REGISTRATION OF

FORMULATION PLANT
PROTECTION
PRODUCTS

José Joao D. Carvalho

PhD Chemistry
European Regulatory
Affairs Manager
Dossier Services
Agrochemicals
Dr. Knoell Consult GmbH

Private & Confidential

www.knoell.com

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DISCLAIMER

Certain views and opinions expressed in this presentation are those of the
author and do not necessarily reflect the views of DR. KNOELL CONSULT GmbH.

This presentation contains no confidential information.

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OUTLOOK

Overview of EU regulatory processes for agrochemicals

Regulation 1107/2009 – Key points
Product authorisation and authorisation renewal
(MS Level)
Data Requirements and dossier structure for formulated products
Critical regulatory issues for formulators
Summary & Questions

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OVERVIEW OF EU REGULATORY PROCESSES
FOR AGROCHEMICALS

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THE EU IN A NUTSHELL
Population: 510 million inhabitants
Member States: 28 countries
GDP (2012): 16.584 trillion US dollars (23% global GDP)

EU Members States (MS)

European Free Trade Association

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EU INSTITUTIONS AND DECISION –MAKING PROCESS
The European Union legislative triangle

Proposes
legislation

Co-decision

Implementation Directorate-General for Health and Food Safety

Agencies
and Execution (ex-DG SANCO, ex- DG Health and Consumers )
(ex-DG SANCO)

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… and MS governments
INSTITUTIONS AND DECISION –MAKING PROCESS

Chemicals (REACH)
Biocidal Products
Nanomaterials
C&L

(Ex-DG SANCO)

Decision:
PPPs
Commission Seeds
and MS* GMs
Advice, no
decision
* via the Standing Committee on Plants, Animals, Food and Feed
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(PAFF) - Section Phytopharmaceuticals. Previously called SCFCAH:
Standing Committee on the Food Chain and Animal Health.
THE EUROPEAN UNION SECONDARY LAW

Non – PPP regulations

Legal Text Applicable to Entry to force Authority Applicable
All chemicals
REACH (including PPPs co-
Jun. 2007 EChA EU - wide
Regulation (EC) 1907/2006 formulants but NOT the
active substances)
Biocidal products
BPR (including active
Sep. 2013 EChA EU – wide
Regulation (EU) 528/2012 substance for NON
agriculture use)

All chemicals Jan. 2009

CLP* for substances
(including active EChA EU – wide
Regulation (EC) 1272/2008 Jun. 2015
substances and PPPs) for mixtures

*Regulation on classification, labelling and packaging (CLP) of substances and mixtures to align existing EU legislation with the United Nations
Globally Harmonized System (GHS): same hazards will be described and labelled in the same way all around the world.
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THE EUROPEAN UNION SECONDARY LAW

PPP regulations
Entry to
Legal Text Applicable to Authority Applicable
force
EU – wide
Regulation (EC) 1107/2009 Agrochemicals EU Commission, for a.s.
Repealing Directive 91/414/EEC of (a.s. and formulated Jun. 2011
1991 products)
MS, EFSA MS
or products
Sustainable Uses of Pesticides Uses
Sep. 2013 MS MS
Directive 2009/128/EC (Agrochemicals )
Food and feed EFSA, EU
MRLs
(treated with Set. 2009 Commission, EU, MS
Regulation (EC) 396/2005
Agrochemicals ) MS
CLP Also Jan. 2009
EChA EU – wide
Regulation (EC) 1272/2008 Agrochemicals Jun. 2015

MRL - Maximum Residue Level (~Import Tolerances)

CLP - classification, labelling and packaging
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DEFINING REGULATION

General: Principle or rule (with or without the coercive power of law) employed
in controlling, directing, or managing an activity, organization, or system.

Law: Rule based on and meant to carry out a specific piece of legislation (such as
for the protection of environment). Regulations are enforced usually by a
regulatory agency formed or mandated to carry out the purpose or provisions of
a legislation. Also called regulatory requirement.

