Updated: 26th June 2026
Reviewed by: David Small BSc (Hons), MSc, MTOPRA (Founder & CEO)
What Is Biological Evaluation?
Biological Evaluation is a structured, risk-based process used to determine whether a medical device is biologically safe for its intended clinical use. Rather than relying solely on laboratory testing, Biological Evaluation considers the device’s materials, manufacturing processes, nature and duration of patient contact, existing scientific evidence and potential biological hazards to demonstrate that any biological risks have been reduced to an acceptable level.
Under the EU Medical Device Regulation (MDR) and the ISO 10993 series of standards, Biological Evaluation forms a fundamental part of the medical device design, development and conformity assessment process. It provides documented evidence that the materials used within a device are suitable for their intended purpose and that any potential biological risks have been appropriately identified, assessed and controlled before the device is placed on the market.
Importantly, Biological Evaluation is not the same as biocompatibility testing. Laboratory testing may form part of a Biological Evaluation where evidence gaps exist, but many devices can be adequately justified using existing clinical experience, published scientific literature, material characterisation and toxicological risk assessment without performing every ISO 10993 biological test. The objective is to adopt a proportionate, science-based approach that generates sufficient evidence to support the device’s safety throughout its entire lifecycle.
Today, Biological Evaluation is closely integrated with Risk Management (ISO 14971), Clinical Evaluation, Post-Market Surveillance (PMS) and the wider Technical Documentation required under the EU MDR. As new clinical evidence becomes available or a device undergoes design, material or manufacturing changes, the Biological Evaluation should be reviewed and updated to ensure it continues to reflect the current biological safety profile of the device.
New to the EU Medical Device Regulation (MDR)?
Biological Evaluation is just one component of achieving compliance with the EU Medical Device Regulation (EU MDR 2017/745). If you're looking for a complete introduction to CE marking, device classification, General Safety and Performance Requirements (GSPRs), Technical Documentation, Clinical Evaluation, Risk Management, Post-Market Surveillance and the overall regulatory pathway, read our Complete Guide to the EU MDR.
Why Is Biological Evaluation Required?
Biological Evaluation is required to demonstrate that a medical device is safe for its intended clinical use and does not present unacceptable biological risks to patients, users or other individuals. Every medical device interacts with the human body in some way, whether through direct tissue contact, contact with circulating blood, exposure to body fluids or indirect contact through connected medical systems. Manufacturers must therefore assess how the materials used within a device could affect the body throughout its intended lifetime.
Under the EU Medical Device Regulation (EU MDR 2017/745), manufacturers are required to demonstrate compliance with the General Safety and Performance Requirements (GSPRs), including those relating to chemical, physical and biological properties. Biological Evaluation provides the scientific evidence that supports these requirements by identifying potential biological hazards, assessing the associated risks and demonstrating that appropriate risk control measures have been implemented.
The process is closely aligned with the principles of ISO 10993-1, which promotes a risk-based approach to Biological Evaluation. Rather than requiring every medical device to undergo the same laboratory tests, manufacturers are expected to consider a range of evidence sources, including material characterisation, existing clinical experience, published scientific literature, previous testing data and toxicological assessments before determining whether additional biological testing is necessary. This approach helps ensure that testing is scientifically justified, proportionate to the device and avoids unnecessary animal testing wherever possible.
As medical devices evolve throughout their lifecycle, Biological Evaluation also supports ongoing regulatory compliance. Changes to materials, manufacturing processes, sterilisation methods, intended purpose or clinical evidence may all affect the biological safety profile of a device and should trigger a review of the Biological Evaluation. Together with Risk Management, Clinical Evaluation and Post-Market Surveillance, Biological Evaluation forms an integral part of the evidence required to maintain continued compliance with the EU MDR.
Biological Evaluation vs Biocompatibility Testing
One of the most common misconceptions in medical device regulatory affairs is that Biological Evaluation and biocompatibility testing are the same thing. In reality, biocompatibility testing is only one possible component of a much broader Biological Evaluation process.
Biological Evaluation is a structured, science-based assessment that considers all available evidence relating to the biological safety of a medical device. This includes the device’s intended purpose, the nature and duration of patient contact, material composition, manufacturing processes, chemical characterisation, published scientific literature, previous clinical experience, toxicological assessments and any existing biological testing data. The objective is to determine whether the device presents an acceptable biological risk throughout its intended lifecycle.
Biocompatibility testing, by contrast, refers to the laboratory tests that may be performed to investigate specific biological endpoints, such as cytotoxicity, sensitisation or irritation. These tests are not automatically required for every medical device. Instead, ISO 10993-1 promotes a risk-based approach in which manufacturers first evaluate existing evidence before deciding whether additional laboratory testing is scientifically justified.
