ISO/TS 5798:2022 インビトロ診断テストシステム—核酸増幅法による重症急性呼吸器症候群コロナウイルス2（SARS-CoV-2）の検出のための要件と推奨事項 | ページ 6

3.1

severe acute respiratory syndrome coronavirus 2

SARS-CoV-2

virus that causes coronavirus infectious disease 2019 (COVID-19)

3.2

specimen

primary sample

discrete portion of a body fluid, breath, hair or tissue taken for examination, study or analysis of one or more quantities or properties assumed to apply for the whole

Note 1 to entry: The Global Harmonisation Task Force (GHTF) uses the term specimen in its harmonized guidance documents to mean a sample of biological origin intended for examination by a medical laboratory.

Note 2 to entry: In some countries, the term “specimen” is used instead of “primary sample” (or a subsample of it), which is the sample prepared for sending to, or as received by, the laboratory and which is intended for examination.

[SOURCE:ISO 15189:2012, 3.16^[6] modified — Note 2 to entry was removed and Note 3 to entry was renumbered as Note 2 to entry.]

3.3

sample

one or more parts taken from a primary sample (3.2)

[SOURCE:ISO 15189:2012, 3.24^[6]]

3.4

reverse transcription

RT

process of making complementary DNA [ cDNA (3.6) ] from an RNA (3.20) template (3.22) , using the enzymatic activity of a reverse transcriptase associated with one or more oligonucleotide primers under a suitable set of conditions

[SOURCE:ISO 16577:2016, 3.180^[7], modified — Replaced “DNA” with “complementary DNA (cDNA)”.]

3.5

deoxyribonucleic acid

DNA

polymer of deoxyribonucleotides occurring in a double-stranded (dsDNA) or single-stranded (ssDNA) form

[SOURCE:ISO 22174:2005, 3.1.2^[8]]

3.6

complementary DNA

cDNA

single-stranded DNA (3.5) , complementary to a given RNA (3.20) and synthesised in the presence of reverse transcriptase to serve as a template (3.22) for DNA amplification

[SOURCE:ISO 20395:2019, 3.5^[9]]

3.7

analytical specificity

capability of a measuring system, using a specified measurement procedure, to provide measurement results for one or more measurands which do not depend on each other nor on any other quantity in the system undergoing measurement

Note 1 to entry: Lack of analytical specificity is called analytical interference (see ISO 18113-1:2009, A.3.2).

[SOURCE:ISO 18113-1:2009, A.3.4^[10]]

3.8

limit of detection

LOD

measured quantity value, obtained by a given measurement procedure, for which the probability of falsely claiming the absence of a component in a material is 0,05, given a probability of 0,05 of falsely claiming its presence

[SOURCE:ISO/IEC Guide 99:2007, 4.18^[11], modified — “β, given a probability α” was replaced by “0,05, given a probability of 0,05” and Notes 1 to 3 to entry were deleted.]

3.9

verification

provision of objective evidence that a given item fulfils specified requirements

[SOURCE:ISO/IEC Guide 99:2007, 2.44^[11], modified —EXAMPLES 1 to 3 and Notes 1 to 6 to entry were deleted.]

3.10

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 word “validated” is used to designate the corresponding status.

[SOURCE:ISO 9000:2015, 3.8.13^[12], modified — Notes 1 and 3 to entry were deleted and Note 2 to entry was renamed Note 1 to entry.]

3.11

amplicon

specific DNA (3.5) fragment produced by a DNA-amplification technology, such as the polymerase chain reaction (PCR) (3.12)

[SOURCE:ISO 13495:2013, 3.3.1^[13]]

3.12

polymerase chain reaction

PCR

enzymatic procedure which allows in vitro amplification of DNA (3.5) or RNA (3.20)

[SOURCE:ISO 22174:2005, 3.4.1^[8], modified — “or RNA” added to the end of the definition and “in vitro” has been unitalicized in accordance with the ISO House Style.]

3.13

reference material

material, sufficiently homogeneous and stable with reference to specified properties, which has been established to be fit for its intended use in measurement or in examination of nominal properties

[SOURCE:ISO/IEC Guide 99:2007, 5.13^[11], modified — Notes 1 to 8 to entry and EXAMPLES 1 to 5 were deleted.]

