HOKLAS SC-35
Issue No. 2
Issue Date: 18 September 2013
Implementation Date: 1 November 2013
Page 1 of 13
HOKLAS Supplementary Criteria No. 35
“Medical Testing” Test Category – Cytogenetics
1
Introduction
1.1 This Supplementary Criteria is an amplification and interpretation of the
requirements of HKAS 002 and HOKLAS 015 for the accreditation of tests and
examinations in medical genetics within the Medical Testing Test Category.
This document sets out only those specific requirements which require further
elaboration but does not include all the accreditation requirements. Therefore,
this Supplementary Criteria needs to be read in conjunction with HKAS 002,
HOKLAS 015 and HOKLAS SC No. 33.
1.2 The checklists given in the Annex serve as guidance for laboratories to
self-assess their management system and operation procedures against the
requirements given in HOKLAS 015 and this document.
2
Scope of accreditation
2.1 HOKLAS provides accreditation for the following areas:
2.1.1 Constitutional Cytogenetics (prenatal and postnatal)
2.1.2 Cancer Cytogenetics (excluding solid tumours)
2.1.3 Fluorescence in situ hybridization (FISH)
3
Personnel
3.1
A qualified pathologist providing consultation and clinical interpretation for
test results in cytogenetics shall have obtained the Fellowship of the Hong
Kong College of Pathologists in an appropriate specialty plus qualification in
cytogenetics from a university and/or professional body and two years' post
fellowship full time equivalent laboratory training in an ISO15189-accredited
cytogenetic laboratory, or at least 5 years of laboratory experiences in a
HOKLAS SC-35
Issue No. 2
Issue Date: 18 September 2013
Implementation Date: 1 November 2013
Page 2 of 13
cytogenetic laboratory before 1 September 2008 (the launching date of
HOKLAS for the accreditation of tests and examinations in Medical Genetics).
4
3.2
A medically qualified person providing consultation and clinical interpretation
for test results in constitutional cytogenetics shall have obtained Fellowship in
an appropriate specialty (e.g. Obstetrics & Gynaecology, Paediatrics) plus
qualification in cytogenetics from a university and/or professional body and
two years' post fellowship full time equivalent laboratory training in an
accredited constitutional cytogenetic laboratory, or at least 5 years of
laboratory experiences in a constitutional cytogenetic laboratory before 1
September 2008.
3.3
A biomedical scientist reporting test results in constitutional cytogenetics
without clinical interpretation shall be MLT Board Part I registered (or
exempted from such registration) and have obtained a BSc degree or above in a
relevant subject plus 5 years of post-Part I registration supervisory experience
in constitutional cytogenetics, or have obtained a recognised overseas
qualification in cytogenetics.
Laboratory equipment
4.1
Procedures to assure and verify the proper functioning of equipment shall meet
acceptable professional standards, e.g.
4.1.1 Tissue culture incubators shall have a system to monitor the temperature
continuously, and an alarm system to alert laboratory staff of abnormal
culture conditions.
5
Pre-examination procedures
5.1
Both the request forms and specimens submitted for cytogenetic studies shall
each contain at least two independent identifiers for unique identification of the
patient. The identifying information on the request form shall be identical to that
on the specimen tube label. There shall be a system to identify the person
collecting the specimen for such tests.
HOKLAS SC-35
Issue No. 2
Issue Date: 18 September 2013
Implementation Date: 1 November 2013
Page 3 of 13
6
7
8
Examination procedures
6.1
Each prenatal specimen for cytogenetic studies shall be divided, cultured in
two separate incubators and maintained with independent cell cultures, media
and reagents. Duplicate or independently established cultures should be
included if adequate specimen is available.
6.2
For cytogenetic studies, adequate number of banded metaphases should be
examined. In general, a minimum of 5 cells (10 for cancer cytogenetics) should
be analysed, and at least two cells shall be checked by a qualified personnel as
defined in clause 3.1 to 3.3. When there is evidence of mosaicism or clonal
evolution, further cells should be examined.
