|Fig. 1: The complexity of clinical logistics starts well before the trial materials are shipped. Credit: Brizzey|
In many ways, the business of providing logistics for clinical trial materials (CTMs) is perfectly awful. Relative to conventional supply-chain and logistics activities, the clinical world suffers from:
- Limited or no “market” signals; i.e., knowing when products are to be shipped out to meet demand (in this case, the availability of recruited patients for a trial).
- Widespread geographies, along with extraordinary import/export constraints (trials are being conducted all over the world—on purpose—and many countries have non-standard ways of allowing trial supplies to enter).
- Non-standard products—many trials require both the trial drug and comparator or placebo drugs, which are intentionally “randomized” during the course of the trial. Different trial protocol: different labeling. Different geography: different labeling.
- High-risk performance standards; high-value products—trial supplies can be expensive, with newly created biomolecules that require careful handling and storage.
- Low-performance expectations by end users (“end users” being the physicians and researchers who run trials at investigator sites; they are not trained supply-chain managers).
This internationalization is well documented; the IQPC organization, which runs conferences on both commercial and clinical supply chain issues, has developed a “heat map” showing the distribution of 2013 trials (Fig. 1). Pizzie likes to present a chart (Fig. 2) that differentiates between commercial supply operations and those that occur in the clinical space. He goes on to say that the beneficial element of how the clinical logistics field has evolved is better use of technology—IT systems for tracking and managing trial complexity—but that their use is still uneven across the range of service providers.
It’s difficult to put a figure around the totality of the CTM logistics business. Pharmaceutical Commerce’s annual “Biopharma Cold Chain Sourcebook” estimated the total spending at $2.99 billion in 2014, rising at about a percentage point annually over the next five years to $3.16 billion in 2018. However, uncertainties in how to analyze CTM activity (which can include both outbound delivery of CTMs and return delivery of tissue samples and other CTMs), combined with the expected expansion of biosimilar drug development in the remainder of this decade make that figure less certain. Other industry estimates put CTM logistics as 5% or more of overall drug trial R&D spending; at an estimated $130 billion worldwide in current spending, that would point to a higher figure of $5-7 billion.
Market leaders in pure-play CTM logistics are World Courier, now a subsidiary of AmerisourceBergen, and Marken, with other express-courier companies like Quick (New York, NY) also involved. The big life sciences logistics providers, including DHL and FedEx, are active in the CTM space as well.
At World Courier, there is an expectation that IT will play a more central role in the company’s operations, in part through its acquisition by AmerisourceBergen (ABC). ABC has had a years-long corporate-wide implementation of the SAP enterprise planning system under way; with the integration of the two companies, that will also be a platform for World Courier. “We have a variety of IT systems already in place, but with the SAP implementation, we will be developing a network-wide level of operational excellence that is appealing to multinational pharma clients,” says John Butler, president of the World Courier unit.
Good use of the latest IT and communications technology can—and has—shaped the very structure of clinical trials. A case in point is from FedEx, which has been commercializing its SenseAware program (a combination of a datalogger and an online information service) for the past several years. According to Chris Swearingen, a business development manager there, SenseAware was successfully used recently to perform a pediatric trial of an inhaled asthma drug with a very complex protocol: the drug had to be used three times a day, for two weeks, with fresh product being delivered daily under temperature-controlled (2-8°C) conditions. The ability to track compliance of the drug (administered at patient homes) was critical. FedEx worked with a CTM company, Clinical Supply Management (Fargo, ND) to manage the logistics; with the SenseAware device, delivery could be confirmed and temperature conditions documented over the course of the successfully concluded trial.
Direct to patient
“Patient centricity” is a theme that Ariette Van Strien, SVP of Commercial Operations at Marken, emphasizes in describing Marken’s evolving services. “There is a definite movement toward ‘direct to patient’ trials, which have been shown to be beneficial in maintaining the involvement of patients in trials until they are concluded,” she says. “Logistically, this requires delivery of CTMs to the patient’s home, and in many cases, coordination with others such as nurses who would provide injection or infusion services.” Marken has set up a DTP service specifically for this function.
Van Strien also notes that there is an increasingly blurred crossover between formal clinical trials and prescribed-drug delivery to patients, in the area of orphan drugs and rare diseases. A number of orphan-drug programs have long-term trials that are stretched out by the difficulty in locating patients with these conditions (“rare” diseases are defined in the US as having fewer than 200,000 patients; there is also an evolving “ultra-orphan” market where patients can be as few as a couple thousand).
For CTMs generally, there is something of a land grab going on right now in building out capacity to handle the volume of products being shipped. Marken has expanded its global network of depots (where CTMs can be stored and, in some cases, where kit production can be carried out on an as-needed basis), especially in Latin America. World Courier touts its depot network of 13 worldwide, and the company has recently expanded its Australian depot to serve clients shipping into that region. Sam Herbert, VP of strategy at the firm, also notes that the company has doubled the size of its fleet of certified, temperature-controlled delivery vehicles in Europe, the better to serve the growing need for regional deliveries at greater cost efficiencies than air transport, all while meeting the stricter documentation requirements there. FedEx is in the process of building a major life sciences distribution center in Memphis.
The capacity race is also being energized by a number of clinical research organziations and clinical manufacturing organizations. Packaging Coordinators, Inc. (Philadelphia, PA) has built out new distribution centers in Rockford, IL and Wales specifically for CTMs. Parexel and Quintiles, both major CROs, have added capacity and services.
“It’s hard to dispute the fact that running clinical trials is harder today,” says Dr. Margaret Hurley, president of Hurley Consulting Associates (Summit, NJ), an advisory firm on drug trials. “The drugs address more complex conditions with more expensive, harder-to-handle biological products. Adaptive trial designs add complexity, as does the desire to have head-to-head comparative trials of new and existing products, which makes obtaining comparator drugs more essential.” Aligning the needs of drug developers with the expanding capabilities of CTM service providers will keep both sides of the market very busy in the next few years.