Implantation Test — ISO 10993-6

What Is Implantation?

The implantation test evaluates the local biological response the material produces in surrounding tissue after being placed in living tissue. Inflammation, fibrous-capsule formation, necrosis and the material's degradation behaviour are determined by histological examination.

Purpose of Implantation

The purpose is to show that the implanted material does not produce an unacceptable reaction in surrounding tissue and establishes a tissue-compatible interface.

Which Products Is Implantation Applied To?

Orthopaedic implants
Dental implants
Cardiovascular implants and stents
Absorbable suture and screw materials
Tissue-support and patch materials

In Which Sectors Is Implantation Used?

Medical DeviceHealthcarePharmaceuticals

Standards Related to Implantation

ISO 10993-6Local effects after implantation test
ISO 10993-1
ISO 10993-11sistemik toksisite test
ISO 11607end product sterile barrier packaging test

Implantation Conditions

Implantation site: Muscle, bone or subcutaneous; chosen according to the device's clinical site of use
Time: Short- and long-term assessment; if the material degrades, planned according to the degradation time
Control: A reference material with a known biological response is implanted in parallel

Equipment for Implantation

Surgical infrastructure and animal-care facility
Histology laboratory (sectioning, staining)
Light microscope and image analysis system
Radiological imaging (for bone applications)

Sample Requirements for Implantation

The specimen must represent the final, sterilised product
Not raw material — the product that has gone through all manufacturing and sterilisation processes is submitted
The specimen quantity is determined according to the surface-area/extraction ratio prescribed by the standard
The device's type and duration of body contact must be stated
The sterilisation method and, if applicable, residue information must be shared
Implant geometry must be prepared to the dimensions prescribed by the standard
It must be of a size that can be matched with the reference control material

Duration of Implantation

The assessment period extends from weeks to months depending on the material; for absorbable materials it is monitored until degradation is complete.

Implantation Procedure

1The implantation site and durations are planned according to the device's use.
2The specimen and reference control material are prepared and sterilised.
3They are surgically implanted.
4Specimens are retrieved together with surrounding tissue at the planned times.
5Histological sections are prepared and stained.
6Inflammation, capsule thickness, necrosis and degeneration are scored.
7Assessment is made by comparison with the reference material.

Implantation Acceptance Criteria

The acceptance criterion is that the test material's tissue response is not significantly more severe than that of the reference control material. The scoring system and assessment approach are defined in ISO 10993-6.

Evaluation of Results

Assessment is made comparatively against the reference material, not on an absolute score. For absorbable materials, the degradation rate and the change in tissue response over time are interpreted together.

Implantation Report

Applied standard and revision
Specimen description, batch number and sterilisation method
Extraction conditions (solvent, temperature, duration, ratio)
Positive and negative control results
Test results and grading
Assessment and conclusion
Implantation site and durations
Histological scoring tables and micrographs

Accreditation

EUROLAB holds internationally recognised accreditation obtained from accreditation bodies party to the IAF and ILAC multilateral recognition arrangements, under ISO/IEC 17025 for laboratory testing, ISO/IEC 17020 for inspection and surveillance, and ISO/IEC 17021-1 and ISO/IEC 17065 for system and product certification. This chain ensures the reports and certificates issued are accepted worldwide.

Whether this test can be offered within accredited scope depends on your product and the standard applied; since accreditation is method-based, the scope is confirmed in writing at the quotation stage.

Scope and authorisations

Related Regulations

MDR (EU) 2017/745
Ethical and legal regulations on animal testing

Medikal Cihaz Testleri — What Does This Testing Field Cover?

The section below describes the field that the Implantation test belongs to; the conditions and acceptance criteria of this particular test are given in the sections above. The scope specific to your product is confirmed in writing at the quotation stage.

Medical device testing shows that a device is safe for the patient and the user and maintains its intended performance. In this family safety is not only about avoiding harm; a device failing to perform its expected function is also treated as a risk. A monitor missing an alarm or a pump delivering the wrong dose is directly a patient safety event.

At the centre of the field is RISK MANAGEMENT, and this is what sets medical apart from other sectors. The risk management process run under ISO 14971 also determines which tests are required. The test list is not copied from a table of standards; it is derived and justified from the device's intended use, the nature and duration of patient contact, the use environment and foreseeable misuse.

Assessment consists of several separate bodies of work, each with its own set of standards. Biocompatibility runs through the ISO 10993 series, electrical device safety through the IEC 60601 series, sterilisation through ISO 11135/11137/17665, packaging through ISO 11607, software through IEC 62304 and usability through IEC 62366. The quality system (ISO 13485) is the framework that binds these together.

Which tests are required is determined by the device's CLASS and its MODE OF CONTACT WITH THE BODY. A product in brief contact with skin and an implant entering the bloodstream do not go through the same test set; the scope is set by a biological evaluation plan prepared under ISO 10993-1. That plan justifies in writing which endpoints are required and why the others are not.

Packaging and sterilisation are taken as seriously as the device itself in this field. For a sterile device the packaging is not a transport container but the barrier that maintains sterility; if the barrier is breached, the device is no longer sterile. Packaging processes are therefore validated and shelf life is supported by real-time ageing data.

For devices containing software, assessment shifts from testing towards PROCESS assurance. IEC 62304 defines which development and verification steps must be followed according to the safety class of the software; the evidence is the traceability of the development process. Testing software does not make it safe — the process record does.

The clinical side is a separate column of the technical file. Test reports show that the device is technically safe; clinical evaluation establishes that the device delivers the intended clinical benefit and that the benefit-risk balance is acceptable. Neither replaces the other.

Method groups in this field

Biocompatibility
Cytotoxicity, irritation, skin sensitisation, systemic toxicity, haemocompatibility, genotoxicity and local effects after implantation. The required endpoints are set by the ISO 10993-1 plan.
Electrical device safety
IEC 60601-1 basic safety and essential performance; EMC, alarm, usability and environmental requirements through the collateral standards.
Sterilisation validation
Validation of sterilisation processes by ethylene oxide, radiation or moist heat; bioburden and sterility assurance level studies.
Packaging
Integrity of the sterile barrier system, seal strength, distribution simulation and shelf-life studies.
Microbiological tests
Bioburden determination, sterility testing, bacterial endotoxin and, where required, carrier validation studies.
Software and usability
IEC 62304 life cycle evidence and use-error focused evaluation under IEC 62366.

Commonly confused in this field

Cytotoxicity alone is not evidence of biocompatibility; the required set of endpoints is determined and justified according to ISO 10993-1.
An ISO 13485 certificate does not confer CE marking; classification under the MDR, the technical file and the notified body process run separately.
Accelerated ageing does not replace real-time ageing; a shelf life claim is supported by real-time data.
A change of material (supplier, pigment, sterilisation method) may require the biological evaluation to be repeated; it is not a silent change.
An assessment made without the collateral and particular standards for IEC 60601-1 is incomplete; which -1-x and -2-x standards were applied must appear in the report.
In vitro diagnostic devices fall under the IVDR rather than the MDR, and laboratory equipment is often on the IEC 61010-1 side.

Which decisions these results support

MDR/IVDR technical file and notified body assessment
Completing the biological evaluation plan
Sterilisation and packaging validation
Determining shelf life and storage conditions
Determining the scope of reassessment after a design change

Related Tests

Frequently Asked Questions About Implantation

Why is a reference control material needed?

The surgical procedure itself also produces a tissue response. The reference material allows this surgical response to be separated from the material's own effect; assessment is comparative, not absolute.