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Standard operating procedure

Title: Article 29(4) referral procedures (MRP/DCP referrals)

Status: PUBLIC Document no.: SOP/H/3177 Lead author Approver Effective date: 04-SEP-12 Name: Thomas Larsson Name: Noel Wathion Review date: 04-SEP-15 Signature: ON FILE Signature: ON FILE Supersedes:

SOP/H/3177 (02-OCT-08) Date: 02-AUG-12 Date: 03-SEP-12 TrackWise record no.: 2296

1. Purpose

To describe the procedure for handling of referral procedures under Article 29(4) of Directive 2001/83/EC as amended for marketing authorisation(s)/application(s) under the mutual recognition procedure (MRP) or decentralised procedure (DCP) for medicinal products for human use.

2. Scope

This SOP applies to the Patient Health Protection Unit, the Human Medicines Development and Evaluation Unit, the Veterinary Medicines and Product Data Management Unit, the Information and Communications Technology Unit and Directorate.

The staff involved in this procedure is member of:

• Regulatory, Procedural and Committee Support Sector: Community Procedures Section, Regulatory Affairs Section, Scientific Committee Support Section

• Safety and Efficacy of Medicines Sector

• Quality of Medicines Sector

• Product Data Management Sector: Product and Application Business Support Section, Product Database Management Section, Document and Information Services Section

• Medical Information Sector: Product Information Quality Section, Public Information and Stakeholder Networking Section

• Communications Sector

• Legal Service Sector

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3. Responsibilities

It is the responsibility of each Head of Sector to ensure that this procedure is adhered to within their own Sector. The responsibility for the execution of a particular part of this procedure is identified in the right-hand column of section 9. Procedure.

4. Changes since last revision

Extensive revisions to rewrite SOP.

5. Documents needed for this SOP

A list of all relevant templates (such as letters, time table, and sign-off slips) can be found in Word/File/New/Referrals and the templates themselves on the X:\ drive (X:\Templates\Others\H – Referral\Article 29(4)) and on the X:\ drive (X:\Templates\Filenew\H-Opin QRD).

Templates for CHMP opinion, CHMP assessment report, timetable for translations and for opinion related letters and the action list for product secretaries (covering opinion, day 27 after adoption of opinion and at the end of the Standing Committee phase) can be found in Word/File/New/H-Opin QRD Templates.

Other templates:

• Templates for translations (http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/document_listing/document_listing_000134.jsp&murl=menus/regulations/regulations.jsp&mid=WC0b01ac0580022c59#section2 path: Home \ Regulatory \ Human medicines \ Product information \ Product information templates \ MR/DC/Referral procedures - product information templates)

• QRD form 2 (http://www.ema.europa.eu/htms/human/qrd/docs/qrdform2.doc path: Home \ Regulatory \ Human medicines \ Product information \ Linguistic review \ Linguistic review process)

• Template for Q-and-A for an Article 29 referral (Location: X:\Templates\Others\H - Q-and-A documents)

• Template for transmission slip for referral publications (Location: Word/File/New/Transmissions Slips/TS – Referrals)

6. Related documents

Legislation

• Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to medicinal products for human use, as amended (http://ec.europa.eu/health/files/eudralex/vol-1/dir_2001_83_cons2009/2001_83_cons2009_en.pdf)

• Commission Regulation (EC) No 1662/95, of 7 July 1995, laying down certain detailed arrangements for implementing the Community decision-making procedures in respect of marketing authorisations for products for human or veterinary use (http://ec.europa.eu/health/files/eudralex/vol-1/reg_1995_1662/reg_1995_1662_en.pdf)

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Guidance documents

• Notice to Applicants Volume 2A – Procedures for marketing authorisations, Chapter 3 – Community referral procedures (http://ec.europa.eu/health/files/eudralex/vol-2/a/vol2a_chap3_rev09-2007_en.pdf)

• EC Guideline on Summary of Product Characteristics (SmPC), Chapter 2C in the Notice to Applicants (http://ec.europa.eu/health/files/eudralex/vol-2/c/smpc_guideline_rev2_en.pdf)

• Guideline on the definition of a potential serious risk to public health in the context of article 29(1) and (2) of Directive 2001/83EC (March 2006) (http://ec.europa.eu/health/files/eudralex/vol-2/c/smpc_guideline_rev2_en.pdf)

• Commission communication on the Community marketing authorisation procedures for medicinal products (http://ec.europa.eu/health/files/eudralex/vol-1/com_1998/com_1998_en.pdf)

• EMA Questions and Answers on referrals (http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/q_and_a/q_and_a_detail_000018.jsp&murl=menus/regulations/regulations.jsp&mid=WC0b01ac0580024e97 path: Home \ Regulatory \ Human medicines \ Referral procedures \ Q&A)

• Guidance to applicants on CPMP oral explanations in relation to centralised procedures (http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/document_listing/document_listing_000168.jsp&murl=menus/regulations/regulations.jsp&mid=WC0b01ac0580027256# path: Home \ Regulatory \ Human medicines \ Pre-authorisation \ Guidance \ Application and Evaluation \ Evaluation)

• Convention to be followed for the EMA-QRD templates (http://www.ema.europa.eu/htms/human/qrd/docs/convention.pdf path: Home \ Regulatory \ Human medicines \ Product information \ Guidance \ QRD Templates)

