ISO 10993-5 — Standard

About the Standard

Scope title: in vitro cytotoxicity

ISO 10993-5 is a standard published by International Organization for Standardization (ISO). The international standards organisation; it publishes the widest body of management system, test method and product standards.

See the other 310 codes from ISO

Coverage areas

What Is ISO 10993-5?

ISO 10993-5 assesses the toxic effect of medical device materials on cell cultures. It is the first step of the biological evaluation series and in practice serves as a SCREENING function: a material found toxic at cell level is reconsidered before being taken forward to further animal testing.

The test is carried out by bringing the device itself or an extract of it into contact with a cell culture. Changes in cell viability, proliferation and morphology are measured. The standard defines several methods: the extract method, the direct contact method and indirect contact methods (agar diffusion, filter diffusion). The choice is made according to the geometry of the device and the use scenario.

THE EXTRACTION CONDITIONS directly determine the result, and this is the most critical parameter of the test. In which solvent, at what temperature, for how long and at what surface-to-volume ratio the extraction is carried out changes the result. The conditions are chosen to represent the device's real use scenario and are justified; an arbitrary choice of conditions makes the result impossible to interpret.

Its place within the series as a whole matters. ISO 10993-1 provides the evaluation framework determining which biological endpoints are required for which device; -5 addresses cytotoxicity, -10 irritation and skin sensitisation, -11 systemic toxicity, -4 interaction with blood, -6 local effects after implantation and -3 genotoxicity. Which parts are required is determined by the type and duration of the device's contact with the body.

The output of the assessment is not ON ITS OWN a conformity decision. The result is interpreted within the biological evaluation plan run under ISO 10993-1 and within the risk management file. A material with a negative cytotoxicity result cannot be declared biocompatible if the other required endpoints have not been assessed.

Why Does This Standard Exist?

The history of biocompatibility assessment was shaped by the increasing duration and closeness of medical devices' contact with the body. A surgical instrument contacts for minutes; a heart valve stays for life. The same material may be unproblematic in one and unacceptable in the other.

The ISO 10993 series therefore establishes not a list of tests but a DECISION TREE. The type of contact (skin, mucous membrane, breached surface, blood, tissue, bone) and the duration of contact (limited, prolonged, permanent) are determined; these two axes determine the required endpoints.

The reason cytotoxicity is the first step is its sensitivity. Cell culture responds more sensitively to toxic substances than animal models and the result comes within days. If a material shows marked toxicity here, there is no point in spending resources on further testing.

The philosophy of the series has changed in recent years and that change matters: REDUCING animal testing is now an explicit aim of the standard. Using existing data, chemical characterisation (ISO 10993-18) and toxicological risk assessment (ISO 10993-17), many endpoints can be closed without animal testing. This approach delivers both an ethical and an economic gain.

The rise of chemical characterisation changed the approach fundamentally. If the substances that could be released from the material (extractables and leachables) are identified and assessed toxicologically, the need for biological testing falls markedly. Modern files prefer that route.

Which Products Require It

All medical device materials that contact the body
Implants and surgical instruments
Catheters, tubing and infusion sets
Wound dressings and skin contact products
Dental materials and orthopaedic components
Packaging materials (where they contact the device)

Related Legislation and Schemes

It is used in the biological safety part of the general safety and performance requirements under MDR (EU) 2017/745
It is carried out together with the ISO 10993-1 evaluation framework and ISO 14971 risk management
In the United States the FDA accepts the ISO 10993 series through its own guidance document
Chemical characterisation runs through ISO 10993-18 and toxicological risk assessment through ISO 10993-17
On the quality system side, ISO 13485 applies

How the Assessment Runs

1The evaluation planThe type and duration of contact are determined under ISO 10993-1; the required endpoints and the justification for those not required are written down.
2Sample and extractionThe final form of the device (sterilised, packaged) is used; the extraction solvent, temperature, duration and ratio are justified.
3Method selectionThe extract, direct contact or indirect contact method is chosen according to the geometry of the device.
4The cell culture testContact is established with a defined cell line; viability, proliferation and morphology are assessed.
5InterpretationThe result is interpreted within the biological evaluation plan and the risk management file; further endpoints are addressed where required.

Neighbouring Standards and the Differences

ISO 10993-1
The evaluation framework. It determines which endpoints are required; -5 is not sufficient on its own.
ISO 10993-10
Irritation and skin sensitisation. An endpoint frequently required for devices contacting skin and mucous membranes.
ISO 10993-18
Chemical characterisation. In modern files, the route that reduces the need for biological testing.
ISO 10993-17
Toxicological risk assessment; the method for drawing a safety conclusion from chemical data.

