Blog

Blood vessel with hemostatic agent 

In the world of material science and product design, understanding and measuring rapid rheological transitions is crucial. These transitions, which can be triggered by various stimuli such as UV light, electrical fields, or chemical interactions, play a significant role in applications ranging from hemostatic agents to 3D printing materials. While standard methods exist for common applications, less conventional scenarios often lack specialized tools for accurate measurement.

The Challenge of Rapid Rheology Transitions

Conventional methods for measuring rapid rheological changes often face limitations:

1. Large sample volume requirements
2. Inability to capture transitions faster than one second
3. Lack of quantitative accuracy for rapid changes

For instance, the stir bar stop method, while useful for qualitative ranking, falls short in providing precise measurements for transitions occurring in less than a second.

Stir bar stop method typically used as a qualitative metric to measure near rapid rheological transitions. Example shown for crosslinking. Time accuracy is only as good as the human pressing the start/stop button on a stopwatch.

A Novel Approach: Custom Vane and Baffled Cup Geometry

To address these challenges, an innovative method was developed using a custom-designed vane and baffled cup geometry. This approach offers several advantages:

• Reduced sample volume: Only 6 mL required, compared to ~20 mL for standard vane accessories
• Rapid mixing capability: High-speed rotation ensures near-instantaneous mixing
• Precise measurement: Captures transitions within seconds of stimulus application

Experimental Setup and Calibration

CAD sketch of custom vane (left) and custom baffled cup (middle). Machined vane and 3D printed baffled cup assembly (right).

The custom setup consists of:

1. A TA Instruments DHR-2 rheometer
2. A 3D-printed baffled cup
3. A CNC-machined aluminum vane fixture

Due to the smaller-than-recommended gap, the geometry required calibration using both concentric cylinder and parallel plate analogies to determine accurate stress and strain factors.

Measuring Rapid Absorption Kinetics

The method was applied to measure the absorption kinetics of a powder absorbent in a liquid "spill":

1. The vane rotates rapidly in the liquid
2. Powder absorbent is added to the cup
3. Torque is monitored until a threshold is reached
4. The test switches to oscillatory mode to measure slurry modulus

Results and Implications

Powder absorbent added to liquid “spill.” Blue curve from the initial mix step: powder added at ~3.7 seconds, mixed rapidly for ~0.5 seconds until a predetermined torque threshold was surpassed indicating the slurry was sufficiently mixed. Red (G’) and green (G”) curves: modulus growth kinetics shows crossover within ~1.8 seconds after addition of powder and full absorbency within 17.9 seconds from addition of powder.

The custom method yielded impressive results:

• Crossover time: 1.79 seconds after powder addition
• Full absorbency: Achieved within 17.85 seconds

These precise measurements provide valuable insights into the rapid rheological changes occurring in the absorbent material system.

Conclusion

This novel approach to quantifying rapid rheological changes offers a powerful tool for material scientists and product designers. By overcoming the limitations of conventional methods, it enables more accurate and detailed analysis of fast-acting materials, potentially leading to improved designs in various applications, from spill cleanup to medical treatments. The ability to capture such rapid transitions with minimal sample volumes opens new possibilities for research and development in fields where material behavior in the first few seconds is critical. As we continue to push the boundaries of material science, tools like this will play an increasingly important role in understanding and optimizing rapid rheological phenomena.

 

Read the full application note.

 

Medical device development relies heavily on standards to ensure patient safety, efficacy, and regulatory compliance. Organizations such as ASTM, AAMI/ISO, and USP establish critical test methods to ensure adequate cleaning and sterility, mechanical performance, biocompatibility, and material integrity. These standards streamline innovation while safeguarding patients, reducing redundant testing, and maintaining U.S. competitiveness in global markets.

The FDA’s Critical Role in Standards Development

For decades, FDA scientists and regulators have been active participants in shaping these medical device standards and often hold leadership roles on individual standards or committees. Their direct experience with reviewing ~20,000 medical device submissions per year renders their input invaluable on both the types of standards needed and the specific content needed within those standards. Because biomedical technology is advancing rapidly, particularly in design innovation and material selection, it is critical to patient safety that standards keep pace. Up-to-date standards not only protect patients but also benefit U.S. companies by streamlining the regulatory process. With well-defined, current standards, US manufacturers can focus on conducting only the studies necessary for patient safety, and avoid unnecessary, costly and time-consuming testing that would put them at a disadvantage in the global market.

Executive Order Freezes Communication and Participation in Standards Development

A chair of an AAMI working group announced last week that the FDA will be pulling away from communication and participation in standards development within AAMI and ISO as a result of a January 20, 2025 executive order from the White House. Other FDA scientists confirmed the freeze applies to all regulatory activities, including their ASTM participation. The freeze is not a permanent cessation of standard development activities, but no timeline has been given.

