A ND Global Guide on Biological Evaluation

INTRODUCTION – The approach taken to address biological risk, or biocompatibility, for medical devices is described in depth in the Biological Evaluation Plan. The medical device’s configuration, material composition, manufacturing process, intended use, testing history, and any existing testing data must all be examined in a biological evaluation plan, which is a mandatory. Following the identification of any biocompatibility gaps for the medical device, the Biological Evaluation Plan will offer professional advice on how to close these gaps based on ISO 10993-1 and documents unique to the product or nation.

While the choice of appropriate tests varies depending on the item, assessments used to ascertain the biological risks of medical devices are outlined in ISO 10993 and product-specific standards. The European Union first released the updated global ISO 10993-1:2018 standard as EN ISO 10993-1:2020, which was subsequently translated into national EN ISO 10993-1:2021 versions. Taking this into consideration, a few adjustments need to be made. “This document does not intend to provide a rigid set of test methods, including pass/fail criteria, as this could result in either an unnecessary constraint on the development and use of novel medical devices, or a false sense of security in the general use of medical devices,” states the introduction of the new standard.

The ISO 10993 series is designed to be used by professionals who have received the necessary training and experience to understand its requirements and evaluate each medical device individually, taking into account all relevant factors, the device’s intended use, and the state of knowledge about the device at the time of evaluation as determined by reviews of the scientific literature and prior clinical experience.

Risk management operations have to be prearranged in accordance with ISO 10993-1:2018 Appendix B.2.2 (the biological evaluation plan). A biological evaluation plan is necessary because biological evaluation is a risk management activity. It is stressed that meeting the standards does not mean only preparing to test against every biocompatibility factor listed in Annex A.

WHAT IS A BIOLOGICAL EVALUATION PLAN (BEP)?

A biological evaluation plan, or BEP, is a crucial stage in the manufacturing of medical devices. The international set of standards for the biological assessment of medical devices, ISO 10993, is in line with this plan. A methodical strategy to assessing possible risks and damages between a medical equipment and the human body is described in the 10993 series.

This important document details the components of the device, its intended usage, and the length of patient interaction. Based on these specifics, it determines which tests are necessary to evaluate the device’s safety.

WHAT IS THE PURPOSE OF A BIOLOGICAL EVALUATION PLAN?

A biological evaluation plan’s main objective is to minimise patient harm by ensuring the medical device’s safety and biocompatibility. It evaluates the possible risks that might occur from the gadget making touch with the patient’s body. This covers all biological risks that may injure the patient directly by causing tissue or cell damage or indirectly by releasing noxious compounds. Additionally, biological assessment helps prove adherence to legal requirements like ISO 10993. This aids in receiving regulatory body approval, allowing the equipment to be released onto the market and improve patient care.

WHAT IS THE BIOLOGICAL EVALUATION PLAN PROCEDURE?

The biological evaluation process is a coordinated endeavour that starts with learning about the medical equipment, how it will be used, and any potential dangers. Biocompatibility testing is carried out once an ISO 10993-compliant BEP has been created, and the results are evaluated in conjunction with thorough risk assessments.

Create a biological assessment plan (BEP): Make a BEP using the guidelines found in ISO 10993. The tests required to assess the device’s biocompatibility and safety should be specified in the BEP.
Evaluations of risks and testing: Test for biocompatibility in accordance with ISO 10993 and BEP recommendations. Through a variety of tests conducted in specialised laboratories, it fully investigates the possible impacts on the biological system of a patient.
Report on biological evaluation (BER): For thorough documentation, the data collected during the testing phase is analysed and recorded in a BER. A judgement regarding the benefit/risk ratio for biological risks is made in accordance with ISO 14971. The device’s biocompatibility is determined once a risk evaluation is completed.

It’s critical to keep in mind that biological evaluation is a continuous process that necessitates regular post-market oversight and modifications in order to comply with changing criteria.

WHAT ARE THE FACTORS CONSIDERED DURING BIOLOGICAL EVALUATION?

Accountabilities: This lists each person’s duties, qualifications, and areas of expertise related to the evaluation process.
Material selection: The best materials are chosen at this stage by assessing the device’s possible materials in light of their characteristics and clinical experiences.
Material characterization: In accordance with ISO 10993 guidelines, this step describes the components, manufacturing method, and possible residues used in the device’s construction. It entails determining and measuring materials and compounds that can be leached, as well as evaluating the properties of degradable materials.
Review of the literature: In accordance with ISO 10993-1 and ISO 14971, a review of the literature is conducted, looking at the materials’ possible biological hazards as well as any toxicological data that are already available.
Testing selection: In accordance with ISO 10993-1 and ISO 14971, the final step entails choosing appropriate tests, particularly in cases when the risk level is not compatible with the planned use of the device.

