# ISO 10993

The ISO 10993 set entails a series of standards for evaluating the biocompatibility of medical devices to manage biological risk. These documents were preceded by the Tripartite agreement and is a part of the international harmonisation of the safe use evaluation of medical devices. For the purpose of the ISO 10993 family of standards, biocompatibility is defined as the "ability of a medical device or material to perform with an appropriate host response in a specific application".

## ISO 10993-1:2009 & FDA endpoints for consideration

The following table provides a framework for the development of a biocompatibility evaluation. Different biological endpoints may require evaluation for particular medical devices, including either additional or fewer endpoints than indicated. If it is unclear in which category a device falls, consulting device-specific guidances or contacting the appropriate US Food and Drug Administration (FDA) review division for more information is possible. The table "Endpoints to be addressed in a biological risk assessment" was revised by the 2018 edition of ISO 10993-1. The selection of endpoints for the biocompatibility evaluation is determined by the nature of body contact (e.g. implant device) and contact duration (e.g. long term contact of more than 30 days).
| Medical device categorization by | Medical device categorization by | Medical device categorization by | Biological Effect | Biological Effect | Biological Effect | Biological Effect | Biological Effect | Biological Effect | Biological Effect | Biological Effect | Biological Effect | Biological Effect | Biological Effect | Biological Effect | Biological Effect |
| Nature of Body Contact | Nature of Body Contact | Contact Duration A-limited (≤24 h) B-prolonged (>24 h to 30 d) C-permanent (> 30 d) | Cytotoxicity | Sensitization | Irritation or Intracutaneous Reactivity | Acute Systemic Toxicity | Material-Mediated Pyrogenicity | Subacute/Subchronic Toxicity | Genotoxicity | Implantation | Hemocompatibility | Chronic Toxicity | Carcinogenicity | Reproductive/Developmental Toxicity | Degradation |
| Category | Contact | Contact Duration A-limited (≤24 h) B-prolonged (>24 h to 30 d) C-permanent (> 30 d) | Cytotoxicity | Sensitization | Irritation or Intracutaneous Reactivity | Acute Systemic Toxicity | Material-Mediated Pyrogenicity | Subacute/Subchronic Toxicity | Genotoxicity | Implantation | Hemocompatibility | Chronic Toxicity | Carcinogenicity | Reproductive/Developmental Toxicity | Degradation |
| Surface device | Intact skin | A | X | X | X | | | | | | | | | | |
| Surface device | Intact skin | B | X | X | X | | | | | | | | | | |
| Surface device | Intact skin | C | X | X | X | | | | | | | | | | |
| Surface device | Mucosal membrane | A | X | X | X | | | | | | | | | | |
| Surface device | Mucosal membrane | B | X | X | X | O | O | O | | O | | | | | |
| Surface device | Mucosal membrane | C | X | X | X | O | O | X | X | O | | O | | | |
| Surface device | Breached or compromised surface | A | X | X | X | O | O | | | | | | | | |
| Surface device | Breached or compromised surface | B | X | X | X | O | O | O | | O | | | | | |
| Surface device | Breached or compromised surface | C | X | X | X | O | O | X | X | O | | O | O | | |
| External communicating device | Blood path, indirect | A | X | X | X | X | O | | | | | X | | | |
| External communicating device | Blood path, indirect | B | X | X | X | X | O | O | | | | X | | | |
| External communicating device | Blood path, indirect | C | X | X | O | X | O | X | X | O | X | O | O | | |
| External communicating device | Tissue/bone/dentin | A | X | X | X | O | O | | | | | | | | |
| External communicating device | Tissue/bone/dentin | B | X | X | X | X | O | X | X | X | | | | | |
| External communicating device | Tissue/bone/dentin | C | X | X | X | X | O | X | X | X | | O | O | | |
| External communicating device | Circulating blood | A | X | X | X | X | O | | O | | X | | | | |
| External communicating device | Circulating blood | B | X | X | X | X | O | X | X | X | X | | | | |
| External communicating device | Circulating blood | C | X | X | X | X | O | X | X | X | X | O | O | | |
| Implant device | Tissue/bone | A | X | X | X | O | O | | | | | | | | |
| Implant device | Tissue/bone | B | X | X | X | X | O | X | X | X | | | | | |
| Implant device | Tissue/bone | C | X | X | X | X | O | X | X | X | | O | O | | |
| Implant device | Blood | A | X | X | X | X | O | | O | X | X | | | | |
| Implant device | Blood | B | X | X | X | X | O | X | X | X | X | | | | |
| Implant device | Blood | C | X | X | X | X | O | X | X | X | X | O | O | | |
| X = ISO 10993-1:2009 recommended endpoints for consideration ||||||||||||||||
| O = Additional FDA recommended endpoints for consideration ||||||||||||||||

## List of the standards in the 10993 series

Part 1: Evaluation and testing within a risk management process
Part 2: Animal welfare requirements
Part 3: Tests for genotoxicity, carcinogenicity and reproductive toxicity
Part 4: Selection of tests for interactions with blood
Part 5: Tests for in vitro cytotoxicity.
Part 6: Tests for local effects after implantation
Part 7: Ethylene oxide sterilization residuals
Part 8: Selection of reference materials (withdrawn)
Part 9: Framework for identification and quantification of potential degradation products
Part 10: Tests for skin sensitization
Part 11: Tests for systemic toxicity
Part 12: Sample preparation and reference materials (available in English only)
Part 13: Identification and quantification of degradation products from polymeric medical devices
Part 14: Identification and quantification of degradation products from ceramics
Part 15: Identification and quantification of degradation products from metals and alloys
Part 16: Toxicokinetic study design for degradation products and leachables
Part 17: Establishment of allowable limits for leachable substances
Part 18: Chemical characterization of medical device materials within a risk management process
Part 19: Physico-chemical, morphological and topographical characterization of materials
Part 20: Principles and methods for immunotoxicology testing of medical devices
Part 22: Guidance on nanomaterials
Part 23: Tests for irritation
Part 33: Guidance on tests to evaluate genotoxicity