Biocompatibility Evaluation Endpoints by Device Category

The following is a framework for the development of a biocompatibility evaluation and is not a checklist for testing.

For particular medical devices, different biological endpoints may warrant evaluation, including either additional or fewer endpoints than indicated. If it is unclear in which category a device falls, the FDA recommends consulting device-specific guidances or contacting the appropriate Center and review division for more information. For example, the FDA has historically considered devices used to drain fluids (such as Foley catheters) as externally communicating devices rather than as surface devices contacting mucosal membranes.

Note: On this page, FDA's Biocompatibility Guidance on Use of ISO 10993-1 refers to Use of International Standard ISO 10993-1, "Biological evaluation of medical devices - Part 1: Evaluation and testing within a risk management process." The content on this page comes from this guidance, unless otherwise noted.

Tables for Endpoints by Device Category

Tables: Each of the tables on this page lists biological effects for contact duration periods by specific medical device categorization and nature of body contact. The contact duration periods are:

Limited: Less than or equal to 24 hours
Prolonged: Greater than 24 hours to 30 days
Long term / Permanent: More than 30 days

Endpoints for Consideration: The endpoints for consideration listed in the tables include:

ISO 10993-1 recommended endpoints for consideration
Additional FDA recommended endpoints for consideration

Refer to FDA's Biocompatibility Guidance on Use of ISO 10993-1, Attachment A for details on which endpoints are included in ISO 10993-1 recommendations and which are additional FDA recommended endpoints.

Important: All recommended endpoints should be addressed in the biological safety evaluation, either through the use of existing data, additional endpoint-specific testing, or a rationale* for why the endpoint does not require additional assessment.

* For certain devices that contact intact skin, specific information may be provided in premarket submissions instead of a biocompatibility evaluation to address the applicable endpoints. Refer to FDA's Biocompatibility Guidance on Use of ISO 10993-1, Attachment G for more information on this policy.

Other endpoints (not included in the tables) to be addressed are:

Reproductive and developmental toxicity: Should be addressed for novel materials, materials with a known reproductive or developmental toxicity, devices with relevant target populations (for example, pregnant women), and/or devices where there is the probability for local presence of device materials in the reproductive organs.
Degradation information: Should be provided for any devices, device components, or materials remaining in contact with tissue that are intended to degrade.

Surface Device: Intact Skin

Biological Effect	Limited Duration	Prolonged Duration	Long Term
Cytotoxicity	✔	✔	✔
Sensitization	✔	✔	✔
Irritation or Intracutaneous Reactivity	✔	✔	✔

Notes:

You may not need to assess these endpoints if your device or components of your device are made from certain common materials, as identified in Attachment G of the FDA's Biocompatibility Guidance on Use of ISO 10993-1.
Other endpoints you may need to address: Reproductive and development toxicity, degradation information.
If novel materials or manufacturing processes are used, you may need to do additional biocompatibility evaluations.

Surface Device: Mucosal Membrane

Biological Effect	Limited Duration	Prolonged Duration	Long Term
Cytotoxicity	✔	✔	✔
Sensitization	✔	✔	✔
Irritation or Intracutaneous Reactivity	✔	✔	✔
Acute Systemic Toxicity		✔	✔
Material-Mediated Pyrogenicity		✔	✔
Subacute/Subchronic Toxicity		✔	✔
Genotoxicity			✔
Implantation		✔	✔
Chronic Toxicity			✔

Notes:

Other endpoints you may need to address: Reproductive and development toxicity, degradation information.
If novel materials or manufacturing processes are used, you may need to do additional biocompatibility evaluations.

Surface Device: Breached or Compromised Surface

Biological Effect	Limited Duration	Prolonged Duration	Long Term
Cytotoxicity	✔	✔	✔
Sensitization	✔	✔	✔
Irritation or Intracutaneous Reactivity	✔	✔	✔
Acute Systemic Toxicity	✔	✔	✔
Material-Mediated Pyrogenicity	✔	✔	✔
Subacute/Subchronic Toxicity		✔	✔
Genotoxicity			✔
Implantation		✔	✔
Chronic Toxicity			✔
Carcinogenicity			✔

Notes:

Other endpoints you may need to address: Reproductive and development toxicity, degradation information.
If novel materials or manufacturing processes are used, you may need to do additional biocompatibility evaluations.

