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European Medicines Agency

Standard Operating Procedure



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Title: Tasks of the product team on the handling of the initial Marketing Authorisation Application
PUBLIC
Document no.: SOP/H/3004
Lead Author Approver
Effective Date: 15-OCT-07
Name: Evdokia Korakianiti Name: Patrick Le Courtois
Review Date: 15-OCT-10
Signature: On file Signature: On file
Date: 01-OCT-07 Date: 09-OCT-07
Supersedes:
SOP/H/3004 (15-JUL-01)
1. Purpose
The SOP describes the tasks of the Product Team at different steps of the centralised procedure for an
EU marketing authorisation from pre-submission through publication of the EPAR and the final
transfer of responsibilities from the Pre-Authorisation to the Post-Authorisation Unit. For generics,
hybrids, biosimilars, products intended for compassionate use, or Article 58 procedures certain steps
of this SOP may not apply or additional steps may need to be taken. When handling such applications
consult the additional available guidance.
The SOP also describes the tasks relating to the withdrawal of an application.
For the detailed activities, reference is made to the appropriate SOPs, WINs and other related
documents.
2. Scope
This SOP applies to the Human Pre- and Post-Authorisation Units, Inspections Sector, Executive
Support, Document Management and Publishing (DM&P) Sector, and Infrastructure Services
(ISERV) Sector (mailroom).
3. Responsibilities
It is the responsibility of each Head of Unit/Sector to ensure that this procedure is adhered to within
their own Unit/Sector. The responsibility for the execution of a particular part of this procedure is
identified in the right-hand column of 9. Procedure.
4. Changes since last revision
Revision of SOP title.
Extensive revision to re-write SOP.
5. Documents needed for this SOP
PTX nomination distribution list in Outlook
Invented Name Database
SIAMED database
Product Overview database
Orphan Drugs database

Templates (always use the current version)

Where available, templates must be generated from SIAMED.

1. Nomination Form for European Experts (for the appointment of CHMP Rapporteur/Co-
Rapporteur and their assessment teams) (Located at: WORD/File/new/experts)

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2. Validation templates (Located at: WORD/File/new/H-Validation)
3. Peer review template and guidance documents (Located at: EDMS\Projects\Scientific Projects -
Human Cross Sectors\Peer Review\Background documents\Peer review SOP)
4. D80 AR Guidance documents (Located X:\Templates\Others)
5. D80 AR Templates (Located X:\Templates\Others)
6. AR Cover letter to (Co)Rapporteur (Located at: WORD/File/new/H-AR-LoQ-LoOI-SMOP)
7. D120 LoQ template (Located X:\Templates\Others)
8. D150 JAR templates (Located X:\Templates\Others)
9. D180 LoOI template (Located X:\Templates\Others)
10. D180 JAR templates (Located X:\Templates\Others)
11. CHMP Assessment Report template (Located at: WORD/File/new/H-AR-LoQ-LoOI-SMOP)
12. Letter of Undertaking template (Located at: WORD/File/new/H-AR-LoQ-LoOI-SMOP)
13. Opinion template (Generate from SIAMED)
14. Pre-CHMP Summary of Opinion templates I and II (Located at: WORD/File/new/H-AR-LoQ-
LoOI-SMOP)
15. Correspondence templates (Generate from SIAMED)
16. EPAR preparation 1
st
letter to applicant on confidentiality (Located at: WORD/File/new/H-AR-
LoQ-LoOI-SMOP)
17. Post-Opinion Action list for product secretaries with relevant correspondence templates
(WORD/File/New/H-Opin Corr and SIAMED respectively).
18. Change of PTL template (Located at: WORD/File/new/H-Opin Corr)
19. Withdrawal letter template (Located at: WORD/File/new/H-AR-LoQ-LoOI-SMOP)
6. Related documents
Always refer to the latest version of the document.
*All documents marked with an asterisk are in draft form at the time of approval of this SOP.

SOPs and WINs

1. SOP/EMEA/0009 on PIQ/QRD review of product information for Initial Applications and Annex
II applications
2. *SOP/EMEA/0028 on Processing of requests for fee reduction falling under Article 9 of Council
Regulation (EC) No 297/95
3. SOP/EMEA/0038 on SME Fee Reductions, Fee Deferrals and Conditional Fee Exemptions
4. SOP/EMEA/0048 on QRD Post-opinion Review of Product Information for Renewal
Applications, Annual Reassessments, Type II Variations (60/90 Days). For urgent 30-day Type II
variations the linguistic review takes place in parallel to the scientific assessment. See Linguistic
Review Process of Product Information in the Centralised Procedure
5. SOP/H/3009 on Validation of new applications for marketing authorisation, applications for
extensions and Article 58 Opinions
6. *SOP/H/3013 on Checking of Mock-ups and Specimens for New Applications and Extensions
7. SOP/H/3015 on Peer review/Q&A of Day 120 CHMP List of Questions and Assessment Reports
8. SOP/H/3022 on Check of Experts for Product evaluation
9. SOP/H/3043 on Harmonisation of European Antimicrobial Susceptibility Testing Breakpoints
determined by EMEA/CHMP and EUCAST
10. SOP/H/3048 on Orphan fee reductions
11. SOP/H/3063 on PTX Names in Product Overview Database
12. SOP/H/3101 on Determination of Fees (Medicinal Products for Human Use)
13. *SOP/H/3103 on Handling of risk management aspects of new applications and annex II
applications
14. *SOP/H/3106 on Master Files of medicinal products for human use
15. *SOP/H/3129 on Organisation of SAG meetings and reporting of SAG position to the CHMP
16. SOP/H/3131 on Preparation and updates of EPAR summaries by the Medical Information Sector
17. SOP/H/3137 on Preparation of Question and Answer documents for withdrawals of marketing
authorisation applications by the Medical Information Sector.

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18. SOP/H/3138 on Regulatory advice to applicants on the eligibility to EMEA procedures as
medicinal products (according to Directive 2001/83/EC)
19. *SOP/H/3143 on CHMP Rapporteur /Co-Rapporteur appointment in the Centralised Procedure
20. *SOP/H/3181 on Assessment of similarity of medicinal products
21. *SOP/H/3182 on Accelerated assessment of initial marketing authorisation applications (human
use)
22. *SOP/H/3190 on Review of orphan designation criteria at the time of granting/amending a
marketing authorisation
23. *SOP/H/3191on Consultation of environmental competent authorities on genetically-modified
organisms with respect to environmental risk assessment in product evaluation
24. *WIN/H/3111 on Pre-submission meetings

