Evaluation of active substances under the Review
programme and its impact on biocidal products
authorisation process and placing on the market
Dr Andy Adams
Bayer Environmental Science, Lyon, France
Workshop on REACH and EU Biocides legislation,
Belgrade 31st May – 1st June 2012
Introduction
How it was supposed to happen
Where are we?
What has been the impact?
Rodenticides
Insecticides
What does it mean for formulators?
Summary
page 2 • Title • 22 March 2016
BPD Timetable (according to the text)
Anticipates approx. 2 years from submission to decision
Completeness check
Evaluation
Decision-making
Comments
3
12
Product Registration
Annex I listing
3
6-18
PT14:
Rodenticides
PT18:
Insecticides
List 1:
28/03/2004
30/04/2006
Presentation • March 22, 2016 • Slide 3
31/07/2007
31/10/2008
Where are we?
The Commission website provides a consolidated list of inclusion decisions.
http://ec.europa.eu/environment/biocides/index.htm
May 2012 summary:
List 1 (2004)
– PT8, 25 inclusion decisions (16 decisions to come)
- PT14 13 inclusion decisions (2 decisions to come)
List 2 (2006)
- PT18, 15 inclusion decisions (48 decisions to come)
- PT19, 4 inclusion decisions (12 decisions to come)
List 3 (2007)
- PT12, 1 inclusion decision (42 decisions to come)
(18 PTs with no inclusion decisions yet)
Total: 58 inclusions, approx. 650 decisions remaining.
page 4 • Title • 22 March 2016
What has been the impact on rodenticides?
Most of the anti-vitamin K (AVK), anti-coagulant rodenticides were defended under BPD
Cholecalciferol was identified but not notified, diphacinone was notified but not
defended.
(Under 91/414, for plant protection purposes, the only AVKs that remain approved are
bromadiolone, warfarin and difenacoum.)
So, the substances remain, but restrictions on their use are significantly greater than
before through the introduction of risk mitigation measures as conditions for product
authorisation.
The issues have been related to different timings for the substances, national procedures
not compatible with genuine harmonisation. Plus, inclusion is for 5 years, only, and
then will come « comparative assessment ».
page 5 • Title • 22 March 2016
Rodenticides included in Annex I
Category
Substance
Date of inclusion into Annex I
Expiry date inclusion into Annex I
Acute poison
Alphachloralose
1 July 2011
30 June 2021
Gas
Carbon dioxide
1 November 2009
31 October 2019
Aluminium phosphide
releasing phosphine
1 September 2011
31 August 2021
1 July 2011
30 June 2016
1 July 2011
30 June 2016
1 February 2012
31 January 2017
1 February 2012
31 January 2017
First
Coumatetralyl
generation
Chlorophacinone
anticoagulants
Warfarin
Warfarin sodium
Second
Difethialone
generation
anticoagulants Difenacoum
All the anticoagulants
(first and second
1 November 2009
31generation)
October 2014
only included in Annex I for 5 years
1 April 2010
31 March 2015
Bromadiolone
1 July 2011
30 June 2016
Flocoumafen
1 October 2011
30 September 2016
Brodifacoum
1 February 2012
31 July 2017
Product authorisation and mutual
recognition
One of the great hopes for the BPD was that mutual recognition would work well
to reduce administrative load and promote harmonisation, thereby fostering
free-trade.
Unfortunately, and perhaps, understandably, Member States are not keen to give
up their national practises and sovereign responsibilities.
An additional factor comes with the post-Annex I procedure where product
dossiers are compiled by formulators who rely on a letter of access from the
active substance manufacturer who secured the Annex I inclusion.
A formulator in Italy may only operate in the Italian market, while another in
France may operate in Spain and Belgium, for example. But both formulate
essentially the same product (a wax block with x% of rodenticide A)
Post-Annex I « Gentlemen’s agreement »
10 yr data protection starts
Dossier preparation (submission?)
Standing
Committee
Annex I inclusion.
Vote
???
