Training Session Product File Note and Registration Reports, 23 October Product File Note (PFN) Maarten Derudder - Olivier Guelton Federal Public Service of Public Health, Food Chain Safety and Environment Service Pesticides and Fertilizers

Federal Public Service ‘Public Health, Food Chain Safety and Environment’ 2 Overview Product File Note Introduction General administrative aspects Data protection Overview of the standard document Physico-chemical properties and analysis Toxicology Biology Residues Ecotoxicology Fate and behaviour Other information / administrative aspects / confidential info

Federal Public Service ‘Public Health, Food Chain Safety and Environment’ 3 Introduction Target of Product File Note (PFN) Diminish work load Section Pesticides and Fertilizers (no new staff, existing delay) Leave possibility of priorisation of dossiers to firms (no more changing dossiers in waiting line, call for an ‘urgent dossier’) PFN is the only possibility for a quicker evaluation Pro-active: applicants more aware of completeness of dossier + more complete proposal/evaluation Type of dossiers concerned: ‘National Dossiers’ Only for applications for products based on old active substances which are not (all) included in annex I of directive 91/414/EEC. authorisation of formulation containing new active substance + one or more old active substances: possible with PFN IF engagement firm to furnish Registration Reports once all active substances included in annex I See fast track procedures document

Federal Public Service ‘Public Health, Food Chain Safety and Environment’ 4 General Administrative Aspects (1) Working procedures when treating a dossier with a PFN: completeness check by administration if not complete: PFN sent back ( ) to applicant for modification/ completion if complete: product on agenda Authorisation committee once accepted by secretary of Authorisation Committee: PFN sent back to applicant, applicant sends by post a paper copy to officialize PFN GOAL = gain time for Pesticide Service

Federal Public Service ‘Public Health, Food Chain Safety and Environment’ 5 General administrative aspects (2) Cfr. circulaire! classical application form: still required, reference can be made to PFN PFN has to be furnished digitally (CDRom or (for old dossiers in queue – confidentiality? – composition details in annex to file note)) model will be placed on Phytoweb (Eng, Fr, Dutch) dossiers with PFN treated with priority, dossiers without PFN will also be treated! In framework Aarhus convention: reports of Authorisation committee will be placed on Phytoweb – file note as well, minus the confidential parts

Federal Public Service ‘Public Health, Food Chain Safety and Environment’ 6 General Administrative Aspects (3) PFN is only a model: non-relevant parts should be removed – with TRACK CHANGES PFN for all types of applications, not only authorisation but also renewal, prolongation, change of composition, extension treatment of PFN: OG & MD, following date of reception

Training Session Product File Note and Registration Reports, 23 October Data Protection Scope: at Belgian level data protection can be granted by the Service Pesticides and Fertilizers at the request of the notifier (art. 13 of the Royal Decree of 28/02/1994)

Federal Public Service ‘Public Health, Food Chain Safety and Environment’ 8 Data Protection: General Requirement The following studies are always necessary to obtain a registration:  GLP analysis of 5 samples of a.s.  Analysis of physical & chemical properties of the formulation  Toxicological studies (acute oral & dermal (& inhalation), irritation skin & eyes, sensibilization potential)  Ecotoxicological studies on water organisms (algae, Daphnia & fish) The notifier must not require the protection for these data

Federal Public Service ‘Public Health, Food Chain Safety and Environment’ 9 Data Protection: Particular Cases Data protection can be granted in the case of : 1. Additional data submitted by the authorisation holder in order to modify the current registration For example: residue (& biological) studies for a label extension, study on the biodegradibility, … 2. Additional data required by the Belgian Authorisation Committee and necessary to preserve the registration For example: mesocosm study, … The notifier must require the protection for these data (and has to fill in the table)

Federal Public Service ‘Public Health, Food Chain Safety and Environment’ 10 Request For Data Protection The table has to be filled in by the applicant but only for the particular cases DossierDataProtectio n for Expiry date of protectio n Holder of protectio n Confirma- tion of the protectio n Study reference (title, author, year, ref n° of applicant, ref n° of lab) (Active substance active, ev. formulation type, N number if known) Mesocos m study Reductio n of bufferzon e Applicant Author, Year, Source (where different from company) Company, Report No. GLP or GEP status (where relevant) Published or Unpublished

Federal Public Service ‘Public Health, Food Chain Safety and Environment’ 11 Data Protection: Decision Making  Treatment of the request by the Service Pesticides and Fertilizers  Advice of the expert (quality of the study (GLP), …)  Proposal to the Authorisation Committee  Decision by the Authorisation Committee (Protection Yes/No) Decision concerning data protection will be mentioned in the letter sent to the registration holder Start: date on the letter sent by the Service Pesticides and Fertilizers

Federal Public Service ‘Public Health, Food Chain Safety and Environment’ 12 Data Protection: Validity Of The Protection Annex II dataAnnex III data Not included new a.s.None Included new a.s.10 years after inclusion 10 years after authorisation Not included old a.s.10 years after authorisation 5 years after maintenance of authorisation None Included old a.s.5 years after inclusion 10 years after re- registration