6.3
For FISH studies, an effort should be made to examine a few metaphases with
reverse DAPI chromosome staining to confirm that the correct probes have
been used and to identify any unusual signal pattern. If metaphase is absent or
inherent control signal is not available, the test should be repeated in parallel
with another sample known to have the target of the probes.
6.4
There shall be a clear and consistent definition of fluorescence signals and also
criteria for false positive and false negative signals.
6.5
Adequate number of interphase nuclei or metaphases should be examined. In
general, a minimum of 5 metaphases and/or 100 interphase nuclei should be
studied and scored. FISH signals shall be scored independently by 2 people.
Assuring the quality of examination procedures
7.1
For tests that give quantitative results, the laboratory shall make an effort to
estimate the uncertainty of measurement and document the uncertainty
components. An example of such tests is FISH study with quantitative results.
7.2
All staff taking part in the testing activities shall participate in appropriate
external quality assessments or interlaboratory comparison programmes.
Post-examination procedures
8.1
A minimum of two karyotypes/images shall be prepared and archived.
HOKLAS SC-35
Issue No. 2
Issue Date: 18 September 2013
Implementation Date: 1 November 2013
Page 4 of 13
8.2
9
Storage of the primary specimen and other laboratory samples shall be in
accordance with the requirements given in Table 1. Laboratories should retain
records and/or materials for a longer period of time than specified when such is
appropriate for patient care, education, quality improvement needs or legal
requirements, etc.
Reporting of results
9.1
The description of test results shall follow the latest version of the
International System for Human Cytogenetics Nomenclature (ISCN). For
cancer cytogenetics and FISH studies in Haematology, the tests shall be
reported by a qualified haematologist with appropriate training and laboratory
experience.
9.2
For FISH studies in Anatomical Pathology, the tests shall be reported by a
qualified anatomical pathologist with appropriate training and laboratory
experience.
9.3
For constitutional cytogenetics, the tests shall be reported by a medically
qualified person with appropriate training and laboratory experience as
required in section 3.1 and 3.2. For those tests with normal results, numerical
autosomal or sex chromosome abnormalities of well-recognised syndromes
and common chromosomal polymorphism (an indicative list is given in
Appendix 1), they may be reported by a biomedical scientist. To ensure that
the test results on such reports would not be misinterpreted, the following
mandatory remark shall also be shown on each of these reports: "Test results
shown on this report require clinical interpretation and comments by a
qualified pathologist (or equivalent as advised by the Hong Kong College of
Pathologists)."
9.4
The laboratory shall keep information of available genetic counselling service.
9.5
Where appropriate, the test report shall include a recommendation that the
patient should obtain genetic counselling from a qualified healthcare
professional.
- End -
HOKLAS SC-35
Issue No. 2
Issue Date: 18 September 2013
Implementation Date: 1 November 2013
Page 5 of 13
Table 1 Retention of Laboratory Records and Materials
General
Cytogenetics/Fluorescence
in situ hybridization
Record/material
Requirement
Records of employee signatures,
initials, and identification codes
10 years
Referring doctor's request
3 years after dispatch of final
report.
Indefinite for request form which
contains clinical information not
readily accessible in the patient’s
notes but used in the interpretation
of test result.
Where the request form is used to
record working notes or as a
worksheet, it should be retained as
part of the laboratory record.
Copies of reports
Indefinite
Patient information/karyotypes
Indefinite
Slides
3 years after final report if
photographic record kept; 5 years
otherwise, unless degeneration
evident
Original specimen and container/wet
specimen/tissue
1 month after reporting
Fixed chromosome preparation
(blood, bone marrow)
Abnormal: indefinite
Normal: 6 months
Tissue culture/cell culture
Cryopreserved, and indefinite when
appropriate
Diagnostic images (digitised or
ngatives)
Indefinite
N.B.: Indefinite means without limit of time, but not less than 30 years.