Source: http://www.businessdictionary.com/definition/regulation (9th January 2013) 11

 THE 1107 REGULATORY AGENCY
EC/MS/EFSA/ECHA

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1107: Regulation EC 1107/2009 (EU plant protection products regulation)
THE HAZARD-BASED CRITERIA

Hazard Risk
USA
Brazil
Japan
European Union
Russia
OECD

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 HAZARD AND RISK

Hazard: fire

Risk: getting burned

Slide 14
HAZARD AND RISK

https://www.youtube.com/watch?v=VF-8QksiU7c
Slide 15
THE EU PARTICULARITY

One step 2-step process

a.i. and formulated a.s. approval + step II for
products products

Rest of the world European Union

(+Switzerland, Norway, Iceland)

2-step process: first the active subtance (a.s., also called active ingredient in the rest of the world) needs to be
approved at EU level during a Europe-wide review and thereafter can the products by authorised at National Level by
each of the 28 Member States, i.e. national decision on products authorisation 16
AGROCHEMICALS REGULATION

• The EU is not a federation of Member States (MS)

• There is EU decision and Member States decision (ex. UK, France, Sweden, etc. )
• Agrochemicals are regulated through a mix process of decision-making:
• active substances are approved at EU level (if a majority of countries agree)
• formulated products containing the active substance are authorised by the MS

2-step process
A plant protection product can only be authorised in one or
more Member States if the active substance has been
previously approved at EU level (by the MSs).
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AGROCHEMICALS REGULATION

• The active substance (a.s.) within a plant protection product is the molecule or material
responsible for the action against the target pest, weed or fungal. (*)

• The term ‘plant protection products’ (PPP) designates the form in which the final user
applies the products. A PPP contains one or several active substances along with other
materials, usually called co-formulants (solvents, carriers, wetting agents , etc.), i.e. the final
formulation.

Step 1: A.S. approval

Step 2: PPP authorisation

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(*) active ingredient in the old terminology.
 AGROCHEMICALS REGULATION

• Active substance is evaluated and approved at EU level

• Included in a positive list of approved substances (former Annnex I
listing)

• Product is authorised at member state level

• Must meet the Uniform Principles* to achieve authorisation
• Zonal evaluation process and Mutual Recognition between Member
states
• “Negative listing” of co-formulants at Members states level (ex.
Germany and Spain)
• Authorisation is still granted at National Level! Even if evaluation is
conducted under the Zona evaluation process (assessment)

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*Uniform Principles – Regulation (EC) No 546/2011 setting out clear requirements for the evaluation and decision-making by the different MS
AGROCHEMICALS REGULATION

The triptych of PPPs

Regulation
1107/2009
Regulation Directive
396/2005 EU Approvals of 2009/128
active substances
EU Maximum Sustainable use of
Residue Level pesticides
(MRL) National (MS set National
Authorisations of Action Plans, IPM)
Products

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REGULATION 1107/2009 –
KEY POINTS

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REGULATION 1107/2009 AIMS
To ensure a high level of protection of both human and animal health and the
environment and to improve the functioning of the internal market through the
harmonization of rules on the placing on the market of plant protection products, while
improving agricultural production.

Increase free movement and availability of products throughout the EU

Harmonised system for both actives and products, including mutual recognition
between different Member States (MSs)
EU is divided into zones to facilitate authorisation of products in more countries
MSs may still refuse an authorisation of a product as a result of specific
environmental or agricultural circumstances or where a high level of protection of
human and animal health and the environment cannot be guaranteed.
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REGULATION 1107/2009 AIMS

Northern zone

Central zone

Southern zone
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REGULATION 1107/2009 AIMS

Increase predictability, efficiency and consistency

Speed up the review process by establishing strict deadlines
Possibility of amendment or withdrawal of approved substances
Introduces comparative assessment and substitution
Including comparison with non-chemical methods
New hazard based cut-off criteria (ED, POPs, Mutagenic, Carcinogenic, etc.)
Simplified process for low risk substances
Introduction of basic substances
Specific rules for minor uses

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REGULATION 1107/2009 AIMS

Reduce animal testing

Develop non-animal test methods (ex. Skin sensitization, irritation, corrosion)
Compulsory sharing of vertebrate data
Introduction of similar rules to active substances for safeners and synergists
Guidance was expected by 14 December 2014 but has been postponed
Substances will only be evaluated once these rules are established
Establishment of a list of co-formulants that may not be used in plant protection
products (still to be proposed by the EU Commission)

