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GLP Laboratories · ISO 10993-1:2025 Product-Specific Strategy

Biological Safety of Medical Devices – Product-Specific Biocompatibility Strategy

in Accordance with ISO 10993

Metecon develops product-specific biocompatibility strategies with a clear rationale: from material selection and manufacturing processes to toxicological risk assessment. We translate laboratory results into transparent regulatory documentation—relevant to patients and robust even in the face of changes.

10+ experts in biocompatibility and regulatory affairs · Medical Devices · In-Vitro Diagnostics
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Frequently Asked Questions →
10+
Years of experience with ISO 10993
50+
BEP/BER-supported
Product-Specific Rationale
Instead of generic test lists
NEW · NOV. 2025 ISO 10993-1:2025 Published – Take Action Now:

The sixth edition of ISO 10993-1 (November 2025) introduces new requirements: foreseeable misuse in the hazard analysis, more precise cumulative exposure calculation, and greater integration with ISO 14971. Existing BEPs may be affected. Request a gap analysis →

Biological Safety at Metecon: A Product-Specific Strategy Instead of a Generic Test List

Biological safety is a central component of the safety and performance validation and is therefore directly relevant to patients. The difference lies in the approach: Metecon does not develop generic test lists, but rather product-specific biocompatibility strategies with a clear rationale—consistently structured from material selection through manufacturing processes to toxicological risk assessment. The goal is robust biocompatibility information without unnecessary tests and without gaps.

3 Common Challenges in Biological Assessment—and How Metecon Solves Them

Challenge 1 · Testing Strategy

The testing strategy is unclear or overly extensive

Manufacturers invest in tests that are not required by regulations—or overlook relevant biological effects, which leads to inquiries and additional requirements during the Notified Body’s evaluation.

Metecon Solution: A product-specific testing strategy with a clear rationale—every biological effect is derived from data, and no test is superfluous.

Challenge 2 · Data Gaps

Material and process data are incomplete

Evaluations become unreliable; changes in suppliers or processes trigger time-consuming reassessments because the starting point is missing.

Metecon Solution: Material gap analysis and structured database—reliable even when suppliers or processes change.

Challenge 3 · Consistency

Evaluations are not consistently aligned with risk, intended purpose, and materials

Inconsistencies between biological evaluation, risk management, and intended purpose lead to follow-up questions and rework in the assessment.

Metecon Solution: End-to-end consistency between BEP/BER, risk management files, intended purpose, and material data—with verifiable traceability.

Biological Safety and Biocompatibility: Why ISO 10993 Is Mandatory

Every medical device that comes into contact with the body must demonstrate biological safety. Data sheets are not sufficient—ISO 10993 requires a systematic, risk-based evaluation process.

Biological Safety

General Principle: When used as intended, the medical device must not pose any unacceptable biological risks. Basic safety and performance requirements according to MDR Annex I, No. 10—this applies to all medical devices that come into direct or indirect contact with the body, regardless of the risk class.

Biocompatibility

A specific aspect of biological safety: the compatibility of the material and product with biological systems. A biocompatible product does not cause toxic, immunogenic, mutagenic, or carcinogenic reactions. Verification is conducted in accordance with ISO 10993-1 through a risk-based evaluation process—primarily via material characterization, chemical analysis, biological testing, and toxicological risk assessment.

Contact Categorization According to ISO 10993-1:

Which biological endpoints must be tested depends on two factors:

  • Type of exposure: direct/indirect (surface contact, penetration, implantation)

  • Duration of exposure (short-term <24 hours, extended 24 hours–30 days, long-term >30 days)

This categorization is the first outcome of the Biological Evaluation Plan (BEP) and determines the overall scope of testing.

5 Steps to a Review-Ready Biocompatibility File

1

Create a BEP
categorization, biological effects, test strategy
2

Material Characterization, including Chemical Characterization
materials, composition, data basis
3


Chemical Analyses
(if required)
risk-based, data for TRA/BER
4

TRA (ISO 10993-17)
toxicological risk assessment
(initial & update)
5

BER
overall assessment, evidence, traceability

Biocompatibility: Our Approach

Metecon prioritizes testing strategies that minimize animal testing, based on material characterization, chemical characterization, and toxicological risk assessment. The current ISO 10993-1 standard and the FDA guidance on the “3R” principle (reduce, replace, refine) explicitly support this risk-based approach. As a result, the biological evaluation can be achieved in many projects without additional animal testing.