• Procedural advice on the re-examination of CHMP opinions (EMEA/CHMP/50745/2005) (http://www.ema.europa.eu/pdfs/human/euleg/5074505en.pdf path: Home \ Regulatory \ Human medicines \ Post-opinion \ Opinion/Decision making)

SOPs and WIN

• SOP/EMA/0048 on QRD post-opinion review of product information for post-authorisation procedures affecting the annexes, excluding Annex II applications

• SOP/H/3193 on Master file for referrals

• WIN/H/3145 on sending out documents in the context of referrals (Article 5(3), 5(11), 13, 20, 29(4), 29 (paediatric), 30, 31, 36 and 107 for medicinal products for human use)

• WIN/H/3205 Preparation of referral opinions for publication on the EMA website (Referrals according to Article 5(3), 5(11), 6(12), 6(13), 13, 20, 29(4), 29 (paediatric), 30, 31, 36 and 107 for medicinal products for human use)

• WIN/EMA/0070 Redaction of documents in relation to access to documents

• SOP/EMA/0101 Conducting checks for conflicts of interest of Agency employees assigned duties relating to medicinal products for human or veterinary use

• SOP/H/3129 Organisation of Scientific Advisory Group (SAG) meetings and reporting of SAG position to the CHMP

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• SOP/H/3176 CHMP rapporteur/co-rapporteur appointment for referrals

• SOP/EMA/0111 Preparation, dissemination and publication of safety-related EMA press releases and question-and-answer documents

• WIN/H/3234 on Preparation for publication of annexes to the CHMP meeting highlights by the CHMP Secretariat and CP Section.

7. Definitions

Article 29(4) referral of Directive 2001/83/EC, as amended

The Article 29(4) referral regards marketing authorisation(s)/ application(s) under the mutual recognition procedure (MRP) and the decentralised procedure (DCP), where (a) concerned Member State(s) consider(s) that the marketing authorisation of a medicinal product may present a potential serious risk to public health in relation to the quality, safety or efficacy of the medicinal product.

Referral team:

The referral team includes the appointed product team leader for the referral procedure from the Community Procedures Section and the product team members from the Regulatory Affairs Section, the Legal Service Sector and from the Quality of Medicines sector as appropriate.

Abbreviations:

AR: Assessment report

CHMP: Committee for Medicinal Products for Human Use

CMDh: Coordination Group for Mutual Recognition and Decentralised Procedures - Human

CMS: Concerned Member State

CTFG: Clinical Trials Facilitation Group

D-CM: Communication Sector

DCP: Decentralised procedure

D-LS: Legal service

DREAM: Document Records and Electronic Archive Management system

EC: European Commission

EMA: European Medicines Agency

H-QM: Quality of Medicines Sector

H-SE: Safety and Efficacy Sector

INN: International non-proprietary name

JAR: Joint assessment report

LoOI: List of outstanding issues

LoQ: List of questions

LoR: Letter of representation

MAH: Marketing authorisation holder

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MMD: Management of Meeting Documents system

MRP: Mutual recognition procedure

MS: Member State

NCA: National competent authority

OE: Oral explanation

P-CI: Compliance and Inspections Sector

PI: Product information

P-MI-PIN: Public Information and Stakeholder Networking Section

P-R-CP: Community Procedures Section

P-R-RA: Regulatory Affairs Section

PSM: Product shared mailbox

PTL: Product team leader for the referral procedure

PTM: Product team member

PTM-Q: Product team member from H-QM

PTM-RA: Product team member from P-R-RA

Q&A: Questions and Answers document

QRD: Quality Review of Documents

r-MF: Referral master file

RMS: Reference Member State

SAG: Scientific Advisory Group

SC: Standing Committee

SH: Section Head

SOP: Standard operating procedure

ToD: Table of decisions

TT: Timetable

V-PD-BUS: Product and Application Business Support Section

V-PD-DBM: Product Database Management Section

V-PD-DIS: Document and Information Services Section

WIN: Work instructions

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8. Process map(s)/ flow chart(s)

START

1. Receive referral notification from RMS.Create folder in DREAM.

2. Identify PTL.Assign responsibilities to administrative assistant and

PTL secretary.

4. Request appointment of PTM-RA.

5. Appoint PTM-RA.

6. Allocate procedure reference number. Add to database.

7. Create PSM.

14. Attend internal pre-referral meeting.

16. Receive annex I, LoR and dossier.

17. Circulate annex I to RMS and CMS for validation. Finalise annex I.

8. Inform CHMP Secretariat.

9. Request consolidated report from RMS.

10. Table report in MMD for CHMP discussion. Redact report to be sent to MAH/applicant.

15. Propose (co-)rapporteur and request agreement.

18. Verify LoR.

19. Generate draft LoQ, TT and cover letter.

20. Prepare scientific parts of draft LoQ.Table draft LoQ and TT inMMD.

3. Need for PTM-Q?Yes

No

3.1 Appoint PTM-Q.

11. Record and track procedure in tracking table.

12. Inform MAH/applicant of upcoming referral procedure and request annex I, LoR and dossier.

13. Organise internal pre-referral meeting.

Continue with step 21.

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21. Attend CHMP.Ensure (co-)rapporteur appointment.

24. Finalise LoQ and TT and table in MMD.

22. Identify and agree if PI is affected.

25. Prepare and send correspondence and documentation to MAH/applicant.

26. Include start of procedure in CHMP meeting highligths. Verify CHMP ToD, Minutes and Monthly

Report.

