EFSA Manual on the application for MRLs in accordance with Article 6 to 11 of
Regulation (EC) No 396/2005
EFSA Manual
on the
Submission of applications in accordance with
Article 6 to 11 of Regulation (EC) No 396/2005
Routine MRL applications
15 July 2008
http://www.efsa.europa.eu
1 of 15
EFSA Manual on the application for MRLs in accordance with Article 6 to 11 of
Regulation (EC) No 396/2005
TABLE OF CONTENTS
ABBREVIATIONS
3
BACKGROUND
4
RISK ASSESSMENT
5
1.
1.1.
1.2.
1.3.
1.4.
1.5.
2.
2.1.
2.2.
2.3.
2.4.
2.5.
2.6.
3.
3.1.
3.2.
3.2.1.
3.2.2.
3.3.
4.
APPLICATIONS
Who is entitled to apply for setting, amending or deleting of MRLs ?
To whom to submit the application ?
What is required for an application ?
Who has to be informed on the receipt of an application ?
Where to find information on applications made in MS ?
EVALUATION
Who is doing the evaluation ?
What is the format of the evaluation report?
How to perform the consumer intake calculation ?
Does the EMS need to provide the endpoints in the format of the EFSA PROFile?
Deadlines for the evaluation
How to submit the evaluation report to EFSA ?
RISK ASSESSMENT
How Does EFSA process the submitted evaluation reports ?
What is the procedure for the risk assessment in EFSA ?
Procedure to be completed within 3 months
Procedure to be completed within 6 months
Additional data necessary for completing the assessment
FINAL REASONED OPINION
5
5
5
5
7
7
8
8
8
8
9
9
9
10
10
10
10
11
12
13
RISK MANAGEMENT
14
ANNEX 1: FLOWCHART DESCRIBING THE RISK ASSESSMENT PROCEDURE
15
http://www.efsa.europa.eu
2 of 15
EFSA Manual on the application for MRLs in accordance with Article 6 to 11 of
Regulation (EC) No 396/2005
ABBREVIATIONS
ADI
Acceptable Daily Intake
ARfD
Acute Reference Dose
COM
European Commission
CXL
Codex MRL
EAS
Existing Ective Substance
EMS
Evaluating Member State
ER
Evaluation Report prepared by the Evaluating Member State
GAP
Good Agricultural Practice
MRL
Maximum Residue Level
MS
Member State
NAS
New Active Substance
PRAPeR Expert Meeting
The PRAPeR Expert meeting is a meeting of experts on
pesticides which is already organised on a regular basis in the
framework of the peer review of Directive 91/414/EEC which
are also considered appropriate for discussing issues related to
Regulation (EC) No 396/2005.
PRAPeR MRL Team
PRAPeR MRL Team - part of the Pesticide Risk Assessment
and Peer Review Unit managing all tasks related to Regulation
(EC) No 396/2005
PRAPeR MRL Workspace Document management system to exchange between EFSA,
European Commission and Member States all information
related to the tasks defined by Regulation (EC) No 396/2005.
PRIMo
Pesticide Residue Intake Model
PROFile
Pesticide Residue Overview File
Regulation
Regulation (EC) No 396/2005 of the European Parliament and of
the Council of 23 February 2005 on maximum residue levels of
pesticides in or on food and feed of plant and animal origin and
amending Council Directive 91/414/EEC, OJ L 70, 16.3.2005, p.
1.
RMS
Rapporteur Member State
http://www.efsa.europa.eu
3 of 15
EFSA Manual on the application for MRLs in accordance with Article 6 to 11 of
Regulation (EC) No 396/2005
BACKGROUND
Chapter II (Article 6 to 11 and Article 14(1)) of Regulation (EC) No 396/2005 1of the
European Parliament and of the Council on Maximum Residue Levels (MRLs) for pesticides
describes the procedure for applications for MRLs. This new procedure will become
applicable on 2 September 2008. It is important to know that the overall procedure for setting
MRLs has to be completed before an authorisaion or provisional authorisation can be granted
by a Member State. Any delays in the procedure of MRL setting will consequently have an
impact on granting authorisation of the plant protection product at national level. It is
therefore essential to establish an efficiant process with defined deadlines and resposibilities
to avoid unnecessary delays.
According to the legislation different tasks and responsibilities are assigned to the parties
involved in the MRL setting process which are