For many well-established materials with a documented history of safe clinical use, existing evidence may be sufficient to demonstrate biological safety without performing extensive new testing. Conversely, devices incorporating novel materials, new manufacturing processes or different patient contact characteristics may require additional biological testing to address identified evidence gaps.
This evidence-led approach not only improves the scientific quality of Biological Evaluation but also supports more proportionate regulatory decision-making. By focusing testing on genuine biological uncertainties, manufacturers can reduce unnecessary laboratory work, minimise the use of animal testing where appropriate and ensure resources are directed towards generating meaningful evidence that supports patient safety.
When Is Biocompatibility Testing Actually Required?
Biocompatibility testing is not automatically required for every medical device. Learn how manufacturers determine whether laboratory testing is necessary under ISO 10993 by considering existing evidence, material characterisation, chemical information, clinical experience and biological risk assessment in our Guide to When Biocompatibility Testing Is Required.
The Biological Evaluation Process
Biological Evaluation is not a single document or laboratory test but a structured process that begins during medical device design and continues throughout the product lifecycle. ISO 10993-1 provides a risk-based framework that enables manufacturers to identify potential biological hazards, evaluate the available scientific evidence and determine whether additional biological testing is necessary to demonstrate safety.
Categorising the Medical Device
Before developing the Biological Evaluation strategy, manufacturers should first categorise the medical device in accordance with ISO 10993-1. This categorisation forms the foundation of the Biological Evaluation because it determines which biological endpoints require consideration and what level of evidence is necessary to demonstrate biological safety.
ISO 10993-1 requires manufacturers to consider three fundamental characteristics of the device before determining the appropriate evaluation strategy.
Device Contact Category
Medical devices are first categorised according to how they interact with the human body.
The three principal categories are:
- Surface-contacting devices – devices that contact intact skin, mucosal membranes or breached/compromised surfaces.
- Externally communicating devices – devices that provide a pathway between the external environment and internal tissues, blood or body fluids, such as urinary catheters, infusion sets and dental devices.
- Implant devices – devices that are wholly or partially implanted within the body and remain in contact with tissue, bone or circulating blood.
Each category presents different biological hazards and therefore different Biological Evaluation requirements.
Nature of Body Contact
Manufacturers should then identify the tissues or body fluids contacted by the device.
Typical contact types include:
- Intact skin
- Mucosal membrane
- Breached or compromised surface
- Tissue or bone
- Circulating blood
- Indirect blood path
Different contact sites present different biological risks and influence which biological endpoints require assessment.
Duration of Patient Contact
ISO 10993-1 also requires manufacturers to consider the cumulative duration of patient contact.
| Contact Duration | Typical Exposure |
|---|---|
| Limited | Up to 24 hours |
| Prolonged | More than 24 hours up to 30 days |
| Long-term / Permanent | More than 30 days |
The duration of contact should represent the total foreseeable exposure of the device throughout its intended use, rather than the duration of a single clinical procedure.
Together, the device category, contact type and duration of contact establish the initial biological endpoints that should be considered during the Biological Evaluation.
Preparing the Biological Evaluation Plan (BEP)
Once the device has been categorised, the development of a Biological Evaluation Plan (BEP) should take place. This document defines the scope of the evaluation by considering the device’s intended purpose, materials of construction, manufacturing processes, nature and duration of patient contact, applicable biological endpoints and the overall evaluation strategy. The BEP provides a clear roadmap for gathering and assessing the evidence required to support biological safety.
The BEP should document the device materials, manufacturing processes, sterilisation method, applicable biological endpoints and identified biological risks. It should also review the available scientific evidence to determine whether sufficient information already exists or whether additional chemical characterisation, toxicological assessment or biological testing is required to demonstrate biological safety.
Biological Endpoints and Supporting Assessments Under ISO 10993
The biological endpoints requiring evaluation depend upon the device category, contact type, duration of exposure and the identified biological risks. Not every endpoint will apply to every medical device, and ISO 10993-1 expects manufacturers to justify which endpoints require further evaluation.
