FDA revises guidance on essential drug delivery device performance
The US Food and Drug Administration (FDA) issued revised draft guidance on Thursday aimed at assisting sponsors of drug-device combination products in designing and developing essential drug delivery device performance characteristics (EDDCs) for their products.
EDDCs are intended to demonstrate the consistent performance and functionality of the drug delivery device component of a human drug or biological product, including syringes, injectors, infusion products, nasal sprays, inhalers, nebulizers, and vaginal systems.
The recommendations in the guidance aim to “improve the consistency” of performance information in applications and “to facilitate transparency and predictability in development and regulatory review, FDA said. Ultimately, these recommendations are intended to facilitate and streamline development and lifecycle management of drug delivery devices.”
The guidance replaces a draft version issued in July 2024. (RELATED: FDA drafts guidance on essential outputs for drug delivery devices, Regulatory Focus 1 July 2024)
The guidance has undergone significant revisions compared to the previous version. FDA stated that these changes aim to align the guidance with the Quality Management System Regulation (QMSR). The term essential drug delivery output (EDDO) has been replaced with EDDCs. Additionally, the sections regarding design verification testing and control strategies have been changed.
The guidance addresses identifying EDDCs, verifying and validating EDDC specifications, design and development verification of EDDCs, preconditioning, and post-market changes that may impact EDDCs.
The guidance states that EDDCs “are the key aspects of device drug-delivery that warrant development of and submission to FDA of performance information and data to ensure delivery of the intended drug dose to the intended delivery site.”
For instance, in the case of a prefilled syringe (PFS) that includes a needle and uses silicone oil as a lubricant, the glide force is an example of an EDDC. Yet the amount of silicone used, and the inner diameter of the needle are not classified as EDDCs, as these factors are already considered when measuring glide force. Additionally, injection depth is not considered an EDDC because it depends on the user's technique.
When it comes to verifying and validating EDDC specifications, the guidance states that the appropriate verification activities for EDDCs depend on various conditions, such as environmental factors that the product will encounter during production, shipping, storage, and preparation and usage. It adds that “examples of conditions that may impact performance include, but are not limited to, temperature, pressure, humidity, vibration and shock, and physical orientation.”
FDA notes that “preconditioning” is also necessary to mimic the stressors that a product might encounter during storage and shipping. Applicants should identify the specific preconditions relevant to their product, and conduct verification to evaluate the product’s ability to endure those stressors.
The guidance adds that “overall, the design and development verification assessment of EDDC specifications should occur after appropriate preconditioning. Depending on the product, the EDDC, and the specific types of preconditions, there may be different types of testing to demonstrate that an EDDC specification is met throughout the range of conditions and use environments described in the proposed labeling.”
The guidance includes four appendices. Appendix A outlines the key performance characteristics for drug delivery devices specifically designed for prefilled syringes, while Appendix B focuses on the EDDCs for autoinjectors. Appendix C provides examples of EDDCs for various drug delivery devices, and Appendix D presents a sample control strategy for an autoinjector with an extended needle length.
