Regulatory agencies worldwide require extensive risk assessments and biological safety evaluations on medical devices to ensure their safety and effectiveness. A key part of this evaluation is the creation of a Biological Evaluation Plan (BEP), which assesses biological risks in a structured manner.
Having a BEP in place before biocompatibility testing is performed helps companies choose the most appropriate testing procedure and avoid unnecessary tests, including those conducted on animals.
Why is the BEP needed?
The standard ISO 10993-1 on the biological evaluation of medical devices emphasizes the need to prepare a structured biological evaluation plan to assess the biological risks associated with the use of a medical device. The ultimate goal is to determine whether the risks are acceptable in relation to the device’s clinical benefits.
The BEP plays an important part in demonstrating that medical devices are compliant with FDA and EU regulations:
The FDA recognizes ISO 10993-1, which outlines the need for a BEP, as a consensus standard that manufacturers should follow when assessing medical device biocompatibility.1
While the Biological Evaluation Plan is not explicitly mentioned in the EU Medical Device Regulation (MDR), the regulation does obligate manufacturers to provide detailed information on their devices’ biocompatibility and the way it has been evaluated.2
Who can prepare the Biological Evaluation Plan?
According to ISO 10993-1, the BEP must be “planned, carried out, and documented by knowledgeable and experienced professionals”.3 Measurlabs can provide the BEP for companies aiming to bring medical devices to market and help with all the necessary biocompatibility tests.
What information should the BEP include?
The BEP includes information on the device, its intended uses, target patients, foreseeable risks, and a plan for biocompatibility testing to address these risks. Some important details can include:4
Physical description of the device and its components
Intended clinical use, including target patient groups
Nature of body contact and contact duration
List of raw materials and chemicals used to manufacture the device
Existing data on the toxicological profile of raw materials
Description of the packaging
Information on the cleaning and sterilization procedure, including possible residuals
The shelf life of the product
Existing chemical characterization and biocompatibility reports, if available
A plan for conducting further chemical and biological testing to address the risks not sufficiently covered by existing data
Medical device testing in accordance with the BEP
The BEP helps manufacturers determine which biocompatibility tests are needed, as it identifies gaps in existing data on the device and suggests a testing procedure for addressing them. The extent of testing is principally based on the nature, degree, frequency, and duration of patient exposure to the medical device and the risks associated with the device’s physical and chemical composition.5
Regardless of the device, chemical characterization (ISO 10993-18) should be completed before biological testing.6 Almost all devices also require cytotoxicity (ISO 10993-5), sensitization (10993-10), and irritation (ISO 10993-23) testing.
Depending on the device and the identified risks, other necessary tests might include implantation effects (ISO 10993-6), genotoxicity (ISO 10993-3), carcinogenicity (ISO 10993-3), hemocompatibility (ISO 10993-4) and material-mediated pyrogenicity (ISO 10993-11). ISO 10993-11 can be used for a variety of additional toxicity tests, including acute systemic toxicity, subacute and subchronic toxicity, and chronic toxicity.7
Determining the exact tests your medical device requires can be complex. Measurlabs is ready to help prepare a BEP for your device and provide all the biocompatibility tests needed to ensure regulatory compliance. You can contact our experts through the form below to learn more.
References
1 U.S. Food and Drug Administration’s (FDA) recognition of ISO 10993-1 as a consensus standard.
2 See Annex II, Section 6.1 of Regulation (EU) 2017/745.
3 Section 4.1, ISO 10993-1, Biological evaluation of medical devices - Part 1: Evaluation and testing within a risk management process
4 Section 4.1 of ISO 10993-1
5 Section 4.4 of ISO 10993-1
6 Section 4.3 of ISO 10993-1
7 Section 6.3.2 of ISO 10993-1