Federal Public Service ‘Public Health, Food Chain Safety and Environment’ 13 Overview of the Standard Document Physico-chemical properties and analysis 1. Active Substance 2. Physchem parameters Toxicology Biology Residues Ecotoxicology Fate and behaviour Other information / administrative aspects

Training Session Product File Note and Registration Reports, 23 October Overview of the Standard Document: Physico-chemical properties and analysis Active Substance 1. Data Requirement 2. Evaluation 3. Technical Equivalence Formulation 1.Data Requirement 2.Evaluation

Federal Public Service ‘Public Health, Food Chain Safety and Environment’ A.S.: Data Requirement 1.1. Specifications of the a.s. Minimum purity of a.s. Maximum concentration of impurities incl. CAS n°, formules, IUPAC denomination ! 1.2. GLP analyse of 5 production batches of technical a.s Manufacturing process of a.s. Remark: Data required for a new origin (authorisation or alternative source) and renewal

Federal Public Service ‘Public Health, Food Chain Safety and Environment’ A.S.: Evaluation (1) 2.1. Quality of the submitted documents: secretariat & expert 2.2. Evaluation of the results: Respect of FAO standard (if existing): Yes: evaluation goes on No: no authorisation (origin not acceptable)

Federal Public Service ‘Public Health, Food Chain Safety and Environment’ A.S.: Evaluation (2) If a.s. already authorised in Belgium: Min. purity  Min. purity reference and no new impurity: Yes: evaluation goes on No: demonstration of technical equivalence New impurity or known impurity but at a concentration > concentration in the reference: Yes: demonstration of technical equivalence No: evaluation goes on

Federal Public Service ‘Public Health, Food Chain Safety and Environment’ A.S.: Technical Equivalence (1) Technical equivalence according to: Guidance document on the assessment of the equivalence of technical materials of substances regulated under council directive 91414EEC (Sanco10597/2003) Document & instructions available on Technical equivalence must be demonstrated before the granting of the authorisation

Federal Public Service ‘Public Health, Food Chain Safety and Environment’ A.S.: Technical Equivalence (2) 1)Tier I required (Part I and Part II): analytical aspect 2 cases: -the new source is equivalent to the reference source: evaluation goes on -if the equivalence of the new source can not be established based on Tier I criteria alone: Tier II evaluation is required 2) Tier II required: tox. & ecotoxicity aspects included Studies can be necessary to assess the equivalence (case by case)

Federal Public Service ‘Public Health, Food Chain Safety and Environment’ A.S.: Technical Equivalence (3) Conclusion of Tier II: Technical equivalence of the new source regarding to the reference? Yes: evaluation goes on No: no registration (application not acceptable)

Federal Public Service ‘Public Health, Food Chain Safety and Environment’ 21 FORMULATION Data requirement (1):  All parameters relevant for the formulation for which an authorisation is asked (see PFN) (and according to the right method !)  Well-argued justification in case of data gap  Data before storage and after storage 2 weeks at 54°C must be present in the application dossier (+ storage under cold conditions if required)

Federal Public Service ‘Public Health, Food Chain Safety and Environment’ 22 FORMULATION: Data requirement (2)  Explanation in case of unusual storage conditions (for example, 8 weeks at 40°C instead of 2 weeks at 54°C)  If new origin of calcium sulphate, clay, vermiculite, natrolite- phonolite, calcium aluminates and clinoptilotite of sedimentary origin: - analysis of dioxin and furan content of this new origin by a GLP laboratory or a recognized laboratory - if concentrations > norms MD June 7th 2006: risk assessment is required Acceptable risk must be demonstrated before the granting of the registration

Federal Public Service ‘Public Health, Food Chain Safety and Environment’ 23 FORMULATION: Evaluation  Completeness check: Secretariat  Physico-chemical properties: Alain Dubois  Prolongation condition: analysis after storage 2 years at ambient temperature  Dioxin and furan aspect: Samira Jarrah (based on the norms published by the Ministerial Decree of June 7 th 2006 concerning trade and use of products intended to be used for animal feeding) If risk unacceptable: change of origin

Federal Public Service ‘Public Health, Food Chain Safety and Environment’ 24 Overview of the Standard Document Physico-chemical properties and analysis Toxicology Biology Residues Ecotoxicology Fate and behaviour Other information / administrative aspects

Federal Public Service ‘Public Health, Food Chain Safety and Environment’ 25 Overview of the standard document: toxicology (1) standard data package: acute oral, dermal and inhalation studies, irritation skin and eyes, sensibilisation with formulation other studies (long term, …): also evaluated – fast evaluation, in depth will be done once annex III dossier all furnished data must be mentioned on PFN (to be added in existing table (cfr. ecotoxicology)) operator exposure (for new applications with new active substances)