HOKLAS SC-35
Issue No. 2
Issue Date: 18 September 2013
Implementation Date: 1 November 2013
Page 6 of 13
Appendix 1
An indicative list of the numerical autosomal or sex chromosome abnormalities of
well-recognised syndromes and common chromosomal polymorphism.
A. Non-mosaic numerical abnormalities:
1. Down Syndrome
2. Turner Syndrome
3. Patau Syndrome
4. Edwards Syndrome
5. Klinefelter Syndrome
6. Triple X
7. XYY
8. Triploidy Syndrome
B. Common chromosomal polymorphism:
1. Pericentric inversion of chromosome 9
SC-35 Annex: Checklist on compliance with HOKLAS requirements - Cytogenetics
HOKLAS Requirement
Clause
(HOKLAS
015, 4th
edition and
relevant SC)
Clause
(HOKLAS
015, 5th
edition and
relevant SC)
Page 7 of 13
Issue No. 2
*1
Y
N
NA
Lab’s
Document
Reference or
Remarks2
Please ensure that the General Checklist (HOKLAS 021) is also completed for each discipline.
Discipline Specific Management Requirements
Quality and technical records
4.13
Do laboratory records indicate the media used, culture
conditions and incubation times for all preparations?
4.13.3 (d)
4.13 (e)
●
Do laboratory records include the number of cells counted,
analyzed microscopically and the cells from which
photographic or digitalized karyotypes are prepared?
4.13.3 (d)
4.13 (h)
●
Do laboratory records include an assessment of banding
resolution to indicate whether metaphase analysis is
satisfactory?
4.13.3 (d)
4.13 (h)
●
Discipline Specific Technical Requirements
Laboratory equipment
5.3
Does the laboratory have adequate number of image
processing systems?
5.3.1
5.3.1.1
●
Are microscopes equipped for high-resolution cytogenetics
analysis?
5.3.2
5.3.1.1
●
Note: 1. The assessor should concentrate on items marked with a ●; other items will be checked by the team leader.
2. Please put down the laboratory’s document reference(s) where there are descriptions or procedures related to the requirement.
Assessment Team’s remarks /
questions to be asked at the
laboratory
SC-35 Annex: Checklist on compliance with HOKLAS requirements - Cytogenetics
Page 8 of 13
Issue No. 2
Clause
(HOKLAS
015, 4th
edition and
relevant SC)
Clause
(HOKLAS
015, 5th
edition and
relevant SC)
Are cell cultures manipulated under conditions that ensure
sterility and protect staff?
5.3.2
5.2.6
●
Is there a class II biosafety cabinet that is certified
annually in the laboratory?
5.3.2
5.3.1.5
●
Are incubators fitted with alarms or override systems that
protect against malfunction of temperature and CO2
controls?
SC35 4.1
SC35 4.1
●
Is the quality of optical image-capture system high enough
to minimize image degradation?
5.3.2
5.3.1.2
●
Pre-examination procedures
5.4
Does the information provided on the request form include
gender and date of birth which are important for
interpretation of genetic testing results?
5.4.1 (e)
5.4.3 (a)
●
Are there procedures to verify sample identity and
integrity?
5.4.2
5.4.4.3
●
Are at least two unique identifiers provided in both the
request forms and specimens submitted for cytogenetic
studies
SC35 5.1
SC35 5.1
●
Is there a system to ensure the person collecting the
specimens for cytogenetics and FISH tests can be
identified?
SC35 5.1
SC35 5.1
●
HOKLAS Requirement
*1
Y
N
NA
Lab’s
Document
Reference or
Remarks2
Note: 1. The assessor should concentrate on items marked with a ●; other items will be checked by the team leader.
2. Please put down the laboratory’s document reference(s) where there are descriptions or procedures related to the requirement.
Assessment Team’s remarks /
questions to be asked at the
laboratory
SC-35 Annex: Checklist on compliance with HOKLAS requirements - Cytogenetics
HOKLAS Requirement
Clause
(HOKLAS
015, 4th
edition and
relevant SC)
Clause
(HOKLAS
015, 5th
edition and
relevant SC)
Page 9 of 13
Issue No. 2
*1
Examination procedures
5.5
Is each lot of culture medium checked for sterility?