the applicant applying for an authorisation of a plant protection poduct in a Member
State,
other applicants: parties demonstrating a legitimate interesst in health, including civil
society organisations, commercially interested parties such as manufacturers, growers,
importers, producers, which are entitled to apply for setting, modifying or deletion of
MRLs
competent authorities for the application of MRLs in Member States,
the European Commission and
EFSA.
EFSA proposed a procedure for implementing Chapter II of the Regulation which was
presented to COM and MSs during the Standing Committee on the Food Chain and Animal
Health of 1 February 2008. Following this presentation MSs were invited to submit comments
by 15 March 2008. Taking into account the comments received EFSA revised the proposal
which is now explained in detail in this document.
The scope of this manual is to provide practical guidance to MSs regarding those steps of the
procedure where exchange of information or data with EFSA is foreseen. For reasons of
completness the steps which involve the data or information exchange among other parties
involved in the procedure are mentioned, but are not further elaborated in detail. This manual
is not meant to interfere with the risk management procedures elaborated by MSs and COM.
The manual is also not intended to provide any legally binding procedures or scientific
guidance on the risk assessment of MRLs.
For exchange of information with EFSA in the framework of the MRL setting activities, the
PRAPeR MRL Workspace should be used. Where relevant, the manual will provide practical
guidance on the use of this communication tool.
1
Regulation (EC) No 396/2005 of the European Parliament and of the Council of 23 February 2005 on
maximum residue levels of pesticides in or on food and feed of plant and animal origin and amending Council
Directive 91/414/EEC, OJ L 70, 16.03.2005, p. 1-16.
http://www.efsa.europa.eu
4 of 15
EFSA Manual on the application for MRLs in accordance with Article 6 to 11 of
Regulation (EC) No 396/2005
RISK ASSESSMENT
1.
APPLICATIONS
1.1.
WHO IS ENTITLED TO APPLY FOR SETTING, AMENDING OR DELETING OF
MRLS ?
An application for setting, amending or deleting of MRLs can be made by
a) the party requesting an authorisation or provisional authorisation in a
MS if the GAP for which the authorisation is seeked needs a
modification or the setting of a new MRL,
b) other applicants as specified in Artilce 6(2) of the Regulation, such as
parties demonstrating an interest in health, including civil society
organisations, commercially interested parties (manufactors, growers,
importers and producers of food commodities),
c) Member States which identify the need to set, modify or delete an
MRL.
TO WHOM TO SUBMIT THE APPLICATION ?
In case 1.1.a (application in the contaxt of an application for authorisation of a
plant protection product) the applications have to be submitted to the MS in
which the authorisation is seeked.
In case of an application for an import tolerance the application is submitted
to the Rapporteur Member State designated in the framework of Directive
91/414/EEC. In the following the Rapporteur Member State will be refered to
as the Evaluating Member State in the framework of the application
procedure.
Flowchart step 1
1.2.
Rapporteur Member States
The list of Rapporteur Member States can be found in the PRAPReR MRL Workspace in the
Library section (Official Contact Points). Follow the link:
https://sciencenet.efsa.europa.eu/portal/server.pt?open=17&objID=1344&DirMode=1&parentna
me=Dir&parentid=12&mode=2&in_hi_userid=15006&cached=true
1.3.
WHAT IS REQUIRED FOR AN APPLICATION ?
An application for setting, amending of MRLs or for setting import toleranes
consists of
a) general information on the application (applicants should contact the
national authorities concerning the formats of the applications. EFSA
developed an application form which includes the data relevant to
EFSA. If national authorities agree this template may be used for
applications. )
http://www.efsa.europa.eu
5 of 15
EFSA Manual on the application for MRLs in accordance with Article 6 to 11 of
Regulation (EC) No 396/2005
Application form proposed by EFSA
The proposed application form can be found on the PRAPeR MRL Workspace in the
Library section (General information, EFSA Manuals and templates for data
submission). Follow the link:
https://sciencenet.efsa.europa.eu/portal/server.pt?open=17&objID=1309&DirMode=1&
parentname=Dir&parentid=12&mode=2&in_hi_userid=15006&cached=true
b) the detailed description of the GAP in the standard format related to
the MRL application,