Guidance documents

25. EMEA/328/98 Guideline on the Acceptability of invented names for Human Medicinal Products
processed through the centralised procedure
(http://www.emea.europa.eu/pdfs/human/regaffair/032898en.pdf)
26. EMEA/5542/02 Linguistic Review Process
(http://www.emea.eu.int/pdfs/human/regaffair/554202en.pdf)
27. EMEA/101669/2004 CHMP AR - Guidance document (Located at: WORD/File/new/H-AR-
LoQ-LoOI-SMOP)
28. EMEA/239350/2005 Reflection Paper: Publication of Withdrawals of Marketing Authorisation
applications for Human Medicinal Products
(http://www.emea.europa.eu/pdfs/human/euleg/23935005en.pdf)
29. EMEA/282954/2005 Guideline on therapeutic areas within the mandatory scope of the centralised
procedure for the evaluation for marketing authorisation applications with reference to article 3
and point 3 of Annex of Regulation (EC) No 726/2004
(http://www.emea.europa.eu/pdfs/human/regaffair/28295405en.pdf)
30. EMEA/311355/2005 Reflection Paper: Publication of CHMP Negative Opinion and Refusal of
Marketing Authorisation applications for Human Medicinal Products
(http://www.emea.europa.eu/pdfs/human/euleg/31135505en.pdf)
31. EMEA/357981/2005 Guideline on the procedures for the granting of a Marketing Authorisation
under exceptional circumstances, pursuant to Article 14(8) of Regulation (EC) No 726/2004
(http://www.emea.europa.eu/pdfs/human/euleg/35798105en.pfd)
32. EMEA/419127/05 Guideline on the procedure for accelerated assessment pursuant to Article
14(9) of Regulation (EC) No 726/2004
(http://www.emea.europa.eu/pdfs/human/euleg/41912705en.pdf
33. EMEA/75401/2006 Guidance document: Time allowed for applicant to respond to questions and
issues raised during the assessment of new Marketing Authorisation Applications in the
centralised procedure (http://www.emea.europa.eu/pdfs/human/regaffair/7540106en.pdf)
34. EMEA/305821/2006 Mock-up and Specimen review process
(http://www.emea.europa.eu/pdfs/human/regaffair/30582106en.pdf)
35. EMEA/355619/2006 Practical measures to reduce Quality-related Follow-Up Measures (FUMs)
(Located at: documentum\Docbases\EDMS\Projects\Scientific Projects - Human Cross
Sectors\Quality sector\FUM-Q)
36. *EMEA/509951/2006 Guideline on the scientific application and the practical arrangements
necessary to implement Commission Regulation (EC) No. 507/2006 on the conditional marketing
authorisation for medicinal products for human use falling within the scope of Regulation (EC)
No 726/2004 (http://www.emea.europa.eu/pdfs/human/regaffair/50995106en.pdf)
37. *EMEA/149650/2007 PIM Guidance for Applicants for the Centralised Procedure for Human
Medicinal Products (Located at: documentum\Docbases\EDMS\Projects\02-004-00014-PIM
Implementation\Guidance\Guidance for Applicants\Version 1.0 Proposed As Final - Remaining
Comments)
38. CPMP/2390/01 Guidance to Applicants on CPMP Oral Explanations in relation to centralised
applications (http://www.emea.europa.eu/pdfs/human/regaffair/239001en.pdf)
39. CPMP/2270/02 Guidance on the Rapporteurs meetings with applicants on the CHMP LoQ
(http://www.emea.europa.eu/pdfs/human/regaffair/227002en.pdf)

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40. CHMP/50745/2005 Guideline on procedures for re-examination of CHMP Opinion
(http://www.emea.europa.eu/pdfs/human/euleg/5074505en.pdf)
41. EMEA pre-submission meeting guidance
(http://www.emea.europa.eu/htms/human/presub/index.htm)
42. EMEA Pre-Submission Meeting Request Form
(http://www.emea.europa.eu/htms/human/presub/presubform.doc)
43. Explanatory note on fees payable to the EMEA
(http://www.emea.europa.eu/htms/human/presub/39418705en.pdf)
44. *Guideline concerning the optional scope of the centralised procedure in accordance with Article
3(2) of Regulation (EC) No 726/2004
(http://ec.europa.eu/enterprise/pharmaceuticals/pharmacos/docs/doc2005/12-
05/optional_scope_publ_21_12_05.pdf)
45. *PIM Review System Process User Manual
46. Rules for the determination of strength for the purpose of calculation of fees (Q11 of the Pre-
Submission Guidance) (http://www.emea.europa.eu/htms/human/presub/list.htm)
7. Definitions
- AR: Assessment Report
- ASMF: Active Substance Master File
- BPWP: Blood Products Working Party
- BWP: Biologics Working Party
- CdT: Translation Center for the Bodies of the European Union (Luxembourg)
- CHMP: Committee for Medicinal Products for Human Use
- CIG: Central Information Group
- (Co)Rapporteur: both Rapporteur and Co-Rapporteur
- D: Day e.g. D80 means day 80 in the procedure
- EC: European Commission
- eCTD: Electronic Common Technical Document
- EDMS: Electronic Document Management System
- EMCDDA: European Monitoring Centre for Drugs and Drug Addiction
- EN: English Language
- EPAR: European Public Assessment Report
- EUCAST: European Committee on Antimicrobial Susceptibility Testing
- FDA: US Food and Drug Administration
- FUM: Follow-up measure
- GCP/GMP: Good Clinical Practice/Good Manufacturing Practice teams in Inspections Sector
- GL: Group Leader. It may be the Specialised Group Leader from the QoM Sector or the
Therapeutic Group Leader from the S&E or PASE Sectors.
- GMO: Genetically-modified organism
- HoS: Head of Sector
- INN: International Non-proprietary Name
- JAR: Joint Assessment Report
- LoOI: List of Outstanding Issues
- LoQ: List of Questions (authored by the CHMP and addressed to the Applicant at Day 120)
- MAA: Marketing Authorisation Application
- MIS: Medical Information Sector
- MS: Member States
- NRG: Invented Name Review Group
- OE: Oral Explanation
- OMP: Orphan Medicinal Product
- PASE: Pharmacovigilance and Post-Authorisation Safety and Efficacy of Medicines Sector
- PhV: Pharmacovigilance
- PhVWP: Pharmacovigilance Working Party
- PI: Product information
- PIM: Product Information Management (for more info see http://pim.emea.europa.eu)
- PIQ: Product Information Quality

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- PL: Package Leaflet
- Pre-Authorisation Phase: covers all procedures until the granting of a Marketing Authorisation
- PTM: Product Team Member (Includes members from QoM, S&E, PASE, regulatory affairs,
Risk Management Team, GCP, GMP, QRD and SAOD. The PTM is the nominated person
responsible for providing ongoing input in his/her main area of expertise during the procedure.
The PTM should when necessary, in continuous communication with PTL, take the lead for
topics in his/her area of expertise. This means providing full assistance and continuous feedback
to the PTL during the procedure in his/her area of expertise, including when necessary,
discussions with Rapporteurs, assessors and/or the applicant, organisation of expert meetings, and
finalisation of relevant documents. In case of absence the PTM is responsible to assign his/her
back up from his/her specialised/therapeutic group.)
- PTL: Product Team Leader (The team member responsible for overall co-ordination of the
procedure, including input in his/her main area of expertise. He/she is the main internal and
external contact point during the procedure and is responsible for providing the product team with
regular feedback on the progress of the application. In case of controversial procedural and/or
scientific issues, the PTL will always keep the Group Leader(s) of the main area of expertise
informed, and when necessary organise internal meetings to find a solution. In case of absence
the PTL is responsible to assign his/her back up from his/her specialised/therapeutic group.)
- PTLS: Product Team Leader Secretary
- PTX: Product Team Leader and Product Team Members
- Q&A: summary of opinion for products with negative opinion
- QoM: Quality of Medicines Sector
- QRD: Quality Review of Documents group
- RA: Regulatory Affairs
- RAOS: Regulatory Affairs and Organisational Support Sector
- RMC: Risk Management Coordinator
- RMP: Risk Management Plan
- SAG: Scientific Advisory Group
- SAOD: Scientific Advice and Orphan Drugs Sector
- SC: Standing Committee
- S&E: Safety and Efficacy Sector
- SIAMED: EMEA database for centralised procedures
- SME: Small and medium-sized enterprise
- SMOP: Summary of Opinion for products with positive CHMP Opinion
- SO: Specific Obligations
- SPC: Summary of Product Characteristics
- ToD: Table of Decisions
- VWP: Vaccines Working Party
- WP: Working Party
- WPAR: Withdrawal Public Assessment Report

