Biocompatibility testing data is always required for medical devices with direct and indirect contact. ISO 10993-1:2018 through the Biological Evaluation Plan (BEP) allows to determine the potential risk based on the data provided by the Sponsor (information on raw materials, packaging, production conditions and previously performed studies).
Based upon the above normative provisions, this document is intended to give documented evidence of the requested prospective and risk-based biological planning process and to finally conclude on the biological testing strategy which should be executed in order to comply with the relevant normative requirements as applicable for the investigational medical device.
A Biological Evaluation Plan is used to prove the safety of the device by demonstrating compliance to corresponding standards and avoiding unnecessary testing of the device.
Since biological evaluation is a risk management activity, a Biological Evaluation Plan is required, and this forms part of the Risk Management Plan.
The biological evaluation plan should be drawn up by a knowledgeable and experienced team and that includes:
- arrangements for gathering of applicable information from the published literature
- arrangements for review and approval of the plan as part of the overall design control process
- arrangements for review of the final conclusions of the evaluation and the approval of any additional testing required
- arrangements for the final review and approval of the outcomes of the biological risk assessment
REGULATORY BACKGROUND AND NORMATIVE REQUIRMENTS
- ISO 10993 standards
- FDA Guidance on ISO 10993
- Regulation 2017/745 (MDR)
Factors considered during Biological Evaluation
- The material(s) of construction (i.e., all direct and indirect tissue contacting materials);
- Medical device configuration (e.g., size, geometry, surface properties)
- Intended additives, process contaminants and residues during the manufacturing of the device
- The manufacturing processes
- Packaging materials that directly or indirectly contact the medical device
- Leachable substances & Degradation products
- Other components and their interaction in the final product
- The performance and characteristics of the final product
- The physical and chemical characteristics of the device
- Systemic effects and local effects of implantable devices
- Biological hazards of every material and final product
- Existing toxicology and other biological safety data
IDENTIFICATION OF BIOLOGICAL HAZARDS TO BE ADDRESSED
Based on product classification and considering the aforementioned the ISO 10993-1:2018 Table A.1, as well as the FDA Guidance document „Use of International Standard ISO 10993-1, ‘Biological Evaluation of Medical Devices Part 1: Evaluation and Testing within a Risk Management Process”, dated 4 September 2020, the following biological risks will be identified to be particularly relevant and applicable for the medical device.
DETERMINATION OF REQUIRED TESTING BASED UPON EXISTING EXPERIMENTAL EVIDENCE
The above assessment of critical aspects which must be subjected to testing and/or justification based upon alternative evidence (e.g. results from scientific literature, test reports of chemically identical/similar products or materials), the following requirements for experimental testing could be identified.
- Drug/device interaction