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Decision Intelligence was not a term I was overly familiar with before attending this year’s Gartner Supply Chain Symposium (London, Sept. 27–29) and I admit that on hearing it I thought it was somewhat tautological. Don’t intelligence and decision-making go hand in hand? Surely you can’t make decisions without intelligence… (That was rather naïve of me; anyone who follows politics might say, “Clearly, some decisions are made without intelligence.”) But anyway, I was missing the point. Decision Intelligence is a term used by California-headquartered company Aera concerning the application of artificial intelligence (AI) and applied analytics (AA) to the decision-making process.

Aera leverages technologies, including AI and machine learning (ML), and domain expertise to “improve and automate decision-making across supply chains for pharma companies.” The idea is that the technology relieves decision-makers of the burden of making the less crucial decisions; companies get automated messages about shortages and spikes in demand, as well as recommendations on how to fix the issue. ITPro Today noted that Aera’s cloud-based search and data modeling platform “can ingest data from any enterprise system, aggregate the data and perform predictive analytics along a company's supply chain, correlating demand, inventory .and revenue streams.”

 The company counts among its clients Big Pharma firms such as Merck KGaA, Darmstadt, Germany, whose head of group smart manufacturing, Michelangelo Canzeroni, told the conference how using this technology has helped the company streamline its 49 data sources in an attempt to “get to a single source of truth.”

Canzeroni explained, “I don’t want to spend so much time analyzing my data that I am too late to make a decision.” He added that the impact of the new technology has been a 10% reduction in inventory and a 3% reduction in waste.

Decision Intelligence is just one of the analytical decision-making technologies that are set to transform the pharmaceutical supply chain. Gartner has observed that the next three to five years “will see an increase in the adoption of digital supply chain technologies, as well as technologies that improve human decision-making.”

By 2026, across all industries, more than 75% of commercial supply chain management application vendors will deliver embedded AA, AI, and data science. As well in decision-making, AI, ML, and robotics are set to make strides in supply chain areas such as inventory management and warehouse automation. Gartner also predicts that by 2026, 75% of large enterprises will have adopted some form of intralogistics smart robots in their warehouse operation and 25% of supply chain execution (SCE) vendors will have rewritten their core application to a microservices architecture. There is also a warning, however: “Through 2026, 80% of companies will suffer significant value loss due to a failure to merge their digital supply chain twin and control tower initiatives.” 

Those companies who believe that the AI-driven supply chain is still some way into the future might need to sit up and start making some intelligent decisions today.

1. “Aera Brings AI Decision-Making to Merck Supply Chain,” Oct. 14, 2019, 

2. “Gartner Predicts the Future of Supply Chain Technology,” April 20, 2022, 

Julian Update is Pharmaceutical Commerce's former Editorial Director.

Decision-making technologies come to the forefront of the AI space

Decisive Moves on the Digital Supply Chain

By definition, in the US, a rare disease is defined as one that occurs in 200,000 or fewer people. In the EU, the classification is any condition that has a prevalence of one in 2,000 or less. While the incidence rate for any given rare disease is small, the numbers add up quickly in terms of overall prevalence. Today, more than 400 million people worldwide, and 30 million people in the US are affected by one of the nearly 10,900 rare diseases that have been identified to date, according to advocacy group RareX.

 Unfortunately, less than 10% of all such diseases have an FDA-approved treatment, according to the National Organization for Rare Disorders (NORD).

In the US, the Orphan Drug Act (ODA) of 1983 is widely heralded for spurring ongoing innovation in rare diseases that may have otherwise not garnered attention by offering lucrative incentives to drive innovation and reduce risk for drug developers. These include:

Tax credits for qualified clinical testing

Qualification for expedited development programs

Waiver of the Prescription Drug User Fee (which can be several million dollars for a new drug)

The opportunity for the drug to receive seven years of market exclusivity

Exclusion from the Pediatric Research Equity Act

Prior to 1983, only 38 orphan drugs had received regulatory approval. In the nearly four decades that have followed since the ODA went into effect, nearly 1,090 orphan drugs have been approved in the US.

Interestingly, thanks to sustained effort among small- and large-sized biopharmaceutical companies, in 2020, more than half of all new molecular entity (NME) and biological approvals by FDA were for treatments aimed at rare diseases, notes Tim Coté, CEO of Only Orphans Coté LLC, a consultancy focusing on drug development for rare diseases. Worldwide, orphan drug sales were forecast to grow at a compound annual growth rate of 12.3% from 2019 to 2024—nearly double the rate projected for the non-orphan drug market.

Many consider the path carved by the ODA to be an unqualified success. “You can’t argue with success,” says Coté. “Today, almost all countries have legislation to spur innovation in rare diseases that is modeled after the ODA.”

“The majority of rare diseases are now recognized to have genetic drivers, and tremendous scientific advances are being made in understanding genomic drivers and molecular pathways and mechanisms through which diseases occur and progress,” adds Animesh Arun, principal, rare diseases insights, for Axtria, a cloud software and data analytics company. “Such breakthroughs are making it possible to identify very specific therapeutic targets during drug development, and open the door for more specific diagnostic testing options and protocols to help patients with these genetic mutations or biomarkers to be identified more quickly.”

Under the ODA, one of the most important incentives for drug developers has been the seven-year period of market exclusivity that is provided for first-in-class orphan products upon approval. However, in recent years, the definition of which products will actually be protected under this exclusivity clause has grown murky.

“Drug law hinges on the question of ‘what’s the same and what’s different?’” says Coté. “Under the ODA, this concept has very different implications compared to how ‘same’ and ‘different’ are considered in the review division.” From 2007 to 2011, Coté was the director of the Office of Orphan Product Development for FDA, and personally signed off on 1,400 orphan-drug designation applications in that role.

Coté explains: “While esters and salts of the same therapy may be deemed the same product, things become less clear when it comes to monoclonal antibodies, gene therapies, enzyme therapies, and the microbiome—all of which are being explored to address rare diseases; so case law is evolving very rapidly to keep up with competing claims related to market exclusivity provisions.”

For instance, today, you can get an orphan drug approved based on its moiety, “but if another drug developer comes along with a different formulation of the same moiety and it is proven to be clinically superior (in terms of being safer, more effective, or providing a major contribution to patient quality of life), it may also gain FDA approval—thereby essentially breaking the initial exclusivity provision of the ODA and instead allowing both therapies to enter the market for the same indication, viewed as being sufficiently ‘different’ despite having the same moiety,” says Coté.

Importantly, he adds that “this is not an unanticipated loophole—rather, it was an intentional aspect of the original ODA regulations, driven by the idea that if a therapy that was indeed better came along, it too could be approved to address unmet clinical need—even if it has the same moiety as the first-in-class approved therapy.”