27. Update tracking table.

23. Type of workflow?Rapporteur-led

Standard

28. Receive repsonses to LoQ from MAH/applicant.

29. Save reponses in DREAM.Receive PI.

Continue with step 40.

Go to step 59.

30. Receive AR on responses from (co-) rapporteur.

31. Save AR on responses in DREAM.

32. Forward AR to PTMs.

34. Send redacted AR to MAH/applicant.Request updated PI.

35. Receive comments from CHMP members on AR on responses.

37. Save comments in DREAM.Compile comments.

36. Did (co-) rapporteur receive same comments?

No

Yes

36.1 Exchange comments.

38. Need for LoOI?No

Yes Go to step 89.

39. Generate draft LoOI and cover letter.Update TT.

Sta

ndar

d w

orkf

low

Continue from step 20.

33. Redact AR.

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46. Update tracking table.

47. Receive responses to LoOI from MAH/applicant.

40. Prepare scientific parts of LoOI.Discuss need for SAG/Ad Hoc Expert meeting and LoQ.

41. Receive comments on LoOI, SAG/expert LoQ and TT. Amend accordingly.

45. Organise ad hoc Expert meeting. Verify CHMP ToD and Minutes.

48. Save responses in DREAM.

49. Receive JAR on responses from (co-) rapporteur.

50. Save JAR in DREAM.

Continue from step 39.

42. Table LoOI, SAG/Expert LoQ and TT in MMD.

43. Attend CHMP discussion. Table final documents in MMD.

44. Prepare and send letter with LoOI, SAG/Expert LoQ and TT to MAH/applicant.

54. Send JAR to MAH/applicant.Request updated PI.

55. Receive comments from CHMP members on JAR.

51. Forward JAR to PTMs.

58. Attend SAG/ad hoc Expert meeting Send minutes of SAG/ad hoc Expert meeting to (co-)rapporteur.

Continue with step 89.

57. Save comments in DREAM.Compile comments.

56. Did (co-) rapporteur receive same comments?

No

Yes

56.1 Exchange comments.

Sta

ndar

d w

orkf

low

52.Redact JAR.

53. Discuss need for oral explanation.

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65. Save AR in DREAM.

66. Forward AR to PTMs.Redact AR.

59. Finalise TT and table in MMD.

60. Prepare and send correspondence and documentation to MAH/applicant.

64. Receive AR from (co-)rapporteur.

67. Send AR to MAH/applicant.Request updated PI.

Continue from step 23

61. Include start of procedure in CHMP meeting highlights.

Verify CHMP ToD and Minutes.

62. Update tracking table.

63. Receive translations of INN from MAH/applicant

68. Receive comments from CHMP members on AR.

Continue with step 76.

70. Save comments in DREAM.Compile comments.

69. Did (co-) rapporteur receive same comments?

No

Yes

69.1 Exchange comments.

Rap

porte

ur le

d w

orkf

low

71. LoQ or Opinion?

LoQ

Opinion

Go to step 89.

74. Attend CHMP. Finalise LoQ and TT.Table LoQ and TT in MMD.

75. Prepare and send correspondence and documentation to MAH/applicant.Organise ad hoc Expert meeting.

72. Generate draft LoQ and cover letter.Update TT.

73. Prepare scientific parts of LoQ.Table draft LoQ and TT in MMD.

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Continue from step 75.

95. Inform P-MI of expected opinion.

96. Prepare draft Q&A.

89. Update annex I.

93. Prepare scientific parts of CHMP opinion and AR. Liaise internally and with (co-) rapporteur.

97. Provide comments on draft Q&A.

Continue from step 38, 58, 71

90. Prepare oral explanation, if applicable.

91. Generate draft CHMP opinion and AR.

92. Prepare TT for translations and cover letters.

Rap

porte

ur le

d w

orkf

low

76. Verify CHMP ToD and Minutes.

77. Update tracking table.

78. Receive repsonses to LoQ from MAH/applicant.

79. Save reponses in DREAM.

80. Receive AR on responses from (co-) rapporteur.

81. Save AR on responses in DREAM.

84. Discuss need for oral explanation.

85. Send redacted AR to MAH/applicant.Request updated PI.

Attend SAH/ad hoc Expert meeting.

86. Receive comments from CHMP members on AR on responses.

88. Save comments in DREAM.Compile comments.

87. Did (co-) rapporteur receive same comments?

No

Yes

87.1 Exchange comments.

94. Inform V-PD-DIS on upcoming translations.

Continue with step 98.

82. Forward AR to PTMs.

83. Redact AR.

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Continue from step 97.

98. Table draft CHMP opinion, AR and Q&A in MMD.

107. Send final translations to EC, IS and NO and MAH/applicant.

106. Re-examination?Yes

No

106.1 Handle re-examination.

110. Comments from SC?

No

Yes

109. Save draft Commission Decision in DREAM.

108. Receive dates of SC consultation.

112. Save final Commission Decision in DREAM.

113. Update Q&A and send to Webteam for publication.

99. Attend CHMP. Update CHMP opinion and AR accordingly.

Request and verify updated PI.Table final documents in MMD.

