An article exclusively for ColdChainInfo.com by cold chain expert Jeff Wodrich
Introduction
Negotiating the many facets of storage and distribution of temperature controlled or cold chain products can be a difficult task. When dealing with products that not only hold significant monetary value but are also critical components to the quality of human life, the stakes are high. Companies who manufacture and distribute healthcare related products such as those in the Biotech, Pharmaceutical, Diagnostic and Blood and Tissue industries are aware of this and so are the regulatory bodies who govern their activities. There has been a growing awareness and therefore a growth in regulatory documents and industry guidance documents around the world which can be difficult to navigate for those who are tasked with the distribution of a cold chain product. There are numerous companies, products, regulations, conferences and opinions available that can be helpful in finding ways to approach cold chain management. Although you would be hard pressed to find a single standard, document or guidance that can apply to every situation perfectly, it is important to be aware of the those that do exist so that you can be as prepared as possible to properly manage your Cold Chain products from the point of manufacture through storage and distribution and all the way to the final user. This article will attempt to provide a brief summary of the various documents and organizations that are shaping this critical industry.
USP (United States Pharmacopeia)
The United States Pharmacopeia (USP) is the official standards setting authority for healthcare products manufactured, sold and distributed with in the United States. Additionally, many USP standards are recognized around the world. If you are involved in storing or transporting a healthcare product, you should be specifically aware of USP General Chapter <1079> Good Storage and Distribution Practices. General Chapter <1079> is a guidance on “Good Distribution Practices” (GDPs) and applies to practices surrounding the maintenance of a products “quality and purity” during transportation and storage. In essence, it is a guide on how to develop the proper processes and (of course) documentation that lead to product quality and patient safety. General Chapter <1079> was first published in 2005 and has just recently been revised, as seen at http://www.pharmacopeia.cn/v29240/usp29nf24s0_c1079.html. Although General Chapter <1079> deals with healthcare distribution practices beyond temperature controlled distribution, there are specific references to cold chain in the chapter. General Chapter <1079> is at the core of good distribution practices for cold chain products and is a good place to start if you want to build procedures that can stand up to regulatory scrutiny.
WHO (World Health Organization)
The World Health Organization (WHO) serves a number of roles with in the United Nations health system. One of those roles is to provide leadership on global health standards and policies. The WHO has also issued a document that addresses cold chain distribution: working document QAS/04.068 on Good Distribution Practices. The goal of the document is to …”ensure the quality and integrity of pharmaceutical products during all aspects of the distribution process.” It is important to note the word “all” in this statement. As in USP General Chapter <1079> the implication is that good storage and distribution includes everything from the point of manufacture to the patient. This document specifically addresses temperature and relative humidity stating that “where special storage conditions are required … these should be checked, monitored and recorded.” Working document QAS/04.068 is an important read for those with cold chain responsibility.
PDA (Parenteral Drug Association)
The Parenteral Drug Association (PDA) is an active organization that is comprised of individual members from the pharmaceutical and biopharmaceutical industry who work together to influence industry practices as well as regulation of the industry. Within the PDA there are a number of interest groups with particular areas of expertise. One such group that has formed under the PDA’s umbrella is the Pharmaceutical Cold-Chain Interest Group (PCCIG). In the past 6 years, this group has published 2 technical reports (3 including revisions) through the PDA. The first was a general guidance that addressed the main issues surrounding the Cold Chain called PDA Technical Report No. 39 (PCCIGTR 39), Guidance for Temperature Controlled Medicinal Products, Maintaining the Quality of Temperature-Sensitive Medicinal Products through the Transportation Environment. This guidance was first released in 2005 and a revised version was released in 2007. The latest version of Technical Report No. 39 has become one of the most influential documents currently available. It is a comprehensive, guide on developing a cold chain management system. It encompasses packaging design and qualification, distribution processes, and creates the essential framework needed for developing good cold chain practices. Additionally, the PCCIG released a second technical report in 2010, Technical Report No. 46 Last Mile. This is more focused on Good Distribution Practices for the proper handling of cold chain products in the final stages of distribution.The PCCIG is currently looking to publish additional documents that will further add to the relevance and influence of this group as a guiding force in cold chain for healthcare products.
ICH (International Conference on Harmonization)
ICH, the International Conference on Harmonization purposes to bring together European, Japanese and US regulatory bodies related to healthcare products. “ICH's mission is to achieve greater harmonization to ensure that safe, effective, and high quality medicines are developed and registered in the most resource-efficient manner.” The document, International Conference on Harmonization (ICH) - Guidance for Industry: Q1A(R2) Stability Testing of New Drug Substances and Products has significant application to cold chain distribution, particularly in relation to managing temperature excursions within the distribution environment. As stated in the document: “a drug product should be evaluated under storage conditions (with appropriate tolerances) that test the thermal stability and, if applicable, its sensitivity to moisture or potential for solvent loss. The storage conditions and the lengths of studies chosen should be sufficient to cover storage, shipment, and subsequent use.” Furthermore, “data from the accelerated storage condition and, if appropriate, from the intermediate storage condition may be used to evaluate the effect of short term temperature excursions outside the label storage conditions (such as might occur during shipping).” Understanding how to apply your products thermal stability to your processes is key to developing a robust and effective system for the cold chain.
IATA (International Air Transport Association)
The Perishable Cargo Regulations (PCR) manual published by IATA, International Air Transport Association currently includes the suggested use of their time and temperature label to ensure proper handling of temperature sensitive healthcare products. The adoption of this label has begun and is currently voluntary but that may change in 2012 when IATA will require that all healthcare shipments use this label. This upcoming change could have significant impact on the ability to move products effectively through the air-freight distribution system. Keeping up to date on the developments surrounding the ongoing implementation of IATA’s Time & Temperature Label for Healthcare Products could prove valuable.
Packaging Design and Testing Standards
There are other documents that address the specific areas within the cold chain that are also helping to shape industry practices. ISTA, the International Safe Transit Association and ASTM, the American Society for Testing and Materials have both been involved in creating standardized methods for testing temperature controlled shipping containers. ASTM’s D3103 was issued in 2007 as a test method for evaluating the performance of thermal insulated packaging. This standard is widely referred to by thermal test labs that qualify (Operational Qualification) cold chain packaging. ISTA released their Standard 20 process in 2010. Standard 20 incorporates both design and qualification processes creating a framework for the entire progression from designing a cold chain solution to performing both operational and performance qualification testing. Coupled with Standard 20 is Standard 7E. Standard 7E is a standard test method for cold chain packaging. Included are ambient test profiles derived from real world data. Both organizations provide certifications for test labs who qualify this type of packaging and these test labs can be found on the ASTM and ISTA web sites. When starting the process of developing and qualifying cold chain packaging it is imperative to have an understanding of these standards.
Concluding Statements
The documents and guidance referred to in this paper do not represent a comprehensive list. Many regulatory bodies within individual countries have their own regulatory standards that apply specifically to distribution to, from, through and within that country. This article is meant to provide an introduction to the core guidance in the cold chain industry as a basis for further investigation. In the end, understanding these core guidance documents provides the framework for understanding how to approach the supply chain for temperature controlled healthcare products.
Author
Jeff Wodrich has extensive cold chain experience in many areas within the cold chain industry. He currently works as Director of BioPharma Solutions at Pelican Products, Inc.