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  1. Biocompatibility Assessment Resource Center

Glossary of Biocompatibility Terms

Unless otherwise noted, the source for the terms in this glossary is the Use of International Standard ISO 10993-1, "Biological evaluation of medical devices - Part 1: Evaluation and testing within a risk management process" guidance document, also referred to as FDA's Biocompatibility Guidance on Use of ISO 10993-1.

Absorbable material
Medical device material intended to absorb over time, where absorb/absorption is defined as "action of a non-endogenous (foreign) material or substance, or its decomposition products passing through or being assimilated by cells and/or tissue over time."
[SOURCE: ISO 10993-6: 2016, Clause 3.1]

Common Examples of Absorbable Material Product Codes
Absorbable hemostatic agent PMX, LMF, LMG
Absorbable adhesion barrier MCN
Absorbable lung biopsy plug OMT
Absorbable drug-eluting stent PNY
Absorbable bone fixation device MRY, PBQ
Absorbable surgical mesh OWT, OXM, OXI, OXL, OWW, OXF, OXC, OWZ
Absorbable staples LBP, OLL, MNU
Absorbable sutures GAK, GAL, HMO, GAN, GAM, NEW

Aggregate/aggregation
"Particle comprising strongly bonded or fused particles where the resulting external surface area is significantly smaller than the sum of surface areas of the individual components."
[SOURCE: FDA's Biocompatibility Guidance on Use of ISO 10993-1, and ISO/TS 80004-6:2021 (E) (primary source)]

Anatomical location
The tissues in the body to which a medical device is applied during device use. In ISO 10993-1:2018, this is referred to as the "nature of body contact" and is one factor used to categorize devices to determine what endpoint assessments are relevant for biocompatibility evaluation. The FDA uses the same "nature of body contact" categories in FDA's Biocompatibility Guidance on Use of ISO 10993-1, Attachment A.

Biocompatibility
"The ability of a device material to perform with an appropriate host response in a specific situation." [SOURCE: FDA's Biocompatibility Guidance on Use of ISO 10993-1, and Black, J., "Biological Performance of Materials: Fundamentals of Biocompatibility." Boca Raton: CR Press, 2006 (primary source)]

Chemical characterization
"Process of obtaining chemical information, accomplished either by information gathering or by information generation, for example by literature review or chemical testing."
[SOURCE: ISO 10993-18:2020 and Amendment 1 (2022), Clause 3.6]

Color additive
"A dye, pigment, or other substance made by a process of synthesis or similar artifice, or extracted, isolated, or otherwise derived, with or without intermediate or final change of identity, from a vegetable, animal, mineral, or other source, and…when added or applied to a food, drug, or cosmetic, or to the human body or any part thereof, is capable (alone or through reaction with other substance) of imparting color thereto; except that such term does not include any material which the Secretary, by regulation, determines is used (or intended to be used) solely for a purpose or purposes other than coloring." See also the FDA's Center for Devices and Radiological Health webcast presentation and transcript for Webinar: Color Additives for Medical Devices (2016).
[SOURCE: Section 201(t) of FD&C Act.]

Combination product
Includes:

  • "A product comprised of two or more regulated components (i.e., drug/device, biologic/device, drug/biologic, or drug/device/biologic), that are physically, chemically, or otherwise combined or mixed and produced as a single entity;"
  • "Two or more separate products packaged together in a single package or as a unit and comprised of drug and device products, device and biological products, or biological and drug products;"
  • "A drug, device, or biological product packaged separately that according to its investigational plan or proposed labeling is intended for use only with an approved individually specified drug, device, or biological product where both are required to achieve the intended use, indication, or effect and where upon approval of the proposed product the labeling of the approved product would need to be changed (for example, to reflect a change in intended use, dosage form, strength, route of administration, or significant change in dose);" or
  • "Any investigational drug, device, or biological product packaged separately that according to its proposed labeling is for use only with another individually specified investigational drug, device, or biological product where both are required to achieve the intended use, indication, or effect."

[SOURCE: 21 CFR 3.2(e)]

Contact, Tissue:

  • Direct contact: "A device or device component that comes into physical contact with body tissue."
  • Indirect contact: "A device or device component through which a fluid or gas passes, prior to the fluid or gas coming into physical contact with body tissue (In this case, the device or device component itself does not physically contact body tissue)."
    Common examples include packaging materials, solution administration sets, and blood administration sets.
    [SOURCE: ISO 10993-1:2018, Clause 4.3 c), Clause 5.2.3 a)]
  • Non-contact: "A device or device component that has no direct or indirect contact with the body (for example, stand-alone software or database), and for which no biocompatibility information would be needed other than confirmation that there is no contact with the human body."
  • Transient contact: "A device or device component that comes into very brief/transient contact with body tissue (for example, hypodermic needles that are used for less than one minute)."

