Molecular in vitro diagnostic examinations - Specifications for pre-examination processes for Fine Needle Aspirates (FNAs) - Part 2: Isolated proteins

This document gives guidelines on the handling, documentation, storage and processing of fine needle aspirates (FNAs) intended for protein examination during the pre-examination phase before a molecular examination is performed.
This document is applicable to molecular in vitro diagnostic examinations including laboratory developed tests performed by medical laboratories and molecular pathology laboratories that examine proteins isolated from FNAs. It is also intended to be used by laboratory customers, in vitro diagnostics developers and manufacturers, biobanks, institutions and commercial organisations performing biomedical research, and regulatory authorities.
Different dedicated measures are taken for collecting, stabilizing, transporting and storing of core needle biopsies (FNA Biopsy or FNA B) and are not covered in this document, but in EN ISO 20184-2, Molecular in vitro diagnostic examinations - Specifications for pre-examination processes for frozen tissue - Part 2: Isolated proteins and EN ISO 20166-2, Molecular in vitro diagnostic examinations - Specifications for pre-examination processes for formalin fixed and paraffin-embedded (FFPE) tissue - Part 2: Isolated proteins.
This document is not applicable for protein examination by immunohistochemistry.
NOTE International, national or regional regulations or requirements can also apply to specific topics covered in this document.

Molekularanalytische in-vitro-diagnostische Verfahren - Spezifikationen für präanalytische Prozesse für Feinnadelaspirate - Teil 2: Isolierte Proteine

Dieses Dokument gibt Leitlinien für die Handhabung, Dokumentation, Lagerung und Verarbeitung von Feinnadelaspiraten (FNAs) zur Proteinuntersuchung während der präanalytischen Phase vor Beginn der molekularen Analyse.
Dieses Dokument ist anzuwenden für molekulare in vitro-diagnostische Untersuchungen, wozu auch laboreigene Prüfungen zählen, die von medizinischen Laboratorien und Laboratorien der molekularen Pathologie zur Untersuchung der aus FNAs isolierten Proteine durchgeführt werden. Es soll auch von Laborkunden, Entwicklern und Herstellern von In vitro-Diagnostika, Biobanken, Einrichtungen und kommerziellen Organisationen, die in der biomedizinischen Forschung tätig sind, sowie Aufsichtsbehörden angewendet werden.
Für die Entnahme, die Stabilisierung, den Transport und die Lagerung von Stanzbiopsien (FNA Biopsie oder FNA B) werden verschiedene spezielle Maßnahmen ergriffen, die nicht in diesem Dokument behandelt werden, sondern in EN ISO 20184 2 Molekularanalytische in vitro-diagnostische Verfahren — Spezifikationen für präanalytische Prozesse für gefrorene Gewebeproben —Teil 2: Isolierte Proteine und EN ISO 20166 2 Molekularanalytische in vitro-diagnostische Verfahren — Spezifikationen für präanalytische Prozesse für formalinfixierte und paraffineingebettete (FFPE) Gewebeproben — Teil 2: Isolierte Proteine.
Dieses Dokument ist nicht anzuwenden für Proteinuntersuchungen durch Immunhistochemie.
ANMERKUNG   Zu bestimmten Bereichen, die in diesem Dokument behandelt werden, können auch internationale, nationale oder regionale Bestimmungen oder Anforderungen gelten.

Analyses moléculaires de diagnostic in vitro - Spécifications pour les processus préanalytiques pour les ponctions à l’aiguille fine - Partie 2 : Protéines extradites

Molekularne diagnostične preiskave in vitro - Specifikacije za predpreiskovalne procese pri aspiraciji s tanko iglo (FNA) - 2. del: Izolirani proteini

Ta dokument podaja smernice za obravnavo, dokumentiranje, shranjevanje in obdelavo aspiratov, pridobljenih z aspiracijsko biopsijo s tanko iglo (FNA), namenjenih za pregled proteinov med predpreiskovalno fazo, preden se izvede molekularna preiskava.
Ta dokument se uporablja za molekularne diagnostične preiskave in vitro, vključno z laboratorijsko razvitimi preskusi, ki jih izvajajo v medicinskih laboratorijih in laboratorijih za molekularno patologijo, kjer preiskujejo proteine, izolirane iz aspiratov, pridobljenih z aspiracijsko biopsijo s tanko iglo. Namenjen je tudi temu, da ga uporabljajo laboratorijske stranke, razvijalci in proizvajalci diagnostike in vitro, biobanke, institucije in komercialne organizacije, ki izvajajo biomedicinske raziskave, ter regulativni organi.
Za zbiranje, stabiliziranje, prevoz in shrambo aspiratov, pridobljenih z aspiracijsko biopsijo z debelo iglo (biopsija FNA oz. FNA B) se uporabljajo drugačni namenski ukrepi, ki niso zajeti v tem dokumentu, temveč v standardih EN ISO 20184-2, Molekularne diagnostične preiskave in vitro – Specifikacije za predpreiskovalne procese za zamrznjena tkiva – 2. del: Izolirani proteini in EN ISO 20166-2, Molekularne diagnostične preiskave in vitro – Specifikacije za predpreiskovalne procese za tkiva, ki so fiksirana v formalinu ter položena v parafin – 2. del: Izolirani proteini.
Ta dokument se ne uporablja za preiskave proteinov z imunohistokemijo.
OPOMBA:   Za določene teme, ki so zajete v tem dokumentu, lahko veljajo tudi mednarodni, nacionalni ali regionalni predpisi ali zahteve.

General Information

Status
Published
Publication Date
21-Dec-2021
Current Stage
6060 - Definitive text made available (DAV) - Publishing
Start Date
22-Dec-2021
Due Date
01-Dec-2020
Completion Date
22-Dec-2021

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Standards Content (Sample)

SLOVENSKI STANDARD
SIST-TS CEN/TS 17688-2:2022
01-februar-2022
Molekularne diagnostične preiskave in vitro - Specifikacije za predpreiskovalne
procese pri aspiraciji s tanko iglo (FNA) - 2. del: Izolirani proteini

Molecular in vitro diagnostic examinations - Specifications for pre-examination processes

for Fine Needle Aspirates (FNAs) - Part 2: Isolated proteins
Molekularanalytische in‐vitro‐diagnostische Verfahren - Spezifikationen für
präanalytische Prozesse für Feinnadelaspirate - Teil 2: Isolierte Proteine
Analyses moléculaires de diagnostic in vitro - Spécifications pour les processus

préanalytiques pour les ponctions à l’aiguille fine - Partie 2 : Protéines extradites

Ta slovenski standard je istoveten z: CEN/TS 17688-2:2021
ICS:
11.100.10 Diagnostični preskusni In vitro diagnostic test
sistemi in vitro systems
SIST-TS CEN/TS 17688-2:2022 en,fr,de

2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.

