International Symposium, Kitasato University, 2008/3/16

Quality Assurance of Genetic

Testing Services
- Proposal from Japan and ISO Perspectives -

Tadashi Kawai, MD, PhD

International Clinical Pathology Center Tokyo,
Japan; tkawai@gakushikai.jp
Three major issues on
provision of quality genetic testing services
1. Ethical, legal and social issues (ELSI)
・Careful consideration should be given that test results
will influence not only to the individual concerned,
but also his/her relatives and children
・Privacy related to test results should be protected
2. Clinical practice issues
・Pre- and post-examination counseling of the individuals
concerned must be under a medical geneticist or its
equivalent specialist
・Clinical practice should respect adequate national/
international guidelines, when available
3．Quality issues in genetics laboratory
・Quality management system and technical competence
Tadashi Kawai, 2008
 Principal guidelines on genetic researches and
clinical services in Japan(1)
Governmental: (http://www2.ncc.go.jp/elsi/)
・Guideline for research on the human genome and genes, 2001
issued by Ministry of Education, Culture, Sports, Science and
Technology (MEXT), Ministry of Health, Labour and Welfare
(MHLW)＆Ministry of Economy, Trade and Industry (METI)
Commercial/business-oriented:
・Ethical principle for providing genetic testing in referral labs,
issued by the Japan Registered Clinical Laboratories
Association 2001, revised 2007 (http://www.jrcla.or.jp/)
・Principle (final draft) for non-medical facility providing genetic
information, issued by the Japan Council for Protection of
Individual Genetic Information, 2008
Tadashi Kawai, 2008
 Principal guidelines on genetic researches and
clinical services in Japan (2)

Academic:
・Guideline for genetic testing, issued co-jointly by 10 societies,
 2003, available in both Japanese and English (www.jshg.jp/)
Japan (or Japanese) Society of (or for):
Human Genetics, Genetic Counseling, Familial Tumor,
Obstetrics and Gynecology, Pediatric Genetics,
Gene Diagnosis and Therapy, Teratology, Inherited
Metabolic Diseases, Mass Screening, and Laboratory
Medicine

Tadashi Kawai, 2008

 Guideline for Genetic Testing
by 10 academic societies in Japan, 2003
Preface
I. Scope
II. Practice of genetic testing
III. Disclosure of genetic test results
IV. Genetic testing and genetic counseling
V. Important points concerning genetic testing for specific
individuals
In conclusion
Proposals (to the authority, academic society, medical facility, clinician
and medical professional, and public)
References
Terms and definitions (21 terms listed)
Tadashi Kawai, 2008
 Activities related to standardization in
molecular genetic testing in Japan
・Various academic societies in different disciplines of
 laboratory medicine, not harmonized among each other
・Technical committees in the Japan Bioindustry Association,
1999 ∼ 2006, partly under the auspices of the government
・Proposal to ISO/TC212 on quality and competence in genetic
 testing, 2005∼, Jp National Committee for ISO/TC212
・EU/Eurogentest Project, 2005∼
・OECD recommendation on quality assurance in molecular
genetic testing, 2007
・ JCCLS/Technical committee on gene-related testing, 2007∼
 2009, under the auspices of the Ministry (METI)

Tadashi Kawai, 2008

 ISO/TC212, Clinical laboratory testing and
in vitro diagnostic test systems (1)
・Established in 1995, ＠Secretariat: ANSI/CLSI(USA)
・Four working groups:
WG1: Quality and competence in the medical laboratory
WG2: Reference systems
WG3: In vitro diagnostic products               WG4:
Antimicrobial susceptibility testing
・ISO 15189, Medical laboratories ‒ Particular requirements
for quality and competence, 1st ed. (2003), 2nd ed.(2007)

Tadashi Kawai, 2008

ISO 15189:2007, Medical laboratories ‒ Particular
requirements for quality and competence
Foreword
Introduction

1 Scope
2 Normative references
3 Terms and definitions Based on ISO/IEC 17025 :
General requirements for
4 Management requirements
testing and calibration
5 Technical requirements laboratories, and ISO 9001
Annex A (informative), Annex B (informative),
Annex C (informative): Ethics in laboratory medicine, Bibliography

Tadashi Kawai, 2008

ISO 15189:2007
1 Scope
1.1 This International Standard specifies requirements for
quality and competence particular to medical
laboratories.
1.2 This International Standard is for use by medical
laboratories in developing their quality management
systems and assessing their own competence, and for
use by accreditation bodies in confirming or recognizing
the competence of medical laboratories.
・No mention whatsoever about genetic testing in the
 International Standard, but not excluded it.

