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products from the start of production through dispatch from their main supply warehouse until the products reach the first point of shipment. This point may be a local operating company, wholesaler, or a hospital. However, while accountable, the drug sponsor can only have an indirect influence on cold chain compliance. The drug sponsor may indicate how the products should be stored and handled based on evidence from preclinical studies and basic knowledge about therapeutic drug physico-chemical properties and requirements. An effective cold chain strategy must also recognize when responsibility lies with a support services component of the supply chain.

Specific compliance requirements for establishing an effective cold chain structure and governance strategy are based upon a combination of regulatory requirements defined by the corresponding regulatory body such as FDA, EMA, WHO, Health Canada, etc. However, industry best practice guidances from organizations such as the International Safe Transit Association (ISTA), United States Pharmacopeia (USP), International Air Transport Association (IATA), International Committee on harmonization (ICH), and the Parenteral Drug Association (PDA) offer important, practical information on the details and considerations required.

Product Stability ICH

Understanding the impact of environmental variation on a product’s safety and efficacy is a prerequisite to establishing a cold-chain strategy. ICH Q1A (R2), which addresses stability testing of new drug substances and products, is a central industry best practice for building an effective stability program. This data will be used to understand the impact, considering the magnitude and duration of temperature excursions that could occur in the distribution process. Data derived from intermediate and accelerated environmental conditions can be used to determine the potential impact of short-term excursions that could occur in the shipping and distribution process.

Packaging Design and Qualification USP

The United States Pharmacopeia (USP) 39 chapter 1079 describes “Good Storage and Shipping Practices” with guidance for handling cold chain pharmaceutical products. This chapter provides the requirements for ensuring a product’s “identity, strength, quality, and purity” across the entire distribution channel - from manufacturer to end user covering the handling and storage of products in warehouses, during transit, and in pharmacies. This chapter states: “Operational and performance testing should be part of a formal qualification protocol.” Thermal testing qualification may be performed using a validated controlled temperature chamber or actual transit testing using the expected transport method and shipping lanes (from origin to destination). Certified test labs use validated environmental chambers to simulate the ambient temperature that the package may encounter using standard profiles that simulate the transit of the package through the distribution channel with changes in temperature and duration. The profiles are established by the International Safe Transport Association (ISTA) and cover both land and air transport of various times and package configurations. Detailed test reports are obligatory to demonstrate support of the regulatory requirements.


The ISTA organization focuses on the specific concerns of transport packaging. ISTA is the leading industry developer of testing protocols and design standards that define how packages should perform to ensure protection of their contents during the ever-changing risks of the global distribution environment. ISTA 2 provides the requirements and standards protocols for environmental testing including temperature, pressure and humidity. | 23 | July/August 2016

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