A key factor in maintaining the quality of a pharmaceutical product throughout its shelf life is the integrity of its packaging.
Preventing moisture from permeating through the packaging is an important function of the container-closure system used for
medicines. Today, moisture uptake is a common cause of product package failures in the pharmaceutical industry—and a topic
that the US Pharmacopeial Convention (USP) is addressing with an upcoming revision to United States Pharmacopeia–National Formulary (USP–NF) General Chapter <671> Containers—Performance Testing for Plastic Containers.
Updating General Chapter <671>
Initially developed in the 1970s primarily for use by pharmacists dispensing medications into the familiar amber vial, General
Chapter <671> has become heavily relied upon over the years by pharmaceutical manufacturers, packagers, repackagers, and FDA
because it is referenced in the agency’s Guidance for Industry: Container Closure Systems for Packaging Human Drugs and Biologics. However, the general chapter has had only minor edits and additions in intervening years. Because it is being used beyond
its original scope and utilizes an older permeation test, modifications to the general chapter have become necessary. This
effort is supported by industry, and the newly proposed standard builds on method development work completed over the past
decade by the Product Quality Research Institute (PQRI). PQRI is a nonprofit consortium of organizations that conducts research
to generate specific scientific information on issues of interest to FDA and to standards-setting organizations such as USP.
One of the key ways the general chapter is being updated is through the proposal for a new moisture vapor transmission rate
test method for solid oral-dosage forms. The current test method is a gravimetric method that is not very robust, which can
lead to variation in test results. The proposed new method is also gravimetric, but is more reproducible and uses more rigorous
environmental test conditions. Both the older and newly proposed methods measure weight gain over time. However, the information
yielded by the new method will give end-users a more accurate assessment of how much protection their packaging is affording
to the final product.
The proposed general chapter, including the new method for calculating moisture vapor transition rate, aligns with the recently
released ASTM International standard: “ASTM D7709–12 Standard Test Methods for Measuring Water Vapor Transmission Rate (WVTR)
of Pharmaceutical Bottles and Blisters.” ASTM sets international voluntary consensus standards. The revised USP general chapter
is included in Pharmacopeial Forum 39(2) March–April 2013, and USP invites comment on the proposal at www.usp.org/usp-nf/pharmacopeial-forum.
An underlying issue relevant to this activity is the USP classification system for packaging. At present, USP specifies the
categories of “well-closed” and “tight” in its classification, with the latter used much more frequently. Certain medications,
however, require packaging beyond “tight”—requiring no moisture permeation. While no change to the classification system was
included in the new proposal, USP would like to open a dialogue with regulators, manufacturers, contract packagers and repackagers,
and other stakeholders about whether, and how, this classification system could be expanded. The classification system—along
with applications of the new <671> method, manufacturer case studies, current regulatory thinking from FDA, and other areas
affected by the new method (e.g., desiccant choice, which is particularly important with the method change)—will be among
the important areas of discussion at a May 20–21, 2013 workshop cosponsored by USP and PQRI in Rockville, MD.