What the Report Must Contain

To be usable, a report must carry the information below. An incomplete report may not be accepted in the supply chain or in an inspection even when its result is correct.

Sample description: material, final form, method of sterilisation
Extraction conditions: solvent, temperature, duration, surface-to-volume ratio and their justification
The method applied: extract, direct or indirect contact
The cell line used and the positive/negative controls
Cell viability results and morphological observations
Reference to the biological evaluation plan

Commonly Confused Points

Cytotoxicity alone is not evidence of biocompatibility; the required set of endpoints is determined and justified according to ISO 10993-1.
Extraction conditions directly affect the result; the conditions must be justified against the device's use scenario.
A change of material (supplier, colour pigment, sterilisation method) may require the assessment to be repeated.
The test is carried out on the FINAL FORM of the device; a result from a sample taken before sterilisation is not valid.
A raw material supplier's biocompatibility declaration is not sufficient for your device; processing and sterilisation change the material.
A negative cytotoxicity result does not remove the need for chemical characterisation.

Structure of the Code

Published by: ISO
Serial number: 10993
Part: 5

The last "5" is the section number of the standard. Chapters organize different coverages of the same series; The requirements of whichever section is written in the specification are applied.

Codes in the library without release year is kept. The current version changes over time; If the year is specified in your specification, that version is taken as basis, if not specified, the most current version is applied.

Scope

Test
Medical Device Testing
Medical Device Testing

Related Tests and Services

Of the 2 pieces of content this code is referenced in, the 1 with their own published page are listed below.

Test · 1

Sitotoksisite – ISO 10993-5

Technical Requirements

Standard texts are copyright of the relevant organization; test condition, sample and acceptance criteria cannot be fitted here.

Basis: The part structure of the ISO 10993 series and the method options of ISO 10993-5 (extract, direct and indirect contact); the ISO 10993-1 evaluation framework and the ISO 10993-17 and -18 references; the relationships with the MDR and ISO 14971.

Technical requirements specific to your product, once we clarify the scope At offer stage shared in writing.

Relevant Product Groups and Legislation

This code is included in the standard tag of the product pages below.

medical device

These product pages carry notes for the following markets: European Union, United Kingdom, USA. Whether the standard is mandatory in the relevant market varies depending on the product group and the applicable legislation.

Regulations published with this code on the same product pages:

(EU) 2017/745MDRThe Medical Device Regulation. Classification (I, IIa, IIb, III), clinical evaluation, technical documentation and post-market surveillance obligations; the notified body's role grows as the class rises.
(EU) 2017/746IVDRThe In Vitro Diagnostic Medical Devices Regulation. In vitro diagnostic devices fall under this regulation instead of the MDR.
(AB) 2017/745 art. 33EUDAMEDThe European medical device database. From 28 May 2026, the actor registration, UDI/device, certificate and market surveillance modules are mandatory; placing on the market is not possible without a valid SRN.
2006/42/ATMachinery Directive (overlap)Relevant essential requirements also apply to medical devices that also qualify as machinery.
2011/65/EURoHSRestriction of hazardous substances in electrical and electronic equipment.
(EC) 1907/2006REACHRegistration, evaluation, authorisation and restriction of chemicals; SVHC notification.

Other Parts of the Same Series

ISO 10993 series is also present in the library with the following parts.

Related Standards

Frequently Asked Questions About ISO 10993-5

Cytotoxicity came back negative — can we say it is biocompatible?

You cannot. The required set of endpoints is determined by the plan under ISO 10993-1; cytotoxicity is only the first step.

Is our raw material supplier's report sufficient?

Usually not. The test is carried out on the final form of the device; processing, moulding and sterilisation change the material's release profile.

Do we have to carry out animal testing?

Not necessarily. Many endpoints can be closed through chemical characterisation and toxicological risk assessment; reducing animal testing is an explicit aim of the series.

We changed the colour pigment — is a repeat required?

A change of pigment can change the release profile; at a minimum the effect must be assessed through chemical characterisation.

Frequently Asked Questions

Is this standard mandatory for my product?

Whether it is mandatory depends on the product group, the target market and the applicable legislation. Once you tell us your product and market, we clarify in writing whether this standard is required.

How long does the test process take?

Duration depends on the scope of the standard, the number of specimens and current capacity. The exact duration is shared, together with the specimen and scope details, at the quote stage.

Do you issue certification against this standard?

Which activity is carried out under which accreditation scope is separately confirmed at the application stage. Up-to-date scope information is published on our corporate page.

What happens if the standard I need is not here?

The library is based on a continuously growing inventory. If you cannot find the code you are looking for, you can send it through the quote form; we will assess the relevant scope and get back to you.