External Communicating Device: Blood Path, Indirect

Biological Effect	Limited Duration	Prolonged Duration	Long Term
Cytotoxicity	✔	✔	✔
Sensitization	✔	✔	✔
Irritation or Intracutaneous Reactivity	✔	✔	✔
Acute Systemic Toxicity	✔	✔	✔
Material-Mediated Pyrogenicity	✔	✔	✔
Subacute/Subchronic Toxicity		✔	✔
Genotoxicity			✔
Implantation			✔
Hemocompatibility	✔	✔	✔
Chronic Toxicity			✔
Carcinogenicity			✔

Notes:

Other endpoints you may need to address: Reproductive and development toxicity, degradation information.
If novel materials or manufacturing processes are used, you may need to do additional biocompatibility evaluations.

External Communicating Device: Tissue/Bone/Dentin

Biological Effect	Limited Duration	Prolonged Duration	Long Term
Cytotoxicity	✔	✔	✔
Sensitization	✔	✔	✔
Irritation or Intracutaneous Reactivity	✔	✔	✔
Acute Systemic Toxicity	✔	✔	✔
Material-Mediated Pyrogenicity	✔	✔	✔
Subacute/Subchronic Toxicity		✔	✔
Genotoxicity		✔	✔
Implantation		✔	✔
Chronic Toxicity			✔
Carcinogenicity			✔

Notes:

Tissue includes tissue fluids and subcutaneous spaces.
Other endpoints you may need to address: Reproductive and development toxicity, degradation information.
If novel materials or manufacturing processes are used, you may need to do additional biocompatibility evaluations.

External Communicating Device: Circulating Blood

Biological Effect	Limited Duration	Prolonged Duration	Long Term
Cytotoxicity	✔	✔	✔
Sensitization	✔	✔	✔
Irritation or Intracutaneous Reactivity	✔	✔	✔
Acute Systemic Toxicity	✔	✔	✔
Material-Mediated Pyrogenicity	✔	✔	✔
Subacute/Subchronic Toxicity		✔	✔
Genotoxicity	✔ (see note)	✔	✔
Implantation		✔	✔
Hemocompatibility	✔	✔	✔
Chronic Toxicity			✔
Carcinogenicity			✔

Notes:

Genotoxicity: For all devices used in extracorporeal circuits.
Other endpoints you may need to address: Reproductive and development toxicity, degradation information.
If novel materials or manufacturing processes are used, you may need to do additional biocompatibility evaluations.

Implant Device: Tissue/Bone

Biological Effect	Limited Duration	Prolonged Duration	Long Term
Cytotoxicity	✔	✔	✔
Sensitization	✔	✔	✔
Irritation or Intracutaneous Reactivity	✔	✔	✔
Acute Systemic Toxicity	✔	✔	✔
Material-Mediated Pyrogenicity	✔	✔	✔
Subacute/Subchronic Toxicity		✔	✔
Genotoxicity		✔	✔
Implantation		✔	✔
Chronic Toxicity			✔
Carcinogenicity			✔

Notes:

Tissue includes tissue fluids and subcutaneous spaces.
Other endpoints you may need to address: Reproductive and development toxicity, degradation information.
If novel materials or manufacturing processes are used, you may need to do additional biocompatibility evaluations.

Implant Device: Blood

Biological Effect	Limited Duration	Prolonged Duration	Long Term
Cytotoxicity	✔	✔	✔
Sensitization	✔	✔	✔
Irritation or Intracutaneous Reactivity	✔	✔	✔
Acute Systemic Toxicity	✔	✔	✔
Material-Mediated Pyrogenicity	✔	✔	✔
Subacute/Subchronic Toxicity		✔	✔
Genotoxicity	✔	✔	✔
Implantation	✔	✔	✔
Hemocompatibility	✔	✔	✔
Chronic Toxicity			✔
Carcinogenicity			✔

Notes:

Other endpoints you may need to address: Reproductive and development toxicity, degradation information.
If novel materials or manufacturing processes are used, you may need to do additional biocompatibility evaluations.