Acute Particulate Testing
Acute Particulate Testing for Medical Devices
Acute particulate testing evaluates particles that may be generated or released from a medical device during preparation, delivery, deployment, use, retrieval, or withdrawal.
For intravascular and blood-contacting devices, released particles may enter the circulation and travel downstream from the treatment location. The potential clinical effect depends on factors such as particle size, quantity, composition, shape, vascular destination, and patient anatomy.
Testing is therefore used to characterize the particulate associated with a clinically relevant device-use sequence, investigate potential particle sources, compare devices or manufacturing processes, and support a device-specific assessment of particulate-related patient risk.
What Is Acute Particulate Testing?
Acute particulate testing measures particles released during a defined medical device procedure.
The evaluation generally covers the time from introduction of the device and accessories through their removal at the end of the procedure. Typical acute procedures may last two hours or less, although some acute applications may extend for as long as 24 hours.
Depending on the device, the simulated procedure may include:
Device preparation and flushing
Loading into a delivery system
Passage through an introducer or hemostasis valve
Tracking through a tortuous anatomical model
Deployment or expansion
Recapture or repositioning
Retrieval
Retraction and withdrawal
Repeated manipulation
Exposure to clinically relevant fluids and temperatures
The test fluid is collected or analyzed in-line to determine the number and size distribution of particles released during the simulated procedure.
Microscopic examination, particle imaging, morphology assessment, or chemical identification may also be performed when the probable source or clinical relevance of the particulate requires further investigation.
Scope of AAMI TIR42:2021
AAMI TIR42:2021 provides technical guidance for evaluating particulate acutely released from intravascular medical devices and accessories that directly contact circulating blood.
The document addresses:
Development of appropriate test methods
Identification of particulate sources
Particle counting and sizing
Particle shape and composition
Simulated-use testing
Clinical-risk assessment
Development of device-specific particulate limits
The scope includes particulate associated with:
Device materials
Surface coatings
Manufacturing
Packaging
Delivery accessories
Acute clinical use
The TIR does not address chronic particulate released from an implanted device after the delivery system and associated accessories have been removed.
AAMI TIR42 is a Technical Information Report rather than a prescriptive test standard. It provides recommended approaches, but it does not establish one universal test method, size distribution, or acceptance limit for every vascular device.
Why Medical Device Particulate Is a Clinical Concern
Particulate released from an intravascular medical device may enter the bloodstream and travel into smaller downstream vessels.
Depending on the particles and the location of device use, potential clinical concerns may include:
Distal embolization
Obstruction of small blood vessels
Local tissue ischemia
Infarction
Inflammatory response
Foreign-body reaction
Organ-specific injury
Accumulation of persistent polymeric or metallic debris
The level of concern can differ substantially among vascular territories. Particulate entering the cerebral, coronary, pulmonary, or peripheral circulation may have different potential consequences.
Patient-related factors can also influence risk, including:
Age
Vessel size
Comorbidities
Existing vascular disease
Collateral circulation
Intended treatment location
Ability to tolerate embolic injury
Not every detected particle presents the same level of risk. Particulate findings should be interpreted in the context of the device, clinical application, particle characteristics, patient population, and overall benefit-risk profile.
Key Characteristics of Medical Device Particulate
A meaningful particulate evaluation considers more than particle count alone.
Particle size
Particle size may influence how far a particle travels and where it becomes lodged within the vascular system.
Particle quantity
The clinical significance of a particulate burden may depend on both the total number of particles and their size distribution.
Particle composition
Polymeric, metallic, biological, fibrous, and other materials may produce different biological responses and levels of persistence.
Particle shape
Irregular, sharp, elongated, or fibrous particles may behave differently than spherical particles of a similar measured size.
AAMI TIR42 defines a fiber as a particle with a length-to-width ratio of at least 10:1. Fibers may require microscopic evaluation because automated particle counters may not size them accurately.
Particle source
Understanding whether particulate originated from the device, coating, delivery system, packaging, manufacturing process, or test setup is important for risk assessment and corrective action.
Where Does Medical Device Particulate Come From?
Particles detected during acute particulate testing may originate from multiple sources. They should not automatically be attributed to a functional coating.
Potential sources include:
Functional surface coatings
Hydrophilic or lubricious coatings
Antithrombotic or polymer coatings
Base device materials
Catheter shafts and polymer tubing
Metallic components
Adhesives
Delivery-system components
Introducers and hemostasis valves
Guidewires and guiding catheters
Manufacturing residues
Cutting, grinding, polishing, or spraying processes
Packaging materials
Cleaning or assembly processes
Contact between device components
Shipping and distribution stresses
Sterilization-related material changes
Simulated-use fixtures
Test containers, tubing, and fluids
Environmental or laboratory contamination
Understanding the source is important because corrective actions differ depending on whether particulate originates from the coating, base device, accessory, packaging, manufacturing process, or test setup.
