The United State Pharmacopeia Convention (USP), the organization responsible for setting the public standard for drug manufacturing, plans to give Chapter PACKAGING & STORAGE REQUIREMENTS a serious makeover. The document provides some general definitions for packaging and includes specific directions with respect to storage conditions of drug products. The most complex of these —also the most confusing and contested, is that of Controlled Room Storage, or CRT. USP’s current definition of CRT states: “the temperature maintained at the usual and customary working environment of 20°–25° C.” But it is weighted down with a host of conditions and caveats and its lack of clarity has led to numerous debates on its intent and application—and long stymied shipping and distribution practices.

In a stimuli article that appeared in the November-December 2013 issue of USP Pharmacopeia Forum, a proposal was made to expand the range of CRT from its current 20°–25° C to a yawning 2°–30° C when appropriate for specific products. The article (authored by David A. Ulrich, Rishard Poska, and Arminda Montero of AbbVie; Chris Chandler of GS1; and Dr. Desmond G. Hunt Scientific Liaison at USP), lends strong scientific support for such a change. It should be noted that Chris Chandler and Dr. Hunt are both members of the USP Expert Committee (EC) for Packaging, Storage & Distribution, and any changes to Chapter would fall under that committee’s purview. Last month, in response to public comment generated by the article, the USP formed an Expert Panel under the auspices of the Packaging Storage & Distribution EC aimed at making recommendations for changes to Chapter with particular attention given to the definition of CRT.

Expanding the range of CRT is an interesting idea whose time has come, given the broad understanding and routine methodologies that industry now uses for performing stability studies and cycling studies that didn’t exist when USP’s definition first appeared in PF 35 nearly ten years ago. At that time, and to err on the side of caution, regulations for “cold chain” shipping practices required that distributed products had to be shipped under labeled storage conditions, regardless of unlabeled storage conditions supporting otherwise, and little consideration was given to CRT products. But such a dearth in stability data rarely exists anymore and changes in the global regulatory landscape have expanded to the point where it is no longer about “cold chain” but “good temperature management” for all drugs, including CRT products, especially during distribution.

Currently marketed CRT products are not labeled to conform with any standard naming convention as are cold chain products. CRT ranges on products often vary—even within an organization—and can also differ from the USP definition. In many instances, only an upper or lower limit is given.

The industry has come a long way in understanding product stability over the past decade. The current USP temperature range for CRT does not take into account recently expanded drug product stability data that heretofore pigeonholed products into unnecessarily tight storage conditions. This often leads to perceived and inconsequential excursions that do not adversely affect the quality of the drug product, but which trigger costly and time consuming investigation responses.

The industry’s active pursuit of expanding its knowledge and scope when it comes to understanding the stability of time and temperature-sensitive drug products has generated much data,. In many cases, these data strongly support storing and shipping products over a wider temperature range, as they are proving to be more thermally robust than we ever gave them credit for. This is good news for just about everyone (with the possible exception of specialized packaging providers). Shippers have long had difficulty meeting the requirements of CRT as defined by USP. Excursions encountered during shipment are frequent.

A change to the USP definition of Controlled Room Temperature would help facilitate the distribution of products, remove uncertainty, and promote long-term value to industry by building a strong foundation of stability data. This will allow for greater flexibility in how products are distributed, promote more efficiencies in distribution and require less specialized packaging, lowering packaging and shipping costs. It will also help to standardize the definition of CRT and develop a range more consistent with other countries’ Ministries of Health and current global distribution models. 

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Kevin O’Donnell
Contributing Editor

Kevin O’Donnell is senior partner at Exelsius Cold Chain Management Consultancy – U.S. He is a member of the USP Expert Committee on Packaging, Storage and Distribution, a temporary advisor and certified mentor to the World Health Organization (WHO), co-author of PDA Technical Report No. 39, a member of the International Safe Transit Association (ISTA) Thermal Council, and the former chair for the International Air Transport Association (IATA) Time & Temperature Task Force. He blogs at www.clutchcargo.us. He can be reached at kevin.odonnell@exelsius.us.