5.1 The methods described herein allow for in vitro characterization of DCB drug coating attributes that, along with pre-clinical and clinical safety and effectiveness data, establish that the DCBs, with the characterized coating attributes, are safe and effective. Clinical safety and therapeutic benefit may be affected by nonuniform distribution of the active pharmaceutical ingredient, coating anomalies on the device, and particulate release. Variability in drug coating may result in insufficient or excessive drug availability and inconsistent device performance.

5.2 Individual characterization tests may not have direct clinical relevance, although bench-based characterization results can be combined with other data to provide insight to characteristics that influence clinical safety and effectiveness. Bench testing is performed under repeatable and controlled conditions, providing information about drug coating integrity, thickness, uniformity, particulate shedding, particulate identity, and particulate crystallinity.

5.3 Distribution of the drug coating is characterized by coating integrity, thickness, and uniformity. Particulate counts can provide a measure of manufacturing repeatability, and may provide an indication of in vivo safety if simulated use particulates and in vivo particulates are shown to be similar, or if particulate testing results are correlated to in vivo safety. Chemical identity of particulates and crystallinity may further advise the kinetics related to the potential for particulate persistence, dissolution, or other characteristics which may relate to in vivo safety. Conducting this testing and gathering the data further allows for the potential comparison of devices (e.g., demonstrating equivalence between pre-clinical and clinical devices for these coating attributes).

5.4 The methods described in this guide are for characterization purposes and are not intended for production release testing of drug-coated balloon catheters. However, some content may be applicable to generating release data. The general guidelines presented here may be used for product control at various stages of the product development process.

1.1 This guide describes recommended acute in vitro characterization methods for drug-coated balloon (DCB) coatings. These methods include: coating integrity, coating thickness, drug coating uniformity, and released particulates. Specifically, this guide details:

1.1.1 Characterization of integrity by inspection of the coated balloon surface.

1.1.2 Measurement of coating thickness.

1.1.3 Quantitation of drug coating uniformity (uniformity of drug distribution over the balloon surface) longitudinally and circumferentially.

1.1.4 Quantitation of the number of particulates released, in various size ranges, during simulated use testing (insertion, tracking, deployment, retraction, and withdrawal) along with chemical and crystallinity characterization of particulates.

1.2 This document does not address:

1.2.1 Mechanical testing of drug-coated balloons (DCBs).

1.2.2 Drug substance evaluation (e.g., assay, related substances, uniformity of dosage units) of DCBs.

1.2.3 Production release and stability testing, although some sections may be applicable in whole or in part.

1.2.4 Standard analytical testing (e.g., drug content, drug related substances, drug uniformity of dosage).

1.3 The values stated in SI units are to be regarded as standard. No other units of measurement are included in this standard.

1.4 This standard does not purport to address all of the safety concerns, if any, associated with its use. It is the responsibility of the user of this standard to establish appropriate safety, health, and environmental practices and determine the applicability of regulatory limitations prior to use.

1.5 This international standard was developed in accordance with internationally recognized principles on standardization established in the Decision on Principles for the Development of International Standards, Guides and Recommendations issued by the World Trade Organization Technical Barriers to Trade (TBT) Committee.