Material characterization according to ISO 10993-18Toxicological risk assessment according to ISO 10993-173R approach FDA Guidance 2023based on literature data

Our Range of Services: From Material Selection to Interface Consistency

  • Strategic Support from the Very Beginning

    Support in selecting biocompatible materials during the design phase. Preparation of the biological evaluation plan (BEP), including risk assessment, literature search strategy, standard categorization, and definition of biological effects. Integration of country-specific requirements and product-specific standards—e.g., for dental products, gas-conducting systems, or intraocular lenses.

  • Chemical & Biological Testing Strategies

    Planning and selection of suitable testing methods and laboratories (ISO 17025 / GLP). Evaluation of accreditations and certifications. Selection of specialized testing laboratories—such as those for gas-conducting products or intraocular lenses. This results in a testing strategy that is both regulatory-compliant and economically sound.

  • Evaluation & Risk Assessment

    Integration of test results and literature data into the biological evaluation report (BER). Toxicological risk assessment in accordance with ISO 10993-17 for critical substance levels. Identification of necessary additional tests in the event of new risks or data gaps. Evaluation of preclinical data, including verification and validation data, for the biological evaluation.
    .

  • Interdisciplinary expertise included

    Close coordination with risk management, technical documentation, verification/validation, and sterilization, packaging, and reprocessing processes. Development and evaluation of reprocessing and hygiene concepts in accordance with ISO 17664-1/-2. Classification of sterility-related evidence, e.g., for EO sterilization according to ISO 11135 and for EO/ECH residues according to ISO 10993-7.

NEW: ISO 10993-1:2025 Biological Equivalence: The New Concept of the Sixth Edition:

ISO 10993-1:2025 introduces the concept of biological equivalence as a formalized evaluation approach: Manufacturers can demonstrate the biocompatibility of a new product based on an already evaluated reference product—provided that the materials, manufacturing process, sterilization method, and contact categorization can be shown to be comparable. This can reduce the testing effort. Metecon evaluates within the BEP whether biological equivalence can be demonstrated for your product—and prepares the justification compliant with the standard`s requirements .

BEP, BER, and TRA: The Three Core Documents of Your Biocompatibility File

The biological evaluation plan, biological evaluation report, and toxicological risk assessment are core components of the biological evaluation according to ISO 10993. Metecon prepares all three documents in full and in a format suitable for Notified Bodies.

Our Services at a Glance

Biological Evaluation Plan (BEP)

BEP according to ISO 10993-1:2025: Contact categorization, biological effects, test strategy, acceptance criteria. Integration of biological risks into the existing risk management process.

Biological Evaluation Report (BER)

Final biocompatibility evaluation report – all data, test results, and conclusions consolidated and prepared for review by Notified Bodies.

Toxicological Risk Assessment (TRA)

ISO 10993-17: Derive the tolerable intake (TI), quantify exposure, and evaluate toxicological effects—by qualified toxicologists.

Chemical Characterization (ISO 10993-18)

Extractables & leachables (E&L) analysis: Identification and quantification of relevant substances as a basis for toxicological risk assessment.

External Laboratory Coordination

Laboratory strategy, selection of GLP-accredited testing laboratories, coordination, evaluation of results, and integration into the technical documentation.

Biocompatibility Evaluation for Medical Devices in Accordance with the MDR and IVDs in Accordance with the IVDR

BEP, BER, TRA, chemical characterization, and external laboratory coordination—fully compliant with ISO 10993-1:2025, MDR, IVDR Annex I, and FDA Guidance 2023.

ISO 10993-1:2025 – NOVEMBER 2025 What the new standard means for your documentation:

The sixth edition establishes three new key focuses: (1) Predictable misuse must be explicitly considered in the biological hazard analysis. (2) Cumulative exposure during intermittent use is calculated more precisely. (3) Integration with ISO 14971 is further strengthened. Metecon will conduct your BEP gap analysis.

