Preparation and sterilization of an implantable drug-delivery microdevice for clinical use.

Implantable drug-delivery microdevices are a key diagnostic and therapeutic tool in medicine with increasing applications. Preparation of such combination drug-delivery devices for human studies requires the development of methods to ensure sterility, safety and integrity on both the device and drug side. Despite growing applications for these technologies, there has been a lack of clear methodology regarding sterilization and preparation to meet strict guidelines set forth by the Food and Drug Administration (FDA). Our laboratory developed a set of widely applicable and straightforward procedures to prepare drug-device combination products for clinical use that consistently achieve the high-quality standards provided by the FDA. This includes several newly developed methods for preparation of the implant including endotoxin removal, appropriate sterilization of raw materials, formulation of novel pharmaceutical agents, and loading of agents into drug delivery reservoirs. We also discuss protocols and methods developed with FDA to meet regulatory guidelines to ensure continual sterility and endotoxin testing, as well as longer-term stability testing of drugs and biologic agents.•Endotoxin removal and sterilization of raw materials for clinical use.•Formulation and device loading of novel pharmaceutical agents.•Continued testing of pharmaceutical agents and devices to meet regulatory guidelines.