Medical Device Biocompatibility Testing & Regulatory Compliance

Medical devices must be designed and manufactured to minimize risks to patients, healthcare professionals and end users. Manufacturers are responsible for demonstrating the biological safety of any patient-contacting device, regardless of the regulatory pathway or submission route.

Medical Devices Consumer Products

A Foundation for Regulatory Compliance

ISO 10993-1 provides the framework for evaluating biological risks and defining appropriate testing.

Presentation at Medica: Dr. Anja Gerharts ISO 10993 and ISO 18562 Test Methods for Biocompatibility

Biocompatibility evaluations, planned using ISO 10993-1, provide the objective evidence needed to identify hazards, assess biological risks and determine whether chemical or biological testing is required. This evaluation supports regulatory documentation for FDA premarket submissions (510(k) and PMA), EU MDR technical documentation and other international approvals.

Hohenstein Medical provides ISO 17025-accredited and GLP-compliant testing, along with scientific expertise, to design targeted biocompatibility strategies. With one partner for planning, testing and interpretation, you gain a clear and defensible path to FDA, EU and global market approval.

Why Biocompatibility Matters

Biocompatibility ensures the device is biologically safe for patients.

Biocompatibility evaluates how a medical device interacts with the body, including materials and any manufacturing or sterilization residues that could cause harmful biological responses during intended use.

A complete evaluation confirms that the finished device will not trigger irritation, sensitization or systemic effects. When this work is overlooked or incomplete, patients face preventable biological risks, and manufacturers face regulatory delays, test failures, redesigns and potential market withdrawal.

ISO 10993 requires a risk-based approach to determine if testing is needed and what can be justified with existing data. A well-planned biocompatibility program helps build a defensible biological safety case for FDA, EU MDR and global submissions.

projectmedtech Podcast: Navigating Biocompatibility in MedTech

Biological Safety Testing Framework

ISO 10993-1

Medical device biocompatibility process flowchart showing BEP strategy, risk-based testing, and BER final risk assessment. — ISO 10993-1 sets the framework for biocompatibility by defining the biological endpoints needed for regulatory submissions for medical devices.

The ISO 10993-1 standard establishes a risk-based framework for evaluating the biological safety of medical devices. Rather than defaulting to predefined test panels, it emphasizes structured evaluation planning aligned with device type, contact duration and clinical use.

Chemical characterization and Toxicological Risk Assessment (TRA) provide the scientific foundation for this process, linking material constituents and patient exposure to justified testing strategies.

A typical process flow includes biological safety planning, risk-based testing where required and final biological safety assessment to support FDA and EU MDR submissions.

Article: The Hidden Cost of Unplanned Biocompatibility Testing

ISO 10993-1
Process
Reasonably Foreseeable Misuse

ISO 10993-1

ISO 10993-1: Framework for Biological Safety Evaluation

ISO 10993-1 defines the framework for assessing biological safety by identifying the relevant biological effects (referred to as biological endpoints in current FDA submissions) that must be evaluated for a medical device.

Under ISO 10993-1, the standard:

Defines biological evaluation and testing within a risk management process
Links the device category and nature of body contact to relevant biological effects/endpoints
Addresses biological hazards, potential harms and associated risks
Serves as the biological safety framework used in:
- FDA regulatory submissions (using biological endpoints)
- EU MDR submissions (using biological effects, per ISO 10993-1)

Process

Medical Device Biocompatibility Process

Biological safety evaluation is conducted using a structured, evidence-based approach:

A Biological Evaluation Plan (BEP) identifies biological hazards, applicable biological effects/endpoints, existing data and data gaps
If gaps are identified, risk-based biological testing is performed to address potential harms
Depending on materials and exposure, this may include:
- Extractables and leachables (E&L) studies
- Toxicological risk assessment (TRA)
All data and rationale are compiled into a Biological Evaluation Report (BER), which documents:
- Biological effects/endpoints evaluated
- Risk acceptability
- Overall biological safety and regulatory compliance

Reasonably Foreseeable Misuse

Reasonably Foreseeable Misuse in Biocompatibility Planning

Considering Realistic Use Scenarios Under ISO 10993-1

ISO 10993-1 requires manufacturers to evaluate reasonably foreseeable misuse when determining biological safety requirements for a medical device. This concept recognizes that devices may not always be used exactly as intended, and biological risks must be evaluated for realistic use conditions that could occur in clinical practice.

In biocompatibility planning, this means considering whether variations in device use could change patient exposure, contact duration or affected tissues. These potential scenarios must be evaluated when defining the Biological Evaluation Plan (BEP) and selecting appropriate biological endpoints.

What Is Reasonably Foreseeable Misuse?
Reasonably foreseeable misuse refers to predictable patterns of device use that differ from the intended instructions but may still occur during real-world clinical use.

This concept is not meant to capture rare or purely hypothetical situations. Misuse scenarios must be supported by evidence, such as:

Post-market surveillance (PMS) data
Clinical literature
User feedback and complaint data
Risk management analysis under ISO 14971

The goal is to identify realistic use variations that could influence biological safety.

Examples:
Misuse scenarios may influence how a device interacts with the body and therefore may affect biocompatibility requirements.

Extended use duration
A device intended for short contact may occasionally remain in place longer than planned.
Different tissue contact
A device designed for one tissue type may inadvertently contact another biological surface.
Use in different patient populations
Devices may be used in patients with different physiological characteristics or sensitivities.
Repeated or intermittent use
Intermittent use over long periods can result in a cumulative exposure duration that falls into a different regulatory contact category.

