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
1
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
Introduction of AQSIQ
AQSIQ
General Administration of Quality Supervision, Inspection
and Quarantine of People’s 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.
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
Consumer
safety
AQSIQ
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
Bottom-up support of alternatives in China
Exchange and Consultations of
Regulations/Directive 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
AQSIQ
Consensus
platform
Validation and Administration
Acceptance
multi-center validation
bi-center validation
accepted by AQISQ
Standardization
GLP of in vitro lab
GCCP guideline
Alternative methods transfer
Lab certification by CNAS
Technology service
Industries
Enterprise
The third part institutes
Training and Education
Standards training
In vitro testing training
Animal welfare and 3Rs
education
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.
AQSIQ SN standards/guidelines acceptance
•Good Laboratory Practice for Cosmetics Alternative Testing In vitro. SN/T2285-2009
•Cosmetics Acute Toxicity of Keratinocyte Cytotoxicity Test. SN/T 2328—2009.
•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.2010B072
• 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
………
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
organization
Management
team
Auditor
Independent statistics: the
statistical society members
Chemical distribution:
professional third-party
outsourcing company
The professional transport
National new drug safety
assessment center
China National Accreditation
Service for Conformity
Assessment(CNAS)
Guangdong
Lab
CAIQ lab
Beijing Lab
Shanghai
Lab
L`oreal R&I
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
Promote the integrated test strategy for cosmetics
safety and efficacy
Efficacy test
safety/toxicity test
Non-animal testign:
QSAR、TTC、Read-across
Eye irritation ：
HET-AM+BCOP+RBC+Epiocular
Skin irritation：3D skin
phototoxicity：3T3 NRU,3D skin
Skin Sensitization：DPRA, HCALT, co-culture
Genotoxicity testing：3D model
Acute oral toxicity predictive：
cytotoxicity:
embryotoxicity：EST
Endocrine disruptor screening
…….
Integrated
Test
Strategy
Human testing
Adaptability and 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
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(CAMVA+BCOP,HET-CAM+BCOP,MDCK-FL+BCOP), skin irritation
(keratinocyte, EpiSkin), phototoxicity(3T3 NRU-PT+RBC-PT) and skin sensitization(DPRA,HCALT ).
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.
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
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
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.
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.
GDCIQ`s workshop has become China's most influential alternatives meeting.
Continuous education and trainings promotes the no animal testing alternative methods
development in China.
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
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
Obstacle: Segmentation of management mode
complex network to promote animal free testing- Good Outcome Pathway
Standardization Admi
nistration of China
(SAC)
--cosmetics
-labanimal
-dangerous chemicals
-pesticide
Pharmacopoeia
•
•
•
•
•
National
Local government
National
department
International
cooperation
Industrial policy
cosmetics
Chemicals
household
medicines
Third part Co.
Hi-tech service
outsourcing
Commercial Supplier
Cell culture consumables
3D skin model
Instrument in vitro
Regulation
accept
National CaVAM?
Industries prevalidation
CNAS
School education
Higher education
Continue education
Vocational education
Public education
MOH
MEP
MOA
AQSIQ
MOST
Good Outcome Pathway (GOP) for Animal Free Testing
External
motivation
3Rs
conception
Toxicology
Moderization
1990`s
2008
Initiating
Event
Valided
accepted
and
Standard
methods
Application
2008
Cellular
Response
Cellular
Response
Organ
Response
Local
industries
laboratories
New methods
innovation
validation
Cosmetics
animal
testing ban
2020
2020 ?
Outspread
2014
Organism
Response
Animal free
testing universal
Regulatory
accept
?
Many thanks for your attention
Dr.Prof. Shujun Cheng
Guangdong Entry-Exit Inspection & Quarantine Bureau Technology Center
Website：Chinese Center for Alternative Research and Evaluation(CCARE)
http://www.vitrotox.com
Email：chengsj@126.com
Tel：8620-38290670；13602811627
Add: #1211 B tower, No.66 Huacheng Avenue, Guangzhou, China