100. Submit Opinion and cover letter for signature.

101. Prepare and send correspondence and documentation to MAH/applicant and EC.

104. Verify CHMP ToD and Minutes.

105. Update tracking table.

110.1 Send update to EC and MAH/

applicant.

END

103. Send annexes to V-PD-DIS and MAH/applicant for translation. Receive translations from V-PD-DIS and

MAH/applicant.

111. InformEC that no comments were received.

102. Prepare sign-off folder for publication of Q&A in English and send it to Webteam.

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9. Procedure

Step Action Responsibility

Before the start of procedure

1 Receive the “Notification to the CHMP/EMA secretariat of a referral” (hereafter referred to as notification) from the RMS.

Forward the notification and other documents received electronically to the SH P-R-CP, CHMP secretariat and V-PD-DBM.

Create subfolders in DREAM under 01. Evaluation of medicines \ Referrals \ H – Article 29(4) and save any document received on CD-ROM (see SOP/H/3193).

V-PD-BUS

2 Identify a scientific administrator from P-R-CP to act as PTL for the referral procedure and check possible conflicts of interest according to SOP/EMA/0101.

Inform the appointed PTL about the referral procedure and the appointment as PTL for the referral procedure. Forward documents received to the PTL.

Assign responsibilities to an administrative assistant and PTL secretary from P-R-CP and inform them accordingly.

SH P-R-CP

3 Consider the need for involvement of a PTM-Q.

If involvement is needed, contact the relevant SH in H-QM and request the nomination of a PTM-Q. Go to step 3.1.

If no involvement is needed, go to step 4.

SH P-R-CP

3.1 Appoint the PTM-Q and inform the PTM-Q and PTL accordingly. SH H-QM

4 Request appointment of the PTM-RA for the procedure from the SH P-R-RA as per the latest ‘RA Section Product and Project Portfolio’s Allocation’.

PTL

5 Appoint the PTM-RA and inform the PTM-RA and PTL accordingly. SH P-R-RA

6 Allocate a procedure reference number with ‘A-29’ as prefix and add the procedure to the referral database.

V-PD-DBM

7 Create a PSM for the procedure. V-PD-DBM

8 Inform the CHMP secretariat that the notification needs to be added to the agenda of the CHMP following the receipt of the notification.

Table the notification in MMD for discussion at CHMP.

PTL

PTL secretary

9 Request the consolidated report from the RMS (see template).

Receive the report and save it in the procedure folder in DREAM.

PTL secretary

10 Table the consolidated report in MMD for discussion at CHMP.

Redact any confidential information in the consolidated report from

PTL

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Step Action Responsibility

the RMS if needed (see WIN/EMA/0070) and save the redacted version to be sent to the MAH/applicant in the procedure folder in DREAM.

PTL secretary

11 Record and track the procedure in the tracking table. Administrative assistant

12 Inform the MAH/applicant of the upcoming referral procedure and request the annex I, LoR and dossier (see template).

PTL secretary

13 Organise an internal pre-referral meeting with the PTL, PTL secretary, Administrative assistant, PTMs, CMDh secretariat and D-LS if applicable.

PTL secretary

14 Attend the internal pre-referral meeting to check the notification and to discuss the referral procedure.

PTL, PTMs, D-LS, CMDh secretariat, Administrative assistant, PTL secretary

15 Propose the (co-)rapporteur (based on RMS and objecting MS) and request agreement from the (co-)rapporteur by e-mail (see template).

PTL

16 Receive the draft annex I, LoR and dossier from the MAH/applicant and save them in the procedure folder in DREAM.

Forward the draft annex I and LoR to the administrative assistant.

PTL secretary

17 Circulate the draft annex I to the RMS and all involved CMSs contact points requesting validation of the list (see template).

Receive comments from the NCAs and implement in track changes.

Finalise annex I and send it to the MAH/applicant for checking and completion (if necessary).

Administrative assistant

18 Verify the LoR and compliance with the draft annex I. Liaise with the NCAs and/or MAH/applicant if necessary to solve any discrepancies.

Administrative assistant

19 Generate the draft LoQ, TT and cover letter (see templates) and prepare the administrative parts of the draft LoQ and TT.

Save the documents in the procedure folder in DREAM.

PTL secretary

20 Prepare the scientific parts of the draft LoQ.

Liaise with or send to the (co-)rapporteur the draft LoQ and TT for comments prior to submission to CHMP for discussion.

Table the draft LoQ and TT in MMD for discussion at CHMP.

PTL

PTL secretary

Initial CHMP discussion and start of procedure

21 Attend the CHMP discussion on the referral procedure and ensure PTL

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Step Action Responsibility

confirmation of the (co-)rapporteur (see SOP/H/3176).

22 Identify and agree with the rapporteur on whether the PI is affected.

PTL

23 Follow the CHMP discussion and confirm with the CHMP whether to follow the standard workflow or the rapporteur-led workflow.

For the standard workflow, go to step 24.

For the rapporteur-led workflow, go to step 59.

PTL

Standard workflow

List of questions

24 Finalise the LoQ and TT taking into account the CHMP discussion.

Inform the PTL secretary about the adoption of the LoQ and TT.

Table the final documents in MMD for adoption by CHMP.

PTL

PTL secretary

25 Prepare the correspondence (see template) and documentation to be sent to the MAH/applicant (cover letter, official notification, adopted CHMP LoQ and TT and redacted consolidated report).