No LoA
Compliance
deadline is the
limit for re-reg
(4y after entry
into force)
Submission deadline
Sell out ……
Publication
Review
24 months
3m
LoA
12 months
Completeness check
9 months Mutual recognition
2 months to apply; 4
months for MS to
evaluate; 3 month
« buffer »
Problems with compliance deadline
The compliance deadline is written into national law with the transcription of the
BPD, so all products linked to the included ai/PT must be approved by then.
Respecting timelines has not been a feature of the review process.
Problems with the first actives, dichlofluanid, difethialone …
EMS took too long, no time for MR!!!
What were the implications in practise?? ………………..
Real impacts!!
The German case:
UK was late completing evaluation of dichlofluanid products, no time
for Germany to grant MR before the deadline, companies were
forced to withdraw products from the market because there was
no pre-existing authorisation.
This meant large costs (withdrawal, destruction of stocks), cost jobs
and led to legal cases for companies who were trying to comply
and products that were being defended to meet the gold standard
of the BPD!!!!
In other MS, the authorities found ways to extend existing
authorisations until the mutual recognition procedure was
completed.
Real impacts
Numerous implications for industry:
time to adapt to risk mitigation measures, new labels and use conditions etc.
seasonal supply to outlets, sell out,
logistics of manufacturing timing versus decision on authorisation
conditions…
These issues hit those who are complying with the standards set by the BPD and
introduce more cost while their competitors remain on the market with
products that have not been evaluated yet due to delays in the review.
Big incentive to slow things down and stay on the market.
Totally contrary to the aims of the legislation.
Administering Mutual Recognition
In principle, a product dossier is submitted to an Evaluating Member State (EMS)
EMS conducts evaluation and grants authorisation
Applicant makes formal MR application to other MS
Other MS base their examination on summary
dossier and the authorisation conditions from the
EMS
Other MS recognise the approval conditions as
determined by EMS according to uniform principles
A « simple » case
Active substance A is defended by one company which is also the only
formulator in EU. They provide formulated product to third parties to place on
local markets under own brands.
A is formulated into 5 products and these 5 dossiers are reviewed by one
Evaluating Member State (EMS).
Upon authorisation in the EMS, applications for mutual recognition are made to
15 other MS for the 5 products, with the additional notification of specific
marketing companies in those countries.
Net result, 5 evaluations (one for each product), 80 authorisations (16 countries,
5 products each) plus administrative marketing authorisations (no evaluation
needed).
A less simple case
Active substance A is defended by a task force of 3 companies.
Each company formulates its own 5 products, submits to a different Evaluating
Member State, and applies for mutual recognition in 10 countries.
Each company also provides Letter of Access to 2 local formulators in 15
countries.
Each local formulator manufactures 5 products that are essentially the same as
above, and submits 5 dossiers to their local Competent Authority
The risk of duplication …..
In this case, potentially:
Manufacturers: 3 x 5 evaluations, with 3 EMS …….. then mutual recognition ..
Formulators: 2 x 15 x 5 evaluations with 15 EMS
Net result: 165 evaluations, involving 18 MS
(and then mutual recognition??)
But, we are still in a scenario where 5 evaluations from 1 MS should suffice!!!
Unnecessary work, and unnecessary costs!!
The risk of duplication
The real case of difenacoum ….
Several companies can grant access to a. s. dossier
Some may defend end use products themselves
Or supply a.s. to formulators who defend their own products
Net result: less than 10 formulation types with slight variations (block, pellet,
paste, grain …) at the same concentration of active substance. 10 evaluations
would be plenty. But, more than 100 dossiers submitted!!
Already R4BP shows 4000 MR applications!!!!!!!
page 16 • Title • 22 March 2016
Risk Mitigation Measures
Where the fun really starts ….
Rodenticides are a particulary difficult group of substances for all stakeholders
because, by definition, they are highly toxic to mammals, plus the concerns
about secondary poisoning risks to birds of prey.