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SIST-TS CEN/TS 17688-2:2022
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SIST-TS CEN/TS 17688-2:2022
CEN/TS 17688-2
TECHNICAL SPECIFICATION
SPÉCIFICATION TECHNIQUE
December 2021
TECHNISCHE SPEZIFIKATION
ICS 11.100.10
English Version
Molecular in vitro diagnostic examinations - Specifications
for pre-examination processes for Fine Needle Aspirates
(FNAs) - Part 2: Isolated proteins

Analyses moléculaires de diagnostic in vitro - Molekularanalytische in-vitro-diagnostische Verfahren

Spécifications pour les processus préanalytiques pour - Spezifikationen für präanalytische Prozesse für

les ponctions à l'aiguille fine - Partie 2 : Protéines Feinnadelaspirate - Teil 2: Isolierte Proteine

extradites

This Technical Specification (CEN/TS) was approved by CEN on 15 November 2021 for provisional application.

The period of validity of this CEN/TS is limited initially to three years. After two years the members of CEN will be requested to

submit their comments, particularly on the question whether the CEN/TS can be converted into a European Standard.

CEN members are required to announce the existence of this CEN/TS in the same way as for an EN and to make the CEN/TS

available promptly at national level in an appropriate form. It is permissible to keep conflicting national standards in force (in

parallel to the CEN/TS) until the final decision about the possible conversion of the CEN/TS into an EN is reached.

CEN members are the national standards bodies of Austria, Belgium, Bulgaria, Croatia, Cyprus, Czech Republic, Denmark, Estonia,

Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway,

Poland, Portugal, Republic of North Macedonia, Romania, Serbia, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey and

United Kingdom.
EUROPEAN COMMITTEE FOR STANDARDIZATION
COMITÉ EUROPÉEN DE NORMALISATION
EUROPÄISCHES KOMITEE FÜR NORMUNG
CEN-CENELEC Management Centre: Rue de la Science 23, B-1040 Brussels

© 2021 CEN All rights of exploitation in any form and by any means reserved Ref. No. CEN/TS 17688-2:2021 E

worldwide for CEN national Members.
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CEN/TS 17688-2:2021 (E)
Contents Page

European foreword ....................................................................................................................................................... 3

Introduction .................................................................................................................................................................... 4

1 Scope .................................................................................................................................................................... 5

2 Normative references .................................................................................................................................... 5

3 Terms and definitions ................................................................................................................................... 5

4 General considerations .............................................................................................................................. 11

5 Outside the laboratory ............................................................................................................................... 12

5.1 Specimen collection ..................................................................................................................................... 12

5.1.1 General ............................................................................................................................................................. 12

5.1.2 Information about the specimen donor/patient .............................................................................. 12

5.1.3 Information about the specimen ............................................................................................................ 13

5.1.4 Selection of the primary FNA collection device ................................................................................. 13

5.1.5 FNA specimen collection and processing from the donor/patient ............................................ 13

5.2 Specimen storage and transport ............................................................................................................ 15

6 Inside the laboratory .................................................................................................................................. 15

6.1 Specimen reception ..................................................................................................................................... 15

6.2 Specimen/sample storage after transport and reception ............................................................. 15

6.2.1 General ............................................................................................................................................................. 15

6.2.2 Storage of FNA specimen/samples using collection devices with stabilizer .......................... 16

6.2.3 Storage of FNA specimen/samples using collection devices without stabilizers ................. 16

6.3 Specimen/sample processing for cytological examination prior to protein isolation ....... 16

6.3.1 General ............................................................................................................................................................. 16

6.3.2 Handling of cell suspension ...................................................................................................................... 17

6.3.3 Preparation of paraffin-embedded cell blocks.................................................................................. 18

6.3.4 Preparation of cell suspension slides ................................................................................................... 19

6.4 Evaluation of the pathology of the specimen or sample(s) ........................................................... 19

6.5 Processed sample storage, transport and reception ....................................................................... 20

6.5.1 General ............................................................................................................................................................. 20

6.5.2 Storage and transport of cell suspension ............................................................................................ 20

6.5.3 Storage and transport of paraffin-embedded cell blocks .............................................................. 20

6.5.4 Storage and transport of cell suspension slides ............................................................................... 21

6.6 Isolation of protein ...................................................................................................................................... 21

6.6.1 General ............................................................................................................................................................. 21

6.6.2 Using a commercial protein isolation kit intended for diagnostic use ..................................... 21

6.6.3 Using the laboratory’s own protein isolation procedure .............................................................. 22

6.6.4 Isolation of proteins from specific sample types .............................................................................. 22

6.7 Quantity and quality assessment of isolated proteins.................................................................... 23

6.8 Storage of isolated proteins ..................................................................................................................... 23

Bibliography ................................................................................................................................................................. 25

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CEN/TS 17688-2:2021 (E)
European foreword

This document (CEN/TS 17688-2:2021) has been prepared by Technical Committee CEN/TC 140 “In

vitro diagnostic medical devices”, the secretariat of which is held by DIN.

Attention is drawn to the possibility that some of the elements of this document may be the subject of

patent rights. CEN shall not be held responsible for identifying any or all such patent rights.

Any feedback and questions on this document should be directed to the users’ national standards body.

A complete listing of these bodies can be found on the CEN website.

According to the CEN/CENELEC Internal Regulations, the national standards organisations of the

following countries are bound to announce this Technical Specification: Austria, Belgium, Bulgaria,

Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland,

Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Republic of

North Macedonia, Romania, Serbia, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey and the United

Kingdom.
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CEN/TS 17688-2:2021 (E)
Introduction

Molecular in vitro diagnostics has enabled significant progress in medicine. Further progress is expected

by new technologies analysing profiles of nucleic acids, proteins, and metabolites in human tissues and

body fluids. However, the profiles of these molecules can change drastically during the pre-examination

process, including the specimen collection, transport, storage and processing.

