The FDA has released a preliminary guide to aid developers of drug-device combination products in creating essential drug delivery outputs- EDDOs that ensure consistent performance. Products covered by this guide include syringes, injectors, infusion products, nasal sprays, inhalers, nebulizers, and vaginal delivery systems. Information about the delivery devices must be included in the relevant investigational or marketing application for combination products reliant on a delivery device. The guide explains that drug-device combination products may be more intricate than their individual parts since, in addition to the individual parts, the interactions of the constituent parts also need to be evaluated, characterized as well as controlled all through the product design, development, and also production. The FDA suggests that determining EDDOs may facilitate the development of combination products by indicating the type of data to submit in applications, which would ensure that the appropriate device design attributes and manufacturing process steps are evaluated during lifecycle changes. EDDOs can also be made use of to compare drug delivery performance and assist the assessment for bridging or even leveraging data across products.
The guide outlines three processes for developing EDDOs:
- Identifying the EDDO to define the product’s device drug-delivery function and guiding design and development efforts to ensure appropriate drug delivery
- Controlling to ensure the product meets the quality standards for device drug-delivery function
- Maintaining to ensure that any product changes made during clinical development or post-marketing that could negatively impact the EDDO are evaluated
In the identification stage, applicants should carry out design verification activities, such as preconditioning studies, to confirm that the device’s drug-delivery function is maintained in accordance with its instructions for use. For instance, this preconditioning can involve exposing products to multiple stressors that may affect the device’s drug-delivery function during shipping, storage, and use. The preconditions to simulate storage may include subjecting the product to specific temperatures, temperature fluctuations, pressure changes, and humidity. During shipping, a product might be exposed to varying conditions, such as ground by truck to air, ground by truck to boat, ground by rail to air, or ground by truck. Conditions when it comes to simulating storage may go on to include subjecting the product to certain particular temperatures, erratic temperature fluctuations, pressure changes as well as humidity. For reusable devices, the preconditioning methods should simulate the worst-case number of repeat use and reprocessing cycles. This should include cleaning and sterilization or disinfection methods mentioned in the proposed labeling. The guide explains that the results from these studies can be included in a submission. Additionally, the guide provides examples of developing EDDOs for a prefilled syringe and an autoinjector.
