Updated: 26th June 2026
Reviewed by: David Small BSc (Hons), MSc, MTOPRA (Founder & CEO)
Why Biological Evaluation Is Essential
Biological evaluation is one of the most important activities undertaken during the development and regulatory approval of a medical device. Before a manufacturer can place a device on the market, they must demonstrate that the materials used within the finished product are biologically safe for their intended use and do not present unacceptable risks to patients or users.
Under the EU Medical Device Regulation (EU MDR 2017/745), manufacturers are expected to adopt a risk-based approach when assessing biological safety. Rather than performing every available biological test, manufacturers should evaluate the nature of body contact, duration of contact, material composition, manufacturing processes and available scientific evidence to determine the biological endpoints that require assessment.
Today, biological evaluation extends far beyond laboratory testing. It combines biological risk assessment, chemical characterisation, toxicological assessment, clinical evidence and risk management into a structured scientific process that demonstrates the biological safety of the finished medical device throughout its lifecycle.
This guide explains the complete biological evaluation process, including ISO 10993, Biological Evaluation Plans (BEPs), Biological Evaluation Reports (BERs), biological testing, toxicological risk assessment and the relationship between biological evaluation, ISO 14971 and Clinical Evaluation.
Further Reading:
If you’re looking for more detailed guidance on individual aspects of biological evaluation, you may also find these articles useful:
What Is Biological Evaluation?
Biological evaluation is the systematic process used to determine whether a medical device is biologically safe for its intended purpose.
Rather than relying on a single laboratory test, biological evaluation considers all available evidence relating to the interaction between a medical device and the human body. This includes information about the materials used within the device, manufacturing processes, duration of body contact, existing scientific literature, chemical composition, toxicological data and, where appropriate, biological testing.
The objective of biological evaluation is to demonstrate that the medical device does not present unacceptable biological risks throughout its intended lifecycle.
Manufacturers should consider factors including:
- Type of body contact.
- Duration of patient contact.
- Material composition.
- Manufacturing residues.
- Sterilisation methods.
- Chemical constituents.
- Potential degradation products.
- Clinical experience.
- Post-market surveillance data.
- Risk management documentation.
The conclusions of the biological evaluation ultimately support the overall Technical Documentation required for regulatory approval.
Biological Evaluation Under the EU MDR
The Medical Device Regulation (EU) 2017/745 requires manufacturers to demonstrate that medical devices achieve an acceptable benefit-risk profile while meeting the General Safety and Performance Requirements (GSPRs).
As part of this process, manufacturers must evaluate whether the materials used within their devices present any unacceptable biological hazards.
Biological evaluation supports compliance with several areas of the EU MDR, including:
- General Safety and Performance Requirements (Annex I).
- Technical Documentation (Annex II).
- Risk Management.
- Clinical Evaluation.
- Design Verification and Validation.
- Post-Market Surveillance.
Rather than existing as a standalone activity, biological evaluation forms an integral part of the overall regulatory strategy for demonstrating device safety.
Understanding ISO 10993
The internationally recognised framework for biological evaluation is provided by the ISO 10993 series of standards.
ISO 10993 does not simply prescribe laboratory tests. Instead, it provides a structured risk management framework that helps manufacturers determine which biological endpoints require evaluation based on the characteristics of the finished medical device.
The standard recognises that every medical device is different. Factors such as material composition, intended purpose, duration of body contact and manufacturing processes all influence the extent of biological evaluation required.
Modern biological evaluation therefore combines:
- Biological risk assessment.
- Chemical characterisation.
- Toxicological risk assessment.
- Existing scientific evidence.
- Clinical experience.
- Laboratory testing where necessary.
This risk-based approach helps manufacturers avoid unnecessary testing while ensuring that sufficient evidence exists to demonstrate biological safety.
ISO 10993-1: The Foundation of Biological Evaluation
At the heart of the ISO 10993 series is ISO 10993-1 – Biological Evaluation of Medical Devices: Evaluation and Testing Within a Risk Management Process.