metabolism of primary crops
metabolism in rotational corps
metabolism in animal commodities
nature of residues in processed commodities
analytical methods for enforcement (plant and animal
commodities)






storage stability
supervised field trieals
magnitude of residues in processed commodities
magnitude of residues in rotational crops
feeding studies
toxicological data to establish an ADI and an ARfD in those
cases where no agreed toxicological reference values have been
derived in the EU (this will mainly apply for import tolerances
for active substances which are not used in Europe),
Step 1, continued
c) a dossier with the data listed in Annex II and III to Directive
91/414/EEC relevant for setting the MRLs, in particular on the
following elements
If the data relevant for the application have already been submitted
and assessed in the framework of the Peer Review under Directive
91/414/EEC, it is sufficient to make a reference to these data and
the respective assessment reports .
d) a summary of the dossier and
e) an index of the documentation (list of studies)
In case of an application for deletion of an MRL the applicant has to provide a
scientific justification supported by the necessary documents to underpin the
argumentation.
http://www.efsa.europa.eu
6 of 15
During the evaluation the EMS may ask the applicant for further information
if considered necessary to complete the dossier. The EMS has to specify the
time limits to provide the additional information which may not exceed a
period of two years.
It is recommended that the applicant should contact the MS to which the
application will be submitted to comply with the national application formats.
The MS receiving an application shall immediately forward a copy of the
application form to the COM and EFSA. The notification to EFSA should be
sent via email to the RPAPeR MRL mailbox (praper.mrl@efsa.europa.eu)
indicating in the subject the name of the active substance and MRL
application. If a national application form is used, the EMS has to make sure
that at least the information specified in the EFSA application template is
submitted.
1.5.
Step 2
WHO HAS TO BE INFORMED ON THE RECEIPT OF AN APPLICATION ?
WHERE TO FIND INFORMATION ON APPLICATIONS MADE IN MS ?
Upon receipt of the notification mentioned above, EFSA will create a new
project in the PRAPeR MRL Workspace (Collaborative workspace for MRL
risk assessment) and upload the application form in the subfolder. The project
folder will during the whole procedure provide the user all relevant
information regarding the details of the application, the supporting
documentation and the correspondence.
All ongoing projects are summarised in an overview table (MRL Risk
Assessment Table) which can be consulted to get information on activities in
another MS, e.g. on on an application related to the same active substance. It
is recommended that a bilateral exchange of information should be envisaged
if MS are working on the same active substance or on similar applications in
order to safe resources at an early stage of the evaluation and to avoid
conflicting evaluations.
http://www.efsa.europa.eu
Step 3
1.4.
Step 1, cont
EFSA Manual on the application for MRLs in accordance with Article 6 to 11 of
Regulation (EC) No 396/2005
7 of 15
EFSA Manual on the application for MRLs in accordance with Article 6 to 11 of
Regulation (EC) No 396/2005
2.
EVALUATION
2.1.
WHO IS DOING THE EVALUATION ?
A MS to which the application has been submitted will evaluate the dossier.
As mentioned before, MSs working on similar applications should come in
touch to find out whether the tasks on the evaluation can be shared.
MS can contact the COM to prepare a commitology procedure to re-allocate
the work where a MS encounters difficuties in evaluating an application or
where a re-distribution of the tasks would avoid duplication of the work.
2.2.
WHAT IS THE FORMAT OF THE EVALUATION REPORT?

B.5.2 Analytical methods (residues) for plants, plant products,
foodstuffs of plant and animal origin, feedingstuffs

B.6 Toxicology and metabolism (in particular 6.10 Summary of
mammalian toxicology and proposed ADI and ARfD )

