Registration Procedures for Agrochemicals in the ... - ACS Publications

Chapter 25

Registration Procedures for Agrochemicals in the European Union

Downloaded by UNIV MASSACHUSETTS AMHERST on September 25, 2012 | http://pubs.acs.org Publication Date: June 16, 1999 | doi: 10.1021/bk-1999-0724.ch025

Jorge-I. Celorio Hoechst Schering AgrEvo GmbH, Building K607, D-65926 Frankfurt—AM—Main, Germany

With Directive 91/414 the European Union has achieved a harmonized approach for the registration of plant protection products. The procedures foresee evaluation and registration in two phases: 1) assessment of an active substance and recommendation by a Rapporteur Member State; 2) registration in the Member States of the formulated products containing the active substance, if it has been accepted by the Standing Committee on Plant Health. If rejected, the active substance will be banned in the EU. For reregistrations, the active substances to be reviewed are published by the Commission. All companies interested in defending the registrations of a given active substance must notify their intention. For both new and old compounds, the notifiers have to provide the Rapporteur Member State with the corresponding dossier. The assessment by the Rapporteur Member State leads to the production of a draft Monograph, which is discussed within expert groups and includes the recommendation of acceptance/rejection. This leads to the voting within the Standing Committee on Plant Health.

For years the European Union had been striving to achieve the harmonisation of registration procedures for plant protection products in all Member States. These efforts crystallized in 1991 with the publication of Directive 91/414 (7) — which laid the base for a common procedure for the (re)registration of old and new products — with the goal of reviewing all existing active substances in the EU (over 700) in twelve years. This Directive was followed by a series of Regulations, Directives, Guidelines, etc., which demonstrate how complex the European agricultural situation is, affected by climatic, political and cultural factors which differ radically between the northern and southern Member States. The intention of this paper is to give an overview of the current EU procedure.

206

© 1999 A m e r i c a n C h e m i c a l Society

In International Pesticide Product Registration Requirements; Garner, W., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1999.

207 Directive 91/414/EEC


M

Directive 91/414 (7) is titled concerning the placing of plant protection products on the market" and sets the basic procedures for accomplishing this. Basically, it foresees the registration of plant protection products in two phases. In the first phase, the assessment of an active substance (a.s.) is allocated by the Commission to a Member State. The designated Rapporteur Member State (RMS), after reviewing the documentation presented, makes a recommendation to the Commission (favorable or unfavorable). At the Standing Committee on Plant Health (SCPH) a vote is held on the recommendation, and if a certain majority is obtained, the a.s. will be listed in the so-called 'positive list', the Annex I to Directive 91/414. Once the compound is in Annex I, the submitter can proceed with the second phase, which is the registration at the national level of the plant protection product. If the a.s. cannot be included in Annex I, it will be banned in the entire EU, and all Member States must revoke the registrations of plant protection products containing this active substance. Directive 91/414 contains six annexes, as shown below: Positive list of evaluated and accepted active Annex I substances Data requirements for the active substance Annex II Annex III Data requirements for formulation(s) Annex IV Risk phrases Annex V Safety phrases Annex VI Uniform principles The data requirements are described below (cf. Documentation). The Uniform Principles contain guidance for the evaluation and decision making concerning the submitted data, including trigger values for acceptance/rejection and for demanding further studies. The Commission Directive 91/414 has been followed by at least ten Directives,fiveRegulations, eighteen Decisions and twenty-three Guidelines/Working Documents (Tables I and II). Commission Regulation 3600/92 (2) laid down "the detailed rules for the implementation of the first stage of the programme of work referred to in Article 8(2)" of Directive 91/414. This Regulation, which listed the first 90 substances to be reviewed, was subsequently amended by Regulations 933/94 (which listed the substances to be assessed and their distribution among 12 Member States) (3) and 491/95 (which integrated the new Member States of Austria, Finland, and Sweden in the review process and redistributed the remaining 87 active substances among all 15 Member States) (4) (Table III). Although the intended goal was to review all existing active substances in the EU (over 700) in twelve years, this goal cannot be achieved, since the amount of work and the complexity of certain issues (e.g., data protection) were grossly underestimated. Even the basic philosophy toward agrochemicals in general can lead to controversial views within the EU for both new and old substances. In some Member States in Northern Europe, agriculture plays a secondary role, representing maybe less than 5% of the gross national product (GNP). In Southern Europe, however, agriculture may represent 40% of the GNP. This taints politically the


208 Table I. EU Documents: Directives, Decisions and Regulations


Document No. Dir. Dir. Dir. Dir. Dir. Dir. Dir. Dir. Dir. Dir. Dir.

