ISO 10993-12-2021 amd1-2025 PDF

Full title and description

ISO 10993-12:2021/Amd 1:2025 — Biological evaluation of medical devices — Part 12: Sample preparation and reference materials — Amendment 1. This amendment updates and clarifies requirements and guidance for selection and preparation of test samples and reference materials used in biological evaluations of medical devices, and applies as an addition to ISO 10993-12:2021.

Abstract

ISO 10993-12 provides requirements and guidance for selecting representative portions of a medical device, preparing test samples and extracts, selecting and using reference materials and experimental controls, and documenting sample handling for biological testing performed under the ISO 10993 series. Amendment 1 (2025) supplies additional clarifications and minor technical/editorial updates to the 2021 edition to improve consistency with other parts of the ISO 10993 series and to address issues identified by users and technical committees. The amendment is short (2 pages) and intended to be read alongside ISO 10993-12:2021.

General information

• Status: Published
• Publication date: August 2025 (ISO publication listing: 2025-08)
• Publisher: International Organization for Standardization (ISO)
• ICS / categories: 11.100.20 — Biological evaluation of medical devices
• Edition / version: Edition 5 (ISO 10993-12:2021) with Amendment 1 (2025)
• Number of pages: Amendment: 2 pages (base document ISO 10993-12:2021 — 21 pages)

Scope

This part of ISO 10993 specifies requirements and gives guidance on procedures for selecting test samples and representative portions of medical devices, preparing samples and extracts, choosing and using experimental controls and reference materials for biological testing, and documenting handling and traceability. It is intended for use with one or more parts of the ISO 10993 series. The document does not apply to live cells (but may be relevant to combination products containing cellular components). Extractions for chemical characterization are addressed primarily in ISO 10993-18; several clauses of ISO 10993-12 can also be applied to chemical-characterization extractions where noted. Amendment 1 provides clarifications and corrections to the 2021 text; users should consult the amendment alongside the 2021 edition to determine the exact changes.

Key topics and requirements

• Selection of test samples and representative device portions that reflect clinical use and worst‑case material exposures.
• Preparation procedures for solid samples, finished devices, and extracted test articles (including extraction media, conditions, and ratio of sample mass to extraction volume where applicable).
• Requirements and recommendations for selection, characterization and use of reference materials and experimental controls.
• Documentation, labelling and traceability of samples, extracts and reference materials throughout testing workflows.
• Consideration of sterilization, aging, processing residues and manufacturing variability when preparing test samples.
• Interface and consistency with ISO 10993-1 (biological evaluation strategy), ISO 10993-11 (toxicity testing) and ISO 10993-18 (chemical characterization).
• Guidance on when sample preparation clauses may (or may not) apply to combination products or special test systems.

Typical use and users

ISO 10993-12 and its 2025 amendment are used by medical device manufacturers, biocompatibility and toxicology scientists, contract testing laboratories, regulatory and quality professionals, notified bodies and auditors. Typical uses include: designing sample-preparation procedures for biocompatibility studies, developing extract preparation methods for in vitro and in vivo testing, selecting and documenting appropriate reference materials and controls for test reports, and ensuring consistency and traceability of samples used in regulatory submissions and design dossiers.

Related standards

ISO 10993-12 is part of the ISO 10993 series (biological evaluation of medical devices) and is typically used together with: ISO 10993-1 (evaluation and testing within a risk‑management process), ISO 10993-5 (in vitro cytotoxicity), ISO 10993-6 (local effects after implantation), ISO 10993-10 (irritation and sensitization), ISO 10993-11 (systemic toxicity), ISO 10993-17 (toxicological risk assessment), and ISO 10993-18 (chemical characterization of medical devices). It also interfaces with other standards and guidance relevant to sterilization, endotoxins and materials of animal origin where those topics impact sample preparation.

Keywords

biological evaluation, sample preparation, reference materials, extracts, test samples, biocompatibility, medical devices, ISO 10993, experimental controls, traceability

FAQ

Q: What is this standard?

A: ISO 10993-12:2021 is a part of the ISO 10993 family that gives requirements and guidance for selection and preparation of test samples and reference materials used in biological evaluation of medical devices. Amendment 1 (2025) adds clarifications and corrections to the 2021 edition.

Q: What does it cover?

A: It covers how to select representative device portions for testing, how to prepare solid samples and extracts, how to choose and characterize reference materials and controls, and how to document sample handling and traceability for biological tests. It also indicates where its clauses intersect with chemical-characterization requirements (ISO 10993-18).

Q: Who typically uses it?

A: Medical device manufacturers, biocompatibility/toxicology experts, testing laboratories, regulatory affairs and quality personnel, and conformity assessment bodies use this standard to ensure consistent, defensible sample preparation and reporting for biocompatibility testing.

Q: Is it current or superseded?

A: ISO 10993-12:2021 is the current base edition (Edition 5). Amendment 1 published in August 2025 is a current published amendment that modifies or clarifies parts of the 2021 text; users should apply the amendment together with the 2021 edition. Check your national standards body or ISO for the official consolidated text if required.

Q: Is it part of a series?

A: Yes — it is part of the ISO 10993 series, which addresses biological evaluation of medical devices across multiple parts (testing strategy, cytotoxicity, systemic toxicity, chemical characterization, etc.).

Q: What are the key keywords?

A: Key keywords include: sample preparation, reference materials, extracts, test samples, biocompatibility, biological evaluation, medical devices, ISO 10993.