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GDP standards drive higher performance standards for packaging
Fig. 1. UPS’ Med 100-400 series of containers for individual-dosage to carton-size shipments. Credit: UPS
For the better part of a decade, the global pharma industry—mostly under a self-imposed duty—has been aggressively upgrading its shipping practices for temperature-controlled pharmaceuticals. The traditional “cold chain” perspective has given way to comprehensive temperature control. Much of this culminated in 2013 as the European Union codified its Good Distribution Practices (GDPs), which are gradually becoming the required guidance in many locations globally.
In what might be a first for GDP compliance in Europe, a Norwegian health-products distributor, Norges NaturmedisinSentral AS, has had its Wholesale Distributor Authorisation (an EMA-regulated certification) partially withdrawn in January. The reason, according to a report on a news site* run by the ECA (European Compliance Alliance), was “operations [that] were not managed under GDP” for cold chain products. (The ECA is a European-based nonprofit that runs educational programs for GMP, GDP and other types of life sciences operations.)
“Industry is taking GDP requirements very seriously,” observes Dan Bell, regulatory compliance and technical affairs vice president at Marken (Research Triangle Park, NC), the clinical trial logistics provider. “There’s an interrelationship between temperature control across refrigerated, frozen and controlled room temperature (CRT), and the stability of drugs as they are tested. It’s best to stop talking about ‘cold chain management’ and start talking about a ‘temperature controlled network,’” he says.
Vendors of temperature-controlled products, especially packaging, have responded to the heightened regulatory restrictions with a growing array of materials and technologies to transport pharma products safely, as have the distributors and third-party logistics (3PL) firms that manage these shipments for pharma clients. (Digital and analog condition monitors, and the tracking systems they power, will be covered in a later issue of Pharmaceutical Commerce.)
In a like manner, the clinical trial materials (CTMs) logistics business has also seen a dramatic upgrading in capabilities and capacity. The two leading, dedicated CTM providers, World Courier (now a unit of AmerisourceBergen) and Marken have been building out larger depots with more CTM-associated services (such as refrigerative and frozen storage capacity). Most recently, World Courier expanded a Melbourne, Australia depot to provide both clinical and commercial drug-delivery services, with the facility implementing 3PL services (such as order-to-cash) adapted from ICS, another unit of AmerisourceBergen.
Fig. 2. Sonoco ThermoSafe’s new pallet shipper. Credit: Sonoco
In both commercial and clinical operations, the trend seems to be toward rationalizing services and technologies to provide a near-global uniformity. At the same time, pharma companies managing their shipping are looking at economies of scale and cost savings to be had with better technologies. “For the past 18 months, we’ve been engaged in a program to have a portfolio of available packaging solutions, for refrigerated, frozen and controlled room temperature shipping requirements, with each temperature range having a set of products with their own value propositions,” says Ben VanderPlas, global product manager at Sonoco ThermoSafe (Arlington Heights, IL). “Clients, whether a shipper, a freight forwarder or a research lab, increasingly want to match their requirements with a tailored solution.”
Case in point: UPS Healthcare Logistics (Atlanta, GA), which provides 3PL services around the world, is now offering what amounts to branded packaging solutions for its clients. As announced at the beginning of this year, its released a Temperature True line, ranging from an insulated envelope (for direct-to-patient delivery of single doses) to carton sizes to handle refrigerated, frozen and CRT shipments. The packaging (which is delivered to the shipper) also aligns with UPS’ Temperature True service options, which allow for preselected overnight, two-day or other delivery options. “Healthcare customers benefit from more expertise and options created to minimize costs and maximize efficiency when time and temperature control is the highest priority,” said John Menna, UPS VP of global strategy for healthcare logistics, in a statement.
The range of sizes and temperature control covers many applications in clinical trials, diagnostic specimens, direct-to-patient or -physician deliveries of single doses and commercial-scale shipments. Capacities range from 1.2 to 39.6 liters. Temperature regimes cover frozen (
Susan Li, manager of the Temperature True packaging lines at UPS, notes that having a standardized CRT package is a fairly new development on the market (CRT is one more part of the EU GDP standards; whereas 5-10% of today’s shipping is refrigerated, CRT represents most of the rest. Heretofore, many CRT pharma shipments went under “ambient”—i.e., no temperature control—conditions.) “CRT packaging can be more expensive than 2-8°C refrigerated,” she says, “because you need to use phase-change materials in the container that cover a wider temperature range than 2-8°C materials.” “This will be a struggle,” she notes, for cost-effective shipping solutions in the CRT regime.
Fig. 3. Sonoco ThermoSafe’s Via vacuum-panel shipper (left) and Cold Chain Tech’s instant shipper (right).
Sonoco ThermoSafe’s PolarPack gel packs, and other Sonoco components, are used in some of the configurations; other contractors include MP Global Products (Norfolk, NE) and NanoCool (Albuquerque, NM).