Supporting Scientific Assessments
| Biological Evaluation Topic | Purpose | Primary ISO 10993 Reference |
|---|---|---|
| Chemical Characterisation | Identifies and characterises chemicals that may be released from the medical device or its materials. | ISO 10993-18 |
| Toxicological Risk Assessment | Evaluates whether identified chemicals present an acceptable toxicological risk. | ISO 10993-17 |
| Ethylene Oxide (EtO) Residuals | Establishes acceptable limits for residual ethylene oxide, ethylene chlorohydrin (ECH) and ethylene glycol (EG) following EtO sterilisation. | ISO 10993-7 |
| Degradation Products | Evaluates degradation products generated by medical devices where applicable. | ISO 10993-9 (supported by material-specific degradation standards) |
Biological Endpoints
| Biological Endpoint | Purpose | Primary ISO 10993 Reference |
|---|---|---|
| Cytotoxicity | Assesses whether device materials or extracts damage living cells. | ISO 10993-5 |
| Sensitisation | Evaluates the potential to induce allergic reactions. | ISO 10993-10 |
| Irritation | Assesses local irritation or inflammatory responses. | ISO 10993-23 |
| Material-Mediated Pyrogenicity | Assesses the potential for device materials to induce a pyrogenic response. | ISO 10993-11 |
| Acute Systemic Toxicity | Evaluates harmful systemic effects following short-term exposure. | ISO 10993-11 |
| Subacute / Subchronic Toxicity | Evaluates systemic effects following repeated exposure. | ISO 10993-11 |
| Chronic Toxicity | Assesses long-term systemic effects. | ISO 10993-11 |
| Genotoxicity | Determines whether materials may damage genetic material. | ISO 10993-3 |
| Carcinogenicity | Evaluates carcinogenic potential where applicable. | ISO 10993-3 |
| Reproductive & Developmental Toxicity | Assesses potential effects on reproduction and development where relevant. | ISO 10993-3 |
| Haemocompatibility | Evaluates interactions with blood, including haemolysis and thrombogenicity. | ISO 10993-4 |
| Implantation | Assesses local tissue responses following implantation. | ISO 10993-6 |
Note: The standards shown above represent the principal parts of the ISO 10993 series associated with each biological endpoint. The applicable endpoints and evaluation strategy should always be determined using a risk-based approach in accordance with ISO 10993-1, taking into account the device’s contact category, tissue contact, duration of contact, materials, manufacturing processes and intended clinical use.
Chemical characterisation performed in accordance with ISO 10993-18 may include extractables and leachables studies, analytical chemistry and material characterisation. The resulting chemical data are then evaluated using the toxicological risk assessment principles described in ISO 10993-17 to determine whether identified substances present an acceptable biological risk or whether additional evaluation is required.
Learn More About Extractables & Leachables Testing
Extractables and Leachables (E&L) studies are a key component of chemical characterisation under ISO 10993 and help identify substances that may migrate from medical device materials during clinical use. Discover how E&L testing supports Biological Evaluation, toxicological risk assessment and regulatory compliance in our Complete Guide to Extractables & Leachables Testing.
Learn More About Cytotoxicity Testing
Cytotoxicity testing is often one of the first biological endpoints considered during a medical device Biological Evaluation. Learn how ISO 10993-5 in vitro cytotoxicity testing is used to assess the effects of medical device materials on living cells, when testing is required and how it supports Biological Evaluation in our Complete Guide to Cytotoxicity Testing.
Learn More About Skin Irritation Testing
Skin irritation is a key biological endpoint that may need to be evaluated for medical devices with skin or mucosal contact. Discover how ISO 10993-23 supports in vitro skin irritation testing, when testing is required and how it contributes to a risk-based Biological Evaluation in our Complete Guide to ISO 10993-23 Skin Irritation Testing.
Learn More About Drug Stability Testing
For combination products and drug-contacting medical devices, Biological Evaluation may also require an assessment of drug stability. Discover how stability studies for syringes, infusion sets and administration bags help demonstrate material compatibility, identify potential drug-device interactions and support regulatory compliance in our Complete Guide to Drug Stability Testing for Medical Devices.
Reviewing Existing Biological Evidence
Once the Biological Evaluation Plan (BEP) has been established, manufacturers should review all available evidence relevant to the biological safety of the medical device. The objective is to determine whether sufficient evidence already exists to address each applicable biological endpoint before considering additional laboratory testing.
Evidence reviewed during this stage may include:
- Material specifications and supplier information.
- Chemical characterisation data.
- Published scientific literature.
- Previous biological testing.
- Clinical experience with equivalent materials or devices.
- Toxicological risk assessments.
- Manufacturing processes, processing aids and sterilisation information.
- Post-Market Surveillance (PMS) data, where available.
This evidence should be critically appraised to determine its quality, relevance and applicability to the finished medical device. Existing evidence should always be considered before commissioning new biological testing.
Identifying Evidence Gaps and Additional Evaluation
Following the evidence review, manufacturers should determine whether any biological endpoints remain insufficiently supported. Where evidence gaps are identified, additional evaluation may be required to demonstrate biological safety.
Depending on the device and the identified risks, this may include:
- Additional chemical characterisation.