BEP, BER, and TRA: Core Components of Biological Assessment

The MDR requires manufacturers to systematically assess and control risks arising from the product’s contact with the human body (MDR Annex I, Article 10). In practice, the biological evaluation is often structured in accordance with the ISO 10993 series of standards, although other product-specific standards on biocompatibility may also be applied.

BEP, BER, and TRA are typical documents used to document procedures and results:
– BEP (biological evaluation plan): Systematic assessment of biological risks and data gaps,
– BER (biological evaluation report): A well-founded overall assessment of biocompatibility for the intended purpose,
– TRA according to ISO 10993-17: Toxicological risk assessment of relevant substances and exposures.

BEP, BER, and TRA: Our Complete Range of Services

Biological Evaluation Plan (BEP) in Accordance with ISO 10993-1:2025

Preparation of the BEP in accordance with ISO 10993-1:2025: product and application context, material and substance basis (as a separate document for material characterization, if necessary), contact categorization (type and duration), identification of relevant biological effects, risk-based testing strategy with justification for animal-free alternatives, acceptance criteria, and link to risk management in accordance with ISO 14971. The BEP is a central component of the biological evaluation within the framework of conformity assessment and is typically prepared early in the process. It also determines whether an argument for biological equivalence to a reference product is robust and where additional testing is required. Metecon prepares BEPs for all risk classes and a wide range of product types.

Gap Analysis of Existing Biocompatibility Dossiers

Review of existing BEPs and BERs against the requirements of ISO 10993-1:2025, MDR/IVDR Annex I, and current FDA guidance: technical evaluation with recommendations for action. Of particular relevance: compliance with the new sixth edition (Nov. 2025) and the FDA Final Guidance (Sep. 2023).

Literature Review and Material Characterization

Systematic literature review of materials, process chemicals, and their respective ingredients, as the basis for an animal-testing-free approach. Evaluation of existing data sheets, certificates of conformity, and raw material documentation to assess their relevance for biocompatibility assessment.

Biological Evaluation Report (BER) – Complete Biocompatibility Dossier

The BER is the final document of the entire biocompatibility evaluation and provides a consolidated summary of all activities and results: material characterization, literature data on materials and leachables, chemical characterization results (ISO 10993-18), toxicological risk assessment (TRA according to ISO 10993-17), laboratory test results with evaluation and an overall conclusion on biological safety. The BER is prepared for Notified Body reviews and provides complete traceability of the biological evidence. In the event of product changes, Metecon assesses the impact on the biological evaluation and documents whether the existing evaluation remains valid or whether the BEP, BER, and, if necessary, the TRA must be updated.

Toxicological Risk Assessment (TRA) in accordance with ISO 10993-17

Toxicological risk assessment by qualified toxicologists: Derive toxicologically based reference values, tolerable intake levels, or other appropriate toxicological reference values in accordance with ISO 10993-17, quantify exposure based on contact type and duration, calculate safety margins, and document the risk characterization. ISO 10993-17 explicitly requires qualified toxicologists—a lack of expertise on the part of the evaluator is one of the most common reasons for audit nonconformities. Metecon works with certified toxicologists and uses recognized, regularly updated specialized databases for substance evaluation. The TRA is an essential part of the overall biological evaluation and forms the basis for determining the need for further testing or for a final positive overall assessment.

Prompt Assistance with Inquiries from the Notified Body Regarding Biocompatibility

Inquiries from Notified Bodies regarding BEP, BER, or TRA are addressed promptly by Biokomp specialists with direct experience communicating with Notified Bodies.

ISO 10993-18 Chemical Characterization: E&L Analysis Instead of Animal Testing

Chemical characterization in accordance with ISO 10993-18 identifies relevant substances in the product. These substances are quantified on a product-specific basis through chemical analyses—which form the basis for the TRA without animal testing.

ISO 10993 Series of Standards: Which Parts Apply to Your Product

The BEP specifies which parts of ISO 10993 are relevant to your specific product. For medical devices with gas-mediated contact with the respiratory tract, such as ventilator tubing, breathing masks, and gas pathway components, the ISO 18562 series of standards applies in addition to the ISO 10993 series.