Risks of Reduced FDA Participation

Without FDA’s frontline regulatory experience, standards may lag behind medical device advancements, in areas such as AI-driven devices, nanotechnology, and biocompatible materials. Outdated standards could fail to address emerging risks, including cybersecurity vulnerabilities in connected devices or novel biomaterial interactions. U.S. manufacturers may face redundant testing to meet divergent global standards, increasing costs and time-to-market compared to international competitors.

If the freeze becomes permanent, the lack of FDA participation in standards development is likely to increase the regulatory and development burden, and therefore increase costs on American medical device manufacturers, causing delays to get products on the market and potentially put patients at risk. We sincerely hope that the new administration permits continued involvement of FDA personnel in the standards process.

NAMSA, a medical device contract research organization, announced last week the acquisition of the US medical device testing operations of WuXi AppTec, a biopharmaceutical and medical device testing laboratory headquartered in China. This acquisition is part of a recent trend of acquisitions of medical device testing laboratories by larger multinational testing conglomerates over the past few years. This trend, predicted to continue, results in larger, consolidated operations with higher volumes and the ability to offer routine standardized testing on complex projects. However, it comes with a cost.

Challenges in Biological Safety Evaluation

Evaluation of the biological safety of medical devices with compliance to new standards and revisions of existing standards has become increasingly challenging.  Given the shift in regulatory expectations, along with an increase in the use of unique materials and manufacturing processes, each premarket submission often requires a custom-designed strategy for assessing biological safety that takes in to account the details of the device’s indication and composition.  This approach dictates constant communication between engineers and regulatory affairs specialists at the medical device manufacturer, the research lab conducting the biological endpoint and chemical characterization testing, and the toxicologists and biologicals safety specialists conducting the biological evaluation and making a final determination on safety.

CPG’s Collaborative Approach to BSE

Material scientist and biocompatibility specialists at Cambridge Polymer Group work directly with the client through the submission process to ensure a successful outcome with regards to evaluation of the biological safety of the device.  Although communication often begins with a conversation between a single engineer at a medical device company and a scientist at CPG, CPG in-house experts often become part of the cross-functional team that is necessary to effectively address FDA feedback. As needed, CPG can also rapidly bring in additional external expertise to further support the submission process.

The customer-driven, interactive approach offered by CPG has resulted in a high success rate with premarket submissions. Ultimately, the support offered by in-house experts at CPG, along with external partners to CPG, can reduce the timeline and overall cost for bringing a medical device to market.  Turnkey contracts for biological safety evaluation may increase the risk that the premarket submission does not meet current regulatory expectations.

The recent announcement of INEOS's decision to permanently close its ABS (acrylonitrile butadiene styrene) production facility in Addyston, Ohio, has sent ripples through the medical device manufacturing industry. This closure, set to begin in the second quarter of 2025, will significantly impact manufacturers who rely on ABS plastics for various medical applications. The situation calls for a comprehensive strategy to address supply chain challenges and regulatory requirements.

Understanding ABS and Its Applications in Medical Devices

ABS is a versatile thermoplastic polymer widely used in the medical device industry due to its durability, chemical resistance, ease of processing, and biocompatibility. Applications include:

• Diagnostic equipment housings, including imaging machines and laboratory instruments
• Drug delivery devices, such as nebulizers, auto-injectors, and portable drug delivery systems
• Intravenous Access Devices, including components of IV connectors and luers
• Respiratory care devices, such as ventilator valves, medical masks, and tracheal tubes
• Non-absorbable sutures and tendon prostheses

ABS can be sterilized using methods like ethylene oxide gas, gamma radiation, or steam. The material can be easily colored and shaped to meet specific design requirements.

Challenges for Medical Device Manufacturers: Supply Chain Disruptions

The closure of the Addyston facility may lead to potential shortages and longer lead times for ABS materials. Manufacturers will need to diversify their supplier base and potentially look for alternative sources.

Cost Implications: A change in the ABS supplier could result in ship holds during qualification of a new supplier, resulting in a loss of profit from medical device sales. Further, the supplier change could impact material costs, potentially affecting the cost of medical devices.

Quality and Regulatory Concerns: ABS from new suppliers will need to be qualified to ensure that safety and effectiveness have not been impacted. 

Innovation Pressure: This situation may accelerate the exploration of alternative materials to reduce dependency on traditional ABS.

Specific Healthcare Manufacturing Aspects

1. Drug Delivery Systems. Impact: Potential redesign of portable drug delivery devices and auto-injectors
2. Diagnostic Equipment. Impact: Possible delays in production of imaging machine housings and laboratory instruments
3. Respiratory Care. Impact: Potential shortages of components for ventilators and other respiratory devices
4. Surgical Instruments. Impact: Possible delays in production of certain non-absorbable sutures and prostheses

In each of these areas, the challenge will be maintaining biocompatibility and device specifications with new materials.

