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EN ISO 10993-23

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EN ISO 10993-23

EN ISO 10993-23:2021 ist eine von der Internationalen Organisation für Normung (ISO) veröffentlichte und vom Europäischen Komitee für Normung (CEN) übernommene Norm mit dem Titel „Biologische Bewertung von Medizinprodukten – Teil 23: Tests for irritation“, d. h. „Biologische Bewertung von Medizinprodukten – Teil 23: Reizungstests“. Der Haupttext der Norm ISO 10993-23:2021 (erste Ausgabe) wurde auf europäischer Ebene als EN ISO 10993-23:2021 angenommen.

Change to regulatory status and scope: ISO 10993-23 was developed to cover irritation testing, which was previously dealt with alongside sensitisation in ISO 10993-10:2010, in a separate standard. Under this new arrangement, sensitisation is covered in ISO 10993-10:2021, whilst irritation is covered in ISO 10993-23:2021. The standard has been recognised as a harmonised standard under the EU Medical Devices Regulation (MDR 2017/745). The status and scope of recognition by the FDA (particularly with regard to the in vivo sections) should be verified before submitting an application.

The basic principle of the standard is to assess the potential of medical devices, their materials or extracts to cause local irritation following contact with the skin, eyes or mucous membranes. The assessment is carried out as part of a tiered approach; following chemical characterisation and the evaluation of the available data, suitable test methods are selected. For methods relating to the preparation of extracts, reference is made to ISO 10993-12.

The most important feature of the standard is the preference for in vitro methods. Where appropriate and validated, in vitro models of the reconstructed human epidermis (RhE) are preferred to in vivo tests. This approach is in line with the 3Rs principles (Replacement, Reduction, Refinement).

In vitro methods (primarily)

  • Models of the reconstructed human epidermis (RhE): irritation tests using human skin equivalents validated in accordance with OECD TG 439 (e.g. EpiSkin, EpiDerm, SkinEthic RHE, epiCS).
  • Die Testsubstanz oder der Extrakt wird auf das RhE-Gewebe aufgetragen; nach einer bestimmten Zeit wird die Zellviabilität mittels MTT-Test gemessen.
  • The irritant potential is classified (irritant / non-irritant) on the basis of the percentage viability value and in comparison with validated threshold values.
  • In the case of solid substances, direct contact takes place; for liquids or extracts, suitable application methods may be used.

In vivo method (if necessary)

  • Skin irritation test on rabbits (Draize test): Used in cases where in vitro methods are not applicable or are insufficient.
  • The test substance or extract is applied as a single dose to the depilated rabbit skin (usually 0.5 mL or 0.5 g) and left under a semi-occlusive dressing for 4 hours.
  • Following application, erythema and oedema are assessed at 1, 24, 48 and 72 hours using a standard assessment system (on a scale of 0 to 4).
  • Die Ergebnisse werden den GHS/CLP-Kategorien für Hautreizungen (Kategorie 1, Kategorie 2 oder nicht klassifiziert) zugeordnet.

The standard also provides a general framework for the assessment of eye and mucous membrane irritation; however, these assessments are based on the relevant OECD test guidelines (e.g. OECD TG 437, 438, 492, 405) and sector-specific regulations.

The key parameters reported in the study are:

  • The test method used (RhE in vitro or in vivo in rabbits) and the rationale for its use
  • Conditions for the preparation of the test substance/extract (in accordance with ISO 10993-12)
  • Dosage/application rate, contact time and covering conditions
  • For in vitro tests: cell viability (%) and threshold assessment
  • For in vivo tests: erythema and oedema scores (per animal, per observation time point)
  • Average scores and assessment of reversibility
  • Validity of positive and negative controls
  • Result: irritating / non-irritating; classification and GHS/CLP category
  • Data on measurement uncertainty and repeatability

Why is the test carried out?

EN ISO 10993-23 is carried out for the following scientific and regulatory purposes:

  • Assessment of the safety of medical devices: Determination of the potential of product materials or their extracts to cause local irritation following contact with the skin, eyes and mucous membranes
  • MDR compliance: Provision of the data required for the biological safety assessment under the EU Medical Devices Regulation (2017/745)
  • Risk management: Assessment and mitigation of the risk of irritation from those parts of the product that come into contact with patients and users
  • Material selection and development: Early identification of potentially irritating materials and evaluation of alternatives as part of the product development process
  • Animal welfare (3Rs): Reducing animal testing by prioritising in vitro RhE methods; supporting regulatory trends towards reducing animal testing in accordance with the MDR and the FDA Modernisation Act 2.0
  • Support with regulatory documentation: for use as part of the biocompatibility dossier in applications to the FDA, in accordance with the EU MDR and other regulatory authorities
  • Approach to assessing the weight of evidence: Contribution to the holistic assessment of the product in conjunction with data on chemical characterisation (ISO 10993-18), cytotoxicity (ISO 10993-5), sensitisation (ISO 10993-10) and other biocompatibility data

EN ISO 10993-23 does not, on its own, cover the entire biocompatibility profile of the product. The results must be interpreted in conjunction with the chemical characterisation, other biological tests and clinical data. The applicability of in vitro RhE methods for extracts from medical devices must be assessed on the basis of the product’s characteristics and the available validation data.

As part of our nano-testing services, we carry out irritation assessments in accordance with EN ISO 10993-23, applying scientific rigour within the framework of our accredited laboratory infrastructure and our quality management system. Our scope of services includes the following:

Drawing up a test strategy and a protocol

  • Establishment of a multi-stage testing strategy based on the type of contact (skin, eyes, mucous membranes), the duration of contact and the material composition of the product
  • Evaluation of the available chemical characterisation (ISO 10993-18) and toxicological data
  • Prioritisation of the in vitro RhE method; assessment of feasibility and justification
  • In cases where the in vitro method is not suitable, justification for the in vivo rabbit test
  • Establishment of a strategy for extract preparation in accordance with ISO 10993-12 (polar/non-polar solvents, temperature, duration)
  • Planning of positive and negative controls; compliance with ethical and regulatory requirements

For information on test strategies, the applicability of in vitro RhE, extract preparation, sample acceptance criteria, the test schedule and reporting procedures as part of your irritation assessments in accordance with EN ISO 10993-23, please feel free to contact Nano-Test.

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