Dr. Prof. Shu Jun Cheng

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Promote Animal-free Testing in China Through
Bottom-up Way
Dr. Prof. Shu Jun Cheng Toxicology Dept. of
Guangdong Inspection Quarantine Technology
Center, Guangzhou, China
2015.11.20
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Content

• Introduction of AQSIQ
• Bottom-up way retrospect of Alternatives in China
• Activities of standardization and validation
• Administration accept alternative methods
• Promote the application in Industries
• Continuous Education and Training
• Difficulties and challenges

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Introduction of AQSIQ
AQSIQ
General Administration of Quality
Supervision, Inspection and Quarantine of
Peoples Republic of China (AQSIQ) , as the
ministry organization directly led by State
Department to exert administration and execute
laws, AQSIQ supervise national quality,
measurement, entry-exit commodity inspection,
entry-exit sanitation quarantine, entry-exit
animals and plants quarantine, import and export
food/cosmetics safety, certification and
accreditation and standardization work, etc..
35 Inspection and Quarantine bureaus
directly under AQSIQ.
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Bottom-up way of Alternatives in China
Motivation
Regulations of global trade Cosmetics ban of
animal testing, Chemicals/REACH advocate
non-animal testing and animal only as last
resort, Food additive, packaging material,
pesticides risk assessment Biology
product/medicine pre-clinical testing Environment
safety assessment
Science and technology development Omics
Computer and predicity Stem cells and
engineering tissue Cell engineering and
culture High throughput/content screening
Society development Animal protection movement
Awakening of animal welfare consciousness
---2010/63/EU --- Guideline on Humane
Treatment to LaboratoryAnimals(Ministry of
Science and Technology )
Competition of testing service new testing
field new technology/ standards
service import-export enterprise customization
testing service
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Bottom-up support of alternatives in China
Exchange and Consultations of Regulations/Directiv
e of Main Trade Countries Cosmetics
2003/15/EC,1223/2009/EC Chemical
REACH(1907/2006) Food EFSA,SCCP Labanimal and
welfare 2007/526/EC, 2010/63/EU
New Methods R D Government project Cooperation
Consensus platform
AQSIQ
Validation and Administration Acceptance multi-cen
ter validation bi-center validation accepted by
AQISQ
Standardization GLP of in vitro lab GCCP
guideline Alternative methods transfer Lab
certification by CNAS
Training and Education Standards training In
vitro testing training Animal welfare and 3Rs
education
Technology service Industries Enterprise The
third part institutes
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Standardization and administration acceptance
AQSIQ as administration responsible for
exit-entry inspection which support the
alternatives through set up SN testing
standards/guidelines for AQSIQ system. Also
provide the in vitro CRO service and third-part
entrusted testing. The Ministry of Health(MOH)
and CFDA as authority of the domestic cosmetics
responsible for issue and implement Cosmetics
Health Standards(2007 version), new Cosmetics
Safety Technical Specification(draft revision)
still insist on animal testing and will not
abolition old or add new test methods including
alternative methods.
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AQSIQ SN standards/guidelines acceptance
Good Laboratory Practice for Cosmetics
Alternative Testing In vitro. SN/T2285-2009 Cosme
tics Acute Toxicity of Keratinocyte Cytotoxicity
Test. SN/T 23282009. Cosmetics Ocular
Corrosive and Irritant HET-CAM Test
Method.SN/T2329-2009 Embryrotoxicity and
Developmental Toxicity of Mice Embryonic Stem
Cell Test. SN/T2330-2009 Cell line NRU test for
eye irritation Local lymph node assay (LLNA) for
skin sensitization Cosmetics guideline for
risk assessment strategy and decision-tree.No.2010
B072 cosmetics phototoxicity test for combined
RBC methods.No. 2010B074 cosmetics testing in
vitro for good cell culture practices and sample
preparation principles.No. 2010B075 cosmetics
guideline for alternative methods validation and
acceptance.No. 2010B076 cosmetics skin
irritation test for isolated skin. No. 2010B079
cosmetics developmental toxicity test for whole
embryo culture.No. 2010B269k
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Scientific validation activities

• 2010, AQSIQ set up validation criterion and
  procedure with reference to the EURL-ECVAM, OECD,
  ICCVAM related validation guideline.
• 2011-2013,multi-center validation for skin
  irritation by equivalent skin model Episkin(made
  in China)
• Milestone event for alternative methods
  validation in China

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organization
Management team
Auditor National new drug safety assessment
center China National Accreditation Service for
Conformity Assessment(CNAS)
Independent statistics the statistical society
members Chemical distribution professional
third-party outsourcing company The professional
transport
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• New Alternative Methods Development
• Short Time Exposure (STE) test for Cosmetics,
  an Alternative to Draize Eye Irritation Test
• A Modified Short-Time Exposure (mSTE) Test for
  Cosmetics an Alternative to the Draize Eye
  Irritation Test
• Screening of skin irritation using monolayer
  cells
• A Combined Test Skin Irritation Evaluation
  Monolayer cell, 3-dimensional Skin Model tests
  and Human Patch test
• The alternatives in oral mucous membrane
  irritation
• The integrated testing for eye irritation to
  personal and household care products
• Combination of CAMVA and BCOP to predictive the
  eye irritation of cosmetics.
• Establishing an in vitro screening test for
  developmental neurotoxicity
• Personal care products in vitro test based on the
  clinical characteristics of children's skin
• The role of TRP channels family at infant skin
  development and mechanism of mediated skin
  sensitization
• Anti-irritation study by 3D reconstructed skin
  model in vitro test
• Integrated screening methods study for personal
  care product skin sensitization