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REGULATION 1107/2009 AIMS

Co-formulants

Negative listing (future) Positive listing by EPA:

Members state rules apply (e.g. Germany and Inertfinder EPA database (food and

Spain) non food use);

Minimal risk FIFFRA Section 25(b)
inerts;
USDA National Organic Program;

Registration not required. EPA Registration of inerts

(unless covered by REACH regulation) mandatory!
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REGULATION 1107/2009 – KEY POINTS

Centralised EU process for a.s. but the assessment is performed by MSs (RMS, co-RMS)
Assessment by RMS
All MS can comments on the evaluation
EFSA issues a scientific conclusion (non-binding)
EU Comm approves/refuses the a.s.
Higher Standards
Hazard-based “Cut-off criteria” and substitution of a.s. (ED, CMR, POP, PBT, vPvB)
Comparative assessment of PPPs (for products containing a.s. candidates for substitution)
Mandatory data sharing for vertebrate studies
Extended scope: a.s., safeners and synergists (not co-formulants)
Candidates for Substitution (a.s)
list available Q1 2015

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REGULATION 1107/2009 KEY POINTS

Active substance
renewal of approval

RMS - Rapporteur Member State

EFSA - European Food Safety Authority
PAFF - Standing Committee on Plants,
Animals, Food and Feed (previously
named SCFCAH)
RAR - Renewal Assessment Report

PAFF
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REGULATION 1107/2009 – CUT-OFF CRITERIA

Hazard based cut-off criteria for non-approval or non-renewal of active substance

i.e. not subject to risk assessment considering the intended uses.

Human health Environmental safety

Mutagen (M1A & M1B) PBT (persistent, bioaccumulative & toxic)
Carcinogen (C1A & C1B)* POP (persistent and organic pollutant)
Reproductive toxicity (R1A & R1B)* vPvB (very persistent, very bioaccumulative)
Endocrine disruptor* Endocrine disruptor*

* unless the exposure, under realistic proposed conditions of use, is negligible; (…) the PPP is used in closed
systems or in other conditions excluding contact with humans and where residues on food and feed do not exceed
the default value set in accordance with
Article 18(1)(b) of Regulation (EC) No 396/2005.
REGULATION 1107/2009 KEY POINTS

Comparative assessment
(for products containing a.s. candidates for substitution)
No authorisation or restricted authorisation if another product for the same use exists:
With significantly lower risks for human health or the environmental identified on a case-by-
case basis by MS authorities;
Similar effects on target organisms without entailing significant economic or (Annex IV says
“and”) practical disadvantage for users .
Decision at MS level – product replaced in one MS and not in another MS: competitive
advantage for some MSs?

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REGULATION 1107/2009 KEY POINTS

Comparative assessment
(for products containing a.s. candidates for substitution)
No authorisation or restricted authorisation if another product for the same use exists:
With significantly lower risks for human health or the environmental identified on a case-by-
case basis by MS authorities;
Similar effects on target organisms without entailing significant economic or (Annex IV says
“and”) practical disadvantage for users .
Decision at MS level – product replaced in one MS and not in another MS: competitive
advantage for some MSs?