An overview of the most important sub-standards of ISO 10993:

  • ISO 10993-1:2025 – Framework

    Categorization, Effects, Testing Strategy – The Basis for All Biocompatibility Assessments

    EN ISO 10993-1:2025 –Biological evaluation of medical devices – Part 1: Requirements and general principles for the assessment of biological safety within a risk management process

    The objective is the systematic selection and evaluation of appropriate tests based on the type, duration, and nature of contact between the medical device and the body—the foundation of all biocompatibility assessments.

  • ISO 10993-5 – Cytotoxicity

    In-vitro cytotoxicity test—the most common initial test for new materials

    EN ISO 10993-5:2009/A11:2025 – Biological evaluation of medical devices – Part 5: Tests for in-vitro cytotoxicity 

    The objective is to assess potential harmful effects on cells caused by released substances or materials—the most common initial test for both new materials and routine screening

  • ISO 10993-10 – Sensitization

    Potential for skin sensitization—particularly with repeated or prolonged contact

    EN ISO 10993-10:2023 – Biological evaluation of medical devices – Part 10: Tests for irritation and skin sensitization

    The objective is to assess the risk of allergic reactions resulting from repeated skin contact.

  • ISO 10993-23 – Irritation

    Skin irritation test using 3D skin models (in-vitro alternative)

    EN ISO 10993-23: 2021 + A1:2025 – Biological evaluation of medical devices – Part 23: Tests for irritation

    The objective is to evaluate local reactions such as redness, swelling, or tissue damage resulting from contact using a skin irritation test with 3D skin models (in-vitro alternative).

  • ISO 10993-17 – Toxicological Evaluation

    Derive the Tolerable Intake (TI), quantify exposure, and calculate the safety margin—only by qualified toxicologists

    EN ISO 10993-17:2023 + A1:2025 – Biological evaluation of medical devices – Part 17: Toxicological risk assessment of medical device constituents

    The objective is the toxicological evaluation and derivation of safe limit values based on the determined exposure—to be performed only by qualified toxicologists.

  • ISO 10993-18 – Chemical Characterization

    EN ISO 10993-18:2020 + A1:2023 – Biological evaluation of medical devices – Part 18: Chemical characterization of medical devices materials within a risk management process.

    The objective is to assess potential toxicological risks based on chemical composition and exposure—the basis for an animal-free approach.

  • ISO 10993-6 – Implantation Effects

    Macroscopic and microscopic evaluation of implants.

    EN ISO 10993-6:2016 – Biological evaluation of medical devices – Part 6: Tests for local effects after implantation.

    The objective is to assess irritation, inflammation, and tissue changes at the implantation site.

  • ISO 10993-11 – Systemic Toxicity

    Acute and chronic systemic toxicity for implants and medical devices intended for long-term contact.

    EN ISO 10993-11:2018 – Biological evaluation of medical devices — Part 11: Tests for systemic toxicity.

    The objective is to evaluate acute, subacute, and subchronic toxic effects on the entire organism.

  • ISO 10993-4 – Hemocompatibility

    Blood-contacting products: Hematology and thrombosis tests.

    EN ISO 10993-4: 2017 + A1:2025 – Biological evaluation of medical devices – Part 4: Selection of tests for interactions with blood.

    The objective is to assess risks such as thrombosis, hemolysis, or activation of blood components by the product.

  • ISO 10993-3 – Genotoxicity

    Genotoxic effects—during long-term contact or contact with implants.

    EN ISO 10993-3:2014 – Biological evaluation of medical devices – Part 3: Tests for genotoxicity, carcinogenicity and reproductive toxicity.

    Identification and evaluation of potential DNA damage and long-term risks caused by released substances.

  • ISO 10993-12 – Sample Preparation

    Extraction methodology and parameters—critical for the validity and reproducibility of the tests.

    EN ISO 10993-12:2021 + A1:2025 – Biological evaluation of medical devices — Part 12: Sample preparation and reference materials.

    The goal is the standardized and reproducible preparation of test solutions (extracts) as a basis for further evaluation.