What Devices May Require Acute Particulate Testing?
Acute particulate testing may be appropriate for a wide range of vascular and blood-contacting medical devices, including:
Stents and covered stents
Stent grafts
Vascular graft delivery systems
Catheters
Guidewires
Balloon catheters
Embolic protection devices
Blood filters
Thrombectomy devices
Neurovascular devices
Implantable frames
Delivery and retrieval systems
Coated vascular devices
Other intravascular devices and components
The appropriate test method depends on the device design, materials, delivery system, clinical procedure, and particulate-related risks.
Why Simulated Use Is Important
A static soak or simple rinse may not reproduce the mechanical interactions that generate particulate during clinical use.
Many vascular and catheter-based devices experience:
Friction against a delivery catheter
Compression within an introducer
Bending through tortuous anatomy
Contact with valves and seals
Interaction with guidewires or sheaths
Expansion or deployment
Recapture or repositioning
Retrieval
Repeated advancement and withdrawal
Movement between device components
A simulated-use model reproduces relevant portions of the clinical procedure before or during particle collection. This provides a more representative evaluation of particulate that may be released during actual device use.
The simulated-use procedure should incorporate, as applicable:
Preparation steps described in the instructions for use
Appropriate accessory devices
Clinically representative tracking
Deployment or expansion
Recapture or retrieval
Relevant tracking and deployment times
Applicable deployment pressures
Device withdrawal
Post-procedure flushing or particle recovery
Unless otherwise justified, the test fluid and simulated pathway should be maintained at physiological temperature of approximately 37 ± 2°C.
Simulated-Use Model Design
For vascular devices, the simulated-use model should reproduce challenging but clinically relevant anatomy.
The model may include:
A tortuous pathway
Anatomically representative tubing
A deployment location with appropriate diameter and compliance
Introducers
Guiding catheters
Guidewires
Sheaths
Hemostasis valves
Device-specific delivery or retrieval components
If the device can be used in more than one vascular territory, the most challenging clinically relevant pathway should generally be selected or scientifically justified.
Important model considerations include:
Tortuosity
Tracking-path length
Vessel dimensions
Deployment-site geometry
Deployment-site compliance
Model material
Fluid volume
Flow or flush rate
Model orientation
Recovery of large and small particles
The model should be constructed from materials that do not contribute excessive particulate to the test system.
Test Articles and Worst-Case Selection
Test articles should represent the finished device as intended for clinical use.
They should ordinarily have undergone all applicable:
Manufacturing processes
Cleaning processes
Coating processes
Packaging
Sterilization
Shipping or environmental conditioning
Aging, when applicable
Worst-case selection may consider:
Maximum device size
Maximum coating or exposed surface area
Longest tracking path
Most tortuous anatomy
Tightest compatible delivery system
Most challenging deployment configuration
Highest number of allowed manipulations
Repeated recapture or repositioning
Maximum deployment pressure
Maximum sterilization exposure
Shelf-life-aged materials
Device configuration most likely to generate friction
When a product is available in multiple sizes, testing should include representative sizes or provide a documented rationale for the selected worst-case configuration.
Testing multiple manufacturing lots may be appropriate during verification, validation, or process characterization.
Aging, Sterilization, Shipping, and Packaging
Particulate generation may change during the product life cycle.
Aging may affect:
Polymer flexibility
Coating adhesion
Material brittleness
Oxidation
Drying
Stress cracking
Delamination between material layers
Sterilization may alter materials through:
Heat
Moisture
Pressure
Chemical exposure
Radiation-related polymer degradation
Embrittlement
Cracking
Corrosion
Shipping and environmental conditioning may introduce:
Vibration
Component rubbing
Package-to-device contact
Pressure changes
Temperature extremes
Mechanical shock
The effects of aging, sterilization, packaging, shipping, and distribution should therefore be evaluated or scientifically justified as part of the particulate-testing strategy.
Sample Size and Study Variability
Acute particulate testing can be highly variable.
The number of devices tested should be sufficient to represent the device, manufacturing process, and intended comparison. The sample size should be justified before testing begins.
Sample-size planning should consider:
Expected test variability
Number of device configurations
Number of manufacturing lots
Comparative study design
Development versus verification testing
Statistical objectives
Regulatory expectations
Availability of predicate or comparator data
Testing multiple devices and lots can help distinguish normal variability from a design, process, coating, or manufacturing issue.
