1 dr. prof. shu jun cheng toxicology dept. of guangdong inspection & quarantine technology...
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1
Dr. Prof. Shu Jun Cheng
Toxicology Dept. of Guangdong Inspection & Quarantine Technology Center, Guangzhou, China
2015.11.20
Promote Animal-free Testing in China Through Bottom-up Way
• 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
Content
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.
Introduction of AQSIQ
AQSIQ
MotivationRegulations of global tradeCosmetics ban of animal testing,Chemicals/REACH advocate non-animal testing and animal only as last resort,Food additive, packaging material, pesticides risk assessmentBiology 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
Competition of testing servicenew testing fieldnew technology/ standards serviceimport-export enterprise customization testing service
Society development Animal protection movement Awakening of animal welfare consciousness ---2010/63/EU --- Guideline on Humane Treatment to LaboratoryAnimals ( Ministry of Science and Technology )
ConsumersafetyAQSIQ
Bottom-up way of Alternatives in China
Exchange and Consultations of Regulations/Directive of Main Trade Countries Cosmetics: 2003/15/EC,1223/2009/ECChemical: REACH(1907/2006)Food: EFSA,SCCPLabanimal and welfare: 2007/526/EC, 2010/63/EU
Standardization
GLP of in vitro lab
GCCP guideline
Alternative methods transfer
Lab certification by CNAS
Technology service
Industries
Enterprise
The third part institutes
New Methods R & DGovernment project Cooperation
Training and EducationStandards trainingIn vitro testing trainingAnimal welfare and 3Rs education
Validation and Administration Acceptance
multi-center validationbi-center validationaccepted by AQISQ
Consensus platform
Bottom-up support of alternatives in China
AQSIQ
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.
Standardization and administration acceptance
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
… … …
• 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
Scientific validation activities
organization
Management team
GuangdonGuangdong Labg Lab
CAIQ lab Beijing Beijing LabLab
Shanghai Lab
L`oreal R&I
AuditorNational new drug safety
assessment centerChina National Accreditation
Service for Conformity Assessment(CNAS)
Independent statistics: the statistical society membersChemical distribution: professional third-party outsourcing companyThe professional transport
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
Integrated Test
Strategy
safety/toxicity test Efficacy test
Non-animal testign:QSAR 、 TTC 、 Read-acrossEye irritation :HET-AM+BCOP+RBC+EpiocularSkin irritation : 3D skinphototoxicity : 3T3 NRU,3D skinSkin Sensitization : DPRA, H-CALT, co-cultureGenotoxicity testing : 3D modelAcute oral toxicity predictive :cytotoxicity:embryotoxicity : ESTEndocrine disruptor screening…….
WhiteningNutrition Anti-oxidant Anti-ageingAnti-inflammationAngiogenesisHair growingAnti adipose Basic cytomicsRepair in vitro Patch testAnti-UV lesion( Photo ) patch testSPF test in vitro
Human testing
Adaptability and Efficacy test
Support and Help Industries Application of Alternative MethodsRecent 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,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.
Third part animal free testing service in China
Test methods covered
• The number of testing increased every year
• OECD or valided methods Toxicity testing• Market size forecasting only 2 million
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 ChinaThe 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.
Continuous Education and Training
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.
The 5th Workshop of Alternative Methods
Consensus Platform for Alternatives
Chinese Center for Alternatives Research & Evaluation (CCARE)http://www.vitrotox.comCCARE 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
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
………
Difficulties and challenge
Bottom-up support ----may be slowly ----enterprise actively support gradually ----obeying market rules ----alternatives acceptance is the scientific practice rather than movement
government
serv
ice
Policy
plan
standards
Standardization Administration of China
(SAC)--cosmetics
-labanimal-dangerous chemicals
-pesticidePharmacopoeia
cosmeticsChemicalshousehold medicines
Third part Co.Hi-tech serviceoutsourcing
• National• Local government• National
department• International
cooperation• Industrial policy
School educationHigher educationContinue educationVocational educationPublic education
MOHMEPMOAAQSIQMOST
Commercial SupplierCell culture consumables 3D skin modelInstrument in vitro
valid
ati
on
Regulationaccept
National CaVAM?Industries prevalidation CNAS
commerical
Obstacle: Segmentation of management mode complex network to promote animal free testing- Good Outcome Pathway
educatio
nin
dust
ri
es
Good Outcome Pathway (GOP) for Animal Free Testing
Initiating Event
Cellular Respons
e
Organism Response
Organ Response
Valided accepted
and Standard methods
Application
Local industries
laboratories
Outspread
New methods innovation
validation
Cosmetics animal testing
ban
Animal free testing
universal
Regulatory accept
3Rs conception
Toxicology Moderizatio
n
External motivation
1990`s2008
2008
2014 2020
2020 ?
?
Cellular Respons
e
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 : [email protected] : 8620-38290670 ; 13602811627Add: #1211 B tower, No.66 Huacheng Avenue, Guangzhou, China