Regulatory Challenges

Qualifying new ABS suppliers involves navigating complex regulatory pathways, which vary based on the device's risk classification. For 510K cleared devices, a supplier change can be documented with a letter to file that confirms verification with the new material or, if the new material impacts safety or effectiveness, in a new 510(k) submission.  For PMA cleared devices, a supplier change can be documented in the annual report or, if the new material impacts safety or device effectiveness, in a PMA supplement.  

How CPG Can Help

CPG can assist medical device manufacturers in developing a tailored regulatory strategy for qualifying new ABS suppliers. This strategy will consider:

1. Supplier Qualification Process: Developing criteria for selecting and evaluating new ABS suppliers based on FDA expectations, as well as REACH, RoHS, Prop-65, and MDR compliance.
2. Testing Protocol Development: Designing and implementing necessary tests to qualify ABS to ensure safety and effectiveness of the device have not been impacted. 
3. Regulatory Documentation Preparation: Assistance in preparing documentation that support the continued safety and effectiveness of the device, including biological risks assessments, memos, and letters to file. If necessary due to a change in safety or effectiveness, CPG can also assist in the preparation of new 510(k) submissions and PMA supplements.

By leveraging CPG's services, medical device manufacturers can navigate this supply chain challenge efficiently, minimizing disruptions to their production and market access while maintaining regulatory compliance. Collaboration between manufacturers, regulators, and material scientists will be crucial to maintain the quality and availability of essential medical products.

Holiday Hours

Please note that our lab will be closed on the following dates to allow our team to enjoy the holidays:

• December 24 - 25 (Christmas Eve & Day)
• December 31 - January 1 (New Year's Eve & Day)

We will resume normal business hours on January 2nd, ready to tackle your new materials challenges in the coming year.

If you have any questions or need assistance on existing quotes or projects, feel free to reach out by email or contacting us at 617-629-4400.

Additionally, if you have any new consulting or testing needs, we would be happy to discuss how we can assist you.

We are truly grateful for your partnership and look forward to providing you with game-changing material science consulting and testing in 2025 and beyond.

Warmly,

The Cambridge Polymer Group Team

ASTM recently published a new version of F2459 "Standard Test Method for Extracting Residue from Medical Components and Quantifying via Gravimetric Analysis.” This updated standard expands its scope beyond metallic implants to include ceramic and polymeric medical devices.

Key Updates and Applications

• Expanded Scope: The standard now covers residue assessment for metallic, ceramic, and polymeric medical devices.
• Cleanliness Assessment: It serves as a high-level evaluation method for medical device cleanliness.
• Additive Manufacturing: The standard provides a basis for preparing extracts for particulate residue assessment in additive manufacturing standards.
• FDA Recognition: The FDA recognizes this standard for quality assessment of medical device manufacturing facilities.

Significance and Contributions

• The standard identifies two techniques to quantify extractable residue on medical components.
• It allows investigators to compare relative levels of component cleanliness.
• The method's applicability has been demonstrated through numerous literature reports.

Impact on the Medical Device Industry

The expansion of ASTM F2459 to include ceramic and polymeric medical devices is a significant development for the industry. As medical technology advances, the materials used in device manufacturing have diversified, necessitating more comprehensive testing methods. This update ensures that a wider range of medical devices can be assessed for cleanliness using a standardized approach. 

Benefits for Manufacturers

1. Consistency: Provides a uniform method for cleanliness assessment across different material types.
2. Quality Assurance: Helps manufacturers maintain high standards of cleanliness in their production processes.
3. Regulatory Compliance: Aligns with FDA expectations, potentially streamlining the approval process.

Implications for Patient Safety

The enhanced standard contributes to patient safety by:

• Ensuring more thorough cleanliness assessments for a broader range of medical devices.
• Reducing the risk of contamination-related complications in patients.
• Promoting confidence in the safety and quality of medical devices.

The Role of Gravimetric Analysis

Gravimetric analysis, the core technique in ASTM F2459, involves precise weighing of residues extracted from medical components. This method:

• Provides quantitative data on the amount of extractable residue.
• Is highly sensitive, capable of detecting minute amounts of contaminants.
• Offers reproducible results, crucial for quality control and regulatory compliance.

Future Directions

As the medical device industry continues to evolve, particularly with the rise of additive manufacturing and novel biomaterials, standards like ASTM F2459 will likely undergo further changes. Areas of potential future development include:

• Integration with other analytical techniques for more comprehensive residue characterization.
• Adaptation to emerging manufacturing technologies and materials.
• Enhanced protocols for specific types of medical devices or materials.

Scientists from Cambridge Polymer Group contributed to the revisions of this standard and regularly conduct this test. Our involvement underscores the collaborative nature of standards development, bringing together expertise from industry, academia, and regulatory bodies.

This update reflects the evolving needs of the medical device industry, particularly in light of new manufacturing technologies like additive manufacturing. As the industry continues to innovate, the importance of robust, adaptable standards like ASTM F2459 becomes increasingly critical in ensuring the safety and efficacy of medical devices.