Today, as the global COVID-19 pandemic grinds on, the supply chains of nearly every industry in the world are stressed. Retail stores have empty shelves; automakers can’t get a sufficient supply of microchips; cargo ports are backlogged; the list goes on. The pharma supply chain is not immune to these stresses: even after the heroic efforts to get newly developed vaccines distributed to much of the world (and we hope this heroism will someday be recognized), sudden surges in infections create new demands for test kits, while hospitals deal with shortages of needed instruments, drug treatments, staffing and ICU capacity.
All these supply chain challenges are creating new emphasis on improved supply chain performance. With a bias toward the needs of pharma supply chains, and especially pharma cold chains, here is a list of top five factors for improved performance.
The ability to look “down” the supply chain to see where holdups are occurring, or where supply and demand are out of balance, has been a long-sought goal of supply chain managers. Today’s digitized reporting systems are vastly superior to what was available in the past, but there continue to be shortcomings, especially where demand sensing and forecasting are concerned. A recent survey from Supply Chain Insights LLC, a consulting firm, found that 74% of the respondents from companies that were engaged in a digital transformation of their supply chains were looking for “driving better supply chain visibility” as a focus of their efforts. Cloud-based IT systems, combined with the dataloggers and sensors that can report status in near real time, are addressing these shortcomings, but there is a lot of work yet to do.
The new frontier in these efforts is to apply artificial intelligence and machine learning (AI/ML) to the data that broad-based visibility systems generate.
Nick Basta, Founder of Pharmaceutical Commerce
The expectation is that this business intelligence will be able to predict supply chain disruptions (the better to prepare for them) and to minimize inefficiencies such as overstocking, supply shortfalls or avoidable delivery delays. For the pharma cold chain specifically, the ability to combine transportation processes with other factors like weather, warehousing capacity or the real-time conditions in transportation modes (air, ground, ocean). Ultimately, better supply chain visibility will be a factor in overall financial performance of a pharma company—that is the concern of the C-suite. More immediately, better visibility will enable supply chain managers to sleep at night.
2. Condition Monitoring
Hand in hand with knowing where pharma products are, and where they are going, is the need to know their condition. For the pharma cold chain, obviously, the most important factor is temperature, but trends in the development of newer pharmaceutical products are calling for additional conditions: shock or vibration (which can damage sensitive biomolecules) and humidity are two of the growing concerns.
Historically, temperature monitoring meant, simply, ensuring that a predetermined temperature range (usually 2-8 °C) was not exceeded at both the upper and lower ends of the range. Chemical indicators that turned color depending on the temperature they sensed were the norm (and in fact, some drug-transportation situations don’t need more than this simple “good/bad” indication). With microelectronics, the ability to track a temperature profile over the course of a transit could be achieved; quality personnel could extract the temperature profile retroactively and determine when and if temperature limits were exceeded. More recently, temperature sensing can occur—and be reported—in near real-time. This combined with the visibility drive of (1) enable corrective actions or on-the-spot reassessments to occur for a shipment. The classic example of this is the need to recharge a carton or containers chilled with wet or dry ice en route to its destination. (Normally, a sealed pharma carton would not be opened in transit, so this is a measure that has to be taken in a closely coordinated fashion.) In these days of supply chain turmoil, these actions could include rerouting a shipment via alternative transportation, or to a different destination. The important factor is that the shipment can remain in control of the shipper while en route.
3. Stability Budgets
It has been a recognized practice, in the pharma industry and among pharma regulators, that occasional temperature excursions can be allowed for a shipment, as long as they are not too long or too severe. How long, and how severe? To provide a scientifically grounded answer to that question, the manufacturer conducts thermal stability tests of the drug in question, running tests for days or weeks to measure the point where a temperature excursion has become a disqualifying factor. Those time and temperature variations (with a generous margin of error) become the “stability budget” of the drug.