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CANDIDATES FOR SUBSTITUTION (CIS)
Active substance CAS No Use
1-Methylcyclopropene 3100-04-7 PG
Aclonifen 74070-46-5 HB
Amitrole (aminotriazole) 61-82-5 HB
Bifenthrin 82657-04-3 IN, AC
Bromadiolone 28772-56-7 RO
Bromuconazole 116255-48-2 FU
Carbendazim 10605-21-7 FU
Chlorotoluron (unstated stereochemistry) 15545-48-9 HB
Copper hydroxide CAS No 20427-59-2
Copper oxychloride CAS No 1332-65-6 or 1332-40-7
Copper compound Copper oxide CAS No 1317-39-1 FU
Bordeaux mixture 8011-63-0
Tribasic copper sulphate CAS No 12527-76-3
Cyproconazole 94361-06-5 FU
Cyprodinil 121522-61-2 FU
Diclofop CAS No 40843-25-2 (parent) CAS No 257-141-8 (diclofop-methyl) HB
Difenacoum 56073-07-5 RO
Difenoconazole 119446-68-3 FU
Diflufenican 83164-33-4 HB
Dimethoate 60-51-5 IN, AC
Dimoxystrobin 149961-52-4 FU
Diquat (dibromide) 2764-72-9 (ion), 85-00-7 (dibromide) HB, DE
Epoxiconazole 135319-73-2 (formerly 106325-08-0) FU
Esfenvalerate 66230-04-4 IN
Ethoprophos 13194-48-4 NE, IN
Slide 32
CANDIDATES FOR SUBSTITUTION (CIS)
Active substance CAS Use
Etofenprox 80844-07-1 IN
Etoxazole 153233-91-1 IN
Famoxadone 131807-57-3 FU
Fenamiphos 22224-92-6 IN
Fenbutatin oxide 13356-08-6 AC
Fipronil 120068-37-3 IN
Fludioxonil 131341-86-1 FU
Flufenacet (formerly fluthiamide) 142459-58-3 HB
Flumioxazine 103361-09-7 HB
Fluometuron 2164-17-2 HB
Fluopicolide 239110-15-7 FU
Fluquinconazole 136426-54-5 FU
Glufosinate 77182-82-2 HB
Haloxyfop-P (Haloxyfop-R) Acid: 95977-29-0 Ester: 72619-32-0 HB
Imazamox 114311-32-9 HB
Imazosulfuron 122548-33-8 HB
Isoproturon 34123-59-6 HB
Isopyrazam 881685-58-1 FU
Lambda-cyhalothrin 91465-08-6 IN
Lenacil 2164-08-1 HB
Linuron 330-55-2 HB
Lufenuron 103055-07-8 IN
Mecoprop 7085-19-0 HB
Metalaxyl 57837-19-1 FU
FU, IN, HB,
Metam (incl. -potassium and -sodium) 144-54-7
NE
Slide 33
CANDIDATES FOR SUBSTITUTION (CIS)
Active substance CAS Use
Metconazole 125116-23-6 (unstated stereo-chemistry) FU, PG
Methomyl 16752-77-50 IN
Metribuzin 21087-64-9 HB
Metsulfuron-methyl 74223-64-6 HB
Molinate 2212-67-1 HB
Myclobutanil 88671-89-0 FU
Nicosulfuron 111991-09-4 HB
Oxadiargyl 39807-15-3 HB
Oxadiazon 19666-30-9 HB
Oxamyl 23135-22-0 IN, NE
Oxyfluorfen 42874-03-3 HB
Paclobutrazol 76738-62-0 PG
Pendimethalin 40487-42-1 HB
Pirimicarb 23103-98-2 IN
Prochloraz 67747-09-5 FU
Profoxydim 139001- 49-3 HB
Propiconazole 60207-90-1 FU
Propoxycarbazone 145026-81-9 HB
Prosulfuron 94125-34-5 HB
Quinoxyfen 124495-18-7 FU
Quizalofop-P-tefuryl 119738-06-6 HB
Sulcotrione 99105-77-8 HB
Tebuconazole 107534-96-3 FU

Slide 34
CANDIDATES FOR SUBSTITUTION (CIS)

Active substance CAS Use

Tebufenpyrad 119168-77-3 AC
Tepraloxydim 149979-41-9 HB
Thiacloprid 111988-49-9 IN
Tri-allate 2303-17-5 HB
Triasulfuron 126535-15-7 Reg. indicates: 82097-50-5 HB
Triazoxide 72459-58-6 FU
Warfarin (aka coumaphene) 81-81-2 RO
Ziram 137-30-4 FU, RE

Slide 35
REGULATION 1007/2009 KEY POINTS

Comparative assessment
(for products containing a.s. candidates for substitution)
No authorisation or restricted authorisation if another product for the same use exists:
With significantly lower risks for human health or the environmental identified on a case-by-
case basis by MS authorities;
Similar effects on target organisms without entailing significant economic or (Annex IV says
“and”) practical disadvantage for users .
Decision at MS level – product replaced in one MS and not in another MS: competitive
advantage for some MSs?

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