• Decrease font size
  • Return font size to normal
  • Increase font size
U.S. Department of Health and Human Services

Recognized Consensus Standards

  • Print
  • Share
  • E-mail
Super Search Devices@FDA
510(k) | DeNovo | Registration & Listing | Adverse Events | Recalls | PMA | HDE | Classification | Standards
CFR Title 21 | Radiation-Emitting Products | X-Ray Assembler | Medsun Reports | CLIA | TPLC

New Search Back To Search Results
Part B: Supplementary Information Sheet (SIS)
FR Recognition List Number 054 Date of Entry 07/06/2020 
FR Recognition Number 2-276
ISO 10993-18 Second edition 2020-01
Biological evaluation of medical devices - Part 18: Chemical characterization of medical device materials within a risk management process.
This document specifies a framework for the identification, and if necessary, quantification of constituents of a medical device, allowing the identification of biological hazards and the estimation and control of biological risks from material constituents, using a generally stepwise approach to the chemical characterization which can include one or more of the following:
- the identification of its materials of construction (medical device configuration);
- the characterization of the materials of construction via the identification and quantification of their chemical constituents (material composition);
- the characterization of the medical device for chemical substances that were introduced during manufacturing (e.g. mould release agents, process contaminants, sterilization residues);
- the estimation (using laboratory extraction conditions) of the potential of the medical device, or its materials of construction, to release chemical substances under clinical use conditions (extractables);
- the measurement of chemical substances released from a medical device under its clinical conditions of use (leachables).
This document can also be used for chemical characterization (e.g. the identification and/or quantification) of degradation products. Information on other aspects of degradation assessment are covered in ISO 10993-9, ISO 10993-13, ISO 10993-14 and ISO 10993-15.
The ISO 10993 series is applicable when the material or medical device has direct or indirect body contact (see ISO 10993-1 for categorization by nature of body contact).
This document is intended for suppliers of materials and manufacturers of medical devices, to support a biological evaluation.
Extent of Recognition
Partial recognition. The following part(s) of the standard is (are) not recognized:
Clause 5.5 second and third sentences.
Clause 7, second paragraph, phrase "to assist in any toxicological risk assessment"
Table D.3 in Clause D.5 of Annex D
Formula E2 AND paragraph preceding Formula E2 AND two paragraphs following Formula E2 in Clause E.3 of Annex E
Example C2 in Clause E.4 of Annex E
Rationale for Recognition
This standard is relevant to medical devices and is recognized on its scientific and technical merit and/or because it supports existing regulatory policies.
This standard is recognized in part because:
Clause 5.5 second and third sentences are in conflict with published literature articles, see literature article #1-2 listed below.
Clause 7, second paragraph, phrase "to assist in any toxicological risk assessment" is in conflict with published literature, see literature articles #3-5 listed below.
Table D.3 in Clause D.5 of Annex D is not supported by the cited article and in conflict with published document, see reference #6.
Formula E2 AND paragraph preceding Formula E2 AND two paragraphs following Formula E2 in Clause E.3 of Annex E include technical errors and will be corrected by ISO in the following publication.
Example C2 in Clause E.4 of Annex E is in conflict with another recognized standard, see clause 5.2 and Table 1 of ISO TS 21726 listed below.
Transition Period
FDA recognition of ANSI/AAMI BE83:2006/(R)2011 [Rec# 2-238] will be superseded by recognition of ISO 10993-18 Second edition 2020-01 [Rec# 2-276]. FDA will accept declarations of conformity, in support of premarket submissions, to [Rec# 2-238] until July 10, 2022. After this transition period, declarations of conformity to [Rec# 2-238] will not be accepted.
Relevant FDA Guidance and/or Supportive Publications*
1. Luis Cuadros-Rodríguez, Marta Lazúen-Muros, Cristina Ruiz-Samblás, Natalia Navas-Iglesias, Leachables from plastic materials in contact with drugs. State of the art and review of current analytical approaches, International Journal of Pharmaceutics 583 (2020),119332.
2. Moyer, J. Scull, Extractables and leachables, Book title "Specification of Drug Substances and Products: Development and Validation of Analytical Methods", Maryville, 2014, ch. 13, pp. 265-289.
4. Broschard, T.H. et al. Assessing safety of extractables from materials and le.achables in pharmaceuticals and biologics - Current challenges and approaches, Regulatory Toxicology and Pharmacology, 81(2016), 201-211.
5. Escher, S.E. et al. (2019) Towards grouping concepts based on new approach methodologies in chemical hazard assessment: the read-across approach of the EU-ToxRisk project. Arch Toxicol, 93 (2019), 3643-3667.
6. Guidance for Industry: Preparation of Premarket Submissions for Food Contact Substances (Chemistry Recommendations), Issued 2007.
7. ISO 10993-12 Biological evaluation of medical devices - Part 12: Sample preparation and reference materials.
8. Guidance for Industry and Food and Drug Administration Staff: Use of International Standard ISO 10993-1, "Biological evaluation of medical devices--Part 1: Evaluation and testing within a risk management process", Issued June 2016. Updated September 2020.
9. ISO TS 21726 First edition 2019-02 Biological evaluation of medical devices - Application of the threshold of toxicological concern (TTC) for assessing biocompatibility of medical device constituents.
FDA Technical Contacts
 Jennifer Goode
 Irada Isayeva
Standards Development Organization
ISO International Organization for Standardization https://www.iso.org/
FDA Specialty Task Group (STG)
*These are provided as examples and others may be applicable.