How Acute Particulate Testing Is Performed
A device-specific testing program generally includes the following steps.
1. Define the test objective
The study should begin with a clear question.
Examples include:
How much particulate is released during simulated use?
Does a coating process affect particulate release?
Does a design change affect particulate generation?
Are different device lots comparable?
Does aging or sterilization change particulate release?
Which step in the procedure generates the most particulate?
What is the probable source of recovered particles?
2. Define the clinical-use sequence
The procedure should reproduce relevant preparation, delivery, deployment, retrieval, and withdrawal steps.
3. Select representative or worst-case test articles
The selected devices should represent the finished, processed, packaged, sterilized, and—when applicable—aged product.
4. Select or develop the simulated-use model
The model should represent challenging clinical anatomy and include relevant accessory devices.
5. Establish contamination controls
Background particles from the fluid, fixture, laboratory, and accessories should be characterized before device testing.
6. Perform the simulated-use procedure
The device should be prepared and used according to the defined protocol and applicable instructions for use.
7. Collect or count released particles
Particles may be collected in test fluid, recovered by flushing, captured on a filter, or measured in-line.
8. Count and size the particles
The particle population should be reported using predefined size categories.
9. Examine representative particles
Microscopy or chemical analysis may be used to evaluate shape, morphology, composition, and source.
10. Interpret the findings
Results should be evaluated against controls, comparator data, proposed limits, clinical use, and device-specific risk.
Background Controls and Test-System Suitability
Particulate testing requires careful control of contamination from the test environment and apparatus.
Potential background sources include:
Test fluid
Glassware
Collection containers
Tubing
Anatomical models
Introducers
Valves
Filters
Laboratory air
Operator handling
Cleaning materials
Analytical equipment
Testing should be performed in an appropriately controlled environment using clean equipment, suitable gowning, particle-free or filtered fluids, and validated cleaning procedures.
Before testing a device, the baseline number and size distribution of particles generated by the test apparatus should be established.
The background should be sufficiently low to allow accurate measurement of device-associated particles.
Controls may include:
Fluid blanks
Test-system blanks
Fixture blanks
Accessory-device controls
Delivery-system controls
Environmental controls
Uncoated devices
Reference or comparator devices
Following simulated use, the test pathway should be flushed or monitored until a predefined baseline or termination criterion is reached.
Particle Collection Methods
Beaker-capture method
The device is used within a simulated pathway, and the resulting fluid is collected in a clean container.
Additional flushes may be needed after the device is removed to recover particles remaining in the model.
Important considerations include:
Preventing air bubbles
Maintaining particle suspension
Controlling mixing
Avoiding particle agglomeration
Avoiding breakup of larger particles
Accounting for the entire collected fluid volume
In-line counting
An in-line system measures particles during the simulated-use procedure.
Advantages may include real-time measurement and identification of particle-generation events.
Important considerations include:
Filtered test fluid
Appropriate flow rate
Minimal downstream connections
Avoidance of particle trapping
Prevention of particle breakup
Compatibility with the particle counter
System recovery and validation
The selected method should be appropriate for the device, expected particle population, test fluid, and study objective.
What Particle Sizes Should Be Evaluated?
The particle-size ranges selected for acute particulate testing should be based on the device, intended vascular location, patient population, clinical-use conditions, analytical method, and device-specific risk assessment.
AAMI TIR42:2021 identifies the following as commonly validated cumulative particle-size bins:
≥10 µm
≥25 µm
≥50 µm
Larger cumulative bins, such as ≥70 µm and ≥100 µm, may also be evaluated and validated when appropriate for the device and clinical application.
These are cumulative thresholds. For example, the ≥10 µm count includes particles that are also ≥25 µm and ≥50 µm. The test protocol and report should clearly state whether results are presented as cumulative thresholds or as discrete size intervals.
AAMI TIR42 notes that the commonly used 10 µm and 25 µm thresholds were likely influenced by USP <788>. However, the clinical relevance of these specific thresholds has not been fully established for intravascular medical devices. Additional smaller or larger particle-size categories may therefore be appropriate.
For example, smaller particles may warrant additional consideration for devices used in the neurovasculature or in pediatric and neonatal patients. Larger particles should also be characterized carefully. If ≥50 µm is the largest reported bin, a 75 µm particle and a 2 mm particle would be grouped together even though they may present substantially different clinical concerns.
The selected size bins should provide enough resolution to characterize the particulate distribution and support a meaningful clinical risk assessment. Microscopic evaluation may also be appropriate for unusually large, irregular, or fibrous particles that cannot be adequately described by automated particle counting alone.
