ISO TS 21726-2019 PDF

Full title and description

ISO/TS 21726:2019 — Biological evaluation of medical devices — Application of the threshold of toxicological concern (TTC) for assessing biocompatibility of medical device constituents. This technical specification provides a framework for selecting and applying TTC values when assessing trace constituents (identified or unidentified) present in, on, or released from medical devices to support biocompatibility and toxicological equivalence assessments.

Abstract

The document explains the basis for selection of TTC values and their general applicability for comparing analytical extract concentrations or estimated exposure doses against protective TTC intake limits. It clarifies applicability limits (for example, TTC is not used when adequate toxicity data exist or for cohorts of concern) and notes that conversion between TTC (µg/day) and concentrations (µg/mL) is addressed by ISO 10993-18.

General information

• Status: Published.
• Publication date: February 2019.
• Publisher: International Organization for Standardization (ISO).
• ICS / categories: 11.100.20 (Medical equipment and devices; biological evaluation of medical devices).
• Edition / version: Edition 1 (2019-02).
• Number of pages: 7.

Scope

ISO/TS 21726:2019 defines how to apply the Threshold of Toxicological Concern (TTC) approach to individual constituents associated with medical devices. It is intended for use when specific tolerable intake values are not available and can be applied to compare analytical extract concentrations or estimated exposure doses, and to support toxicological equivalence between materials. The specification also describes exclusions, limitations and situations where TTC is not appropriate (for example, cohorts of concern and some substance classes) and points users to related parts of the ISO 10993 series for conversion and exposure assessment guidance.

Key topics and requirements

• Definition and rationale for TTC values applicable to medical‑device constituents.
• Guidance for selection of TTC based on device contact duration/category (limited, prolonged, long‑term exposure) and use conditions.
• Recommended protective TTC intake thresholds and their role in screening analytical extract or exposure estimates.
• Explicit exclusions and “cohort of concern” guidance — substances and scenarios where TTC is not applicable (e.g., certain potent genotoxins, some organohalogens, heavy metals, high‑molecular‑weight polymers, particles, proteins, ceramics, radioactive materials).
• Use cases: compare TTC to maximum extract concentrations, support toxicological equivalence claims, or compare to estimated exposure doses when tolerable intake (TI) values are not available.
• Reference to ISO 10993-18 for conversion of TTC (µg/day) to concentration (µg/mL) and to ISO 10993-17 for integration with toxicological risk assessment processes.

Typical use and users

Common users include medical‑device manufacturers, toxicologists, regulatory affairs professionals, extractables & leachables (E&L) specialists, and contract testing laboratories. Typical uses are preliminary safety screening of extractables/leachables, supporting material equivalence dossiers, and providing toxicological justification when specific TI values are not available.

Related standards

ISO/TS 21726 is part of the biological‑evaluation ecosystem and is used alongside other ISO and regulatory references such as ISO 10993-1 (biological evaluation framework), ISO 10993-17 (toxicological risk assessment / establishment of allowable limits), ISO 10993-18 (chemical characterization and conversion guidance), and the ISO 18562 series for gas‑pathway exposures. It is also used in the context of established regulatory toxicology guidance (for example ICH M7 approaches for mutagenic impurities) when assessing extractables/leachables and low‑level constituents.

Keywords

Threshold of Toxicological Concern (TTC), biocompatibility, medical devices, extractables and leachables (E&L), ISO 10993, toxicological equivalence, cohort of concern, exposure assessment.

FAQ

Q: What is this standard?

A: ISO/TS 21726:2019 is a Technical Specification that provides guidance on applying the Threshold of Toxicological Concern (TTC) approach to assess biocompatibility risks from constituents present in or released from medical devices.

Q: What does it cover?

A: It covers the rationale, selection and applicability of TTC values for comparing analytical extract concentrations or estimated exposure doses, supporting toxicological equivalence, and indicating where TTC is not appropriate (including cohorts of concern and certain substance types). It also points to ISO 10993-18 for TTC-to-concentration conversion and to ISO 10993-17 for toxicological risk assessment integration.

Q: Who typically uses it?

A: Medical device manufacturers, toxicologists, regulatory affairs specialists, E&L scientists and testing laboratories use this TS for screening and justification when specific toxicity-derived tolerable intake values are not available.

Q: Is it current or superseded?

A: As published in February 2019, ISO/TS 21726:2019 is a published Technical Specification. The ISO lifecycle indicates the document is under review for revision; users should confirm the current status with ISO or their national standards body before relying on it for regulatory submissions.

Q: Is it part of a series?

A: Yes — it is used in conjunction with other parts of the ISO 10993 series (notably ISO 10993-1, ISO 10993-17 and ISO 10993-18) and with guidance addressing specific exposure pathways (e.g., the ISO 18562 series for gas pathways).

Q: What are the key keywords?

A: TTC, threshold of toxicological concern, biocompatibility, medical device constituents, extractables and leachables, toxicological equivalence, ISO 10993.