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Promote the integrated test strategy for
cosmetics safety and efficacy
safety/toxicity test
Efficacy test
Whitening Nutrition Anti-oxidant
Anti-ageing Anti-inflammation Angiogenesis Hair
growing Anti adipose Basic cytomics Repair in
vitro Patch test Anti-UV lesion (Photo) patch
test SPF test in vitro
Non-animal testign QSAR?TTC?Read-across Eye
irritation HET-AMBCOPRBCEpiocular Skin
irritation3D skin phototoxicity3T3 NRU,3D
skin Skin SensitizationDPRA, H-CALT,
co-culture Genotoxicity testing3D model Acute
oral toxicity predictivecytotoxicity embryotoxic
ityEST Endocrine disruptor screening .
Integrated Test Strategy
Human testing Adaptability and Efficacy test
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Support and Help Industries Application of
Alternative Methods
Recent years, Chinese brands gradually accept
alternative methods for safety assessment and /or
functional evaluation. We through various ways to
promote the application of these methods,
including training, testing services and other
customization mode. For toxicology assessment
covered acute toxicity prediction(3T3 NRU,KC NRU,
target tissue cytotoxicity), eye
irritation(CAMVABCOP,HET-CAMBCOP,MDCK-FLBCOP),
skin irritation (keratinocyte, EpiSkin),
phototoxicity(3T3 NRU-PTRBC-PT) and skin
sensitization(DPRA,H-CALT ). For in vitro
efficacy ingredients screening, for example
antioxidant(ring-CAM, fibroblast ROS),
sunscreen(keratinocyte P53, inhibition ET-1) and
whitening (anti-tyrosinase activity, inhibition
keratinocyte uptake). It is also helpful for the
safety evaluation and efficacy claims of
products. 
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Third part animal free testing service in China

• The number of testing increased every year
• OECD or valided methods Toxicity testing
• Market size forecasting only 2 million

Test methods covered
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Continuous Education and Training
1.Education and Scientific public Alternatives
Laboratory Animal Methods principle and
Application, Science Press,2010 The Three Rs and
the Humanity Criterion( Chinese version) ,Science
Press,2014 Predictive toxicology and guideline of
alternative methods, Science Press,2016 2.
Academic seminar
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Continuous Education and Training
From 2013, the formal alternative training
meeting were hold 1-2 times every year host by
Guangdong Inspection and Quarantine Technology
Center (GDCIQ). The first workshop hold in March
of 2013 at Guangzhou which the theme is Humane
Cosmetics Testing a new starting point for
China The 2nd hold in Aril of 2014 at Guangzhou
which the theme is the 3Rs Road from ideas to
practice. The 3rd hold in Nov. of 2014 at Chengdu
which the theme is the Alternatives
standardization and new technology application .
The 4th hold in April of 2015 at Guangzhou which
the theme is the Modernization of animal testing
and alternatives progress.
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The 5th Workshop of Alternative Methods
The 4th will be held 2nd-5th in Dec of 2015 at
Shanghai which the theme is the Animal free
testing in chemical and cosmetics
assessment. GDCIQs workshop has become China's
most influential alternatives meeting. Continuous
education and trainings promotes the no animal
testing alternative methods development in China.
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Consensus Platform for Alternatives Chinese
Center for Alternatives Research Evaluation
(CCARE) http//www.vitrotox.com

• CCARE Purpose
• Promote the knowledge and acceptance of the 3Rs
  alternatives at public
• Establish and maintain a sharing database on
  alternative resource
• Promote the standardization and application of
  alternatives
• Provide the communication platform between
  scientists, administrations and public

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Difficulties and challenge

• Promote animal free testing regulations approved
  in Chinese need
• Reconstructed animal welfare concept
• Filling the gap between animal welfare/3Rs
  concept and scientific realized way
• Support and help industries application
  alternative methods
• Reach a consensus between local industries and
  regulators
• Outspread application of alternative methods in
  the country, set up a laboratory network
• Need(policy and time) to set up corresponding
  related industry support
• National validation center and Data sharing

Bottom-up support ----may be slowly
----enterprise actively support gradually
----obeying market rules ----alternatives
acceptance is the scientific practice rather than
movement
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Obstacle Segmentation of management mode
complex network to promote animal free testing-
Good Outcome Pathway
Third part Co. Hi-tech service outsourcing
cosmetics Chemicals household medicines
Standardization Administration of China
(SAC) --cosmetics -labanimal -dangerous
chemicals -pesticide Pharmacopoeia 
industries
service
standards
Commercial Supplier Cell culture consumables
3D skin model Instrument in vitro
commerical
Regulation accept
Policy plan
government
validation
education
MOH MEP MOA AQSIQ MOST

• National
• Local government
• National department
• International cooperation
• Industrial policy

School education Higher education Continue
education Vocational education Public education
National CaVAM? Industries prevalidation CNAS
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Good Outcome Pathway (GOP) for Animal Free Testing
Organ Response
External motivation
Cellular Response
Organism Response
Initiating Event
Cellular Response
Valided accepted and Standard methods Application
Animal free testing universal Regulatory accept
Local industries laboratories Outspread
3Rs conception Toxicology Moderization
New methods innovation validation
Cosmetics animal testing ban
1990s 2008
2014
2020
?
2008
2020 ?
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Many thanks for your attention
Dr.Prof. Shujun Cheng Guangdong Entry-Exit
Inspection Quarantine Bureau Technology
Center WebsiteChinese Center for Alternative
Research and Evaluation(CCARE)
http//www.vitrotox.com Emailchengsj_at_126.com Tel
8620-3829067013602811627 Add 1211 B tower,
No.66 Huacheng Avenue, Guangzhou, China