This page provides basics on biocompatibility assessment, including sources for more detailed information as well as links to glossary definitions.
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."
On this page:
- What the FDA Assesses or Evaluates
- How the FDA Assesses or Evaluates Biocompatibility
- Biocompatibility Factors of Interest to the FDA
- Background on the FDA's Guidance on Biocompatibility
"Medical devices that come into direct contact or indirect contact with the human body" are evaluated "for the potential for an unacceptable adverse biological response resulting from contact of the component materials of the device with the body."
Note that the term body can refer to a patient undergoing a medical procedure or any other person such as a medical practitioner.
- Source: "For the purposes of this document, the term 'human body' refers to either patient tissues or the clinical practitioner." FDA's Biocompatibility Guidance on Use of ISO 10993-1, I. Introduction.
- Source: "For example, masks or gloves intended for protective purposes by clinical practitioners should be assessed for biocompatibility. Similarly, medical devices such as implants or skin electrodes also should be assessed for biocompatibility." FDA's Biocompatibility Guidance on Use of ISO 10993-1, I. Introduction.
If a device does not have any direct or indirect tissue contact, then the FDA does not need biocompatibility information in the submission.
Source: "When assessing new devices, the sponsor should specifically state if the device does not have any direct or indirect tissue contact, and no further biocompatibility information would be needed." FDA's Biocompatibility Guidance on Use of ISO 10993-1, I. Introduction.
It is the intention of the FDA to assess biocompatibility in a way that is least burdensome for both industry and FDA reviewers.
The FDA assesses the biocompatibility of the whole device and not just the component materials.
- Source: "This guidance considers the assessment of biocompatibility to be an evaluation of the medical device in its final finished form, including sterilization, if applicable. However, sponsors should understand the biocompatibility of each device component and any interactions between components that could occur. This is particularly important when the combination of device components could mask or complicate interpretation of a biocompatibility evaluation. For example, if a metal stent has a polymer coating that may separate over time, then the results of a final device biocompatibility assessment may not fully reflect the longer-term clinical performance of the device, and biocompatibility evaluation of the stent with and without the coating may be needed. Similarly, for an in situ polymerizing and absorbable sealant, where the materials present will change over time, separate evaluations of the pre-polymerized, polymerized, and degrading sealant may be needed." FDA's Biocompatibility Guidance on Use of ISO 10993-1, Section IV. ISO 10993 - Part 1 and the FDA-Modified Matrix.
Final finished form: "The Agency makes a clearance or approval decision for a medical device as it is supplied in its final finished form. The Agency does not clear or approve individual materials that are used in the fabrication of medical devices. Therefore, the risk assessment should evaluate not only the materials used in the device, but also the processing of the materials, the manufacturing methods (including the sterilization process), and any residuals from manufacturing aids used during the process."
- Source: FDA's Biocompatibility Guidance on Use of ISO 10993-1, Section III. A. Risk Assessment of the Medical Device.
It is not possible to describe and discuss all possible scenarios for assessing biocompatibility on this page. The FDA strongly encourages sponsors to read FDA's Biocompatibility Guidance on Use of ISO 10993-1 and determine the relevant recognized consensus standards.
Consensus Standards recognized by the FDA (either wholly, or in part) are maintained and are searchable in the FDA's Recognized Consensus Standards database. Refer to Standards and Conformity Assessment Program and the resources listed on the page for information regarding the appropriate use of consensus standards. Also, refer to Accreditation Scheme for Conformity Assessment (ASCA) for information regarding the accreditation of testing laboratories to perform premarket testing.
Generally, the biocompatibility factors of interest to the FDA are:
- Nature of contact: With which tissues does the device or part of the device come into contact?
- Type of contact: Is there direct or indirect contact?
- Frequency and duration of contact: How long is the device in contact with tissues?
- Materials: What is the device made from?
Source: "Such a process should generally begin with assessment of the device, including the material components, the manufacturing processes, the clinical use of the device including the intended anatomical location, and the frequency and duration of exposure." FDA's Biocompatibility Guidance on Use of ISO 10993-1, Section III. Risk Management for Biocompatibility Evaluations.
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.
In 1986, the FDA, Health and Welfare Canada, and Health and Social Services UK issued the Tripartite Biocompatibility Guidance for Medical Devices. The FDA then issued General Program Memorandum G87-1 "Tripartite Biocompatibility Guidance" (April 24, 1987), which was used by FDA reviewers and device manufacturers until 1995, to select appropriate tests to evaluate the adverse biological responses to medical devices. FDA then issued Blue Book Memorandum G95-1 "Use of International Standard ISO-10993, "'Biological Evaluation of Medical Devices Part- 1: Evaluation and Testing,'" (May 1, 1995).
The FDA's Biocompatibility Guidance on Use of ISO 10993-1 was first published in 2016 and replaced both G87-1 and G95-1. It provides clarification and information on the use of International Standard ISO 10993-1 to support applications to FDA and includes the same seven general principles for biocompatibility evaluation (Section IV.B.) as discussed in G87-1 and G95-1. The FDA's Biocompatibility Guidance on Use of ISO 10993-1 includes considerations not previously discussed in #G95-1 (such as the use of risk-based approaches to determine if biocompatibility testing is needed).
Since the FDA's Biocompatibility Guidance on Use of ISO 10993-1 first published in 2016, it was updated in 2020 (minor update to clarify that the guidance applies to CBER-regulated devices) and again in 2023 (added Attachment G: Biocompatibility of Certain Devices in Contact with Intact Skin, and minor updates to ensure alignment with current versions of recognized consensus standards).