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8. Process Map(s)/ Flow Chart(s)
High-level Process Map
END
START
Pre-submission Phase
(steps 1-14)
Submission/Validation Phase
(steps 15-16)
Post-Opinion Phase
(steps 76-86)
Commission Decision Phase
(steps 87-89)
Post-Commission Decision Phase
(steps 90-93)
Evaluation Phase
(steps 17-75)
Withdrawal of a MAA
(sub-procedure steps 1-4)


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Go to 39
23. Review of Day 80 AR
24. EMEA internal Peer Review
25. CHMP Comments on Day 80 AR
27. Receive the outcome of PIQ and mock-up
check
28. Peer Review teleconference
29. Preparation of Day 120 LoQ
33. Adoption of LoQ
32. Identification of need for SAG/FDA
teleconference/Expert Group meeting
31. Check for potential similarity issues
22. Check for confidential information and
mailing to applicant
21. Receipt of Day 80 (Co)Rapporteurs AR
37. Receipt and distribution of responses to
LoQ
36. Clarification meeting on LoQ
35. Check of CHMP ToD and Minutes
34. Mailing of LoQ to applicant
38. Check for potential similarity issues
20. Check of mock-ups and specimens
26. Identification of the need for WP
discussion
30. WP discussion (if required)
12. Products containing GMO
11. SME translations
18. Peer review process (start)
17. Check for potential similarity issues
14. Possible submission of eCTD and PIM
test version
15. Submission of MAA
16. Validation of MAA
5. Receipt of Pre-submission meeting request
START
1. Receipt and processing of eligibility
request
2. Appointment of PTX
8. Appointment of (Co)Rapporteurs
6. Check for potential similarity issues
4. Receipt of letter of intent
7. Pre-submission meeting
3. Invented name review
9. Confirmation of experts
10. Fee reduction requests
13. Request for accelerated procedure
19. PIQ technical review on EN PI


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Go to 76
63. Check of CHMP ToD and Minutes
64. Compilation of draft CHMP AR
From 38
No
Yes
From 56
No
Yes
Go to 57
44.
Outstanding Issues?
46. Check for potential similarity issues
45. Check and circulation of Day 180 LoOI
48. Identification of need for WP discussion
52. Check of CHMP ToD and Minutes
51. Mailing of LoOI
50. Adoption of LoOI
53. Receipt of written responses to LoOI
55. Receipt of revised JAR on written
responses to LoOI
40. Drafting of CHMP AR
41. Receipt of Day 150 JAR
42. Check of JAR
43. CHMP comments on Day 150 JAR
39. QRD review of EN PI and check of
revised mock-ups
47. SME translations
49. Identification of need for SAG / FDA
teleconference
54. Check for potential similarity issues
56. Check of revised JAR on responses to
LoOI and mailing to applicant
66. Request for Letter of Undertaking and
other documentation
67. Receipt of Letter of Undertaking
70. Preparation, check and circulation of
documentation
69. Preparation of SMOP or Q&A document
as applicable
68. Preparation of CHMP Opinion
71. Check for potential similarity issues
72. CHMP discussion
73. Informing the applicant of the outcome of
the CHMP discussion
74. Adoption of Opinion
75. Finalisation of Opinion
57. Identification of need for SAG / WP /
Expert Group meeting
58. Receipt of CHMP comments on revised
JAR
59.
Oral Explanation requested?
61. Circulation of LoOI for OE if applicable
60. Preparation for Oral Explanation
62. Oral Explanation
65.
Opinion outcome?
Negative
Positive


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START
1. Potential withdrawal of a MAA
2. Receipt of Withdrawal letter
3. EMEA Press Release
4. Q&A and WPAR preparation
END
Sub-procedure for withdrawal of a Marketing Authorisation Application
88. Commission Decision Phase
Review of comments, amendments and
mailing to EC
From 75
Yes
No
Negative
Positive
76. Press Release and Monthly Report
78. EPAR preparation
77. Check of CHMP ToD and Minutes
79.
Request for re-examination
of Opinion?
81.
Opinion outcome?
82. Negative Opinion: Translations of
Opinion annexes
83. Negative Opinion: Mailing of
translations of Opinion annexes to EC
80. Re-examination of
Opinion
86. Mailing of translations of Opinion
annexes to EC
87. Check for potential similarity issues
85. Receipt of revised translations of
Opinion annexes
89. Receipt of Commission Decision
90. Publishing of EPAR
93. Transfer of responsibilities to Post-
Authorisation Unit
END
91. Updating of EMEA databases
(SIAMED, scientific memory)
92.
Commission
Decision
outcome?
Positive
Negative
84. Organisation of translations of
Opinion annexes


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9. Procedure

Step Action Responsibility

Presubmission Phase


The timelines mentioned in the pre-submission phase are approximate and
serve only as general guidance.

1.
Approx. 7-18 months prior to submission: Eligibility to the centralised
procedure
- Receive the eligibility request in the dedicated mailbox
- Add the eligibility request to the CHMP agenda
- Organise the internal EMEA eligibility meeting and table the
eligibility report for discussion at CHMP (see EMEA/282954/2005
and Guideline on Optional scope document (no. 44)).
- Update the eligibility report to reflect the CHMP discussion and add it
in the CHMP post-mail
- Send a letter to the applicant informing them of the CHMP outcome
- Provide PTL with a copy of the letter


CIG/RA
CHMP secretariat
RA


RA

CHMP secretariat
CHMP secretariat
2.
Approx. 7-18 months prior to submission: Appointment of PTX
The PTX appointment may be triggered by the eligibility request, the pre-
submission meeting request or the letter of intent, depending on which is
submitted first.
See SOP/H/3063

GLs S&E/QoM/
PASE, Inspections,
SAOD, RAOS,
RMC
3.
Invented Name Review
The invented name review may take place at any stage of the procedure
(see EMEA/328/98)
(Even if no invented name is agreed before the opinion, the opinion can be
adopted using the INN name of the active substance, or the common name
and the MAA name this can also carry through to the Decision).

NRG secretariat
4.
Approx. 7 months prior to submission: Receipt of letter of intent
- Receive the letter of intent from applicant and forward it to CHMP
secretariat and PTX

CIG
5.
Approx. 3-6 months prior to submission: Pre-Submission meeting
request
- Receive the Pre-submission meeting request and forward it to
PTL/PTX
- Create folder in EDMS
- Organise the pre-submission meeting (see WIN/H/3111) and follow-
up on receipt of all documents in advance of the meeting


CIG

CIG
CIG
6.
Approx. 3-6 months prior to submission: Check for potential
similarity issues
- Initiate the check for potential similarity
- Check the claimed indication for potential overlap with the indication
of authorised orphan medicinal products using:
- the community register of designated orphan medicinal products
(http://ec.europa.eu/enterprise/pharmaceuticals/register/index.htm)
- and SIAMED
- Discuss outcome with the relevant GLs and SAOD.
- If potential similarity is identified see SOP/H/3181


PTL
PTX-S&E




PTL/PTX-S&E
PTL
7.
Approx. 3-6 months prior to submission: Pre-submission meeting
- Organise the pre-submission meeting (see WIN/H/3111). Involve SME
office, if applicable.
- Organise an internal preparatory meeting with relevant PTMs, if
needed.

