EU Regulation 1107/2009, recent developments and how to work with it

EU Regulation 1107/2009, recent
developments and how to work with it
David Kirkpatrick
Regulation 1107/2009 – key issues
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Where are we now?
Regulatory review timelines
Data requirements
Risk assessment guidance
Hazard criteria
– Endocrine disruption
– PBT
• Substitution candidates and comparative
assessment
• Classification, labelling and packaging (CLP)
Where are we now?
• Regulation 1107/2009 has been in operation for
one year
• 67 new active substances that were delayed in
EFSA by the 91/414 review programme, are still in
the system (Regulation 188/2011)
• First new active substances submitted under
1107/2009 are expected to reach EFSA in 2013
• Resources at EFSA are an issue
• New data requirements close to finalisation
• New guidance being developed in many areas of
risk assessment
Timeline for new substance review under
1107/2009
Applicant submits dossier to RMS
RMS does completeness check:
45 days
RMS requests additional information/studies: max 3 months
RMS prepares DAR and submits to
EFSA and Commission: 12 months
RMS requests additional information/studies: max 6 months
EFSA sends DAR to other MS:
30 days
Other MS can comment: 60 days
EFSA requires expert meeting: 30 days
EFSA adopts conclusion: 120 days
EFSA requires more information: Applicant 90 days, RMS 60 days
Commission presents report and draft regulation to SCFCAH: 6 months
The review process
Should be faster than under 91/414 but…
…to minimise delays:
– Try to make the dossier as complete as possible
– Reduce scope for authorities to request additional
information
– Try to reduce potential need for new studies
• There will still be questions and requests for
information
– These should be answered as quickly as possible
• Remember, there is no provisional approval
process
Data requirements – current status
• Most recent drafts dated March 2012
• Active substance
– SANCO/11802/2010 Rev. 3
(POOL/E3/2010/11802/11802R3-EN.doc)
• Plant Protection Product
– SANCO/11803/2010 Rev.3
(POOL/E3/2010/11803/11803R3-EN.doc)
• Final versions expected Q3 2012
• Two year window before obligatory
• But best to pay attention now – will apply to AIR 3
Main new data requirements:
human risk assessment
Discipline
Toxicology
Residues
New requirement
Status
Purpose
Comparative in vitro metabolism
Mandatory
Toxicology species
relevance to man
Toxicokinetic data in short and long-term
and reproductive studies
Mandatory (but
not all studies)
Dose selection
Interpretation of
toxicology studies
Phototoxicity, Photomutagenicity
Conditional
Developmental neurotoxicity – where
indicated by other studies or MoA
Conditional
Human risk
assessment
Residue trials in crops – possible reduction
in requirements
Mandatory
Fish metabolism, feeding
Conditional
Rotational crop metabolism and residues –
new approach
Conditional
Residues in honey
Conditional
Dietary risk
assessment
Main new data requirements:
environmental risk assessment
Discipline
Environmental
fate
Ecotoxicology
New requirement
Status
Purpose
Field soil dissipation – additional DT90
triggers
Conditional
Capture biphasic
cases
Aged sorption
Optional
Higher tier model
inputs
Indirect photolysis in water
Conditional
Aerobic mineralisation in surface
water, OECD 309
Mandatory in
most cases
Environmental risk
assessment
Amphibian metamorphosis, choice
of fish studies – 21-day, short term
repro, sexual development, life cycle
Conditional
Endocrine disruption
tests
Fish bioconcentration: New trigger
hydrolysis DT90 >24 hr.
