The role of the Biological Evaluation Plan (BEP) in the biocompatibility evaluation of medical devices

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?

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. Similarly, standard ISO 18562-1 on the biological evaluation of devices with a breathing gas pathway explicitly states that "a biological evaluation plan shall be created".¹

The ultimate goal of the BEP is to determine whether the biological risks are acceptable in relation to the device’s clinical benefits. The document also plays an important part in demonstrating that medical devices are compliant with FDA and EU regulations:

• The FDA recognizes ISO 10993-1 and ISO 18562-1, which outline the need for a BEP, as consensus standards that manufacturers should follow when assessing medical device biocompatibility.²

• 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.³

Who can prepare the Biological Evaluation Plan?

According to ISO 10993-1, the biological evaluation must be "conducted and reported by competent personnel, capable of making informed decisions based upon scientific data and knowledge of relevant medical devices".⁴ As an experienced medical device testing provider with a broad network of accredited and GLP-certified partner laboratories, Measurlabs can provide the BEP and all the necessary biocompatibility tests for companies planning to bring medical devices to market. After testing has been completed, we can also provide a Biological Evaluation Report (BER) to summarize the findings.

What information should the BEP include?

The BEP should include information on the device, its intended uses, target patients, foreseeable risks, and a plan for biocompatibility testing to address these risks. Some important details typically include:

• Physical description of the device and its components

• Intended clinical use, including target patient groups

  • With the 2025 update of ISO 10993-1, "reasonably foreseeable misuse" should also be documented in the BEP

• 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 gap analysis and 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 outlines a testing procedure to address 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 Most new devices also require cytotoxicity (ISO 10993-5), sensitization (ISO 10993-10), and irritation (ISO 10993-23) tests.

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 also be followed for a variety of additional toxicity tests, including acute systemic, subacute, subchronic, and chronic toxicity.

In case the device has a breathing gas pathway that may expose the patient to hazardous substances, the testing plan typically includes evaluations for particulate matter (ISO 18562-2), volatile organic substances (ISO 18562-3), and leachables in liquid condensate (ISO 18562-4).

Determining the exact tests your medical device requires can be complex. Measurlabs is here 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 for more information and a quote.