This standard establishes the overall framework for biological evaluation and emphasises that biological safety should be assessed using a structured scientific process rather than relying solely on laboratory testing.
ISO 10993-1 requires manufacturers to:
- Identify potential biological hazards.
- Assess patient exposure.
- Determine relevant biological endpoints.
- Evaluate existing scientific evidence.
- Perform additional testing where justified.
- Document conclusions within a Biological Evaluation Report.
Importantly, the standard promotes reducing unnecessary animal testing wherever sufficient scientific evidence or alternative methods exist, supporting both ethical considerations and modern regulatory expectations.
Risk-Based Biological Evaluation
Chemical characterisation has become one of the most important elements of biological evaluation under modern ISO 10993 guidance.
Rather than immediately proceeding to biological testing, manufacturers are encouraged to first understand exactly what chemical substances may be present within the finished medical device.
Chemical characterisation typically investigates:
- Raw material composition.
- Additives.
- Processing aids.
- Manufacturing residues.
- Degradation products.
- Extractable compounds.
- Leachable substances.
- Surface coatings.
This information provides valuable evidence regarding potential patient exposure and frequently allows toxicologists to determine biological safety without requiring extensive laboratory testing.
Chemical characterisation is primarily performed in accordance with ISO 10993-18 and forms a key component of the overall biological evaluation strategy.
Chemical Characterisation
Critical for devices like intravascular catheters and cardiovascular implants, this provides guidelines for selecting the correct tests to evaluate interactions between medical devices and blood components.
Toxicological Risk Assessment
Once the chemical composition of the medical device has been characterised, the identified substances should undergo a toxicological risk assessment.
The purpose of this assessment is to determine whether any chemicals released from the medical device could present unacceptable risks to patients during normal clinical use.
A toxicological assessment considers factors such as:
- Chemical identity.
- Estimated patient exposure.
- Route of exposure.
- Frequency of exposure.
- Duration of exposure.
- Published toxicological data.
- Thresholds of toxicological concern (TTC).
- Margin of safety.
Rather than focusing solely on whether a chemical is hazardous, toxicological risk assessment evaluates whether the anticipated level of patient exposure is likely to cause harm.
In many cases, a robust toxicological assessment can demonstrate biological safety without the need for additional biological testing.
This approach aligns with modern regulatory expectations and supports the reduction of unnecessary animal testing wherever scientifically justified.
Biological Evaluation Plan (BEP)
The BEP acts as the roadmap for the entire biological evaluation process, defining how biological safety will be demonstrated before evidence is collected.
A well-developed Biological Evaluation Plan should include:
- Device description and intended purpose.
- Material composition.
- Nature and duration of body contact.
- Applicable regulatory requirements.
- Relevant ISO 10993 standards.
- Biological hazards requiring assessment.
- Proposed biological endpoints.
- Literature review strategy.
- Chemical characterisation strategy.
- Toxicological assessment methodology.
- Proposed biological testing (where necessary).
- Acceptance criteria.
- Planned Biological Evaluation Report structure.
By establishing the evaluation strategy at the beginning of the project, manufacturers can ensure that evidence is collected systematically and consistently throughout device development.
The Biological Evaluation Plan should be reviewed whenever significant design, material or manufacturing changes occur to ensure that the planned evaluation remains appropriate.
Why Some Devices Require Very Little Biological Testing
One of the most common misconceptions is that every medical device must undergo a full suite of ISO 10993 biological tests.
In reality, this is rarely the case.
Modern ISO 10993 promotes a weight-of-evidence approach, allowing manufacturers to combine information from multiple sources to demonstrate biological safety.
Depending on the device, sufficient evidence may already exist through:
- Published scientific literature.
- Previous biological testing.
- Chemical characterisation.
- Toxicological risk assessment.
- Clinical experience.
- Existing post-market surveillance data.
- Material history of safe use.
Only where significant evidence gaps remain should additional laboratory testing be considered.
This risk-based methodology not only reduces unnecessary testing costs but also shortens development timelines while remaining fully aligned with current regulatory expectations.