CIG

PTL/PTLS


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Step Action Responsibility
- Chair the meeting and request minutes from the applicant within two
weeks.
- If the MAA refers to an antimicrobial agent intended for systemic use
discuss with the applicant their possible interaction with EUCAST (see
SOP/H/3043).
- After receiving the meeting minutes from applicant, forward them to
EMEA attendees for comments within two weeks.
- Provide the applicant with the revised minutes and ask the applicant to
confirm its agreement.
PTL

PTM-S&E


PTL/PTLS

PTL/PTLS
8.
Approx. 2-6 months prior to submission: Appointment of
(Co)Rapporteurs
- Appointment of (Co)Rapporteurs (see SOP/H/3143).


CHMP secretariat
9.
Approx. 2-6 months prior to submission: Confirmation of experts
- Contact the (Co)Rapporteurs to confirm the composition of the
evaluation teams (Template 1).
- Check the experts proposed for the product evaluation (See
SOP/H/3022).

PTL/PTLS

PTL/PTLS/CIG

10.
Approx. 2 months prior submission: Fee reduction requests
- Fee reduction for orphan drugs (see SOP/H/3048).
- Fee deferral for SMEs (see SOP/EMEA/0038).
- Other fee reduction requests (see SOP/EMEA/0028).

SAOD
SME office
CIG
11.
Approx. 2 months prior to submission: SME translations
- Contact SME applicant, if applicable, and confirm translation
requirements.

SME office

12.
Approx. 2 months prior to submission: Product containing GMO
- If the product contains a GMO, initiate the consultation process with
the environmental competent authorities (see SOP/H/3191).

PTL
13.
Approx. 1 month prior to submission: Request for accelerated
procedure
See EMEA/419127/05 and SOP/H/3182


PTL
14.
Approx. 1 month prior to submission: Submission of eCTD and/or
PIM test version, if applicable
- Receipt of submission.
- Check compliance with the current EMEA technical requirements, in
liaison with the relevant IT support group, if necessary.
- Inform the applicant on the acceptability of the technical approach
used. If issues are raised, request a revised test version and repeat the
check until the EMEA technical requirements are met.


CIG
CIG

CIG
Submission/ Validation Phase
15.
Submission of MAA
- Register application in SIAMED and allocate EMEA procedure
number.
- Create SI
2
fee record.
- Inform the relevant PTX of the availability and location of the paper
and/or electronic version of the dossier for validation together with the
deadline for validation (see SOP/H/3009).
- Archive the dossier (see SOP/H/3009).

CIG

CIG
CIG


CIG/Mailroom
16.
Validation of MAA
- Validate the respective modules of the dossier in accordance with the
dossier requirements (See SOP/H/3009) (Template 2).
- Check the claimed indication for potential overlap with the indication
of authorised orphan medicinal products, see step 6
- If the applicant has provided an eCTD and/or PIM submission perform

PTX

PTL

CIG

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Step Action Responsibility
the technical validation of the submission in liaison with the relevant
IT support group, if necessary and notify the PTL of the outcome.
- The PTM-QoM and S&E to liaise with the Pediatrics group to ensure
that the formulation development and the studies in pediatrics patients,
respectively, have been conducted in accordance with the agreed PIP,
if applicable.
- If the validation outcome is positive include timetable for start of
procedure in the CHMP agenda.
- Calculate the fees that should be paid for the MAA (See SOP/H/3101)
- If the applicant is an SME, inform the SME office of the receipt of a
valid MAA.
- For any designated OMP:
Contact SAOD PTM to inform of the receipt of the application
concerning an OMP.
Confirm receipt of the Report on the Maintenance of
Designation Criteria at the time of Marketing Authorisation
with SAOD PTM.
If the above mentioned Report has not been submitted, add a
reminder in the validation letter that it should be provided
within one month from the start of the procedure and inform
the SAOD sector secretariat who will follow-up with the
applicant.


PTM-QoM/S&E



CIG

PTL
PTL

PTL
Evaluation Phase

The applicant may withdraw a MAA at any time during the evaluation
procedure. In case of a withdrawal go to step 1 of the sub-procedure at the
end of Section 9 of this SOP.


Important note: If the applicant has used PIM for the submission of the
product information, the PTL should read this SOP in conjunction with the
PIM Review System Process User Manual for the steps that need to be
taken when handling the product information.

17.
Day 1-30: Check for potential similarity issues
- Check the claimed indication for potential overlap with the indication
of authorised orphan medicinal products. See step 6.
- If potential similarity is identified see SOP/H/3181.

PTL/PTX-S&E

PTL
18.
Day 1 -112: Peer Review process
- Coordinate and perform the EMEA Peer Review in liaison with the
relevant PTX (SOP/H/3015) (Template 3).

PTL/PTLS

19.
Day 80-110: PIQ-technical review on EN PI
- Request from the PTL the English product information.
- Provide the English product information to the QRD secretariat.
- Organise the PIQ-technical check (See SOP/EMEA/0009 and
EMEA/5542/02).

PTM-QRD
PTL/PTLS
PTM-QRD
20.
Day 80-110: Check of mock ups and specimens
- Send the English and multi-lingual (worst-case) colour mock-up of
the outer and immediate packaging for each pharmaceutical form in
each container type in the smallest pack-size to the MIS.
- Organise the mock up check (See SOP/EMEA/3013 and
EMEA/305821/2006).

CIG


MIS
21.
Day 80: Receipt of Day 80 (Co)Rapporteurs assessment reports (AR)
- Receive the ARs and forward to QoM, S&E, Inspection (GCP/GMP)
and RMP PTMs.
- If the ARs have not been circulated by the deadline adopted by the
CHMP, send a reminder to the relevant (Co)Rapporteurs contact

CIG

PTL/PTLS


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SOP/H/3004, 15-OCT-07
Step Action Responsibility
points.
- Once received, save the ARs in EDMS.
(Templates 4 and 5).

PTL/PTLS
22.
Day 80: Check of day 80 AR for confidential information and mailing
to the applicant
- Check and remove any confidential information from the day 80 AR
(e.g. reference to the assessment of another medicinal product,
information on closed part of the ASMF).
- Confirm by email to the PTL that no confidential information is
included in the AR and save the email in EDMS.
- Send the day 80 ARs to the applicant (and if applicable, the
confidential sections to the ASMF holder) via Eudralink, using
standard text from Template 6.


PTM-QoM/S&E


PTM-QoM/S&E

PTL/PTLS
23.
Day 80: Review of day 80 AR
- Read/review the day 80 ARs and corresponding SPC/labelling/PL and
identify possible controversial issues in each area of expertise. For the
review of the RMP (see SOP/H/3103).
- If the active substance is a new substance for which a potential for
dependence and abuse has been identified, inform the EMEA contact
point for interaction with EMCDDA and the World Anti-Doping
Agency (WADA).
- Check if the experts involved in the assessment are the ones nominated
by the (Co)Rapporteurs initially. If not, check the experts used in the
product evaluation (See SOP/H/3022).
- Check if there are any possible regulatory/legal issues that would
require involvement of PTM RA.
- If applicable, put request for GCP/GMP product related inspection to
CHMP.
- If a proposal for sampling and testing in the post authorisation phase is
included in the quality part of the AR, forward it to the relevant person
in the Inspections Sector.

