Finalminutes
Efficacy evaluator meeting- Southern Zone (9th – 10th June 2015)
Objective: Sharing experience and discuss to improve the zonal evaluation.
Dates: Day 1: Tuesday 9th June (afternoon) – Day 2: Wednesday 10th June (whole day).
Location: Anses, 14 rue Pierre et Marie Curie, 94700 Maisons-Alfort.Copernic building.
Contact points :Véronique Mironet.Laurent Thibault.
Participants: refer to Appendix 1.
Day 1 –Introduction and presentations / Discussion / Conclusions1 / Description of the authorization / evaluation organization in each MS + Focus on efficacy teams. / All present MS displayed the organization of authorization and evaluation in their respective countries (FR, HR, IT, EL, SP, PT) and then focus on efficacy teams. In IT (different sites: Piacenza, Milan, Roma, Piza…) and HR (HR: 14 efficacy experts), efficacy evaluation is not a full time activity, whereas it is in other MS. Efficacy teams: FR: 10 to 15 evaluators. PT: 5 evaluators. SP: 3 evaluators. EL: 5 evaluators. Between the evaluators of the different sections, there is direct communication when the teams are located in the same offices (sometimes through a coordinator).
2
/ Update on the revision of dRR format. / The dRR new templates (all sections, Part Bfrom 0 to 10, Part A, Part C) will be effective in January 2016. They are available on the EU commission website since June 2015 (procedural guidance => Format of a dRR – version 2015). In the southern zone, FR(as chairman) and EL(as member of the subgroup) were involved in the revision of the dRR template – Part B section 3 (efficacy section).
What’s new?
-“Section 7” becomes “Section 3” (in line with the DAR chaptering – active substances).
-A new part B - section 0 is created, with general information (such as the GAP table).
-The chapter “summary and conclusion” is now placed at the beginning of the dRR and written by the zRMS
-The efficacy chaptering changed and it is now compliantwith the EU regulation 284/2013.
There is no new requirement in the template for efficacy section. However, clarification is brought and the template formalizesthe expected information – currently missing: major / minor status of uses, new PPP / new use / renewal, justification of the association and ratio in case of co-formulated products…This new format is expected to improve the quality of submitted dossier. On a volunteer basis, applicants can start to use the new format.
Day 1 – Open discussion on general subjects / Discussion / Conclusions
3 / Feedback with the use of commenting boxes/rewriting, when transforming a dRR into a RR. / All SZ MS are using only commenting boxes, except FR which uses both (deleting / rewriting or commenting boxes). Both options are still possible; however, the zRMS should clearly describe it’s approach in introduction, to avoid any doubts for cMS when reading the (d)RR.
4 / Feedback with the use of commenting and reporting tables: How to improve their use? / The commenting stages are appraised and give transparency. EL comments all dRR, even if they are not cMS, in case of a future demand of mutual recognition. FR comments only dRR when FR is a known cMS. FR always considers possible (if commented or not) to have a different opinion compared to the zRMS, if argued (quite rare for efficacy section).
It was concluded that even in the absence of comments, each MS that has read the dRR can make a comment like “Agree with the zRMS”, for the zRMS to distinguish if the other MS agree or has not consulted the document.
Most of SZ MS accept new data at the commenting stage (usually FR does not accept them, but it depends). If inclusion of new data, it was suggested that zRMS highlights in introduction of the RR in which chapter the new data has been added. If this new data lead to a change of the zRMS conclusion (unacceptable becoming acceptable…), the other cMS will not have the opportunity to comment it, so it is preferable to let open the conclusion (= to be confirmed at MS level).
In case of typical “French dossiers” (e.g. cereals, sugar beet…): for a number of dossiers, we can see that the applicant wrote it only for registration in France, with a high majority of trials carried out in the Maritime EPPO zone, and Mediterranean (FR) and Maritime data mixed together (…). In that case, we first should ensure that there are no other cMS than France. Then, FR proposes to conclude that in case of a future mutual recognition, the dossier does not comply with the expected requirements for a registration in other SZ MS (so, decision will be taken at MS level).