Log POW >3 still
applies
Capture long term
exposure
Studies with bees – new guidance
being developed
Mandatory
Protection of
pollinators
Environmental risk assessment
guidance
• Aquatic:
– Existing document (SANCO 3268/2001) to be split into
four separate guidance documents
– EFSA has requested a mandate extension. Public
consultation of first document expected Autumn 2012
• Terrestrial
– Existing document (SANCO 10329/2002) to be split
into six separate guidance documents
– Opinion on bees published May 2012
– EFSA’s deadlines for the others range from March
2014 to June 2017
Risk assessment for bees: key questions
• Impact of pesticides on colony development and survival
• Effects of long-term exposure to low concentrations of
pesticides
• Cumulative effects of combinations of pesticides
– Honey bees have the lowest number of detoxification
enzymes in the insect kingdom
• Measurement of exposure in field studies
• Ability of current field tests to detect small increases in
daily mortality or sub-lethal effects
EFSA Journal 2012;10(5):2668
http://www.efsa.europa.eu/en/efsajournal/pub/2668.htm
Risk assessment for bees:
EFSA proposals
• Separate assessment schemes for honey bees and for
bumble bees/solitary bees
• Initial testing to include an exposure period of seven to
ten days for both adult bees and larvae.
• Investigation of exposure via both nectar and pollen
• Improvements to design of existing semi-field and field
tests
• Statistical analysis of test results
• Of course this is all open to public comment before it
becomes “Guidance”
• But there will be new data requirements
Other areas where guidance is being
revised or under development
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Persistence in soil
Probabilistic dietary risk assessment
Cumulative dietary risk assessment
Operator, worker, bystander, resident risk
assessment
• Protected crops
• Concept of Threshold of Toxicological Concern
Hazard criteria
• For approval
– Carcinogenic, mutagenic, toxic for reproduction
(CMR), category 1A or 1B
– Endocrine disrupter
– Environmental properties: POP, PBT, vPvB
• For substitution (additional to approval criteria)
– ADI, ARfD or AOEL much lower than other competitor
active substances
– 2 of PBT criteria
– Neurotoxic or immunotoxic effects of concern
– Active substance contains inactive isomers
Endocrine disruption – provisions of
1107/2009
• By 14 December 2013, Commission must present a
draft proposal of specific scientific criteria for the
determination of endocrine disrupting properties
• Pending the adoption of these criteria:
• Substances classified as C2 and R2, shall be considered
to have endocrine disrupting properties
• Substances classified as R2 and which have toxic effects
on the endocrine organs, may be considered to have
endocrine disrupting properties
(Annex II, 3.6.5 and 3.8.2)
The OECD framework for Testing and
Assessment of Endocrine Disrupters
Level
Test types
1
Sorting & prioritization based upon existing information
2
In vitro assays providing mechanistic data
3
In vivo assays providing data about single endocrine
mechanisms and effects
4
In vivo assays providing data about multiple endocrine
mechanisms and effects
5
In vivo assays providing adverse effects data from
endocrine & other mechanisms
http://www.oecd.org/document/58/0,3343,en_2649_34377_2348794_1_1_1_1,00.html
Recent progress
• February 2012: Commission report
– “State of the Art of the Assessment of Endocrine
Disruptors”
– Issues:
• Appropriate tests and endpoints for the identification
of ED properties need to be implemented
• Criteria for the translation of test outcomes into
regulatory decisions need to be developed
Some recommendations on testing:
human health
• Testing in whole organisms is required to identify an
endocrine disrupter
• Tests from OECD Level 5 should be mandatory
• ED endpoints should be added to reproductive studies
(2-gen or extended 1-gen, OECD 416 or 443)
• Developmental neurotoxicity and immunotoxicity are
of particular relevance
• OECD Level 2 in vitro tests should be included in
requirements
• Uterotrophic and Hershberger tests are of questionable
value
Some recommendations on testing:
ecotoxicology
• Current testing requirements limited – could only
detect ED effects on birds and possibly fish
• Most OECD Level 4 and 5 tests still under
development
• For now, assessment has to rely on currently
available OECD Level 3 tests
• To demonstrate wildlife ED effects, inclusion of all
validated test guidelines for non-mammalian
species at Levels 3, 4 and 5 will have to be
considered
Decision criteria considered
• Adversity – are there effects in intact organisms?
• Mode of action - has to be ED
• Potency - linked to STOT RE classification - very
controversial
– For, Germany, UK; against, Denmark, France
• Lead toxicity - ED effects at lower doses than other
effects
• Specificity - direct MoA or environmental species
specificity
• Severity - should effect be classed as C, M or R?