After signature by the SH P-R-CP, send the correspondence and documentation to the MAH/applicant (cc (co-)rapporteur) in accordance with WIN/H/3145 and verify receipt of documents.

PTL secretary

26 Include the start of procedure in the annexes to the CHMP meeting highlights (see WIN/H/3234).

Verify the CHMP ToD and CHMP minutes with regard to the procedure and provide comments to the CHMP secretariat if necessary.

PTL

27 Update the tracking table based on the CHMP ToD. Administrative assistant

Receipt of responses to list of questions

28 Receive responses to the LoQ from the MAH/applicant.

Forward the responses to the PTL and PSM.

V-PD-BUS

29 Save responses to the LoQ from the MAH/applicant in the procedure folder in DREAM.

Receive the PI as Word document (if applicable) and translations of the INN from the MAH/applicant and save them in the procedure folder in DREAM.

PTL secretary

30 Receive the (co-)rapporteur’s assessment reports on the responses.

Forward the reports to the PTL and PSM.

V-PD-BUS

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Step Action Responsibility

31 Save the (co-)rapporteur’s assessment reports in the procedure folder in DREAM.

PTL secretary

32 Forward the assessment reports to the PTMs as appropriate. PTL

33 Redact any confidential information in the (co-)rapporteur’s assessment reports (see WIN/EMA/0070) and save the redacted version in the procedure folder in DREAM.

PTL

34 Send the redacted (co-)rapporteur’s assessment reports by Eudralink to the MAH/applicant (see template and WIN/H/3145) and verify receipt of documents.

Request the MAH/applicant to implement comments and to submit a revised PI to the PTL and (co-)rapporteur, if applicable.

PTL secretary

35 Receive comments on the (co-)rapporteur’s assessment reports from other CHMP members.

Forward the comments to the PTL and PSM.

V-PD-BUS

36 Forward the comments to the PTMs as appropriate.

Check with the (co-)rapporteur whether they have received comments and if the comments received are the same.

If yes, go to step 37.

If no, go to step 36.1.

PTL

36.1 Send the (co-)rapporteur any comments that they have not received and/or ask them to send any comments that have not yet been provided to the Agency.

PTL

37 Save the CHMP members’ comments in the procedure folder in DREAM. Forward compiled CHMP members’ comments to the PSM.

PTL secretary

38 Discuss with the (co-)rapporteur whether a LoOI is required and inform the CHMP secretariat accordingly.

If yes, go to step 39.

If not, go to opinion phase - step 89.

PTL

List of outstanding issues

39 Generate the draft LoOI and cover letter (see templates) and prepare the administrative parts of the draft LoOI.

Generate the TT (including recalculation of number of active days).

Save the draft LoOI, TT and cover letter in the procedure folder in DREAM.

PTL secretary

40 Prepare the scientific parts of the draft LoOI.

Discuss with the (co-)rapporteur whether a Scientific Advisory Group (SAG) or an ad hoc Expert meeting needs to be convened,

PTL

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Step Action Responsibility

and inform the CHMP secretariat accordingly. If applicable, inform the SAG secretariat about the need to organise a SAG meeting according to SOP/H/3129.

Liaise with or send to the (co-)rapporteur (and PTMs, as applicable) the draft LoOI, draft list of questions for the SAG/ ad hoc Expert meeting, if relevant, and TT for comments.

41 Receive comments from the (co-)rapporteur (and PTMs) on the draft LoOI, draft list of questions for the SAG/ ad hoc Expert meeting, if relevant, and TT.

Amend the documents accordingly.

PTL

42 Table the draft LoOI, draft list of questions for the SAG/ ad hoc Expert meeting, if relevant, and TT in MMD for discussion at CHMP.

PTL secretary

43 Attend the CHMP meeting including discussions where the list of attendees for the SAG/ ad hoc Expert meeting is adopted, if relevant.

Amend the draft LoOI, draft list of questions for the SAG/ ad hoc Expert meeting, if relevant, and TT taking into account the CHMP discussion.

Inform the PTL secretary about the adoption of the LoOI, list of questions for the SAG/ ad hoc Expert meeting, if relevant, and TT.

Table the revised documents in MMD for adoption by CHMP.

PTL

PTL secretary

44 Prepare the correspondence informing the MAH/applicant about the LoOI adopted by CHMP(see template). In case an oral explanation to the CHMP was deemed necessary, include information on the oral explanation (see template). Inform the MAH/applicant about the adoption of a list of questions for a SAG/ ad hoc Expert meeting if relevant.

After signature by the SH P-R-CP, send the cover letter and documentation to the MAH/applicant (cc (co-)rapporteur) in accordance with WIN/H/3145 and verify receipt of documents.

PTL secretary

45 Organise the ad hoc Expert meeting, if applicable.

Verify the CHMP ToD and CHMP minutes with regard to the procedure and provide comments to the CHMP secretariat if necessary.

PTL

46 Update the tracking table based on the CHMP ToD. Administrative assistant

Receipt of responses to list of outstanding issues

47 Receive responses to the LoOI from the MAH/applicant.

Forward the responses to the PTL and PSM.

V-PD-BUS

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Step Action Responsibility

48 Save responses to the LoOI from the MAH/applicant in the procedure folder in DREAM.

PTL secretary

49 Receive the JAR on the responses to the LoOI from the (co-) rapporteur.

Forward the JAR to the PTL and PSM.

