Safeguarding Biologics—Blending Engineering Ingenuity and Managerial Excellence

The coordinated steps required to safeguard biologic medications, vaccines, and personalized cell and gene therapies (CGTs) from the moment they begin the journey from origin to destination are notoriously complex. Many best practices and lessons learned have emerged in recent years as pharma/life sciences companies, along with their third-party logistics partners and vendors that supply specialized packaging and monitoring solutions, have all weathered the COVID-19 pandemic together and continued to support ongoing growth in the pipeline of therapeutic products that must be continuously maintained at refrigerated, frozen, or ultra-frozen temperatures.

There is no room for failure if any of these high-value—and increasingly one-of-a-kind—therapy options are allowed to experience temperature excursions. “Especially when it comes to autologous CGT products, the need to track the shipment from the donor patient to the processing center (laboratory or manufacturing location) and back to the patient is of paramount importance,” says John Bermudez, vice president, product marketing, TraceLink.

“What really complicates CGT shipping in particular is that these high-stakes shipments must be customized for smaller-sized, highly individualized parcels,” notes Shea Vincent, senior marketing director of BioLife Solutions. “With some of today’s gene therapies priced at $1, $2, or even $3 million, failure is not an option during distribution.”

Room for improvement

While the industry has learned a lot during the steep and fast learning curve imposed by the pandemic, and many of the lessons learned are now routinely being applied to optimize the shipment of both larger-volume biologic products and vaccines and smaller-volume CGTs, “the reality is that the tactical implementation of these specialized supply chains for CGT products has yet to be fully established on an industry-wide scale,” says Vivian Berni, director of product management and strategic marketing for Sonoco ThermoSafe. “This leaves a significant burden on manufacturers of today’s cell-based products to distribute their products reliably. Unknowns cause doubt, uncertainty, and risk—and these are not friendly ingredients in a discipline that strives for repetition and predictability.”

“There are already a lot of capabilities in place—experienced cold-chain couriers, state-of-the-art insulated containers, the ability to track and monitor with reliable, cost-effective sensors—so it’s more about pulling the right mix of the elements together in the most strategic and effective way to maximize visibility and minimize the risk,” says Bermudez.

Cold chain planning and execution “… continues to be impacted by not only the pandemic but by other factors, such as air cargo capacity being down, instability related to inflation, the Russia/Ukraine conflict, and more, but despite it all, you still have patients depending on what you’re delivering,” notes Rob Coyle, senior vice president, healthcare strategy, Kuehne+Nagel. As such, he says that stakeholders handling high-end CGT products “need to be really honest about the risks and plan for them ahead of time. Developing a robust backup plan (and having all parties agree to it) ahead of time allows for seamless pivot and rapid response should any delay arise en route.”

For many routes, it makes sense to use passive shipping containers, as they require no power infrastructure, have a more favorable carbon footprint, and can often provide a lower-cost option if appropriate. “With careful planning, we’re often able to replace active shippers with passive units by leveraging existing infrastructure, ongoing advances in insulation materials, phase-change materials (PCM), and container designs, using advanced GPS and other monitoring devices to ensure continuous access to real-time location, temperature, and other data,” adds Scott Ohanesian, senior vice president, commercial operations, QuickStat, a Kuehne+Nagel company.

“Those handling temperature-sensitive pharma products and biologics have experienced a lot of frustration over the past few years due to strategic shortages and supply-chain issues related to dry ice, liquid nitrogen, and the types of specialized packaging that is needed,” says Vincent. “Fortunately, newer materials such as advanced insulation materials and PCMs that continue to come to market are setting up the industry for a better, more reliable future.”

PCMs are engineered materials—based on paraffins, fatty acids, alcohols, hydrated salts, and more—that are conditioned to the refrigerated or frozen setpoint temperature at the outset and placed inside the specialized transportation container. They are able to store and release energy (undergoing a change in phase as they are warmed and cooled) as needed to maintain the critical setpoint temperatures inside the passive thermal containers throughout the trip. Meanwhile, to ensure dock-to-dock shipping integrity, Vincent says it’s important “to develop a backup plan and to ensure that all stops on the trip have sufficient ultra-low-temperature (ULT) storage capacity, or the ability to access more dry ice or recondition the PCM.” She notes that the planning gets more complicated when the customer will be shipping product by the pallet but then dividing the pallet to repackage smaller volumes to ultimately reach many different destinations.

Technology advances

“The Holy Grail for the pharma cold chain is ‘how do I get perfect service at a more economical price?’” says Dan Gagnon, vice president of global strategy for UPS Healthcare. Economies of scale and tighter overall integration can help to coax out some unnecessary expenditures.

A particular challenge is that the end-to-end distribution of biologics often requires handoffs among multiple partners using disparate systems, and this creates unnecessary complexity. “Today, existing tools can be used to reliably track individual shipments, but the challenge is that it has to be coordinated with actual patients and the labs that process the cells,” notes Bermudez. “The ability to closely coordinate all handoffs improves visibility and gives timely alerts when a shipment has gone out of temperature range or needs intervention.”

In other cases, pharma/life sciences stakeholders producing biologics and CGT products enlist multiple vendors and partners to create complex end-to-end distribution routes. “Stakeholders should choose partners who take a consultative approach,” says Amy DuRoss, president, cell and gene therapies, CSafe Global. “They can help to identify the challenges ahead of time and address them effectively when they do arise.”