Historically, breakthrough orphan drugs have been pursued by smaller companies and startups. However, what smaller, pre-revenue life sciences R&D companies may have in the way of a winning candidate therapy and a nimble mindset they often lack in a deeper bench of expertise, experience, and funding. Thus, it should come as no surprise that in recent years, Big Pharma has turned its attention toward the orphan drug/rare disease space as well.

“Big Pharma was tentative at first because these companies understood that pursuing orphan drugs would involve a completely different business model,” says John Doyle, group vice president of health sciences at Exponent, and adjunct assistant professor in the Department of Epidemiology, Mailman School of Public Health, at Columbia University. “However, much of the low-hanging fruit in mass markets has already been harvested, yet orphan and rare opportunities still enable value-based pricing power.”

Similarly, “market saturation across most larger disease states creates considerable competition for patients, and this creates a particular challenge for drug companies—beyond even the initial challenge of getting a new medication approved for use in a crowded therapeutic space,” adds Maria Kirsch, general manager of patient services for EVERSANA.

Larger pharma companies have more stable footing to operate in the clinical trial, or pre-revenue phase longer, and absorb potential downturns—and in some cases, are able to give life to promising yet abandoned programs or molecules shelved by smaller companies, according to Ela Lourido, vice president of biopharma services for Biologics by McKesson, an independent specialty pharmacy. “And when larger companies collaborate with smaller innovator companies through license agreements and other funding or partnering arrangements or acquisitions, it can provide momentum for all stakeholders,” she says.

“Similarly, a large pharmaceutical company that has previously navigated the clinical development process multiple times will have a clear advantage compared to one doing it for the first time,” adds Scott Swain, director of regulatory sciences and real-world evidence (RWE) for Cardinal Health. “Smaller biotech companies often rely on multiple rounds of fundraising, which can delay research and development, an issue which is much less problematic for Big Pharma.”

Nevertheless, encompassing both segments, Amanda Powers-Han, chief marketing officer for Greater Than One (GTO), a marketing agency with specialized expertise in rare diseases, notes that about half of GTO’s book of business is dedicated to orphan drugs for rare indications.

“The optimist in me believes that Big Pharma and the overall industry is investing more heavily in orphan drugs for the promise they provide for better health outcomes, but they also don’t really have a choice,” she says. “Gone are the days of the big blockbuster drugs targeted at millions of patients that can provide one cash cow to help fuel the company’s fortunes.”

Growing interest in orphan indications is also a natural consequence of the industry's improved understanding of the pathophysiology of disease, notes Swain.

“As the precision medicine wave has helped to redefine specific forms of any given disease as rare, and identify potential treatments as orphan drugs, Big Pharma had no choice but to grab a board and surf the waves,” he says.

The role of RWE derived from analysis of and formal studies involving real-world data (RWD)—such as electronic health record (EHR) and claims databases, published literature, laboratory testing and prescription data, patient-reported outcomes, registries, digital health, and wearable device data and more—to support the orphan drug space continues to become more multifaceted. RWE-based efforts are now being used to support drug discovery, patient diagnosis, clinical trial enrollment, and postmarketing studies to confirm longer-term clinical outcomes when an orphan drug is approved on a limited data set.

For many orphan treatments, FDA approval has often been granted on trials that involve just a small number of patients and are operated for shorter-than-usual durations, notes Ray Huml, vice president of scientific and medical strategy for Syneos Health, and head of the company’s Rare Disease Consortium. By way of example, Exondys 51 (eteplirsen) from Sarepta Therapeutics, the first therapy to receive FDA approval for the treatment of a particular form of Duchenne muscular dystrophy (DMD) that impacts just 13% of all DMD patients, only had 12 patients enrolled in the registration trial.

 “In such cases, an orphan drug could receive initial regulatory approval, but the company will then be required to carry out longer-term confirmatory studies and develop real-world evidence to confirm the clinical benefit, safety, and durability of the therapy over longer time frames,” adds Huml.

Small trial populations and expedited approval processes often translate to a dearth of clinical insights at market launch, and this can impact physician prescribing behaviors, patient acceptance, and payer coverage, Nancy Young, vice president of commercialization services on AmerisourceBergen’s global consulting team, points out. “RWE studies have become a necessity to ensure continued commercial success among orphan drugs, and to inform both clinical decision-making and coverage negotiations,” she says.

In turn, armed with this information, payers are more routinely implementing innovative strategies to address access and reimbursement issues associated with these promising yet high-cost medicines—to ensure they receive optimal value from their pharmacy spend.

"Post-marketing studies undoubtedly enable data-informed payer support, which then improves patient access to these lifesaving therapies,” contends Lourido.

Diagnosis and trial recruitment challenges

For patients with a rare disease, it can take anywhere from five to 10 years, and interactions with dozens of doctors and specialists, to get a proper diagnosis.

 “It’s important to get the diagnosis correct, and to identify relevant genetic mutations, as this can help connect the patient to a trial or approved therapy that is specified for that particular form of the disease,” says Huml. The executive speaks from experience, as he and his wife are parents to a son and a daughter each living with the rare condition facioscapulohumeral muscular dystrophy, a a disorder characterized by muscle weakness and wasting (atrophy). Huml is the editor and author of 

Rare Disease Drug Development: Clinical, Scientific, Patient and Caregiver Perspectives

“The sense of urgency in rare disease therapies cannot be overlooked,” adds Kirsch. “When it takes years for a patient to be diagnosed, that’s additional years of pain, struggles, and uncertainty.” Such delays not only slow down access to an approved therapy or the ability to participate in a relevant clinical trial, but for some types of rare diseases, the lost time can lead to irreversible disease progression or loss of motor skills, organ function, or cognitive capabilities.

Fortunately, as GTO’s Powers-Han points out, rapidly expanded capabilities in advanced data mining and data analytics using artificial intelligence (AI), machine learning (ML), and simulation are helping to power the process of finding needles in a haystack. These tools can connect seemingly unrelated data to identify a matrix of symptoms to help to connect the right patients with the right clinical trial opportunities more quickly.

EVERSANA’s head of data and analytics, Simon Andrews, adds: “Today, using a predictive model deployed in the technology stack, a hospital can analyze significant quantities of de-identified patient-level data, helping physicians to improve the odds of a timely, accurate diagnosis at the point of care for a particular patient, or suggesting a potential diagnosis that would then prompt the doctor to order appropriate blood or genetic testing.”

Arun of Axtria cites an example of using patient-progression modeling to identify anonymous patients that are likely to have a particular rare disease or progress in their disease. This enables timely flagging by their physicians, and can provide a critical opportunity for timely intervention and initiation of therapy, he says.

“Physicians will often wrongly assume the most likely diagnosis but rarely consider a diagnosis of a rare disease, while today’s AI/ML and advanced data-analytics techniques will do the opposite,” adds Harlen Hays, director of research analytics for Cardinal Health.