PTM-QoM/S&E/
RMP

PTM-S&E



PTL


PTL

PTM-GMP/PTM-
GCP
PTM-QoM
24.
Day 80-100: EMEA internal Peer Review
- Coordinate the EMEA peer review process. Involve the PTM-PASE
(see SOP/H/3015) (Use Template 3).

PTL/PTLS
25.
Day 80-110: CHMP comments on day 80 AR
- Receipt of CHMP members comments.
- Forward CHMP members comments to PTM QoM, S&E and RMP.
- Save the MS comments in EDMS.

CIG
CIG
PTL/PTLS
26.
Day 80-115: Identification of need for WP discussion
- Identify, as appropriate, with the (Co)Rapporteurs, the need for a
discussion at the relevant WP and the questions that need to be
addressed by the experts. For clinical issues the coordinator is the
PTM-S&E, for quality issues the PTM-QoM and for a mixture of
Quality, Safety and Efficacy issues the PTL.
(Note: Biological products are always discussed at BWP, VWP or BPWP
as appropriate)
If there is a need for a WP discussion see step 30.

PTM-QoM/S&E
27.
Day 110: Receipt of the outcome of the PIQ and mock-up check
- Receive the outcome of the EN PIQ and the mock-up check.

PTL
28.
Day 112: Peer review teleconference
- Participate in the Peer review teleconference. This step applies to all
PTX as necessary in view of the issues identified in advance of the
teleconference (See SOP/H/3015). Involve the SME Office, if
applicable.

PTX

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Step Action Responsibility
29.
Day 115: Day 120 List of questions (LoQ)
- Receive and forward draft LoQ prepared by Rapporteur to
QoM/S&E/RMP PTMs.
- Save the draft LoQ in EDMS.
- Provide comments on the draft LoQ, when relevant, to PTL. Make
sure that Peer Review comments and comments from CHMP members
have been considered in the LoQ.
- Check that the draft LoQ is in the appropriate format (Template 7).
- Check draft LoQ for confidential information, highlight as appropriate,
and confirm with the Rapporteur that this information has been
removed.
- Provide the LoQ to the CHMP secretariat for circulation at CHMP
according to the relevant procedure.

CIG

PTL/PTLS
PTM-
QoM/S&E/RMP


PTL
PTM-QoM/S&E


PTL/PTLS
30.
Day 115: WP discussion
If there is a need for a WP discussion:
- Inform the relevant WP secretariat to include the product in the WP
agenda for discussion.
- Follow up the topic during and after the meeting.


PTM-QoM/S&E

PTM-QoM/S&E
31.
Before Day 120: Check for potential similarity issues
- Check the claimed indication for potential overlap with the indication
of authorised orphan medicinal products. See step 6.
- If potential similarity is identified see SOP/H/3181.

PTL/PTX-S&E

PTL
32.
By Day 120: Identification of need for a SAG meeting/FDA
teleconference/Expert Group meeting
- Identify, as appropriate, with the (Co)Rapporteurs, the need for a SAG
meeting or for a teleconference with FDA and the questions to be
addressed by the experts.
- Inform the relevant secretariat.
- For SAGs, contact the applicant and organise the meeting (see
SOP/H/3129).
- Follow up the topic during and after the meeting.


PTM-QoM/S&E


PTM-QoM/S&E
SAG secretariat

PTM-QoM/S&E
33.
Day 120: Adoption of LoQ
- Be present at CHMP during the discussion and finalise the LoQ
(Template 7), with (Co)Rapporteurs and assessors, taking into account
the CHMP discussion. Ensure consistency of the PI, LoQ and other
documents used for the assessment.

PTM-QoM/S&E
34.
Day 120: Mailing of Day 120 LoQ to applicant
- In case there are questions related to the restricted parts of the dossier
e.g. ASMF, the adopted LoQ should be split into separate open and
restricted documents and archived accordingly (electronic).
- Send the adopted LoQ to the applicant (only electronically) together
with the outcome of the EN PIQ (as a separate set of comments) and
the mock-up check. Ensure that the EN PIQ comments and the CHMP
comments on the PI are not conflicting. Ensure that the restricted parts
and any indication about the origin of specific comments (i.e. which
MS made them) are not included in the LoQ. When applicable, send
restricted part of the LoQ electronically to the manufacturer(s) e.g.
ASMF LoQ.
- Provide a paper copy of the LoQ to CIG.
- Include a copy of the LoQ in the CHMP post mail.
- Send adopted LoQ to the applicant including information on the time
allowed for the submission for the responses (paper) see
EMEA/75401/2006. When applicable, send the restricted part of the
LoQ to the manufacturer e.g ASMF LoQ (paper).

PTL/PTLS


PTL/PTLS







PTLS
PTLS
CIG

PUBLIC Page 15/23
SOP/H/3004, 15-OCT-07
Step Action Responsibility
35.
After Day 120: Check of CHMP ToD and Minutes
- Check if the text in the CHMP Minutes corresponds to the CHMP
discussion on the List of Questions, in liaison with the relevant PTX.

PTL
36.
During clock stop: Clarification meeting on LoQ
- If requested by the applicant, organise a clarification meeting with the
Rapporteurs after adoption of the List of Questions. (See
EMEA/2270/02).

PTL/PTLS
37.
Day 121: Receipt and distribution of responses to LoQ
- Receive and archive (paper and/or electronic) the applicants responses
to the CHMP LoQ.
- Notify QoM/S&E and RMP PTMs. If revised mock-ups have been
submitted provide them to MIS.
- Ensure that responses regarding GMP Inspections are also distributed
to the Quality PTX. Responses regarding GCP Inspections to be
reviewed by the S&E PTM in connection with the contact person in
Inspection Sector.
- Prepare a response timetable.
- If an accelerated procedure has been agreed by CHMP see
SOP/H/3182.
- If the applicant has used before day 1 Word format for the submission
of the PI and chooses to convert to a PIM submission at day 121,
handle the revised PI as described in the PIM Review System Process
User Manual.

CIG/mailroom

CIG

PTM-QoM/S&E/
Inspection


CIG
PTL

PTL
38.
Day 121: Check for potential similarity issues
- Check the claimed indication for potential overlap with the indication
of authorised orphan medicinal products. See step 6.
- If potential similarity is identified see SOP/H/3181.

PTL/PTX-S&E

PTL
39.
Day 121-165: QRD review of the EN PI and check of the revised
mock-ups
- Request from the PTL the English product information
- Send the revised EN word version of the product information to the
PTM-QRD.
- Organise the QRD review of the EN PI (see SOP/EMEA/0009 and
EMEA/5542/02).
- Check the revised mock ups.
- Receive the outcome of the QRD review and the revised mock-up
check and send it to the applicant.