Tadashi Kawai, 2008

 ISO/TC212, Clinical laboratory testing and
in vitro diagnostic test systems (2)
・Responses in ISO/TC212 to the new proposal from Japan
．Common understanding that ISO/TC212 cannot be a
bystander on quality issue of genetic testing
・Some P-members in favor, while others in reluctance at
 the current circumstance
•ILAC (accreditation bodies) - unnecessary
・Postponed to its decision until an OECD guideline or
Eurogentest project recommendation be out

・Established in WG1 the genetic testing project group to

recommend further action on the Japanese proposal and OECD
guideline until June 2008 in the next ISO/TC212 meeting
Tadashi Kawai, 2008
Recommendation to ISO/TC212 by the genetic
testing project group (Leader: Dr. Joe Boone)
・ISO premise to avoid any ethical/social issue
・No stand-alone standard needed on quality and competence
 in genetic testing , although guideline(s) could be produced,
if necessary
・Some amendments in the existing edition of ISO 15189 to be
recommended
•Definition of genetic testing still under discussion
•Some corrections or additions in: 3
Terms and Definition ‒ medical/clinical laboratory
4 Management and 5 Technical Requirements,
Annex C (Ethics in laboratory medicine)
Tadashi Kawai, 2008
 Harmonization on molecular genetic testing
by JCCLS/METI

・OECD guideline accepted in principle, but its feasibility to be

evaluated for further actions in Japan
・JCCLS established under the auspices of the Ministry (METI)
the Technical Committee on genetic testing in 2006,
represented by many academic societies and organizations
・The aim of the Committee is to produce a nationally accepted
best-practice guideline, which shall be harmonized globally, or
based on OECD recommendation Com on Gene-Related Testing
・The scope is to include entirely the clinical laboratory tests,
using molecular biotechnology ‒ diagnostic, screening, or others
・What will be the title of the Committee , then?
Tadashi Kawai, 2008
 Confusion in Terminology in Japan

遺伝子検査
Gene
Testing
Pathogens Human bodies
Somatic cells Germ-line cells
Nucleic acid testing Gene-based testing Genetic testing
核酸検査 遺伝子検査 遺伝学的検査

・Researchers and investigators tend to use the term gene

 testing, believing by themselves that they have been doing
 something new and special .
Tadashi Kawai, 2008
Current status in harmonization on gene-
related testing in Japan (1)
・No consensus on terminology, yet
・Personnel requirements and certifications, available on
clinical geneticist(MD) and 3 kinds of technical scientists for
chromosome and/or genetic testing(clin. cytogeneticist, etc.)
・Standard operating procedures for chromosome and genetic
analyses, available only on a few test items by various
academic societies nationally and also internationally(CLSI, etc.)
・Standards for reporting of the test results, recommended by
national (JSHG) and international societies/organizations
・In vitro diagnostic medical devices: regulated by the authority  in
Japan, and also internationally (GHTF, etc.)

Tadashi Kawai, 2008

Current status of molecular gene-related testing
in Japan (2)
・Protection of personal genetic information by both the Medical
 Practice Law, and the Act on the Protection of Personal
Information(2003)
・Clinical laboratories ‒ will be accredited voluntarily by ISO Std
・Proficiency testing or external quality assessment scheme:
not available on molecular genetic tests, but some on nucleic
acid tests for various important micro-organisms and a few
gene-based tests
・Medical insurance policy: mostly on pathogenic micro-
organisms, and also a few neoplastic and genetic diseases
・Direct-to-consumer service: will be voluntarily controlled by
the Council for Protection of Individual Genetic Information
Tadashi Kawai, 2008
Tadashi Kawai, 2008