3.14

pseudo-virus

virus or virus-like particle that can integrate the envelope glycoprotein of another virus to form a virus with an exogenous viral envelope, and the genome retains the characteristics of the retrovirus itself

3.15

digital PCR

dPCR

procedure in which nucleic acid templates (3.22) are distributed across multiple partitions of nominally equivalent volume, such that some partitions contain template and others do not, followed by PCR (3.12) amplification of target sequences and detection of specific PCR products, providing a count of the number of partitions with a positive and negative signal for the target template

Note 1 to entry: Nucleic acid target sequences are assumed to be randomly and independently distributed across the partitions during the partitioning process.

Note 2 to entry: The count of positive and negative partitions is normally based on end point detection of PCR products following thermal cycling, however real-time qPCR (3.16) monitoring of PCR product accumulation is additionally possible for some dPCR platforms.

[SOURCE:ISO 20395:2019, 3.10^[9]]

3.16

quantitative real-time PCR

qPCR

enzymatic procedure which combines the in vitro amplification of specific DNA (3.5) or RNA (3.20) segments with the detection and quantification of specific PCR (3.12) products during the amplification process

Note 1 to entry: While the PCR is producing copies of the relevant DNA sequence, the fluorescent marker fluoresces in direct proportion to the amount of DNA present, which can theoretically be back-calculated to infer the original amount of that particular DNA present in a sample (3.3) prior to initiation of PCR.

[SOURCE:ISO 20395:2019, 3.25^[9], modified — “RNA” was added.]

3.17

quantification cycle

C_q

quantitative real-time PCR (qPCR) (3.16) cycle at which the fluorescence from the reaction crosses a specified threshold level at which the signal can be distinguished from background levels

Note 1 to entry: Quantification cycle is a generic term which includes cycle threshold (C_t), crossing point (C_p), take off point and all other instrument specific terms referring to the fractional cycle which is proportional to the concentration of target in the qPCR assay.

Note 2 to entry: The quantification cycle is based either on a threshold applied to all samples (3.3) or on a regression analysis of the signal, for each sample.

Note 3 to entry: The quantification cycle is a measure with poor reproducibility and cannot be used when comparing kit performance.

Note 4 to entry: Laboratory based considerations sometimes lead to selection of a cut-off for the cycle number. The cut-off cannot be chosen not to have a detrimental influence on available limit of detection (3.8) .

Note 5 to entry:C_q does not apply for digital PCR (3.15) and isothermal amplification methods.

[SOURCE:ISO 20395:2019, 3.8^[9], modified — Notes 3 to 5 to entry have been added.]

3.18

clinical specificity

diagnostic specificity

ability of an in vitro diagnostic examination procedure to recognize the absence of a target marker associated with a particular disease or condition

Note 1 to entry: Also defined as “percent negativity” in samples (3.3) where the target marker is known to be absent.

Note 2 to entry: Clinical specificity is expressed as a percentage (number fraction multiplied by 100), calculated as 100 × the number of true negative values (TN) divided by the sum of the number of true negative plus the number of false positive (FP) values, or 100 × TN/ (TN + FP). This calculation is based on a study design where only one sample is taken from each subject.

Note 3 to entry: The target condition is defined by criteria independent of the examination procedure under consideration.

[SOURCE:ISO 18113-1:2009, A.3.16^[10]]

3.19

clinical sensitivity

diagnostic sensitivity

ability of an in vitro diagnostic examination procedure to identify the presence of a target marker associated with a particular disease or condition

Note 1 to entry: Also defined as “percent positivity” in samples (3.3) where the target marker is known to be present.

Note 2 to entry: Diagnostic sensitivity is expressed as a percentage (number fraction multiplied by 100), calculated as 100 × the number of true positive values (TP) divided by the sum of the number of true positive values (TP) plus the number of false negative values (FN), or 100 × TP/(TP + FN). This calculation is based on a study design where only one sample is taken from each subject.

Note 3 to entry: The target condition is defined by criteria independent of the examination procedure under consideration.

[SOURCE:ISO 18113-1:2009, A.3.15^[10]]

3.20

ribonucleic acid

RNA

polymer of ribonucleotides occurring in a double-stranded or single-stranded form

[SOURCE:ISO 22174:2005, 3.1.3^[8]]

3.21

calibrator

measurement standard used for calibration

[SOURCE:ISO 20395:2019, 3.4^[9], modified — Note 1 to entry and the EXAMPLE were deleted.]