• Irreversibility
• Relevance - human or environmental health
Some overall recommendations
• Develop further guidance documents for the
interpretation of test data
• Consider the creation of a separate regulatory
class “Endocrine Disrupter” (ED)
• Develop weight-of-evidence procedures and
use them to consider all proposed criteria in
parallel
• Abandon “potency” as a rigid cut-off criterion
Substitution candidates and
comparative assessments
Objectives:
• To reduce risks from the use of plant
protection products by gradually replacing
those containing substitution candidates by
methods or products of lower risk
• To benefit human health and the
environment, whilst minimising the economic
and practical disadvantages for agriculture
Regulatory framework
• Active substances
– Identification as candidates for substitution is a
community level process – EFSA, MS, COM
– Approval periods will be limited
– Selection based on hazard criteria
– List of candidates to be published by Dec 2013
• Plant protection products (PPP)
– Comparative assessment and substitution is a
Member State process
Article 50(1) – mandatory comparative assessment
of a PPP containing a candidate for substitution
• MS shall not authorise or shall restrict the use if
– A product or non-chemical method exists which is
significantly safer for human or animal health or the
environment
– The substitution does not present significant
economic or practical disadvantages
– The chemical diversity of active substances or
methods and practices are adequate to minimise the
occurrence of resistance, and
– The consequences on minor uses are taken into
account
Comparative assessment: criteria to be
considered
Criterion 1a
Is there an alternative product or non-chemical method
available?
Criterion 1b
Has sufficient experience of the alternative been gained?
Criterion 2
Is there a negative effect of efficacy?
Criterion 3
Is chemical diversity protected?
Criterion 4
Are minor uses protected?
Criterion 5
Are there significant practical or economic disadvantages?
Criterion 6
Are the risks to man and the environment significantly
lowered?
Over time it is important to consider experience gained on the consequences
of substitution
Annex IV of Regulation 1107/2009 states that all criteria should
be met before substitution applies
Comparative assessment responsibility for
guidance
• Efficacy
• Risk of developing resistance
• Practical/economical disadvantages,
and effects on minor uses
EPPO
• Risks for health and the environment
• Final decision (risk/benefit)
Sweden
proposal
Sweden believes that products fulfilling all
provisions for substitution will probably be few
Comparative assessment:
ECPA Position
“Comparative assessment must be applied using
pragmatism, rigor and robust scientific principles to
prevent unwarranted substitutions and further
deterioration of the competitiveness of European
agriculture.”
• Notifier should be asked to comment during the
assessment
• Notifier should be informed prior to any decision being
made
• It is not possible for human health to take precedence
over environmental health and vice versa
Persistence, Bioaccumulation, Toxicity
• Persistence criterion is most easily triggered
– E.g. DT50 soil > 60 days applies to many active substances
– Introduction of OECD 309 may bring in more substances
• Bioaccumulation is rarely triggered
– Few substances have BCF > 2000
• Toxicity – range of test organisms is wide, so this can be
an issue
• For approval to be refused, all 3 criteria have to be met
so rarely a problem
• For substitution candidacy only 2 have to be met –
trade-off between persistence and toxicity
Classification
• In addition to 1107/2009, plant protection products
(PPP) are subject to the Classification, Labelling and
Packaging (CLP) Regulation 1272/2008
• Manufacturers, importers and downstream users are
responsible for proposing a classification before a
substance is placed on the market
• For PPPs the situation is complicated because the RMS
or EFSA may propose a classification that the notifier
does not agree with
• EFSA , ECHA and MSCAs are developing a plan on how
to work together
ECHA = European Chemicals Agency, MSCA = Member State Competent Authority
Conclusions
• Regulation 1107/2009 has introduced some major
changes to the way PPPs are approved in Europe
• Time to registration should be faster than under 91/414
but “Provisional Approval” no longer exists
• Industry is concerned about “substitution”
– It remains to be seen how this will work
• Immediate changes to data requirements are not major
but eventually there will be significant additions relating
to endocrine disruption and bees
• Development of risk assessment guidance will continue
for many years to come
• Europe is a large market and it is still worth going for
registration