Another factor that hinders timely disease diagnosis and, in turn, clinical trial enrollment, is that today’s medical coding systems, experts agree, do not provide sufficient nuance for many rare disease categories. “Of the 10,600 rare diseases known today, only about 500 of them have formal ICD-10 codes,” notes Huml on the international classification of diseases coding system used by the US healthcare system. “If you’re mining databases in search of trial candidates or are trying to assess the potential market size for a drug, you will find some mechanistically related patients lumped together under the same code. But the apparent findings will be overinflated because you won’t be able to easily identify just the specific subset of patients you want based on a particular undifferentiated ICD-10 code.”

 to allow researchers to improve the identification of patients using claims databases without strict reliance on ICD-10 codes. “This is accomplished by leveraging the prevalence of clinical presentations clusters known to be associated with the correct phenotypes,” explains Andrews of EVERSANA.

Drug distribution: Streamlined yet complex

Due to their small overall volumes, nearly all rare disease medicines are subject to an exclusive or otherwise highly limited network arrangement defined by the manufacturer prior to regulatory approval, explains McKesson’s Lourido.

“Because orphan drugs typically must be stored in temperature-controlled settings, distribution requires a white-glove mindset to ensure these expensive and low-availability products make it safely to the end patient,” adds Danny Williams, president of channel management for EVERSANA

Temperature studies, he says, should be carried out prior to transportation, and rigorous protocols should be followed to maintain these products within the required temperature range throughout storage and transportation, using specialized cold chain packaging materials and protocols.

For example, because healthcare providers typically don't stock rare and orphan products for a period of time, distributors often focus on “just-in-time” shipping from a few strategic locations. “To minimize delays, the distribution partner must have a connected network of facilities in the right parts of the country or world with redundant systems to ensure continuity and swift responses in the event of a shutdown or emergency,” says Adam Blatney, vice president of specialty sourcing and distribution for AmerisourceBergen.

Similarly, the distribution partner should have established customer relationships across all classes of trade, particularly as additional drug indications are received, and have broad health system penetration. “These existing relationships increase the likelihood of timely shipping, existing credit lines accounting for the provider’s full portfolio of products, and familiarity with ordering processes, helping to ensure a more seamless customer experience at launch,” adds Blatney.

Premium pricing: Getting what you pay for

Orphan drugs are typically among the most expensive therapies on the market, with prices that can easily go from hundreds of thousands to millions of dollars per patient. Today, value-based contracts (also known as outcomes-based agreements), which aim to reduce risk by linking payer coverage directly to actual clinical outcomes, continue to grow in popularity, and many stakeholders agree that they make particularly good sense in the orphan drug sphere.

While such agreements among biopharma companies, payers, and others offer a promising option to share risk more equitably, creating them produces yet another challenging hurdle for drug developers, argues Doyle.

“All parties must decide what are the most essential metrics, endpoints, or surrogate endpoints to demonstrate clinical success, and then carry out modeling and simulation (i.e., epidemiological, actuarial, economic), collecting and analyzing many forms of RWD to design the novel contract terms and manage them over time.”

One recent example is the gene therapy Zynteglo, also known as beti-cel, from Bluebird Bio, a one-time treatment for the rare blood disorder transfusion-dependent beta-thalassemia (TDT). The condition afflicts about 1,500 patients in the US, and the lifetime cost of caring for a patient with TDT can eclipse $6 million, according to the company.

Prior to the drug’s US approval in August, the Institute for Clinical and Economic Review (ICER) “unanimously determined that evidence is adequate to demonstrate that beti-cel provides a net health benefit compared to standard clinical management based on an anticipated (pre-approval) price of $2.1 million—as long as the price is subject to 80% payback for patients who do not achieve and maintain transfusion independence over a five-year period.”

When the therapy entered the market this summer, Bluebird Bio set the average wholesale acquisition cost (WAC) of $2.8 million per patient—a price the company says reflects the potentially curative nature of the drug and its ability to reduce the need for a lifetime of blood transfusions in 89% of Zynteglo patients.

 To help model risk-sharing arrangements among drug developers and payers, Doyle notes that Bluebird Bio shared publicly an outcomes-based contracting strategy featuring a one-time, up-front payment with a potential rebate up to 80% of that one-time therapy cost if patients don’t achieve transfusion independence. Specifically, the company is offering payers an outcomes-based deal that would refund up to 80% of Zynteglo’s cost if a patient fails to achieve and maintain blood transfusion independence up to two years after infusion.

Alnylam Pharmaceuticals has also devised an outcomes-based contract with certain payers for Onpattro (patisiran), its orphan drug for the treatment of polyneuropathy caused by the rare condition HATTR amyloidosis, to soften the blow of the drug’s $445,000/year WAC. The value-based agreement for Onpattro with pharmacy benefits manager Prime Therapeutics allows for a refund in the event that one of two endpoints is triggered—drug continuation by the physician or progression to liver transplant.

“If you are able to generate the evidence to support the value of your product, you’ll be paid an adequate return on your investment, but I can’t underscore enough how important it is to demonstrate value in many ways, especially in this era when drug developers are often being attacked for drug pricing,” says Doyle.

By design, the commercialization strategy for orphan drugs must be inherently patient-centric and high touch. More so than in other disease states or drug categories, “the drug developer must function as an ‘ecosystem integrator’—creating the backbone for the many types of support programs, providing the technology and the data science that is needed for it to all work seamlessly,” says Doyle. He notes that this may include not only clinical and financial support, but programs related to nutrition, transportation, social service, and other environmental elements that will improve the long-term outcomes for such patients; this is a new strategy for many pharma companies, according to Doyle.

"It’s expensive to find the right people and build infrastructure needed to support any launch, especially a rare one,” adds Kirsch. “In most instances, it doesn’t make sense to build a pharmacy or distribution center, so it’s critical to invest in a third-party partner that can do that for you, and one that knows the industry.”

To increase the odds of success during the clinical trial process, stakeholders agree that orphan drug developers, no matter the size, should foster a strong working relationship with FDA as early as possible—well in advance of the regulatory drug filing.