B.7 Residue data
Step 4
The evaluation performed by the EMS shall follow the provisions of Annex
VI to Directive 91/414(EEC). The format of the report is not specified in the
legislation, but for reasons of comparability and compatibility with the
assessments under Directive 91/414/EEC is recommended to follow the
structure of the DAR. The studies and information submitted by the applicant
should be reported as provided in Annex B of the DAR for the following
sections:
In addition, a short summary corresponding to Volume 1 of the DAR
(Reasoned statement of the overall conclusions drawn by the Evaluating
Member State) should be presented.
EFSA prepared a template which may be used by MS for writing the
evaluation report.
EFSA template for the Evaluation Report to be drafted by MS
The proposed evaluation report template can be found on the PRAPeR MRL Workspace in
the Library section (General information, EFSA Manuals and templates for data
submission).
2.3.
HOW TO PERFORM THE CONSUMER INTAKE CALCULATION ?
For the consumer intake calculation the most recent PRIMo (pesticide residue
intake model) should be used.
http://www.efsa.europa.eu
8 of 15
EFSA Manual on the application for MRLs in accordance with Article 6 to 11 of
Regulation (EC) No 396/2005
EFSA model for consumer risk assessment
The EFSA model for consumer risk assessment (PRIMo- pesticide residue intake model)
can be found on the PRAPeR MRL Workspace in the Library section (General
information- Templates and Calculators).
https://sciencenet.efsa.europa.eu/portal/server.pt?open=17&objID=1311&DirMode=1&par
entname=Dir&parentid=12&mode=2&in_hi_userid=15006&cached=true
DOES THE EMS NEED TO PROVIDE THE ENDPOINTS IN THE FORMAT OF
THE EFSA PROFILE?
No. The EMS does not have to fill in the PROFile for an application made in
the framework of a MRL setting procedure. The PROFile has been developed
for the review of MRLs in accordance with Article 12(1) and 12(2). However,
for those active substances for which the re-evaluation of existing MRLs has
already been completed and a revision of the PROFile is available in the
PRAPeR MRL workspace, the PROFile will be updated by EFSA with the
information provided by the EMS. This procedure should ensure that no
conflicting versions of the PROFile are created by different MS working on
applications related to the same active substance.
2.5.
Step 4, cont.
2.4.
DEADLINES FOR THE EVALUATION
Article 8 of the Regulation requires that the EMS draws up the evaluation
report without undue delay.
If an application is withdrawn, the EMS should inform EFSA and the COM
immediately.
HOW TO SUBMIT THE EVALUATION REPORT TO EFSA ?
According to Article 9 of the Regulation, the EMS has to send the evaluation
report (ER) to the COM which will forward it without delay to EFSA.
To simplyfiy the procedure EFSA proposes that the evaluation report and the
supporting dossier should be uploaded directly in the relevant project folder
on the PRAPeR MRL workspace.
http://www.efsa.europa.eu
Step 5 and 6
2.6.
9 of 15
EFSA Manual on the application for MRLs in accordance with Article 6 to 11 of
Regulation (EC) No 396/2005
How to upload the evaluation report on the PRAPeR MRL Workspace?

Save the evaluation report on your local drive as Evaluation_[country
code]_[name of the active substance].doc
(e.g. Evaluation_AT_azoxystrobin.doc)

Select the project in the “Collaborative workspace for MRL risk assessment”,

Click on the subject describing the project the and upload the file in the folder
“2. Evaluation report” using the Upload single file function.

The supporting dossier can be uploaded in the foler “3. Supporting Dossier”.

3.
RISK ASSESSMENT
3.1.
HOW DOES EFSA PROCESS THE SUBMITTED EVALUATION REPORTS ?
In most routine cases of MRL applications a three months deadline will be
proposed. However, in the following cases the extended six month period
should be applicable:



