Article | March 6, 2018

The Importance of Proactive Clinical Returns Planning

Source: Catalent

Q&A with Dianne Coughlan, Global Supply Chain Director, and Rognvald Lamb, Global Transportation Manager, Catalent

The Importance of Proactive Clinical Returns Planning

Accurate and timely delivery of clinical trial supplies helps to ensure that a study’s timeline stays on track. Sponsors often focus on upfront planning to ensure sites are prepared to reach clinical milestones but ignore the logistical challenges of reconciling and destroying clinical returns. Dianne Coughlan, Global Supply Chain Director, and Rognvald Lamb, Global Transportation Manager, recently shared their thoughts around managing the clinical supply returns process and how their efforts at Catalent help sponsors design a more holistic strategy.

Understanding the Clinical Product Lifestyle
Why are clinical returns often overlooked in the planning process and does it make a difference in a study? Dianne explains what she has encountered in her work.

“I think clinical returns aren’t at the forefront of a sponsor’s mind because it’s a process that takes place at least 6 to 12 months down the line. With many other priorities in the clinical journey, returns are often an afterthought,” she says.

“Neglecting this detail can have consequences,” adds Rognvald. “Given that forecasted patient recruitment will vary from actual recruitment, most studies sites will have unwanted, unused or even damaged product that will need to be cleared from the study sites,” he said.

“Sponsors may intend that 100% of a clinical study product is used by the end of the study, but this rarely happens and lack of planning can affect the timely destruction of unused materials. Without a plan in place to account for clinical supplies, sponsors could potentially delay the closure of the study, and therefore the approval of a drug with regulatory agencies.”

Anticipating the Requirements for Clinical Returns
Working with their clinical supply team, the returns and reconciliation should be an important part of the planning conversations, explains Dianne. “The ideal scenario is to scope a sponsor’s needs at the beginning of a project. Then we can understand where we will face challenges and determine the level of service needed to align with the clinical protocol.”

Potential levels of service, from basic to complex, include:

  • Performing simple destruction of the product
  • Coordinating return of the product for reconciliation and then destruction
  • Providing individual counts to measure the amount of unused product or estimate how much product was actually used by patients

If a return strategy is developed after study starts, the operational team may not understand the level of accountability needed for the product and may encounter rework, delays and potential changes in the cost of returns. Pre-planning helps avoid this issue by providing a clear estimate or time and cost for the end-to-end process.

Coordinating Complex Logistics
When running a global investigational study, clinical supply providers are aware of the challenges with timely shipping and clearing customs in each country. Sponsors coordinating the timely return and destruction of clinical supplies also encounter these same hurdles.

“Generally, as a rule of thumb, we would use the same shipment routes for the returns,” says Dianne. “But with imports to some countries, we face a complicated customs process. For those countries, such as Brazil, or Argentina, or China, we import one large shipment to a depot and then distribute on-demand to the sites. The same reverse logistics would apply.”

Adds Rognvald, “We ultimately want to avoid having a clinical site creating export documentation. That become onerous for the sites. It isn’t their core competency and doesn’t add to the value of the study. That’s why it makes sense to use a depot model to take care of the returns and destruction.”

Understanding Country-Specific Differences
In some countries, a clinical product cannot be exported for destruction, says Rognvald. “Serbia, for example, is one area where they don’t allow the export of clinical waste,” he explains. “In addition, they do not have commercial or even centralized incineration facilities.”

For Serbia, and other countries with similar restrictions, Catalent works directly with the clinical research organization (CRO) to help the clinical sites carry out the destruction at their own facilities. “This requires a good working relationship with the CRO to ensure that they account for this requirement at their study sites,” says Rognvald.

Sponsors must be aware that other countries have limiting factors that impact the returns process. Explains Rognvald, “Taiwan requires an import permit that specifies the quantity of product. Here, all unused investigational product must remain in Taiwan for the duration of the study. Given that many sites will not have the space to store unused product for up to two years, a return depot can accommodate the unused product over time. Then, a single export can economically return all the samples to Catalent for destruction, or we can arrange for destruction in Taiwan through our partner depot.”

Keeping Up With Regulations
Along with unique import/export requirements in each country, the clinical supply team must also keep up with international regulations and standards.

“In the last couple of years, we are seeing a shift where some countries are now classifying expired medication as medical waste,” says Rognvald. “This change means that in some areas we can’t export the unused product for destruction and have to plan for local destruction.”

Adds Dianne, “Catalent is aware that regulations can change and therefore we consider what alternatives for continuity in study timelines exist. It helps that we have the support of our partnering CROs when it comes to changes in returns.”

At the site level, the type of product also factors into the returns strategy. Controlled substances are typically reconciled down to the number of doses returned while some sites will not accept products with sharps unless they are removed.

One regulatory constant is documentation retention. Currently, all study documentation is expected to be electronically stored for seven years past the life of the study per GMP requirements.

The Top 3 Clinical Returns Considerations for Sponsors
Knowing that every day counts when advancing a product to market and maximizing the return on investment, sponsors need to consider the avoidable cost of delays associated with returns and destruction.

Rognvald and Dianne summarize three considerations to efficiently return and destroy unwanted clinical supplies.

  1. Understand the natural variances in returns
    It can be difficult for sponsors to foresee the levels of returns at each site given the inherent variances in patient recruitment, which can impact the level of product consumed and the percentage of waste. It is important to understand how reconciling these unused products will affect the completion of a study.
  2. Develop a forward-thinking strategy
    Sponsors need to evaluate the level of accountability required for their clinical returns, as early as possible in their planning process, to ensure the returns align with the clinical protocol. Knowing these requirements helps the clinical supply provider to plan ahead for transport, storage and the destruction, ultimately giving the sponsor a more predictable budget.
  3. Educate study sites
    With a full understanding of their proposed clinical supply strategy, sponsors should evaluate how well they can educate the clinic and CRO on the clinical returns process. Working with their clinical supply provider, they can guide the site to assist with the returns process and ensure sufficient time is set aside to complete the returns and create the associated documentation.

As clinical studies become more complex and face increasing pressure to uncover efficiencies and quickly advance to market, sponsors need to understand where their studies face risks and how to capitalize on opportunities to improve the drug development process. As a clinical supply chain expert, Catalent helps sponsors map out their endto- end needs, from timely product supply to returns, reconciliation and destruction. Get in touch to learn how we can help your team overcome common logistical challenges in the clinical supply chain and keep your timelines and budgets on track.