Federal Public Service ‘Public Health, Food Chain Safety and Environment’ 26 Overview of the standard document: toxicology (2) data protection: table to be filled out (see above) MSDS: composition to be mentioned! applicant must furnish labelling proposition first aid dossier Evaluation by Christiane Vleminckx

Federal Public Service ‘Public Health, Food Chain Safety and Environment’ 27 Overview of the Standard Document Physico-chemical properties and analysis Toxicology Biology Residues Ecotoxicology Fate and behaviour Other information / administrative aspects

Training Session Product File Note and Registration Reports, 23 October Overview of the standard document: BIOLOGY Table intended use (1) : - has to be completely filled in - application stage: according to BBCH code - Pre-harvest interval not always required (depending on application stage) - MRL: not to be filled in

Federal Public Service ‘Public Health, Food Chain Safety and Environment’ 29 Biological dossier: partim efficacy Required for new intended use Have to be demonstrated by means of GEP studies accordingly EPPO Not required in case of copy product With Letter of Access (LoA): no additional retribution Without LoA: additional retribution (to be paid before the granting of the authorisation)

Federal Public Service ‘Public Health, Food Chain Safety and Environment’ 30 Biological dossier: partim selectivity Required for new product, new intended use and composition change Not required in case of copy product with LoA

Federal Public Service ‘Public Health, Food Chain Safety and Environment’ 31 EVALUATION Evaluation of the biological dossier by: François Cors: fungicides, insecticides, acaricides and rodenticides Bernard Weickmans: herbicides and growth regulators

Federal Public Service ‘Public Health, Food Chain Safety and Environment’ 32 Overview of the Standard Document Physico-chemical properties and analysis Toxicology Biology Residues Ecotoxicology Fate and behaviour Other information / administrative aspects

Federal Public Service ‘Public Health, Food Chain Safety and Environment’ 33 Overview of the standard document: Residues only for new or changed applications (if relevant) – to be removed if not relevant data protection Evaluation by Frédéric Joris or Bruno Dujardin

Federal Public Service ‘Public Health, Food Chain Safety and Environment’ 34 Overview of the Standard Document Physico-chemical properties and analysis Toxicology Biology Residues Ecotoxicology Fate and behaviour Other information / administrative aspects

Training Session Product File Note and Registration Reports, 23 October Overview of the standard document: ECOTOXICOLOGY Requirements (1):  Ecotoxicological studies of the preparation on water organisms (algae, daphnia and fish) With another preparation: composition to be provided + argumentation With a.i. : acceptable for preparation containing a.i. and inerts only

Federal Public Service ‘Public Health, Food Chain Safety and Environment’ 36 ECOTOXICOLOGY: Requirements (2)  Only for the products registered in orchards or intended to be used in orchards: Effect of the preparation on Typhlodromus pyri if product registered (or application for a registration) in apple Effect of the preparation on Anthocoris nemoralis if product registered (or application for a registration) in pear For new application or renewal submitted before October 23 rd 2006: condition for prolongation For new application submitted after October 23 rd 2006: condition for registration

Federal Public Service ‘Public Health, Food Chain Safety and Environment’ 37 Table - risk assessment - evaluation If the dossier (for example Annex III dossier) contains other studies than the 3 «classic» studies on water organism: all the studies have to be mentioned (add rows to the table and fill them in like for the aquatox studies) Proposal for labelling and risk assessment for aquatox have to be joined Evaluation by Ilse Pittomvils

Federal Public Service ‘Public Health, Food Chain Safety and Environment’ 38 Overview of the Standard Document Physico-chemical properties and analysis Toxicology Biology Residues Ecotoxicology Fate and behaviour Other information / administrative aspects

Federal Public Service ‘Public Health, Food Chain Safety and Environment’ 39 Overview of the standard document: Fate and behaviour Only for active substances already on annex I or in case of specific problems (e.g. ground water contamination) Of importance if an annex III dossier has been furnished while the old procedure is still possible (national dossier) Data protection Evaluation by Sébastien Vanhiesbecq

Federal Public Service ‘Public Health, Food Chain Safety and Environment’ 40 Overview of the Standard Document Physico-chemical properties and analysis Toxicology Biology Residues Ecotoxicology Fate and behaviour Other information / administrative aspects / confidential info

Federal Public Service ‘Public Health, Food Chain Safety and Environment’ 41 Overview of the standard document: administrative aspects retribution paid: only after reception of invoice! instructions for first aid (see website phytoweb) non-confidential dossier: still required (legislation) additional retribution: cfr. part biology label: to verify completeness of furnished label Confidential part: separate file

Federal Public Service ‘Public Health, Food Chain Safety and Environment’ 42 Remarks – experience in practice?? remove non relevant parts – track changes mention all furnished data, e.g. toxicology: not only acute tox if also other studies have been furnished composition of formulations used in studies!! references to studies must be complete (title, author, year, reference number applicant, reference number lab) On the whole: sent in PFNs fairly well done