Is Your Medical Device Safe? Understanding Biological Evaluation

Sebastian Skorka • Biological Evaluation • Updated June 01, 2025

Medical devices, from simple bandages to complex implants, are designed to help patients. But how do we ensure they don't cause harm when they interact with the human body? This is where biological evaluation comes in. It's a crucial process that investigates the biocompatibility of a device – essentially, how compatible it is with living tissues.

The main goal is patient safety. We need to be confident that a device won't cause unwanted reactions like toxicity, allergic responses, or other harm when used as intended.

Why is a Biological Evaluation Required? The Regulatory Angle

Regulators worldwide require proof that medical devices are safe before they can be sold. In the European Union, the Medical Device Regulation (EU) 2017/745 (MDR) sets the rules. Specifically, Annex I outlines the General Safety and Performance Requirements (GSPR) that all devices must meet.

Several GSPRs relate directly to biological safety, requiring manufacturers to:

Design and manufacture devices to minimize risks from substances leaching out, degradation products, or processing residues (GSPR 10.1).
Ensure devices are compatible with the tissues, cells, and body fluids they contact, considering the intended use (GSPR 10.1).
Pay special attention to evaluating and minimizing risks associated with invasive devices and those containing potentially hazardous substances like those classified as carcinogenic, mutagenic, or toxic to reproduction (CMR) or endocrine-disrupting chemicals (EDCs) (GSPR 10.4).

Meeting these MDR requirements is mandatory for placing a device on the EU market.

The "How-To" Guide: ISO 10993

While the MDR states what needs to be achieved (biological safety), it doesn't specify exactly how to prove it. That's where international standards come in. The key standard series for biological evaluation is ISO 10993, "Biological evaluation of medical devices."

The most important part is ISO 10993-1: Evaluation and testing within a risk management process. This standard provides the framework and overall strategy. It emphasizes a risk-based approach, meaning:

It's not just a checklist of tests.
The evaluation is integrated into the device's overall risk management process (which often follows another standard, ISO 14971).
The focus is on understanding the device, its materials, and how it interacts with the body before jumping to testing.

The Biological Evaluation Process (Following ISO 10993-1)

Think of biological evaluation as a structured investigation:

Planning: It starts with a Biological Evaluation Plan (BEP). This plan outlines the strategy, describes the device (materials, manufacturing, intended use), categorizes it, reviews existing knowledge, and identifies potential biological risks and any information gaps.
Gathering Information: Before any new tests are done, manufacturers must gather all available information. This includes:
- Material Characterization: What exactly is the device made of? This involves understanding the chemical makeup (guided by ISO 10993-18: Chemical characterization) and physical properties.9
- Literature Review: What does scientific literature say about the safety of these materials in similar uses?
- Manufacturing Information: Could any manufacturing steps (like sterilization or cleaning agents) leave residues that pose a risk?
- Clinical History: Has this material or a very similar device been used safely before?
Device Categorization: Devices are grouped based on the nature and duration of contact with the body:
- Nature of Contact: e.g., Surface contact (skin, mucosal), External communication (blood path, tissue), Implant (bone, tissue, blood).
- Duration of Contact: Limited (≤ 24 hours), Prolonged (> 24 hours to 30 days), Permanent (> 30 days).
Identifying Potential Risks (Endpoints): Based on the category, ISO 10993-1 (in its Annex A) lists potential biological effects ("endpoints") to consider. Common endpoints include:
- Cytotoxicity (ISO 10993-5): Does it kill cells?
- Sensitization (ISO 10993-10): Could it cause an allergic reaction?
- Irritation (ISO 10993-10): Could it cause redness or swelling at the contact site?
- Systemic Toxicity (ISO 10993-11): Could substances absorbed from the device harm organs elsewhere in the body?
- Material-Mediated Pyrogenicity: Could it cause fever?
- Implantation Effects (ISO 10993-6): How does tissue react locally to an implant?
Gap Analysis & Testing Strategy: Compare the required information (endpoints) with the gathered data. Are there any gaps? Testing is only performed to fill these specific gaps. The goal is to avoid unnecessary testing, especially animal testing, aligning with the "3Rs" principle (Replace, Reduce, Refine).
Evaluation and Reporting: All the collected information – literature data, chemical analysis, test results (if any) – is compiled and analyzed in a Biological Evaluation Report (BER). This report justifies the approach taken, explains why certain tests were or weren't necessary, and concludes whether the device is biologically safe for its intended use. The BER is a critical part of the technical documentation submitted for regulatory approval.

Applicable Guidances?

The Medical Device Coordination Group (MDCG) publishes guidance documents to help manufacturers and authorities interpret and implement the MDR uniformly. While there isn't one single MDCG document dedicated to biological evaluation methodology (as ISO 10993 is the primary reference), several MDCG guidance documents touch upon biocompatibility data, for example:

MDCG 2020-5 (Clinical Evaluation - Equivalence): Explains that when claiming a new device is equivalent to an existing one, biological characteristics (like materials in contact with the body, contact duration, release of substances) must be comparable. This relies heavily on biological evaluation data.
MDCG 2020-13 (Clinical Evaluation Assessment Report): Biocompatibility data from the biological evaluation feeds directly into the overall clinical evaluation, which assesses the device's safety and performance.

An Example: A Sterile Wound Dressing

Let's consider a simple sterile wound dressing intended for short-term use on broken skin.

Plan (BEP): Outline the dressing's components (e.g., adhesive, absorbent pad, backing film), intended use (contact with breached skin, duration up to a few days), and sterilization method.
Gather Info: Identify the specific polymers, adhesives, and any processing agents used. Search literature for safety data on these materials in wound care. Perform chemical characterization (ISO 10993-18) if materials are not well-established or if processing raises concerns.
Categorize: Surface device, breached skin contact, limited duration (or prolonged, depending on exact intended use).
Identify Endpoints: Based on ISO 10993-1, endpoints like cytotoxicity, sensitization, and irritation are key considerations for skin-contacting devices. If it contacts circulating blood indirectly (e.g., absorbing exudate), haemocompatibility might also be considered.
Gap Analysis & Testing: If the materials are common (e.g., standard acrylic adhesive, polyurethane film, cotton pad) with a long history of safe use in dressings, and chemical analysis confirms no harmful leachables, existing data might be sufficient. If novel materials are used, or if chemical data is lacking, tests like in vitro cytotoxicity (ISO 10993-5) and skin irritation/sensitization (ISO 10993-10) might be needed.
Report (BER): Document all findings: material data, literature review, chemical analysis results, any test results, and the final conclusion that the dressing is biocompatible for its intended use.

Conclusion

Biological evaluation is a fundamental part of ensuring medical device safety. It's a rigorous, science-based process guided by the ISO 10993 standards and mandated by regulations like the EU MDR. By systematically evaluating how a device interacts with the body, manufacturers can identify and mitigate potential biological risks, ultimately protecting patients and bringing safe, effective therapies to market.

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