At the same time, it is widely recognised that these products provide important
benefits by controlling pests that pose a serious risk to the human population,
through potential disease transmission, damaging the fabric of buildings,
consuming stored goods etc etc …
The authorities have a duty to protect the public and the environment and how
they achieve this may vary from country to country.
page 17 • Title • 22 March 2016
Harmonised risk mitigation measures – at
the active substance level (1)
 In the Annex I inclusions for the anticoagulants it states that:
 All packaging of anticoagulant rodenticides is required to show safety
precautions for the protection of humans, animals or the environment in the
form of standard phrases.
 Ready-to-use products shall not contain more than X% w/w of the active
substance, or products which contain more than X mg/kg of the active
substance shall only be placed on the market for use by professionals
trained to use them.
 Products shall contain an aversive agent and where appropriate, a dye.
 Products shall not be used as a tracking powder. [Doesn’t apply to the first
generation anticoagulants.]
In addition, it says…
Harmonised risk mitigation measures – at
the active substance level (2)
 Primary as well as secondary exposure of humans, nontarget animals and the environment are minimised, by
considering and applying all appropriate and available risk
mitigation measures. These include, amongst others, the
category of user and the restriction to professional only,
area of use, the formulation, setting an upper limit to
package size, specific product design and laying down
obligations to use tamper resistant and secure bait boxes
and codes of good practice.
 These measures are deferred to the product authorisation stage and
Member State level.
Risk Mitigation Measures
Considering mutual recognition in our two cases of « simple » and « less simple »
If one EMS grants an authorisation with specific risk mitigation measures, these
may be adopted directly, or amended by other MS (additional procedure for
change in user category)
.
If 18 MS review the same product and apply their own risk mitigation measures,
and then those measures are considered by other MS via mutual recognition
…….
The net result will be that each MS will still apply the risk mitigation measures that
it considers appropriate to each specific product!
(In fact, one could argue that the evaluation is unnecessary since the products are
so well known and MS have already decided what retrictions they will apply!!)
page 20 • Title • 22 March 2016
What it means in practise
Enormous duplication of effort when we are already way behind in time and can
least afford to waste our resources.
Those who worked hardest to comply were hit with restricted uses while their
competitors remained on the market with their « old » labels (brodifacoum
inclusion is more than 2 years after difethialone)
Those who came first were investing enormous time and resources in coping
with being the guinea pigs and fire-fighting the issues with the compliance
deadline
Every incentive to delay the process, not to expeditie it!!
page 21 • Title • 22 March 2016
Comparative assessment
The exclusion criteria included in the new Regulation were not part of the BPD,
but aspects of hazardous properties meant that substances could be identified
as candidates for substitution – the second gen AVKs meet the criteria for
« PBT » (Persistent, Bioaccumulating and Toxic).
Comparative assessment occurs at the product re-authorisation stage following
active substance renewal. How will it work?????
2nd gen AVKs are included for 5 years and renewal dossiers need to be submitted
550 days (18 months ) before expiry ……… ie 3.5 years after inclusion.
Since product authorisations are arriving more than 2 years after inclusion,
rodenticide manufacturers are in almost constant action to defend actives and
products.
page 22 • Title • 22 March 2016
Difethialone – timeline in reality
Theoretical
Substance
Product dossier Date of 1st
submission
authorisation
Date of mutual
recognitions
Process finished
Difethialone
1 November
2009
1 February
2011
1 August 2011
1 November
2011
Substance
Product
dossier
submission
Date of 1st
authorisation
Date of mutual
recognitions
Process finished
Difethialone
1 November
2009
UK - 20 and 27
April 2011
NLD – 11
September 2011
?????
Reality
By the 1st November
2011
product authorisations
(via mutual recognition)
in Netherlands, Denmark,
Germany, Slovakia and
Switzerland
Difethialone status – 29 March 2012
Authorisation granted
Discussion ongoing
Dossier submitted
NO
I
E
SW
FI
DK
UK
NL
BE
LX
DE
PL
CZ
FR
PT
AU
SW
I
SK
IT
ES
GR
Difethialone authorisations – Indoor use
only
Indoor use for consumer
& professional
Indoor use for consumer
& in and around
buildings for prof.
