International Safe Transit Association (ISTA) Profiles & Standards for Temperature-Controlled Supply Chains

The International Safe Transit Association (ISTA) is a global organization comprised of shippers, carriers, suppliers, laboratories, and institutions focused on creating global quality standards and test protocols for transport packaging.1 Along with publishing test procedures, they certify packaging facilities, professionals and packing systems. This application note outlines the main ISTA documents relevant to pharmaceutical distribution, 7E and Standard 20. These have been created to help qualify temperature-controlled shipping containers according to the CDER’s process validation recommendations.2

To meet regulatory requirements, containers and packaging methods must be qualified, proving their performance in shipping temperature-sensitive products within required ranges throughout distribution.3 ISTA’s test procedures and standards were created to help cold chain managers and engineers achieve scientifically sound qualification protocols for packaging systems in a more efficient manner. To help you decide whether or not ISTA Standard 20 and 7E thermal profiles can aid in qualifying your cold chain processes, this application note describes, in brief, the scope, processes and costs involved.

Standard 7E & Standard 20 BackgroundISTA has two types of test protocols: performance tests and development tests. The former is a pass/fail assessment “used to determine the viability of a packaged-product to survive normal shipment”. The latter compares the “relative performance of two or more designs or the same design from different suppliers”.Most ISTA tests are called procedures because they have been validated as effective and because the testing methodology seldom changes. The most relevant tests that ISTA offers regarding cGMP compliance and qualification of your cold chain are Procedure 7E and Standard 20.

/ APPLICATION NOTE

COLD CHAIN COMPLIANCE

“ISTA 7E + Standard 20 = The first Global Method for Standardizing the Establishment of Insulated Shipping Container Performance” available at http://www.ista.org/forms/ISTAStandard20.pdf

Traditionally ISTA’s 7 series tests were a combination of protocols for qualifying equipment. These tests have been replaced by the 7E set of hot/cold temperature profiles used in combination with the Standard 20 testing procedure,4 which contains templates for design and operational qualifications. The 7E is the first data-based thermal profile created through the collaboration of a packaging standards association, packaging manufacturers, drug manufacturers, and logistics providers. Standard 20 outlines how to create test protocols.

ISTA requirementsIf you want your packaging systems to be certified by ISTA, you need three items to meet the requirements of Standard 20. First, you require two of your employees involved in documentation and reporting to be ISTA-certified. Second, you need your test protocol documentation to be in ISTA’s accepted format. Finally you’ll have to undergo and audit by an ISTA thermal transport lab auditor.

Standard 20 tests include design testing, thermal qualification, physical qualification and thermal qualification.5 The 7E profiles are used to see whether the package design is meeting product requirements. Further laboratory tests confirm the “accuracy and repeatability” of those tests. Then, physical qualification involves testing for package integrity and thermal qualification involves field testing for comparison against lab test results, with sensor placement the same in the field as it was in the lab.

Whereas the FDA offers guidelines on process validation that can be applied to qualifying the cold chain, ISTA’s 7E standard provides statistically validated test parameters. Such a standard allows for comparisons between real-world and lab tests of hot/cold profiles with thermal profiles derived from a 3-year study of both hot and cold shipping environments in 82 shipping lanes in America, Hawaii, Alaska and Puerto Rico.

According to ISTA’s overview of Standard 7E6 the thermal profiles therein can be used as a “standalone” standard in qualifying insulated shipping containers. Combined with Standard 20, 7E thermal profiles can be used for comparative analyses of shipping package thermal properties. The standards in combination also give comparison information on time and temperature ranges. Using statistically validated data will reduce the possibility for thermal profile data that is subjective to be accepted on its face. In addition, cold chain managers save time and costs on performing their own thermal performance testing with no validated statistical data for comparison.

The ISTA standards and document templates, profiles and test services are a cost-effective method of ensuring that temperature-sensitive pharmaceuticals and biologicals are shipped in a supply chain that has undergone rigorous design and performance qualification processes. Using ISTA to qualify elements of your cold chain will help ensure you can meet increasing regulatory scrutiny. It is important to note however that using ISTA standards does not replace the requirement for performance qualification. Standard 20 and the 7E profiles are the first protocols of their kind; they simply provide statistically validated data for comparison in creating your own qualified packaging.7

Standard 20 Requirements

Two ISTA-Certified Employees

ISTA AcceptedFormat

ISTAAuditor

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Ref. B211237EN-A ©Vaisala 2012This material is subject to copyright protection, with all copyrights retained by Vaisala and its individual partners. All rights reserved. Any logos and/or product names are trademarks of Vaisala or its individual partners. The reproduction, transfer, distribution or storage of information contained in this brochure in any form without the prior written consent of Vaisala is strictly prohibited. All specifications — technical included — are subject to change without notice.