V-PD-BUS

50 Save the JAR in the procedure folder in DREAM. PTL secretary

51 Forward the JAR to the PTMs as appropriate. PTL

52 Redact any confidential information in the JAR (see WIN/EMA/0070) and save the redacted version in the procedure folder in DREAM.

PTL

53 Discuss with the (co-)rapporteur whether there is a need for an oral explanation to the CHMP. Inform the CHMP secretariat about the need for an oral explanation.

Receive information whether or not the MAH/applicant will attend the oral explanation and who will be attending, if applicable. Inform the CHMP secretariat accordingly.

PTL

54 Send the redacted JAR by Eudralink to the MAH/applicant (see template and WIN/H/3145) and verify receipt of documents.

Request the implementation of comments and submission of a revised PI to the PTL and (co-)rapporteur, if applicable.

Forward the JAR to the SAG/ ad hoc Expert meeting members in preparation of their meeting, if applicable.

Attend the SAG/ ad hoc Expert meeting.

PTL secretary

PTL

55 Receive comments on the JAR from other CHMP members.

Forward the comments to the PTL and PSM.

V-PD-BUS

56 Forward the comments to the PTMs as appropriate.

Check with the (co-)rapporteur whether they have received comments and if the comments received are the same.

If yes, go to step 57.

If no, go to step 56.1.

PTL

56.1 Send the (co-)rapporteur any comments that they have not received and/or ask them to send any comments that have not yet been provided to the Agency.

PTL

57 Save CHMP members’ comments in the procedure folder in DREAM. Forward compiled CHMP members’ comments to the PSM.

PTL secretary

58 Send the minutes of the SAG/ ad hoc Expert Meeting to the (co-) rapporteur, if applicable.

PTL

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Step Action Responsibility

Continue with step 89.

Rapporteur led procedure

Initial assessment by the (co-)rapporteur

59 Finalise the TT taking into account the CHMP discussion.

Inform the PTL secretary about the adoption of the TT.

Table the final document in MMD for adoption by CHMP.

PTL

PTL secretary

60 Prepare the correspondence (see template) and documentation to be sent to MAH/applicant (cover letter, official notification, adopted CHMP TT and redacted consolidated report).

After signature by the SH P-R-CP, send the correspondence and documentation to the MAH/applicant (cc (co-)rapporteur) in accordance with WIN/H/3145 and verify receipt of documents.

PTL secretary

61 Include the start of procedure in the annexes to the CHMP meeting

highlights (see WIN/H/3234).

Verify the CHMP ToD and minutes with regard to the procedure and provide comments to the CHMP secretariat if necessary.

PTL

62 Update the tracking table based on the CHMP ToD. Administrative assistant

63 Receive the translations of the INN from the MAH/applicant and save them in the procedure folder in DREAM.

PTL secretary

64 Receive the (co-)rapporteur’s assessment reports.

Forward the reports to the PTL and PSM.

V-PD-BUS

65 Save the (co-)rapporteur’s assessment reports in the procedure folder in DREAM.

PTL secretary

66 Forward the assessment reports to the PTMs as appropriate.

Redact any confidential information in the (co-)rapporteur’s assessment reports (see WIN/EMA/0070) and save the redacted version in the procedure folder in DREAM.

PTL

67 Send the redacted (co-)rapporteur’s assessment reports to the MAH/applicant (see template and WIN/H/3145) and verify receipt of documents.

Request the MAH/applicant to implement comments and to submit a revised PI to the PTL and (co-)rapporteur, if applicable.

PTL secretary

68 Receive comments on the (co-)rapporteur’s assessment reports from other CHMP members.

Forward the comments to the PTL and PSM.

V-PD-BUS

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Step Action Responsibility

69 Forward the comments to the PTMs as appropriate.

Check with the (co-)rapporteur whether they have received comments and if the comments received are the same.

If yes, go to step 70.

If no, go to step 69.1

PTL

69.1 Send the (co-)rapporteur any comments that they have not received and/or ask them to send any comments that have not yet been provided to the Agency.

PTL

70 Save the CHMP member’s comments in the procedure folder in DREAM. Forward compiled CHMP members’ comments to the PSM.

PTL secretary

71 Attend the CHMP meeting where the discussion and possible trend vote on the procedure takes place.

• if the trend vote is negative or if the trend vote is positive, but the MAH/applicant needs time to accept the conditions to the MA or to amend the changes to the PI, go to step 72 (LoQ)

• if the trend vote is positive and no conditions to the MA or further changes to the PI are required or if the trend vote is positive and the MAH/applicant has accepted the conditions to the MA or agreed to amend the PI, go to step 89 (opinion phase).

PTL

List of questions

72 Generate the draft LoQ and cover letter (see template) and prepare the administrative parts of the draft LoQ.

Generate the TT (including recalculation of number of active days).

Save the draft LoQ, TT and cover letter in the procedure folder in DREAM.

PTL secretary

73 Prepare the scientific parts of the draft LoQ.

Discuss with the (co-)rapporteur whether a Scientific Advisory Group (SAG) or an ad hoc Expert meeting needs to be convened, and inform the CHMP secretariat accordingly. If applicable, inform the SAG secretariat about the need to organise a SAG meeting according to SOP/H/3129.