NanoCool figures in another recent new product announcement: For several years, NanoCool has been offering an innovative chilling technology for cold chain shipments, based on evaporative cooling rather than refrigerant packs or dry ice. Now, it is bringing the global reach to its side through a partnership with Cold Chain Technologies (CCT; Holliston, MA) and its European partner, Topa Thermal Packaging. CCT is now offering the KoolTemp GTS Instant container, first unveiled at the Cool Chain Logistics Conference (Jan. 26-29, Frankfurt, Germany).
The NanoCool technique uses a bladder of very low-pressure water as part of the container. When the bladder is punctured, the water begins evaporating, and the heat consumed in that phase change generates “on demand” cooling. The rest of the package uses fairly standard packaging and insulation materials (according to NanoCool literature, there are some instances where the evaporative cooling is complemented with dry ice or other refrigerants). The end result is upwards of 96 hours of maintaining 2-8°C conditions, in boxes with capacities up to about 54 liters.
By reducing or avoiding refrigerants altogether, notes Jamie Chasteen, senior product manager, the GTS Instant package saves weight and materials, and doesn’t require pre-conditioning of the package. In theory, too, the cooling could be initiated at various points in the supply chain (for example, after leaving a temperature-controlled storage area).
Clinical business drivers
The traditional practice in clinical logistics was that cost didn’t matter. The value of CTMs is so high (with entire multimillion-dollar trials riding on safe delivery of test drugs or patient samples), that ensuring the shipments are properly managed was worth practically any cost. This is now changing: clinical trials are more of a global activity, and delivering CTMs to remote locations (remote, at least, from major international airports), combined with the increasing rigor of regulations, make cost control a growing factor.
At the same time, the clinical trials business is growing again, having plateaued in the 2009-2012 period. Pharmaceutical Commerce, in its annual Biopharma Cold Chain Sourcebook, projects a near doubling of the growth rate for clinical trial activity—from about 1.5% per year to 2.5% per year, through 2019. FDA is approving more new drugs, faster, with a recent record of 41 approved in 2014. Many of those are biologics, and usually biologics require temperature control.
A third factor could be the overlap between clinical research and commercialization, especially for rare diseases/orphan drugs. Doug Cook, president of global specialty logistics at AmerisourceBergen, says one of the reasons for the expansion of the Melbourne facility is to be a “bridge” between clinical and commercial. “Our ICS 3PL business unit has long experience in the US market in logistics for pharmaceuticals with complex handling requirements; now we’re taking that model and combining it with the local knowledge of the World Courier network.” World Courier has 13 depots around the world, as well as 140 offices in 50 countries.
Another example of CTM logistics growth can be found at Parexel (Waltham, MA), which opened a European Coordination Hub and Distribution Center in Berlin-Schonefeld, Germany. It will service trials being conducted throughout Europe. “Our new European distribution center reflects a commitment to simplify the important end-to-end supply-management aspect of the drug-development journey,” said Mark Goldberg, president and COO of the company, in a statement.
The facility has 65,000 cu.m. of storage space, with capacity for medical devices and ambient, refrigerated and frozen medicinal products, including controlled substances. On-site Qualified Person (QP), Quality Control (QC) and production personnel will manage regulatory-compliance requirements. They will also streamline product import, receipt, storage, packaging and labeling, release, shipment, return and destruction timelines, says the company. New CTM depots are also being opened in Buenos Aires, Argentina and São Paulo, Brazil.
The packaging requirements for CTMs parallel those of commercial-scale shipments, with perhaps a greater emphasis on frozen delivery to preserve biological specimens. To address that, UPS Healthcare Logistics began the Temperature True Cryo service, in partnership with Cryoport (Lake Forest, CA). UPS will handle pickup, shipping and delivery of the Cryoport containers which, at customers’ option, can include the UPS Proactive Response Secure service that includes monitoring, insurance and intervention in shipment transitions. Cryoport, whose technology has been on the market for several years, employs liquid nitrogen rather than dry ice, which provides a colder temperature range (as low as -150°C) and avoids the “hazardous material” rating that CO2 operates under in airfreight. Cryoport has similar partnering agreements with FedEx and DHL.
Marken’s Dan Bell notes that ease of service is a desired goal among clinical labs, which generally do not have extensive resources for packaging design and logistics operations. That often translates into “universal packout”—a combination of insulation and coolants that can be used year-round, regardless of season. (The alternative, which is often used in commercial shipping, is one packout configuration for winter, and another for summer.) Simplifying the packout configuration provides savings on inventories, and better assurance that the package can meet performance targets. Also, to ensure package integrity, Marken recommends “hardshell” outer boxes for the shipment, rather than the corrugated cardboard often used for commercial shipments.
