Issue link: https://www.e-digitaleditions.com/i/678483
"We take a holistic approach to the drug stabilization process, which is more than just predicting the failure in chemical assay or in the impurity level using Arrhenius or modified Arrhenius equations," Nair said. "We study all the physical attributes—hardness, friability, drug release, disintegration and dissolution times—and define critical quality attributes of the product." He said that the FDA is focused on assay and impurity, "but they don't like it when a product fails to release the drug properly even if the assay is correct." Degradation studies and package modeling also align with Quality-by-Design principles. "The FDA is saying to incorporate your quality not by testing but by understand- ing the process, understanding why you select a specific package. The report that we provide is in line with Quality by Design, and customers use that in their filing." Currently, regulators won't accept modeling results as a replacement for real-life ICH stability studies, but they will eventually, Nair said. "There is a long way to go but if they're really look- ing to speed up develop- ment, then they have to do it. It's a way to reduce healthcare costs by reducing the cost of manufacturing the medicines." Other kinds of modeling are also gaining acceptance, including for dissolution. "It's not just about assay. If your product becomes hard and it does not dissolve on time, that's a failure. Especially with a blister pack: If the hard- ness goes below the push-through force of the product and it breaks when patients push it through, that's a failure. I'm happy to see people working on [models for] that." Bilcare also offers FastPack, a package-design service that takes just 15 days. "The customer doesn't have to do anything except send us the tablet," Nair said. After that, the company provides the package's specifications and a drawing of the tooling required to make it. The barrier properties of the film are paramount, but the size and shape of the tablet also influence its in-package stability. "If you use the same film formed in a different way or drawn to different sizes, then you end up getting a differ- ent barrier," Nair said. Even small differences between the R&D and commer- cial packages can be important. "It can happen when you develop the package using an R&D pilot machine, do the stability study, and then write a [blister] specification on that basis," Nair said. "Then, when the production batch is run on a commercial machine using a different tool, the stability can fail, and they wonder why there's a problem, so they come to us. What we find is that the moisture permeation of the formed cavity was different from what they used for the stability study, even though the film had the same specifications." The Optima and FastPack services are available to any company. FreeThink Technologies Founded by Ken Waterman in 2011, FreeThink Technologies offers its stability and formulation modeling software, ASAPprime, under license. Or it will do the work in-house on behalf of customers. The focus is on the product, not the package, Waterman said. "The pack- age is important but it's only one of the things you might do with [the data]. You might want to see whether your generic product is as good as the originator. Or is a tablet as good as a capsule? Or is this capsule better than that capsule? It's not just packaging that people are interested in, but 'What formulation should be used? How do we make a tablet?'" That requires understanding a formulation's excipients. "We offer a process so you can make a tablet or capsule formulation in a much shorter time than the traditional way," Waterman said. "We don't do excipient compatibil- ity studies the old-fashioned way, so we've been able to speed the process up significantly." Results are typically ready in 3 weeks. By using data based on a range of exposure conditions, FreeThink's modeling often represents reality better than extrapolations from long-term stability tests, Waterman said. Those tests, he said, can be "noisy" because each analysis is done independently and often involves differ- ent analysts and instrumentation. ASAPprime is also more accurate because it doesn't assume linearity, as the ICH tests do. "They assume whatever happened in 6 months you can just double and see what would happen in 1 year, 12 May 2016 Tablets & Capsules Companies also want to understand whether temperature or moisture excursions will impair their products. Bilcare's Optima service identifies what packaging is needed to preserve stability. Its FastPack service specifies the package and designs the tooling required to form the blister. Photo courtesy of Bilcare, Delaware City, DE A screenshot of FreeThink's ASAPprime modeling software.