- Extractables and leachables studies.
- Toxicological risk assessment.
- Cytotoxicity testing.
- Sensitisation testing.
- Irritation testing.
- Haemocompatibility studies.
- Other endpoint-specific evaluations required under the ISO 10993 series.
Importantly, ISO 10993 promotes a risk-based approach rather than a standard testing matrix. Additional testing should only be performed where it is scientifically justified and necessary to address identified uncertainties within the Biological Evaluation.
Preparing the Biological Evaluation Report (BER)
Once all available evidence has been reviewed and any additional investigations completed, the findings are documented within the Biological Evaluation Report (BER).
The BER summarises the evidence considered throughout the Biological Evaluation, documents the rationale for the chosen evaluation strategy, presents the biological risk assessment and concludes whether the medical device is biologically safe for its intended clinical use.
Like the Biological Evaluation Plan, the BER should be treated as a living document. It should be reviewed whenever significant changes are made to the device, its materials, manufacturing processes, sterilisation methods or intended purpose, or when new clinical evidence, scientific literature or post-market information becomes available.
Together, the Biological Evaluation Plan (BEP) and Biological Evaluation Report (BER) provide the documented evidence demonstrating that biological risks have been systematically identified, evaluated, controlled and continuously reviewed throughout the medical device lifecycle.
How ISO 10993 Supports Biological Evaluation
The ISO 10993 series of international standards provides the globally recognised framework for evaluating the biological safety of medical devices. Rather than prescribing a fixed list of laboratory tests, ISO 10993 promotes a science-based, risk management approach that enables manufacturers to determine the most appropriate evaluation strategy based on the characteristics of their device and its intended clinical use.
The cornerstone of the series is ISO 10993-1, which establishes the overall Biological Evaluation framework. It requires manufacturers to consider factors such as the nature and duration of body contact, the materials used within the device, manufacturing processes, chemical constituents and available clinical evidence before determining whether additional biological testing is necessary. This ensures that Biological Evaluation remains proportionate to the identified risks while avoiding unnecessary testing where sufficient evidence already exists.
The wider ISO 10993 series addresses specific aspects of Biological Evaluation, including chemical characterisation, cytotoxicity, irritation, sensitisation, systemic toxicity, genotoxicity, implantation studies and many other biological endpoints. Not every standard applies to every medical device. Instead, manufacturers should select the relevant assessments based on the device’s intended purpose, patient contact and identified biological hazards.
Importantly, ISO 10993 is closely aligned with ISO 14971 Risk Management. Biological hazards should be identified, evaluated and controlled using the same structured risk management principles applied to all other device risks. This integrated approach helps ensure that Biological Evaluation contributes to the overall safety and performance of the medical device rather than existing as an isolated regulatory activity.
As scientific knowledge evolves and new evidence becomes available, Biological Evaluation should also evolve. Manufacturers should periodically review their Biological Evaluation to ensure it remains consistent with current scientific understanding, applicable standards and post-market experience, helping to maintain ongoing compliance throughout the medical device lifecycle.
What's Changed in ISO 10993-1:2025?
The latest edition of ISO 10993-1 strengthens the risk-based approach to Biological Evaluation, placing greater emphasis on chemical characterisation, scientific justification, lifecycle evidence and integration with ISO 14971 Risk Management. Explore our Complete Guide to ISO 10993-1:2025 to understand the key changes and what they mean for medical device manufacturers.
Biological Evaluation Throughout the Medical Device Lifecycle
Biological Evaluation should not be viewed as a one-off activity undertaken solely to achieve regulatory approval. Instead, it is a continuous process that begins during device development and continues throughout the entire medical device lifecycle. As new information becomes available, manufacturers should review the existing Biological Evaluation to confirm that it continues to demonstrate the biological safety of the device.
During the design and development phase, Biological Evaluation supports material selection, identifies potential biological hazards and helps determine the evidence required to demonstrate safety. Information gathered during this stage contributes to the Biological Evaluation Plan (BEP), Risk Management File, design verification activities and the wider Technical Documentation required for CE marking.
As development progresses, manufacturers continually evaluate new evidence. This may include material characterisation data, toxicological assessments, published scientific literature, previous biological testing, clinical evidence and, where necessary, additional testing performed in accordance with the ISO 10993 series. The objective is to ensure that all identified biological risks have been appropriately assessed and reduced to an acceptable level before the device is placed on the market.
Following market release, Biological Evaluation continues to evolve alongside the device. Information obtained through Post-Market Surveillance (PMS), customer complaints, vigilance reporting, Post-Market Clinical Follow-up (PMCF), manufacturing changes and emerging scientific knowledge may all influence the biological safety profile of the device. Manufacturers should periodically review this information to determine whether updates to the Biological Evaluation Report (BER) are required.
