Packaging Preserves the Cold Chain

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.

Packaging trends

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. 

Meeting requirements

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.

Testing

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).

Cold-chain options

Innovations in temperature-controlled packaging center on sustainability, performance, and cost. To improve sustainability, OptumRx, a pharmacy care services provider, has transitioned from rarely recycled foam packaging to recyclable packaging made from renewable cotton-based Kodiakotton from Kodiakooler, which was recently acquired by Airlite Plastics. The Kodiakotton insulating material is biodegradable, compostable, reusable, and recyclable. OptumRx projects the new packaging will save millions of gallons of water, pounds of carbon dioxide, and kilowatt-hours of energy (3). “OptumRX has had great success with our sustainable products,” reports Corbin. “Part of the initiative is ongoing education for their consumers on the benefits of recyclable materials,” he adds. 

In addition to Kodiakotton liners, Kodiakooler offers the patented Kwikpack system. This is a bundled kit of two Kodiakotton liners with an easy-to-remove, recyclable band. The liner bundle cuts insertion time and results in a packout-ready shipper in less than six seconds (4). 

Fiber-based options, which can be recycled in the corrugated or waste-paper streams, also are popular. To address this market, Thermo Fisher Scientific has developed the Invitrogen Paper Cooler. The 100% paper alternative to EPS foam coolers meets thermal requirements for overnight shipments (5). Another paper-based product, ClimaCell insulation from TemperPack, is designed to replace EPS insulation and reduce packaging waste. In addition to being recyclable in the corrugated stream, the ClimaCell material protects temperature-sensitive shipments for up to 80 hours. The material also is moisture-resistant and can be customized with printed graphics/messages (6). 

Another player in the insulation market, va-Q-tec, has opened a US headquarters and production facility in Langhorne, PA, to manufacture its small boxes and containers. The location also serves as a rental and repair station. The company, which is headquartered in Germany, specializes in vacuum insulation panels and phase-change materials that offer five-day temperature protection without the need for external energy sources. A rental service business offers a fleet of cold-chain containers and boxes (7).

Reuse is possible with the AcuTemp Plus Series of shippers from CSafe Global through its Repaq program. Proprietary, high-performance ThermoCor vacuum-insulated panels control payload temperatures. Simple to deploy, the shippers are available in multiple sizes and temperature profiles with integrated track-and-trace options (8). 

Although reusable packaging has gained ground, one-way shippers remain a viable choice and continue to evolve. AeroSafe Global, a supplier of reusable shippers, has added a disposable option to its portfolio. The A20 insulated shipper is designed to serve shipments needing protection for 24 to 48 hours. It is fully prequalified to ISTA 7D summer and winter profiles. Minimal components simplify packouts (9).

Gore Sta-Pure flexible freeze containers from Gore PharmBIO Products are designed to protect high-value bulk drug substances from container breakage or leakage during frozen handling. “Traditional single-use bags are constructed from materials that typically become brittle when exposed to temperatures below -40 °C, which can lead to cracks or leaks in the bags,” explains Cintavy. The proprietary high-strength fluoropolymer material used for the Sta-Pure flexible freeze containers is durable after freezing at -86 °C (-123 °F) and offers the convenience and scalability of a single-use system that efficiently uses freezer space. In addition to durability, the container’s chemically inert, biocompatible, high-purity fluoropolymer composite film has a low extractables profile (10).

Gore Sta-Pure flexible freeze containers come in sizes from 50 mL to 12 L with tubing and connector options to meet different pharmaceutical and bioprocess applications. A hard-shell carrier is available for easier handling. If carbon dioxide or oxygen permeation is a concern, an optional, vacuum-sealable, secondary barrier wrap minimizes ingress (11).

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. 

Introductions from Pelican BioThermal include a new version of its ProEnvision web-based asset management track-and-trace software, which allows integration of its CoolPall Flex bulk shipper into the Internet of Things. The CoolPall Flex shipper serves refrigerated, frozen, and room temperature ranges. A high level of flexibility allows the system to address different time, weight, and payload requirements. 

For cryogenic products, SAVSU Technologies has expanded its portfolio of dry vapor shippers, which maintain biologic payloads at -196 °C during storage and transport. Positioned between the DV4 and the DV10 shippers, the DV7 unit offers seven days of thermal autonomy and a more compact form factor with a payload capacity similar to the DV10 shipper. With its smaller size, the DV7 shipper is easier to handle and store and less expensive to ship (12). 

Cryoport Express Advanced Therapy Shippers from Cryoport have been developed to meet demand from biopharma customers and in anticipation of more stringent government regulations. The shippers are dedicated to human use and certified as such. Validated to ISTA 3A and 7E Transportation Standards, a new vapor plug design further doubles the holding time if shippers are mis-orientated during transit. The shippers also provide complete traceability of use history and assurance that each dewar is requalified for each trip for physical suitability, cleanliness, liquid nitrogen capacity, and shipment hold times. Validated cleaning processes reduce the risk of cross-contamination during use, delivery, and distribution (13). 

Future possibilities

Sustainability continues to be a major driving force with suppliers and users of temperature-controlled packaging. As a result, work continues on developing designs that meet performance requirements that will be more renewable, recyclable, reusable, and/or compostable. Kodiakooler, for example, is working on biodegradable EPS foam. “We are constantly looking for ways to reduce the carbon footprint of temperature-controlled packaging materials,” says Corbin. 

References

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.
3. OptumRx, “OptumRx Introduces 100% Sustainable Packaging for Medication Home Delivery,” Press Release, Aug. 16, 2018.
4. KodiaKooler, “Kwikpack, Assembly Instructions,” Video, kodiakooler.com.
5. Thermo Fisher Scientific, “Invitrogen Paper Cooler,” Thermofisher.com/order/catalog.
6. TemperPack, “TemperPack Launches ClimaCell, a Certified Recyclable Packaging Solution for Perishable Shipments,” Press Release, May 10, 2018.
7. va-Q-tec, “va-Q-tec Expands in US,” Press Release, Jan. 19, 2018.
8. CSafe Global, “CSafe Expands Cold Chain Offerings for the Cell and Gene Therapy Market with Launch of High-Performing Acutemp Plus Series of Temperature-Controlled Packaging,” Press Release, Dec. 13, 2019.
9. AeroSafe Global, “AeroSafe Global Introduces Lower-Cost, Single-Use A20 Insulated Shipper Line,” Press Release, Oct. 23, 2018.
10. W.L. Gore & Associates, Inc., “Gore to Launch GORE STA-PURE Flexible Freeze Containers at BioProcess International,” Press Release, August 24, 2018.
11. W.L. Gore & Associates, Inc., “GORE STA-PURE Flexible Freeze Containers,” Gore.com.
12. SAVSU Technologies, “SAVSU Technologies Launches Two New evo Smart Shipper Models to Improve Apheresis Collection Shipments and Cryopreserved Cell and Gene Therapies,” Press Release, Jan. 22, 2019. 
13. Cryoport, Inc., “Cryoport Introduces Cell & Gene Industry’s First Dedicated Shipper for Advanced Therapies,” Press Release, Sept. 18, 2019.  

About the author

Hallie Forcinio is packaging editor at BioPharm International, editorhal@sbcglobal.net.

Article Details

BioPharm International
Vol. 33, No. 4

April 2020
Pages: 38–43

Citation

When referring to this article, please cite it as H. Forcinio, “Packaging Preserves the Cold Chain" BioPharm International 33 (4) 2020.