5.5.1
5.3.2.3
●
Are there independently established or duplicate cultures to
backup against unexpected failures, unless the sample
contains insufficient cells to do so?
SC35 6.1
SC35 6.1
●
Are at least two cells checked by a qualified personnel?
SC35 6.2
SC35 6.2
●
When there is evidence of mosaicism or clonal evolution,
are further cells examined?
SC35 6.2
SC35 6.2
●
Y
N
NA
Lab’s
Document
Reference or
Remarks2
●
Constitutional Cytogenetics
Is prenatal specimen for cytogenetic studies divided,
cultured in two separate incubators and maintained with
independent cell cultures, media and reagents?
5.5.1
SC35 6.1
5.5.1.1
SC35 6.1
●
Are duplicate prenatal culture flasks or dishes harvested
independently?
5.5.1
5.5.1.1
●
For prenatal cultures, are at least two independent cultures
analyzed?
5.5.1
5.5.1.1
●
Are the band level, quality of banding and resolution
sufficient to render the reported interpretation?
5.5.1
5.5.1.1
●
Note: 1. The assessor should concentrate on items marked with a ●; other items will be checked by the team leader.
2. Please put down the laboratory’s document reference(s) where there are descriptions or procedures related to the requirement.
Assessment Team’s remarks /
questions to be asked at the
laboratory
SC-35 Annex: Checklist on compliance with HOKLAS requirements - Cytogenetics
HOKLAS Requirement
Are at least 5 cells counted?
Clause
(HOKLAS
015, 4th
edition and
relevant SC)
Clause
(HOKLAS
015, 5th
edition and
relevant SC)
5.5.1
5.5.1.1
Page 10 of 13
Issue No. 2
*1
Y
N
NA
Lab’s
Document
Reference or
Remarks2
●
SC35 6.2
SC35 6.2
SC35 6.2
●
Are culture methods, culture media and additives selected
according to the nature of neoplastic disorder under study?
5.5.1
5.5.1.1
●
Are at least 10 cells analyzed, if possible?
5.5.1
SC35 6.2
5.5.1.1
SC35 6.2
●
Are at least 2 karyotypes per mainline and 1 karyotype each
from pertinent sidelines generated for each case?
5.5.1
5.5.1.1
●
Has the laboratory established the reference range(s) for
each probe used?
5.5.2
5.5.2
●
Are metaphases with DAPI chromosome staining to
confirm that the correct probes have been used and identify
any unusual signal pattern?
SC35 6.3
SC35 6.3
●
If metaphase is absent or inherent control signal is not
available in FISH studies, is the test repeated in parallel
with another sample know to have the probe target?
SC35 6.3
SC35 6.3
●
Are there a clear and consistent definition of fluorescence
signals and also criteria for positive and false negative
signals?
SC35 6.4
SC35 6.4
●
Are at least 5 cells analyzed?
Cancer Cytogenetics
FISH analysis
Note: 1. The assessor should concentrate on items marked with a ●; other items will be checked by the team leader.
2. Please put down the laboratory’s document reference(s) where there are descriptions or procedures related to the requirement.
Assessment Team’s remarks /
questions to be asked at the
laboratory
SC-35 Annex: Checklist on compliance with HOKLAS requirements - Cytogenetics
Page 11 of 13
Issue No. 2
Clause
(HOKLAS
015, 4th
edition and
relevant SC)
Clause
(HOKLAS
015, 5th
edition and
relevant SC)
Are at least 5 metaphases and/or 100 interphase nuclei
studied and scored?
SC35 6.5
SC35 6.5
●
Are FISH signals scored independently by 2 people?
SC35 6.5
SC35 6.5
●
If breakage studies are performed, are they performed with
concurrent controls in the same manner as patient
specimen?
5.5.1
5.6.2.2
●
Post-examination procedures
5.7
Are at least two karyotypes/images prepared and archived?