When such conditions are reasonably foreseeable, they should be incorporated into the biological evaluation strategy.

Impact on Biological Evaluation Planning
Considering foreseeable misuse can affect several aspects of biological evaluation, including:

Device contact classification
Contact duration category
Selection of biological endpoints
Exposure assumptions used in toxicological risk assessment

In practice, these scenarios may lead to additional justification, alternative testing strategies or expanded risk evaluation within the BEP and Biological Evaluation Report (BER).

Evidence-Based Risk Assessment
Regulators expect misuse scenarios to be systematically evaluated and documented. The analysis should demonstrate how the manufacturer determined whether a misuse scenario could affect biological safety.

When properly addressed, this process strengthens the scientific justification of the biological evaluation and supports transparent regulatory review.

When to Engage a Biocompatibility Expert

Early: to reduce risk, cost and submission delays.

An ISO 10993 biocompatibility expert helps you avoid over-testing, delays and overspending.

Engaging an expert early in development helps you:

Select materials with established safety information
Identify biological risks before they affect testing
Define the finished device for ISO 10993 planning
Clarify which endpoints require testing and which can be supported with existing data
Streamline development of the biological evaluation plan (BEP) and support FDA and EU MDR submission strategy
Align engineering, regulatory and quality teams around a consistent device profile

Early planning reduces the likelihood of unexpected biological responses, supports predictable timelines and improves the efficiency of the overall evaluation.

Consult a Biocompatibility Expert

Tests for Biological Safety of Medical Devices

Our testing portfolio delivers the biocompatibility data and documentation required for global market approval.

Pre-market

Pre-Market Submission Support

Material Selection Validation - Confirm biological safety for 510(k), PMA, De Novo and EU MDR submissions
Toxicological Risk Assessment (TRA) - Biological safety evaluation using ISO 10993-17 and ICH guidelines
Material Performance Analysis - Test properties after aging, degradation and real-world use
Cleaning & Reprocessing Validation - ISO 17664 protocols recognized by regulators worldwide

Post-market

Post-Market Compliance & Monitoring

Ongoing Safety Monitoring - Product performance and safety assessment per global post-market surveillance requirements
Multi-Market Documentation - FDA, EU MDR and international filing requirements
Quality System Integration - Alignment with FDA QSR, ISO 13485 and global quality standards

Biological Assessment

In-Vitro Biological Safety Testing

Testing for Cytotoxic, Allergenic and Irritant Effects

We provide GLP-compliant testing that reduces the need for animal studies. Services include:

ISO 10993-5: Cytotoxicity testing
Cell culture assays for cytotoxic substances
ISO 10993-10, Annex C: Sensitization testing
In-chemico and in-vitro methods
- Direct Peptide Reactivity Assay (DPRA)
  In chemico testing for sensitization via covalent protein binding
- KeratinoSens™ (ARE-Nrf2 Luciferase Assay)
  In vitro testing for activation of epidermal keratinocytes
- IL-18 RhE Test
  In vitro testing for cytokine release in reconstructed human epidermis
- U-SENS™
  In vitro testing for activation of dendritic-like cells
ISO 10993-23: Irritation testing
Human 3D skin model for irritation potential
HET-CAM (DB-ALM Method No. 96): Skin irritation and mucosal damage testing
Validated alternative to animal irritation models
ISO 10993-12: Sample preparation
Standardized extraction and test protocols

Chemical Characterization

Chemical Characterization of Medical Device Materials

ISO 10993-18

Understanding which substances may be released from your device materials is essential for FDA, EU MDR and other global submissions. Our GLP-certified, ISO/IEC 17025–accredited lab performs extractables and leachables testing (E&L) with advanced analytical methods to support toxicological risk assessment and biological evaluation.

ISO 10993-18 Chemical Characterization Testing

Ageing & Storage

Ageing and Shelf Life in Biocompatibility

Device safety extends beyond initial testing. Materials can change over time due to storage, transport or sterilization, which may alter their biological response. As part of a biocompatibility strategy, ageing and shelf-life studies provide evidence that your device will continue to meet ISO 10993 requirements throughout its intended lifecycle.

Regulatory bodies expect biocompatibility to reflect the entire shelf life of a device
Chemical and physical changes may impact cytotoxicity, sensitization or irritation outcomes
Ageing studies support both risk assessment and regulatory submissions

Storage & Shelf Life

Respiratory Gas Pathways

Biocompatibility of Respiratory Gas Pathways

ISO 18562 Series

ISO 18562 provides a clear framework for evaluating the biological safety of breathing-gas pathways in respiratory and inhalation devices.

ISO 18562-1 describes how manufacturers classify gas pathways, review existing data and select the appropriate tests within a risk-management process.

Test Methods of Breathing Gas Pathways:

ISO 18562-2: Particle emissions
ISO 18562-3: Volatile organic compound (VOC) emissions
ISO 18562-4: Leachables in condensates

These methods align with ISO 18562-1 to support FDA, EU MDR and global respiratory-device submissions.

Factsheet - Biocompatibility Testing - Respiratory Gas Pathways (ISO 18562)pdf

Blog: ISO 18562 standard series – Biocompatibility evaluation of breathing gas pathways in healthcare applications

Find ISO 10993 Biocompatibility Test Requirements by Medical Device Type

GLP and ISO Certified Biocompatibility Lab

Hohenstein is ISO/IEC 17025 accredited and Good Laboratory Practice (GLP) certified for biological, chemical and physical testing. This ensures validated methods, reliable data and regulatory-accepted reports for FDA, EU MDR and other global submissions.

Biocompatibility Lab Accreditations