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 require 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.

Device categorization information can be obtained informally via email, or as a part of the Q-Submission process. Refer to the FDA's guidance document, Requests for Feedback and Meetings for Medical Device Submissions: The Q-Submission Program: Guidance for Industry and Food and Drug Administration Staff.

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

Within each table, endpoints are listed by:

• Surface Device
  • Intact Skin
  • Mucosal Membrane
  • Breached or Compromised Surface
• External Communicating Device
  • Blood Path, Indirect
  • Tissue/Blood/Dentin
  • Circulating Blood
• Implant Device
  • Tissue/Bone
  • Blood

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.

* 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.

Limited Contact: Surface Device

Notes:

• For certain devices that contact intact skin, you may not need to assess these endpoints if your device or components are made from 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.

Limited Contact: External Communicating Device

Notes:

• Tissue includes tissue fluids and subcutaneous spaces.
• 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.

Limited Contact: Implant Device

Biological Effect	Tissue/Bone	Blood
Cytotoxicity	✔	✔
Sensitization	✔	✔
Irritation or Intracutaneous Reactivity	✔	✔
Acute Systemic Toxicity	✔	✔
Material-Mediated Pyrogenicity	✔	✔
Genotoxicity		✔
Implantation		✔
Hemocompatibility		✔

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.

Prolonged Contact: Surface Device

Notes:

• For certain devices that contact intact skin, you may not need to assess these endpoints if your device or components are made from 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.

Prolonged Contact: External Communicating Device

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.

Prolonged Contact: Implant Device

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.

Long Term / Permanent Contact: Surface Device

Notes:

• For certain devices that contact intact skin, you may not need to assess these endpoints if your device or components are made from 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.

Long Term / Permanent Contact: External Communicating Device

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.

Long Term / Permanent Contact: Implant Device

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.