Tasks of the Product Team on the Handling of the Initial Marketing Authorisation Application

European Medicines Agency Standard Operating Procedure

Page 1/23

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)

PUBLIC Page 2/23 SOP/H/3004, 15-OCT-07

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 1st 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.


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)


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


- 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


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)


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


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)


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


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


Go to 76


64. Compilation of draft CHMP AR

From 38

No

Yes

From 56

No

Yes

Go to 57

44.Outstanding Issues?


45. Check and circulation of Day 180 LoOI

48. Identification of need for WP discussion


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


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


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


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


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


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


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


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 SI2 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


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


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



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



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


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


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


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



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


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


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



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


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


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



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


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.