ISO 10993-12-2021 PDF

Full title and description

ISO 10993-12:2021 — Biological evaluation of medical devices — Part 12: Sample preparation and reference materials. This International Standard specifies requirements and gives guidance on procedures for preparing test samples and selecting reference materials used in biological evaluation of medical devices (sample selection, representative portions, sample preparation, experimental controls and extract preparation).

Abstract

Provides requirements and guidance for preparing medical device samples and reference materials for biological testing in the ISO 10993 family. Topics include selection of test samples and representative portions, preparation of extracts, use of experimental controls and characteristics and selection of reference materials. The document is intended to support biological tests described in other parts of ISO 10993 and is not applicable to live cells (though it can be relevant to components of combination products that contain live cells).

General information

• Status: Published.
• Publication date: January 2021 (ISO edition 5, 2021-01).
• Publisher: International Organization for Standardization (ISO).
• ICS / categories: 11.100.20 — Biological evaluation of medical devices.
• Edition / version: Edition 5 (2021).
• Number of pages: 21 pages (official ISO edition).

(Core bibliographic and edition details above are drawn from the ISO catalogue entry for ISO 10993-12:2021.)

Scope

Specifies requirements and gives guidance on procedures for preparing samples of medical devices for biological testing within the ISO 10993 series. Includes selection of test materials, selection of representative portions from devices, test sample preparation, selection and requirements for reference materials (used as experimental controls or comparators), and preparation of extracts. The standard clarifies applicability to device components, and notes that extraction for chemical characterization is principally covered by ISO 10993-18.

Key topics and requirements

• Test sample selection: preference for testing the final product where practical; otherwise representative portions or representative specimens preconditioned by the same processing as the final product.
• Selection of representative portions: proportional representation of each material in multi-material devices; consideration of surfaces exposed by cutting or lumen exposure.
• Test sample preparation: cleanliness, avoidance of contamination, consideration of residues from manufacturing/cleaning/sterilization and effect of sterilization/re-sterilization on samples.
• Experimental controls and reference materials: use of well-characterized positive and negative controls, requirements for reference materials (homogeneity, stability, documentation) and recommendation for long‑term availability/traceability of RMs/CRMs.
• Preparation of extracts: defined extraction procedures and conditions to support biological assays; cross-reference to ISO 10993-18 for chemical characterization where applicable.

(Summarized from clauses and informative annexes describing experimental controls, RM characteristics, sample preparation and extraction principles.)

Typical use and users

Used by medical device manufacturers, biocompatibility and analytical testing laboratories, regulatory affairs professionals, notified bodies and conformity assessment organizations. Typical applications include establishing appropriate sample selection and extraction methods for cytotoxicity, sensitization, irritation and other biological tests; validating test systems using reference materials; and documenting sample preparation and control practices for regulatory submissions and internal quality systems.

Related standards

Part of the ISO 10993 series (biological evaluation of medical devices). Most closely related to ISO 10993-1 (evaluation and testing within a risk management process), ISO 10993-18 (chemical characterization and extraction for chemical analysis) and ISO/TS 10993-19 (physico-chemical, morphological and topographical characterization). Users should consult the other parts of the 10993 family for test‑specific procedures and requirements.

Keywords

Sample preparation, reference material, extract preparation, biological evaluation, biocompatibility, experimental controls, medical device testing, ISO 10993.

FAQ

Q: What is this standard?

A: ISO 10993-12:2021 is Part 12 of the ISO 10993 series and provides requirements and guidance for preparing device samples and selecting reference materials used in biological (biocompatibility) testing of medical devices.

Q: What does it cover?

A: It covers test sample selection, how to choose representative portions from devices, test sample handling and preparation, characteristics and use of reference materials and preparation of extracts for biological assays. It complements other parts of ISO 10993 and points to ISO 10993-18 for chemical characterization of extracts.

Q: Who typically uses it?

A: Medical device manufacturers, test laboratories, regulatory professionals and conformity assessment bodies use it when planning and documenting biocompatibility testing and when selecting/using reference materials as controls.

Q: Is it current or superseded?

A: The 2021 edition (Edition 5) is the current base publication. An Amendment (ISO 10993-12:2021/Amd 1:2025) was published in August 2025 to clarify and align certain references and wording; users should apply the 2021 edition together with any applicable amendment(s) (e.g., the 2025 amendment) where required. Use absolute dates in documentation (ISO 10993‑12:2021; amendment published 13 Aug 2025).

Q: Is it part of a series?

A: Yes — it is Part 12 of the ISO 10993 family (biological evaluation of medical devices); it is intended to be used alongside other parts of ISO 10993 that specify particular biological tests and evaluation strategies.

Q: What are the key keywords?

A: Sample preparation; reference materials; extract preparation; experimental controls; biocompatibility testing; medical devices; ISO 10993.