EN ISO 10993-12:2021/A1:2025

Biological evaluation of medical devices - Part 12: Sample preparation and reference materials - Amendment 1 (ISO 10993 12:2021/Amd 1:2025)

Biologische Beurteilung von Medizinprodukten - Teil 12: Probenvorbereitung und Referenzmaterialien - Änderung 1 (ISO 10993 12:2021/Amd 1:2025)

Évaluation biologique des dispositifs médicaux - Partie 12: Préparation des échantillons et matériaux de référence - Amendement 1 (ISO 10993 12:2021/Amd 1:2025)

Biološko ovrednotenje medicinskih pripomočkov - 12. del: Priprava vzorcev in referenčni materiali - Dopolnilo A1 (ISO 10993 12:2021/Amd 1:2025)

General Information

• Status: Published
• Publication Date: 23-Sep-2025
• ICS: 11.100.20 - Biological evaluation of medical devices
• Technical Committee: CEN/TC 206 - Biocompatibility of medical and dental materials and devices
• Current Stage: 6060 - Definitive text made available (DAV) - Publishing
• Start Date: 24-Sep-2025
• Completion Date: 24-Sep-2025
• Directive: Harmonized Standard2017/745 - Regulation (EU) 2017/745 of the European Parliament and of the Council of 5 April 2017 on medical devices, amending Directive 2001/83/EC, Regulation (EC) No 178/2002 and Regulation (EC) No 1223/2009 and repealing Council Directives 90/385/EEC and 93/42/EEC
• Mandate: M/575 - Medical devices in support of Regulation (EU) 2017/745 and in vitro diagnostic medical devices in support of Regulation (EU) 2017/746
• Mandate: M/575 AMD 2 - Medical devices in support of Regulation (EU) 2017/745 and in vitro diagnostic medicial devices in support of Regulation (EU) 2017746
• Ref Project: SIST EN ISO 10993-12:2021/A1:2025 - Biological evaluation of medical devices - Part 12: Sample preparation and reference materials - Amendment 1 (ISO 10993 12:2021/Amd 1:2025)

Relations

• Referred By: EN 60601-1:2006/A2:2021 - Medical electrical equipment - Part 1: General requirements for basic safety and essential performance
• Effective Date: 09-Feb-2026
• Referred By: CEN/TS 15277:2006 - Non-active surgical implants - Injectable implants
• Effective Date: 28-Jan-2026
• Referred By: EN 455-3:2006 - Medical gloves for single use - Part 3: Requirements and testing for biological evaluation
• Effective Date: 28-Jan-2026
• Consolidated By: ISO 10993-12:2021/Amd 1:2025 - Biological evaluation of medical devices — Part 12: Sample preparation and reference materials — Amendment 1
• Effective Date: 12-Feb-2026
• Amends: EN ISO 10993-12:2021 - Biological evaluation of medical devices - Part 12: Sample preparation and reference materials (ISO 10993-12:2021)
• Effective Date: 15-Nov-2023

Overview

EN ISO 10993-12:2021/A1:2025 is an amendment to the established European Standard for the biological evaluation of medical devices, specifically focusing on sample preparation and reference materials. Published by the European Committee for Standardization (CEN), this amendment aligns with the requirements of Regulation (EU) 2017/745 for medical devices. The updated standard clarifies terminology, references, and procedures to ensure consistency and compliance within biological testing frameworks across Europe.

This standard is integral for manufacturers, testing laboratories, and regulatory stakeholders engaged in risk management and biocompatibility evaluation of medical devices. It supports the demonstration of conformity with key safety and performance requirements through standardized sample preparation and referencing of materials during testing.

Key Topics

• Sample Preparation for Biological Evaluation
  EN ISO 10993-12 provides detailed protocols for preparing samples of medical devices before testing to ensure reproducibility and reliability. The amendment introduces specific guidance for devices containing absorbent materials, impacting extraction volumes and ratios.

• Reference Materials
  The standard defines requirements and considerations for selecting and using reference materials during biological evaluations, essential for comparability across laboratories.

• Relation to Risk Management Standards
  References and aligns with key ISO standards, such as ISO 14971 (risk management) and ISO 10993 series, ensuring that biological evaluations are integrated with comprehensive risk management practices.

• Harmonization with EU Regulation
  EN ISO 10993-12:2021/A1:2025 serves as a voluntary means to demonstrate conformity with the General Safety and Performance Requirements of Regulation (EU) 2017/745, supporting regulatory submissions and CE marking for medical devices.

• Clarified Testing Definitions and References
  The amendment updates references to ISO 10993-1, ISO 10993-18, and ISO/TS 10993-19 and ensures the terminology aligns with current regulatory frameworks.

Applications

• Medical Device Manufacturers
  Ensures consistent and validated methods for preparing device samples for biocompatibility testing, supporting product development and regulatory compliance.

• Testing Laboratories
  Provides standardized extraction ratios and methodology, especially for devices with absorbent materials, ensuring robust and repeatable results.