Examination of proteins is commonly used in clinical practice. This includes e.g. prognostic and predictive

biomarker examinations. This is a fast growing field in molecular diagnostics.

Fine needle aspiration is a non-surgical procedure that uses a thin, hollow-bore needle and syringe to

collect a specimen from patients for cytopathological and molecular investigation. As a minimally-

invasive technique, fine needle aspirates (FNAs) are commonly used to diagnose and monitor for example

a range of cancer types, e.g. breast, lung and thyroid cancer, and other diseases, such as inflammatory

diseases. FNAs also provide the opportunity to sample metastatic sites (e.g. lymph nodes) and otherwise

non-resectable tissues.

Besides cytological assessment, molecular biological analysis of FNAs is expected to become increasingly

used for cancer and other disease diagnostics, including companion diagnostics.

One of the challenges facing molecular analysis of FNA samples is their small size and diversity in

composition (cells, blood, body fluid). The low cellular content of FNAs means that the yield of isolated

proteins is typically towards the lower end of detection for molecular examination. Therefore, the protein

isolation procedure should provide a sufficient amount of protein as required by the specific examination.

Protein profiles, protein integrities, and protein–protein interactions in FNAs can change drastically

during and after collection (due to, e.g. gene induction, gene down regulation, protein degradation and

modification). Protein species amounts can change differently in different donors’/patients’ FNAs.

Therefore, standardization of the entire process from specimen collection to protein examination is

needed to minimize protein degradation and protein profile changes during and after FNA collection. This

document describes special measures which need to be taken to obtain good quality FNA

specimens/samples and isolated protein therefrom for molecular examination.
In this document, the following verbal forms are used:
— “shall” indicates a requirement;
— “should” indicates a recommendation;
— “may” indicates a permission;
— “can” indicates a possibility or a capability.
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CEN/TS 17688-2:2021 (E)
1 Scope

This document gives guidelines on the handling, documentation, storage and processing of fine needle

aspirates (FNAs) intended for protein examination during the pre-examination phase before a molecular

examination is performed.

This document is applicable to molecular in vitro diagnostic examinations including laboratory developed

tests performed by medical laboratories and molecular pathology laboratories that examine proteins

isolated from FNAs. It is also intended to be used by laboratory customers, in vitro diagnostics developers

and manufacturers, biobanks, institutions and commercial organisations performing biomedical

research, and regulatory authorities.

Different dedicated measures are taken for collecting, stabilizing, transporting and storing of core needle

biopsies (FNA Biopsy or FNA B) and are not covered in this document, but in EN ISO 20184-2, Molecular

in vitro diagnostic examinations — Specifications for pre-examination processes for frozen tissue — Part 2:

Isolated proteins and EN ISO 20166-2, Molecular in vitro diagnostic examinations — Specifications for pre-

examination processes for formalin fixed and paraffin-embedded (FFPE) tissue — Part 2: Isolated proteins.

This document is not applicable for protein examination by immunohistochemistry.

NOTE International, national or regional regulations or requirements can also apply to specific topics covered

in this document.
2 Normative references

The following documents are referred to in the text in such a way that some or all of their content

constitutes requirements of this document. For dated references, only the edition cited applies. For

undated references, the latest edition of the referenced document (including any amendments) applies.

EN ISO 15189, Medical laboratories - Requirements for quality and competence (ISO 15189)

3 Terms and definitions

For the purposes of this document, the terms and definitions given in EN ISO 15189:2012 and the

following apply.

ISO and IEC maintain terminological databases for use in standardization at the following addresses:

— ISO Online browsing platform: available at https://www.iso.org/obp
— IEC Electropedia: available at https://www.electropedia.org/
3.1
aliquot

portion of a larger amount of homogenous material, assumed to be taken with negligible sampling error

Note 1 to entry: The term is usually applied to fluids. Tissues are heterogeneous and therefore cannot be

aliquoted.

Note 2 to entry: The definition is derived from the Compendium of Chemical Terminology Gold Book.

International Union of Pure and Applied Chemistry. Version 2.3.3., 2014; the PAC, 1990,62,1193 (Nomenclature for

sampling in analytical chemistry (Recommendations 1990)) p. 1206; and the PAC 1990, 62, 2167 (Glossary of

atmospheric chemistry terms (Recommendations 1990)) p. 2173.
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3.2
ambient temperature
unregulated temperature of the surrounding air
[SOURCE: EN ISO 20166-1:2018, 3.2]
3.3
analyte
component represented in the name of a measurable quantity
[SOURCE: ISO 17511:2020, 3.2, modified — Deleted example.]
3.4
biomolecule

organic molecule produced by living organisms that is involved in the maintenance and metabolic

processes of organisms

Note 1 to entry: Examples of organic molecules are protein, carbohydrate, lipid, or nucleic acid.

3.5
cell block
paraffin-embedded cell clot
3.6
cell clot

cell-rich liquid specimen/sample concentrated into a compact cell aggregate for subsequent processing

3.7
cytocentrifugation

cytology method that is specifically designed to concentrate cells on a slide by centrifugation

3.8
deoxyribonucleic acid
DNA

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

form
[SOURCE: EN ISO 22174:2005, 3.1.2]
3.9
diagnosis

identification of a disease from its signs and symptoms, where the diagnostic process can involve

examinations and tests for classification of an individual's condition into separate and distinct categories

or subclasses that allow medical decisions about treatment and prognosis to be made

[SOURCE: EN ISO 20166-1:2018, 3.7]
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3.10
examination
analytical test

set of operations with the objective of determining the value or characteristics of a property

Note 1 to entry: Processes that start with the in situ detection using antibodies, nucleic acid probes or dyes and

include all kinds of parameter testing or chemical manipulation for quantitative or qualitative examination.

[SOURCE: EN ISO 15189:2012, 3.7, modified — Notes to entry 1 to 3 have been removed. Note 1 to entry

has been added and “analytical test” has been added as a preferred term.]
3.11
examination manufacturer
analytical test manufacturer
entity that manufactures and/or produces a specific analytical test
3.12
examination performance
analytical test performance
analytical performance

accuracy, precision, and sensitivity of a test to measure the analyte of interest

Note 1 to entry: Other test performance characteristics such as robustness, repeatability can apply as well.

