Advances in clinical trial logistics

Pharmaceutical manufacturers face a multitude of challenges as they work to bring new products to market. Rising R&D costs, difficult recruitment and retention of patient populations for clinical trials, increased competition among manufacturers of all sizes, more stringent scrutiny over medication prices: All of these factors and countless others are driving manufacturers to be more mindful of costs. As a result, manufacturers constantly search for ways to be more cost-efficient in both clinical and commercial operations, seeking optimal value to streamline development costs, timing and processes. Mindful of this thinking among the manufacturer community, World Courier shares our thoughts on several key trends in clinical trial logistics—as well as their implications for manufacturers’ ever-present balancing act of cost versus value.

Proliferating trial protocols

The two largest issues plaguing clinical trials are patient recruitment and retention. The need to find increasingly specific patient groups for specialty products—including those who are treatment-naïve, are diagnosed with rare diseases or have genetic abnormalities—is driving the movement of new trials to emerging markets, such as Asia, Latin America and the Middle East. Access to broader patient populations can significantly increase recruitment and retention, but working in emerging markets can pose a number of obstacles on the logistics front.

From a macro perspective, patient recruitment can vary in speed and numbers depending on the site, and it often differs from forecasted recruitment patterns. As a result, the supply chain needs to be dynamic and adaptive. It needs to ensure that product arrives at the correct site at the right temperature as quickly and cost-effectively as possible, while also limiting future waste in the supply chain. This is difficult in any environment, but especially in nontraditional markets.

Brazil, for example, stands out as a particularly attractive clinical trial market. For companies looking to launch products in Japan, Brazil’s large Japanese population enables manufacturers to meet trial requirements for the Japanese market at a lower cost than conducting the trials in Japan.

Many manufacturers, however, do not have clinical trial experience or the full breadth of infrastructure to support the clinical trials they would like to conduct in the region. To combat this challenge, manufacturers are applying a collaborative partnership approach to clinical-trial product storage and depot-to-trial-site delivery. They are leaning on local services like in-market clinical storage depots and depot-to-site delivery to serve as virtual extensions of the resources the manufacturers might run themselves in more mature markets.

Infrastructure in many emerging markets remains inconsistent from city to city. Where some airports are able to store shipments of clinical trial products or patient samples at a verifiable, controlled temperature, other airports do not have the onsite capabilities.

Even in cases where temperature-controlled storage is available, our data has shown discrepancies between temperature ranges stated by the airport and actual temperatures recorded by on-shipment thermometers. At one airport in Argentina, the stated range for controlled ambient storage is 15°C to 17°C. Because this storage is located next to the refrigerated area and is only separated by a curtain, the actual temperature is consistently much closer 
to 6°C.

Key takeaway: As emerging markets continue to take on a more prominent role in clinical trials, manufacturers are working more collaboratively with logistics partners to match global goals with local expertise, requirements and conditions. Doing so allows manufacturers to create a holistic picture of the challenges they must overcome on a market-by-market basis. That picture can then inform manufacturers’ analysis of which emerging markets can create the most value on an immediate basis.

Evolving regulations

Conducting trials in multiple geographies also produces a number of regulatory issues to be addressed. Each country has its own clinical-trial regulatory requirements, and those regulations are constantly changing. Failing to adhere to regulations can derail timelines and budgets, so vigilantly monitoring market-specific requirements 
is essential.

Take, for example, three international quality standards relevant to clinical trials: Good Clinical Practice (GCP), Good Distribution Practice (GDP) and Good Manufacturing Practice (GMP) [collectively, these are often referred to as GxP]. GCP focuses on clinical trial conduct, but also ties to GMP (i.e., Investigational Medicinal Products—IMPs—need to be manufactured, stored and distributed following GMP principles). GDP also ties to general GMP rules, and specifies storage and distribution requirements in greater detail. Suffice it to say, failure to remain current on these overarching quality standards puts clinical trials at substantial risk.

Taking this a step further, each country has leeway to interpret standards. In the United Kingdom, the Medicines and Healthcare Products Regulatory Agency (MHRA) interprets GDP principles more stringently than other European Union countries. Among the MHRA’s additional requirements is the Wholesale Distribution Authorisation (WDA), a benchmark certifying quality systems and processes for storing and distributing pharmaceuticals. Designed to ensure patients safely receive the proper medications, the regulation serves as a verification measure to enforce yet another regulation, the EU’s Falsified Medicine Directive, which includes measures that keep counterfeit medical products from entering the legal supply chain.

Key takeaway: There can be many layers and nuances of regulation even within a single, mature market, like the UK. When trials are conducted across multiple markets—some of which might be far less mature—navigating the compliance maze can be burdensome and confusing at best. At worst, it can be error-prone and inject delays and budget overruns into a clinical trial process whose success depends on speed, quality and efficiency.

Multinational logistics service networks

Most manufacturers have—for lack of a clearer term—lumpy global scheduling and activity with clinical trials. Their clinical trial needs vary greatly over time. One month, an active study might require focus and resources in Brazil, but later in the year, another study might shift the focus to South Africa or China. Local product storage in each country allows manufacturers to move quickly and ensure product integrity, but the cost of building the necessary infrastructure and maintaining requisite quality standards is often excessive and an inefficient utilization of resources.