91/414 93/71 94/37 94/43 94/79 95/35 95/36 96/12 96/46 96/68 97/57

Context Basic registration directive Efficacy Data Identity and Physicochemical Data Establishes the Uniform Principles (annulled) Toxicology, Metabolism and Operator Exposure Derogates GLPfromtesting on bénéficiais and for residues Environmental Fate Ecotoxicology Analytical Methods Residues Establishes the (new) Uniform Principles

Reg. 3600 / 92 Reg. 933 / 94 Reg. 491/95 Reg. 2230 / 95 Reg. 1199 / 97

Establishes the rules and lists thefirst90 active substances Allocation of 89 as. among 12 Rapporteur Member States Re-allocation of 87 as. among 15 Rapporteur Member States Re-establishes deadline for the submission of dossiers Amends Reg. 3600/92

Dec. Dec. Dec. Dec. Dec. Dec. Dec. Dec. Dec. Dec. Dec. Dec.

Cancellation of cyhalothrin registrations in the EU Cancellation of azinphos-ethyl and ferbam registrations in the EU Recognizes completeness of the dossier of kresoxim-methyl Recognizes completeness of the dossier of flurtamone Recognizes completeness of the dossier of quinoxyfen Recognizes completeness of the dossier of prohexadione-calcium Recognizes completeness of the dossier of chlorfenapyr Recognizes completeness of the dossier of spiroxamine Recognizes completeness of the dossier of azoxystrobin Recognizes completeness of the dossier of isoxaflutole Cancellation of propham registrations in the EU Recognizes completeness of the dossiers of prosuHuron and cyclanilide Recognizes completeness of the dossiers of azimsulfuron, flupyrsulfuron-methyl and Paecilomyces fiimosoroseus Recognizes completeness of the dossier of Ps. chloroaphis Recognizes completeness of the dossiers of carfentrazone-ethyl, fluthiamide and fosthiazate Establishing Scientific Committees in thefieldsof consumer health and food safety (DG XXIV) Recognizes completeness of the dossiers of ethoxysulfuron, mefenoxam, famoxadone and Ampelomyces quisqualis Recognizes completeness of the dossier of flumioxazine

94 / 643 95 / 276 96 / 266 96/341 96/457 96 / 520 96/521 96 / 522 96 / 523 96 / 524 96 / 586 97 /137

Dec. 97/164 Dec. 97 / 248 Dec. 97 / 362 Dec. 97 / 579 Dec. 97/591 Dec. 97 / 631



209

Table Π. EU Documents: Guidelines and Working Documents Document No.

Context

2949 / V I / 93 9016 / VI / 93 1654 / VI / 94 1663 / VI / 94 7109 / VI / 94 1606 / VI / 95 1614 / VI / 95 1642 / VI / 95 1663 / VI / 95 1694 / VI / 95 4952 / VI / 95 4992 / VI / 95 4993 / VI / 95 7017 / VI / 95 7027 / VI / 95 7531 / VI / 95 7600 / VI / 95 4754 / VI / 96 6476 / VI / 96 7617 / VI / 96 8538 / VI / 96 1607 / VI / 97 1635 / VI / 97

Article 12 Overview of the state of main works in DG VI Preparation of Monograph by Rapporteur Member State Preparation of dossiers ApplicabiUty of GLP Contact addresses Working procedure for 'old active substances Ecotoxicology Working procedure for new active substances Modeling Environmental Fate: Leaching Modeling Environmental Fate: Leaching Microorganisms and viruses Microorganisms and viruses Acceptability of data re GLP Completeness check of dossiers Setting acceptable operator exposure levels Biological assessment dossier (Efficacy data) Data protection Modeling Environmental Fate: Surface water Modeling Environmental Fate: Soil Draft on completeness check of dossiers Generation of residue data Inclusion of diquat in Annex I 1


210 decision-making process and leads to compromises and delays. Besides, the EU is formed by 15 independent states, and EU guidance may be influenced at the national level by local legal restrictions.