[SOURCE: FDA's Biocompatibility Guidance on Use of ISO 10993-1]

Degradation
"Decomposition of the device, possibly through the generation of new chemicals or absorption of the material, leading to loss of mechanical and/or physical properties of the device (device function) over time."
[SOURCE: FDA's Biocompatibility Guidance on Use of ISO 10993-1]

Device component
"Any raw material, substance, piece, part, software, firmware, labeling, or assembly which is intended to be included as part of the finished, packaged, and labeled device."
[SOURCE: 21 CFR 820.3(c) definition for "component"]

Duration of exposure/contact
The residence time a medical device or extracted chemicals are applied to tissues in the body during device use. This can include single or repeat use of the same device or a new device. In ISO 10993-1:2018, this is referred to as the "contact duration" and is one factor used to categorize devices to determine what endpoint assessments are relevant for biocompatibility evaluation. The FDA uses these same "contact duration" categories in Attachment A of the FDA's Biocompatibility Guidance on Use of ISO 10993-1.

  • Limited exposure: "Medical devices whose cumulative sum of single, multiple, or repeated duration of contact is up to 24 hours."
    [SOURCE: ISO 10993-1:2018, Clause 5.3.1 a)]
  • Prolonged exposure: "Medical devices whose cumulative sum of single, multiple or repeated contact time is likely to exceed 24 hours but not exceed 30 days."
    [SOURCE: ISO 10993-1:2018, Clause 5.3.1 b)]
  • Long-term/Permanent exposure: "Medical devices whose cumulative sum of single, multiple or repeated contact time exceeds 30 days." [SOURCE: ISO 10993-1:2018, Clause 5.3.1 b)]
  • See also: "Transient contact," a subset of "Tissue Contact"

Equivalence:

  • Biological equivalence: "Situation where two materials or medical devices demonstrate material and contact equivalence." [SOURCE: ISO 10993-18:2020 and Amendment 1 (2022), Annex C.2.]
  • Contact equivalence: "Situation where the intended clinical use of two materials or medical devices is sufficiently similar that the endpoints of biological evaluation identified in ISO 10993-1:2018, A.1 are identical." [SOURCE: ISO 10993-18:2020 and Amendment 1 (2022), Annex C.2.]
  • Material equivalence: "Situation where two materials or medical devices demonstrate chemical and physical equivalence." [SOURCE: ISO 10993-18:2020 and Amendment 1 (2022), Annex C.2.]
  • Chemical equivalence: "Situation where the chemical characteristics of two materials or medical devices are sufficiently similar, such that the composition and processing do not result in additional or different toxicological concerns." [SOURCE: ISO 10993-18:2020 and Amendment 1 (2022), Annex C.2.]
  • Physical equivalence: "Situation where the physical characteristics of two materials or medical devices are sufficiently similar, such that the configuration, morphology, topography (per ISO/TS 10993-19) and tribology do not result in additional or different biocompatibility concerns." [SOURCE: ISO 10993-18:2020 and Amendment 1 (2022), Annex C.2.]

Externally communicating medical device
"Medical device or medical device component that is partially or wholly located outside the body but has either direct or indirect contact with the internal body fluids and/or tissues."
[SOURCE: ISO 10993-1:2018, Clause 3.7 (see also Clause 5.2.3)]

Extractable
"Substance that can be released from a medical device or material using either extraction solvents or extraction conditions, or both, that are expected to be at least as aggressive as the conditions of clinical use."
[SOURCE: FDA's Biocompatibility Guidance on Use of ISO 10993-1 ]

Extraction conditions
"Volume of solvent used per surface area of test article" and temperature and duration of extraction.
[SOURCE: FDA's Biocompatibility Guidance on Use of ISO 10993-1: Section II. Scope and Section V. E. Test Article Preparation for Extract Testing]

Extraction, exhaustive
"Extraction conducted until the amount of extractable material in a subsequent extraction is less than 10% by gravimetric analysis (or that achieved by other means) of that detected in the initial extraction."
[SOURCE: FDA's Biocompatibility Guidance on Use of ISO 10993-1 ]

Final finished form
"A device or device component that includes all manufacturing processes for the 'to be marketed' device including packaging and sterilization, if applicable."
[SOURCE: FDA's Biocompatibility Guidance on Use of ISO 10993-1]

GRAS
"Status of a device material or component as "generally recognized as safe" (GRAS) by FDA as a food additive may or may not be informative for a medical device risk assessment because it may not be appropriate to extrapolate use in food to device-specific tissue contact, such as muscle or circulating blood".
[SOURCE: FDA's Biocompatibility Guidance on Use of ISO 10993-1: Section III. C. Considering Available Information to Identify and Mitigate Risks]

Implant
"A device that is placed into a surgically or naturally formed cavity of the human body. A device is regarded as an implant for the purpose of this part only if it is intended to remain implanted continuously for a period of 30 days or more, unless the Commissioner determines otherwise in order to protect human health." [SOURCE: 21 CFR 860.3]

As described in ISO 10993-1 , this term is used by the regulated medical device community to also include devices used for less than 30 days as a "medical device which is intended to be totally introduced into the human body or to replace an epithelial surface or the surface of the eye by means of clinical intervention and which is intended to remain in place after the procedure." [SOURCE: ISO 10993-1:2018, Clause 3.10].

