NOT SO GENERIC?
Over the years our team has been involved in a number of generic Advair Diskus device developments. We've seen a number of approaches from completely novel architectures from early adopters who didn't want to infringe on GSK's strip-peeling patent, to later attempts at copycat designs. In September 2013, FDA's Office of Generic Drugs issued draft guidance which clarified the requirements for generic Advair products, causing at least one company to rethink their strategy.
With the draft guidance as a convenient starting point, we set out to develop a compelling device concept.
Similar But Different
According to the draft guidance the device would need to have the following characteristics:
- Passive (breath-actuated) device
- Pre-metered multi-dose format
- 60 doses
- External operating procedures consisting of (1) Open, (2) Click, (3) Inhale, and (4) Close
- Similar size and shape to the R product
- Comparable device resistance to the R product
- Dose counter
In addition, the robustness of the T product should be demonstrated.
These high-level requirements belied the technical challenge: to create a product which would be capable of mimicking the in vitro, PK and PD performance of the reference product, itself known to be reasonably variable, left very little scope for changing the fundamental device architecture. We opted for a strip-peeling architecture.
There was a further, unwritten constraint: to demonstrate substitutability. Ideally a patient familiar with using Advair Diskus would be able to use the generic device intuitively and the Instructions For Use (IFU) would map across. We conducted some Human Factors studies and found that a common complaint with the reference device was the size of the dose counter. We concluded that the one way in which the device could be improved without deviating from the IFU would be to provide a larger, clearer and more prominent dose counter.
Despite the seemingly impossible physical constraints, we developed a high-clarity, centrally mounted dose counter with only two moving parts. The design had the additional innovation of displaying an arrow to prompt the user to actuate the lever when the device is in the open state. We have applied for a patent to protect the dose counting technology and we have reconfigured it for use in other devices including a 120-dose pMDI.
In Vitro performance
The litmus test for a generic inhaler is how well it matches the reference product in vitro. We did some initial testing by taking some strips from marketed products and retro-fitting them into our device. We had already optimised the airflow through the device using CFD and our in-house digital Airflow Characterisation Test Rig (ACTR) connected to LabView so we were reasonably confident. Even so, we were surprised at just how closely our Aerodynamic Particle Size Distribution (APSD) profile matched the reference products in an A/B test.