Selecting the Appropriate Biological Endpoints
One of the most important decisions during biological evaluation is determining which biological endpoints require assessment.
ISO 10993-1 does not prescribe a fixed list of biological tests for every medical device. Instead, manufacturers should identify the relevant biological endpoints by considering the characteristics of the finished device and the potential biological risks associated with its intended use.
The selection of biological endpoints is influenced by several factors, including:
- Nature of body contact.
- Type of tissue contacted.
- Duration of patient contact.
- Device materials.
- Manufacturing processes.
- Sterilisation method.
- Clinical application.
- Existing scientific evidence.
This risk-based approach ensures that biological evaluation remains proportionate to the potential risks presented by the medical device.
Biological Endpoints by Device Type
ISO 10993-1 categorises medical devices according to the way they interact with the human body.
The three principal categories are:
Surface Devices
Surface devices come into contact with:
- Intact skin.
- Mucosal membranes.
- Breached or compromised surfaces.
Examples include wound dressings, surgical gloves, external sensors and dental products.
Externally Communicating Devices
These devices communicate with internal tissues while remaining partially outside the body.
Examples include:
- Urinary catheters.
- Infusion sets.
- Endoscopes.
- Dialysis tubing.
- Vascular access devices.
Because these devices often contact blood or internal tissues, additional biological endpoints may require evaluation.
Implant Devices
Implantable medical devices remain partially or completely within the body for varying periods.
Examples include:
- Orthopaedic implants.
- Dental implants.
- Breast implants.
- Cardiac implants.
- Neurostimulators.
Implantable devices generally require the most comprehensive biological evaluation because of prolonged tissue exposure and the potential for long-term biological effects.
Contact Duration
The duration of patient contact plays a significant role when selecting biological endpoints.
ISO 10993 generally considers three categories:
Limited Contact:
Less than 24 hours.
Prolonged Contact:
Between 24 hours and 30 days.
Long-Term Contact:
Greater than 30 days.
As contact duration increases, additional biological hazards may require assessment due to prolonged patient exposure.
Manufacturers should also consider cumulative exposure where devices are repeatedly used over time.
Understanding the ISO 10993 Series
The ISO 10993 family contains numerous standards covering different aspects of biological evaluation.
Rather than treating each standard independently, manufacturers should apply only those standards relevant to their specific medical device and biological risk assessment.
Some of the most frequently applied standards include:
| Standard | Purpose |
|---|---|
| ISO 10993-1 | Biological Evaluation Framework |
| ISO 10993-5 | In Vitro Cytotoxicity |
| ISO 10993-10 / ISO 10993-23 | Skin Sensitisation and Irritation |
| ISO 10993-11 | Systemic Toxicity |
| ISO 10993-17 | Toxicological Risk Assessment |
| ISO 10993-18 | Chemical Characterisation |
| ISO 10993-23 | In Vitro Skin Irritation |
Together, these standards provide manufacturers with a structured framework for demonstrating biological safety while avoiding unnecessary testing.
Biological Evaluation Report (BER)
Once all relevant biological evidence has been collected and critically assessed, the findings should be documented within a Biological Evaluation Report (BER).
The BER provides the scientific justification that the medical device is biologically safe for its intended purpose and forms an important component of the Technical Documentation required for regulatory approval.
A typical Biological Evaluation Report includes:
- Device description.
- Material characterisation.
- Intended purpose.
- Nature and duration of body contact.
- Biological risk assessment.
- Chemical characterisation.
- Toxicological assessment.
- Literature review.
- Biological testing (where applicable).
- Conclusions regarding biological safety.
- Recommendations for future review.
The report should be prepared or reviewed by individuals with appropriate scientific expertise, such as experienced toxicologists or biological safety specialists.
As new clinical evidence, material changes or post-market information become available, the Biological Evaluation Report should be reviewed and updated accordingly.
Relationship with ISO 14971
Biological evaluation should never be considered in isolation.
Instead, it forms part of the manufacturer’s overall risk management process in accordance with ISO 14971.