“So many pharma companies are terrified of the agency, and this creates a serious obstacle in terms of both missed opportunities to streamline the process earlier, and analysis paralysis that could be overcome with a few good conversations early on,” says Coté, as noted, himself a former FDA official in the orphan drug space. “There’s no such thing as a bad meeting. The agency is honestly and earnestly looking for ways to help drug developers bring their lifesaving therapies to market as quickly as possible.”

https://rare-x.org/case-studies/the-power-of-being-counted/

https://www.evaluate.com/thought-leadership/pharma/evaluatepharma-orphan-drug-report-2019

3. “Controversy Surrounds Exondys 51 Approval: What to Know,” 

https://www.managedhealthcareexecutive.com/view/controversy-surrounds-exondys-51-approval-what-know

4. Huml, R.A. et al., “Use of Big Data to Aid Patient Recruitment for Clinical Trials Involving Biosimilars and Rare Diseases,” 

5. Ainslie Tisdale et al., “The IDeaS initiative: pilot study to assess the impact of rare diseases on patients and healthcare systems,” 

https://doi.org/10.1186/s13023-021-02061-3

6. ICER Publishes Final Evidence Report and Policy Recommendations on Beti-Cel Gene Therapy for Beta Thalassemia, ICER Press Release, July 2022. 

https://icer.org/news-insights/press-releases/icer-publishes-final-evidence-report-and-policy-recommendations-on-beti-cel-gene-therapy-for-beta-thalassemia/

7. Iskowitz, Marc, “Bluebird’s $2.8M gene therapy opens the door to pricing questions,” 

https://www.mmm-online.com/home/channel/bluebirds-2-8m-gene-therapy-opens-door-to-pricing-questions/

8. Peebles, Angelica, “The Most Expensive Drug in the US is a Rare-Disease Game Changer,” Bloomberg newsletter, August 2022. 

https://www.bloomberg.com/news/newsletters/2022-08-24/the-most-expensive-drug-in-the-us-is-a-rare-disease-game-changer

9. “Bluebird Bio Ends Commercial Operations in Europe,” 

https://ashpublications.org/ashclinicalnews/news/5779/Bluebird-Bio-Ends-Commercial-Operations-in-Europe

While all drug development efforts are fraught with peril, a growing number of biopharma companies—large and small—are staking a claim in the rare disease treatment space, chasing odds that could yield clinical and financial rewards 

Betting the House on Orphan Drugs

Service providers and equipment vendors supporting the global pharmaceutical cold chain market in the past couple years have done double duty: not only did they have to drastically step up their supply of containers, refrigerants, and transportation services, but they also developed a raft of new configurations and service capabilities.

Those new capabilities are now providing benefits to the “rest of” the pharma cold chain—the biologic and temperature-sensitive formulations that the pharma industry is increasingly bringing to market. Cases in point:

 Envirotainer brought out the Releye container, designed to convey up to four US or five European-style pallets with a lower weight and smaller carbon footprint. The just-introduced va-Q-one 300P, from Va-Q-Tec, is designed for single-use shipments to countries where the return of a lease air-freight container is difficult; the container’s use of vacuum insulated panels (VIPs) is said to significantly reduce its weight. Sonoco ThermoSafe introduced the company's Pegasus pallet-size, passive unit load device (ULDs generally meet FAA requirements as aircraft equipment) in 2020; now, it has been approved for use at a half-dozen international air carriers. SkyCell, which offers a “hybrid” container combining passive cooling with powered airflow, introduced the 1500X container, pallet-sized and rated for up to 270 hours of uninterrupted service. Tower Cold Chain, a British passive-container provider, has announced a doubling of the capacity of its global network of leased containers, used in air and ground transportation modes.

 Traditional expanded polystyrene (EPS) is on the run, being replaced by all-paper containers (designated as “curbside recyclable”) from Sonoco ThermoSafe (its EOS brand) and Truetemp Natural from Packaging Technology Group (now a business unit of Cold Chain Technologies). Meanwhile, Lifoam has introduced Bioffex, an insulation material made from plant sources of polylactic acid, which the company says can be composted and essentially eliminated in a matter of weeks. All of these new forms of insulation have been rated by the standard ISTA testing for their insulating performance. The other tack to take is to invest in reusable containers, which usually involves close coordination with the packaging vendor.

 helped accelerate a transformation of how data are gathered and analyzed for cold chain shipments, with several private-equity funded companies bringing Silicon Valley-style IT innovation to supply chain management. Among these are ParkourSC, Roambee, and Controlant, and include in-house systems at global logistics providers. The companies tout the addition of artificial intelligence (AI)/machine learning (ML) techniques to the analytics, so that logistics providers can predict and address delivery problems before a container loses its temperature control.

 Also spurred on by the pandemic, but continuing a growth trend that has been building for a decade, major logistics providers are bringing new capacity online around the world. UPS Healthcare says it will be adding four million square feet of warehousing in the next several years; DHL announced a $400-million plan to add three million square feet in the US alone, and recently opened a 344,000 square-foot facility near Frankfurt. Kuehne + Nagel has built a 166,000 square-foot facility 

in Indianapolis, IN, and is expanding the temperature-conditioning facilities (which can prepare or recharge cold chain containers) in its QuickStat network of express courier locations worldwide. Late last year. FedEx opened a 138,000 square-foot facility at Miami International Airport, including a 70,000 square-foot cold chain facility, said to be the largest in the FedEx global network.

 The infrastructure for managing the booming field of cell and gene therapy (CGT) technologies, which often involve conveying living cells under cryogenic conditions, is being built out. Cryoport, a leader in this field, has opened new facilities in New Jersey and Texas, and recently acquired Cell Matters, a Belgian company that standardizes the cryopreservation of cells that have been harvested from patients; more recently it announced a partnership with BioLife Plasma Services, a unit of Takeda Pharmaceutical that manages cell-collection (apheresis) facilities. Jerrell Shelton, CEO, notes that the company has added to biomaterial storage capabilities in its network, as well as a logistics service provider, CryoPDP—all with a goal of facilitating both research and commercialization for CGT developers. CryoPDP has been bulked up by recent acquisition of Polar Expres, a Spanish logistics provider. BioLife Solutions, a provider of cryopreservation solutions, has acquired Sterling Ultracold, a maker of ultra-low temperature mechanical freezers, and Sexton Biotechnologies, a supplier of CGT media and materials. In the past year, Envirotainer has also jumped into the CGT space with CryoSure containers—dewars for storing and transporting biologic materials at temperatures down to -70°C.

Most sensor/datalogger vendors include some type of data collection with their devices. Elpro, a leading datalogger vendor, offers the Elpro Cloud service that not only collects in-transit condition data, but also includes data from the stationary refrigerators it monitors at labs. Packaging vendors, especially those handling pallet-scale shipments and air freight, do the same by incorporating dataloggers into their containers. And among 3PLs, it is common to provide a data collection service as part of their service-level agreements with their customers.

As alluded to, this data-gathering process is now being enhanced by third-party data aggregators, who can be hired by the pharma shipper to consolidate data from the sensors, the freight carriers, and others to present what is claimed to be a real-time, end-to-end solution. (In reality, “real time” usually involves some lag, or dropouts, such as the time in transit on an aircraft.)

“Real-time tracking enables resilience through control tower monitoring,” says Bobby Criss, digital supply chain leader, Johnson & Johnson. “The data from sensors can also be combined with other sources to understand lane trends and risks. Whether we are making decisions in real-time or using the sensors data for historical analysis, real-time tracking data provides considerable value and helps to maintain product flow to our customers.” (Criss will be expanding on this topic at the IQPC Temperature Control and Security meeting in Philadelphia, Nov. 1-3.)