[SOURCE: EN ISO 20184-1:2018, 3.4]
3.13
fixative

solution used to preserve or harden FNA specimens for microscopic and molecular examination

3.14
formalin

saturated aqueous formaldehyde solution which at 100 % contains 37 % formaldehyde by mass

(corresponding to 40 % by volume)
[SOURCE: EN ISO 20166-1:2018, 3.11]
3.15
fine needle aspirate
FNA

specimen withdrawn by a non-operative procedure that uses a thin, hollow-bore needle

3.16
FNA primary collection device

thin, hollow-bore needle or syringe used for collecting the FNA specimen from the donor/patient

3.17
FNA secondary collection device

suitable container into which the specimen is transferred from the FNA primary collection device

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3.18
homogeneous
uniform in structure and composition
[SOURCE: EN ISO 20166-1:2018, 3.31]
3.19
laboratory developed procedure

modified commercially available in vitro diagnostic device or fully in house developed procedure

3.20
nonconformity
nonfulfillment of a requirement
[SOURCE: EN ISO 9000:2015, 3.6.9]
3.21
paraffin embedding

process in which a sample is placed in paraffin to generate a hard surrounding matrix so that thin

microscopic sections can be cut
3.22
pre-examination process
pre-analytical workflow
pre-analytical phase
pre-examination phase

process that starts, in chronological order, from the clinician’s request and includes the examination

request, preparation and identification of the patient, collection of the primary sample(s), transportation

to and within the analytical laboratory, isolation of analytes, and ends when the analytical examination

begins

Note 1 to entry: The pre-examination phase includes preparative processes that influence the outcome of the

intended examination.

[SOURCE: EN ISO 15189:2012, 3.15, modified — An additional term was added and more detail was

included.]
3.23
primary sample
specimen

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

[SOURCE: EN ISO 15189:2012, 3.16, modified — The term and definition is used here without the original

Notes.]
3.24
proficiency test

evaluation of participant performance against pre-established criteria by means of inter-laboratory

comparisons

[SOURCE: EN ISO/IEC 17043:2010, 3.7, modified — Term and definition are used here without the

original Notes.]
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3.25
protein

type of biological macromolecules composed of one or more chains with a defined sequence of amino

acids connected through peptide bonds
3.26
protein profile

amounts of the individual protein molecules that are present in a sample and that can be measured in the

absence of any losses, inhibition and interference
3.27
protein species

amounts of a chemically clearly-defined protein corresponding to one spot on a high-performance two-

dimensional gel electrophoresis pattern
[SOURCE: [16]]
3.28
post translational modifications
PTM

chemical alterations to a primary protein structure, often crucial for conferring biological activity on a

protein
[SOURCE: [17]]
3.29
ribonucleic acid
RNA

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

[SOURCE: EN ISO 22174:2005, 3.1.3]
3.30
room temperature
temperature in the range of 18 °C to 25 °C
Note 1 to entry: Local or national regulations can have different definitions.
[SOURCE: EN ISO 20166-1:2018, 3.22]
3.31
sample
one or more parts taken from a specimen
[SOURCE: EN ISO 15189:2012, 3.24, modified — Example has been removed.]
3.32
stability

ability of a sample material, when stored under specified conditions, to maintain a stated property value

within specified limits for a specified period of time

[SOURCE ISO Guide 30:2015, 2.1.15, modified — The words “reference material” were replaced by

“sample material”.]
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3.33
stabilizer

substance which has the ability to maintain a stated property value within specified limits for a specified

period of time of a sample material

Note 1 to entry: The substance can contain a fixative belonging to different fixative subgroups, e.g. crosslinking

fixatives (e.g. formalin) or coagulating fixatives (e.g. methanol, ethanol).
3.34
stabilization

process of maintaining a stated property value within specified limits for a specified period of time of a

specimen/sample material
3.35
standard buffered formalin solution
neutral buffered formalin
NBF

10 % formalin solution in water with a mass fraction of 3,7 % (corresponding to a volume fraction of 4

%) formaldehyde, buffered to pH 6,8 to pH 7,2

Note 1 to entry: Standard buffered formalin solutions often contain small amounts of methanol to inhibit

oxidation and polymerisation of formaldehyde.
[SOURCE: EN ISO 20166-1:2018, 3.25]
3.36
storage

prolonged interruption of the pre-analytical workflow of a sample or analyte respectively, or of their

derivatives, under appropriate conditions in order to preserve their properties

Note 1 to entry: Long-term storage typically occurs in laboratory archives or in biobanks.

[SOURCE: EN ISO 20184-1:2018, 3.21, modified — Example has been removed.]
3.37
tissue processor

automated instrument where tissue fixation, dehydration, clearing and impregnation (with paraffin)

occur
[SOURCE: EN ISO 20166-1:2018, 3.27]
3.38
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 term “validated” is used to designate the corresponding status.

[SOURCE: EN ISO 9000:2015, 3.8.13, modified — Note 1 and Note 3 have been omitted.]

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3.39
verification

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

Note 1 to entry: The term “verified” is used to designate the corresponding status.

Note 2 to entry: Confirmation can comprise activities such as:
— performing alternative calculations;

— comparing a new design specification with a similar proven design specification;

— undertaking tests and demonstrations;
— reviewing documents prior to issue.

[SOURCE: EN ISO 9000:2015, 3.8.12, modified — Note 1 and Note 2 have been omitted.]

3.40
workflow
series of activities necessary to complete a task
[SOURCE: EN ISO 20166-1:2018, 3.30]
4 General considerations

For general statements on medical laboratory quality management systems and in particular on

specimen collection, reception and handling (including avoidance of cross contaminations) see

EN ISO 15189, EN ISO/IEC 17020 or EN ISO/IEC 17025. ISO/TS 20658 and EN ISO 20387 (for

biobanking) can also apply. The requirements on laboratory equipment, reagents, and consumables

according to EN ISO 15189 shall be followed; EN ISO/IEC 17020 and EN ISO/IEC 17025 can also apply.

All steps of the pre-examination, examination and post-examination processes (i.e. the entire workflow)

can influence the diagnosis or research study results.

