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Platform 3Rs in Regulation
An important objective of EPAA is to improve the implementation
of 3Rs in European regulatory testing and decision making. It
therefore aims to identify optimised approaches on testing and
risk assessment strategies in existing and upcoming legislation
and their implementation so as to avoid double and redundant,
as well as unnecessary testing. In this respect, EPAA strives
to share experience and evaluate consistency across sectors,
analyse hot spots and to identify policy drivers for testing.
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Integrated Testing Strategies
In the framework of its activities on "Integrated Testing
Strategies and their impact on the 3Rs", the 2011 EPAA
Lead Theme, the EPAA organized a workshop on ITS in Brussels
on 26 September 2011.
For EPAA, the term ITS (Integrated Testing Strategies) is meant
to cover more than a strategic combination of tests. An ITS
might well include non-testing methods (computer based tools
such as QSARs, non animal- based ADME-models, etc), and even
in vivo models. Essentially, as standalone, the individual components
of an ITS cannot provide all information needed for decision
making but their strategic combination can.
The objective of the workshop is to explore how industry is
already adopting ITS in decision making and to discuss its (potential)
use in regulatory compliance procedures. Several EPAA members
representatives of different industry sectors will present their
general approaches to ITS, setting out their common limits and
strengths. They will also address their perceived impact on
the 3Rs. In addition, individual companies from these sectors
will present case studies of ITS effectively being implemented
in their decision making or having past the "proof of concept"
phase.
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Workshop on
ITS and their impact on the 3Rs
26 September 2011, Brussels
Programme
ITS
Fact Sheet
Flash
report
Presentations |
Optimized testing strategies for skin sensitization
- LLNA and beyond
The meeting will build upon the findings of the 2010 LRI Workshop
on the Local Lymph Node Assay (LLNA). The intention is to share
industry sector experience thereby laying the foundations to
discuss and recommend future initiatives in skin sensitization
testing. |
Skin sensitisation training workshop: Moving forward with non-animal testing strategies
A joint workshop from EPAA and Cefic LRI
Helsinki, Finland – 4th February 2013
Press release
EPAA Cross Sector
Workshop
19 and 20 September 2011, Brussels
Programme
Flash
report |
3Rs
in acute toxicity testing
A cross-sector review of the drivers for acute systemic toxicity
testing and of alternative approaches was carried out by an
EPAA Task Force in collaboration with the HSI (Humane Society
International) and the NC3Rs (National Centre for the Replacement,
Refinement and Reduction of Animals in Research). The review
resulted in several recommendations for promoting reduction
and refinement in the area of acute toxicity (e.g. deletion
of the requirement for acute toxicity testing of active/individual
substances by dermal route for classification and labelling,
particularly for plant protection products and industrial chemicals).
The findings will be published in the Journal Toxicological
Sciences and will be discussed with regulators at a workshop
planned for 16 September 2010 in Brussels. The publication (Seidle
et al., 2010) is already available online via Advance Access
(
http://toxsci.oxfordjournals.org/ ).
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Workshop
"Cross-Sector Review of Drivers and Alternative Approaches for
Acute Systemic Toxicity Testing"
16 September 2010, Brussels
Final
report
ACUTE TOXICITY Round Table,
to address the hypothetical situation "How could C&L
decisions in the agrochemical and chemical sectors be made if
stand-alone acute toxicity testing were prohibited?
28 September 2012, Brussels
Flash
report
Full report |
Consistency
approach in vaccines testing
The consistency approach is based upon the principle that the
quality of a vaccine is the consequence of the strict application
of a quality system and of a consistent production of batches.
Through the application of this principle, which has been implemented
for some novel human vaccines, agreed product characteristics
can be tested in vitro during the manufacturing process of a
batch and shown to be similar to those of batches demonstrated
to be safe and effective in clinical trials. The concept of
consistency may therefore be applied to conventional vaccine
production in order to replace in vivo tests with in vitro tests
indicative of the quality and quantity of the product whilst
maintaining the highest quality and safety standards.
The vaccines project team has conducted a survey of 3Rs alternatives
to current animal tests that are available for use or under
development. We hope that the survey
and accompanying presentation
will be useful and informative to those working in this field
and we welcome comments and contributions to keep the survey
accurate and up to date. All contributions should be sent to
the Project Coordinator, Dr Ian
Ragan.