ParkourSC, to cite one data-aggregation player, has added AI/ML to its offering to enable predictive analytics to the supply chain monitoring it provides. In early 2021, it announced a relationship with Cold Chain Technologies, as the latter ramped up its packaging volumes to help handle distribution of the Moderna COVID vaccine. “Beyond 

vaccines, the combined solution will track critical parameters for drugs and biologics, such as location, temperature, and vibration, along with data streams about weather, traffic, flight schedules, and more, to not only remove blind spots in the supply chain but flag potential issues so that they can be rectified before product is compromised,” say the companies.

Data aggregator Roambee touts the capability of its Honeycomb Visibility Platform not only for monitoring and reacting to temperature excursions for a cold chain shipment, but also to manage inventories, safety stock, and related distribution issues, such as the ability to manage inventory by the expiry dates of inventory.

The 3PLs that serve the pharma industry have their own version of data aggregation. UPS Healthcare, for example, is building out the UPS Premier service announced a couple years ago, by adding new levels of precision to its data capabilities (UPS Premier is available as silver, gold, and soon, platinum levels; the latter provides real-time tracking of 

shipments throughout the UPS network as well as contractors that UPS uses). DHL’s version of this aggregation is called LifeTrack; FedEx touts the combination of its SenseAware dataloggers with the Surround platform for analytics and predictive support.

Dan Gagnon, VP of global strategy at UPS Healthcare, notes that while its Premier services provide peace of mind to its pharma clients, it also has significant internal benefits for the company (which ultimately will translate into better customer service). “UPS Premier enables our operators to track packages moving through our network, when they enter one of our buildings, when they move through it, and when they leave," he says. "We might be handling thousands of packages hourly, but the operator can locate an individual package with a handheld device. The ‘secret sauce’ to our >99.9% on-time performance is that connection to operators.”

As management of the pharma cold chain tightens, other aspects of the process become better understood. An example of this is the transit from a specialty pharmacy (whose products typically involve cold chains) to the end user—the patient’s home or the hospital where a dosage might be administered.

The IT company ParcelShield, which works with many such pharmacies, says that its predictive tracking tools have prevented more than $3 billion annually in wastage in US distribution, by enabling logistics companies, or ParcelShield contractors (the company says it has 900 such contractors located all over the country) to intervene when shipments are at risk from temperature excursions or have been misrouted. The company bases its predictive ability on a database of distribution pathways, weather forecasting, and other factors; it also helps client shippers select logistics providers based on past performance. “About 90% of our business has been with pharmacies, including a just-announced relationship with Walmart,” says Sebastian Pistritto, marketing VP at the firm. “A growing part of our business is working directly with pharma companies."

Specialty pharmacies have another driver of their attention—the need to demonstrate compliance with the 4.0 version of URAC standards. URAC is a nonprofit that certifies the operational performance of pharmacies (among other tasks); many drug purchasers, such as pharmacy benefit managers, require that certification to do business with them. Specialty pharmacies have had to manage their cold chain shipments well under URAC 3.0; now under the newer standard, they need to ensure safe delivery of room-temperature (i.e., non-cold-chain) pharmaceuticals as well. Both AmerisourceBergen and Cardinal Health have set up advisory services to help their pharmacy customers meet URAC 4.0 standards.

While making a case for the lesser carbon footprint of its powered, reusable containers, Envirotainer has gathered data indicating that only 10% of the pharma industry’s overall carbon footprint is involved in logistics and distribution; the bulk is generated during raw material sourcing and manufacturing. Of that 10%, the great majority of carbon emissions would come from transportation—fuel consumption and related activity. The global logistics industry overall is trying to address those transportation deficits through actions like encouraging the production of so-called “sustainable aviation fuel,” produced from biologic sources, using electric vehicles for ground transportation, and deploying photovoltaic panels to power warehouse environmental control.

All that being said, when it comes to the pharma cold chain, the most glaring environmental problem is the accumulation of single-use, expanded polystyrene (EPS) insulation in pharma packaging. Technically, EPS is recyclable (and that is performed sometimes, in some locations), but the drive has been to develop alternative insulation materials or packaging methods—specifically reusable or recyclable containers.

The all-paper containers from Sonoco ThermoSafe or Cold Chain Technologies are gaining market share, according to conversations with those companies, even though those curbside-recyclables containers have a higher price than EPS containers. The same is true of Lifoam’s Bioffex compostable polylactic acid insulation, although pricing is influenced by the volume of packaging being ordered by clients.

On the reuse front, knowledgeable observers say that upwards of 20% of the boxes are lost after initial use; returned boxes need inspection and refurbishment, and in addition, the expense of reverse logistics needs to be accounted for. Over recent years, the concept of a reusable container has shifted from simply ordering such boxes to a “cold-chain-as-a-service” orientation. The packaging vendor works closely with the pharma shipper to devise trade lanes and return practices. In addition, boxes are being delivered prebuilt and preconditioned, relieving the shipper from those tasks. (It can take upwards of a couple days storage in a refrigerated room or chamber to precondition a cold chain box.)

Peli Biothermal was one of the originators of reusable-container services; Adam Tetz, director of global marketing, says that the company has around 70 locations worldwide where its containers are returned and readied for reuse. “Customers tell us it’s how we’re going to win their business,” he says. Most other major container providers have set up similar programs.

The pandemic, which stressed all participants in the pharma cold chain, has not stopped innovation in industry practices, as exploration of the main drivers shows 

Cold Chain Tech Continues to Evolve

Cell and gene therapies (CGTs) require complex manufacturing and distribution processes that are often difficult to scale.

 Unlike conventional pharmaceuticals such as small molecules and biologics, many advanced therapies are made to order and have an extremely limited shelf life. This is especially true for 

 therapies: living cells are collected from donors, transported to manufacturing sites, manipulated, and delivered to the patient. The separation in distance and time between each step in the process demands that cells be cryogenically frozen to maintain their viability and function.

 A temperature below the glass transition of water (Tg), about -135°C, is recommended, as it halts metabolic activity and inhibits degradation.

 Warming above this threshold, even briefly, can damage cells and threaten the efficacy of treatment.

A robust and coordinated cold chain is, therefore, necessary to ensure that cell and gene therapies are delivered on time with high quality. This article discusses the challenges of building a cold chain for CGTs and proposes strategies to improve their reproducibility and traceability for better clinical studies and more successful commercialization.


Cells are at risk of damage once separated from the body. Routine handling in and out of storage or during transport can expose CGT materials to temperatures above Tg, threatening their viability and downstream efficacy. Given the large temperature differential between storage and working conditions, even short exposures to ambient temperature can lead to rapid warming for cryopreserved materials.