Thus, this entire workflow shall be specified, verified and validated during the development of the

examination, including the development of in vitro diagnostic (IVD) medical devices. This includes

specifically all pre-examination process steps such as the examination request, preparation and

identification of the patient, collection of the primary sample(s), transport to and within the medical

laboratory, storage and isolation of analytes. The specifications about the specimen transport and storage

shall also include information on the stability of the specimen's analyte profile including the timeframe

between collecting the specimen and its examination and storage conditions such as duration,

temperature limits and freeze/thaw cycles. The verification and validation shall take into account the

impact of the FNA specimen variability (e.g. by tissue type, heterogeneity, specimen quantity, presence

of blood cells) on the examination.

During the design and development of a FNA protein based examination, a risk assessment shall be

performed (see also EN ISO 14971). Mitigation measures for eliminating or reducing identified risks shall

be established, where required, for ensuring the performance of the examination. It shall especially be

investigated and ensured that the specific protein profile(s) intended to be analysed is/are not

compromised in a manner impacting the examination performance. This includes investigations on

whether and/or how the protein profile intended to be examined changes during storage and transport.

This can be done, e.g. by applying the intended examination to specimens/samples which underwent time

course studies, reflecting the individual pre-examination process steps such as transport and storage and

by implementing measures to prevent or reduce impacts by the identified pre-analytical variables.

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NOTE A time course experiment is a research design that involves repeated observations of the same variables

at specific intervals over a relevant time period (e.g. time 0, 12 h, 24 h, 36 h, 48 h). This is expected to reflect any

knowledge on the stability of the protein(s) of interest. Typically, this involves using aliquots from a homogeneous

starting material.

During the whole pre-examination process, precautions shall be taken to avoid cross contamination

between different specimens/samples (e.g. using single-use material whenever feasible or appropriate

cleaning procedures between processing of different specimens/samples), and to avoid mixing up of

specimens/samples.

During transportation and transient storage between pre-analytical workflow steps of viable cells,

protein profiles can change. In order to minimize pre-analytical impacts on protein profiles, the specimen

should therefore be placed in a collection device containing an appropriate stabilizer solution. The

maximum duration until the specimen is placed into stabilizer solution should be specified and verified.

The duration and the temperature before stabilization shall be documented.

Safety instructions for the whole pre-examination process shall be in place and followed. Safety

regulations on specimen/sample transport and handling shall be considered (see EN ISO 15189,

EN 15190 and ISO/TS 20658). If transport is required over public areas, corresponding regulations or

laws for packaging and transport apply (e.g. International Air Transport Association (IATA) for air

transport).

The manufacturer's material safety data sheet shall be considered for any potentially hazardous material

(e.g. stabilizers such as formaldehyde and methanol).

For all pre-examination steps, the examination manufacturer's instructions shall be followed.

Where, for justified reasons (e.g. unmet patient needs), a commercial product is not used in accordance

to the manufacturer's instructions, responsibility for its ver
...

SLOVENSKI STANDARD
kSIST-TS FprCEN/TS 17688-2:2021
01-september-2021
Molekularne diagnostične preiskave in vitro - Specifikacije za predpreiskovalne
procese pri aspiraciji s tanko iglo (FNA) - 2. del: Izolirani proteini

Molecular in vitro diagnostic examinations - Specifications for pre-examination processes

for Fine Needle Aspirates (FNAs) - Part 2: Isolated proteins
Molekularanalytische in‐vitro‐diagnostische Verfahren - Spezifikationen für
präanalytische Prozesse für Feinnadelaspirate - Teil 2: Isolierte Proteine
Analyses moléculaires de diagnostic in vitro - Spécifications pour les processus

préanalytiques pour les ponctions à l’aiguille fine - Partie 2 : Protéines extradites

Ta slovenski standard je istoveten z: FprCEN/TS 17688-2
ICS:
11.100.10 Diagnostični preskusni In vitro diagnostic test
sistemi in vitro systems
kSIST-TS FprCEN/TS 17688-2:2021 en,fr,de

2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.

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kSIST-TS FprCEN/TS 17688-2:2021
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kSIST-TS FprCEN/TS 17688-2:2021
FINAL DRAFT
TECHNICAL SPECIFICATION
FprCEN/TS 17688-2
SPÉCIFICATION TECHNIQUE
TECHNISCHE SPEZIFIKATION
July 2021
ICS 11.100.10
English Version
Molecular in vitro diagnostic examinations - Specifications
for pre-examination processes for Fine Needle Aspirates
(FNAs) - Part 2: Isolated proteins

Analyses moléculaires de diagnostic in vitro - Molekularanalytische in-vitro-diagnostische Verfahren

Spécifications pour les processus préanalytiques pour - Spezifikationen für präanalytische Prozesse für

les ponctions à l'aiguille fine - Partie 2 : Protéines Feinnadelaspirate - Teil 2: Isolierte Proteine

extradites

This draft Technical Specification is submitted to CEN members for Vote. It has been drawn up by the Technical Committee

CEN/TC 140.

CEN members are the national standards bodies of Austria, Belgium, Bulgaria, Croatia, Cyprus, Czech Republic, Denmark, Estonia,

Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway,

Poland, Portugal, Republic of North Macedonia, Romania, Serbia, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey and

United Kingdom.

Recipients of this draft are invited to submit, with their comments, notification of any relevant patent rights of which they are

aware and to provide supporting documentation.

Warning : This document is not a Technical Specification. It is distributed for review and comments. It is subject to change

without notice and shall not be referred to as a Technical Specification.
EUROPEAN COMMITTEE FOR STANDARDIZATION
COMITÉ EUROPÉEN DE NORMALISATION
EUROPÄISCHES KOMITEE FÜR NORMUNG
CEN-CENELEC Management Centre: Rue de la Science 23, B-1040 Brussels

© 2021 CEN All rights of exploitation in any form and by any means reserved Ref. No. FprCEN/TS 17688-2:2021 E

worldwide for CEN national Members.
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FprCEN/TS 17688-2:2021 (E)
Contents Page

European foreword ....................................................................................................................................................... 3

Introduction .................................................................................................................................................................... 4

1 Scope .................................................................................................................................................................... 5

2 Normative references .................................................................................................................................... 5

3 Terms and definitions ................................................................................................................................... 5

4 General considerations .............................................................................................................................. 11

5 Outside the laboratory ............................................................................................................................... 12