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ECVAM/EPAA Workshop on The Consistency
Approach for Quality Control of Vaccines – a 3Rs opportunity
11-12 January 2010, Brussels
More information
here
Final
report
Workshop on the Application
of the Three Rs and the Consistency Approach for Improved Vaccine
Quality Control
7 April 2011, Brussels
More information here
Flash
report
DTaP vaccines workshop
30 - 31 August 2012, Den Dolder
Flash
report
EPAA-EURL ECVAM Workshop on
Replacement of In Vivo Human Rabies Vaccine Potency Testing
by In Vitro Glycoprotein Quantification Methods: Validation
Status and Implementation Strategies
8 - 9 October 2012, Arcachon, France
Flash
report
EPAA workshop on implementation
strategies of the consistency approach for veterinary inactivated
rabies vaccines
5 - 6 November 2012, Brussels, Belgium
Flash
report
Vaccines consistency approach workshop:
Clostridial Vaccines
19 March 2013, Brussels, Belgium
Flash report
Introduction
to the survey
EPAA
survey on vaccines consistency approach |
Extended
one-generation study
This EPAA action focuses on the evaluation of opportunities
for the more widespread application of testing strategies being
developed as the Agricultural
Chemical Safety Assessment (ACSA) approach for reproductive
toxicity, e.g., for regulatory testing under REACH.
The extended one-generation reproductive toxicity study design
is currently under consideration as an alternative to the current
one- and two-generation tests, with potentially widespread applicability
and impact on chemical safety assessment across many industry
sectors. The EPAA evaluated whether this new approach developed
for agrochemicals, could also be applied to other sectors (e.g.
industrial chemicals). This will deliver animal welfare benefits
with regard to both refinement and a reduction in the number
of animals used.
The extended one-generation study as a replacement of the classical
two-generation study would lead to a significant reduction in
animal numbers used for testing of one substance (1400 instead
of 2600 animals, representing a reduction of 45 %). In addition,
through more sophisticated measurements and the inclusion of
additional endpoints, the extended one-generation study would
be a refinement when compared to the classical two-generation
study. An OECD expert group was set up end of 2007 to develop
a draft guideline and evaluate the validity of the endpoints
used. The draft version of the guideline can be downloaded from
the OECD
homepage.
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The
extended one generation study
Workshop
on Triggering and Waiving Criteria for the Extended One-Generation
Reproduction
Toxicity Study 14-15 April 2008, Barza d'Ispra
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Investigating
regulatory requirements and drivers
In a series of sector specific workshops, the EPAA has mapped
the regulatory landscape and identified priority areas and drivers
to the implementation of alternative approaches. Participants
formulated a series of recommendations that were subject of a
specific EPAA follow-up, or are covered by activities by the EPAA
or the European Commission otherwise initiated.
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Sector
specific workshops
Implementation and Reporting
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Supporting
validation
EPAA has a great potential to bring new levels of efficiency
to the prioritisation and process of validation, by promoting
closer collaboration between the European Center for the Validation
of Alternative Methods (ECVAM) and industry.
From the first survey among the industry members of EPAA on availability
of data for alternative methods, it emerged that most substances
and data had already been provided at earlier stages, due to the
way that substance selection is implemented. In addition, for
certain substances, no data were available, or data were available
but for a different set of substances. A fine-tuned framework
for collaboration will be used for the next calls for substances.
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Collaboration
framework
Selected method profiles
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Overcoming barriers to validation
EPAA has identified a number of barriers to validation, some
of which are administrative, others of a scientific nature.
The following recommendations stemming from current debates
are being actioned:
• Systematic application of identical procedures for all submissions
for validation;
• Definition and disclosure of criteria for admitting a method
for validation;
• Avoidance of proprietary substances and data in selection
of materials;
• Complementing the selection of substances by calls at an early
stage before the finalization of study protocols, and;
• Optimisation of the peer-review process.
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Debates
Work in progress
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Overcoming barriers to regulatory
acceptance
EPAA has demonstrated its potential to serve as an inter-sectoral
platform and as a catalyst for cross-fertilization. Comparing
mechanisms and solutions from different sectors helps to identify
the most efficient approaches while respecting sectoral specificities
and needs. Currently, the EPAA is following up on the following
suggestions made in recent debates and workshops:
• the involvement of regulators at an early stage of method
validation;
• better dissemination of information about available alternatives;
and
• the inclusion of 3Rs on the agendas of all relevant international
regulatory meetings.
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Debates
Work in progress
- Ongoing work on regulatory modules
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Case studies; regulatory compliance
Case studies across sectors have been initiated to verify how
3R approaches can be developed to meet regulatory requirements,
taking benefit of the cross-fertilisation potential offered
by the EPAA. These include the developing criteria for using
possibilities to waive animal testing under REACH, harnessing
existing weight-of-evidence approaches and expert judgment across
sectors to avoid any additional animal testing for purposes
of classification under the GHS, verifying the relevance of
current data requirements in different sectors on acute toxicity
where only very limited value is obtained, or sharing information
on testing requirement stemming from bilateral dialogues between
companies and authorities. |
- Acute
toxicity
- Weighted evidence as a tool for the GHS
- Waivers of animal testing under REACH
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