Logistically Speaking

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A Guide to Global Clinical Trial Coordination

The cost of bringing a new drug to market can now exceed 800 million dollars – triple the cost of ten years ago. The entire drug development process is not only costly, but is associated with many difficulties and risks. And with so much time and effort devoted to managing key study components, often one of the last issues to be addressed is logistics. The timely, safe and documented transport of investigational drugs, supplies and specimens can make or break a clinical study and can be the weakest link in the entire clinical trial process.

More Projects, Less Patients
It is estimated that the number of drugs developed in the world has gone up from 4,194 in 1997 to 7,067 in 20021 with the majority registered in North America and Western Europe. This exponential growth has created stiff competition amongst researchers, who are enrolling subjects from the same, limited investigator and patient pools, effectively leading to lengthy R&D delays and spiraling project costs. It is estimated that 80% of clinical trials fail to recruit on time.2

To overcome these obstacles, many Canadian biotechnology and pharmaceutical companies have turned to the overseas markets, specifically the emerging markets of Latin America, Eastern Europe and Asia, to conduct their clinical trials. The benefits are obvious: large pools of patients and investigators from multiethnic and multiracial backgrounds, access to treatment-naïve populations where study participation can offer access to quality health care and medicines that may not be otherwise affordable, rapid patient recruitment and potential savings of up to 50% on overall project costs as compared to the West.

Regulatory Compliance & Distribution
Globalization presents some special challenges. For example, although not a logistical issue, the time required to obtain regulatory approval to conduct clinical trials overseas can be lengthy. While this is often offset by rapid recruitment rates, the poor planning of the regulatory requirements of a study can devastate a project altogether.

It is critical to any study's timeline that clinical trial supplies be available at investigator sites when required. The import of investigational drugs is highly regulated and the necessity to comply with country-specific regulations is imperative. Failure to do so could cause unforeseen delays to the study, primarily due to hold-ups and seizures in customs. Consideration must also be given to a country’s current socio-political issues, transport infrastructure, experience of site personnel, language barriers, the level of understanding by local authorities and the time required to obtain appropriate import licenses.

In many countries, import licenses are required for each shipment of investigational drug coming in and often take weeks to obtain. As a result, direct-to-site shipments from a warehouse located outside of the country can become impractical. In most countries where customs regulations are complex and strictly enforced, the slightest issue with the shipment itself or the accompanying paperwork can result in material being held in customs for prolonged periods. Appropriate planning, communication and an understanding of the shipping and import requirements prior to conducting any study will reduce the chance of related delays and seizures.

"By using centralized depots, [companies] can significantly reduce customs delays, improve the regulatory permit process and better meet their strict re-supply timelines," says Wayne Heyland, President and CEO of World Courier Group, a multinational transportation service specializing in the coordination of global clinical trials. "This is particularly important in the emerging markets where interest in conducting clinical trials is growing incrementally [compared] to advancements in the local infrastructure."

Additionally, the qualifications of importers, including pharmacists and CRO's, can add to the complexity of the process. Appropriate training, communication and direct coordination with the transportation provider, customs brokers and agents are required to limit this. "Ensuring international compliance with changing regulations is a huge challenge since today's global study will typically involve a variety of organizations in a variety of industries operating in many different countries… Without far-reaching compliance, the transportation of [clinical trials supplies and] biological specimens becomes more costly and complicated" says Mr. Heyland.

Temperature Control
Implementing the correct shipping system for a particular drug product and overall protocol requirements is vital to verifying the results of a clinical trial. With the current growth in temperature-sensitive shipments and the increasing requirements to demonstrate that a product is maintained within its respective temperature range being enforced by authorities such as the FDA and Health Canada, a strategy to avoid deviation in the cold chain is essential. Although there is no truly active shipping system, there are many pre-qualified shipping solutions readily available in the market that, if utilized properly, can provide a greater degree of confidence when shipping investigational drugs and samples.

Insulated shippers are available in one-way and reusable forms with both summer and winter pack-out configurations. It is important to consult with the packaging supplier to determine the appropriate pre-conditioning requirements set out by the manufacturer since the slightest deviation from performing the recommended pre-conditioning procedures can adversely affect the temperature results of a shipment.

There is also a wide range of temperature recording devices available, ranging from simple labels to sophisticated electronic devices that will allow data to be downloaded. These become extremely useful in establishing that the product was maintained within the required temperature range but also in the event of a deviation in temperature, where it may be helpful in identifying the root of the excursion and in developing remedial actions. Any deviation outside the specified temperature ranges can affect the integrity of the product, reaffirming the need to have stability data for temperature excursions readily available not only to site personnel but to the transportation provider as well. Refusing to disclose this information to a site could result in avoidable delays or a missed enrollment opportunity through a lack of visibility of permitted excursions.3

The Weakest Link
Working with global market partners to develop an effective clinical supply chain will go some way to ensure the success of a study. Research firms are increasingly integrating their transportation providers into their business and are sharing more proprietary information with them than ever. This shift has resulted in a change from employing the more economical express companies to working with dedicated and experienced multinational carriers that offer a consultative approach and a full clinical trial service offering. Most transportation failures can be prevented through extensive preparation and a reliable transportation provider.

The weakest link in clinical trials logistics is not having the appropriate representation to deal with local language barriers, customs authorities, time zone differences, specimen integrity, constantly changing regulations, security matters and overall adherence to protocol instructions.

These are challenges that should become easier to manage with more global experience, new technologies and careful coordination. By cultivating partnerships with suppliers, transportation providers and regulatory authorities, companies will be better able to navigate logistical difficulties and reduce the time it takes to get their new drug to market.

Bio: Paul Saratsiotis is Business Development Manager at World Courier Canada, assisting Canadian biotech and pharmaceutical firms develop logistically-sound transportation solutions from API manufacturing to Phase III clinical trials.


References
1. Kundu, K.K. "India Leads In Clinical Trials" Asia Times Online, May 2005
2. King, J. "Ten Ways To Faster And Easier Patient Recruitment" R&D Directions, April 2004
3. Shannon, R. "Supplying The Needs of Emerging Markets-Understanding
Clinical Trial Logistics"
(CTS; www.cts-almac.com)