The Registration Procedure: New Active Substances The registrant notifies the Commission through a Member State of the intention to register a new a.s. The Commission then allocates the review of the a.s. to a Rapporteur Member State, which may be the one through which the notification was made. The notifier submits the data dossier (5) and the RMS proceeds to make the completeness check and a preliminary evaluation. Once the Commission has confirmed that the submitted dossier is complete, the Member States may issue Provisional Registrations for use of formulated products containing the new active substance. These Provisional Registrations permit the marketing of a product in a given Member State for a maximum of three years. Until October 1997, Provisional Registrations had been granted to the following active substances: azimsulfuron, azoxystrobin, flupyrsulfuron-methyl, flurtamone, kresoxime-methyl, quinoxyfen, and spiroxamine. A complete evaluation of the submitted data is carried out by the RMS (6). If necessary, additional data may be required. The RMS finally prepares a Monograph summarising the principal characteristics of the active substance and its risks and benefits and makes a recommendation of inclusion in or exclusion of Annex I of Directive 91/414 The Registration Procedure: Reregistration of Old Active Substances A list of ca. 90 active substances to be reviewed was prepared by the Commission and published as an EU document (2). All organisations which marketed products containing these active substances had to notify the Commission whether they were interested in reregistering their a.s. at the EU level. A list of notifiers was then published (3), so that the organisations could meet and decide whether they would eventually form a Task Force' for a given a.s. and submit jointly one dossier. The Commission also allocated the active substances among the Member States (5). The notifiers submitted to the corresponding RMS the data relevant to their product. This consisted of the dossiers described below (cf. Documentation). As for new substances, the RMS evaluates the data, ending with a Monograph and a recommendation of inclusion in or exclusionfromAnnex I of Directive 91/414. Decision-Making The Monograph consists of four volumes (6). Volume 1: statement on subject matter, conclusions, decisions and proposals, and further information; Volume 2: list of studies submitted; Volume 3: summary, evaluation and assessment; Volume 4: confidential information.



211 The Monograph, the Tier 2 and 3 summaries (cf. Documentation), and, if need be, the whole dossier are reviewed by all Member States. The Monographs are evaluated and discussed by sections within the European Community Co-ordination (ECCO) expert groups, which consist of 5 experts on each field from the Member States. The first ECCO meetings were organised by the British Pesticides Safety Directorate (PSD) in York and the German Biologische Bundesanstalt (BBA) in Braunschweig. In these meetings the RMS — author of the Monograph — defends the results and the conclusions described in the Monograph. Once the review is finished, a report is sent to the Commission. Based on the RMS's Monograph and recommendation, the ECCO report, and inputs from the Directorates General VI (Agriculture), XI (Environment) and XXIV (Food and Consumer Safety) — inputs which could veto the inclusion in Annex I — a vote is taken at the SCPH, where again the RMS defends, at a political level, the proposal found in the Monograph. Of a total number of votes of 87, a minimum of 62 votes in favor of inclusion in Annex I is needed if the a.s. is to be used in the EU. If 26 votes are against the inclusion, the a.s. has to be prohibited in the EU following Directive 79/117 (7). The distribution of votes among Member States is shown in Table III.

Table ILL Distribution of Active Substances among the Member States of the EU and of Votes in the Standing Committee on Plant Health. Country Austria Belgium Denmark Finland France Germany Great Britain Greece Ireland Italy Luxembourg Netherlands Portugal Spain Sweden

1

No. of A.S. 4 5 3 3 11 11 11 5 3 11 1 5 5 7 4

No. of Votes in SCPH 4 5 3 3 10 10 10 5 3 10 2 5 5 8 4

(1) Comm. Reg. 3600/92 (as amended by Comm. Regs. 933/94 and 491/95) (2) Qualifying majority: 62. Blocking minority: 26. Total: 87.


