Cold Chain Regulation Tightens Globally

The PDA Cold Chain Management Conference, typically held in March near PDA’s Bethesda, MD headquarters, is one of two annual meetings organized by the Pharmaceutical Cold Chain Interest Group (PCCIG), a voluntary working group of industry technical experts and managers concerned with temperature-controlled shipping. The meeting (March 1-2) also brought out about 30 exhibitors of products and services for life sciences companies with temperature-controlled lab and commercial materials.

Business is generally good for providers of cold chain services; the field benefits from a trend toward more cold-chain products, and the ever-tightening requirements of national health authorities around the world, who want to be assured that temperature-sensitive pharmaceuticals are being safely delivered. According to various speakers, Brazil, South Korea and Turkey recently updated their cold-chain shipping regulations.

Manufacturers are confronting these tightening requirements in two ways: expanding the use of data logging to provide documented shipping conditions; and expanding the use of stability data (which needs to be generated for commercial products anyway) in order to give them a definite “time out of storage”—i.e., when temperature excursions are witnessed, which could lead to rejection of a shipment if its transit conditions are not documented.

There is an ICH standard, Q1X, in the works for pharmaceutical stability in transit and under temporary excursions that would build on the existing Q1A standard, which is used to define stability testing and shelf life. A PCCIG task force composed draft document last year that is currently under review by PDA; if it becomes a PDA-referenced guidance, it can then pass to ICH for consideration as an international guidance document. A key element of this concept is the “stability budget”—the amount of time (or the extent of the excursion) that is permissible for a drug shipment before it becomes unacceptable. In theory, supply chain partners (a warehouse manager, a shipping company, a retail pharmacy stockroom) could “share” this budget in some fashion, but the details of that remain to be worked out.

“Firms have used the idea of a stability budget to assign permissible time-out-of-storage for packaging and labeling operations for refrigerated drug product for some time,” said Bob Seevers, principal regulatory consultant at Eli Lilly and co-chair of the task force. “This concept has been expanded in the draft guidance document from PCCIG to include storage and distribution as well.”

Another broad theme of the meeting is the establishment of “Good Distribution Practices” (GDPs) as part of the management and regulation of pharmaceutical transportation and storage. GDPs exist, in various forms, in a number of countries or regulatory jurisdictions (notable the World Health Organisation), and their principles are in place in many contractual agreements between manufacturers and service providers. Establishing GDPs as consistently enforced practices for regulators will make the practice more uniform nationally and internationally.

PCCIG task forces have looked at how GDPs could be set up for refrigerated storage, active shipping containers, and transportation vehicles (such as reefer trucks). The process will look very familiar to manufacturing compliance managers accustomed to GMPs. The equipment and work processes undergo a design qualification (DQ); installation qualification (IQ); operational qualification (OQ) and performance qualification (PQ).

Dave Ulrich, a distribution quality assurance manager at Abbott Labs and group leader within PCCIG, reviewed the 35 countries or jurisdictions where some form of GDP is proposed or in place. Many share the same basic principles: document and verify work processes; test and monitor equipment (including temperature mapping of containers); document actual performance of cold chain tasks. “This is going to be the year of controlled-room temperature shipping,” he says. “GDP systems will extend up into the manufacturer supply chain, and down to commercial deliveries, across all temperature ranges.”

More capacity, more monitoring

While equipment exhibitors at the PDA meeting mostly had extensions or refinements of existing products, some of the carriers and 3PLs had significant announcements of new capacity. Earlier in the year, UPS Healthcare Logistics (Atlanta) had announced a 20% expansion of its worldwide network of dedicated facilities, now amounting to over 4 million sq. ft. New or expanded facilities are being opened in Singapore (43,000 sq. ft., with dedicated cold chain storage), Venlo, Netherlands (245,000 sq. ft.), Burlington, ON (177,000 sq. ft.) and Louisville, KY, adding to the facilities surrounding UPS’ Worldport global air hub.

Singapore is also the focal point of an expansion by Marken Ltd. (London; US offices in New York), which has relocated and expanded a clinical logistics depot there. The 14,500-sq. ft. facility will include a drug vault, storage a 15-25, -2-8, -20 and -80°C temperatures, kit building and specimen storage. Last year Marken, which operates globally, opened a new facility in Tokyo to add to its expanding volume of business in the Asia-Pacific region.

Longistics (Research Triangle Park, NC), a global 3PL provider with a longstanding pharma logistics business, has opened a Commodities Exhibition Center in Suzhou, China, which “will generate opportunities that accelerate the export of products from North Carolina and U.S.-based companies to China,” according to the company. The Suzhou Industrial Park is essentially a free trade zone in China; through it, importers will be able to access Jiangsu Province specifically, and the entire nation.

DHL Global Forwarding Life Sciences (US HQ: Newark, NJ) is upgrading cold chain services at 20 of its regional facilities, called competence centers, where pharma products are transited. The company has obtained Qualified Envirotainer Provider (QEP) accreditation at its Brisbane, CA, facility, and will enhance others over this year. Its European less-than-truckload (LTL) services are also being extended into the Middle East.

Envirotainer itself, the Lagga Marma, Sweden, developer of passive and active unit load devices (ULDs) that can ship pallet-sized, temperature-controlled product in aircraft cargo holds, announced that it had been cleared by FAA to qualify its equipment to be used in US domestic shipments. According to the company, this did not come about via an equipment modification, but rather through a bilateral agreement between FAA and the air authorities in the EU. Envirotainer units (RKN e1 and RAP e2) have been used in flights by non-US carriers, but were barred from US carriers originating in the US. The RAP e2, which has capacity for four pallet loads, was introduced last year and completed its first shipment in February, a delivery for Teva Pharmaceuticals by Air France-KLM.

FedEx Corp. (Memphis) has commercialized its specimens/deep frozen service in partnership with CryoPort (San Diego), involving a prefilled liquid-nitrogen container leased by FedEx; a customer simply orders the 300-cu. in. container, adds the payload and puts a shipping label on, and FedEx both delivers the container and retrieves it when ready. FedEx is also in the process of reorganizing a number of its ground, air and special services into a HealthCare Solutions group.

FedEx—and others—are commercializing real-time data-logging and monitoring systems to enable shippers to track shipments not only by location, but also by temperature, using GPS, cellular and satellite systems. FedEx continuing refinement of its SenseAware System; DB Schenker and Kirsen Security (Berlin; US HQ in Berkeley, CA) gave a presentation on a multimodal container monitoring system of Kirsen’s that can provide both security and condition monitoring.

Meanwhile, TCP Reliable (Edison, NJ), which manufactures insulated packaging and does performance testing for life sciences companies, was displaying a new version of the Mirador xTag system, which uses a localized digital communications standard, Zigbee (IEE802.15.4), to allow battery-powered sensors and readers to communicate with each other; the reader can connect to wide-area networks for a global communications system. With the right engineering, the system could be used to monitor product in the warehouse, as it is moved onto a vehicle, and then during transit. PC