With a boiling point of -196°C, liquid nitrogen (LN2) is the gold standard for cryogenic storage. Samples can be safely stored in either the liquid or vapor phase of LN2. When retrieving samples from an LN2 freezer, both target and non-target (innocent) materials can experience warming.

 Cells moved from -180°C to ambient temperature will reach Tg in about 90 seconds, providing a short window of time for the removal of the target materials and safe return of the innocents. Transient warming events, especially if frequent, can significantly damage cells.

A strong quality management system with safeguards and risk mitigation protocols is necessary to ensure that CGTs are stored safely and securely during their time outside the human body. Facilities for LN2-based cryogenic storage should follow best practices recommended by leading authorities in the industry, such as the International Society of Biological and Environmental Repositories (ISBER).

 For companies lacking the necessary infrastructure or expertise, storing CGT materials and clinical samples offsite with external partners is a viable alternative.

Implementing automation in the cold chain can bring major benefits to reproducibility. Pulling racks by hand to locate the target box or cassette exposes the entire rack to ambient conditions, increasing the risk of damage to innocent materials. Unlike a human, robotics can find and select samples at very low temperatures within the freezer, creating a much more controlled environment for retrieval.

 Manual workflows expose materials to temperature fluctuations that are larger, longer, and more variable than automated systems. Speed and technique can vary considerably between users and even over repeat performances of the same individual. Handling errors further increase the risk to CGT quality, such as pulling the wrong cryobag, misplacing materials, improperly securing freezer doors, and dropping racks. In contrast, a robot is highly consistent when removing and adding materials to/from the storage unit, outmatching a human in terms of reproducibility.

 therapies is significantly more complicated than traditional pharmaceuticals. Advanced therapies not only require nascent, expensive technologies to produce but also significantly increase the burden for tracking critical materials through the cold chain. Take autologous therapies like CAR-T for example. The patient is both the donor and recipient of cells, positioning them upstream as well as downstream of manufacturing. End-to-end tracking of the product—from collection of raw materials to manipulation at the manufacturing site to administration at the clinical site—is critical for patient safety and therapeutic efficacy. Both chain of identity (linking the product back to the original donor) and chain of custody (handling information, storage conditions, and description/date/location of actions performed, etc.) must be thoroughly documented to avoid errors and provide an audit trail in compliance with regulatory standards.

Since building the necessary infrastructure for transportation logistics may be too complex or costly, many CGT companies choose to partner with third parties to ensure proper tracking and delivery of materials. CGT-specialized vendors have developed the core competencies to mitigate risk and deliver efficiencies to the supply chain.

At manufacturing sites, automated storage can streamline many of the tedious and complicated aspects of tracking critical materials. Automated LN2 freezers have built-in software that provides real-time visibility, comprehensive event tracking, and integration with a laboratory information management system (LIMS). The processes of sample addition and removal are more controlled and simplified, especially when the system can automatically scan and register barcode-labeled materials. All transactions are automatically logged, promoting better compliance and traceability. Audit trails and cold-chain-of-custody records are substantially easier to generate and, importantly, are more accurate and thorough than those created by hand. Automated systems can also be implemented with 21 CFR Part 11 compliance in mind to better support clinical trials and commercial operations.

Advanced therapies have the promise to treat previously intractable diseases, yet their fragile and bespoke nature pose major challenges to clinical scale-up and commercial scale-out. It behooves CGT companies to maximize reproducibility and traceability in the cold chain to adequately protect the value of critical materials from collection to product administration. Incorporating automation and working with expert partners can mitigate risk in CGT manufacturing and distribution.

1. Cell and gene therapies: Delivering scientific innovation requires operating model innovation. Deloitte Insights (2020).

2. Meneghel, J., Kilbride, P. & Morris, G. J. “Cryopreservation as a Key Element in the Successful Delivery of Cell-Based Therapies—A Review.” 

3. Hubel, A., Spindler, R. & Skubitz, A. P. N. “Storage of Human Biospecimens: Selection of the Optimal Storage Temperature.” 

4. Angel, S. et al. “Toward Optimal Cryopreservation and Storage for Achievement of High Cell Recovery and Maintenance of Cell Viability and T Cell Functionality.” 

5. Sample Warming During Innocent Exposures From an LN2 Freezer: Comparing Temperature, Time & Workflow Using Manual vs. Automated Systems. Azenta Life Sciences White Paper (2015).

7. ISBER Best Practices: Recommendations for Repositories. 4th ed. International Society for Biological and Environmental Repositories (2018). 

8. ISBER Best Practices Addendum 1: Liquid Nitrogen-Based Cryogenic Storage of Specimens. International Society for Biological and Environmental Repositories (2019). 

9. Sample Warming During Innocent Exposures From an LN2 Freezer. 

10. Cell and gene therapies: Deloitte Insights. 

Sarah Eckenrode, PhD, is Vice President, Sample & Repository Solutions, Azenta Life Sciences.

Strategies to boost the reproducibility and traceability of cell and gene therapies for more effective clinical studies and commercialization

Building a Robust Cold Chain for CGTs

Across all industries, maintaining supply chains is crucial for functioning effectively. Within the cell and gene therapy (CGT) sector, given that shipments are generally living cells, the management of supply chains is challenging, relying heavily on cold chain logistics. Time pressures are often particularly critical because CGT is often the last treatment option available, prescribed only when standard pathway options have been exhausted, meaning the patients involved are often critically unwell. Additionally, the personalized nature of many therapies requires scrutiny around supply chain tracking, as errors or delays could prove to be fatal. When working within such fine parameters, an integrated supply chain ecosystem can help ease time pressures, reduce errors, and improve automation. At TrakCel, we have identified five common areas where integration can help CGT developers support the cold chain logistics their therapies depend on.

Tracking, monitoring, and excursion flagging

Many cold chain specialist couriers can provide a raft of information about the location and status of a shipment. Some can even give insight into the internal temperature of the shipper in real-time. While this information has the potential to be invaluable, the volume of the data generated can make it difficult to harness its true power, particularly if multiple shipping partners are being used. By integrating all shipping providers with a “hub” system like a cell orchestration platform (COP), this data can be automatically recorded against the drug journey. Workflows can also be built in, to alert users to events that might require action, such as a temperature excursion or a delay.

These alerts can be proactively sent to whichever party in the supply chain needs to act, whether the drug developer, the manufacturer, healthcare provider, or another party. This means that regardless of which stakeholder is due to dispatch or receive a shipment, the information can be directed proactively, in real-time. By reaching further into the supply chain ecosystem by connecting to the COP for scheduling information and the events surrounding a shipment, logistics providers can be better informed. If, for example, a patient is unable to make a cell collection appointment, the COP can prompt to cancel or delay a pending shipment to minimize wasted resource and expense.