Indoor use prof only
In and around buildings
for professional
Paste – in
and around
Grain indoors
No clarified position
Difethialone – no amateur use
No amateur use
EU notification sent to the
Commission for restriction to
professional
Application for
consumer uses
withdrawn
Spain & Sweden –
trained professionals.
Denmark – trained
professionals for use
against rats.
Germany & Finland professional
Difethialone – rats and/or mice
Use against rats and mice for
both professional & consumer
Use against mice for amateur.
Rats and mice professional.
Rats and mice professional.
No clarified position
Harmonised risk mitigation measures – at
the product level
 What the European Commission want to do now is harmonise these deferred
risk mitigation measures.
 In December 2011 they presented two papers with a focus on risk
mitigation. One looked at human health and the second at the
environment.
 These papers were discussed again in a second meeting during w/c 27th
February 2012.
 The industry (Cefic, CEPA, BPCA, RRAC etc) had all (or are in the
process of) written papers addressing the suggestions in these papers.
What did these two papers say… ??
Harmonised risk mitigation measures –
human health
 The human health paper proposes the following options for ALL anticoagulants:
 Option A – Restrict all use to professionals only
 Option B – Non professional baits to be supplied and used in proprietary (nonrefillable) tamper-resistant bait stations.
 Option C - Non professional baits to be used in refillable tamper-resistant bait
stations and supplied as inner packs or units containing at most enough for one bait
point (either rat or mouse).
 Option D - Non professional baits to be used in refillable tamper-resistant bait
stations and supplied loose in refill packs.
 Option E - Non professional baits to be used in covered bait points, with bait to be
supplied as inner packs or units, each containing at most enough bait for one bait
point (either rat or mouse).
Proposals
The paper concludes that consumers should be allowed to control small rodent
infestations but the mainstay of rodent (particularly rat) control should be
professional.
For non-professional use against mice the proposal is for option E (covered
baits)
For non-professional use against rats the proposal is for option C (bait stations).
Maximum pack size for consumers of 1.5 kg.
Harmonised risk mitigation measures –
Environmental
 Options for the second generation anticoagulants (SGARs), only.
 Proposal 1 – Restrict use of all SGARs to indoors only
 Proposal 2 – Restrict use of SGARs to in and around buildings
 'In and around buildings' shall be understood as the building itself, and the area
around the building that needs to be treated in order to deal with the infestation of
the building. This would cover uses in sewer system or ships but not in waste
dumps or open areas such as farmlands, parks or golf courses.
 Would affect bromodiolone and difenacoum where the inclusion Directive allows
use ‘in and around’ buildings and open spaces’.
 Proposal 3 – Maintain the status quo of certain Member States
 Proposal 4 – Professional use only
 No proposed conclusions in the environmental paper.
Harmonised risk mitigation measures –
What does this mean?
The human health paper proposes a pragmatic approach whereby homeowners still have
access to products, notably for mouse control. Rat control may often be best left to a
professional.
The environmental paper could have a serious impact on how professionals attempt to
control rodents e.g. no use of second generation anticoagulants in open areas such as
parks, farmland etc.
 The environmental paper proposes that the second generation anticoagulants should
only be used by professionals (as in USA). This could present problems in areas where
mice are resistant to the first generation rodenticides.
National Practise
Harmonisation is a nice objective, but a little utopic for the EU
Many MS have existing, or new « guidance » or « rules » to address risks from
rodenticides
Germany proposes to prevent amateur uses of AVKs (except voles?!!)
Denmark has a list of actives to be selected in order (upon what basis?)
Warfarin, alphacloralose, chloraphacinone, coumatetralyl, difenacoum, bromadiolone
…
UK is re-examining its previous position of only allowing outdoor use of bromadiolone and
difenacoum due to more and more cases of resistance (especially bromadiolone)
Summary comments - rodenticides
A much greater emphasis on safety which may be over-cautious given that most instances
of poisoning are through deliberate mis-use.
