In May, the U.S. Pharmacopeia will host a workshop, “Pharmaceutical Packaging: Moisture Permeation.” One of the main functions of the workshop will be to discuss proposed new revisions to General Chapter <671> Containers—Performance Testing that will be included in Pharmacopeial Forum 39(2 ) March-April 2013.
USP’s Expert Committees are mandated to review chapters every three to four years, but the gravimetric testing method included in <671> for measuring moisture vapor transmission rates (MVTR aka WVTR) of containers has not seen a major revision in years, explains Dr. Desmond Hunt, senior scientific liaison for USP. “This chapter is pretty well entrenched. The chapter was first developed in the 1970s. It is widely used—by pharmacists, manufacturers, packagers, repackagers—and it is even referenced in FDA’s Guidance on Container Closure Systems.”
Industry has been looking forward to a new WVTR method for some time, furthers Hunt. “We need a more robust method, and we need one that reflects the containers used today,” he says.
USP has been working with the Product Quality Research Institute (PQRI), which Hunt says has been a “champion” for the development of a new method. “PQRI has worked for more than 10 years, designing experiments and collecting data to support a revision to the compendial method. The new method will include guidelines for testing the moisture vapor transmission rate (MVTR) for multiple-dose containers, such as bottles; the MVTR for high-barrier unit-dose packaging; and the MVTR for low-barrier unit-dose packaging,” explains Hunt.
Dan Malinowski, senior director, package technology & innovation at Pfizer, has served as chair of PQRI’s Container Closure Working Group (CCWG) for the last 10 years. He says that PQRI set out to decrease the regulatory burden for both FDA and drug manufacturers by increasing understanding of MVTR and container closure performance for solid oral dosage forms.
“The more we know about container closure system performance, the easier it will be to make changes to those systems,” says Malinowski. “We believe that if you can identify a proven acceptable range of container closure system MVTR performance for drug product stability, you can establish baseline conditions and make changes as long as you can prove the new system is equal to or better in terms of MVTR performance.”
Ten years ago, continues Malinowski, “the only performance methods available were USP Chapters <661> and <671>. It was well recognized there were faults with these methods. The methods contained packaging classifications for multiple and unit doses that were so broad that changes may have had a quantifiable effect on drug stability and yet still remained in the same classification. So PQRI set out to develop a new, more robust method for solid oral dosage forms that reports a specific MVTR value.”
The proposed new method is gravimetric, just like the existing one, but Malinowski calls it “more reproducible and discriminating,” using the more stringent conditions of 40°C, 75% RH. “Both the existing and proposed methods measure weight gain over time, but under the new method you can expect more weight gain because the more stringent conditions providing greater resolution. It provides a much better understanding of protective properties of blister films or of a particular bottle and closure system. Also, utilizing an MVTR-per-unit, or per-tablet, principle, could allow changes across packaging systems.”
Malinowski says that the revision of <671> won’t replace the existing method with the new one, just provide an alternative. He adds that the revision is the “next step” after the 2012 publication of ASTM D7709, “Standard Test Methods for Measuring Water Vapor Transmission Rate (WVTR) of Pharmaceutical Bottles and Blisters.”
“The science behind ASTM D7709 and the new method in USP <671> is the same, including the specific conditions, the duration of study, and the method of calculating MVTR,” Malinowski reports. The difference, of course, is that use of ASTM standards is voluntary, whereas compliance with Chapter <671> is mandatory.
“FDA does allow use of different methodology,” he adds. “In your submissions to FDA, you would need to include your rationale justifying the use of that alternate method. But we believe the proposed new method reduces that regulatory burden by providing an additional method in USP Chapter <671>.”
At the same time PQRI began its work, FDA was looking to draft prescriptive guidance documents—PAC PAK—but FDA “has changed course and become less prescriptive,” says Malinowski. FDA is expected to share FDA’s current regulatory perspective on the proposed revision to USP Chapter <671> at USP’s workshop in May.
“Our proposal is that users of this new MVTR method would be able to submit data to FDA demonstrating container closure equivalence rather than having to conduct a new drug stability test,” says Malinowski.
USP’s workshop will also include case studies from companies that have used the new method as well as guidance on how to report MVTR data and how to prepare desiccants.
Hunt adds that the current permeation tests listed in the chapter will also be discussed and hope to obtain feedback as to whether they need to be revised and if so what.
Also to be discussed at the workshop are the “well closed” and “tight” containers definitions. “Packaging systems are more robust these days,” says Hunt. “Think of a foil-foil blister—there is zero permeation, does the current definition of ‘tight’ adequately define the permeation protection provided by a foil-foil blister? We want to know stakeholders’ thoughts around this question and whether a new classification scheme is needed.”
Manufacturers of plastic films commonly used for low- and high-barrier blister packaging were not involved in the development of the proposed revisions, but Hunt says the workshop is meant to involve them along with all other stakeholders. “This chapter has pretty high impact—the more people participating in the workshop, the better.”
Malinowski, too, says the proposal will have impact. “The value comes in how you apply it. It could increase testing of container closure systems, but the positive far outweighs the need for extra drug product testing because of how it eases future changes,” he says. “And there are always drivers for change. We may want to use different containers or be asked to use different sizes or counts. We may also be dealing with resin changes, tooling changes, or supplier changes. ”
A preliminary agenda for the workshop, which will be held May 20-21, 2013, can be found on the USP website:http://uspgo.to/pharma-packaging-workshop.