This lifecycle approach ensures that Biological Evaluation remains aligned with the principles of ISO 14971 Risk Management and the EU MDR. Rather than producing static documentation for regulatory submission, manufacturers maintain a living body of evidence that continues to support the safety and performance of the device throughout its commercial life.
Biological Evaluation and ISO 14971 Risk Management
Biological Evaluation does not exist in isolation. Under the EU MDR and ISO 10993, it forms an integral part of the manufacturer’s overall Risk Management process, ensuring that biological hazards are identified, evaluated, controlled and monitored throughout the medical device lifecycle. Rather than treating biological safety as a standalone exercise, manufacturers should assess biological risks alongside all other hazards that could affect the safety and performance of the device.
The process begins by identifying potential biological hazards associated with the device’s materials, manufacturing processes, chemical constituents and intended clinical use. Manufacturers then evaluate the likelihood and severity of potential harm, determine whether existing evidence adequately addresses those risks and identify any additional data required to support a robust Biological Evaluation. This structured approach ensures that biological safety decisions are based on scientific evidence rather than routine testing.
Risk control measures may include selecting alternative materials, modifying manufacturing processes, introducing protective coatings, reducing patient exposure or generating additional evidence through laboratory testing where appropriate. Any residual biological risks should be documented within the Risk Management File and considered alongside the overall benefit-risk profile of the medical device.
Biological Evaluation also plays an important role after the device has been placed on the market. Information obtained through Post-Market Surveillance (PMS), vigilance reporting, customer complaints, scientific literature and clinical experience may identify new biological hazards or changes to the device’s risk profile. Manufacturers should periodically review this information to determine whether updates to the Biological Evaluation Report (BER) and Risk Management documentation are required.
By integrating Biological Evaluation with ISO 14971 Risk Management, manufacturers can demonstrate that biological risks have been systematically assessed, appropriately controlled and continuously monitored throughout the entire lifecycle of the medical device. This integrated approach supports regulatory compliance while helping to ensure the continued safety of patients and users.
Explore ISO 14971 Risk Management
Biological Evaluation forms part of the wider medical device risk management process. Learn how ISO 14971 supports hazard identification, risk analysis, risk evaluation, risk control, residual risk assessment and lifecycle monitoring in our Complete Guide to ISO 14971 Risk Management.
Biological Evaluation and Clinical Evaluation
Biological Evaluation and Clinical Evaluation assess different aspects of medical device safety, but their conclusions should remain closely aligned. Biological Evaluation focuses on the potential biological effects of the device’s materials, chemical constituents and manufacturing processes, while Clinical Evaluation considers whether the device is safe, performs as intended and delivers an acceptable clinical benefit-risk profile when used in patients.
Evidence generated through Biological Evaluation therefore contributes directly to the wider clinical safety assessment. For example, material characterisation, toxicological risk assessment and biocompatibility evidence may help demonstrate that patient-contacting materials do not introduce unacceptable risks such as irritation, sensitisation, cytotoxicity or systemic toxicity. These findings support the safety conclusions documented within the Clinical Evaluation Report (CER).
Clinical evidence can also inform Biological Evaluation. Post-market experience, clinical investigations, published literature, complaints and vigilance data may reveal biological effects that were not identified during pre-market assessment. Where new information suggests a possible material-related or biological safety concern, manufacturers should review the Biological Evaluation Report (BER), Risk Management File and Clinical Evaluation Report to determine whether further investigation or risk controls are required.
How the Documents Work Together
| Document or Process | Relationship with Biological Evaluation |
|---|---|
| Biological Evaluation Plan (BEP) | Defines the strategy for identifying and evaluating biological risks. |
| Biological Evaluation Report (BER) | Documents the evidence reviewed and concludes whether biological risks are acceptable. |
| Clinical Evaluation Report (CER) | Considers biological safety evidence alongside wider clinical safety, performance and benefit-risk data. |
| Risk Management File | Records biological hazards, risk estimates, controls and residual-risk conclusions. |
| Post-Market Surveillance (PMS) | Provides real-world information that may trigger updates to the BER and CER. |
| Technical Documentation | Brings the Biological Evaluation, Clinical Evaluation and Risk Management evidence together to demonstrate conformity with the EU MDR. |
Maintaining Consistency Across the Technical Documentation
Notified Bodies and regulators expect the conclusions across these documents to be consistent. A biological risk identified in the BER should also be reflected in the Risk Management File and considered within the Clinical Evaluation where it could affect patient safety or the overall benefit-risk profile.