5 / Which options have MS when the applicant dossier is of “bad quality”? / Evaluators said that they try to ask the applicant to rewrite parts of the dRR. However, it was not always possible and sometimes the applicant reply was still not satisfactory. To refuse the dossier on the basis of “bad quality” of dRR is also not really possible or not wanted. zRMS doesn’t have the time to rewrite everything, and it is even impossible in case of a high number of trials and/or high number of uses. MS are afraid that if total impunity, applicants will continue to provide bad documents.
The suggested options are:
-Continue asking to rewrite some tables or parts of text during the “completeness check” / “demand for complementary data”,
-Comment in the (d)RR on the quality of the applicant submission (positive and negative feedbacks) and explain the expected improvements,
-Pre-submission meetings are another way to make a feedback to industry.
6 / GAPtable: how to manage with unprecised GAP? Unprecised cMS? Table of «intended uses» or table of “conclusions of the evaluation”? / It is expected that inconsistencies between the GAP tables of the different sections (and cases where cMS are unknown) will be solved by the new dRR format, with a unique GAP table in section 0. When crops (e.g. cereals) and/or targets (e.g. fungi) are not precise enough, we hope that working groups from EPPO and EU commission will improve future submissions.
The suggested options are:
-Ask for precisions during the “completeness check” / “demand for complementary data”,
-Especially when crops and targets are not detailed enough, the crops and targets should be described very precisely in the efficacy / selectivity evaluation, including possible / not possible extrapolations to other crops / targets of the group.
7 / How to conclude in the RR? Opinion of zRMS / choice of opinion at cMS level.
In the new dRR template (section 3):
zRMS conclusion
-Acceptable…
-Acceptable with further restrictions,
-To be confirmed by cMS,
-Not acceptable / evaluation not possible. / The discussion was based on the options proposed in the new template dRR: these options were harmonized for the different sections, so maybe not always very adapted to the efficacy section. This table is intended to present the zRMS conclusions on a very synthetic way, in order to compile easily the conclusions of all sections. It was said that it will be difficult for efficacy section to conclude in the same way for all MS of the zone, because conclusions and expected data highly depends on trial distribution and context of PPP registration in MS (new PPP, renewal, known or not known a.s. / association…). In addition, reduction of number of applications for resistance management will always be at a national level. For now, we have no experience of use of this conclusion table.
The suggested options are:
-From now, start to include such a conclusion table in the dRR, even if the dRR is not submitted within the new format,
-As the options proposed in the table are limited, it will be necessary to clearly explain the conclusions (especially when different to “acceptable”) in the accompanying text,
-Continue to use grey shading to track any addition / modification proposed in the GAP table,
-In the conclusion table, in case of different conclusions for MS, there are 2 options:
- to fill the same line with detailing the conclusions for each MS (and therefore without color shading),
- OR add 1 or 2 more lines (use “1a” and use “1b”), in order to detail “acceptable” for these MS, or “not acceptable” for these other MS.
-About the conclusion “to be confirmed at MS level”: When possible, it is better to propose a conclusion for all MS or if different, for each MS. When the zRMS has doubts, the first approach in the draft RR can be this “open” conclusion. Then, ES appropriately suggests that we should make bilateral contact in order to deal with the discrepancy and reach agreement.So, it is expected than during the commenting stage, cMS willshare its opinion, for the zRMS to transform the “to be confirmed at MS level” by “acceptable / not acceptable”, as much as possible. After the commenting stage, there is also possibility to exchange by e-mails to try to clarify the cMS opinion. In the final RR, we should try to avoid the conclusion “to be confirmed at MS level” (and if used, to clearly explain why this conclusion is proposed).
Day 2 – Morning (Technical subjects)
1a / Use of guidance documents: EPPO, CEB / Deviations to EPPO guidelines: can be accepted if appropriately justified (e.g. excluded UTC, artificial inoculation…). However, very often, the justification is missing. If zRMS has some doubts, it is possible to exchange with the other MS, to share opinions.
