By Deborah Borfitz

January 24, 2022 | The pandemic has served to highlight shortcomings of traditional practices around the cold-chain transport of biospecimens for clinical trials—including no backup plans when airports, borders, and study sites unexpectedly close. Even in normal times, default choices such as contracting mostly if not exclusively with premium couriers, can “artificially increase the cost of clinical trial conduct,” in the view of Thomas McDonald, associate director of biospecimen logistics for Bristol Myers Squibb Co. (BMS).

The two primary options logistics managers have when moving biospecimens from multiple sites of collection to a central lab for analysis are white-glove couriers such as World Courier and Marken, or the integrator services of package delivery companies such as DHL, UPS or FedEx. Industry-wide, roughly 70% of pharmaceutical samples are currently being moved via premium carrier and it’s a practice that may warrant revision, McDonald says.

It can be “unjustifiably wasteful” to depend so heavily on premium couriers when the integrators have built the network capacity to handle the job, including replenishing dry ice when packages are delayed or caught in customs. McDonald will be making his case during an upcoming presentation on cold chain challenges for the Clinical Supply Management track of the 2022 Summit for Clinical Ops Executives (SCOPE).

Premium couriers don’t generally have their own fleet of aircraft, so they rely heavily on commercial uplift. The pandemic at one point grounded more than 80% of all flights that were globally available in January of 2019, he notes, creating a panicked grab for the limited cargo space.

Moving samples from remote collection sites in Latin America that are seven hours of rainforest away from the nearest airport would be particularly problematic, McDonald says. If samples are being taken from tumors of patients with a late-stage oncology diagnosis, unanticipated local hurdles might well present an ethical dilemma as well.

Before COVID-19 vaccines were available and clinical sites weren’t permitting couriers to pick up samples as they normally would from study sites, companies needed a workaround—e.g., having clinical site mangers physically transport samples to a designated outdoor location, he continues.

The complications associated with the cold-chain shipment of biospecimens is related the fact that the cargo being moved is “invaluable inventory” intended to be translated into a data point that could ultimately help address unmet medical need, says McDonald. Considering that biospecimens are “representative of unique individuals at a particular point in time... [and] may be acquired in a progressive disease state relative to a therapeutic dosing event, they are truly one of a kind and not reproducible.” 

Surprisingly few people in the industry are currently focused on the “reverse supply chain” that accompanies the movement of biospecimens. “Right now, it’s a little bit like the Wild West,” McDonald says.

Then again, there hasn’t ever before been an event like COVID-19 with such protracted impacts on pharma and the supply chain. “A somewhat incongruous parallel could be the volcanic ash events that impacted EU air traffic circa 2010,” says McDonald, who has worked in the field since 1999. “The major difference is where that lasted for weeks [and] COVID-19 supply chain disruptions are now entering calendar year three.”

Global Vs. Local

The difficulties companies face in getting patient samples safely to their destination is a function of their assay strategy, says McDonald. If it is regional, assays are “performed proximally (geographically speaking) to where they are collected.” If their strategy is global, all assays are analyzed by a single lab regardless of where the samples were acquired.

The global approach, “always the most logistically challenging,” has also been most impacted by pandemic-related logistics and supply chain disruptions that continue to present, he adds.

McDonald’s “personal preference” is for regional assays whereby many of the logistical challenges can be avoided. Admittedly, it can entail a “big leap of faith” if results are to be part of a regulatory filing to demonstrate statistical significance.

The confidence level with assay results is generally lower when derived from labs around the world, he explains, even when they are using the same equipment and reagents. “Flow cytometrists especially will tell you that there is an art to running their assays… [such that] assays performed on the same sample in the same lab by different scientists will clearly have [slightly different] results.”

As McDonald is quick to point out, “What is scientifically sound can sometimes be at odds with what is logistically reasonable.” His tactic when working with the global assay model is to challenge couriers and integrators around the world to “be more thoughtful” about how they collect and transport samples.

Case For Redundancy

Regardless of strategy, it makes sense for companies to build redundancy into their logistics approach by including integrators with their own aircraft as a secondary option, thereby avoiding the need for 11th-hour scrambles for alternatives, says McDonald. To be eligible for deployment in studies, those integrators need to be validated along with the premium couriers and named as potential carriers on regulatory documents supporting clinical trial authorization.

On global studies looking to enroll treatment-naïve participants in remote regions of the world, integrators like DHL have proven they can successfully “take over” for grounded incumbents, he notes. They have been unaffected by border closures and flight cancellations by commercial airlines during the current pandemic, enabling companies with alternative logistics providers to “pivot more readily and easily.”

From a budgetary standpoint, the potential savings is eye-opening. For a premium courier to move a sample from a site to a lab in Europe, McDonald was recently quoted $1,100 with an estimated delivery time of more than two days. An integrator offered to do the exact same job for $50 and have the sample to the lab in less than 12 hours from the time of collection.

“Across the industry, there is an awareness that our clinical trials cost too much,” says McDonald. At the same time, he adds, “we are sometimes penny-wise and pound-foolish” when trying to trim the excess.

Future State

Cold chain has emerged as an area of discussion and optimization industry-wide in recent years, says McDonald, pointing to its recent inclusion as a topic at SCOPE. Most recently, COVID-19 virology has helped thrust cold chain logistics into the spotlight.

Stakeholders have also been convening at the LogiPharma conference for supply chain and logistics innovators, he adds, to talk through the obstacles and potential solutions. At the event last year, McDonald says, conversation emerged about a “future state” that might involve cross-company consolidation of samples in the same shipment when clinical trials are being conducted in the same region. Discussions in that direction are already underway with DHL.

Industry collaboration around due diligence and availability of dry ice—a big concern when COVID-19 vaccines were introduced—is what drove McDonald to identify and evaluate a novel container for the transportation of samples that maintains a minus-80-degree environment using only about a quarter of the dry ice of other solutions, he says. He was “tremendously skeptical” until he tested the container in the basement of his home office over the Christmas 2020 holiday.

The container maintained the promised sub-zero temperature using less than six pounds of dry ice when more typically 20-plus pounds would have been used, he says. “Not only did it preserve the environment; it did so for a period of time that was tenfold greater than its competitor and has a reasonable price point.” That product is now being evaluated by numerous companies as a potential standard solution for cold chain moving forward.

Industry buzz in this space is around the capabilities of integrators relative to premium couriers and what sort of temperature monitoring is necessary for biospecimens, McDonald says, in addition to ways of ensuring a better “state of readiness” post-pandemic. All are expected to be topics of an engaging conversation at his SCOPE session, to be presented virtually on Feb. 10.

Editor’s Note: The opinions expressed in this article are those of Thomas McDonald and not BMS.