Equipment and Processing Report
Consider trends for packaging that protects temperature-sensitive drugs.
Proper storage and transport temperatures for drugs, especially biologics, are essential to protect product efficacy and patient safety. “As strong growth continues across the global pharmaceutical industry, the sub-category of temperature-controlled products is surging ahead-growing at twice the rate of the industry overall,” said David Williams, president of Pelican BioThermal in a press release (1).
Joe Cintavey, product specialist at W.L. Gore, agrees, noting, “The pipeline of biologic drugs in development are becoming more temperature-sensitive, resulting in an increase in storage
of bulk drug substance at frozen temperatures (-40 to -70 °C).”
Rory Davidson, Business Development Manager at Almac Pharma Services, adds that labeling, packing, and distributing cell and gene therapy products often requires products to be stored and processed at ultra-low temperatures (-20 to -80 °C), with the products only being defrosted immediately prior to use. “If these products are not kept in exact conditions, they become unusable. We have seen some cases of product becoming unusable within a minute of being out of frozen conditions and so we need to be able to handle and process product at these ultra-low temperatures as quickly and efficiently as possible,” notes Davidson.
In addition to the growing number of temperature-sensitive products, three trends are driving the need for temperature-controlled packaging, according to a survey by Pelican BioThermal. First, quality demands increase as more sensitive products bring logistics complexity and greatly expanded risk. Yet, while awareness of temperature-controlled requirements is high, the survey shows temperature excursions happen frequently (1).
Second, the distribution range is expanding as products move further and through more climatic zones. More than half of survey respondents (51.8%) regularly ship products internationally, creating an increasingly complex web of local, regional, and international connections that require a broad range of transport modes (1).
The third trend identified in the survey is the need to optimize the total cost of ownership (TCO) due to relentless competition and margin pressures. A full 70% of survey respondents agree that TCO is “important” or “very important,” while 10% consider only basic packaging costs and transport rates. This exploration of TCO is spurring interest in reusable containers, with 79% of survey respondents saying reusable containers-though more expensive than single-use containers-are worth the investment. More than one-third of respondents (37.6%) are already using reusable rental programs in their cold-chain logistics operations, and 25% are actively exploring this option (1).
As a result, validated, off-the-shelf, or customized protective packaging options continue to evolve for all temperature ranges, including controlled room temperature, refrigerated, frozen, and cryogenic. “The challenge is optimizing the design, materials, and components to minimize overall size and weight of the shipping solutions,” says Mark Barakat, general manager of Cryopak, a subsidiary of Integreon (formerly TCP Reliable). He continues, “Achieving peak performance while minimizing size, weight, and cost is typically contradictive.” Cold-chain engineering experience and tools like thermal modeling software and testing equipment play important roles in optimizing temperature-controlled packaging.
There is also strong demand for more sustainable designs, including re-use programs to reduce the carbon footprint. Interest in temperature-controlled packaging also is being impacted by changing regulations and standards. For example, “Temperature profiles issued by ISTA [International Safe Transit Association] have changed within the past five years,” reports Barakat.
“Regulations governing these types of highly sensitive products are growing stricter,” adds Adam Tetz, director of worldwide marketing at Pelican BioThermal. “For example,” he says, “China has become particularly strict and requires real-time tracking on all pharmaceutical shipments.”
Many local governments want to reduce or eliminate the use of expanded polystyrene foam (EPS), a common insulating material, because it is rarely recycled. “California and New York are limiting the amount of EPS foam that can be delivered into their states,” says M. Ryan Corbin, director of marketing at Kodiakooler. These requirements are forcing makers of temperature-sensitive drugs and biologics to look for alternatives.
In addition to insulation, temperature-controlled packaging includes single-use and reusable parcel and pallet shippers, thermal pallet covers, and phase-change materials. Sometimes, customized designs are needed, especially for products that will experience particularly hostile conditions or need to be maintained at cryogenic temperatures. Regardless of the application, optimized temperature-controlled packaging depends on the answers to three questions: Where is it being shipped? What temperature must be maintained? How long does that temperature need to be maintained? In addition, “Seasonal temperature changes can substantially affect the internal facility environment and shipping environment,” warns Joe Luke, vice president of sales and marketing for Reed-Lane, a New Jersey-based provider of contract packaging services.
To ensure packaging will perform as specified, Cryopak tests it against extreme ambient temperature profiles in its ISTA-certified lab following protocols and internal standard operating procedures. “Our shipping systems are then qualified with repetitive testing to assure consistency and performance repeatability,” explains Barakat. “The real shipment is then monitored with temperature data loggers to prove operational performance and quality assurance,” he concludes.
To test the durability of reusable, passive thermal packaging systems, Pelican BioThermal is developing a mechanical test method. In addition to mimicking the real-world use environment, the test method also allows assessment of the impact of dynamic use on thermal performance. Tetz reports that results are promising. He says, “The test standard would give pharmaceutical manufacturers even more confidence in choosing reusable thermal packaging over single-use options to reduce costs and advance environmental initiatives.”
“Current standards assess parcel thermal packaging systems during one intense shipment from point A to point B,” explained Bill Mayer, director of research and development at Pelican BioThermal. “Throughout the development of this new test method, we addressed the challenges of exposing systems to the multi-leg and multi-mode shipping route and more of an average trip with parcel thermal packaging used multiple times” (2).
Reed-Lane recently added cold storage (2–8 °C) capabilities and a dedicated climate-controlled room for vial and ampule kitting at its packaging facility in Wayne, NJ (see Figure 1). Temperature and humidity sensors constantly monitor the cold storage area to document conditions and ensure there are no product-damaging temperature excursions. “Most crucially, our environmental monitoring solutions are able to provide email alerts should any specified environmental conditions be exceeded,” says Luke. He explains, “Additional sensors are deployed to provide alerts pertaining to ... power outages, which would result in an immediate onsite power generator startup to maintain specified temperature continuity.” The dedicated room for kitting temperature-sensitive products includes space for labeling vials and ampules and assembling them with other components such as printed literature. Its location adjacent to the cold storage area minimizes intra-facility travels and exposure to temperature excursions.
1. Pelican BioThermal, “Pelican BioThermal Reveals 2019 Biopharma Cold Chain Logistics Survey Insights Amid Surge of Temperature-Controlled Products,” Press Release, July 26, 2019.
2. Pelican BioThermal, “Pelican BioThermal to Present Development of Laboratory Mechanical Testing Protocol for Reusable Thermal Packaging at ISTA Forum,” Press Release, May 14, 2019.
Hallie Forcinio is packaging editor at Pharmaceutical Technology, email@example.com.