French CEB guidelines (in French) are compliant overall with EPPO guidelines. They are still used by applicants and authorities especially because they are more detailed than EPPO guidelines. FR agrees to share CEB guidelines upon MS request and to provide the expected information in English. CEB plans to translate in English the CEB guidelines, with starting with the main ones this year.
The question of how to deal with new products of already known active substances was also discussed. FR stated that according to EPPO PP 1/226(2),reduced data (such as bridging data showing similar behaviour of 2 products) is possible for new products containing already known active substances. In FR, there is also possibility, when data protection no longer apply,to just demonstrate that the composition is similar (verified by phys-chem section+ tox classification), and then registration is possible in France, without other assessment (risk and efficacy).
EL (ES?, IT?) stated that efficacy trials are required as evaluation is conducted on product level and not on active substance level.
At the last Post Annex I meeting (June 2015), it was said that UK, DE, NL and FR publish or wish to publish RR part A and/or part B when they are zRMS (and some of them plan also to publish them when they are cMS).
1b / Statistics / There are lots of cases where statistics are not appropriately used or not adapted to the trial design (e.g. too many number of treatments leading to an insufficient “degree of freedom”). How to manage?
The suggested options are:
-Especially when statistical approach is not valid, be careful when concluding. If regular effect in different trials, trends / tendencies can been used,
-It is interesting to have both statistical analysis with UTC and without UTC (best to show differences between treatments),
-Possible to ask improvements by the applicant during the period of “completeness check” / “demand for complementary data” or to comment in the (d)RR on the bad quality of the statistical approach.
2 / Minor uses, extrapolation / There are existing national lists of “major crops” or “minor crops” (sometimes also “minor uses”) in most MS. zRMS can also refer to the Belgium document on crop distribution across Europe, with crop areas (see in appendix 2). In the new template, it is clearly asked to the applicant to detail the use status (minor / major crops and minor / major use) in each cMS: this is very expected information.
EL proposes only extrapolation when they are reported in EPPO extrapolation tables or DG SANCO document, whereas other MS propose also other extrapolations (based on expert judgment / regulatory experience), not listed in existingtables. It was said that EPPO tables are implemented regularly, but they will never cover all cases. If MS identify a missing extrapolation, they should be shared to be proposed at the EPPO meeting.
Especially, there are no extrapolation tables including arable crops, because they are considered as “major” crops (although some of them are minor in some MS). Based on 2 examples (apples and pears, wheat and triticale), SZ MS agreed that however, it can be possible to enhance the spectrum of extrapolation also to some major crops (in that case, extrapolation will generally mean “reduced data”). Extrapolations can be proposed by the zRMS, but decision will be always taken at MS level.
Some MS accept efficacy data only on the “most sensitive” crop and then accept to extrapolate efficacy to a close crop (less sensitive crop) on a same target. Same reasoning is possible for crop safety.
3 / Valid / invalid trials: which criteria? Delete invalid trials or keep then into the RR? / Considering infestation levels, applicants and zRMS are invited to precise the minimum threshold considered. It was proposed to create an excel table between SZ MS, to share our thresholds. FR will send to the participants a table (we are preparing it), to be completed.
“Invalid trials”: e.g. not sufficient infestation…
“Additional supportive data”: e.g. some deviation to guidelines, practical use trials (when the test PPP is not used alone but in a program)…
It was agreed to not delete “Invalid” trials or “additional supportive trials” in the RR, but just to separate the results. When infestation levels are too low, the trial will not be considered in the efficacy chapter, but can be used for selectivity assessment (including yield assessment).
4 / Distribution of trials / trial grouping / The case of “not good distribution of trials” occurs very often and can lead to different conclusions in the SZ. FR and HR are divided into 2 EPPO climatic zones, whereas others belong to 1 zone (EPPO Mediterranean zone and EPPO South-east zone, for BU). It was said that the climatic boundaries are sometimes not “logical” considering real climate (e.g. north-west of ES, north of PT).