ConclusionThere is no single regulation, standard or guidance for cold chain management, but with some knowledge of widely used standards such as those created by ISTA, you have some basic elements of a scientifically sound and justifiable cold chain quality management system. Unfortunately, the ISTA 7E profiles and Standard 20 have two major weaknesses. First, the cost of attaining ISTA qualifications a Standard 20 thermal lab is well over 20,000.8 Second, ISTA 7E profiles only apply to North America and related regions.9 Many countries have their own regulatory standards which, like North American standards, are often evolving. Since the U.S. exports nearly one-third of the pharmaceuticals sold worldwide,10 collaboration with local consultants may be the best method of ensuring a globally compliant cold chain.

Cold chain consultants can help with building or revamping quality management systems for supply chains.

Clearly, outsourced expertise can never replace in-house competence in any regulated industry. Understanding critical aspects of cold chain quality—such as how to develop a cost-effective means of qualification— is a necessity for managing ever more complex cold chain logistical issues. Nothing is likely to replace the need for senders to qualify their insulated shipping containers and their function during transport. However, having a standard approach can aid in creating criteria for prequalified packaging options for regulated products. If standards like ISTA 7E and Standard 20 attained widespread acceptance and implementation, it could result in significant savings in creating an effective and compliant cold chain.

For more information on cold chain applications, contact your local Vaisala representative, accessible here: www.vaisala.com/lifescience

Sources1 From “Guidelines for Selecting and Using ISTA Test Procedures and Projects” 2012, retrieved 6/8/2012 http://www.ista.org/forms/ISTAGuidelines.pdf

2 See “Guidance for Industry, Q7A Good Manufacturing Practice Guidance for Active Pharmaceutical Ingredients” ICH, 2001 retrieved 6/11/2012 http://www.fda.gov/downloads/regulatoryinformation/guidances/ucm129098.pdf and the CDER’s list of guidance documents, retrieved 6/11/2012 http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm079645.pdf

3 Not covered herein, but also relevant is the ASTM D3103 “Standard Test Method for Thermal Insulation Performance of Distribution Packages” purchased online, retrieved 6/11/2012 http://www.astm.org/Standards/D3103.htm

4 The 7E thermal profiles released in 2012 have replaced the 7D thermal profiles document: “7D: Thermal controlled transport packaging for parcel delivery system shipment”. See “Testing Standard for Thermal Transport Packaging used in Parcel Delivery System Shipment” Retrieved 6/11/2012 http://www.ista.org/forms/7Eoverview.pdf

5 “Testing Standard for Thermal Transport Packaging Used in Parcel Delivery System Shipment” retrieved 6/11/2012 http://www.ista.org/forms/7Eoverview.pdf

6 Overview of Standard 7E and Standard 20, retrieved online 6/11/2012 http://www.ista.org/forms/7Eoverview.pdf

7 “The ISTA 7E Thermal Profiles and how to make them work regionally” Modality Solutions blog, retrieved 6/14/2012 http://www.modality-solutions.com/the-ista-7e-thermal-profiles-and-how-to-make-them-work-regionally/

8 “Impact of ISTA 7E” http://www.samedanltd.com/ ?mod=magazine&id=15&page=article&issid=148&pid=2885&post Retrieved 8/6/2012

9 Hawaii, Alaska and Puerto Rico

10“Pharmaceuticals & Biotech Industry Global Report 2011” International Network of M&A Partners report, p.24 states: “IMAP At present, the global pharmaceutical market is dominated by the US, which accounts for about 28 percent of global sales in 2009, followed by the EU, accounting for nearly 15 percent, and Japan for 12 percent. Together, these three markets represent nearly 55 percent of the global market.” Retrieved 6/14/2012

Consultant Services:

▪ Regulatory compliance, local and/or global

▪ Primary/Secondary package design

▪ Qualification processes (OQ, PQ, re-qualification)

▪ Simulation testing

▪ Route-to-market assessment and optimization