| Part B: Supplementary Information Sheet (SIS) |
|
FR Recognition List Number
|
061
|
Date of Entry 12/18/2023
|
|
FR Recognition Number
|
2-303
|
| Standard | |
ISO 10993-17 Second edition 2023-09
Biological evaluation of medical devices - Part 17: Toxicological risk assessment of medical device constituents |
|
Scope/AbstractThis document specifies the process and requirements for the toxicological risk assessment of medical device constituents. The methods and criteria used to assess whether exposure to a constituent is without appreciable harm are also specified. The toxicological risk assessment can be part of the biological evaluation of the final product, as described in ISO 10993-1.
The process described in this document applies to chemical characterization information obtained in line with ISO 10993-18. When a toxicological risk assessment of either the compositional information or analytical chemistry data (e.g. extractable data or leachable data) are required to determine whether the toxicological risks related to the constituents are negligible or tolerable.
The process described in this document is not intended to apply to circumstances where the toxicological risk has been estimated by other means, such as:
- constituents, excluding cohort of concern or excluded chemicals, that are present in or extracted from a medical device at an amount representative of patient exposure below a relevant, toxicologically-based reporting threshold (see applicable requirements in ISO 10993-18:2020, Annex E and ISO/TS 21726);
- a new or changed medical device for which chemical or biological equivalence has been established with an existing biocompatible or clinically established medical device (see applicable requirements in ISO 10993-18:2020, Annex C).
The process described in this document is also not applicable to:
- medical device constituents that do not contact the body (e.g. in vitro diagnostics);
- biological risks associated with physical interactions of the medical device with the body (i.e. application of mechanical forces, energy or surface morphology, etc.), provided that the chemical exposure is not changed;
- active pharmaceutical ingredients of device-drug combination products or biologic components of device-biologic combination products as additional regulatory considerations can apply;
- exposure to a particular constituent that arises from sources other than the device, such as food, water or air.
|
|
Extent of Recognition
| Partial recognition. The following part(s) of the standard is (are) not recognized: |
- Table B1 in Annex B, second column, unit "g/d"
- Example 6 in Clause B3 of Annex B, phrase "10 is the SF where 50 cm2 is the maximum device surface area, in cm2"
- Table E.2 in Clause E2 of Annex E
- Phrase "e.g. the largest surface area of device which can be in contact with the body is not the same as the surface area of the device which is in contact with the solution during extraction" in the paragraph before formula E.2 of Clause E2 and in the paragraph before formula E.4 of Clause E3.1
|
|
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:
- Table B1 in Annex B, second column, unit "g/d" is a technical error (i.e., "g/d" should be "µg/d").
- Example 6 in Clause B3 of Annex B, phrase "10 is the SF where 50 cm2 is the maximum device surface area, in cm2" has a technical error (i.e., 50 cm2 should be 500 cm2).
- Table E.2 in Clause E2 of Annex E is not supported by the normative text in Clause E2 of Annex E of this standard which states "The number of time points within an exposure period shall be sufficient to address late bolus release of the constituent(s), unless justified with supporting evidence that late bolus release will not occur."
- Phrase "e.g. the largest surface area of device which can be in contact with the body is not the same as the surface area of the device which is in contact with the solution during extraction" in the paragraph before formula E.2 of Clause E2 and in the paragraph before formula E.4 of Clause E3.1 in Annex E is in conflict with Section VI.G. of FDA's biocompatibility guidance, which states "consider the situation where a patient might receive multiple devices of the largest device size to calculate the estimated worst-case patient exposure". See reference #1 listed below. |
|
Transition Period
| FDA recognition of ISO 10993-17 First edition 2002-12-01 [Rec# 2-237] will be superseded by recognition of ISO 10993-17 Second edition 2023-09 [Rec# 2-303]. FDA will accept declarations of conformity, in support of premarket submissions, to [Rec# 2-237] until December 20, 2026. After this transition period, declarations of conformity to [Rec# 2-237] will not be accepted. |
|
Public Law, CFR Citation(s) and Procode(s)*
| 21 CFR 58 Good Laboratory Practice for Nonclinical Laboratory Studies |
|
Relevant FDA Guidance and/or Supportive Publications*
1.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 September 2023.
2. Guidance for Industry and Food and Drug Administration Staff: General Considerations for Animal Studies Intended to Evaluate Medical Devices, issued March 2023.
Appropriate Use of Voluntary Consensus Standards in Premarket Submissions for Medical Devices - Guidance for Industry and Food and Drug Administration Staff, issued September 2018. |
|
| FDA Technical Contacts
|
| Standards Development Organization
|
| FDA Specialty Task Group (STG)
|
| *These are provided as examples and others may be applicable. |
