value of in vitro assays in your reach dossier frédérique van acker 18 november 2014
TRANSCRIPT
Value of in vitro assays in your REACH dossierFrédérique van Acker
18 November 2014
Agenda
Introduction
What are the drivers of in vitro alternatives
Regulatory developments
Value of in vitro in your REACH dossier
New developments
Who drives development of these alternatives
Status of these new developments
Take home message
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Contents of registration dossier
For a proper safety assessment data on multiple topics need to be
provided
Physicochemical properties
Ecotoxicology
Environmental fate
Anticipated human exposure
Toxicology
Focus on Toxicological data
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Toxicological building blocks
For a full assessment different aspects of toxicology need to be
addressed, a.o.
Genetic toxicology
Acute and repeated dose toxicity
Reproduction toxicology
Data on metabolism (TK, ADME)
Continuous scientific and regulatory developments may lead to
considerable changes in the necessary test package for a dossier
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In vivo vs. in vitro
Majority of toxicological data are generated in vivo
For many endpoints the in vivo data are still considered the golden
standard
But an increasing number of endpoints can and is addressed in vitro
Endpoints genotoxicity, phototoxicity, skin and eye irritation have a
tiered approach and performing in vitro assays as first tier is obligatory
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What are the drivers of in vitro alternatives?
Public perception
Regulatory
Image
Technological developments in science
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Public perception
Increased awareness of CSR and sustainability
Animal rights organizations take position
Increased societal pressure
Higher on political agenda
Multiple initiatives emerged to make a good case for alternative
methods.
EU Horizon 2020 call: PHC-33-2015: New approaches to improve
predictive human safety testing (Budget € 88.000.000)
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ECHA’s point of view
REACH
Annex XI states that an in vivo test must be waived when there is a
validated in vitro alternative
2nd ECHA report on the use of Alternatives, 2014 states:
Using animals for testing should be a last resort – only when there
are no other scientifically reliable ways of assessing the potential
effects on humans or the environment.
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Currently in draft: skin sensitization, cell transformation
Regulatory developments in vitro assays
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Cosmetic Products Regulation (EU 1223/2009)
In EU complete ban on animal testing for cosmetic products and
ingredients since July 2013
Consequences: all endpoints need to be addressed in vitro!
Observed ‘workaround’: registration under REACH, pharmaceutical
product
Article 18 of the Cosmetics Products regulation on animal testing:
The toxicological profile of a substance contained in the cosmetic
product should be determined for all relevant toxicological endpoints.
A particular focus on local toxicity evaluation (skin and eye irritation),
skin sensitization, and in the case of UV absorption photo-induced
toxicity shall be made.
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Implications Cosmetics regulation
Skin penetration → systemic availability → assess systemic toxicity
and reprotoxicity
How to deal with these complex endpoints?
Validated in vitro alternatives not yet available, developments ongoing
Regulatory acceptance of alternatives for complex endpoints unclear
Cosmetic industry currently placed in impasse
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Value of these assays in your dossier
Multiple in vitro assays are required by ECHA for a REACH dossier
Some assays fully replace in vivo assays, others are additional
In vitro assays are very useful for mechanistic understanding
Our newly developed in vitro assays may even better predict human
toxicity, due to use of reconstructed ‘organs’ from human origin.
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New developments: human 3D models
13www.mattek.com
New developments: 3D cell culture → spheroids
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New developments: organ on a chip
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Who drives development of these alternatives?
The clients!
We see an increase in demand for in vitro, allowing us to continue our
innovation for the in vitro market
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Status of these new developments
Innovative assays are currently being developed
Increased number of in vitro studies regulatory accepted
More and more in vitro studies preferred as regulatory replacement
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What is the relevance to us?
Regulatory changes determine how dossier is built up
Giving sound advise and consultancy is of great value to us
We are closely following regulatory developments and ongoing
discussions
Knowledge of recent changes allows for a tailor-made & cost efficient
proposal to compile a dossier
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Take home message
Alternative assays are becoming increasingly important in safety
assessment
Recent advances in technology hold great promise for future assays
Organ cultures from human origin may be very useful in mechanistic
evaluation and/or prediction for human safety
Keep an eye out for alternative methods !
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