• Regulatory Affairs and Quality Assurance
  Assists regulatory teams in preparing documentation to demonstrate conformity with EU medical device regulations, specifically for biocompatibility and risk management.

• Research and Development
  Facilitates the development of medical devices by providing clear guidelines for material and sample preparation, impacting product safety and efficacy.

Related Standards

The amendment references several key standards in the biological evaluation and risk management of medical devices:

• ISO 10993-1: Biological evaluation of medical devices - Part 1: Evaluation and testing within a risk management process
• ISO 10993-18: Biological evaluation of medical devices - Part 18: Chemical characterization of medical device materials
• ISO/TS 10993-19: Biological evaluation of medical devices - Part 19: Physico-chemical, morphological, and topographical characterization of materials
• ISO 14971: Application of risk management to medical devices

These referenced standards provide the framework and additional requirements for comprehensive biological evaluations and material characterization.

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Keywords: EN ISO 10993-12, Amendment 1, sample preparation, reference materials, biological evaluation, biocompatibility, medical devices, EU Regulation 2017/745, risk management, CEN standard, ISO 10993 series, extraction ratio, harmonized standards, regulatory compliance.

Standards Content (Sample)

SLOVENSKI STANDARD
01-december-2025
Biološko ovrednotenje medicinskih pripomočkov - 12. del: Priprava vzorcev in
referenčni materiali - Dopolnilo A1 (ISO 10993 12:2021/Amd 1:2025)
Biological evaluation of medical devices - Part 12: Sample preparation and reference
materials - Amendment 1 (ISO 10993 12:2021/Amd 1:2025)
Biologische Beurteilung von Medizinprodukten - Teil 12: Probenvorbereitung und
Referenzmaterialien - ÄNDERUNG 1 (ISO 10993 12:2021/Amd 1:2025)
Évaluation biologique des dispositifs médicaux - Partie 12: Préparation des échantillons
et matériaux de référence - Amendement 1 (ISO 10993 12:2021/Amd 1:2025)
Ta slovenski standard je istoveten z: EN ISO 10993-12:2021/A1:2025
ICS:
11.100.20 Biološko ovrednotenje Biological evaluation of
medicinskih pripomočkov medical devices
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.

EN ISO 10993-
EUROPEAN STANDARD
12:2021/A1
NORME EUROPÉENNE
EUROPÄISCHE NORM
September 2025
ICS 11.100.20
English Version
Biological evaluation of medical devices - Part 12: Sample
preparation and reference materials - Amendment 1 (ISO
10993 12:2021/Amd 1:2025)
Évaluation biologique des dispositifs médicaux - Partie Biologische Beurteilung von Medizinprodukten - Teil
12: Préparation des échantillons et matériaux de 12: Probenvorbereitung und Referenzmaterialien -
référence - Amendement 1 (ISO 10993 12:2021/Amd Änderung 1 (ISO 10993 12:2021/Amd 1:2025)
1:2025)
This amendment A1 modifies the European Standard EN ISO 10993-12:2021; it was approved by CEN on 24 August 2025.

CEN members are bound to comply with the CEN/CENELEC Internal Regulations which stipulate the conditions for inclusion of
this amendment into the relevant national standard without any alteration. Up-to-date lists and bibliographical references
concerning such national standards may be obtained on application to the CEN-CENELEC Management Centre or to any CEN
member.
This amendment exists in three official versions (English, French, German). A version in any other language made by translation
under the responsibility of a CEN member into its own language and notified to the CEN-CENELEC Management Centre has the
same status as the official versions.

CEN members are the national standards bodies of Austria, Belgium, Bulgaria, Croatia, Cyprus, Czech Republic, Denmark, Estonia,
Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway,
Poland, Portugal, Republic of North Macedonia, Romania, Serbia, Slovakia, Slovenia, Spain, Sweden, Switzerland, Türkiye and
United Kingdom.
EUROPEAN COMMITTEE FOR STANDARDIZATION
COMITÉ EUROPÉEN DE NORMALISATION

EUROPÄISCHES KOMITEE FÜR NORMUNG

CEN-CENELEC Management Centre: Rue de la Science 23, B-1040 Brussels
© 2025 CEN All rights of exploitation in any form and by any means reserved Ref. No. EN ISO 10993-12:2021/A1:2025 E
worldwide for CEN national Members.

