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 ： chengsj@126.comTel ： 8620-38290670 ； 13602811627Add: #1211 B tower, No.66 Huacheng Avenue, Guangzhou, China