5.1 Specimen collection ..................................................................................................................................... 12

5.1.1 General ............................................................................................................................................................. 12

5.1.2 Information about the specimen donor/patient .............................................................................. 12

5.1.3 Information about the specimen ............................................................................................................ 13

5.1.4 Selection of the primary FNA collection device ................................................................................. 13

5.1.5 FNA specimen collection and processing from the donor/patient ............................................ 13

5.2 Specimen storage and transport ............................................................................................................ 15

6 Inside the laboratory .................................................................................................................................. 15

6.1 Specimen reception ..................................................................................................................................... 15

6.2 Specimen/sample storage after transport and reception ............................................................. 15

6.2.1 General ............................................................................................................................................................. 15

6.2.2 Storage of FNA specimen/samples using collection devices with stabilizer .......................... 16

6.2.3 Storage of FNA specimen/samples using collection devices without stabilizers ................. 16

6.3 Specimen/sample processing for cytological examination prior to protein isolation ....... 16

6.3.1 General ............................................................................................................................................................. 16

6.3.2 Handling of cell suspension ...................................................................................................................... 17

6.3.3 Preparation of paraffin-embedded cell blocks.................................................................................. 18

6.3.4 Preparation of cell suspension slides ................................................................................................... 19

6.4 Evaluation of the pathology of the specimen or sample(s) ........................................................... 19

6.5 Processed sample storage, transport and reception ....................................................................... 20

6.5.1 General ............................................................................................................................................................. 20

6.5.2 Storage and transport of cell suspension ............................................................................................ 20

6.5.3 Storage and transport of paraffin-embedded cell blocks .............................................................. 20

6.5.4 Storage and transport of cell suspension slides ............................................................................... 21

6.6 Isolation of protein ...................................................................................................................................... 21

6.6.1 General ............................................................................................................................................................. 21

6.6.2 Using a commercial protein isolation kit intended for diagnostic use ..................................... 21

6.6.3 Using the laboratory’s own protein isolation procedure .............................................................. 22

6.6.4 Isolation of proteins from specific sample types .............................................................................. 22

6.7 Quantity and quality assessment of isolated proteins.................................................................... 23

6.8 Storage of isolated proteins ..................................................................................................................... 23

Bibliography ................................................................................................................................................................. 25

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FprCEN/TS 17688-2:2021 (E)
European foreword

This document (FprCEN/TS 17688-2:2021) has been prepared by Technical Committee CEN/TC 140 “In

vitro diagnostic medical devices”, the secretariat of which is held by DIN.
This document is currently submitted to the Vote on TS.
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Introduction

Molecular in vitro diagnostics has enabled significant progress in medicine. Further progress is expected

by new technologies analysing profiles of nucleic acids, proteins, and metabolites in human tissues and

body fluids. However, the profiles of these molecules can change drastically during the pre-examination

process, including the specimen collection, transport, storage and processing.

Examination of proteins is commonly used in clinical practice. This includes e.g. prognostic and predictive

biomarker examinations. This is a fast growing field in molecular diagnostics.

Fine needle aspiration is a non-surgical procedure that uses a thin, hollow-bore needle and syringe to

collect a specimen from patients for cytopathological and molecular investigation. As a minimally-

invasive technique, fine needle aspirates (FNAs) are commonly used to diagnose and monitor for example

a range of cancer types e.g. breast, lung and thyroid cancer, and other diseases, such as inflammatory

diseases. FNAs also provide the opportunity to sample metastatic sites (e.g. lymph nodes) and otherwise

non-resectable tissues.

Besides cytological assessment, molecular biological analysis of FNAs is expected to become increasingly

used for cancer and other disease diagnostics, including companion diagnostics.

One of the challenges facing molecular analysis of FNA samples is their small size and diversity in

composition (cells, blood, body fluid). The low cellular content of FNAs means that the yield of isolated

proteins is typically towards the lower end of detection for molecular examination. Therefore, the protein

isolation procedure should provide a sufficient amount of protein as required by the specific examination.

Protein profiles, protein integrities, and protein–protein interactions in FNAs can change drastically

during and after collection (due to, e.g. gene induction, gene down regulation, protein degradation and

modification). Protein species amounts can change differently in different donors’/patients’ FNAs.

Therefore, standardization of the entire process from specimen collection to protein examination is

needed to minimize protein degradation and protein profile changes during and after FNA collection. This

document describes special measures which need to be taken to obtain good quality FNA

specimens/samples and isolated protein therefrom for molecular examination.
In this document, the following verbal forms are used:
— “shall” indicates a requirement;
— “should” indicates a recommendation;
— “may” indicates a permission;
— “can” indicates a possibility or a capability.
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FprCEN/TS 17688-2:2021 (E)
1 Scope

This document gives guidelines on the handling, documentation, storage and processing of fine needle

aspirates (FNAs) intended for protein examination during the pre-examination phase before a molecular

examination is performed.

This document is applicable to molecular in vitro diagnostic examinations including laboratory developed

tests performed by medical laboratories and molecular pathology laboratories that examine proteins

isolated from FNAs. It is also intended to be used by laboratory customers, in vitro diagnostics developers

and manufacturers, biobanks, institutions and commercial organisations performing biomedical

research, and regulatory authorities.

Different dedicated measures are taken for collecting, stabilizing, transporting and storing of core needle

biopsies (FNA Biopsy or FNA B) and are not covered in this document, but in EN ISO 20184-2, Molecular

in vitro diagnostic examinations — Specifications for pre-examination processes for frozen tissue — Part 2:

Isolated proteins and EN ISO 20166-2, Molecular in vitro diagnostic examinations — Specifications for pre-

examination processes for formalin fixed and paraffin-embedded (FFPE) tissue — Part 2: Isolated proteins.

This document is not applicable for protein examination by immunohistochemistry.

NOTE International, national or regional regulations or requirements can also apply to specific topics covered

in this document.
2 Normative references

The following documents are referred to in the text in such a way that some or all of their content

constitutes requirements of this document. For dated references, only the edition cited applies. For

undated references, the latest edition of the referenced document (including any amendments) applies.

EN ISO 15189, Medical laboratories - Requirements for quality and competence (ISO 15189)

3 Terms and definitions

For the purposes of this document, the terms and definitions given in EN ISO 15189 and the following

apply.