SC35 8.1
SC35 8.1
●
Are fixed preparations of chromosomes and cells stored
indefinitely if abnormal, and for 6 months if normal?
SC35 Table 1
SC35 Table 1
●
Are slides stored for 3 years after final report if
photographic record kept, or 5 years otherwise, unless
degeneration is evident?
SC35 Table 1
SC35 Table 1
●
Are negatives, prints or retrievable electronic media stored
indefinitely?
SC35 Table 1
SC35 Table 1
●
Are copies of reports stored indefinitely?
SC35 Table 1
SC35 Table 1
●
Is original specimen and container/wet specimen/tissue
stored one month after reporting?
SC35 Table 1
SC35 Table 1
●
HOKLAS Requirement
*1
Y
N
NA
Lab’s
Document
Reference or
Remarks2
Chromosome instability syndromes analysis
Note: 1. The assessor should concentrate on items marked with a ●; other items will be checked by the team leader.
2. Please put down the laboratory’s document reference(s) where there are descriptions or procedures related to the requirement.
Assessment Team’s remarks /
questions to be asked at the
laboratory
SC-35 Annex: Checklist on compliance with HOKLAS requirements - Cytogenetics
Page 12 of 13
Issue No. 2
Clause
(HOKLAS
015, 4th
edition and
relevant SC)
Clause
(HOKLAS
015, 5th
edition and
relevant SC)
Is harvested tissue culture/cell culture stored indefinite
when appropriate?
SC35 Table 1
SC35 Table 1
●
Reporting of results
5.8
HOKLAS Requirement
*1
Y
N
NA
Lab’s
Document
Reference or
Remarks2
Does the cytogenetics report contain:
- biological sex of the patient?
5.8.3
5.8.3
●
- description of specimen / tissue studied?
5.8.3
5.8.3
●
- number of cells (metaphases) analyzed, counted and
karyotyped?
5.8.3
5.8.3
●
- banding method(s) used?
5.8.3
5.8.3
●
- diagnosis and classification according to the WHO
classification (for haematology malignancies)?
5.8.4
N/A
●
Is the current International System for Human Cytogenetics
Nomenclature (ISCN) used correctly in the final report for
conventional cytogenetic studies?
SC35 9.1
SC35 9.1
●
Does the FISH report include information on the limitations
of the test applied, on the source of the probe and on the
implications of the result?
5.8.3
5.8.1
●
Is the final report for constitutional cytogenetics reported
by a medically qualified person with appropriate training
and laboratory experience as required in SC35 Clause 3.1
and 3.2?
SC35 9.3
SC35 9.3
●
Note: 1. The assessor should concentrate on items marked with a ●; other items will be checked by the team leader.
2. Please put down the laboratory’s document reference(s) where there are descriptions or procedures related to the requirement.
Assessment Team’s remarks /
questions to be asked at the
laboratory
SC-35 Annex: Checklist on compliance with HOKLAS requirements - Cytogenetics
Page 13 of 13
Issue No. 2
Clause
(HOKLAS
015, 4th
edition and
relevant SC)
Clause
(HOKLAS
015, 5th
edition and
relevant SC)
Do all reports specified in Clause 9.3 reported by a
biomedical scientist show the following mandatory remark:
"Test results shown on this report require clinical
interpretation and comments by a qualified pathologist (or
equivalent as advised by the Hong Kong College of
Pathologists)”?
SC35 9.4
SC35 9.3
●
Are appropriate genetics counselling referrals available for
genetic testing and have these been documented in the
laboratory’s procedures?
SC35 9.5
SC35 9.4
●
HOKLAS Requirement
*1
Y
N
NA
Lab’s
Document
Reference or
Remarks2
Note: 1. The assessor should concentrate on items marked with a ●; other items will be checked by the team leader.
2. Please put down the laboratory’s document reference(s) where there are descriptions or procedures related to the requirement.
Assessment Team’s remarks /
questions to be asked at the
laboratory