ISO 10993-18:2020 医療機器の生物学的評価—パート18：リスク管理プロセス内の医療機器材料の化学的特性 | ページ 6

3.1

accelerated extraction

extraction whose duration is shorter than the duration of clinical use but whose conditions do not result in a chemical change to the substances being extracted

Note 1 to entry: See also Annex D.

3.2

analytical evaluation threshold

AET

threshold below which the analyst need not identify or quantify leachables or extractables or report them for potential toxicological assessment

Note 1 to entry: See Annex E.

3.3

analytically expedient

situation where an extraction vehicle can be directly evaluated with generally available analytical methods with the sensitivity and selectivity necessary to achieve a designated reporting threshold such as the AET

3.4

analytical screening method

method whose purpose is to discover, identify and semi-quantitatively estimate the concentration of all relevant analytes in a test sample above an established reporting threshold (such as the AET)

3.5

analytical targeting method

method whose purpose is to quantify, with an appropriately high degree of accuracy and precision, specified analytes in a specified test sample over a specified concentration range

3.6

chemical characterization

process of obtaining chemical information, accomplished either by information gathering or by information generation, for example, by literature review or chemical testing

3.7

chemical information

qualitative and quantitative, if applicable, knowledge related to the configuration, composition and production of the medical device and/or its materials of construction, thereby establishing the identities and amounts of constituents present in the materials and device

Note 1 to entry: See also 5.2.1, 5.2.2, 5.2.3, and Annex B.

Note 2 to entry: Chemical information can be used to establish the hypothetical worst-case release of chemicals from a medical device, predicated on the circumstance that all chemicals present in the device are released from the device under its clinical conditions of use.

3.8

clinically established

medical device, component, or material of construction which has been used extensively for specified and established clinical uses for which biocompatibility has been established

3.9

component

item which forms one part of a medical device, but is not itself a medical device

3.10

constituent

chemical that is present in a finished medical device or its materials of construction

Note 1 to entry: Constituents may be intentionally present (e.g. an additive such as an antioxidant) or unintentionally present (e.g. an impurity or degradant).

3.11

convertor

person or company who converts or fabricates a basic raw material into a semi-finished product (e.g. a former of lengths of rod, tubing, or plastic components)

3.12

digestion

process of completely solubilizing a medical device, one or more of its components or one or more of its materials of construction by breaking it down into its fundamental structural units, including its elemental constituents or monomeric units

3.13

dissolution

process of completely solubilizing a medical device, one or more of its components or one or more of its materials of construction, generally preserving the molecular structures of its constituents

3.14

exaggerated extraction

extraction that is intended to result in a greater number or amount of chemical constituents being released as compared to the amount generated under the clinical conditions of use

Note 1 to entry: It is important to ensure that the exaggerated extraction does not result in a chemical change of the material or the substances being extracted.

3.15

exhaustive extraction

multi-step extraction conducted until the amount of material extracted in a subsequent extraction step is less than 10 % by gravimetric analysis (or achieved by other means) of that determined in the initial extraction step

3.16

extractable

substance that is released from a medical device or material of construction when the medical device or material is extracted using laboratory extraction conditions and vehicles

3.17

extraction power

ability of an extraction vehicle to extract (or leach) substances from a medical device, component or material of construction

Note 1 to entry: The extraction power of an extraction vehicle is impacted by its physicochemical properties, including, but not limited to, its polarity, pH and dielectric constant.

3.18

extraction vehicle

medium (solution or solvent) which is used to extract (or leach) a test article for the purpose of establishing the test article’s extractables or leachables profile

Note 1 to entry: It is preferred that extraction vehicles be analytically expedient.

Note 2 to entry: For some medical devices (e.g. infusion systems) that are labelled for use with a drug, the most appropriate extraction medium may be the drug product or drug product vehicle.

