The USP standard, currently in draft form, is an effort to provide recommendations for end-to-end supply chain integrity
In quantifying globalization in the pharmaceutical industry, there is an abundance of supporting statistics: According to the US Food and Drug Administration (FDA), roughly 40% of medicines sold in the United States are produced abroad (80% of the active pharmaceutical ingredients used in finished products); half of medical devices used in the country are imported; and drug imports to the United States are increasing by 13% annually. While globalization provides tremendous opportunities, the associated risks have been on full display in recent years. Public visibility of the cracks in the system began in 2007—08, when batches of heparin adulterated with over-sulfated chondroitin sulfate resulted in harm or death to a still-unknown number of US patients; and most recently with FDA warning medical clinics they may have obtained counterfeit versions of the cancer medications Avastin and Altuzan. Such events challenge the prevailing notion that counterfeit and/or adulterated drugs are not a problem in the US, or in developed nations overall.
The threats do not end there: Theft and diversion, natural disasters, and other obstacles can ultimately result in poor-quality medicines reaching patients—potentially jeopardizing people’s health and safety. While stakeholders—regulators, lawmakers, manufacturers, standards-setting bodies, practitioners and patients—seem to concur that this is a paramount concern, disagreement reigns over some of the more promising proposed solutions (e.g., track-and-trace technology). Moreover, even when there is general agreement, a tangled regulatory environment (including an intricate system of state and federal oversight domestically, and widely disparate or even absent regulations internationally), limited resources and technological issues make the situation fraught with complexity.
This is not to say that nothing has been done, including by the pharmaceutical industry itself. Many companies invest substantial resources in protecting supply chains. Furthermore, numerous supply chain guidance documents have been developed across the industry. However, these documents generally tackle individual aspects of the supply chain. What is lacking is an overarching set of best practices that documents a holistic approach to protecting supply chains, from beginning (sourcing of raw materials) to end (final delivery of medicine to patient)—including everything in between. Given the number of nodes in the modern pharmaceutical supply chain—with each point of handoff presenting opportunity for either unintentional error or purposeful mischief—such a resource could play an important role.
A nonprofit scientific organization, the US Pharmacopeial Convention (USP), develops standards for the identity, strength, quality, and purity of medicines and ingredients. These standards are included in the United States Pharmacopeia—National Formulary (USP–NF), and are legally enforceable in the United States by FDA. (They are also used broadly internationally.) In addition to standards for individual medicines and ingredients, USP–NF includes general chapters that either contain tests or other information that apply to multiple medicines or ingredients (often required to demonstrate compliance to specifications), or provide non-mandatory information on various topics affecting medicines’ quality.
USP General Chapters
USP’s General Chapter <1079> Good Storage and Shipping Practices, initially developed in 2005 and updated in 2010 by USP’s Packaging, Storage, and Distribution Expert Committee, was the first general chapter to address distribution practices by setting forth recommendations related to the storage, distribution and shipping of pharmaceuticals. This is widely used by industry today. Building upon this, USP recently proposed the new General Chapter <1083> Good Distribution Practices—Supply Chain Integrity. This informational document is intended as a resource outlining the essential elements of an effective overall strategy for supply chain integrity, helping to ensure that medicines are not adulterated or counterfeited, and are transported to their intended destination with their quality intact.
As the general chapter is written now, it is divided into four sections: importation, counterfeit drugs and medical devices, best practices to combat counterfeit drugs and medical devices, and diversion and theft. However, USP has acknowledged from the time it released the new general chapter in December 2011 that it was seeking broad input from the entire spectrum of stakeholders, and it anticipated significant revision. USP held a workshop to obtain feedback on the proposed general chapter in May 2012, in addition to publishing it in the free Pharmacopeial Forum—the online vehicle through which USP formally accepts comments on proposed standards.
While many disparate views were expressed at the workshop, USP did hear overall support—and a significant need—for this resource. The benefits of having a publically available document that all stakeholders in the industry—regardless of their size, role or geographical location—can rely upon would be a tremendous benefit. Even the largest and best-resourced manufacturers may rely on smaller players to supply ingredients or distribute their products.
While the proposed general chapter is undergoing significant changes based on feedback received (a key benefit of USP’s public comment process), and likely may evolve into multiple general chapters, USP aims to develop something that is sufficiently substantive, but non-prescriptive so as not to hinder stakeholders. This is a tough challenge, but one that USP is in a unique position to address.
ABOUT THE AUTHOR
Desmond Hunt, PhD, is senior scientific liaison to the USP Packaging, Storage, and Distribution Expert Committee. The draft USP <1083> standard is available at: www.usp.org/sites/default/files/usp_pdf/EN/USPNF/revisions/c1083.pdf