Protecting Temperature-Sensitive Pharmaceuticals

As temperature-sensitive drug products travel worldwide, packaging serves as the barrier to a potentially hostile ambient environment. Temperature-controlled shippers not only maintain payloads within frozen, refrigerated, or controlled-room-temperature (CRT) ranges, but also help brand owners and other supply chain participants meet good distribution practice (GDP) standards. The careful control of payload temperature not only protects product quality, but also reduces losses due to temperature excursions and ensures profitability.

“There is plenty of evidence that suggests that a product’s temperature (and the associated fluctuations) can have profound impacts on a product’s stability, and therefore, its therapeutic effectiveness,” explained Désirée Valentine, senior supply-chain manager at BioConvergence, a contract service provider offering formulation development, testing, production, and supply chain services, in a statement associated with a presentation at the 11th Annual Cold Chain GDP & Temperature Management Logistics Global Forum, organized by IQPC, Sept. 30–Oct. 4, 2013 in Chicago, IL (1).

“We are seeing growth in the number of temperature-sensitive shipments due to the increasing cold-chain regulations and expansion of generic products,” said Dirk Van Peteghem, vice-president of UPS Healthcare Logistics, in an announcement discussing UPS’s participation at the same meeting (2).

Other driving forces in the temperature-controlled packaging marketplace include an expanding number of biologics, more attention to CRT distribution, and rapidly growing drug sales in emerging markets. The 2014 Global Cold Chain Report, published by IQPC/Cold Chain IQ, predicts more than 50% of the world’s best-selling drugs will require cold chain protection by 2016. As a result, the study forecasts dramatic growth for the cold-chain logistics market through 2017 with increases of 57% in emerging markets, 46% in Asia, 21% in Europe, and 18% in North America (3). Another market study anticipating strong growth, Global Healthcare Cold Chain Logistics Market Report & Forecast (2013-2018) by IMARC Group, projects an increase in market value from $7.3 billion in 2013 to $11.4 billion by 2018 (4).

Despite advances in temperature-controlled logistics technology and best efforts by manufacturers and other participants in the supply chain, problems still occur. For example, Ampio Pharmaceuticals experienced a disruption in its clinical study of Ampion, an injectable anti-inflammatory for knee pain associated with osteoarthritis, when both the study drug and placebo experienced exposure to temperatures below 15 ºC and may have frozen during shipment to clinical sites in January 2014. “Pivotal clinical-trial drug specifications dictate precise temperature and handling conditions for all study drug product in order to assure that the conclusions about the safety and effectiveness of the tested drugs will be accurate and repeatable during routine clinical use,” reported Michael Macaluso, CEO of Ampio in a statement. “The drug temperature specifications were set because Ampion may lose potency if it is exposed to temperatures approaching freezing” (5). Although the cold-chain lapse delayed the release of the analysis of single-injection study data, other aspects of the clinical trial are proceeding as planned, and Ampio is working with FDA to provide acceptable data to support a biologic license application (BLA). As a result, the company anticipates it will file its BLA for Ampion on schedule by the end of the first quarter of 2015 (6).

Trends in temperature-controlled logistics include growing availability of prequalified shippers, which simplify the validation process, more sophisticated supply-chain services, rising interest in reusable packaging, and advances in temperature-monitoring technology.

References
1. BioConvergance, “BioConvergence Presents Case Study on Temperature Controlled Pharmaceutical Products,” Press Release (Bloomington, IN, Oct. 18, 2013).
2. UPS, “UPS Introduces New Shipment Service Levels for Its Temperature True Portfolio,” Press Release (Atlanta, GA, Oct. 2, 2013).
3. IQPC/Cold Chain IQ, 2014 Global Cold Chain Report, p. 4, accessed Aug. 12, 2014. 
4. MarketReportsOnline.com, “Healthcare Cold Chain Logistics Industry 2018 Forecasts Research Report Now Available at MarketReportsOnline.com,” Press Release (Dallas, TX, Dec. 26, 2013).
5. Ampio Pharmaceuticals, “Ampio Reports That Due to Temperature Deviations Below Product Specifications During Shipments to the Ampion STEP Study Clinical Sites, Release of Data Will Be Delayed,” Press Release (Englewood, CO, August 21, 2014).
6. Ampio Pharmaceuticals, “Letter to the Ampio Shareholders in Regard to the STEP Study and Ampio’s Plans for the Ampion BLA,” Press Release (Englewood, CO, August 25, 2014).

For further information, read the full article, Packaging Addresses Cold-Chain Requirements, in the upcoming October issue of Pharmaceutical Technology.

—Hallie Forcinio is Pharmaceutical Technology's packaging editor, editorhal@cs.com.