Liaise with or send to the (co-)rapporteur (and PTMs, as applicable) the draft LoQ, draft list of questions for the SAG/ ad hoc Expert meeting, if relevant, and TT for comments prior to submission to CHMP for discussion and amend documents accordingly.

Liaise with the PTM-RA, if required.

Table the draft LoQ, drat list of questions for the SAG/ ad hoc Expert meeting and TT in MMD for discussion at CHMP.

PTL

PTL secretary

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Step Action Responsibility

74 Attend the CHMP meeting including discussions where the list of attendees for the SAG/ ad hoc Expert meeting is adopted, if relevant.

Amend the LoQ, draft list of questions for the SAG/ ad hoc Expert meeting, if relevant, and TT taking into account CHMP discussion.

Inform the PTL secretary about the adoption of the LoQ, list of questions for the SAG/ ad hoc Expert meeting, if relevant, and TT.

Table the revised documents in MMD for adoption by CHMP.

PTL

PTL secretary

75 Prepare the correspondence informing the MAH/applicant about the LoQ adopted by CHMP(see template). In case an oral explanation to the CHMP was deemed necessary, include information on the oral explanation (see template). Inform the MAH/applicant about the adoption of a list of questions for a SAG/ ad hoc Expert meeting, if relevant.

After signature by the SH P-R-CP, send the cover letter and documentation to the MAH/applicant (cc (co-)rapporteur) in accordance with WIN/H/3145 and verify receipt of documents.

Organise the ad hoc Expert meeting, if relevant.

PTL secretary

PTL

76 Verify the CHMP ToD and CHMP minutes with regard to the procedure and provide comments to the CHMP secretariat if necessary.

PTL

77 Update the tracking table based on the CHMP ToD. Administrative assistant

Receipt of responses to list of questions

78 Receive responses to the LoQ from the MAH/applicant.

Forward the responses to the PTL and PSM.

V-PD-BUS

79 Save responses to the LoQ from the MAH/applicant in the procedure folder in DREAM.

PTL secretary

80 Receive (co-)rapporteur’s assessment reports on the responses.

Forward the reports to the PTL and PSM.

V-PD-BUS

81 Save the (co-)rapporteur’s assessment reports in the procedure folder in DREAM.

PTL secretary

82 Forward the assessment reports to the PTMs as appropriate. PTL

83 Redact any confidential information in the (co-)rapporteur’s assessment reports (see WIN/EMA/0070) and save the redacted version in the procedure folder in DREAM.

PTL

84 Discuss with the (co-)rapporteur whether there is a need for an oral explanation to the CHMP. Inform the CHMP secretariat about

PTL

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Step Action Responsibility

the need for an oral explanation.

Receive information whether or not the MAH/applicant will attend the oral explanation and who will be attending, if applicable. Inform the CHMP secretariat accordingly.

85 Send the redacted (co-)rapporteur’s assessment reports by Eudralink to the MAH/applicant (see template and WIN/H/3145) and verify receipt of documents.

Request the MAH/applicant to implement comments and to submit a revised PI to the PTL and (co-)rapporteur, if applicable.

Forward the (co-)rapporteur’s assessment reports to the SAG/ ad hoc Expert meeting members in preparation of their meeting, if applicable.

Attend the SAG/ ad hoc Expert meeting.

PTL secretary

PTL

86 Receive comments on the (co-)rapporteur’s assessment reports from other CHMP members.

Forward the comments to the PTL and PSM.

V-PD-BUS

87 Forward the comments to the PTMs as appropriate.

Check with the (co-)rapporteur whether they have received comments and if the comments received are the same.

If yes, go to step 88.

If no, go to step 87.1.

PTL

87.1 Send the (co-)rapporteur any comments that they have not received and/or ask them to send any comments that have not yet been provided to the Agency.

PTL

88 Save CHMP member’s comments in the procedure folder in DREAM. Forward compiled CHMP members’ comments to the PSM.

Send the minutes of the SAG/ ad hoc Expert Meeting to the (co-) rapporteur, if applicable.

PTL secretary

PTL

Opinion

89 1 week before the CHMP meeting, send annex I to the NCA contact points for confirmation of the information. Follow-up with a reminder if necessary.

Receive answers from the contact points.

Update annex I with comments received, if necessary.

Administrative assistant

90 If an oral explanation is required, make preparations for the oral explanation as per the CPMP guidance to applicants on CPMP oral explanations CPMP/2390/01.

PTL

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Step Action Responsibility

91 Generate the draft CHMP opinion and assessment report, including relevant annexes (see templates).

Prepare the administrative parts of the draft CHMP opinion and assessment report, including relevant annexes.

Save the draft CHMP opinion and assessment report, including relevant annexes, in the procedure folder in DREAM.

PTL secretary

92 Prepare the draft TT for translations and draft letters for sending out the opinion, including the sign-off slip for checking and signing by the PTL, P-R-RA and D-LS (see templates and Action list for product secretaries).

Save the documents in the procedure folder in DREAM.

PTL secretary

93 Prepare the scientific parts of the draft CHMP opinion and assessment report, including the scientific conclusions and relevant annexes.

Consider whether the referral procedure needs to be added to the agenda of the Product Oversight meeting and attend the meeting if relevant.

Send the draft documents to the PTMs, SH P-R-CP and (co-) rapporteur if possible at the latest by the Wednesday the week before the CHMP meeting for review (with comments to be provided at the latest by Friday the week before the CHMP meeting).