The measurement system should be validated across the reported particle-size range. AAMI TIR42 recommends demonstrating:
At least 90% recovery for 10 µm and 25 µm reference particles
At least 75% recovery for particle sizes reported above 25 µm
Validation at a minimum largest particle size of at least 50 µm
Particle size should not be evaluated in isolation. Particle quantity, shape, composition, persistence, probable source, and potential vascular destination may also affect the clinical significance of particulate released during device use.
Particle Counting and Characterization Methods
Particle enumeration is commonly performed using light obscuration, microscopy, or a combination of methods.
Light obscuration
Light obscuration measures particle number and apparent size as particles pass through a light beam.
Potential advantages include:
Rapid analysis
Automated counting
Size-distribution data
Established calibration approaches
Limitations include:
No direct information about composition
Limited morphology information
Potential sizing error for fibers
Potential sizing error for irregular particles
Interference from bubbles
Limited suitability for turbid or viscous fluids
Possible loss or undercounting of very large particles
Microscopic analysis
Microscopy allows direct observation of particles captured from the sample.
It may provide information about:
Size
Shape
Color
Transparency
Fibrous morphology
Surface appearance
Irregular or large particle populations
Microscopy can be particularly valuable when:
Fibers are suspected
Large particles are observed
Particle morphology is unusual
Particles are outside the validated range of the automated counter
Chemical identification is planned
Automated counting may not represent the particle population accurately
A combination of automated counting and microscopy may provide a more complete evaluation.
Method Calibration and Validation
The particle-counting equipment and other critical measurement equipment should be calibrated or certified against appropriate references.
The complete simulated-use system—not only the particle counter—should be validated to demonstrate that particles released during testing can be recovered and measured accurately.
Validation commonly includes spike-and-recovery testing using known quantities and sizes of reference particles.
AAMI TIR42 recommends demonstrating:
At least 90% recovery for 10 µm reference particles
At least 90% recovery for 25 µm reference particles
At least 75% recovery for sizes reported above 25 µm
Validation of a largest particle size of at least 50 µm at 75% recovery
An upper recovery limit should also be established because unexpectedly high recovery may indicate counting error, contamination, particle aggregation, or another test-system problem.
Validation should consider:
Model geometry
Model dimensions
Particle settling
Model material
Fluid composition
System orientation
Flow or flush rate
Particle suspension
Particle-counter sampling
Particle loss within the model
Breakup of larger particles
Reference particles larger than 100 µm may be less readily available, but information about larger particles can still be clinically and technically valuable.
How Are Particle Sources Identified?
Not every recovered particle needs to be chemically identified.
Source identification is particularly important when:
Particle levels exceed a proposed limit
Large particles are observed
Particles have an unusual color
Shape or morphology is atypical
Unexpected differences occur between groups
Composition could affect clinical risk
A root-cause investigation is needed
Potential methods include:
Optical microscopy
FTIR spectroscopy
Raman spectroscopy
Scanning electron microscopy
Energy-dispersive X-ray spectroscopy
Comparison with known device materials
Comparison with coating, accessory, packaging, or fixture materials
Separate testing of individual device components
Separate collection from individual procedural steps
When practical, an independent analytical method may be used to confirm the initial particle identification.
Comparative Acute Particulate Testing
Acute particulate testing is often most useful when performed comparatively.
Examples include:
Coated versus uncoated devices
Current process versus proposed process
Design A versus design B
Supplier A versus supplier B
New versus aged devices
Sterilized versus non-sterilized devices
Different coating parameters
Different delivery systems
Different manufacturing lots
Prototype versus production-intent devices
Before and after a manufacturing change
Comparative testing can help identify whether a coating, design, material, supplier, delivery system, or manufacturing change affects particulate generation.
How Alta Biomed Supports Vascular Device Thrombosis Evaluation
Alta Biomed provides acute particulate testing support for vascular, catheter-based, coated, implantable, and other blood-contacting medical devices.
Testing programs can include:
Review of the device and clinical-use sequence
Identification of potential particulate sources
Development of a device-specific test protocol
Customer-supplied or custom simulated-use fixtures
Tortuous-path testing
Clinically representative device preparation and delivery
Physiological-temperature testing
Particle collection
Light-obscuration particle counting and sizing
Microscopic particle examination
Coated versus uncoated comparisons
Design, process, supplier, or lot comparisons
Source-investigation support
Technical reports with data and representative images
Programs are tailored to the device, delivery system, development stage, applicable guidance, and specific particulate-risk questions.
Discuss an Acute Particulate Testing Program
Developing a vascular, catheter-based, implantable, or other blood-contacting medical device?
Alta Biomed can support simulated-use model development, acute particulate collection, particle counting and sizing, comparative studies, and investigation of potential particle sources.