Biological hazards identified during evaluation should be incorporated into the Risk Management File alongside all other device hazards.
Likewise, information generated through risk management may influence the biological evaluation strategy, including the selection of biological endpoints and the need for additional testing.
By integrating ISO 10993 and ISO 14971, manufacturers can demonstrate a consistent and scientifically justified approach to managing biological risks throughout the medical device lifecycle.
Relationship with Clinical Evaluation
Although biological evaluation and clinical evaluation are separate regulatory activities, they support the same overall objective: demonstrating that a medical device is safe and performs as intended.
Biological evaluation focuses on the interaction between device materials and the human body.
Clinical evaluation focuses on clinical performance, clinical benefits and the overall benefit-risk profile of the finished medical device.
Together, these evaluations provide complementary evidence supporting conformity with the General Safety and Performance Requirements (GSPRs) of the EU MDR.
Common Biological Evaluation Mistakes
Many regulatory delays occur because biological evaluation has not been approached using a structured, risk-based methodology.
Common issues include:
- Treating biological evaluation as a laboratory testing exercise rather than a scientific assessment.
- Failing to perform adequate chemical characterisation.
- Poor toxicological justification.
- Selecting inappropriate biological endpoints.
- Incomplete Biological Evaluation Plans.
- Outdated Biological Evaluation Reports.
- Failure to integrate biological evaluation with ISO 14971.
- Limited traceability between risk management, biological evaluation and technical documentation.
- Performing unnecessary biological testing without scientific justification.
A well-planned biological evaluation not only supports regulatory compliance but can also reduce development costs, minimise unnecessary testing and shorten time to market.
Summary
Biological evaluation is a fundamental component of medical device development and regulatory compliance.
Modern ISO 10993 promotes a scientific, risk-based approach that combines biological risk assessment, chemical characterisation, toxicological assessment, existing scientific evidence and targeted biological testing to demonstrate biological safety.
Rather than relying solely on laboratory testing, manufacturers should develop a comprehensive Biological Evaluation Plan, systematically assess biological hazards and document their conclusions within a robust Biological Evaluation Report.
When integrated with Risk Management (ISO 14971), Clinical Evaluation and Technical Documentation, biological evaluation provides the evidence required to demonstrate that a medical device remains safe throughout its entire lifecycle.
How Can Patient Guard Help?
Patient Guard provides comprehensive biological evaluation services for medical device manufacturers seeking compliance with the EU MDR, UK MDR and international regulatory requirements.
Our experienced regulatory specialists can assist with:
- Biological Evaluation Plans (BEPs)
- Biological Evaluation Reports (BERs)
- ISO 10993 gap assessments
- Biological risk assessments
- Chemical characterisation strategies
- Toxicological risk assessments
- Literature reviews
- Biological test planning
- Technical Documentation support
- Notified Body readiness
Whether you are developing a new medical device or maintaining an existing product, Patient Guard can help you develop a scientifically robust biological evaluation strategy that supports regulatory approval and ongoing compliance.
Further Reading
To explore biological evaluation and related regulatory topics in greater detail, read our specialist guides:
- ISO 10993-1:2025 – What’s New in Biological Evaluation
- Cytotoxicity Testing in Medical Device Biological Evaluation
- In Vitro Skin Irritation Testing – ISO 10993-23
- Extractables and Leachables Testing for Medical Devices
- Medical Device Clinical Evaluation
- ISO 14971 and the Risk Management of Medical Devices
Frequently Asked Questions About Medical Device Biological Evaluation (ISO 10993)
Biological evaluation assesses the biocompatibility of a medical device to ensure it is safe for its intended use. It evaluates the interaction between the device’s materials and the patient’s tissues, cells, or body fluids.
Key insight: Biological evaluation is a critical part of the medical device safety assessment and is governed by ISO 10993 standards.
Biological evaluation ensures that the materials used in a medical device:
- Are non-toxic and non-carcinogenic.
- Do not cause adverse reactions, such as irritation or sensitization.