Contents Page
European foreword . 3
Annex ZA (informative) Relationship between this European Standard the General Safety
and Performance Requirements of Regulation (EU) 2017/745 aimed to be covered . 4

European foreword
This document (EN ISO 10993-12:2021/A1:2025) has been prepared by Technical Committee ISO/TC
194 "Biological and clinical evaluation of medical devices" in collaboration with Technical Committee
CEN/TC 206 “Biological and clinical evaluation of medical devices” the secretariat of which is held by
DIN.
This Amendment to the European Standard EN ISO 10993-12:2021 shall be given the status of a
national standard, either by publication of an identical text or by endorsement, at the latest by March
2026, and conflicting national standards shall be withdrawn at the latest by March 2026.
Attention is drawn to the possibility that some of the elements of this document may be the subject of
patent rights. CEN shall not be held responsible for identifying any or all such patent rights.
This document has been prepared under a standardization request addressed to CEN by the European
Commission. The Standing Committee of the EFTA States subsequently approves these requests for its
Member States.
For the relationship with EU Legislation, see informative Annex ZA, which is an integral part of this
document.
Any feedback and questions on this document should be directed to the users’ national standards
body/national committee. A complete listing of these bodies can be found on the CEN website.
According to the CEN-CENELEC Internal Regulations, the national standards organizations of the
following countries are bound to implement this European Standard: Austria, Belgium, Bulgaria,
Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland,
Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Republic of
North Macedonia, Romania, Serbia, Slovakia, Slovenia, Spain, Sweden, Switzerland, Türkiye and the
United Kingdom.
Endorsement notice
The text of ISO 10993-12:2021/Amd 1:2025 has been approved by CEN as EN ISO 10993-
12:2021/A1:2025 without any modification.

Annex ZA
(informative)
Relationship between this European Standard the General Safety and
Performance Requirements of Regulation (EU) 2017/745 aimed to be
covered
This European standard has been prepared under M/575 to provide one voluntary means of
conforming to the General Safety and Performance Requirements of Regulation (EU) 2017/745 of 5
April 2017 concerning medical devices [OJ L 117] and to system or process requirements including
those relating to quality management systems, risk management, post-market surveillance systems,
clinical investigations, clinical evaluation or post-market clinical follow-up.
Once this standard is cited in the Official Journal of the European Union under that Regulation,
compliance with the normative clauses of this standard given in Table ZA.1 and application of the
edition of the normatively referenced standards as given in Table ZA.2 confers, within the limits of the
scope of this standard, a presumption of conformity with the corresponding General Safety and
Performance Requirements of that Regulation, and associated EFTA Regulations.
Where a definition in this harmonised standard differs from a definition of the same term set out in
Regulation (EU) 2017/745, the differences shall be indicated in the Annex Z. For the purpose of using
this standard in support of the requirements set out in Regulation (EU) 2017/745, the definitions set
out in this Regulation prevail.
Where the European standard is an adoption of an International Standard, the scope of this document
can differ from the scope of the European Regulation that it supports. As the scope of the applicable
regulatory requirements differ from nation to nation and region to region the standard can only
support European regulatory requirements to the extent of the scope of the European Regulation for
medical devices ((EU) 2017/745).
NOTE 1 Where a reference from a clause of this standard to the risk management process is made, the risk
management process needs to be in compliance with Regulation (EU) 2017/745. This means that risks have to be
‘reduced as far as possible’, ‘reduced to the lowest possible level’, ‘reduced as far as possible and appropriate’,
‘removed or reduced as far as possible’, ‘eliminated or reduced as far as possible’, ’removed or minimized as far as
possible’, or ‘minimized’, according to the wording of the corresponding General Safety and Performance
Requirement.
NOTE 2 The manufacturer’s policy for determining acceptable risk must be in compliance with General Safety
and Performance Requirements 1, 2, 3, 4, 5, 8, 9, 10, 11, 14, 16, 17, 18, 19, 20, 21 and 22 of the Regulation.
NOTE 3 When a General Safety and Performance Requirement does not appear in Table ZA.1, it means that it is
not addressed by this European Standard.
Table ZA.1 — Correspondence between this European Standard and Annex I
of Regulation (EU) 2017/745 [OJ L 117] and to system or process requirements including those
relating to quality management systems, risk management, post-market surveillance systems, clinical
investigations, clinical evaluation or post-market clinical follow-up
General Safety and Performance Clause(s)/subclause(s) of Remarks/Notes
Requirements of Regulation this EN
(EU) 2017/745
10.1 is only partly covered by this
document, since the document does
not provide requirements on
design and manufacture, nor does
it provide methods to fulfil
characteristics and performance
requirements.
However, this document provides a
means of preparing samples, and
when used in conjunction with
other relevant parts from the EN
ISO 10993 series it can provide
information on “toxicity”, on
10.1 (a), (b) first half sentence
“compatibility with tissues, cells
4, 5, 6, 7, 8, 9, 10 and 11
and (d)
and body fluids” as well as on the
“impact of processes on material
properties”.
Flammability is not covered.
For 10.1 (b), ADME (Absorption,
Distribution, Metabolism and
Excretion) are not covered.
For 10.1 (d), impact of processes on
material properties is covered as
far as they could affect the
biocompatibility, while general
impact on mechanical stability is
not covered.
General Safety and Performance Clause(s)/subclause(s) of Remarks/Notes
Requirements of Regulation this EN
(EU) 2017/745
10.2 is only partly covered by this
document, since the document does
not provide requirements on
design and manufacture and does
not oblige to minimize risk.
However, this document provides a
means of preparing samples to
assess conformi
...