Likewise, changes to materials, coatings, sterilisation processes, manufacturing methods or intended clinical use may affect several documents simultaneously. Manufacturers should therefore assess the impact of significant changes across the BEP, BER, Risk Management File, CER, labelling and Post-Market Surveillance documentation rather than updating each document independently.
This integrated approach helps ensure that biological safety is supported by both pre-market scientific evidence and real-world clinical experience throughout the medical device lifecycle.
Understand Medical Device Clinical Evaluation
Biological Evaluation is one part of the wider evidence required to demonstrate that a medical device is safe and performs as intended. Learn how Clinical Evaluation integrates clinical evidence, Biological Evaluation, Risk Management, Clinical Evaluation Plans (CEPs), Clinical Evaluation Reports (CERs), PMS and PMCF in our Complete Guide to Medical Device Clinical Evaluation.
Common Biological Evaluation Mistakes to Avoid
Biological Evaluation is one of the most frequently scrutinised areas of Technical Documentation during Notified Body conformity assessments. Many non-conformities arise not because manufacturers have failed to perform biological testing, but because the Biological Evaluation process has not been adequately planned, documented or maintained throughout the device lifecycle.
Understanding these common pitfalls can help manufacturers develop more robust Technical Documentation while avoiding unnecessary delays during regulatory review.
Treating Biological Evaluation as a Testing Exercise
One of the most common misconceptions is that Biological Evaluation simply involves completing a series of ISO 10993 laboratory tests. In reality, ISO 10993 promotes a risk-based evaluation process that considers all available scientific evidence before determining whether additional testing is required. Unnecessary testing can increase costs, delay product development and generate evidence that adds little regulatory value.
Failing to Justify Existing Evidence
Manufacturers sometimes rely on historical material data or previous biological testing without adequately demonstrating why that evidence remains applicable to the current device. Biological Evaluation should clearly explain how existing evidence relates to the device’s materials, manufacturing processes, intended purpose and patient contact characteristics.
Poor Integration with Risk Management
Biological hazards identified during the Biological Evaluation should be reflected within the Risk Management File. Likewise, biological risk control measures, residual risks and benefit-risk conclusions should remain consistent across the Biological Evaluation Report (BER), Risk Management documentation and Clinical Evaluation Report (CER). Inconsistencies between these documents are commonly identified during regulatory assessments.
Not Reviewing the Biological Evaluation After Device Changes
Changes to raw materials, suppliers, manufacturing processes, sterilisation methods, packaging or intended clinical use may all affect the biological safety profile of a device. Manufacturers should review the Biological Evaluation whenever significant changes occur to determine whether additional evidence or testing is required.
Treating the BER as a Static Document
The Biological Evaluation Report should remain a living document throughout the product lifecycle. Information obtained through Post-Market Surveillance (PMS), customer complaints, vigilance reporting, scientific literature and clinical experience should be periodically reviewed to confirm that the existing Biological Evaluation continues to support the safety of the device.
By adopting a structured, evidence-based approach and maintaining Biological Evaluation alongside Risk Management, Clinical Evaluation and Post-Market Surveillance, manufacturers can build stronger Technical Documentation while reducing the likelihood of regulatory findings during conformity assessment.
Worked Example: Biological Evaluation of a Silicone Urinary Catheter
To illustrate how Biological Evaluation is performed in practice, consider the development of a sterile, single-use silicone urinary catheter intended for short-term urinary drainage. This example demonstrates how a manufacturer might apply the principles of ISO 10993-1 to determine whether the device is biologically safe for its intended clinical use.
Step 1 – Categorise the Medical Device
The first step is to categorise the device according to ISO 10993-1.
For this example:
- Device: Sterile, single-use silicone urinary catheter
- Device category: Externally communicating medical device
- Nature of body contact: Mucosal membrane
- Contact duration: Prolonged contact (more than 24 hours but less than 30 days)
- Sterilisation method: Ethylene oxide (EtO)
This categorisation establishes the starting point for the Biological Evaluation and helps identify the biological endpoints and supporting assessments that require consideration.
Step 2 – Develop the Biological Evaluation Plan (BEP)
Once the device has been categorised, the manufacturer prepares a Biological Evaluation Plan (BEP).
The BEP defines:
- the intended purpose of the device;
- the materials and manufacturing processes;
- the sterilisation method;
- applicable biological endpoints;
- supporting scientific assessments;
- available biological evidence;
- potential biological hazards;
- the overall evaluation strategy.
At this stage, the manufacturer also determines whether sufficient information may already exist to demonstrate biological safety or whether additional evaluation is likely to be required.