- Are safe for short- and long-term exposure.
Why it matters: Non-compliance can result in regulatory rejection, product recalls, or harm to patients.
The ISO 10993 series of standards governs biological evaluation, with ISO 10993-1 serving as the framework. Key parts include:
- ISO 10993-5: Cytotoxicity testing.
- ISO 10993-10: Irritation and sensitization.
- ISO 10993-11: Systemic toxicity testing.
- ISO 10993-18: Chemical characterization of materials.
Pro tip: Familiarity with these standards ensures a structured and compliant approach to evaluation.
Biological evaluation involves three main steps:
Material Characterization:
- Identifying and analyzing the device materials and any potential leachables.
- Chemical testing and risk assessment.
Biological Testing:
- Conducting in vitro (e.g., cytotoxicity) and in vivo (e.g., sensitization) tests as needed.
- Selecting tests based on the device’s intended use and patient exposure.
Biological Evaluation Report (BER):
- Summarizing findings and demonstrating compliance with ISO 10993 and regulatory requirements.
Best practice: Use a risk-based approach to determine the level of testing required.
ISO 10993-1 provides the framework for biological evaluation, emphasizing:
- A risk management approach to testing.
- Evaluation based on device type, materials, and patient exposure.
- Integration with the overall safety and performance assessment.
Key takeaway: ISO 10993-1 guides manufacturers in creating a scientifically justified evaluation plan.
The scope of biological testing depends on:
- Device classification: Higher-risk devices often require more extensive testing.
- Material composition: Devices with novel materials may need additional studies.
- Patient contact: Duration and nature of patient exposure (e.g., surface contact, implantable).
- Existing data: Leveraging previous testing or material certifications.
Tip for manufacturers: Prioritize leveraging existing data to reduce redundant testing.
Common biological tests include:
- Cytotoxicity: Evaluates if materials are toxic to cells.
- Sensitization: Assesses the potential for allergic reactions.
- Irritation: Determines if materials cause skin or mucosal irritation.
- Systemic toxicity: Evaluates if materials release harmful substances affecting the body.
- Genotoxicity: Assesses if materials cause genetic mutations.
- Hemocompatibility: Determines compatibility with blood (for devices in contact with blood).
Pro tip: Work with an accredited lab for reliable and regulatory-compliant results.
A Biological Evaluation Report (BER) documents:
- The materials used and their characterization.
- Results from biological tests conducted.
- A risk-based assessment of biocompatibility.
- Justification for testing decisions or waivers.
Why it matters: The BER is a key regulatory submission document, demonstrating that the device meets safety standards.
Yes, wherever possible. ISO 10993 encourages the use of alternatives, such as:
- In vitro testing: Cell-based tests (e.g., cytotoxicity).
- Chemical characterization: Identifying material properties to predict biological responses.
Key takeaway: Reducing animal testing aligns with ethical considerations and regulatory trends.
Challenges include:
- Incomplete material data: Collaborate with suppliers to obtain detailed information.
- Regulatory expectations: Stay updated on ISO 10993 revisions and regional guidance.
- Cost of testing: Use a risk-based approach to focus resources on critical tests.
Solution: Partner with regulatory experts to streamline the evaluation process and avoid common pitfalls.
Biological evaluation doesn’t end at market approval. Post-market surveillance (PMS) ensures that:
- Adverse biological reactions are identified and addressed promptly.
- Real-world evidence supports the initial evaluation.
- Material changes or manufacturing updates are re-assessed for biocompatibility.
Best practice: Incorporate biological evaluation into your PMS activities for continuous safety monitoring.
Absolutely! Patient Guard provides end-to-end support for medical device biological evaluation, including:
- Developing ISO 10993-compliant evaluation plans.
- Coordinating biological testing with accredited labs.
- Preparing comprehensive Biological Evaluation Reports (BER).
- Guiding manufacturers through regulatory submissions.
Why choose Patient Guard: With experience assisting over 500 clients, we ensure your biological evaluation meets global regulatory standards.
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