The purpose of the medical device particulates testing is to determine the quantity and size of particles on the device or in the solution. With the addition of TIR 42, it is not only the size of the particulates which is a focus, but also their shape, identification, and quantity.
Particulate matter consists of particles that will not dissolve in solution (other than gas bubbles) and that are unintentionally present on a device or in a solution. Particulate matter can come from many sources in processing. For injectable solutions, limits can be found in the appropriate pharmacopoeia (EP, USP, JP, etc). However, while a few procedures for medical devices exist in other standards, the majority of devices do not have specific procedures for testing or proposed limits. In 2010, the new standard AAMI/TIR 42, Evaluation of Particulates Associated with Vascular Medical Devices, was released.
Medical device particulates testing is performed on injections, parenteral infusions, and medical devices. Since there is no one test method for testing parenteral products or medical devices, NAMSA prepares a test specification for every sample tested, which may be set up in advance of the sample’s arrival. When performing particulate analysis, we consider how manufacturing, sterilization, shipping and distribution, packaging, shelf storage, and use with other devices affect the particulate levels of the medical device.
For injectable (parenteral) products, particulates testing is performed according to USP procedures unless otherwise specified. For medical devices, the solution is analyzed for particulate matter according to USP procedures unless otherwise specified. If a special procedure particulate test (ISO, EP, JP) is needed, please inquire.
According to USP <788> Injections and <789> Ophthalmic Solutions, the Light Obscuration Method and the Microscopic Method are the two methods to analyze particulate matter. The USP states that the Light Obscuration method is to be preferably applied. If limits are not met or the product cannot be tested using this method (examples: solution is colored, too viscous and cannot be diluted, etc) the microscopic method may be used or tested using both methods to reach a conclusion about the number of particles in the solution.
Light Obscuration Method: This method analyzes the device rinse solution or injectable product using a light obscuration particulate analyzer. Four (4) 5 ml portions of the extract are analyzed by the instrument; the data from the first count is discarded. The second through fourth count is averaged and then compensated for the entire extract (or reported in particles per ml.) The advantage to this method is that it is a quick easy method to count particulate, and it can count high amounts of particulate in the solution. A minimum of 25 mL of solution is required to perform this method.
Microscopic Method: This method filters the device rinse solution or injectable product through a 0.8 μm grey gridded filter. The filter is then counted microscopically at 100x to determine the number of particles. This method counts particles in the entire test solution. The disadvantages are that if there are too many particles, they cannot be counted or only a partial count is performed. The test is more labor intensive, and therefore has a longer turn around time and is more expensive than light obscuration.
The data from the Microscopic Method tends to be lower, so the pharmacopoeia makes up for the difference by having lower limits for the microscopic method. Both methods count particles greater than 10 μm and greater than 25 μm (and greater than 50 μm for USP <789> Ophthalmic Solutions.) Note that other sizes may be counted upon request.
Since procedures for testing medical devices are not covered in the USP, it is up to the sponsor to determine the method of testing and the procedure to remove the particulate from the device. Some procedures include flushing, filling, covering, sonicating, rinsing, etc.)
The identity of the particulates and potential source of matter may be an important consideration when investigating or characterizing particulate matter on a medical device. It might be important to consider the identity, source and potential toxicity of each type of particulate as well as the sizes, shapes and quantities of particulates. It is not expected that all particles need to be identified, but efforts at identification should be undertaken when appropriate (e.g., when particulate levels have exceeded limits and as necessary to better derive the source of particles.)