Step 3 – Identify the Applicable Biological Endpoints
Based on the device category, tissue contact and duration of contact, the manufacturer identifies the biological endpoints requiring consideration.
For this catheter these may include:
- Chemical characterisation
- Toxicological risk assessment
- Cytotoxicity
- Sensitisation
- Irritation
- Acute systemic toxicity
- Material-mediated pyrogenicity
- Ethylene oxide residuals
- Where appropriate, additional endpoint-specific assessments identified through the risk assessment
The manufacturer documents the rationale for every endpoint considered, including any endpoints that can be excluded with scientific justification.
Step 4 – Review Existing Scientific Evidence
The manufacturer then reviews all available information relevant to the biological safety of the device.
Evidence may include:
- Material specifications.
- Supplier declarations.
- Chemical characterisation reports.
- Existing extractables and leachables data.
- Previous biological testing.
- Published scientific literature.
- Clinical experience with equivalent silicone materials.
- Toxicological assessments.
- Information relating to the sterilisation process.
Each source of evidence is critically appraised to determine whether it is applicable to the finished medical device and whether it adequately addresses the identified biological risks.
Step 5 – Identify Evidence Gaps
Following the evidence review, the manufacturer determines whether any biological endpoints remain insufficiently supported.
For example, the review may conclude that:
- Existing literature adequately demonstrates the long history of safe clinical use of the silicone material.
- Additional chemical characterisation is required to evaluate potential manufacturing residues.
- Ethylene oxide residual testing is required to demonstrate compliance following sterilisation.
- Existing cytotoxicity data can be justified because the manufacturing process and materials remain unchanged.
This gap analysis forms one of the most important parts of the Biological Evaluation because it determines whether further evaluation is scientifically justified.
Step 6 – Perform Additional Evaluation Where Required
Only where evidence gaps remain should additional evaluation be undertaken.
Depending on the outcome of the gap analysis, this may include:
- Additional chemical characterisation.
- Extractables and leachables studies.
- Toxicological risk assessment.
- Cytotoxicity testing.
- Sensitisation testing.
- Irritation testing.
- Ethylene oxide residual testing.
- Other endpoint-specific investigations required under the ISO 10993 series.
The objective is not to complete every possible biological test but to generate sufficient evidence to demonstrate that the device does not present unacceptable biological risks.
Step 7 – Prepare the Biological Evaluation Report (BER)
Once all available evidence has been reviewed and any additional investigations completed, the manufacturer prepares the Biological Evaluation Report (BER).
The BER documents:
- the Biological Evaluation strategy;
- the evidence reviewed;
- applicable biological endpoints;
- scientific justifications;
- results of any testing performed;
- biological risk assessment;
- overall biological safety conclusions.
The report concludes whether the device is biologically safe for its intended clinical use and whether the available evidence demonstrates compliance with the relevant requirements of ISO 10993 and the EU MDR.
Together, the Biological Evaluation Plan, Biological Evaluation Report and supporting evidence provide a documented justification that the device is biologically safe for its intended clinical use and complies with the relevant requirements of ISO 10993 and the EU MDR.
Step 8 – Maintain the Biological Evaluation Throughout the Device Lifecycle
Biological Evaluation does not end once the device has been placed on the market.
Manufacturers should periodically review the Biological Evaluation whenever there are:
- material changes;
- supplier changes;
- manufacturing process changes;
- sterilisation changes;
- new scientific literature;
- Post-Market Surveillance (PMS) findings;
- vigilance events;
- design changes;
- new clinical evidence.
Where these changes could affect the biological safety profile of the device, the Biological Evaluation Plan (BEP), Biological Evaluation Report (BER), Risk Management File and Technical Documentation should all be reviewed and updated accordingly.
This lifecycle approach ensures that Biological Evaluation remains a living, evidence-based process that continues to support the safety and regulatory compliance of the medical device throughout its commercial life.
Conclusion
Biological Evaluation is far more than a programme of biocompatibility testing. Under the EU MDR and ISO 10993, it is a structured, risk-based process that enables manufacturers to demonstrate that a medical device is biologically safe for its intended clinical use throughout its entire lifecycle.
A robust Biological Evaluation begins by categorising the medical device according to its contact category, tissue contact and duration of patient exposure. Manufacturers then develop a Biological Evaluation Plan (BEP), identify the applicable biological endpoints and supporting scientific assessments, review existing evidence and determine whether additional chemical characterisation, toxicological assessment or biological testing is required. The findings are documented within the Biological Evaluation Report (BER), providing documented evidence that biological risks have been systematically identified, evaluated and controlled.