An inherent advantage that CTM logistics providers have is a robust outbound and inbound structure: in many cases, deliveries to a trial site are combined with a pickup of biological samples to be returned to a central lab as part of the trial. That, in turn, makes reuse of packaging somewhat easier, although, as Ariette van Strien, chief commercial officer for Marken, points out, usually the same package cannot be used in both directions. “A large number of sample return deliveries employ frozen conditions,” she notes. “Even so, interest in reuse or recycling is high among trial managers.”
A survey performed by Sonoco ThermoSafe last year pointed to high interest across the board in reuse/recycling: 51% of respondents indicated that they are reusing or recycling packages now; and 70% said that they are interested in setting up such programs in the future. Sonoco ThermoSafe approaches the issue in two ways: a recycling program (managed by the parent Sonoco organization, a leading packaging provider in many industry sectors) for the expanded polystyrene (EPS) insulation used in some of its packaging; and the Ship2Q service for refurbishment and reconditioning of containers for reuse. In the former case, EPS or other plastics are reconstituted for other industrial purposes; in the latter, obviously, the container goes back into use in life sciences logistics.
The drumbeat appears to be getting louder for support of reuse programs, something that many shippers (including life sciences) have indicated as an interest, but the cost of sustaining the programs has been a limitation. The economics work better with containers based on vacuum insulated panels, and programs have been set up in the past few years by Pelican BioThermal for its Credo Cube containers, CSafe (suppliers of vacuum-panel containers under the Acutemp brand), Cold Chain Technologies and others. CSafe’s program is called Repaq; Cold Chain Tech’s is GreenSmart; in Pelican’s case, the company is positioning reuse as part of an overall asset-management service, called ProEnvision, that entails tracking both inbound and outbound shipments.
Brian Kohr, president and CEO of CSafe (Dayton, OH), notes that a rigorous reuse program should include thermal testing of the container before putting it back into circulation, which the company now accomplishes both in the US and in Europe, through a recently opened packaging supply center in Amsterdam. “Some shippers reuse containers for years without retesting, but regulators are beginning to wise up to that practice,” he says. CSafe clients are averaging reuse rates of 74%—a potentially significant savings, since vacuum-panel containers generally cost several hundred dollars.
Va-Q-Tec (Wurzburg, Germany), which manufactures containers exclusively with vacuum panels, has an interesting variation on reuse: a container rental program. Eligible models range from full pallet sizes to 24-liter boxes.
Despite their higher cost, most vendors of vacuum-panel systems report growing sales (although, to be sure, there is inherent growth in the overall cold chain market). A year ago, Sonoco ThermoSafe introduced its Via line, which incorporates advanced, vegetable-oil based PCMs and vacuum panels. The Via line can be configured for frozen, refrigerated or CRT shipping.
Pelican Biothermal, through the Minnesota Thermal Science business it acquired in 2013, expanded its Credo Cube line of containers with DuraCube, adding a plastic shell to the design.
Packaging vendors are competing aggressively in all sectors of the clinical, commercial, and last-mile market segments, but the competition seems especially intense in pallet-size shippers used in airfreight. The gold standard, for years, had been the heavy-duty, metal boxes supplied by Envirotainer AB (Upplands Vasby, Sweden); CSafe, Luftansa Air Cargo and a few others now manufacturer comparable “unit load devices” (ULDs). These units have self-contained heating and cooling systems, powered by batteries (there are dry ice versions as well). Envirotainer expanded its line a few years ago with the RAP 2 unit, which can contain four US- or five European-size pallets and has a lighter, composite shell.
Against these “active” (powered) units, a growing array of passive containers is being offered. There has been industry chatter in the past couple years that some of these passive units did not meet their performance specifications in use, which of course can have disastrous consequences for the relatively large volumes of products they contain. “The first few designs that came on the market were tested against the vendor’s own performance standards, which varied considerably from vendor to vendor,” says Jamie Chasteen of Cold Chain Technologies. “Shippers are now doing their homework and using tighter performance specifications.” His company has had the KoolTemp pallet containers for several years now.
Sonoco ThermoSafe introduced a new pallet shipper in the past year, Envoy Euro Pallet Shipper, which incorporates convective channels (branded as Convectech) on the inside vertical sections of the container, thus requiring refrigerant packs only on the top and bottom of the unit. A US pallet-size unit is in the works. Additionally, it introduced an LD7 PMC unit, incorporating both the Convectech feature and interlocking corner panels, with either vacuum-panel or foam plastic insulation. (PMC and LD7 are container size designations.)
CSafe’s Brian Kohr notes that his company has had tremendous success with its active RKN pallet containers, but is looking at introducing a passive design in the near future. “There are situations where active containers don’t serve the customer well, such as delivering to remote locations that lack the equipment to recharge the container,” he says. “And while active units are generally regarded as more expensive, there are situations where they can provide better economies.” Ultimately, there’s a place for both technologies, and pharma shippers need to analyze the situations.