In recent years, UPS Healthcare “has made its mission to streamline and integrate the pharma cold chain as much as possible, bringing as much of the end-to-end capabilities—in terms of storage capacity, ocean, ground, and airline networks—in house as possible to maximize quality and visibility,” says Gagnon. “Any time you can remove a handoff between two parties it dramatically reduces the risk of excursion, and our singular, unified system uses the same systems and similar training for all personnel, which provides a complete end-to-end cold chain under one roof.”

In November, UPS Healthcare acquired global healthcare logistics provider Bomi Group, helping to expand its footprint across Europe and Latin America. UPS Healthcare customers now have access to 216 facilities with 17 million square feet of current good manufacturing practice and good distribution practice-compliant healthcare distribution space in 37 countries and territories.

“Scientific advances are always ahead of the regulatory frameworks, so logistics providers need to work closely with regulatory authorities when it comes to CGT distribution,” notes Ohanesian. For example, delays in Customs vary from country to country and can chip away at the limited window for which packages transporting biologics and CGT products is guaranteed to remain at its setpoint temperature. “Customers often make a packaging choice and get locked in, so they don’t really consider qualifying newer packaging options—we see that a lot,” adds Coyle.

For instance, Ohanesian says, “If your quality team has already qualified a particular technology that can ensure the setpoint temperature is maintained for three days, but there exists an option that can maintain it for eight days, you need to consider making the switch.”

“One of the challenges associated with competing technology options is that you need to keep investing in new technology, but you can’t just get distracted by every shiny new technology solution,” adds Gagnon. “You have to critically evaluate which technology advances will bring significant value to customers and focus on which offerings are likely to still be around in the years to come.”

Despite ongoing innovation in supply chain traceability, real-time tracking, and enhanced visibility, DuRoss says, “we urgently need solutions that simplify and standardize CGT operations so that this field can scale. High complexity often translates to higher-than-necessary costs, which results in fewer patients being treated.” To achieve mass adoption within the CGT space, “we need to both industrialize and personalize in parallel,” she continues.

Best practices

Ensure quality and data integrity. “Having a comprehensive commitment to quality is a winning strategy and putting the systems in place now can save you a lot of headaches later,” says Gagnon. Meanwhile, in all partnerships, specific elements (such as hardware, software, service, and more) must go through consistent qualification and validation processes and be demonstrated as suitable for use in the regulated environment, notes Emanuel Schäpper, head of global business management for ELPRO. Coyle adds, “If you don’t have detailed standard operating procedures (SOP) and quality systems in place, and enforce that each of your partners implement them, too, it will open you up to human and process error.”

Invest in offerings that make sense. “Not all technology, tracking devices, and packaging options work across all networks, locations, or applications,” adds Berni. “Understanding the constraints of each option helps all parties to manage expectations and set things up for success.”

Leverage recent developments. “In response to the COVID pandemic, we developed a passive parcel ULT shipper that can transport and store mRNA [messenger RNA] vaccines at a range of -60 °C to -90 °C for up to 30 days, and it has been used to reliably ship COVID-19 vaccines to 180 countries,” says DuRoss of CSafe Global. “We must leverage all of the global COVID-19 learnings and solutions to enable scaleup in CGT.”

Strive for continuous improvement

When it comes to container designs, insulation, and PCM materials, monitoring, and control systems and versatile cloud-based solutions to enable greater visibility, stakeholders should keep up with ongoing advances and be willing to embrace best-in-class solutions, rather than becoming locked into a particular solution. “The entire chain is only as strong as its weakest link,” says Schäpper.

Choose monitoring and tracking devices carefully. “From the perspective of a suitable monitoring solution, care must be taken to ensure that the operability of monitoring devices [is] user-friendly and easy to understand, especially in the case of extensive, global distribution networks,” says Schäpper. “The operating elements must be clear, and the display must provide unambiguous information about the status of the product or the measurement parameters.”

Engage logistics partners and vendors as early as possible

“The more we can get critical information earlier in the product lifecycle, the better we can design systems to optimize each of the steps. This has been one of the biggest learnings in recent years,” says Coyle. Similarly, Berni adds, “Involving packaging providers and logistics partners in the discussions early on enables a more cohesive overall strategy. I cannot emphasize this enough; start the conversation early with all of your partners—don’t wait.”

Choose partner with global reach. “You can’t adequately support CGT patients worldwide when you have cold chain service centers in just a few locations—for instance, you can’t support and service the distributed global CGT infrastructure if you operate just a few locations in North America and Europe,” says DuRoss.

Clinical and commercial teamwork

“More than ever, these two teams—which formerly functioned largely independently of one another—are working hand-in-glove from the earliest phases of drug development, and that’s the way it should be,” says Coyle. “We’re still in the infancy of the era of high-end biopharma and personalized medicine, and while we’re already learned so much, there’s still so much more room for ongoing improvement to minimize the risk of product damage and ensure patient access to these high-value, lifesaving therapies,” says Coyle. As the pharma/life sciences pipeline of biologic therapies, vaccines, state-of-the-art CGTs, and other gene therapies continues to grow, so does the need to push for ongoing innovation in the technologies and practices needed to safeguard them during shipping and storage.

About the author

Suzanne Shelley is a contributing editor to Pharmaceutical Technology.

Article Details

Pharmaceutical Technology
Vol. 47, No.2
February 2023
Pages 20–21, 28

Citation

When referring to this article, please cite it as Shelley, S. Safeguarding Biologics—Blending Engineering Ingenuity and Managerial Excellence. Pharmaceutical Technology 2023, 47 (2), 20–21, 28.