  • FDA Guidance (09/2023) on ISO 10993-1 – Additional FDA expectations for U.S. submissions

    Annex G (skin contact), additional effects, differing recognition of ISO 10993-1.

    FDA Use of International Standard ISO 10993-1, “Biological Evaluation of Medical Devices—Part 1: Evaluation and Testing within a Risk Management Process”—U.S. Market Requirements (09/2023)

    The FDA guidance document specifies the application of ISO 10993-1 in the context of the biological evaluation of medical devices for the U.S. market. The goal is the risk-based selection, justification, and evaluation of tests, taking into account regulatory expectations and available data.

  • ISO 10993-7 – EO Sterilization Residues

    EO sterilization (in accordance with ISO 11135) and its residues can affect biocompatibility—sterilization residues must be determined and evaluated using specific analyses in accordance with ISO 10993-7.

    EN ISO 10993-7:2008 + AC:2009 + A1:2022 – Biological evaluation of medical devices – Part 7: Ethylene oxide sterilization residuals.

    EO sterilization (in accordance with ISO 11135); residues may affect biocompatibility—the objective is to limit and conduct a toxicological evaluation of EO, ECH, and EG residues to ensure patient safety.

External testing laboratories: GLP-compliant, coordinated, and capable of meeting regulatory requirements

Metecon handles all aspects of laboratory coordination: test strategy, selection of appropriate testing laboratories, sample management, evaluation of results, and biological verificatio in accordance with ISO 10993.

External Testing Laboratories: Strategy, Selection, and Coordination

  • What Metecon Handles as Coordinator

    Develops a laboratory strategy (determining which tests are truly necessary—often fewer than expected) · Selects GLP-compliant laboratories from an accredited network · Defines test specifications and sample preparation in accordance with ISO 10993-12 · Coordinates sample shipping · Scientifically evaluates results and integrates them into BER · Fully handles communication between the laboratory and the manufacturer. For particularly challenging issues, Metecon organizes interlaboratory tests upon request to ensure the quality of laboratory data—so that you are as well-prepared as possible for Notified Body audits. Where in-vivo testing is required by regulations (e.g., chronic systemic toxicity, class III implantation effects), Metecon coordinates these tests through GLP-accredited testing institutes.

  • Cytotoxicity (ISO 10993-5)

    Cytotoxicity tests (e.g., L929 fibroblasts) conducted at qualified testing laboratories.

    Irritation (ISO 10993-23):
    Irritation tests (e.g., in-vitro 3D skin models according to ISO 10993-23) at qualified testing laboratories—typically without animal testing.

    • E&L Analysis (ISO 10993-18)

      Chemical analyses for organic E&Ls (Extractables & Leachables): LC-MS, GC-MS, AET calculation (Analytical Evaluation Threshold), identification and quantification of all substances above the AET.

      Chemical analyses for inorganic E&Ls: ICP-MS, identification and quantification of inorganic elements via target analyses

    • Hemocompatibility (ISO 10993-4)

      Blood-contacting products: Hematology and thrombosis tests

      EN ISO 10993-4: 2017 + A1:2025 –Biological evaluation of medical devices – Part 4: Selection of tests for interaction with blood.

      The objective is to assess risks such as thrombosis, hemolysis, or activation of blood components by the product.

Material Compliance, Sterilization, and Reprocessing: Expanded Areas of Expertise

Biocompatibility does not end with the raw material data sheet. Manufacturing processes, sterilization methods, and process chemicals influence the biological properties of the final product—ISO 10993-1:2025 explicitly requires that these factors be taken into account.

Material Compliance: REACH, SVHCs, and Process Chemicals

Biocompatibility begins with material selection. ISO 10993-1:2025 explicitly requires consideration of manufacturing processes and process chemicals. Metecon provides support for systematic material compliance: REACH-compliant material selection, SVHC (Substances of Very High Concern) screening, supplier data management, and process chemical assessment. Of particular relevance: cleaning residues, release agents, and coatings, which must be identified in advance in order to classify leachables in the E&L analysis.