3.22

template

strand of DNA (3.5) or RNA (3.21) that specifies the base sequence of a newly synthesized strand of DNAorRNA, the two strands being complementary

[SOURCE:ISO 16577:2016, 3.206^[7]]

3.23

saliva

whole saliva

bio-fluid of the mouth composed mainly of secretion originating from the three major salivary glands (parotids, submandibular and sublingual glands) and from salivary glands present in the oral cavity

[SOURCE:ISO 4307:2021, 3.15^[14]]

3.24

reverse transcription polymerase chain reaction

RT-PCR

process that combines RT (3.4) and PCR (3.12) to allow amplification of cDNA (3.6) target as a route to detect RNA (3.20) templates (3.22)

Note 1 to entry: This can be conducted using various formats. A popular approach uses real time PCR instrumentation which simultaneously conducts the PCR and the analysis; this is described as reverse transcription quantitative PCR [RT- qPCR (3.16) ].

Note 2 to entry: Adapted from ISO 20395:2019, 3.31 ^[9].

3.25

in vitro diagnostic medical device

IVD medical device

device, whether used alone or in combination, intended by the manufacturer for the in vitro examination of specimens (3.2) derived from the human body solely or principally to provide information for diagnostic, monitoring or compatibility purposes and including reagents, calibrators (3.21) , control materials, specimen receptacles, software, and related instruments or apparatus or other articles

[SOURCE:ISO 17511:2020, 3.21^[15]]

3.26

pre-examination processes

processes that include preparation and identification of the patient, collection of the primary specimen(s) (3.2) , transportation to and within the medical laboratory, and isolation of RNA (3.20)

Note 1 to entry: Pre-analysis or pre-analytics are synonymous with pre-examination.

Note 2 to entry: Adapted from ISO 15189:2012, 3.15 ^[6].

3.27

limit of quantification

LOQ

lowest concentration or content of the analyte of interest per defined amount of matrix (3.31) that can be measured with reasonable statistical certainty consistently under the experimental conditions specified in the method

Note 1 to entry: Generally expressed in terms of the signal or measurement (true) value that will produce estimates having a specified relative standard deviation (RSD).

[SOURCE:ISO 16577:2016, 3.91^[7]]

3.28

positive PCR control

reliable source of well-characterized positive sample (3.3) material, containing intact target nucleic acid sequences for PCR (3.12)

[SOURCE:ISO 16577:2016, 3.150^[7], modified — Note 1 to entry was deleted.]

3.29

internal inhibition control

material acting as an internal control and obtained during the amplification reaction of the target fragment by adding DNA (3.5) or primers

Note 1 to entry: This material is clearly different from the target fragment.

Note 2 to entry: Adapted from ISO 16577:2016, 3.82 ^[7].

3.30

laboratory developed test

LDT

test developed (or modified) and used within a single laboratory to carry out testing on samples (3.3) ここで, the results are intended to assist in clinical diagnosis or to be used in making decisions concerning clinical management

Note 1 to entry: Laboratory developed test needs to be validated for its intended use before putting into service.

Note 2 to entry: Adapted from ISO 17822:2020, 3.23 ^[16].

3.31

matrix

components of a material system, except the analyte

[SOURCE:ISO 15193:2009, 3.6^[17]]

3.32

matrix effect

influence of a property of the sample (3.3) , independent of the presence of the analyte, on the measurement and thereby on the measured quantity value

[SOURCE:ISO 15194:2009, 3.7^[18], modified — Notes 1 to 2 to entry and the EXAMPLE were deleted.]

3.33

no template control

NTC

control reaction containing all reagents except the extracted test sample (3.3) template (3.22) nucleic acid

Note 1 to entry: This control is used to demonstrate the absence of contaminating nucleic acids. Instead of the template DNA, for example, a corresponding volume of nucleic acid free water is added to the reaction. The term “PCR reagent control” is also sometimes used.

[SOURCE:ISO 20395:2019, 3.20^[9]]

3.34

loop-mediated isothermal amplification

LAMP

strategy for achieving isothermal DNA (3.5) amplification by utilizing two or three uniquely designed primer sets and a polymerase with high strand displacement activity

[SOURCE:ISO 16577:2016, 3.94^[7]]