Applications that involve new metabolism studies
Applications that involve new toxicological studies
Other exceptional cases for which an extended time period will
be needed (decisions will be taken on case-by-case basis
considering the complexity of the application)
Step 7-9
As soon as the evaluation report is submitted and the first completness check
is finished, EFSA will decide which deadline for completion of the reasoned
opinion should be applied.
EFSA will send a letter of acknowledgment of the receipt of the application to
the EMS and the COM, indicateing the deadline for the completion of the
reasoned opinion. The correspondence will be archived in the relevant project
folder.
3.2.
WHAT IS THE PROCEDURE FOR THE RISK ASSESSMENT IN EFSA ?
3.2.1. PROCEDURE TO BE COMPLETED WITHIN 3 MONTHS
In routine MRL applications for which only 3 months are foreseen for the
completion of an EFSA reasoned opinion, no consultation with MS will be
possible. However, in the course of the risk assessment, EFSA will stay in
close contact with the EMS to clarify minor issues on short notice.
http://www.efsa.europa.eu
Step 10-12
Depending on the case whether the reasoned opinion has to be finalised within
3 or 6 months, different procedures will be applicable as described below.
10 of 15
EFSA Manual on the application for MRLs in accordance with Article 6 to 11 of
Regulation (EC) No 396/2005
3.2.2. PROCEDURE TO BE COMPLETED WITHIN 6 MONTHS
In those cases where EFSA proposed to go for a 6 month evaluation period
MS will have the oporunity to provide comments on the evaluation report
submitted by the EMS. In particular, MS will be invited to react on the
proposed conclusions regarding the residue definitions and the impact of the
toxicology studies on the derivation of toxicological reference values. The
normal commenting period will be 4 weeks.
Notification of the commenting period to MSs
MSs will be informed about the commenting period by e-mail which will specify the
deadline for submitting comments. In the e-mail the user will also find a hyperlink to the
PRAPeR MRL Workspace. By clicking the task in the e-mail, MSs will be able to view their
task into more details.
The task defined on the PRAPeR MRL Workspace will contain a clear description of the
actions that are expected from MSs and in attachment to the task MSs will also find a
template for comments and the draft opinions for which comments are requested.
MS should submit their comments within the specified deadlines by uploading
them on the PRAPeR MRL Workspace.
How to upload the comments on the PRAPeR MRL Workspace?
 Save the completed comment template on a local drive of your computer as
Comments_[country code]_[name of the active substance].doc
(e.g. Comments_AT_azoxystrobin.doc)
Step 13-15
The MSs will receive a last reminder on the day of the deadline.
 Log on the PRAPeR MRL Workspace using your personal username and password.
 Go to the collaborative workspace for MRL risk assessment
 Select the relevant project established for the application by clicking on the subject
hyperlink.
 Select the Documents tab within this project.
 Upload the PROFile using the Upload single file function in the menue bar.
After the commenting period EFSA will compile all the comments received in
a single consultation table. The EMS will be asked to respond to the
comments submitted in a written procedure within the deadline communicated
by EFSA, usually within 4 weeks. When addressing the concerns raised in the
consultation table, the EMS is encouraged to liase with the applicant if this is
needed to clarify the issues. The completed commenting table and the updated
evaluation report (revision 1 of the evaluation report) should be submitted
through the PRAPeR MRL Workspace using the document up-load fuction.
During this written procedure the EMS should not submit addenda to the
original evaluation report, but incorporate the additional information in an
http://www.efsa.europa.eu
11 of 15
EFSA Manual on the application for MRLs in accordance with Article 6 to 11 of
Regulation (EC) No 396/2005
updated evaluation report. EFSA is of the opinion that this would increase the
transparency and traceability of thw whole process.
In exceptional cases, when issues regarding data requirements or concerns
regarding the consumer exposure identified by MS or EFSA could not be
solved, EFSA will schedule the active substance to an expert meeting. The
expert meetings are not meant to discuss new data or additional GAPs but
should focus on the open issues resulting from the MS consultation. MS
experts will be notified according to the procedure detailed below.
Expert meetings will be scheduled through the PRAPeR MRL Workspace and MSs will
be informed by e-mail. The e-mail will contain clear instructions for nominating
participants for the meeting as well as a hyperlink to the PRAPeR MRL Workspace. By
clicking the hyperlink MSs will be able to view the calander containing a short
description of the agenda.
An official invitation will be sent to the nominees afterwards.