To solve for this, manufacturers are increasingly looking at solutions that offer a multinational service network. The fee-based model allows manufacturers to take advantage of world-class clinical depots and other resources that ensure product integrity and manage secure transport to trial sites—but without incurring the capital costs or risks associated with construction and build-out, inventory management, personnel management, or adherence to GxP. The potential downsides of such a partnership are rooted in trust and cost. Manufacturers must ask themselves if the potential partner has enough of a successful track record developing and managing clinical depots, particularly in emerging markets where expertise in local policies is paramount. Does the partner have flexibility to onboard new projects quickly enough to match the manufacturer’s needs? Does the partner offer the level of consistency and quality across multiple locations to create value out of a preferred vendor strategy versus a best-of-breed strategy?

Key takeaway: More trials and studies conducted across more geographies can be the springboard for manufacturers to think about their supporting infrastructure in a different way. But as manufacturers do so, it’s crucial for them to evaluate partners across multiple dimensions of quality, efficiency and value.

The art and science of temperature control

The importance of specialty packaging has never been greater. In today’s increasingly complex environment, more products require temperature-sensitive transport than ever before, and the need only continues to rise. Manufacturers are seeking the highest performing and most cost-effective methods for packaging, a need that must be balanced against the R&D costs required to test packaging solutions for each specific product.

To assist manufacturers with the packaging selection process, last summer World Courier launched our Climate Optimisation Research & Engineering (CORE) Labs. Science-led and data-driven, CORE Labs is a solutions center focused on helping manufacturer partners evaluate, validate and select the right climate-controlled packaging solutions 
for each specific product and often for a specific route.

What we’ve learned from this endeavor is that manufacturers are expecting more from all their logistics partners. Where 120 hours of validation time for shipping systems was at one point considered high-performing, today it’s becoming more of an industry standard. And where configurations of standard packaging were once suitable for the vast majority of shipments, today we are seeing far greater need for packaging solutions that are individually customized to the needs of a client or the characteristics of a specific product.

Moving forward, the industry will see an even more rapid pace of innovation in this space. More advanced temperature monitoring will provide as close to real-time temperature data from manufacturer to trial site to patient home for administration. RFID-enabled packaging will provide more accurate geo-positioning at a lower cost than current GPS-based solutions. And more careful attention to packaging construction will reduce thermal leakage points, extending the useful range of the package.

Key takeaway: The pace of technological advances in packaging, storage and transportation will match the pace of innovation seen in pharmaceutical and biotech development.

Achieving higher value

As previously mentioned, two of the biggest obstacles to conducting a successful clinical trial are patient recruitment and retention. A trial that has to be abandoned due to patient attrition has large negative ramifications for the manufacturer, as the time and costs associated are immense and the opportunity cost is high. To address this issue, some trial sponsors are creating a trial process that is shaped more around patients’ daily behaviors—specifically, at-home trials.

The promise of a direct-to-patient model is clear and appealing: Conduct the trial in each patient’s home to lower the patient burden and subsequently increase the odds they enroll in a trial, while reducing the odds of them dropping out prior to completion of treatment. The execution of this model has, at times, been frustratingly challenging for manufacturers.

Managing such a decentralized process requires precision in coordinating clinical staff, clinical trial product and the patient. From ensuring the product integrity away from a clinical site, to scheduling delivery of the product during a time that a nurse can be available to administer it, to capturing the right data at the right time during the patient’s course of treatment, the points of risk are not difficult to identify.

But as technologies and processes evolve, at-home trials become more feasible. Mobile technologies allow for accurate monitoring and tracking of products, whether they are at the manufacturer’s facility, a clinical depot, a traditional clinical trial site or a patient’s home. At the same time, partnerships between clinical-trial management companies (clinical research organizations) and specialty logistics providers are opening new possibilities for where, how and how quickly clinical trials can occur.

For example, AmerisourceBergen’s patented CubixxCT unit provides refrigerated storage with remote temperature monitoring, inventory management and access control. The solution removes logistics barriers by allowing clinical trial products to be delivered to patients’ homes and stored securely until the time of administration by a nurse. By addressing challenges like these, new solutions for in-home clinical trials can boost patient retention as high as 95%, and the speed of recruitment can double. *

Key takeaway: Once viewed as unrealistic due to quality and cost concerns, at-home clinical trials using a direct-to-patient approach are now viewed as viable and valuable through technology advances.

These trends in the clinical trial marketplace—growth in emerging markets, evolving regulations, the rise of multinational logistics services, temperature control innovations and the direct-to-patient trial model—present both challenges and opportunities for industry. Optimizing the supply chain and enhancing clinical trial efficiency, and selecting partners who can help them do so, is critical for manufacturers in an increasingly cost-conscious and results-demanding environment.

ABOUT THE AUTHOR

Sam Herbert is chief operating officer at World Courier, a business unit of AmerisourceBergen. Prior to joining World Courier in 2013, he was a partner in Oliver Wyman’s Health and Life Sciences practice where he advised some of the world’s leading pharmaceutical, healthcare and pharmaceutical services companies. Sam holds an AB of Economics, cum laude, from Harvard College and is based in World Courier’s global headquarters in London.

* Source: Medical Research Network (http://www.themrn.co.uk/)