ISO and IEC maintain terminological databases for use in standardization at the following addresses:

— ISO Online browsing platform: available at https://www.iso.org/obp
— IEC Electropedia: available at https://www.electropedia.org/
3.1
aliquot

portion of a larger amount of homogenous material, assumed to be taken with negligible sampling error

Note 1 to entry: The term is usually applied to fluids. Tissues are heterogeneous and therefore cannot be

aliquoted.

Note 2 to entry: The definition is derived from the Compendium of Chemical Terminology Gold Book.

International Union of Pure and Applied Chemistry. Version 2.3.3., 2014; the PAC, 1990,62,1193 (Nomenclature for

sampling in analytical chemistry (Recommendations 1990)) p. 1206; and the PAC 1990, 62, 2167 (Glossary of

atmospheric chemistry terms (Recommendations 1990)) p. 2173.
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3.2
ambient temperature
unregulated temperature of the surrounding air
[SOURCE: EN ISO 20166-1:2018, 3.2]
3.3
analyte
component represented in the name of a measurable quantity
[SOURCE: ISO 17511:2020, 3.2, modified — deleted example.]
3.4
biomolecule

organic molecule produced by living organisms that is involved in the maintenance and metabolic

processes of organisms

Note 1 to entry: Examples of organic molecules are protein, carbohydrate, lipid, or nucleic acid.

3.5
cell block
paraffin-embedded cell clot
3.6
cell clot

cell-rich liquid specimen/sample concentrated into a compact cell aggregate for subsequent processing

3.7
cytocentrifugation

cytology method that is specifically designed to concentrate cells on a slide by centrifugation

3.8
deoxyribonucleic acid
DNA

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

form
[SOURCE: EN ISO 22174:2005, 3.1.2]
3.9
diagnosis

identification of a disease from its signs and symptoms, where the diagnostic process can involve

examinations and tests for classification of an individual's condition into separate and distinct categories

or subclasses that allow medical decisions about treatment and prognosis to be made

[SOURCE: EN ISO 20166-1:2018, 3.7]
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3.10
examination
analytical test

set of operations with the objective of determining the value or characteristics of a property

Note 1 to entry: Processes that start with the in situ detection using antibodies, nucleic acid probes or dyes and

include all kinds of parameter testing or chemical manipulation for quantitative or qualitative examination.

[SOURCE: ISO 15189:2012, 3.7, modified — Notes to entry 1 to 3 have been removed. Note 1 to entry has

been added and “analytical test” has been added as a preferred term.]
3.11
examination manufacturer
analytical test manufacturer
entity that manufactures and/or produces a specific analytical test
3.12
examination performance
analytical test performance
analytical performance

accuracy, precision, and sensitivity of a test to measure the analyte of interest

Note 1 to entry: Other test performance characteristics such as robustness, repeatability can apply as well.

[SOURCE: EN ISO 20184-1:2018, 3.4]
3.13
fixative

solution used to preserve or harden FNA specimens for microscopic and molecular examination

3.14
formalin

saturated aqueous formaldehyde solution which at 100 % contains 37 % formaldehyde by mass

(corresponding to 40 % by volume)
[SOURCE: EN ISO 20166-1:2018, 3.11]
3.15
fine needle aspirate
FNA

specimen withdrawn by a non-operative procedure that uses a thin, hollow-bore needle

3.16
FNA primary collection device

thin, hollow-bore needle or syringe used for collecting the FNA specimen from the donor/patient

3.17
FNA secondary collection device

suitable container into which the specimen is transferred from the FNA primary collection device

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3.18
homogeneous
uniform in structure and composition
[SOURCE: EN ISO 20166-1:2018, 3.31]
3.19
laboratory developed procedure

modified commercially available in vitro diagnostic device or fully in house developed procedure

3.20
nonconformity
nonfulfillment of a requirement
[SOURCE: ISO 9000:2005, 3.6.9]
3.21
paraffin embedding

process in which a sample is placed in paraffin to generate a hard surrounding matrix so that thin

microscopic sections can be cut
3.22
pre-examination process
pre-analytical workflow
pre-analytical phase
pre-examination phase

process that starts, in chronological order, from the clinician’s request and includes the examination

request, preparation and identification of the patient, collection of the primary sample(s), transportation

to and within the analytical laboratory, isolation of analytes, and ends when the analytical examination

begins

Note 1 to entry: The pre-examination phase includes preparative processes that influence the outcome of the

intended examination.

[SOURCE: ISO 15189:2012, 3.15, modified — An additional term was added and more detail was

included.]
3.23
primary sample
specimen

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

[SOURCE: ISO 15189:2012, 3.16, modified — The term and definition is used here without the original

Notes.]
3.24
proficiency test

evaluation of participant performance against pre-established criteria by means of inter-laboratory

comparisons

[SOURCE: EN ISO/IEC 17043:2010, 3.7, modified — Term and definition are used here without the

original Notes.]
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3.25
protein

type of biological macromolecules composed of one or more chains with a defined sequence of amino

acids connected through peptide bonds
3.26
protein profile

amounts of the individual protein molecules that are present in a sample and that can be measured in the

absence of any losses, inhibition and interference
3.27
protein species

amounts of a chemically clearly-defined protein corresponding to one spot on a high-performance two-

dimensional gel electrophoresis pattern
[SOURCE: [16]]
3.28
post translational modifications
PTM

chemical alterations to a primary protein structure, often crucial for conferring biological activity on a

protein
[SOURCE: [17]]
3.29
ribonucleic acid
RNA

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

[SOURCE: EN ISO 22174:2005, 3.1.3]
3.30
room temperature
temperature in the range of 18 °C to 25 °C
Note 1 to entry: Local or national regulations can have different definitions.
[SOURCE: EN ISO 20166-1:2018, 3.22]
3.31
sample
one or more parts taken from a specimen
[SOURCE: ISO 15189:2012, 3.24, modified — Example has been removed.]
3.32
stability

ability of a sample material, when stored under specified conditions, to maintain a stated property value

within specified limits for a specified period of time

[SOURCE ISO Guide 30:2015, 2.1.15, modified — The words “reference material” were replaced by