ADDITIONAL DATA NECESSARY FOR COMPLETING THE ASSESSMENT
If during the commenting period, the assessment of the application by EFSA
or during the expert meeting it turns out that essential data are missing or if a
significant modification of the evaluation report is required, EFSA will inform
the COM, the EMS and the applicant in writing, specifying exactly the nature
of information needed. The Regulation does not stipulate to set deadlines for
submitting missing data. However, the request for additional information will
stop the clock regarding the time limit assigned to EFSA. After the missing
information has been submitted by the applicant the EMS has to incorporate it
in a new revision of the evaluation report. The clock will be started again
when EFSA receives the updated ER from the EMS which will be again be
confirmed in writing. For uploading the revised evaluation report follow the
instructions as described in point 2.6. The fact that the clock is stoped can be
retrieved in the overview table of the PRAPeR MRL workspace by clicking
on the relevant question numer.
http://www.efsa.europa.eu
Step 18-22
3.3.
Step 13-15 cont.
Notification of the expert meeting to MSs
12 of 15
EFSA Manual on the application for MRLs in accordance with Article 6 to 11 of
Regulation (EC) No 396/2005
4.
FINAL REASONED OPINION
Based on the data provided in the evaluation report, the results of the MS
consultation and the conclusions achieved in the expert meeting, EFSA will
draft its reasoned opinion for each application received individually.
In this report EFSA will conclude on whether all aspects of the pesticide
residues risk assessment have been covered in the evaluation. EFSA will then
perform a consumer intake calculations using the EFSA Pesticide Residues
Intake Model (PRIMo) considering:
- the MRLs applied for in the framework of Articles 10 and 11,
- the existing CXLs for the active substance concerned.
If an exceedance of the ADI is observed, the consumer exposure concerns will
be reported indicating the commodities contributing most to the ADI
exhaustion. Commodities for which an acute consumer intake concern is
identified will also be highlighted.
Based on the outcome of the dietary intake calculations EFSA will propose
recommendations regarding
Step 23-25
- the established MRLs of Annex II and Annex III of the Regulation,
- the setting of new MRLs,
- the retention, modification or revocation of existing MRLs,
- whether the propsed MRLs should be included in Annex II or Annex III to
the Regulation,
- the inclusion of the active substance in Annex IV,
- specific processing factors,
The final EFSA opinion will be published on the EFSA website. The
documentation related to the project will be updated accordingly, including
the reference to the reasoned opinion in the workspace, the date of adoption
and date of publication of the opinion.
http://www.efsa.europa.eu
13 of 15
EFSA Manual on the application for MRLs in accordance with Article 6 to 11 of
Regulation (EC) No 396/2005
RISK MANAGEMENT
Within three months of the receipt of the reasoned EFSA opinion the COM has to prepare a
Regulation on the setting, modification or deletion of the MRLs, or prepare a Decision
rejecting the application. The proposal has to be based on the opinion, and other legitimate
factors relevant to the matter.
The COM may request supplementary information to be provided by the applicant or EFSA
at any time after the finalisation of the reasoned opinion if needed to take the final risk
management decision. Such information has to be communicated to MS and EFSA. Upon
request, EFSA will provide additional support to the COM at this stage of the procedure.
http://www.efsa.europa.eu
14 of 15
EFSA Manual on the application for MRLs in accordance with Article 6 to 11 of
Regulation (EC) No 396/2005
ANNEX 1: FLOWCHART DESCRIBING THE RISK ASSESSMENT PROCEDURE
Start
1. Applicant sends
the application to the
EMS
1. Application
3. EFSA creates a
new project in the
PRAPeR MRL
Workspace
2. EMS notifies the
application to COM
and EFSA
4. EMS drafts the ER
2. Evaluation
5. EMS submits the
ER to COM
6. COM forwards the
ER to EFSA
7. EFSA defines the
legal deadline
for EFSA
9. EFSA updates the
project on the PRAPeR
MRL Workspace indicating
the deadline
8. EFSA sends the
acknowledgement
letter of receipt
3. Risk assessment
22. EMS submits
the updated ER to
EFSA
10. Consultation of
MS?
Yes
No
21. EMS drafts the
updated ER
14. MS submit
comments to EFSA
11. EFSA assesses
the application
15. EFSA and EMS
evaluate the MS
comments
20. Applicant
submits additional
information to
EMS
19. EFSA indicates
the clock stop on
the PRAPeR MRL
Workspace
16. Expert
meeting?
17. Discussion in
expert meeting
12. Additional
information?
No
4. EFSA reasoned opinion
Yes
No
18. EFSA informs
COM, applicant and
EMS about the
clock stop
Yes
13. EFSA creates
a comment folder
on the PRAPeR
MRL Workspace
23. EFSA drafts
the reasoned
opinion
24. EFSA
publishes the
reasoned opinion
25. Final update of
the PRAPeR MRL
Workspace
End
http://www.efsa.europa.eu
15 of 15