ISO 11737-3:2023 ヘルスケア製品の滅菌 — 微生物学的方法 — Part 3: 細菌のエンドトキシン検査 | ページ 6

3.1

bacterial endotoxins test

BET

assay for measuring bacterial endotoxins by combining an aqueous test sample or test sample extract with Tachypleus amebocyte lysate (TAL) (3.41) orLimulus amebocyte lysate (LAL) (3.28) reagent and measuring the resulting proportional reaction via visual, turbidimetric (3.42) or chromogenic techniques (3.3)

3.2

batch

defined quantity of a product intended or purported to be uniform in character and quality produced during a specified cycle of manufacture

[SOURCE:ISO 11139:2018, 3.21]

3.3

chromogenic technique

bacterial endotoxins test (BET) (3.1) methodology that quantifies endotoxins on the basis of a measured colour-producing reaction proportional to the interaction of Limulus amebocyte lysate (LAL) (3.28) and endotoxin

3.4

control standard endotoxin

CSE

endotoxin standard preparation whose potency has been standardized against the Reference Standard Endotoxin (RSE) (3.37) for a specific batch of Limulus amebocyte lysate (LAL) (3.28)

3.5

depyrogenation

process used to remove or deactivate pyrogenic substances to a specified level

Note 1 to entry: Pyrogenic substances include bacterial endotoxins.

[SOURCE:ISO 11139:2018, 3.77]

3.6

direct contact

medical device or medical device component that comes into physical contact with body tissue

[SOURCE:ISO 10993‑1:2018, 3.6]

3.7

end product

product samples that have completed the entire manufacturing process

Note 1 to entry: For the purposes of this document, end-product testing can be performed prior to sterilization (pre-sterilization samples) or after sterilization (post-sterilization samples). For limitations see 5.2.6.

3.8

endotoxin

bacterial endotoxin

lipopolysaccharide (LPS) (3.29) component of the cell wall of Gram-negative bacteria that is heat stable and elicits a variety of inflammatory responses in animals and humans

[SOURCE:ISO 11139:2018, 3.101]

3.9

endotoxin limit

maximum allowable amount of endotoxin present on the product or in a product extraction solution

3.10

endotoxin unit

eu

international unit

iu

standard unit of measure for endotoxin activity initially established relative to the activity contained in 0,2 ng of the Reference Standard Endotoxin (RSE) (3.37) Lot EC-2 [US Pharmacopeia (USP) standard reference material]

Note 1 to entry: Currently, the US RSE EC-6, USP Lot G, and the World Health Organization’s primary international endotoxin standard (IS) are sub-lots of the same endotoxin preparation, making the EU and IU equal ^[45].

3.11

end point

most dilute concentration of a test or control solution for which a positive reaction for bacterial endotoxin is observed

Note 1 to entry: This definition is used for concentration dependent bacterial endotoxin testing, in contrast to dilution dependent end point methods described in A.6.1.1.

3.12

enhancement

bacterial endotoxins test (BET) (3.1) anomaly in which a non-endotoxin related factor, usually attributable to a characteristic of the test sample, elicits a test reaction greater than the amount of endotoxin present

3.13

gel-clot technique

bacterial endotoxins test (BET) (3.1) methodology that quantifies or detects endotoxin on the basis of a clot-producing reaction proportional to the interaction of Limulus amebocyte lysate (LAL) (3.28) and endotoxin

3.14

geometric mean end point

antilog of the average of the logarithmic values with respect to the end points (3.11) from replicate dilution series converted back to a base 10 number used to establish the central tendency or typical value from a test solution

3.15

health care product

medical device, including in vitro diagnostic medical device, or medicinal product, including biopharmaceutical

[SOURCE:ISO 11139:2018, 3.132]

3.16

indirect contact

medical device or medical 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 medical device or medical device component itself does not physically contact body tissue)

[SOURCE:ISO 10993‑1:2018, 3.11]

3.17

inhibition

bacterial endotoxins test (BET) (3.1) anomaly in which a non-endotoxin related factor, usually attributable to a characteristic of the test sample, elicits a test reaction less than the amount of endotoxin present

3.18

method suitability

inhibition/enhancement test

test used to determine whether a particular sample contains interfering factors that diminish its accuracy by introducing enhancement (3.12) or inhibition (3.17) into the test system

3.19

interference

interfering factor observed in the performance of the test that exceeds the acceptable threshold for a given bacterial endotoxins test (BET) (3.1) technique (e.g. positive product control that indicates a detected endotoxin level less than 50 % or greater than 200 % or ±2 lambda)

3.20

intraocular , adj.

located or occurring within or administered through the eye

3.21

interfering factors

non-endotoxin related factor, usually attributable to a characteristic of the test sample, that causes inhibition (3.17) or enhancement (3.12)

3.22

intravascular , adj.

located or occurring within or administered through the heart or blood vessels

3.23

intralymphatic , adj.

located or occurring within or administered through a lymph vessel

3.24

intrathecal , adj.