PTM-QRD
PTL

PTM-QRD

MIS
PTL/PTLS
40.
Day 130 170: CHMP AR
- Initiate drafting of the CHMP AR

PTM-QoM/S&E/
PTLS
41.
Day 150: Receipt of Day 150 Joint (Co)Rapporteurs AR
- Receive the ARs and forward to QoM, S&E and RMP PTMs.
- If the ARs have not been circulated by the deadline adopted by the
CHMP, send a reminder to the relevant (Co)Rapporteurs contact
points.
- Once received, save the ARs in EDMS.
(Template 8)

CIG
PTL/PTLS


PTL/PTLS
42.
Day 150: Check of Joint AR
- Check and remove any confidential information from the Joint AR
(e.g. reference to the assessment of another medicinal product, closed
part of the ASMF information, inspection reports of manufacturer
premises).
- Confirm by email to the PTL that no confidential information is
included in the AR and save the email in EDMS.
- Send the Joint AR to the applicant (and if applicable, the confidential

PTM-QoM/S&E



PTM-QoM/S&E

PTL/PTLS

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SOP/H/3004, 15-OCT-07
Step Action Responsibility
section to the ASMF holder) via Eudralink, using standard text from
template 6.
- Check the overall conclusions of the Joint AR. For the review of the
RMP (see SOP/H/3103).
- Liaise with
The Signal Detection Team to check whether any serious
ADRs have been reported for products in the same class.
The PhVWP Secretariat and PASE PTM for ongoing
discussion on products in the same class. Ensure that relevant
class labelling is included in the Product Information.
If issues are raised, inform the PTL and the (Co)Rapporteurs
and see whether the PI or the RMP should be amended
accordingly.
- In case of OMPs, inform the SAOD PTM on the proposed revised
indication as reflected in the day 150 JAR and the likelihood of an
opinion at day 180. Discuss the status of the current (unapproved)
indication versus the designated orphan indication. Flag any
discrepancies to the (Co)Rapporteurs.
- Check if there are any possible regulatory/legal issues that would
require involvement of PTM-RA.


PTM-QoM/S&E
/RMP
PTM-S&E








PTL




PTL
43.
Day 170: CHMP comments on Day 150 Joint AR
- Receipt of CHMP members comments.
- Forward CHMP members comments to PTM-QoM/S&E/RMP.
- Save the MS comments in EDMS.

CIG
CIG
PTL/PTLS
44.
If there are outstanding issues go to step 45.
If there are no outstanding issues the Opinion could be adopted at day 180,
in this case go to step 64.
PTL/PTM-
QoM/S&E/
RMP/PTLS
45.
Around Day 175: Check and circulation of Day 180 List of
outstanding issues (LoOI)
- Provide comments on the draft LoOI, when relevant, to the PTL prior
to the adoption by the CHMP. Ensure that the CHMP members
comments from the respective area of expertise have been considered
- Check if there are any possible regulatory/legal issues that would
require the involvement of the PTM-RA.
- Liaise with the (Co)Rapporteurs and the relevant PTX, to identify the
questions to be addressed in writing and/or during a possible Oral
Explanation.
- Check the draft LoOI is in the appropriate format (Template 9).
- Check the draft LoOI for confidential information, highlight as
appropriate, and confirm with the Rapporteur that this information has
been removed.
- Send the LoOI to the CHMP secretariat for discussion and adoption at
CHMP.


PTM-QoM/S&E/
RMP

PTL

PTL


PTL
PTM-QoM/S&E


PTL/PTLS
46.
Around Day 175: Check for potential similarity issues
- Check the claimed indication for potential overlap with the indication
of authorised orphan medicinal products. See step 6.
- If potential similarity is identified see SOP/H/3181.

PTL/PTX-S&E

PTL
47.
Around Day 180 or at latest 1 month prior to expected Opinion: SME
translations
- For MAAs submitted by SME applicants, liaise with the SME office to
organise the translations.


PTL
48.
By Day180: Identification of need for WP discussion
Proceed as in steps 26 and 30

PTL
49.
Day 180: Identification of need for SAG/FDA teleconference
Proceed as in step 32

PTL/PTLS/PTMs

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SOP/H/3004, 15-OCT-07
Step Action Responsibility
50.
Day 180: Adoption of LoOI
- Be present at CHMP during the discussion and finalise the LoOI with
(Co)Rapporteurs and assessors, taking into account the CHMP
discussion. Ensure consistency of the PI, LoOI and other relevant
documents used for the assessment. Liaise with relevant PTX, if
needed.

PTM-QoM/S&E
51.
Day 180: Mailing of the adopted LoOI to applicant
Proceed as in step 34

PTL/PTLS/CIG
52.
After Day 180: Check of CHMP ToD and Minutes
- Check if the text in the CHMP Minutes corresponds to the CHMP
discussion on the List of Questions, in liaison with the relevant PTX.

PTM-QoM/S&E
If no OE has been requested by CHMP: The clock restarts with the submission of the responses to the
LoOI.
If an OE has been requested by CHMP: The clock restarts on the day of the OE (The OE is part of the
responses to the LoOI, therefore the responses are considered as complete and the clock can restart only
on the day of the OE. The CHMP is assessing the written responses in parallel to the clock stop prior to
the OE). If the OE is cancelled after the receipt of the written responses, the clock restart automatically
reverts to the day of the submission of the written responses.
In both cases go to step 53.
53.
Receipt of written responses to LoOI (clock restarts (Day 181) only if
no OE)
Proceed as in step 37.


CIG/mailroom/PTL
54.
Check for potential similarity issues
- Check the claimed indication for potential overlap with the indication
of authorised orphan medicinal products. See step 6.
- If potential similarity is identified see SOP/H/3181.

PTL

PTL
55.
Receipt of revised Joint AR on the written responses to LoOI (within
20 days)
- Receive the ARs and forward to QoM, S&E and RMP PTMs. For the
review of the RMP (see SOP/H/3103).
- If the ARs have not been circulated by the deadline adopted by the
CHMP, send a reminder to the relevant (Co)Rapporteurs contact
points.
- Once received, save the ARs in EDMS.


CIG

PTL/PTLS


PTL/PTLS
56.
Check of revised Joint AR on the responses to LoOI and mailing to
applicant
- Check and remove any confidential information from the revised Joint
AR (Template 10).
- Send the AR to the applicant (and if applicable, the confidential
section to the ASMF holder) via Eudralink for information.


PTM-QoM/S&E

PTL/PTLS
57.
Identification of need for a SAG/WP /Expert Group meeting
- Proceed as in steps 26, 30 and 32

PTL/PTLS/PTX
58.
Receipt of CHMP comments on the revised Joint AR on the responses
to LoOI (5 days after receipt of the JAR)
- Receipt of CHMP members comments.
- Forward CHMP members comments to PTM QoM, S&E and RMP.
- Save the MS comments in EDMS.


CIG
CIG
PTL/PTLS
59.
If no OE has been requested by CHMP go to step 63
If an OE has been requested by CHMP go to step 60
PTL
60.
During clock stop: Preparation for the OE
- Identify, as appropriate, with the (Co)Rapporteurs and the relevant
PTX, the need to amend the LoOI to be addressed during a possible
oral explanation based on the written responses.
- Organise and attend the briefing meeting with (Co)Rapporteurs, the

PTL


PTL/PTLS

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SOP/H/3004, 15-OCT-07
Step Action Responsibility
EMEA and the applicant (see CPMP/2390/01).
61.
During clock stop: Circulation of LoOI for OE, where applicable
- Send the LoOI for the Oral Explanation to the CHMP secretariat for
discussion at CHMP and adoption.

PTL/PTLS
62.
Day 181: OE (clock restarts)
- Attend the oral explanation, the following CHMP discussion and the
trend vote.
- Hold if necessary a debriefing meeting with the applicant and the
(Co)Rapporteurs to present the outcome of the CHMP discussion and
possible trend vote to the applicant.

PTM-QoM/S&E

PTM-QoM/S&E


63.
After Day 181: Check of CHMP ToD and Minutes
- Check if the text in the CHMP Minutes corresponds to the CHMP
discussion, in liaison with the relevant PTX.
- Prepare a timetable for finalisation of the procedure and inform the
applicant and the (Co)Rapporteurs. In order to ensure timely
submission of the required documentation from the applicant and
review from the (Co)Rapporteurs and EMEA, the PTL is advised to
initiate the preparation of the CHMP Opinion as soon as possible.