Restricting products to professional use, only, may result in infestations being left untreated
(until the situation is worse) to avoid the expense
Restricting products to use in bait stations will certainly reduce efficacy which will mean
either more baiting points or longer times to establish control, or both.
Professional rodent control is much more than simply placing baits according to the label,
so good practise and responsible use must be promoted too.
Comparative assessment and BPR timings mean that rodenticides will be under almost
constant review.
What has been the impact on insecticides?
Originally, just over 100 substances were notified for PT18, but in the end only
half these were supported by dossiers when it came to the submission
deadline in 2006.
Insecticides that have gone:
chlorpyrifos, malathion, temephos, fenitrothion, boric acid, diazinon,
methomyl, phoxim, pirimiphos methyl, bioresmethrin, beta-cyfluthrin,
fenoxycarb, s-hydroprene, several essential oils, fatty acids,
hydramethylnon, propoxur , dichlorvos ….. plus non-inclusion proposal for
bifenthrin
page 35 • Title • 22 March 2016
Why were so many lost?
Costs to update dossier
Costs to compile dossiers
Submission fees
Consolidation in the industry (mergers, acquisitions)
If the insecticide was not defended under 91/414, the data requirements to
upgrade the information package were expensive.
Organophosphates were already under scrutiny for human health reasons so
might not have passed the risk assessments ……….
Limited R and D budgets
page 36 • Title • 22 March 2016
Use restrictions
Passing the environmental risk assessment is not easy and the emission
scenarios for PT18 include very conservative assumptions.
Insecticides have secured Annex I inclusion, but we anticipate that their use
patterns will be much more limited in future (eg. max. dose rates, number of
applications per year, crack and crevice versus broadcast surface spray
treatment).
Generating higher tier studies to mitigate the risk is often expensive and may not
be economically justified.
page 37 • Title • 22 March 2016
Formulators
How it was supposed to happen
Where are we?
What has been the impact?
Rodenticides
Insecticides
What does it mean for formulators?
Summary
page 38 • Title • 22 March 2016
What does it mean for formulators?
Reduced choice of actives.
Currently, any supplier of a supported active can supply to formulators but from
Sept 1st 2013 only sources from the approved list (ie those with a full dossier,
or access to the necessary information) will be able to supply the European
biocides market.
As actives are voted onto Annex I, the (re-)autorisation of those biocidal products
by formulators will require a letter of access from an approved source so
addressing this issue of supply is a critical step.
The 2+ years between decision and inclusion is meant to provide formulators
with time to establish supply agreements, develop dossiers for their product
page 39 • Title • 22 March 2016
Timing
Currently, 15 insecticides are voted onto Annex I, with 40 to go ….. And for some
of these, the inclusion decision is unlikely in the next 2 years.
In mixtures, such as aerosols with a photolabile ‘knockdown’ active plus a
photostable ‘kill’ active, the product re-approval is triggered by the inclusion of
the last active.
PT18 Product authorisation will be spread over at least 6 and probably 10 years.
Significant risk of distortion in the market, amounting to inadvertant unfair
competition.
page 40 • Title • 22 March 2016
Summary and conclusions
Rodenticides will be under almost constant review due to 5 year inclusions, the phasing of
inclusion decisions and comparative assessment.
Restrictions on use to mitigate risk may compromise efficacy and must be linked with an even
greater emphasis on responsible use by professionals
Insecticides will see restricted uses on some products, long before competitors due to the
phasing of inclusion decisions, primarily due to the conservative nature on environmental
risk assessments.
Since the BPD entered into force, 2 rodenticides and more than 50 insecticides have been
withdrawn. Just 2 new insecticides (indoxacarb, metofluthrin) have been introduced.
Reducing risk will not happen thanks to new chemistry – it requires better use of what exists!
page 41 • Title • 22 March 2016
Thank you!