Quality

Ensuring Patient Safety: A Comprehensive Guide to the
Biological Evaluation of Medical Devices

 

Dr. T S Kumaravel Founder Chairman GLR Laboratories, UK

Dr. M R Murali, Dr. S S Murugan, Dr. T S Kumaravel, GLR Laboratories Pvt. Ltd. INTORODUCTION The biological evaluation of medical devices is a crucial part of the regulatory framework aimed at ensuring patient safety. Experts with the necessary knowledge and experience should conduct this evaluation. According to Section B.3.1.4 of ISO 10993-1, “It is critical for the integrity of a biological risk evaluation that it should be conducted by assessors with the necessary knowledge and expertise to determine the appropriate strategy for the evaluation and ability to make a rigorous assessment of the available data and to make sound judgments on the requirements for any additional testing” [1].

Successful biological evaluation depends on collaboration among various stakeholders [Figure 1]. The medical device manufacturer provides essential information about components and materials, including details on manufacturing and cleaning additives. The material supplier offers comprehensive data on composition, including MSDS and CoA. The biomedical engineer selects suitable materials for device construction and designs devices to minimize biological risks. The toxicologist performs toxicological risk assessments, evaluates data from biological tests, and recommends strategies for risk mitigation. The analytical chemist identifies the extraction strategy, selects appropriate solvents, and conducts chemical characterization studies to report extractables. Additionally, the toxicologist, veterinarian, and pathologist carry out standard biocompatibility tests, analyze and report results, and provide scientific interpretations.

Two essential documents in the biological evaluation process are the Biological Evaluation Plan (BEP) and the Biological Evaluation Report (BER). These documents offer a systematic approach to assessing and documenting the biocompatibility of medical devices, ensuring that all potential biological risks are identified, evaluated, and mitigated [Figure 2]. The overall biological evaluation process should be seen as an ongoing cycle of improvement. Post-market surveillance data, feedback from clinical use, and new scientific findings should be continuously integrated into the BEP and BER. This iterative approach helps maintain the relevance and accuracy of the biological evaluation, ensuring the long-term safety and efficacy of the medical device.

BIOLOGICAL EVALUATION PLAN

A biological evaluation plan (BEP) is a strategic document that outlines the approach and rationale for assessing the biological safety or biocompatibility of a medical device. This plan is based on ISO 10993 1, which provides guidelines for the biological evaluation of medical devices within a risk management process. The BEP identifies the necessary tests and evaluations to determine the potential biological risks posed by the device. It considers the materials used in the device, its intended use, and existing data to prescribe a risk-based approach to evaluating device safety. By understanding these factors, the plan identifies potential biological risks and outlines the necessary steps to
address them. Leveraging existing data, including historical data and previous studies, helps reduce redundancy in testing. This strategic approach ensures compliance with regulatory standards and promotes efficiency and resource optimization in the evaluation process.

ISO 10993-1 mandates that the biological evaluation of any medical device intended for human use must be part of a structured biological evaluation plan within a risk management process, in accordance with ISO 14971. The BEP is also instrumental in demonstrating that medical devices comply with FDA and EU regulations. The FDA recognizes ISO 10993-1 as a consensus standard that manufacturers should follow when assessing medical device biocompatibility. This recognition ensures that the BEP aligns with the FDA’s stringent requirements for medical devices, thereby facilitating smoother regulatory approval processes. The FDA’s guidance document on use of ISO 10993-1 further underscores the necessity of developing a BEP to address any knowledge gaps through biocompatibility testing or other evaluations [2]. This approach ensures that all potential risks are adequately assessed and mitigated.

While the Biological Evaluation Plan is not explicitly mentioned in the EU Medical Device Regulation (MDR), the regulation obligates manufacturers to provide detailed information on their devices’ biocompatibility and the methods used to evaluate it [3]. This requirement ensures that all medical devices meet the necessary safety and performance standards before being marketed in the EU.

Key components of the BEP

A holistic approach to the BEP involves not only evaluating individual components but also considering the overall design and intended use of the device. This includes understanding the clinical context in which the device will be used, the duration of contact with the body, and the specific tissues and organs that may be affected. This broader perspective helps identify potential risks that might not be apparent when focusing solely on individual components. The plan starts with a comprehensive review of the device's materials, design, and intended use. By understanding these factors, the BEP identifies potential biological risks and outlines steps to address them, leveraging existing data to reduce redundant testing [4]. Thus, the BEP should include details on the following:

Device description: A comprehensive device description is essential for the biological evaluation plan. This section should provide detailed information about the device, including its materials, manufacturing processes, and intended use. It should also include a description of the medical device family, if applicable and the materials of construction. This information forms the foundation for understanding the potential biological interactions and risks associated with the device.

Intended use: The intended use section outlines the clinical context in which the device will be used. This includes specifying the duration of contact with the body and identifying the specific tissues or organs that will be affected. Understanding the intended use is crucial for selecting the appropriate biocompatibility tests and ensuring that the device is safe for its designated application.

Device categorization: Device categorization involves classifying the device based on several factors, including frequency and duration of contact with the human body. The frequency of contact can be categorized as single use, repeated use, or continuous use. The duration of contact can be classified into limited exposure (less than or equal to 1 day), prolonged exposure (more than 1 day but not more than 30 days) and longterm exposure (more than 30 days). This categorization helps in determining the specific biocompatibility tests required for evaluating the device’s safety.

Reasonably foreseeable misuse: Reasonably foreseeable misuse refers to the use of a medical device in a manner not intended by the manufacturer, but which can result from readily predictable human behaviour. This section addresses potential misuse scenarios to ensure that the device remains safe and effective even when used incorrectly.

Risk assessment: Risk assessment is a crucial component of the biological evaluation plan. It involves identifying potential biological risks based on the device’s materials and intended use. This process includes leveraging existing data to reduce redundant testing, utilizing historical data and previous studies to inform the evaluation. By systematically identifying and assessing risks, the plan ensures that all potential hazards are addressed and mitigated.

Testing strategy: The testing strategy section outlines the selection of appropriate biocompatibility tests to evaluate the device’s safety. This includes tests for cytotoxicity, sensitization, irritation, systemic toxicity, genotoxicity, implantation and hemocompatibility. Additionally, chemical characterization is performed to identify potential hazards associated with the device’s materials. This comprehensive testing approach ensures that all potential biological risks are thoroughly evaluated, providing a robust assessment of the device’s biocompatibility.

Chemical characterization: BEP includes chemical characterization to identify potential hazards associated with the device’s materials. This step is crucial for understanding the material composition and identifying potential leachable and extractable substances. By thoroughly analyzing the chemical makeup of the device, the evaluation can pinpoint any substances that might pose a risk to patient safety. This detailed chemical characterization helps ensure that all potential hazards are recognized and addressed early in the evaluation process.