PTL

PTL
64. By Day 210: Compilation of draft CHMP AR
- Finalise the general part of the CHMP AR and update the AR in your
own area of expertise (Template 11).
- When necessary, organise review of the CHMP AR and product
information within the specialised/therapeutic groups.
- Ensure overall consistency and quality of the draft CHMP AR and
send the draft document to Rapporteur/Co-Rapporteur for comments.
- Distribute the (Co)Rapporteurs comments to the relevant PTX.
- Implement the (Co)Rapporteurs comments, if any.
- Liaise with:
The Signal Detection Team to check whether any serious
ADRs have been reported for products in the same class
The PhVWP Secretariat and PASE PTM for ongoing
discussion on products in the same class. Ensure that relevant
class labellings are included in the Product Information. If
issues are raised, inform the PTL, the PTM-RMP and the
(Co)Rapporteurs and see whether the PI or the RMP should be
amended accordingly
Review list of SO, FUMs and RMP , Annex II & IV of the
Opinion with the PTM-PASE
- If there is an Opinion under exceptional circumstances or a conditional
approval liaise with the applicant as early as possible and seek
agreement on the proposed specific obligations. (See
EMEA/357981/2005 and EMEA/509951/2006).

PTM-QoM/S&E/
PTLS
PTM-QoM/S&E

PTL

PTL
PTM-QoM/S&E
PTM-S&E










PTL
65.
For positive Opinions go to step 66.
For negative Opinions go to step 68.
PTL/PTLS
66.
By Day 210: Positive Opinions - Request for Letter of Undertaking
and other documentation relevant to the Opinion
- Provide the applicant with the template of the Letter of Undertaking
for completion and submission. (Template 12). For Quality FUMs see
also the guidance document EMEA/355619/2006.
- Request the applicant to submit a final draft SPC, the final version of
the RMP and the PhV system, a summary table of the RMP in case the
RMP template has not been used and the agreed specifications for
active substance and finished product.
- Request from the PTL the final draft EN PI to ensure that all QRD
comments have been implemented.


PTL/PTLS


PTL/PTLS



PTM-QRD


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SOP/H/3004, 15-OCT-07
Step Action Responsibility
- Forward to the PTM-QRD the final draft EN PI.
- Confirm via email to PTL that all QRD comments made throughout
the evaluation process have been taken on board in the final draft EN
PI.
- For SME applicants, forward the final EN PI (with track changes
highlighted) to DM&P for finalisation of translations.
- Request the applicant to provide a confirmation that no changes to part
IA of the application form have been introduced to reflect the outcome
of the assessment, or otherwise to provide an amended documentation.
PTL/PTLS
PTM-QRD


PTL

PTL/PTLS
67.
By Day 210: Receipt of Letter of Undertaking
- Receive the Letter of Undertaking.
- Check the letter and proposed deadlines in liaison with the
(Co)Rapporteurs and the relevant PTX, as appropriate.
- The follow up measures and specific obligations (in the case of an
approval under exceptional circumstances or for a conditional MA)
should be checked against the tables of FUMs and SOs in the CHMP
AR to ensure consistency.

PTL
PTL

PTM-QoM/S&E
68.
By Day 210: Preparation of CHMP Opinion
- Prepare and assemble the Opinion, using the appropriate template
(Template 13).
- In case of a controversial Opinion, update the CHMP chair at
teleconference prior to the CHMP meeting. If appropriate, include the
topic in the EMEA/EC teleconference agenda.

For negative Opinions (The Opinion Annexes include only Annex A and
Annex I (Scientific conclusions and grounds for refusal):
- Prepare the scientific conclusions and grounds for refusal and ensure
consistency with the scientific discussion of the CHMP AR.

For positive Opinions:
- Ensure overall consistency and quality of the Annexes.
- In liaison with the PTM-RMP prepare and check consistency of Annex
II and IV (if applicable) of the opinion with PhV and RMP aspects of
the CHMP AR. If there is an Annex IV it should mirror the content of
Annex II. The content of these two annexes in terms of risk
minimisation activities should match the content of the EU Risk
Management Summary table.
- In the case of an Opinion under exceptional circumstances ensure that
the SOs included in the Letter of Undertaking and CHMP AR are
included in Annex II.
- For orphan medicinal products, confirm with SAOD whether the draft
indication as discussed by the CHMP falls within the Orphan
Designation.

PTLS

PTL





PTM-QoM /S&E



PTL/PTLS
PTL/PTM-RMP





PTL


PTL
69.
By Day 210: Preparation of SMOP (for positive opinions) or Q&A (for
negative opinions) and mailing to (Co)Rapp and applicant
For negative Opinions:
- At least a week before the CHMP provide MIS with the latest
(Co)Rapporteurs AR and contact details.
- Prepare the Q&A document highlighting the main findings/concerns
identified by the CHMP. Liaise with the PTL, relevant PTX and
(Co)Rapporteurs to ensure the accuracy of the information.
- Send the Q&A document to the applicant for review and comments
keeping in copy the MIS.
- Receive the applicants comments and liaise to resolve them. Involve
the (Co)Rapporteurs, if necessary.



PTL/PTLS

MIS


PTL/PTLS

PTL/MIS


PUBLIC Page 20/23
SOP/H/3004, 15-OCT-07
Step Action Responsibility

For positive Opinions:
- Prepare the Summary of Opinion, forward to (Co)Rapporteurs for
comments, and to the applicant for information. Use template 14(I),
unless a revised Opinion has been adopted, then use template 14(II)
- Prepare the timetable for translations.


PTL


PTLS
70.
By Day 210: Preparation, check and circulation of required
documentation
- Prepare sign-off folder, including all of the above documents (steps
64- 69) for checking and sign off by PTL, GL and RA.
- Implement RA and GL comments.
- Circulate all opinion documents to CHMP for discussion and adoption.


PTLS

PTL
PTLS
71.
By Day 210: Check for potential similarity issues
- Check the claimed indication for potential overlap with the indication
of authorised orphan medicinal products. See step 6.
- If potential similarity is identified see SOP/H/3181.

PTL/PTX-S&E

PTL
72.
Day 210: CHMP discussion
- Attend the CHMP discussion.
- Ensure overall consistency and quality of the CHMP opinion in case of
amendments, in liaison with the other PTX as appropriate.
- Provide the final opinion to CHMP secretariat for circulation to
CHMP.

PTM-QoM/S&E
PTL

PTLS
73.
Day 210: Informing the applicant of the outcome of the CHMP
discussion
- After the CHMP discussion and prior to the adoption of the Opinion, a
debriefing meeting should take place with the applicant, if needed. In
liaison with the (Co)Rapporteurs, verbally present the outcome of the
CHMP discussion to the applicant, the proposed draft SPC and/or any
final outstanding issues for their consideration prior to the final
adoption of the opinion.


PTM-QoM/S&E
74.
Day 210: Adoption of the Opinion
- Attend the CHMP discussion for the final adoption of opinion and
vote.
- Debriefing meeting with the applicant, if needed: In liaison with the
(Co)Rapporteurs inform the applicant verbally of the outcome of the
adoption of the final CHMP Opinion.
- Inform SAOD about the adoption of the final CHMP Opinion.