Reprocessable Medical Devices and ISO 17664-1 and ISO 17664-2

For reprocessable products (e.g., endoscopes, surgical instruments), biological safety must be demonstrated after reprocessing: Material resistance to cleaning agents and disinfectants, verification of complete removal of biological contamination, and maintenance of biocompatibility after defined reprocessing cycles. Metecon develops the biocompatibility concept for reprocessable products and coordinates reprocessing validations in accordance with the applicable standard.

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FDA Guidance vs. MDR: Additional Requirements for the U.S. Market

The FDA only partially recognizes ISO 10993-1:2018. Annex G (skin contact), additional endpoints for certain categories, and other acceptance limits differ from EU requirements. Metecon prepares documentation that complies with both EU and U.S. requirements.

The FDA does not fully adopt ISO 10993-1 but rather specifies its application through its own guidelines. In particular, Annex G (skin contact), adapted endpoint requirements, and differing evaluation approaches lead to differences from the typical EU application.

ISO 10993-1:2025 is (partially) recognized by the FDA; a transition period for the previous version is in effect until July 1, 2029.

Standards & Guidelines: Biosafety, Medical Devices, MDR

  • MDR (EU) 2017/745 – Annex I, Sections 10 and 11: Biological Safety as a GSPR Requirement
  • EN 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 (framework determining the application of other standards, state of the art)
  • EN ISO 10993-17:2023 + A1:2025 – Biological evaluation of medical devices – Part 17: Toxicological risk assessment of medical device constistuents
  • EN ISO 10993-18:2020 + A1:2023 – Biological evaluation of medical devices – Part 18: Chemical characterization of medical devices materials within a risk management process
  • FDA Use of International Standard ISO 10993-1, "Biological evaluation of medical devices - Part 1: Evaluation and testing within a risk management process" – U.S. market requirements
  • EN ISO 14971:2019 + A11:2021 – Medical devices – Application of risk management to medical devices
  • EN ISO 11135:2014 + A1:2019 – Sterilization of healthcare products – Ethylene oxide – Requirements for the development, validation, and routine  control of a sterilization process for medical devices
  • EN ISO 10993-7:2008 + AC:2009 + A1:2022 – Biological evaluation of medical devices – Part 7: Ethylene oxide sterilization residuals
  • EN ISO 11137-2:2015 + A1:2023 – Sterilization of health care products – Radiation – Part 2: Establishing the sterilization dose
  • EN ISO 11607-1:2020 + A1:2023 – Packaging for terminally sterilized medical devices – Part 1: Requirements for materials, sterile barrier systems, and packaging systems
  • EN ISO 17664-1:2021 – Processing of health care products — Information to be provided by the medical device manufacturer for the processing of medical devices — Part 1: Critical and semi-critical medical devices
  • EN ISO 17664-2:2023 –
  • Processing of health care products — Information to be provided by the medical device manufacturer for the processing of medical devices —
  • Part 2: Non-critical medical devices

IVDR and Biocompatibility: What IVDR Annex I Requires

Similar to the MDR, Annex I of the IVDR also sets out safety and performance requirements for in-vitro diagnostic medical devices (IVDs) with regard to their chemical, physical, and biological properties.

Standards & Guidelines: IVD Biosafety

  • IVDR (EU) 2017/746 – Annex I, No. 10.2: Biological Safety for IVDs
  • EN 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

Clear Definition of Standards in the BEP

Metecon determines in a binding manner which standard applies to your IVD—and prevents costly, unnecessary testing.

Application of ISO 10993 to IVDs

1

IVD devices in direct contact with the body

Blood collection tubes, catheters, wound diagnostics: ISO 10993 applies in full. Contact categorization (type, duration, intensity) determines the required tests.

2

IVD without direct patient contact

Laboratory equipment, reagents: ISO 10993 is limited or not applicable. However, biocompatibility must be considered with regard to work equipment aspects.

IVDR-Specific Aspects of Biosafety

Contact Categorization for IVDs According to ISO 10993-1

Blood-contacting IVDs (e.g., blood collection tubes, capillary tubes): short-term contact—typically requiring cytotoxicity, hemocompatibility, and sensitization testing. IVDs without body contact: minimal or no biocompatibility testing. Metecon clearly explains in the BEP what applies to your IVD—and what does not.