For the purposes of biocompatibility assessments, the duration of device contact is not the only factor in determining if a device is considered an "implant."

in situ polymerizing
A device or material that is generated, partially or totally, at the site of clinical performance, formed from precursor(s) that undergo a chemical reaction at the site of performance.
[SOURCE: Cohn, D. et al., "In Situ Generated Medical Devices", Advanced Healthcare Materials, 8 (2019).

In vivo animal study
"A nonclinical animal study designed to provide initial evidence of device safety, potential performance when used in a living system, and/or the biologic response to the device."
[SOURCE: FDA's Biocompatibility Guidance on Use of ISO 10993-1]

Intended population/subpopulation
"Age group, sex, other demographics" that describe the group for which a device is labeled or is commonly used.
[SOURCE: FDA Guidance Document: Patient-Reported Outcome Measures: Use in Medical Product Development to Support Labeling Claims, Appendix, II.]

Leachable
"Substance that can be released from a medical device or material during clinical use."
[SOURCE: FDA's Biocompatibility Guidance on Use of ISO 10993-1]

Manufacturing material (for example, manufacturing or processing aids such as a mold, a mandrel, a mold release agent, or lubricant)
"Any material or substance used in or used to facilitate the manufacturing process, a concomitant constituent, or a byproduct constituent produced during the manufacturing process, which is present in or on the finished device as a residue or impurity not by design or intent of the manufacturer."
[SOURCE: 21 CFR 820.3(p)]

Material
"The substance or substances of which a thing is made or composed."
[SOURCE: FDA's Biocompatibility Guidance on Use of ISO 10993-1]

Material-mediated pyrogens
"Chemicals that can leach from a medical device during device use… (to) produce a febrile reaction"
[SOURCE: FDA's Biocompatibility Guidance on Use of ISO 10993-1]

See also:

Novel material
Material that has not previously been used in any device that is legally marketed in the U.S.
[SOURCE: FDA's Biocompatibility Guidance on Use of ISO 10993-1]

Physical characteristics
Characteristics that might contribute to tissue response can include surface properties, geometry, and presence of particulates, among others.
[SOURCE: FDA's Biocompatibility Guidance on Use of ISO 10993-1: Section III. Risk Management for Biocompatibility Evaluations, introduction and Section III. B. Identification of Potential Risks]

Note: "Chemical analysis is usually insufficient to identify all of the risks of the device in its final finished form, because it will not consider aspects of the finished device such as surface properties (e.g., rough versus polished surface) or device geometry that could affect the biological response in certain scenarios (e.g., thrombogenicity, implantation)."
[SOURCE: FDA's Biocompatibility Guidance on Use of ISO 10993-1 on Use of ISO 10993-1: Section III. B. Identification of Potential Risks]

Risk assessment
"Overall process comprising a risk analysis (systematic use of available information to identify hazards and to estimate the risk) and a risk evaluation (process of comparing the estimated risk against given risk criteria to determine the acceptability of the risk)"
[SOURCE: FDA's Biocompatibility Guidance on Use of ISO 10993-1]

  • "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]
  • Potential chemical interactions could also be important [See also FDA's Biocompatibility Guidance on Use of ISO 10993-1: Section III. B. Identification of Potential Risks; Section IV. ISO 10993 - Part 1 and the FDA-Modified Matrix, introduction; and Section IV. D. Endpoint Assessment].

Sponsor
"Manufacturer, submitter, or applicant."
[SOURCE: FDA's Biocompatibility Guidance on Use of ISO 10993-1]

Test article
A sample evaluated in a biocompatibility test that is representative of the final finished device in terms of manufacturing and sterilization (if applicable).
[SOURCE: FDA's Biocompatibility Guidance on Use of ISO 10993-1: Section V. A. Use of Medical Device in Final Finished Form or Representative Test Article]

Tissue
"An aggregation of similar cells or types of cells, together with any associated intercellular materials, adapted to perform one or more specific functions. There are four basic tissues in the body: 1) epithelium; 2) connective tissue, including blood, bone, and cartilage; 3) muscle; and 4) nerve."
[SOURCE: Medical Dictionary for the Health Professions and Nursing, 2012; see also FDA's Biocompatibility Guidance on Use of ISO 10993-1: Attachment A]

Toxic
"Capable of causing injury or death, especially by chemical means."
[SOURCE: FDA's Biocompatibility Guidance on Use of ISO 10993-1]

Toxicological hazard
"Potential for a chemical substance or material to cause an adverse biological reaction, taking into account the nature of the reaction and the dose required to elicit it."
[SOURCE: FDA's Biocompatibility Guidance on Use of ISO 10993-1]

 
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