“sample material”.]
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3.33
stabilizer

substance which has the ability to maintain a stated property value within specified limits for a specified

period of time of a sample material

Note 1 to entry: The substance can contain a fixative belonging to different fixative subgroups e.g. crosslinking

fixatives (e.g.formalin) or coagulating fixatives (e.g. methanol, ethanol)
3.34
stabilization

process of maintaining a stated property value within specified limits for a specified period of time of a

specimen/sample material
3.35
standard buffered formalin solution
neutral buffered formalin
NBF

10 % formalin solution in water with a mass fraction of 3,7 % (corresponding to a volume fraction of 4

%) formaldehyde, buffered to pH 6,8 to pH 7,2

Note 1 to entry: Standard buffered formalin solutions often contain small amounts of methanol to inhibit

oxidation and polymerisation of formaldehyde.
[SOURCE: EN ISO 20166-1:2018, 3.25]
3.36
storage

prolonged interruption of the pre-analytical workflow of a sample or analyte respectively, or of their

derivatives, under appropriate conditions in order to preserve their properties

Note 1 to entry: Long-term storage typically occurs in laboratory archives or in biobanks.

[SOURCE: EN ISO 20184-1:2018, 3.21, modified — Example has been removed.]
3.37
tissue processor

automated instrument where tissue fixation, dehydration, clearing and impregnation (with paraffin)

occur
[SOURCE: EN ISO 20166-1:2018, 3.27]
3.38
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 term “validated” is used to designate the corresponding status.

[SOURCE: ISO 9000:2015, 3.8.13, modified — Note 1 and Note 3 have been omitted.]
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3.39
verification

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

Note 1 to entry: The term “verified” is used to designate the corresponding status.

Note 2 to entry: Confirmation can comprise activities such as:
— performing alternative calculations;

— comparing a new design specification with a similar proven design specification;

— undertaking tests and demonstrations;
— reviewing documents prior to issue.
[SOURCE: ISO 9000:2015, 3.8.12, modified — Note 1 and Note 2 have been omitted.]
3.40
workflow
series of activities necessary to complete a task
[SOURCE: EN ISO 20166-1:2018, 3.30]
4 General considerations

For general statements on medical laboratory quality management systems and in particular on

specimen collection, reception and handling (including avoidance of cross contaminations) see

EN ISO 15189, EN ISO/IEC 17020 or EN ISO/IEC 17025. ISO/TS 20658 and EN ISO 20387 (for

biobanking) can also apply. The requirements on laboratory equipment, reagents, and consumables

according to EN ISO 15189 shall be followed; EN ISO/IEC 17020 and EN ISO/IEC 17025 can also apply.

All steps of the pre-examination, examination and post-examination processes (i.e. the entire workflow)

can influence the diagnosis or research study results.

Thus, this entire workflow shall be specified, verified and validated during the development of the

examination, including the development of in vitro diagnostic (IVD) medical devices. This includes

specifically all pre-examination process steps such as the examination request, preparation and

identification of the patient, collection of the primary sample(s), transport to and within the medical

laboratory, storage and isolation of analytes. The specifications about the specimen transport and storage

shall also include information on the stability of the specimen's analyte profile including the timeframe

between collecting the specimen and its examination and storage conditions such as duration,

temperature limits and freeze/thaw cycles. The verification and validation shall take into account the

impact of the FNA specimen variability (e.g. by tissue type, heterogeneity, specimen quantity, presence

of blood cells) on the examination.

During the design and development of a FNA protein based examination, a risk assessment shall be

performed (see also EN ISO 14971). Mitigation measures for eliminating or reducing identified risks shall

be established, where required, for ensuring the performance of the examination. It shall especially be

investigated and ensured that the specific protein profile(s) intended to be analysed is/are not

compromised in a manner impacting the examination performance. This includes investigations on

whether and/or how the protein profile intended to be examined changes during storage and transport.

This can be done, e.g. by applying the intended examination to specimens/samples which underwent time

course studies, reflecting the individual pre-examination process steps such as transport and storage and

by implementing measures to prevent or reduce impacts by the identified pre-analytical variables.

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NOTE A time course experiment is a research design that involves repeated observations of the same variables

at specific intervals over a relevant time period (e.g. time 0, 12 h, 24 h, 36 h, 48 h). This is expected to reflect any

knowledge on the stability of the protein(s) of interest. Typically, this involves using aliquots from a homogeneous

starting material.

During the whole pre-examination process, precautions shall be taken to avoid cross contamination

between different specimens/samples (e.g. using single-use material whenever feasible or appropriate

cleaning procedures between processing of different specimens/samples), and to avoid mixing up of

specimens/samples.

During transportation and transient storage between pre-analytical workflow steps of viable cells,

protein profiles can change. In order to minimize pre-analytical impacts on protein profiles, the specimen

should therefore be placed in a collection device containing an appropriate stabilizer solution. The

maximum duration until the specimen is placed into stabilizer solution should be specified and verified.

The duration and the temperature before stabilization shall be documented.

Safety instructions for the whole pre-examination process shall be in place and followed. Safety

regulations on specimen/sample transport and handling shall be considered (see EN ISO 15189,

EN 15190 and ISO/TS 20658). If transport is required over public areas, corresponding regulations or

laws for packaging and transport apply (e.g. International Air Transport Association (IATA) for air

transport).

The manufacturer's material safety data sheet shall be considered for any potentially hazardous material

(e.g. stabilizers such as formaldehyde and methanol).

For all pre-examination steps, the examination manufacturer's instructions shall be followed.

Where, for justified reasons (e.g. unmet patient needs), a commercial product is not used in accordance

to the manufacturer's instructions, responsibility for its verification, validation, use and performance lies

with the laboratory.
5 Outside the laboratory
5.1 Specimen collection
5.1.1 General

For the collection of the FNA specimen, the requirements for the intended molecular examination (e.g.

disease condition, specimen type; see also Clause 6) shall be considered.
See also EN ISO 15189.
5.1.2 Information about the specimen donor/patient

The documentation shall include the identity of the patient/specimen donor, which can be in the form of

a code.
The documentation should include, but is not limited to:

a) the relevant health status of the patient/specimen donor (e.g. disease type, concomitant disease,

demographics [e.g. age and gender]);

b) the information about routine medical treatment and special treatment prior to FNA collection (e.g.

anaesthetics, medications, surgical or diagnostic procedures);
c) the appropriate consent from the specimen donor/patient.
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