Particulate testing of cardiovascular medical devices is an important and valuable step on the road to regulatory clearance, market success, and patient safety. Device manufacturers that incorporate particulate testing into their product development plans early are better equipped to navigate the regulatory clearance process and potentially reduce time to market. After premarket regulatory clearance is achieved, and the cardiovascular device is on the market in clinical use, postmarket lot release particulate testing and monitoring can help ensure product quality and safety going forward.
Particulate Testing of Cardiovascular Devices: What Is It, and Why Is It so Valuable?
Particulate testing determines the quantity and size of residual materials present on a cardiovascular device. Residual material includes substances resulting from the manufacturing process, such as metal shavings or millings from drilling; substances resulting from the packaging of the product, such as cardboard, packaging lint, or glue resins; and any particulates resulting from handling of the device during the manufacturing, packaging, or shipping processes. Residual material also includes coatings and adhesives present on the device that unintentionally slough off during clinical use, as well as any other foreign contaminants, such as dust or skin cells.
It is important that manufacturers ensure that these contaminants and byproducts of manufacturing are removed as they pose potential health risks to patients. When a device is used on a patient, particles could be released into their bloodstream and become lodged in the patient’s vascular capillary system. Whether this is harmful to the patient depends on the number and size of the particles as well as where and to what degree they cause an occlusion. In some cases, these occlusions could lead to blood clots and even stroke. In addition, the patient’s immune system may react adversely to the particulates.
Though these health risks are rare, a review of the FDA’s warning letters shows that adverse events related to particulates are all too common. As devices become more complex with specialized coatings and components, the device’s potential to release particulates and injure a patient increases. Therefore, the FDA has increased its scrutiny of particulates in cardiovascular devices.
For this reason, most cardiovascular device types are candidates for particulate testing. Chief among these are stents, stent-delivery systems, vascular catheters (guide catheters, angioplasty “balloon” catheters, and microcatheters), coated guide wires, introducers, and guide sheaths.
Active implantable devices—in particular, pacemakers and their associated accessories—are required to be particulate tested in compliance with international standards EN 45502/ISO 14708.
Premarket Product Validation
Particulate testing provides significant value to the manufacturer and, eventually, to the patient using the device. In our experience, manufacturers that follow published guidance and have written justification for their selected test methods, validation of the method, and demonstrated consistency in their particulate test results are more likely to experience a smoother U.S. FDA clearance process and speedier market launch.
Premarket particulate testing incorporated as part of the product validation process includes compliance with the following standards:
- ANSI/AAMI TIR 42 Evaluation of Particulates Associated with Vascular Medical Devices (approved 2010): This report offers guidance to medical device manufacturers in applying analytical methods for particulate testing, identifying potential sources of particulate contaminants, and guidance for developing acceptable limits for particulates.
- FDA’s Class II Special Controls Guidance Document for Certain Percutaneous Transluminal Coronary Angioplasty (PTCA) Catheters (issued 2010): Section 13, “Particulate Evaluation,” is particularly important to manufacturers submitting 510(k) clearance applications, as it lists specific methods FDA wants to see employed in particulate testing, such as worst-case scenario and exercise of the device.
- EN 45502 Active Implantable Medical Devices (published 2010), and ISO 14708 Implants for Surgery – Active Implantable Medical Devices (published 2014): These two harmonized standards set an acceptable level of residual particulate matter for such active implantable medical devices as pacemakers.