A growing number of combination products, along with the overall growth of the pharmaceutical and biologics industry, is driving demand for a more-complex arsenal of tests, report experts. To meet such demand, DDL Inc. is teaming up with another laboratory to increase its family of tests, and it is also offering off-site stability storage for products requiring environmental conditions based on ICH Q1A (R2) specified guidelines. DDL will highlight these new capabilities at MD&M Minneapolis Booth #1832 November 8-9.
DDL has entered into a joint agreement with Gateway Analytical to offer foreign particulate characterization, materials characterization, and extractable/leachable studies. When combined with DDL’s existing device functionality testing and drug stability programs, the lineup offers convenience and efficiency, the company reports.
“Drug+device combination product (DDCP) is merging chemical and mechanical disciplines and becoming a popular approach for many biotech and biosimilar companies for differentiation,” explained Patty Kiang, principal of Kiang Consultant Services, to MD+DI. In addition, “it is required by FDA/EMA to have both drug stability as well as the device functionality tests on the same stability program. The demands will increase for the combined mechanical and chemical testing services to demonstrate that both drug and device are stable and functional through the shelf life of the combination product.”
Dylan Stover, applied engineer for DDL, said the company has always offered characterization of the physical properties of materials, but the testing services that Gateway offers are new to DDL. “These tests play an important role in determining the safety and effectiveness of combination products and contained API,” he said. “They are used to show that contaminants from the manufacture, fill, or seal process have not compromised the drug product. As an example, one thing Gateway checks for is the amount of syringe barrel lubricant that has leached into the product. Stability testing is an important metric for pharmaceutical companies to consider. This gives the manufacturer an idea of shelf-life as well as an understanding of how the product’s characteristics change over time. For example, you may find that with varying time and temperature conditions, the leachables content increases at differing rates. Ultimately this will affect the length of time a product can be used safely.”
In terms of device functionality testing, Kiang said there are only a few testing laboratories that are qualified to perform these device functionality tests. “FDA and EMA mandate the sponsors (drug companies) to perform the device functional tests as well as the regular drug chemical and physical tests for stability program,” she said. “Most of the biotech companies and CMO / CRO do not have the experience nor the capability of device functionality tests. They oftentimes have to rely on device vendors or outsource these tests to a specific testing laboratory to perform these types of tests. The combined offering of chemical and mechanical testing services will make it more attractive and bring convenience to drug companies developing drug+device combination products.”
Regarding the new ICH Q1A testing support, Stover reported that there haven’t been any changes per se with ICH Q1A, “but the guidelines may be new for some companies that are now beginning to offer combination products for the first time.”
New users may face challenges, and DDL is positioning itself to help. One hurdle is “understanding what temperature and humidity are the best for their given testing purposes,” Stover explained. “Since the FDA has only published guidance documents, there are few written rules that would make determining these values easier.”
Users must also ensure that “the same stability conditions are applied for both drug and device for combination products,” added Robin Hwang, principal of IPC Consulting Corp. “A separate accelerated aging study must be performed on empty devices by device vendors to demonstrate the device components’ shelf life, prior to assembly into the combination product with drug product. It’s easier to conduct the accelerated device testing itself. However, the typical storage conditions of biological drugs are 2-8 degrees C and this may not allow for accelerated testing conditions. Thus it will take more time to achieve the shelf-life label claim.”
Off-site stability storage can help in a few ways. “It is more practical and cost efficient for many companies to outsource these types of services versus managing it internally,” said Stover. “Using a third party allows companies to hire out niche experts and not have to worry about training employees, creating a documented process, or the calibration and maintenance of the equipment.”
It also helps companies schedule sufficient time for testing according to regulatory requirements, one of the biggest challenges. “Companies are always under pressure to get their products to market faster, and thus are always working on tight timelines,” he said.
Custom storage conditions and reports are available.
Hwang expects testing needs will continue to evolve for combination products. “The complexity of devices could add challenges to the testing of combination products, especially if they go from mechanical to electromechanical devices and/or devices with mobile health or Internet of things (IoT),” he said. “There will also likely be new and additional tests created as new devices or new technologies are introduced to the market.”
Other tests to consider include performing human factors studies prior to finalizing the device design and performing risk assessment and risk mitigation during the device development process to minimize or eliminate use-risks associated with the combination product, Kiang said.
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