Update the draft CHMP opinion and assessment report as necessary.

PTL

94 Inform V-PD-DIS (translation inbox - translationsrequests@ema.europa.eu) about up-coming translations (annex II and IV), if applicable.

PTL secretary

95 Inform P-MI-PIN about the expected opinion. PTL

96 Prepare a draft Q&A, according to SOP/EMA/0111. P-MI-PIN

97 Provide comments on the draft Q&A to P-MI-PIN. PTL

98 Table the draft CHMP opinion and assessment report in MMD for discussion at CHMP.

Table the draft Q&A, if applicable, in MMD for discussion at CHMP.

PTL secretary

99 Attend the CHMP meeting including the oral explanation and/or the presentation of the outcomes of the SAG/ ad hoc Expert meeting, if applicable.

Update the CHMP opinion and assessment report as needed to reflect the CHMP discussion and if applicable the conclusions of the SAG/ ad hoc Expert meeting, the oral explanation, the voting

PTL

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Step Action Responsibility

and/or any divergent positions.

Request the MAH/applicant (in writing) to provide revised product information incorporating changes suggested during the CHMP discussion, if applicable.

Table the revised documents in MMD for adoption by CHMP.

PTL secretary

100 Submit the sign-off folder with the adopted opinion to the PTL, P-R-RA and D-LS for checking and sign-off and to the CHMP Chair for signature.

Check and update cover letters to the MAH/applicant and EC if necessary.

PTL secretary

Post-opinion phase

101 Prepare the correspondence (see template) and documentation to be sent to the EC, IS and NO and MAH/applicant (cover letter, CHMP opinion and assessment report, together with all annexes and TT for translations, translations of INN/product name) in accordance with WIN/H/3145.

After signature by the SH P-R-CP, send correspondence and documentation to EC, IS and NO and to MAH/applicant (cc (co-) rapporteur), in accordance with the Action list for product secretaries, and verify for receipt of documents.

PTL secretary

102 Prepare the folder and sign-off slip for the publication of the Q&A (English only).

After signature by the SH P-R-CP, send it to the Webteam for publication.

PTL secretary

103 Send annexes I, II, III and IV (if applicable) of the CHMP opinion to V-PD-DIS (translation inbox - translationsrequests@ema.europa.eu) and the MAH/applicant for translation, in accordance with SOP/EMA/0048.

Receive translations from V-PD-DIS and the MAH/applicant.

PTL secretary

104 Verify the CHMP ToD and CHMP minutes with regard to the procedure and provide comments to the CHMP secretariat if necessary.

Liaise with the Compliance and Inspection (P-CI) Sector in case the Clinical Trials Facilitation Group (CTFG) needs to be contacted.

PTL

105 Update the tracking table based on the CHMP ToD. Administrative assistant

106 Check whether a request for a re-examination of the opinion has been received within 15 days of the receipt of the paper copy of the opinion by the MAH/applicant.

If yes, go to step 106.1.

PTL

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Step Action Responsibility

If no, go to step 107.

106.1 In case the MAH/applicant requests a re-examination of the opinion within 15 days of the receipt of the paper copy of the opinion, the remaining steps of this SOP will be put on hold pending the finalisation of the re-examination procedure.

• Upon receipt of the re-examination request, immediately inform the EC.

• Handle the re-examination procedure according to the “Procedural Advice on the re-examination of CHMP opinions (EMEA/CHMP/50745/2005)” document.

Once the re-examination procedure is finalised, continue with step 107.

PTL

107 Prepare the correspondence (see template) and documentation (final translations) to be sent to the EC, IS and NO and MAH/applicant.

After signature by the SH P-R-CP, send the documents to the EC, IS and N and MAH/applicant in accordance with WIN/H/3145 and verify receipt of documents.

PTL secretary

Standing Committee and Commission decision phase

108 Receive an e-mail from the EC with the start and end dates for the SC consultation phase and the draft Commission Decision.

Check the documents and provide comments to the EC, if applicable.

PTL

109 Save the draft Commission Decision in the procedure folder in DREAM and forward the e-mail from the EC to the PSM.

PTL secretary

110 At the end of the SC phase, verify with the PTL if comments have been received.

If yes, go to step 110.1.

If no, go to step 111.

PTL secretary

110.1 Send the updated translations (if any) to the EC and MAH/applicant the day after SC consultation has ended (see templates, Action list for secretaries and WIN/H/3145) and verify receipt of documents.

Go to step 112.

PTL secretary

111 Inform the EC that no comments were received. PTL secretary

112 Receive information from the EC on the adoption of the final Commission Decision.

Retrieve the final Commission Decision documents from the EC website and save them in the procedure folder in DREAM.

PTL secretary

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Step Action Responsibility

Post Commission decision phase

113 Update the Q&A by adding the date of the Commission Decision and send it to V-PD-DIS (translation inbox - translationsrequests@ema.europa.eu) for translation.

Upon receipt of the Q&A translations from V-PD-DIS, prepare all documents for publication (see WIN/H/3205).

Prepare the folder and sign-off slip for publication.

Send it to the Webteam for publication.

PTL secretary

10. Records

All required paper and electronic documents and records received and/or generated during this procedure are filed, saved and archived in the paper and/or electronic referral master file and/or in DREAM in accordance with SOP/H/3193.