Let’s say a nominal 2-8 °C drug has a stability budget of 48 hours at temperatures no higher than, say, 15 °C. The drug shipment goes from the manufacturer to 1) a truck to the airport; 2) the airport ground crew and aircraft loading process; 3) in flight; 4) receiving ground crew/unloading; 5) customer warehouse. If each step in this process assumed that there were 48 hours of temperature excursion, obviously the shipment would be quickly spoiled in transit. Thus, a coordinated approach, where each leg of the journey (or, equivalently, each transportation partner) had a set amount of time for a temperature excursion, AND that an onboard data logger is able to record each excursion’s location and duration. If all the procedures are followed faithfully, the shipment could still arrive safely.
A few years ago, manufacturers and shippers were aware of the stability budget, but lacked the means to parcel it out among shipping vendors. Now, technology and closer QA management allows better control of this aspect of the cold chain.
4. Personalized Medicine
There has been a trend toward developing drugs to treat smaller patient populations. Originally something that went against the grain of the traditional pharma industry, it now enables a host of new treatments. The trend was accelerated by the passage, in the US, of the Orphan Drug Act (ORD; originally in 1983; amended in 2007), which gave manufacturers financial incentives to recoup the costs of developing treatments that might benefit only a few hundred or few thousand (by law, a “rare” disease is one that affects fewer than 200,000) patients.
As of 2020, according to the National Organization for Rare Disorders, there are 599 ORD-defined orphan drugs, of which 552 are commercial); NORD counts over 7,000 rare disorders, so the gap between diseases and approved treatments is still very wide.
A parallel trend with the growth of orphan drugs has been the development of treatments for individual patients based on their genetics. This field was blown open in the early 2000s as the Human Genome Project, which read out the human genome, was completed; in more recent years, new technologies such as CAR-T (Chimeric Antigen Receptor T-cell) or CRISPER (Clusters of Regularly Interspaced Short Palindromic Repeats) are opening up new possibilities, especially for genetic disorders in infants. (Point of fact: the mRNA vaccines against COVID-19 are a form of genetic therapy). So-called “cellular and genetic therapies” (CGTs) are the hot growth area of the global pharma industry. While there are only a few dozen approved CGTs in the world, there are over 1,300 clinical trials going on involving CGT therapies, according to the Alliance for Regenerative Medicine, a trade group. Tens of billions of dollars have been invested in the field.
The common theme for orphan drugs and CGTs, from a transportation perspective, is that they usually require extremely tight temperature control, in packages or shipments that might be intended for a single patient. Some of the early CGT efforts, in fact, were limited by the geographic range of the medical center offering the treatment (a combination of the limited time for the drug to be used, and the limited ability of patients to get to the treatment center). Added to the complexity, a CGT treatment involves a complicated supply chain both from the patient (whose blood or tissue needs to be biopsied) and then returned to the patient for infusion or implantation, a process that has been called “vein to vein” treatment.
2021 was not only a year of pandemic urgency, but also one where the issues around climate change have reached crisis levels. From devastating fires in the American West, Siberia and other parts of the world, to floods, hurricanes, cyclones and tornadoes in the Midwest, Europe and Asia, the consensus around the need for addressing climate has grown (it will never, unfortunately, be a unanimous concern).
The boards and stockholders of global corporations are being challenged to revise their business practices to be less harmful to the environment.
Nick Basta, Founder of Pharmaceutical Commerce
These actions range from reducing greenhouse gases, to employing renewable materials in their products and services, to minimizing waste production.
These are broad, globally oriented goals. In practice, corporations are diving deep into their internal processes, looking for areas of improvement, and, for pharma companies and their vendors, that includes the pharma cold chain.
Thus, the market has improved for packaging and materials that are either recyclable or reusable in cold chain packaging and distribution. These include the insulation materials of the containers (“curbside recyclable” paper products are now being selected), to reusing dataloggers for temperature monitoring, to refurbishing the entire container package for reuse. All of these practices require close rethinking of conventional practices in the cold chain. For example, the economics (and climate-change benefit) of returning an empty container that was used in a cold chain shipment need to be analyzed: there is a cost to the “reverse logistics” return of the package, in addition to the cost of refurbishment. Quality control has to be maintained to ensure that the reused package is as reliable as the first-time use.
Founder of Pharmaceutical Commerce
He is a life science and business journalist and consultant, founder and former editor in chief of the print and online magazine Pharmaceutical Commerce.