How to Properly Prepare Biocompatibility Test Samples for Medical Devices

When developing medical devices, ensuring they are biocompatible is essential for both patient safety and regulatory compliance. Proper sample preparation is a critical step in conducting accurate biocompatibility testing, as even small errors can affect the results. This article explores best practices, regulatory guidelines, and practical steps to help you prepare your biocompatibility test samples effectively.

1. Understanding Biocompatibility Testing Requirements

Biocompatibility testing assesses how a medical device or material interacts with human tissue. This testing is essential for medical devices that come into contact with the human body, as it helps verify that materials will not provoke adverse biological responses. Typically, biocompatibility testing follows the ISO 10993 standard series, which offers comprehensive guidelines for testing methods and sample preparation.

2. Sample Selection and Preparation Considerations
3. Identify the Right Sample Material

The testing process starts by identifying the precise materials that will be in contact with the body. It’s essential to select samples that are representative of the finished device, including any coatings, sterilization, and packaging. Variations between test samples and the final product can lead to inconsistent results, potentially causing unnecessary delays in approval processes.

1. Device Contact Classification
   Medical devices are classified by their intended use and duration of contact with the body, as specified in ISO 10993-1, which provides guidelines for biological evaluation based on these factors. These classifications guide the required testing:

• Contact Duration: Categorized into limited (<24 hours), prolonged (24 hours – 30 days), and permanent (>30 days) exposure.
• Contact Type: Includes skin, mucosal membrane, blood, bone, and more.

This classification, defined in ISO 10993-1, is essential for determining what types of biocompatibility testing are required (e.g., cytotoxicity, sensitization, or hemocompatibility).

3. Best Practices for Sample Preparation

Proper extraction conditions are the essential starting point in biocompatibility testing to ensure accurate results. ISO 10993-12 provides specific guidelines for the preparation of samples and the selection of extraction parameters. For instance:

• Temperature: Typically ranges from 37°C for prolonged exposure to higher temperatures for accelerated aging studies.
• Solvents: Chosen based on compatibility with the sample and intended extraction outcome.

Adhering to these standards ensures reliable, reproducible data, minimizes safety risks, and provides assurance that regulatory requirements are met, increasing the likelihood of test acceptance by regulatory authorities. The following best practices outline key considerations for sample preparation:

1. Cleanliness and Sterility

All samples must be handled with gloves and prepared in a controlled environment to avoid contamination. Cleanliness is crucial because residues from handling, packaging materials, or the environment can interfere with testing outcomes.

1. Sample Size and Surface Area

To get valid results, the sample’s size, shape, and surface area should be carefully considered. The surface area exposed to the extraction medium is especially important, as it can affect the concentration of leachables. The ISO standard typically suggests using a specific surface area to volume ratio, specific to the evaluated medical device.

1. Storage Conditions

Biocompatibility testing must be conducted on products within their validity date to ensure accurate and reliable results. It is essential that samples are stored according to recommended conditions to prevent material degradation or contamination before testing.

1. Device Configuration for Testing

Devices should be prepared in the configuration that represents their use. This means testing in the form in which it will contact the body, such as full or assembled devices, particularly when adhesives or other joining materials are used.

4. Key Steps in Preparing Biocompatibility Test Samples

Here’s a step-by-step overview to help ensure your samples are prepared correctly:

1. Document and Identity: Begin by documenting all aspects of the sample, including the manufacturing batch, materials, and any post-processing steps (e.g., sterilization). Use labels to distinguish between different batches or sample types.
2. Cleaning and Preconditioning: If the device requires cleaning before testing, use validated processes, avoiding any cleaning agents that could interfere with the biocompatibility results.
3. Cutting and Shaping: Cut or shape samples to fit within testing equipment or to achieve the required surface area for testing. Use clean, contamination-free cutting tools. If you decide to cut a part of the device, you must justify this decision based on the device’s intended use and testing requirements. While cutting the product may be necessary in some cases, it’s often preferable to test the whole device or, at the very least, the part of the device that will come into direct contact with the human body. This approach ensures that the testing is representative of the actual conditions under which the device will function.
4. Extraction Methodology: Select appropriate extraction solvents and conditions based on ISO 10993-12, based on the contact duration of the device and material composition. The extraction method should be specified in the Biological Evaluation Plan (BEP) in advance, ensuring consistency throughout the testing process. Confirm that the solvent choices do not interact with the sample and that the method outlined in the BEP is adhered to during testing.
5. Environmental Control: Ensure that sample preparation takes place in a controlled, low-particulate environment. Prepare samples in isolation to reduce contamination risk.

Fortunately, most of these steps will be handled by an experienced testing laboratory, such as EBI, ensuring that the biocompatibility testing is conducted according to the highest standards. Your role will primarily involve cooperating with us throughout the process to ensure smooth and efficient execution.

5. Common Pitfalls in Sample Preparation and How to Avoid Them

• Contamination: Ensure proper handling, storage, and cleanliness protocols.
• Inconsistent Sample Size: Using consistent surface area ratios helps achieve reliable data.
• Incorrect Solvent, Temperature Choices, or Extraction Ratio: Always verify with ISO 10993-12 guidelines and conduct pilot tests if needed.

If you choose an experienced and trusted laboratory, you don’t need to worry about these potential pitfalls. You can simply oversee the process, confident that the testing will be conducted according to the highest standards.

6. Ensuring Compliance and Documentation

Documentation is crucial in sample preparation, as regulatory bodies may request detailed records of sample handling, preparation, and testing. Key elements include:

• Chain of Custody Documentation: Tracking each sample from manufacture through testing.
• Testing Reports: Detailed reports on testing procedures, results, and any deviations from protocols.

Conclusion

Proper preparation of biocompatibility test samples is essential for producing reliable data and avoiding delays in the regulatory approval process. By following ISO 10993 guidelines, selecting appropriate sample sizes and configurations, and maintaining a clean testing environment, companies can ensure the accuracy and compliance of their biocompatibility testing results. Following these best practices not only supports regulatory compliance but also protects patient health by ensuring safe and effective medical devices.

For companies like EBI – European Biomedical Institute, expertise in preparing and testing biocompatibility samples is a core service offering, helping device manufacturers navigate the complexities of regulatory compliance. More information about the number of samples required for each test can be found in the “How many samples for biocompatibility tests?” section on the EBI website.

About the Author: Dr. Damian Matak

Dr. Damian Matak – an expert in medical device biocompatibility testing, serving as the CEO of ISO 17025-accredited and GLP-certified laboratories, including EBI – European Biomedical Institute and NABI – North American Biomedical Institute. As a member of the Polish Society of Toxicology and the I Local Ethical Committee, Dr. Matak contributes significantly to advancing safety standards in the biomedical field.