A change in the climatic zones as defined by the International Committee on Harmonization has gradually made its way to U.S.-based drug manufacturers. In late 2005, ICH advised that stability conditions for Zone IVa (Tropical Dry) be changed to 30°C/65% relative humidity and for Zone IVb (Tropical Wet) changed to 30° C/75% relative humidity.
Why point out a five-year-old change now? Daniel Stagnaro, Klöckner Pentaplast’s business manager of pharmaceutical films for the Americas, says that the ripples of the changes instituted in 2006 have been reaching the industry in 2010. “This change, among others, was introduced to accommodate the storage and stability conditions used by the ASEAN countries who challenged the ICH and the WHO in request [for] test conditions that represent the reality of their climates (Brunei, Cambodia, Indonesia, Laos, Malaysia, Philippines Singapore, Thailand, and Vietnam). Several others countries in South America and Africa decided to participate on the same tropical wet category and were also included (Bolivia, Brazil, Colombia, Cuba, Equator, Peru, Suriname, and Venezuela),” he says.
Most U.S. climate zones are Zone II or Zone III, but U.S.-based drug makers are packaging drugs for Zone IVa and Zone IVb regions, and “some materials may not be adequate now for IVb,” says Stagnaro. “Packages that were developed to withstand moisture levels of 50–55% relative humidity now have to withstand 65% and 75% relative humidity.” There were no changes to temperature or time, he adds.
Drug companies often select packaging materials to accommodate worst-case conditions, and Zone IVb fits that definition. “I don’t know of many companies that package drugs differently for different regions,” he adds.
The change may be hitting drug makers now because “most companies redo their stability studies every two years,” Stagnaro reports. If drug stability is not holding during studies under the new guidelines, drug makers must take action. “We have been helping drug makers over the past year redesign the cavities in their blister packaging using our BlisterPro software. The thickness distribution during thermoforming varies, so companies must look the thinnest distribution for the worst case.”
But if redesign doesn’t help, “companies have had to change their packaging materials,” Stagnaro says. Interestingly, drug companies that had originally built in a safety margin of about 20% when selecting materials and designing cavities should be OK under the new stability conditions, Stagnaro observes.
As the pharmaceutical industry continues to evolve into an increasingly global one, such stability test changes will undoubtedly affect U.S.-based drug packagers. Packages that once sufficiently protected drugs around the world may now require redesign or redevelopment. If you have recently reevaluated your packages because of the change in ICH guidelines, please share your story with us!
Daphne Allen, Editor