FRAMEWORK FOR EVALUATION:

As part of a holistic risk management plan, manufacturers should approach the biological evaluation process. This method entails a comprehensive analysis and assessment of the data that is currently available from multiple sources, along with the possible use of additional testing. This comprehensive assessment improves the safety profile of the gadget by enabling a thorough comprehension of its biological reactions. The main objective is to give manufacturers a methodical and transparent framework that supports them in making informed decisions at every stage of the device’s lifecycle.

Figure 1: Summary of the systematic approach to a biological evaluation of medical devices as part of a risk management process

Figure 2: Endpoints to be addressed in a biological risk assessment

It is crucial to offer a thorough description of a medical device’s chemical composition and characterise its materials before beginning any biological testing. Observing ISO 10993-18 for chemical characterization is part of this. This kind of categorization helps establish suitable toxicological thresholds for deciding whether additional testing is necessary. You can find more information on this procedure in ISO 10993-18, ISO 10993-17, and Annex B.

IMPORTANT LESSONS FOR MANUFACTURER OF MEDICAL DEVICES:

Regulatory Compliance Is Non-Negotiable: It is essential to follow rules and regulations that have been set down, such as the ISO 10993 series. The foundation for guaranteeing the biological safety of medical devices is regulatory compliance.

Adopt Holistic Risk Management: An extensive risk management plan should include

biological evaluation as a fundamental component. It is recommended that manufacturers
include this procedure seamlessly into their overall efforts related to risk assessment, design, and development.

Material Selection Significance: Careful selection and in-depth characterisation are essential. To ensure patient safety, it is essential to obtain a thorough understanding of the biological consequences of device materials.
Give Priority to In Vitro Testing: To reduce dependence on animal testing and preserve ethical standards, give preference to in vitro testing techniques over in vivo ones whenever possible.
5. Constant Monitoring and Adjustment: The assessment of biological systems is a continuous procedure. The biological safety of equipment must be regularly monitored and reevaluated by manufacturers, especially when any modifications are made.

CONCLUSION – The biological evaluation of medical devices is a critical process aimed at ensuring patient safety and minimizing potential risks associated with device interaction within the human body. The Biological Evaluation Plan (BEP) serves as a roadmap for evaluating device safety and biocompatibility, taking into account factors such as device configuration, material composition, intended use, and testing history. By adhering to these principles and guidelines, manufacturers can ensure the biological safety of medical devices, obtain regulatory approvals, and ultimately enhance patient care. Biological evaluation is not a one-time activity but rather a continuous process that requires ongoing attention and adaptation to changing criteria and circumstances. Thus, manufacturers must remain vigilant and proactive in maintaining the safety and efficacy of medical devices.

How ND Global can help: ND Global plays a crucial role in assisting medical device manufacturers throughout the biological evaluation process. With expertise in regulatory compliance and risk management, ND Global offers comprehensive services tailored to meet the specific needs of manufacturers in the medical device industry.

Here’s how ND Global can help:

Regulatory Compliance Assistance: ND Global provides guidance and support to ensure that medical devices adhere to relevant regulations and standards, including ISO 10993 series. By staying updated on regulatory requirements, ND Global helps manufacturers navigate complex compliance landscapes efficiently.
Biological Evaluation Plan (BEP) Development: ND Global assists in the creation of Biological Evaluation Plans (BEPs) aligned with ISO 10993 guidelines. By considering factors such as device configuration, material composition, intended use, and testing history, ND Global helps manufacturers develop comprehensive BEPs tailored to their specific devices.
Risk Management Support: ND Global offers expertise in risk management operations, including risk assessments and mitigation strategies as per ISO 14971. By identifying and addressing potential biocompatibility gaps, ND Global helps manufacturers minimize risks associated with medical device use.
Documentation and Reporting: ND Global assists in the documentation and reporting of biological evaluation findings, including the preparation of Biological Evaluation Reports (BERs). By compiling and analyzing testing data in accordance with regulatory requirements, ND Global helps manufacturers demonstrate compliance and facilitate regulatory body approval.
Testing Coordination: ND Global facilitates the coordination of biocompatibility testing, ensuring that tests are conducted in accordance with ISO 10993 and BEP recommendations. By liaising with specialized laboratories and overseeing testing processes, ND Global helps manufacturers obtain reliable data for evaluating device safety.
Continuous Monitoring and Adjustment: ND Global emphasizes the importance of continuous monitoring and adjustment in biological evaluation. By providing ongoing support and guidance, ND Global helps manufacturers stay proactive in ensuring the biological safety of their devices, especially in response to any modifications or updates.