Hemocompatibility for Blood-Contacting IVDs

ISO 10993-4: Hematology and thrombosis tests for IVD devices that come into contact with human blood. Relevant for blood collection tubes, anticoagulant systems, microfluidic IVD cartridges, and all components that come into contact with blood.

Biocompatibility of Respiratory Tract Devices—the ISO 18562 Series of Standards

For medical devices that come into contact with the respiratory tract via gas, the ISO 18562 series of standards applies in addition to the ISO 10993 series. Metecon assesses the exact scope of application in the BEP and prevents unnecessary duplicate testing.

ISO 18562: Biological Safety in Gas-Mediated Respiratory Exposure

ISO 18562 (harmonized since 2026) consists of four parts and applies whenever medical devices not only come intodirectcontact with the body but also affect the respiratory tract, such as ventilator tubing, breathing masks, and breathing gas pathway components.

Assessment of the Biocompatibility of Respiratory Tracts in Medical Applications

ISO 18562: The Four Parts of the Respiratory Standard

ISO 18562-1

Assessment and testing within a risk management process

General Part — always applicable. ISO18562-1establishesthe general frameworkfor the biological evaluation of breathing gas pathways in medical devices.

The objective is to define risk assessment, testing strategies, and the selection of appropriate tests for potential inhalation exposures.

ISO 18562-2

Tests for Emissions of Particular Matter

ISO18562-2 describes the determination and evaluation of emissions of particular matter in the breathing gas pathway.

The objective is to assess the risk posed by inhaled solid particles from the gas pathway.

ISO 18562-3

Tests for Emissions of Volatile Organic Compounds (VOCs)

ISO18562-3 addresses the determination and evaluation ofvolatile organic substances (VOCs) in the exhaled breath stream.

The objective is the toxicological assessment of exposure to gaseous pollutants.

ISO 18562-4

Tests for Leachable Substances in Condensates

ISO18562-4 describes the determination and evaluation of non-volatile (condensable) substances in the breathing gas pathway of medical devices.

The objective is the toxicological assessment of exposure to inhaled residues from the gas path.

ISO 18562 is fully taken into account

In the BEP, Metecon assesses whether and which parts of ISO 18562 apply to your product—and avoids unnecessary duplicate testing.

ISO 10993 vs. ISO 18562 – Choosing the Right Standard:

ISO 10993 applies to medical devices that come into direct contact with patients. ISO 18562 applies to devices that come into contact with the respiratory tract via gas (without direct physical contact). If both apply, both standards apply. Metecon will clarify in the BEP which standards are relevant for your product.

metecon-carolin-schilpp

Dr. Carolin Schilpp

Team Lead, Biological Safety · Metecon GmbH

Dr. Carolin Schilpp leads the Biological Safety team at Metecon. Areas of focus: product-specific biocompatibility strategies in accordance with ISO 10993-1, preparation of Biological Evaluation Plans (BEPs) and Biological Evaluation Reports (BERs), toxicological risk assessment in accordance with ISO 10993-17, chemical characterization in accordance with ISO 10993-18, ISO 18562 for respiratory tract contact, and reprocessing concepts in accordance with ISO 17664. Carolin and her team support manufacturers from material selection in the design phase through the testing strategy to a consistent interface with risk management, technical documentation, and V&V—using clear, well-reasoned logic rather than generic test lists.

Meet our experts

"We don’t develop generic test lists; instead, we create product-specific biocompatibility strategies with a clear rationale. The goal is to provide robust evidence of biocompatibility—without unnecessary tests and without any gaps in the data."

Dr. Carolin Schilpp, Team Lead, Biological Safety, Metecon

Frequently Asked Questions About Biological Evaluation According to ISO 10993

When should a biocompatibility strategy in accordance with ISO 10993-1 be in place during product development?

Ideally, this should be done early in the development process—when the initial material and process decisions are being made. Those who wait until shortly before approval to establish a biocompatibility strategy risk costly retesting, unnecessary testing, or a failure to detect biological effects. An early, product-specific strategy in accordance with ISO 10993-1 ensures that the material selection, testing strategy, and toxicological risk assessment are consistently structured from the very beginning. Metecon provides support starting with the selection of biocompatible materials during the design phase.
How is consistency in biological assessment maintained when materials or processes are changed?