One of the pressures with cold chain shipping is time, whether it’s a fresh product with a short shelf-life or a cryopreserved one in a shipper with a limited charge period. However, this is magnified in the CGT cold chain, where there’s greater need for an efficient journey to optimize the chance of a good treatment outcome. Integrating key systems within the supply chain journey, such as enterprise resource planning (ERP) systems, manufacturing execution systems (MES), and the COP helps to ensure that courier collections can be made with sufficient advance warning, and delays are also flagged so that they can be minimized. As this happens in, or near to, real-time, the time that is allowed to resolve issues is maximized, reducing the impact on the overall patient journey or instances where product cannot be delivered within critical timelines.

The receiving party details and dispatch information are stored in the COP, as are the rules that might govern a shipment, such as times when there’s customs clearance or a product cannot be received. This can help to prevent errors when scheduling shipping, as workflows can be configured to help users navigate these complex rulesets when scheduling treatments.

Within an integrated digital supply chain landscape, critical tasks and pathways are generally orchestrated by a COP that controls the processes specific to that therapy. This will include critical logistics information that when integrated, reduces what must be manually inputted into logistics booking systems or portals. This not only saves users time but ensures consistency and further reduces the chance of error.

Information that is essential and/or consistent for a particular therapy, shipment type, or site, labeling information and other required details can be set as critical fields and then sent directly by the COP. This direct information transfer to the courier means that there is a guarantee that all parties are seeing the same data rather than outdated or miskeyed information.

In addition to bookings, cancellations can also be requested and sent directly from the COP, informing the dispatcher, courier, and receiver that a shipment has been delayed or postponed so that the relevant actions can be undertaken, and the shipment marked as requiring rebooking.

As digital ecosystems evolve and the CGT market expands, there is potential for the rich data that is gathered by the various systems to drive advanced analytics that will help all parties to manage forecasting and logistics even more finely. This is more of a challenge in a non-integrated system where data is split over multiple systems or paper-records.

Digitizing logistics means that tracking the chain of custody for a shipment becomes far easier, as the COP will not only record the information in real-time but can dynamically search and report the audit trail of multiple/specific therapy journeys.

This change of custody information can be aligned with quality checks that are verified by either or both parties at the point of transfer. This means that should anything go wrong, it is far easier to track down the point of failure in the supply chain. This has important ramifications not just for quality control processes; in an industry where the cost of goods is extremely high, this can help minimize risk and exposure to supply chain partners when processes that are outside of their control fail.

These handover checks can be set up on a supplier, courier, therapy, or shipment basis, recording the specific information that is required at each point of the process and storing the record as a time-and-date-stamped element of the audit trail.

Digital workflows within a connected environment do not have to be limited to the information that is generated by a single system to monitor and safeguard a critical deadline. For example, when managing received or stored samples, information from a courier system relating to the charge life of a shipping container can be overlaid with information from the COP about the key timings of the scheduled events, information from the ERP as to the storage location of the cells at any given point in time, and information from the MES as to when the manufacturing slot for the therapy is scheduled. All of this can combine to create an informed picture as to whether current storage or shipping conditions are suitable or where additional actions are required in order to safeguard cell samples.

These actions can be driven by system-generated prompts to users that trigger at specific points, for example, within hours of the end of the container charge period.

While the infrastructure is yet to be fully established for cold chain (in advanced therapies), companies such as TrakCel are constantly revising the existing framework and putting in place such processes. The five ways the CGT industry can support cold chain shipping that we have explored are some of the main areas where developers are already reaping the benefits of supporting their logistics with an integrated network of supply chain partners. The fragility of the cargo and time-sensitive nature of CGTs means that the industry must support and maintain the supply chains, especially cold chain, as best it can.

Paul Viggers is Chief Commercial Officer, TrakCel.

Outlining five network-focused ways industry can support cold chain shipping of advanced therapy products 

Keys to CGT-Supply Chain Integration

Jay Johnson, senior manager of Labelmaster Services for Labelmaster, is a long-time expert in packaging and logistics solutions for the chemical and biotech industries, with a focus on dangerous goods (DG) and hazardous materials. He has been an active participant and major resource in the development and implementation of international dangerous goods regulations and is an active member of the Council on Safe Transportation of Hazardous Articles (COSTHA) and the Dangerous Goods Trainers Association (DGTA).

 to share his thoughts about recent disruptions and advances in the area of cold chain, and to emphasize that companies need to choose packaging and distribution systems that really fit a checklist of their needs.

: With the pandemic and other crises, what key changes have you seen affecting cold chain in the last couple of years?

 As the global pandemic has exposed logistical problems for lithium batteries and temperature recorders, people are going back to something of an “old school” approach. There had been this desire to have devices that could do everything—track shipments from space, for example—but they take a lot of power to run. And it is annoying to try and figure out whether such devices activate while they’re in the air, which the airlines certainly don’t like from a security standpoint. So, I’ve seen people going back to things like mechanical temperature recorders and chemical monitors, which only tell you when something’s gone out of range. These are inexpensive devices, particularly for last mile, and so are appealing to companies that have been scaling back from a cost standpoint.

Another change is that companies aren’t filling warehouses with Styrofoam coolers anymore. Instead, there are all sorts of things happening with insta-boxes, pop-up liners, fabric bags, cool liners, and products that have reflective metal or recycled material. We’re getting very creative with the new packaging that’s available. Now, we can ask, is all of it good? No. Does all of it work for everything? Hell, no. Companies must map out what they’re doing and select the packaging system that 1), fits their needs; 2), fits their time period; and 3), fits their price point. Now, Styrofoam panels were inexpensive, but it was difficult to sustain the right temperature because of gaps in the panels. And you’ve also got countries that don’t want Styrofoam, as they’re not able to recycle it. But if your system is built so that you can get your molded coolers back, you can run these coolers 10, 20 times. As long as you set up parameters to make sure that they’re not contaminated and you can easily replace the outer box if it gets damaged, the cooler itself could go on not indefinitely, but certainly for a long time, which means major savings.

People always want the less expensive option. They want something that takes up less space and they want something that will work for the duration and at the price point for what they’re doing. But companies should really look at what they’re trying to accomplish. What temperature range do they actually need? Is it 2–8℃? Or could they really go for 0–8℃, which is much easier to maintain? Do they really need seven-day monitoring? Or would they know by the third day if something is wrong and move on? These kinds of questions help them to pick a better price point for what they’re trying to do.

In terms of DG in the cold chain, what else has changed over the last two years?

I think that the way information is being communicated is different. There are still lots of conferences, but there’s not going to be as many as before because people have figured out a way to get their information from other sources. You’ve got people turning more than ever to pay services and websites and trade magazines because they couldn’t get together and hash it out at a conference during the pandemic. And people realized that the world didn’t come to an end when they didn’t go to conferences.