PTM-QoM/S&E

PTM-QoM/S&E


PTL
75.
Day 210: Finalisation of the Opinion
- Finalise the Opinion and CHMP AR.

- Prepare sign-off folder for final signature by PTL, RA, HoS,
(Co)Rapporteurs and CHMP Chair.
- Generate correspondence letters (to EC and applicant) from SIAMED.
- Check correspondence letters and forward to HoS for sign off
(Template 15).
- Provide the CHMP secretariat with the opinion (unsigned version) for
inclusion in the CHMP Post-mail.
- Provide signed opinion documents to CIG, to be forwarded to EC and
the applicant.

PTM-QoM/S&E,
PTLS
PTLS

PTLS
PTL/PTLS

PTLS

PTLS
PostOpinion phase
76.
After day 210: Press Release and Monthly Report
- Check that the text in the CHMP press release and the CHMP monthly
report corresponds to the adopted Opinion.

PTL


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SOP/H/3004, 15-OCT-07
Step Action Responsibility
- Provide the Executive Support with the Summary of Opinion (SmOP)
for positive Opinions or the Q&A document for negative ones for
publication at the EMEA website.
PTL

77.
After day 210: Check of CHMP ToD and Minutes
- Check if the text in the CHMP Minutes corresponds to the CHMP
discussion, in liaison with the relevant PTX.

PTL
78.
Day 210-267: EPAR preparation
- Prepare the EPAR (see SOP/H/3003 and SOP/H/3131) (Template 16).

MIS, PTM-QoM/
S&E, PTLS
79.
By day 225: Request for Re-examination
If there is a request for re-examination go to the step 80.
If there is no request for re-examination go to step 81.

PTL/PTLS
80.
By Day 225: Re-examination
If the applicant requests a re-examination of the Opinion, the remaining
steps of this SOP should be put on hold pending the finalisation of the re-
examination procedure.

- Upon receipt of the re-examination request immediately inform EC. If
the product is an orphan inform also SAOD.
- Include the request for re-examination in the next CHMP monthly
report.
- Handle re-examination procedure according to document
CHMP/50745/2005. Refer to applicable steps of this SOP for the
organisation of SAGs, handling of Oral Explanations, CHMP AR
finalisation and Opinion adoption.
Once the re-examination procedure is finalised go to step 76.





PTL

PTL

PTL



PTL
81.
For negative Opinions go to step 82.
For positive Opinions go to step 84.
PTL/QRD
secretariat
82.
Negative Opinion: Translation of the Opinion Annexes
- Ensure that Annex I of the Opinion (i.e. grounds for refusal) does not
contain any commercially confidential information. Liaise with the
applicant, the relevant PTX and MIS, if needed, to identify and delete
such information.
- Provide DM&P with Annex A and I of the Opinion.
- Organise the translation of the Annexes in all EU languages from CdT
- Provide the translations to the PTL.

PTL



PTL/PTLS
DM&P
DM&P
83.
Negative Opinion: Mailing of translations of the Opinion Annexes to
EC
- Forward the translations to CIG.
- Send the translations of the Opinion Annexes to EC for initiation of
the Standing Committee phase.
Go to step 88.


PTL/PTLS
CIG
84.
By day 215-232: Translations of Opinion Annexes
- Organise the translations of the adopted PI and Annex A in all EU
languages (see SOP/EMEA/0047).

QRD secretariat
85.
Day 232: Receipt of revised translations of Opinion Annexes
- Receive from the QRD secretariat the revised translations of Opinion
annexes (following MS review) (Template 17).

PTLS

86.
By Day 237: Mailing of translations of the Opinion Annexes to EC
- Check the QRD form 2 to ensure that the MS comments on the
translations of the Opinion Annexes have been implemented by the
applicant or that appropriate justification has been submitted and
forward them to CIG. (Template 17)
- Send the translations of the Opinion Annexes to EC for initiation of
the Standing Committee phase.

PTLS



CIG

PUBLIC Page 22/23
SOP/H/3004, 15-OCT-07
Step Action Responsibility
Commission Decision Phase
87.
Day 210-277: Prior to the issue of the Commission Decision: Check for
potential similarity issues
- Check the claimed indication for potential overlap with the indication
of authorised orphan medicinal products. See step 6.
- If potential similarity is identified see SOP/H/3181 and inform EC.


PTL/PTX-S&E

PTL
88.
Day 239-261: Commission Decision Phase Review of comments,
amendments and mailing to EC
- If comments are received during the SC phase, review with applicant
and amend annexes accordingly. Forward amended version(s) only to
EC and remind the applicant to forward the amended text to NO/IS.
- If no comments are received during the SC phase, inform by email the
EC that there are no changes in the translations.
(Template 17).


PTL/PTLS


PTL/PTLS
89.
Day 277: Receipt of the Commission Decision
- Receive and archive the Commission Decision and inform the PTL.

CIG
Post Commission Decision phase
90.
Publishing of EPAR
Once the Commission decision is received, publish the EPAR (see
SOP/H/3050).

PTL/PTLS
91.
Updating of EMEA databases (SIAMED, scientific memory)
- Prepare a hard copy of the information in SIAMED and send to the
PTL for validation.
- Validate information in SIAMED.
- Input all relevant information into the Scientific Memory database.
Prepare a hard copy and send to the PTL for validation.
- Validate information in the Scientific Memory database.

CIG

PTL
Scientific Memory
secretary
PTL
92.
If handling a negative decision, procedure ends.
If handling a positive decision, go to step 93.
PTL
93.
Transfer of responsibilities from Pre to Post-authorisation Unit
- Organise a briefing meeting with the Post-Authorisation PTL and GL
and the relevant PTX in order to provide information on the main
aspects of the dossier (e.g. upcoming FUMs/SOs, specific problems,
indications that have been rejected, important administrative details
etc) and transfer the product.
- Inform the Marketing Authorisation Holder and CIG of the change of
the PTL (Template 18).

PTL




PTL/PTLS



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SOP/H/3004, 15-OCT-07
Sub-procedure in case of withdrawal of a MAA

Step Action Responsibility
The applicant may withdraw a MAA at any time during the evaluation
procedure.

1. Potential withdrawal of a MAA
- As soon as the PTL becomes aware of a potential withdrawal of MAA:
Provide the applicant with the template letter of withdrawal
(Template 19).
Inform the Press Office, MIS, relevant PTX, Rapporteur, Co-
Rapporteur, SME office (if applicable) and CHMP Secretariat.


PTL/PTLS

PTL

2. Receipt of withdrawal letter
Upon receipt of the withdrawal letter
- Check that the appropriate template has been used (Template 19).
- Circulate the letter to the Press Office, MIS, PTX, Rapporteur, Co-
Rapporteur, CHMP Secretariat, CIG, Head of Unit, Head of Sector,
Group Leader.
- Send the latest version of the SPC and if available the CHMP
assessment(s) report(s) to MIS.


PTL
PTL/PTLS


PTL/PTLS
3. EMEA press release
- Prepare the EMEA press release and provide to the PTL and MIS for
comments.
- Check the Press release, in liaison with the relevant PTX.

Executive support

PTL
4. Q&A and WPAR preparation
- Prepare the Q&A document to be published on the EMEA website
(see SOP/H/3137).
- Prepare the WPAR.

MIS

MIS, PTM-QoM/
S&E, PTLS

10. Records
All relevant documents processed during the procedure are forwarded to CIG to be archived in the
Product Master File. Electronic copies are saved in appropriately labelled folders in EDMS.