2


212 If the vote within SCPH is favorable to the inclusion of the a.s. in Annex I, a Directive amending this annex of Directive 91/414 will be published. Then, the notifiers can proceed with the second phase, which is the (re)registration of the formulated product at Member State level. They have 18 months to implement any restrictions on usage and — in the case of old active substances — 5 years to re register the corresponding products. If the vote is not favorable to the inclusion in Annex I, the a.s. will be banned in the EU. For old substances, all registrations in the EU have to be revoked and existing stocks of products containing this a.s. have to be sold and used within 2-3 years.

Documentation The review process asks for an enormous amount of documentation in the form of dossiers for both the a.s. (the so-called Annex II dossier) and a representative formulation (the so-called Annex ΠΙ dossier). These dossiers are organized in Documents' lettered from A to Ν (Table IV) (5): Documents A to J and Ν are common to both the active substance and the formulation, while Documents Κ to M are prepared for each dossier with a series of summaries (the so-called 'Tier* summaries) building a 'pyramid' of information.

Table IV. EU Dossier: Individual Documents Document A Β C D Ε F G H I J Κ L M Ν

Context Statement of context Collective dossiers (Task Forces) Existing national labels Summary of authorized uses in the EU Good Agricultural Practice data Notification following Commission Regulation 3600/92 Statement on permited inerts Safety Data Sheets for inerts Other toxicological/environmental data Confidentiality statement Individual study reports (Annexes II and ΠΙ) Tier 1: Quality check of individual studies Tier 2: Summary and evaluation Tier 3: Overall assessment

The most complicated and time-consuming part is the preparation of Document Κ (formed by the individual study reports) and Document L (the individual quality checks, also called Tier 1 summaries). Of much more interest are Documents


213 M and Ν (Tiers 2 and 3, respectively), which summarize the scientific and technical aspects and assess the risks and benefits of the active substance and the formulation. Documents Κ to Ν are divided into Sections (Table V), which differ somewhat for the a.s. (Annex II) and the formulated product (Annex III).


Table V. EU Dossier: Data Requirements Section

Annex Π (Act Ing.)

Annex III (Form.)

1 2 3 4 5 6 7 8 9 10 11 12

Identity Physicochemical Data Further Information Analytical Methods Toxicology and Metabolism Residues Environmental Behavior Ecotoxicology Summary/Evaluation Sec. 7 and 8 Classification and Labelling Dossier, Annex III

Identity Physicochemical Data Data on Application Further Information Analytical Methods Efficacy Data Toxicology Residues Environmental Behavior Ecotoxicology Summary/Evaluation Sec. 7 and 8 Further Information

The Annex Π dossier includes sections on Identity, Physicochemical, Analytical, Toxicology and Metabolism, Residues, Environmental Fate, and Ecotoxicology data, plus Classification and Labelling. The Annex III dossier — which may refer to the Annex II data, especially where residues are concerned — includes also a section on Biological Efficacy. Most of the studies carried out are conducted following internationally recognised guidelines like OECD, EPPO, FAO/WHO, EPA, etc. Advantages / Disadvantages After many years of trying the European Union hasfinallyestablished a standardized procedure for the registration of plant protection products. The guidelines are uniform for all the Member States, and once the Uniform Principles have been established (8), there will also be standard criteria for the evaluation of the products. Also, the Tier 2 and 3 summaries are structured in such a way that they can be used world wide for registration purposes. The OECD is planning in 1998 to publish guidelines based on the EU dossier format. This means that in the near future — if enough trust is built among the OECD Member States — one dossier would suffice for world-wide registration. I£ e.g., the submission takes place in Canada and a Monograph is prepared by that country's regulatory authorities, this Monograph could be used by all other OECD countries, including the EU, for regulatory purposes, thus reducing the time for decision-making, workload and costs.