From my standpoint as a trainer and educator in the field of dangerous goods, we used to feel that if you didn’t do a DG class live then you weren’t getting trained. Now, people feel very different about that. But it took a pandemic to open that Pandora’s box. There were countries in Europe, Switzerland for example, that previously didn’t allow online training. They have had to make adjustments. Now I’m getting requests globally for training where they don’t expect me to fly over there; they want me to teach the class virtually and answer questions live. That’s a big difference.

Are you seeing changes in the way life sciences companies are approaching cold chain challenges?

People are asking more questions and pharma companies are getting more pushback from different regions internationally regarding packaging. One region might not want a particular item and so the pharma company has to figure out what alternatives they can use to get them even close to the temperature range they were getting at the price point they had previously. I’m getting a question like, “As opposed to Styrofoam or urethane foam, if I used an open-cell polyethylene foam, or even air bubbles or bubble bags, what kind of temperature can I maintain?” I usually try to push back and tell them really need a thermal lab to make sense of that; you can’t just take a chance on bubble wrap.

Pharmaceutical companies are held to a higher standard; it’s about more than just fines and penalties for regulatory noncompliance. If a company starts to cut corners in storage and shipping, people are going to say, “Are they also cutting corners to make the drug that I’m taking? Are they cutting corners to make the device that I’m using to keep me alive?" A pharma company could be setting itself up for a PR nightmare that it really doesn’t need to have, because complying with regulations is going to be significantly cheaper than the PR ramifications of not doing that.

What balance are you seeing in terms of active and passive temperature control?

I’m seeing more active systems, and I think there’s a lot of opportunity there. Couriers can build refrigeration or heating into certain sections of the vehicle that is shipping the goods. I know they’re stiving to make customers feel more comfortable that refrigeration is maintained throughout the entirety of a shipment, without the use of additional insulation or passive materials. If an item is only being shipped from A to B and the courier can guarantee the temperature range without the need for cold chain packaging, then it might be worth companies paying more to ship it that way because they will save on the packaging.This technology is really moving forward because courier operators like UPS and FedEx want to keep all the stuff within their systems. By having active temperature control, whether it’s elevated or refrigerated, couriers can make the customers more dependent on them for a particular route, so I think we will see more investment in this active technology.

A conversation with dangerous goods expert Jay Johnson

‘Old School,’ New Technology

As technology and our understanding of disease advances, how we transport, handle, and store temperature-controlled pharmaceutical products is rapidly evolving. While cold chain products are not new to the industry, the amount of products that need specific temperatures is increasing. In fact, in 2021, 58% of the 50 top-selling pharmaceuticals in the US required cold chain handling and storage.

And, as the number of personalized medicines in the drug pipeline continues to rise—most of which require freezer or deep-freeze temperatures—the need for more cold storage and handling will also increase.

Of course, this growing need for more specialized handling is taking place on top of an already taxed supply chain, exacerbated by the pandemic, a shifting online shopping culture, and even weather pattern changes.

All of this says it’s time to rethink the cold chain as we know it, focusing on a future where we deliver medicine in new and innovative ways by working with other industries and businesses, ultimately building the cold chain of the future.

While there have been advancements in the packaging of temperature-controlled pharmaceuticals, the overall methods have remained the same—either one-use shipping containers that can contribute millions of pounds of waste to landfills, bulky reusable freezer technologies, or refrigerated trucks. These options are used because they fit within the constraints and complexities of the shipping industry; however, while these methods have worked thus far, the influx of products needing specific temperatures, along with shipping delays caused by the overtaxed supply chain, means that these products could be at risk of losing efficacy—or worse—endangering patient lives.

In our case, we recently joined forces with Ember Technologies, known for its smart mugs that can keep drinks at the perfect temperature with an app, to develop a new way to ship temperature-controlled products. By working together, our team was able to understand new technologies, and gain new ideas, while the Ember team was able to better understand the intricacies of the supply chain within the healthcare space, and what’s needed to keep these highly expensive and life-saving medications safe for patients.

This partnership led to the initial design of the Ember Cube, a reusable refrigerated shipping container that uses novel technology designed specifically for these temperature-controlled products.

We know where our shoes and cat food purchases are in the supply chain—so, why not our medications? The real-time monitoring of pharmaceutical products, and specially temperature-controlled therapies, is not a new ask. In fact, it is largely considered one of the most serious challenges affecting the pharmaceutical industry, with 32% of drug manufacturer executives stating that temperature monitoring is their 

Manual checks for temperature excursions may have worked for 2-8°C products, but as the ultra-low and cryo products come to market, these get harder to complete, requiring better technology.

This is punctuated by research that shows that the biopharma industry loses approximately $35 billion every year due to temperature failures. Understanding where products are in the supply chain, when they will get to their destination, and potential risks that might be encountered is no longer a nice to have, but a necessity for the future of the supply chain and the safety of patients.

As part of our project with Ember, the need for real-time tracking of each Ember Cube became essential to the design of the product. We worked with their team to develop a solution that was trackable on a cloud-based dashboard complete with real-time temperature and location monitoring.

Not only does the cloud aspect enable the logistics team to understand where it is, but this could eventually build into access for providers, patients, etc.

Beyond packaging for individual products, we have also found that a temperature-controlled dedicated transportation network can also protect the integrity of these products. Unlike other solutions, these networks use geofencing to track treatments in real-time, which enables larger shipments of products while still keeping the focus on the supply chain visibility. This is especially important because delays in transit are inevitable. While we may not be able to prevent these delays 100% of the time, we can better protect the product during a delay, thereby mitigating the risk of product loss and the potential of a patient not getting their medication when they need it.

Beyond the technical aspects, sustainability is what the future looks like from an environmental standpoint, especially when some research shows that the pharma industry may emit more greenhouse gases than the automotive industry.

Currently, the most common types of cold chain shipments use single-use materials, such as polystyrene and cooling packs, due to the cost-effectiveness and flexibility of these designs, and many manufacturers are looking to invest in more sustainable options in order to meet their aggressive sustainability targets. This has led to the adoption of programs with life cooler returns growing in popularity; however, the success rate of getting coolers back is still low.

With today's greater combination of technology and know-how, we must design new ways to handle sensitive pharmaceuticals—and do it together 

Pharmaceutical Commerce - October 2022

Pharmaceutical Commerce - October 2022 Issue (PDF)

Decisive Moves on the Digital Supply Chain

Betting the House on Orphan Drugs

Cold Chain Tech Continues to Evolve

Building a Robust Cold Chain for CGTs

Keys to CGT-Supply Chain Integration

‘Old School,’ New Technology

Building the Cold Chain of the Future

Choosing the Right Monitoring Device

Global Logistics: A Cold Chain Blueprint

On the (New) Edge of Tomorrow

Telehealth: Connecting the Dots

The Importance of Sub-Zero Labels

Pharma's Future Supply Chains