In France, the registration is one unique GAP (a maximum dose, than can be lowered) for both parts of France. It is very rare to observe differences of efficacy / crop safety between climatic zones. For some a.s. families or mode of action with an action dependent to temperature / humidity / soil type, if we want to see climate / soil effect, it is more appropriate to make comparison between trials under “wet” conditions and trials under “dry” conditions (“hot” vs “cold”, “soil 1” vs “soil 2”…), than making comparison between EPPO climatic zones (differences are rarely seen).
For efficacy conclusions and especially in the case of herbicides (for defining a weed spectrum), FR needs to have a synthesis will all trials covering the French situation (usually both maritime and mediterranean zone data). On the same way, “Mediterranean” MS needs to have an EPPO Mediterranean synthesis. For fungicides and insecticides, it is easier to manage.
Field / greenhouse: Considering the target, it should be identified the worst case scenario(s): what is the most critical situation between F and G? Then the majority of trials can be done in this worst case condition. However, some MS or some situations require for a minimum of data in both situations (at least for major uses).
MS encounter issues (in efficacy section) with the separated data between 1 greenhouse interzonal dRR and 1 field zonal dRR, especially when the first one includes only G data, whereas the other includes only F data, and when the dRR are not available simultaneously. For efficacy section, both F and G data are usually essentialto judge the acceptability of data. In the SZ zone, we all agree that F supportive data should be included in the G dossier (and vice-versa) to provide additional evidence (with separated results). ES: F and G data should not be included in the dRR as a rule. From our point of view, the applicant should have initiative of presenting both data, simultaneously.
5 / Application rates: what the registered dose in each MS? How to define the “minimum effective dose”? / In most SZ MS, the registered dose is a range [min-max]. In France, the registered dose is a “maximum dose” that can be lowered in practice = this is considered as recommendations of use and no data is requested at “registration” level. Technical institutes make their own trials and then give advice to farmers: the conditions of use are adapted to the region, to the pest pressure… and also consider resistance management. In other MS, the existing lower limit of the range is intended to avoid farmer strong dose reduction (which can have various side effects, such as the increase of the resistance risk).
Application rate expressed in LWA (Leaf Wall Area) is rarely seen in dossiers (we have just a very limited examples). When different dose expressions are used in the trial set, this is accepted provided that all the relevant parameters of crop structure are givento facilitate doseexpression conversions.
About the “minimum effective dose = MED”, although defined in the EPPO 1/225 (“dose that is the minimum necessary to achieve sufficient efficacy against a target pest across the broad range of situations in which the product will be applied.”), the term is not understood in the same way by all the participants. Some MS consider it as the maximum dose of the range, whereas others consider that it can be both [min-max]. In practice, the MED chapter (when appropriately fulfilled) can apply to both approaches, based on the same trial set.
When analysing the dose justification, zRMS can explain in which conditions the higher dose is needed: e.g. “The maximum dose rate or the N dose is justified under these conditions: … (weeds, infestation pressure, soil conditions…). The reduced dose(s) (such as 80% of the intended one) provided sufficient control of the targeted pest and can be recommended in these situations: …
All SZ MS regret that the new version of the EPPO 1/225 guideline only requires 1 lower dose (e.g. 0,6Nor 0,8N). Indeed, in that case, a dose effect is almost always seen between 0.6N and N, whereas almost never seen between 0,8N and N => we all agreed to say that 2 lower doses are necessary (e.g. 0,6 N + 0,8N + N). This will be reported to the EPPO and evaluator meeting.
6 / Should the trials be exactly in the conditions described in the GAP table? (with the example of the number of applications, water volumes, crop stages) / Number of application: All participantsagreed to say that for long-lasting diseases, the efficacy trials can be done with a higher number of applications compared to the intended number of application(standalone efficacy trials)- when the number of applications is intended to be low because of resistance management (or because of risk assessment). Practical value trials are interesting to complete the evaluation of the product, to see its efficacy when integrated in a protection program.