Importantly, Biological Evaluation should not be viewed as a one-time regulatory exercise. Changes to device materials, manufacturing processes, sterilisation methods, intended purpose, scientific literature or post-market evidence may all require the Biological Evaluation to be reviewed and updated. By integrating Biological Evaluation with ISO 14971 Risk Management, Clinical Evaluation and Post-Market Surveillance, manufacturers can maintain a robust body of evidence that supports both regulatory compliance and patient safety throughout the medical device lifecycle.
Whether you are developing a new medical device, updating legacy Technical Documentation or preparing for a Notified Body assessment, a well-planned Biological Evaluation is essential for demonstrating compliance with the EU MDR and the ISO 10993 series of standards.
At Patient Guard, our regulatory specialists support manufacturers with every stage of the Biological Evaluation process, from developing Biological Evaluation Plans (BEPs) and Biological Evaluation Reports (BERs) to chemical characterisation strategies, toxicological risk assessments, biocompatibility testing strategies and Technical Documentation reviews. Our risk-based approach ensures that Biological Evaluation is scientifically justified, proportionate to the device and aligned with current regulatory expectations.
Need support with your Biological Evaluation? Contact Patient Guard today to discuss your medical device and learn how our team can help you develop a compliant, evidence-based Biological Evaluation strategy.
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.
References
This guide is based on the following legislation, international standards and official regulatory guidance relating to the biological evaluation, biocompatibility assessment and supporting scientific evidence required for medical devices.
| Organisation | Reference | Why it's relevant |
|---|---|---|
| European Union | Regulation (EU) 2017/745 on Medical Devices (EU MDR) | Requires manufacturers to demonstrate compliance with the General Safety and Performance Requirements (GSPRs), including the identification, evaluation and control of biological risks throughout the medical device lifecycle. |
| International Organization for Standardization (ISO) | ISO 10993-1:2025 – Biological Evaluation of Medical Devices – Part 1: Requirements and General Principles for the Evaluation of Biological Safety Within a Risk Management Process | Provides the internationally recognised framework for Biological Evaluation, including device categorisation, Biological Evaluation Plans (BEPs), biological endpoints, supporting scientific assessments, evidence review and determining whether additional biological testing is required. |
| International Organization for Standardization (ISO) | ISO 10993-17:2023 – Biological Evaluation of Medical Devices – Part 17: Toxicological Risk Assessment of Medical Device Constituents | Provides the methodology for performing toxicological risk assessments of chemicals identified during Biological Evaluation and supports the assessment of patient exposure to leachable substances. |
| International Organization for Standardization (ISO) | ISO 10993-18:2020 – Biological Evaluation of Medical Devices – Part 18: Chemical Characterisation of Medical Device Materials Within a Risk Management Process | Defines how manufacturers identify and characterise chemicals that may be released from medical devices, providing the foundation for toxicological risk assessment and evidence-based Biological Evaluation. |
| International Organization for Standardization (ISO) | ISO 14971:2019 – Medical Devices – Application of Risk Management to Medical Devices | Provides the internationally recognised Risk Management framework that underpins Biological Evaluation by supporting the identification, evaluation, control and monitoring of biological hazards throughout the device lifecycle. |
| International Organization for Standardization (ISO) | ISO 13485:2016 – Medical Devices – Quality Management Systems – Requirements for Regulatory Purposes | Defines the Quality Management System requirements that support Biological Evaluation through design controls, supplier management, material traceability, change control, validation activities and post-market surveillance. |
| U.S. Food and Drug Administration (FDA) | Use of International Standard ISO 10993-1, "Biological Evaluation of Medical Devices – Part 1: Evaluation and Testing Within a Risk Management Process" – FDA Guidance | Explains how the FDA applies ISO 10993-1 when assessing the biological safety of medical devices and provides recommendations for planning Biological Evaluation, determining whether biocompatibility testing is necessary and preparing premarket submissions using a risk-based approach. |
| U.S. Food and Drug Administration (FDA) | Biocompatibility Evaluation Endpoints by Device Category | Provides biological evaluation endpoint tables based on device category, body contact type and contact duration, illustrating how biological endpoints are selected using the principles of ISO 10993-1. |
| U.S. Food and Drug Administration (FDA) | Basics of Biocompatibility: Information Needed for Assessment by the FDA | Explains the FDA's risk-based approach to Biological Evaluation, including how intended use, materials, manufacturing processes, contact type and duration influence the evidence required to demonstrate biological safety. |
Biological Evaluation should always be based on a documented risk management process rather than automatically performing every biological or biocompatibility test. Manufacturers should consult the latest published legislation, recognised international standards and official regulatory guidance when determining the appropriate Biological Evaluation strategy, supporting scientific assessments and evidence required to demonstrate the biological safety of their medical devices.
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