3.19

identification

process of assigning a molecular structure and chemical name to an organic compound or assigning constituent elements or molecular structure as appropriate, and a chemical name to an inorganic compound

3.20

information gathering

process of collecting existing chemical information, including available test results, that is relevant to chemical characterization

3.21

information generation

process of producing chemical information via laboratory testing

3.22

leachable

substance that is released from a medical device or material during its clinical use

Note 1 to entry: For many medical devices, a leachables study is not practical due to challenges with reproducing actual clinical conditions, so simulated-use extraction studies are often performed instead. See definition for simulated-use extraction.

3.23

manufacturer

natural or legal person who manufactures or fully refurbishes a medical device, or has a device designed, manufactured, or fully refurbished, and markets that medical device under its name or trademark

3.24

material composition

listing of the constituents that are contained in a material (qualitative) and the amount of each substance in the material (quantitative)

Note 1 to entry: A material’s composition establishes the hypothetical situation in which the total amount of all substances present in a medical device are released during clinical use. These amounts can be derived directly from known composition; experimentally, they can be derived from digestion, dissolution, and, in many cases, exhaustive extraction studies.

3.25

material of construction

individual raw material that is used to produce a component

3.26

medical device configuration

listing of a medical device’s components (qualitative), including a listing of the component’s materials of construction (qualitative) and the proportion of each material in each component (quantitative)

Note 1 to entry: Device configuration should also take into account the shape and relative arrangement of the parts in the medical device and surface properties (topography and chemistry).

3.27

potentially affected individual

person having direct or indirect body contact with the medical device

Note 1 to entry: See ISO 10993-1 for categorization by nature of body contact.

3.28

qualification

process of establishing that an analytical method is suitable for its intended use

3.29

qualitative analysis

analytical approach which estimates an analyte's concentration by using the response from a surrogate substance (or substances) chosen without specifically addressing or considering the relative responses of the analyte and the surrogate(s)

3.30

quantification

process of assigning a concentration to an analyte present in a sample

Note 1 to entry: There are several possible levels as shown in 3.31, 3.32 and 3.33.

3.31

estimated quantitative analysis

analytical approach which estimates an analyte's concentration by using the response from a surrogate substance chosen without specifically addressing or considering the relative responses of the analyte and the surrogate

3.32

semi-quantitative analysis

analytical approach which provides an analyte’s concentration by using the response from a surrogate substance (or substances), specifically accounting for the relative responses of the analyte and the surrogate

3.33

quantitative analysis

analytical approach which establishes the most accurate estimate of an analyte's concentration by using a response function (calibration curve) generated specifically for the analyte via the use of a reference standard

Note 1 to entry: Estimated quantitative analysis is generally less accurate than semi-quantitative analysis, which is generally less accurate than quantitative analysis.

3.34

safety concern threshold

SCT

threshold below which a leachable (or an extractable as a probable leachable) has a dose so low that it presents a negligible safety concern from carcinogenic and non-carcinogenic toxic effects

Note 1 to entry: See Reference [27].

3.35

simulated-use extraction

extraction using a method that simulates clinical use

Note 1 to entry: A simulated-use extraction is performed to estimate the type and amount of substances that are expected to be released from a medical device during its clinical use. A simulated-use extraction is designed to produce an extractables profile that represents the worst-case leachables profile, meaning that all leachables are also extractables and the levels of all individual extractables are at least equal to the level of all individual leachables.

3.36

solubilisation

action or process of using a vehicle to dissolve part or all of a test article

Note 1 to entry: Leaching, extraction, dissolution, and digestion are (progressively more complete) sub-categories of solubilisation.

3.37

sponsor

individual or organization that plans, commissions, and takes responsibility for testing of a medical device

3.38

supplier

person or company who manufactures or provides the materials of construction or components to be used in the manufacture of a medical device

3.39

threshold of toxicological concern

TTC

level of exposure for constituents, below which there would be no appreciable risk to human health

Note 1 to entry: See ISO/TS 21726 for full context.

3.40

toxicological risk assessment

act of determining the potential of a chemical to elicit an adverse effect based on a specified level of exposure