be efficiently processed.

Early Planning

Sponsor companies can significantly ease the returns process by clearly outlining and agreeing the process for receipt, reconciliation, notification (to sponsor) and destruction of study materials at the outset of the trial. Providing clear and concise instructions to investigator sites from the start – setting out the processes by which samples should be returned – is vital to ensure a smooth returns process. Likewise, clear expectations should be set for the parties providing returns management services, to ensure prompt processing of returned product.

Since investigator sites often have very limited space for storing study materials, sponsors should be prepared for the fact that returns may begin to be received ahead of the conclusion of a study. Prompt and efficient processing of returned study materials is typically best accomplished by dedicated returns management staff, experienced in the training and skills required for this type of precise and exacting service.

Communication Systems

Communication between all parties throughout the returns process is critical. Increasingly, this entails data entry and returns accountability confirmation via common, cloud-based, electronic third-party interactive voice response/ interactive response technology (IVR/IRT) systems.

Choosing the most appropriate system at the start of a study can have a tremendous impact, positively or negatively, on the returns process during and at the conclusion of a trial. Having effective and user-friendly returns modules in the IVR/IRT system can help expedite data processing and timeliness of information reporting. Systems with a poor user experience can encumber the returns process and delay the resolution of discrepancies.

The timing of processing and flow of communications is key to ensure effi cient resolution of any discrepancies between what was perceived to be sent from the investigator site and what was actually received by the returns processor. Both sites and returns processors must understand the implications of discrepancies that may arise. Disparities can tie up valuable time and resources, and potentially inhibit the sponsor’s ability to formally close the study.

It is essential that any discrepancies found upon return are communicated to the sponsor, documented and closed out, so there are no gaps in the chain of custody. If this is clearly defined upfront in the process set-up, there should be fewer issues down the road.

Integrity and Cost Control

Product unblinding can also be a potential issue in the returns process, and both investigator sites and the returns processors need to understand the potential impact to integrity of the study if product unblinding were to occur. Furthermore, it is important to understand that the integrity of a study needs to be maintained for its duration, which can often be 2-3 years; as such, a returns management process that ensures security of the study is essential.

In addition, sponsor companies can benefit from giving forethought as to what will be the disposition once returned drug product is received and processed. It should be determined whether product will be designated to be immediately destroyed, stored and catalogued until the completion of that study/phase, or potentially kept for years.

These discussions can allow a sponsor to establish cost estimates and budgets at the outset; alternatively, the lack of these conversations can lead to 'scope creep' and unexpected costs at the end of a study. Providers of returns management services can help mitigate costs by working with clients to create dialogue on potential options and industry best practices.

A returns management provider must work with sponsor clients early on in their study development to avoid the frustrations that commonly arise in the latter returns management process. This helps sponsors focus their energies on the next phase of their development – and ultimately the successful commercialisation of their life-saving therapy.

1. Herpers M, The truly staggering cost of inventing new drugs, Forbes, 2 October 2012
2. Drug approvals – from invention to market... a 12-year trip. Visit:

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Gavin Morgan is Manager, Global Storage and Distribution, at Packaging Coordinators, Inc. With over 12 years of experience in clinical trial distribution, he is responsible for the direction of the company's European logistics operation. Gavin works to develop and implement effective strategies for storing, processing and transporting supplies to third-party depots and global investigational sites. His role involves ensuring shipments are in compliance with international regulations and standards, and managing the importation and qualifi ed person release of clinical supplies into the EU. Gavin previously worked as a Logistics Manager for DHP Ltd and Bilcare.
Gavin Morgan
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