located, or occurring within or administered through the space under the arachnoid membrane of the brain or spinal cord

3.25

kinetic method

photometric quantitative techniques (turbidimetric or chromogenic) for bacterial endotoxins test (BET) (3.1)

3.26

LAL reactive material

LAL-RM

Limulus amebocyte lysate reactive material

any non-endotoxin compound that will activate the Limulus amebocyte lysate (LAL) (3.28) clotting cascade and cause enhancement (3.12)

3.27

lambda

λ

labelled sensitivity of a Limulus amebocyte lysate (LAL) (3.28) gel-clot reagent, expressed in EU/ml or, for chromogenic or turbidimetric tests, the lowest point (endotoxin concentration) on the referenced standard curve

3.28

Limulus amebocyte lysate

LAL

reagent extracted from amebocytes taken from hemolymph of the horseshoe crab, Limulus polyphemus, that reacts with endotoxin, to form a gelatinous clot and is used to estimate endotoxin levels in bacterial endotoxins test (BET) (3.1) methods

Note 1 to entry: The term LAL is sometimes used to describe Tachypleus amebocyte lysate (TAL) (3.41) , as both are similar lysates that are used in the BET. They also are often generically referred to as “lysate”.

3.29

lipopolysaccharide

LPS

Gram-negative bacterial cell wall component composed of lipid A, a core polysaccharide, and an O-side chain

3.30

maximum valid dilution

MVD

maximum amount a sample can be diluted, or the total extraction volume used relative to the sensitivity of a bacterial endotoxins test (BET) (3.1) in which the specified endotoxin limit (3.9) can be detected

3.31

medical device

[SOURCE:ISO 11139:2018, 3.166]

3.32

non-pyrogenic , adj.

not inducing a fever

Note 1 to entry: Describes an item or product that contains endotoxin levels that conform to specified limits.

3.33

out of specified limits

OSL

sample with a valid bacterial endotoxins test (BET) (3.1) result that exceeds a product endotoxin limit (3.9) specification

Note 1 to entry: The term OSL applies only within the context of this document and does not imply compliance with any other regulatory guidance dealing with out of specification (OOS) results.

3.34

product positive control

PPC

sample spiked with a known amount of endotoxin used for confirmation that the product being tested is not subject to interfering factors (3.21)

3.35

pyrogen

substance that induces a fever

3.36

pyrogenic , adj.

inducing a fever

Note 1 to entry: Describes an item or product that contains endotoxin levels above specified limits.

3.37

Reference Standard Endotoxin

RSE

US Pharmacopeia (USP) endotoxin reference standard that has a defined potency of 10 000 USP EUs per vial

3.38

repeat test

analysis of additional product samples from a previously tested batch or another batch

3.39

retest

reanalysis of previously tested product samples or product sample preparation

3.40

standard control series

serial dilution series of Reference Standard Endotoxin (RSE) (3.37) or control standard endotoxin (CSE) (3.4) used to verify Limulus amebocyte lysate (LAL) (3.28) sensitivity

3.41

Tachypleus amebocyte lysate

TAL

reagent extracted from amebocytes taken from hemolymph of the horseshoe crab, Tachypleus tridentatus, which reacts with endotoxin, to form a gelatinous clot and is used to estimate endotoxin levels in bacterial endotoxins test (BET) (3.1) methods

Note 1 to entry: The term TAL is sometimes used to describe Limulus amebocyte lysate (LAL) (3.28) , as both are similar lysates that are used in the BET. They also are often generically referred to as “lysate”.

3.42

turbidimetric technique

bacterial endotoxins test (BET) (3.1) methodology that quantifies or detects endotoxin on the basis of a measured turbidity reaction proportional to the interaction of Limulus amebocyte lysate (LAL) (3.28) and endotoxin

3.43

validation

confirmation, through the provision of objective evidence, that the requirements for a specific intended use or application have been fulfilled

Note 1 to entry: The objective evidence needed for a validation is the result of a test or other form of determination such as performing alternative calculations or reviewing documents.

Note 2 to entry: The word “validated” is used to designate the corresponding status.

Note 3 to entry: The use conditions for validation can be real or simulated.

[SOURCE:ISO 11139:2018, 3.313]

3.44

verification

confirmation, through the provision of objective evidence, that specified requirements have been fulfilled

Note 1 to entry: The objective evidence needed for a verification can be the result of an inspection or of other forms of determination such as performing alternative calculations or reviewing documents.

Note 2 to entry: The word “verified” is used to designate the corresponding status.

[SOURCE:ISO 11139:2018, 3.314]

3.45

water for bacterial endotoxins test

WBET

purified water employable as a solvent, diluent, and/or extractant that is non-reactive with the lysate employed at the detection limit of the reagent, and does not elicit interference (3.19) with methodology in use (typically Limulus amebocyte lysate (LAL) (3.28) reagent water, water for injection, or other appropriate solution meeting these requirements)