Surface Morphology

A Case Study On Implantation Endpoint

In a previous blog post, we highlighted the essential role of surface characterization in ensuring the biocompatibility of medical devices and the impact of surface properties on biological interactions. Expanding on this foundation, we will now analyze a case study centered around the implantation endpoint.

Implantable medical devices must undergo thorough biocompatibility assessments, including long-term systemic endpoints, in accordance with ISO 10993 and other regulatory guidelines. A key biological endpoint to address is implantation per ISO 10993-6, which evaluates local tissue responses. When a manufacturing change occurs, it may not be necessary to reassess all biological endpoints if there is sufficient information to evaluate the associated risks. If the change does not introduce any new risks, previous biocompatibility testing data can be utilized. Specifically, if the surface properties of the implant remain consistent with those of the previously tested device, additional implantation studies may be unnecessary. Below is a case study highlighting a manufacturing change where surface characterization data demonstrated no significant changes in surface topography, allowing for a risk-based justification to waive further implantation testing.

A medical device manufacturer has implemented a change in the cleaning agent used to remove lubricants during the processing of one of its metal components. The device is classified as having long-term contact duration (exceeding 30 days) with tissue or bone contact. According to ISO 10993-1, the biological effects that must be evaluated for this device include:

• Cytotoxicity
• Sensitization
• Intracutaneous Reactivity
• Material-mediated Pyrogenicity
• Acute Systemic Toxicity
• Subacute/Subchronic and Chronic Toxicity
• Implantation
• Genotoxicity
• Carcinogenicity

All biocompatibility endpoints were met for test articles manufactured using the original cleaning agent. Subsequently, the manufacturer proposed transitioning to a new cleaning agent. No other modifications were made to the implant aside from the introduction of the new cleaning agent.

The manufacturer initially planned to repeat an expensive biological implantation study to evaluate the surface characteristics of their implants. However, after reviewing the device description and manufacturing changes, our team of experts recommended a more cost-effective optical profilometry. This non-destructive technique provides high-resolution surface measurements, allowing for precise comparison of implant topographies without the need for extensive in vivo testing. By adopting this approach, the manufacturer was able to obtain reliable data while significantly reducing study costs and time. This proposal was also accepted by the FDA.

In this case, surface roughness of sterile device test articles was examined using scanning electron microscopy (SEM) and optical profilometry. SEM images showed no significant differences in surface smoothness or irregularities between the originally approved and proposed cleaning agents. Optical profilometry confirmed similar roughness values for both agents, indicating the modified cleaning agent had no significant impact on the devices.

Additionally, the testing results for the new cleaning agent (cytotoxicity, sensitization, intracutaneous reactivity, and material-mediated pyrogenicity) showed no evidence of potential concern for any of these biological endpoints. The potential concerns of any systemic endpoints were addressed with an extractable study. The surface appearance and morphology of the proposed devices (supplemented by results from other biological testing through cytotoxicity, sensitization, irritation, and pyrogenicity testing) were substantially similar to the parts of the originally approved device, showing reasonable assurance of safety in terms of the implantation endpoint.

In conclusion, this case study demonstrates the utility of advanced surface characterization techniques, such as SEM and optical profilometry, to validate the consistency and safety of implantable medical devices following a manufacturing change. By leveraging these high-resolution, non-destructive methods, the manufacturer not only ensured compliance with regulatory standards but also significantly reduced costs and time otherwise associated with animal testing. This approach exemplifies a commitment to both innovation and ethical responsibility in the development and validation of medical devices, reinforcing the importance of thorough surface morphology analysis as another tool to ensure patient safety and device performance.

With our in-house toxicologist, biocompatibility expertise, and SEM capabilities, MED Institute offers a comprehensive suite of surface characterization services that are essential for the development and validation of safe medical devices. MED maintains an ISO/IEC 17025:2017 accreditation and can produce validations for many surface characterization methods. We have extensive experience in assessing the surface roughness of cardiovascular implants, analyzing the wear resistance of orthopedic implants, measuring fatigue, corrosion, and particulates of catheters or stents, or understanding the biological adhesion of drug delivery systems. Whether it is complex or simple surface characteristics of a medical device, MED Institute is equipped to provide detailed and reliable analysis to meet regulatory requirements and support innovation in the medical device industry. Testing packages are not limited to those properties that are relevant to biological evaluation or standards (ISO or ASTM) but also can be customized to evaluate any physical properties of the materials or device. MED institute provides detailed assessments of surface morphology. These evaluations are critical for understanding material interactions with biological systems, supporting biocompatibility assessments in accordance with ISO 10993-18 (chemical characterization) and ISO 10993-19 (physiochemical, morphological and topographical characterization). Additionally, MED Institute experts provide guidance on interpreting results and integrating findings in risk assessment for successful regulatory submissions.

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