214 The disadvantages lie not in the idea but in its current implementation. The EU system is too complex, bureaucratic, and expensive. The decision-making process involving so many different entities is unclear, slow and burdensome and is not based uniquely on scientific reasoning but also on economic and especially political factors — countries like Denmark and Sweden with reduced agriculture are politically motivated to ban agrochemicals — and thus there may be no objectivity when voting at the SCPH. Both the farmer and the agrochemical industry are also at a disadvantage. The farmer will have to wait longer for the availability of new products and may have fewer options in the future. For the industry, the system means increased costs, longer times to obtain registration and thus loss of income. The system also stretches the resources of both industry and officials to the limit or beyond. Costs and Time Although it is difficult to give exact costs (which depend on many changing factors), some idea about the actual costs for the obtainment and defense of registrations can be given: Preparation of dossiers: Further studies: Fees: Total per active substance:

$ 400000.00 $ 700000.00 $ 100000.00 $ 1200000.00

Between notification and inclusion in Annex I, the time interval has to be calculated in years. After notification, the notifier has 12 months to submit the data to the RMS. The evaluation of the data and the preparation of the Monograph should theoretically take place within 12 months after receiving the dossier. Then a further 3 months are necessary before the SCPH can vote on the compound. In theory, therefore, inclusion in Annex I could be achieved in less than two and a half years. In practice, these time frames were grossly underestimated. As of November 1997 — i.e. 6 years after the directive was published and 4 years after being enforced — only one substance of the original 90 found in the first list has been included in Annex I: imazalil, a fungicide. Two further substances, the herbicide diquat and the insecticide fenthion, will probably be included in the near future. No new active substance has been included either. On the other hand, 6 substances have been or will be withdrawn from the market: azinphos-ethyl, cyhalothrin, dinoterb, fenvalerate, ferbam and propham. Before Directive 91/414, registration times among the Member States varied between 11 and 60 months. With Directive 91/414, the registration time has not yet been harmonized, but it seems it will not be under 48 months, if the time needed for the second phase is included. For new registrations, this is unacceptable. The whole process —fromsubmission of the dossier to the RMS to the registration of the plant protection product at the national level — should not take more than 30 months.


215


Conclusions Directive 91/414 was a big step forward in harmonizing the registration requirements and procedures within the European Union. However, although the structure o f the dossiers is basically sound, the practical implementation o f the Directive has stressed both industry and authorities to the limit o f their resources. This has led the Commission to realize that the original goal o f reviewing all active substances in 12 years cannot be achieved. Also, the complexity o f the system — mainly decision making, but also unresolved issues like data protection, mutual recognition, minor crops, and parallel imports — make uncertain the future o f the system, especially for old products. A decision on this issue may fall within the year 1998. After all the effort and cost, three possibilities exist. First, keep the system, but overhaul it by streamlining and agilizing it so that the registration o f plant protection products — especially new products — can take place more rapidly with less bureaucracy, with quicker decision making, trust among Member States, mutual recognition, and harmonization. The second possibility would be to create a central European authority for the scientific evaluation and/or registration o f plant protection products — similar to the European Medicines Evaluation Agency ( E M E A ) for pharmaceuticals, located in London — for phase I registration (inclusion o f the active substance in Annex I) and keep national jurisdiction for phase Π (registration o f the formulated product). The third possibility would be to return to national legislation, which in all probability would lead to still more chaos.

Literature Cited 1. 2. 3. 4. 5. 6. 7. 8.

Council Directive 91/414/EEC, Official Journal of the European Communities No. L 230, 19.8.91, p. 1, as corrected in Official Journal of the European Communities No. L 170, 25.6.92, p. 40. Commission Regulation 3600/92, Official Journal of the European Communities No. L 366, 15.12.92, p. 10. Commission Regulation 933/94, Official Journal of the European Communities No. L 107, 28.4.94, p. 8. Commission Regulation 491/95, Official Journal of the European Communities No.L 49, 4.3.95, p. 50. Working Document1663/VI/94rev. 6, 24.5.95. Working Document1654/VI/94rev. 6.2, 2.2.97. Council Directive 79/117/EEC, Official Journal of the European Communities No. L 33, 8.2.79, p. 36. Proposal for Commission Directive 97/C 240/01, Official Journal of the European Communities No. C 240, 6.8.97, p. 1.


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