Changes in materials, suppliers, or processes often trigger time-consuming re-evaluations—especially when the initial documentation is incomplete. The key is a structured database: If material data, chemical characterization, and toxicological assessment are linked in a traceable manner from the outset, changes can be used to specifically determine what needs to be re-evaluated—and what remains valid. Metecon structures the biological assessment in such a way that it can be reliably continued in the event of changes and coordinates closely with risk management.
How can you tell if a biological assessment report is reliable?

Three indicators: (1) Every biological effect that has been tested—and every biological effect that has NOT been tested—is derived based on a clear line of reasoning. (2) The assessment is consistent with risk management, intended use, and materials. (3) Data gaps are identified and addressed with a strategy for closing them, rather than being ignored. A robust BER withstands the Notified Body’s assessment without triggering inquiries regarding unfounded tests or missing biological effects. Metecon verifies this robustness as part of a material and BER gap analysis.
When can specific tests under ISO 10993 be omitted?

Individual tests may be omitted if biological safety with respect to the biological effect in question can be demonstrated in another reliable manner—for example, through chemical characterization and, if necessary, analyses in accordance with ISO 10993-18 followed by a toxicological risk assessment in accordance with ISO 10993-17, through existing literature data, or through the concept of biological equivalence (ISO 10993-1:2025). The key is a transparent line of reasoning: Every omission must be documented and justified in the BEP/BER. This results in a demonstration of biocompatibility without unnecessary testing—but also without gaps.
How are biological assessment and risk management related?

Biological evaluation is an integral part of risk management process according to ISO 14971: Identified biological risks, residual risks, risk-mitigation measures, and their justification must be consistent between the BER and the risk dossier. ISO 10993-1:2025 reinforces this integration even further. An inconsistent BER creates gaps that will come back to haunt you later in the conformity assessment process or when changes are made. Metecon ensures that biological risks, intended use, and material data are consistently incorporated into risk management and the clinical evaluation.
How can costs and turnaround time be optimized when conducting tests in a testing laboratory?

Costs and duration depend largely on the testing strategy. A product-specific strategy avoids overly broad testing packages: Instead of a generic test list, only those biological effects required by regulations for the specific product are tested. Where possible, chemical characterization and toxicological risk assessment are used to cover biological effects. Metecon plans and selects suitable test methods and laboratories (ISO 17025 / GLP), evaluates accreditations, and coordinates specialized testing laboratories—for example, for gas-permeable products or intraocular lenses. This saves time and avoids duplicate testing.
What is the difference between a biological evaluation plan and a biological evaluation report?

The biological evaluation plan (BEP) is the planning document: It specifies which biological endpoints are relevant for the product, what testing and evaluation strategy will be followed, and what acceptance criteria apply—based on the type, duration, and intensity of exposure. The biological evaluation report (BER) is the final document: It integrates test results, literature data, and toxicological risk assessment into a robust body of evidence. Put simply: The BEP plans, the BER proves. Both must be clearly integrated into the technical documentation and versioned.
How much does Metecon charge for assistance with a biosafety assessment?

The effort involved depends on several factors: product complexity and contact categorization (type, duration, intensity), available material and process data (complete vs. incomplete), the scope of the required chemical characterization and toxicological risk assessment, the number of material variants, and the desired level of support—ranging from strategic consulting through the BEP to a complete BER. A product-specific strategy reduces overall costs by avoiding unnecessary testing. Following a free initial consultation, Metecon provides a transparent cost estimate.

Ready for a product-specific biocompatibility strategy in accordance with ISO 10993?

Start with a free initial consultation on your product, type of contact, and available material data. Within a few business days, we will provide you with an initial assessment—including the next logical steps, such as material characterization, BEP, toxicological risk assessment (TRA), or BER.

Request a Free Initial Consultation

Your contact:

Milan Weiß
Sales Manager
T: +49 621 123469-040
milan.weiss@metecon.de

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