Standard operating procedure

Transcription

1 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.: 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 7 Westferry Circus Canary Wharf London E14 4HB United Kingdom Telephone +44 (0) Facsimile +44 (0) info@ema.europa.eu Website An agency of the European Union European Medicines Agency, Reproduction is authorised provided the source is acknowledged.

2 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 ( ing_ jsp&murl=menus/regulations/regulations.jsp&mid=wc0b01ac c59#section2 path: Home \ Regulatory \ Human medicines \ Product information \ Product information templates \ MR/DC/Referral procedures - product information templates) QRD form 2 ( 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 ( 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 ( SOP/H/3177, 04-SEP-12 Page 2/25

3 Guidance documents Notice to Applicants Volume 2A Procedures for marketing authorisations, Chapter 3 Community referral procedures ( EC Guideline on Summary of Product Characteristics (SmPC), Chapter 2C in the Notice to Applicants ( 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) ( Commission communication on the Community marketing authorisation procedures for medicinal products ( EMA Questions and Answers on referrals ( 18.jsp&murl=menus/regulations/regulations.jsp&mid=WC0b01ac e97 path: Home \ Regulatory \ Human medicines \ Referral procedures \ Q&A) Guidance to applicants on CPMP oral explanations in relation to centralised procedures ( ing_ jsp&murl=menus/regulations/regulations.jsp&mid=wc0b01ac # path: Home \ Regulatory \ Human medicines \ Pre-authorisation \ Guidance \ Application and Evaluation \ Evaluation) Convention to be followed for the EMA-QRD templates ( path: Home \ Regulatory \ Human medicines \ Product information \ Guidance \ QRD Templates) Procedural advice on the re-examination of CHMP opinions (EMEA/CHMP/50745/2005) ( 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 SOP/H/3177, 04-SEP-12 Page 3/25

4 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: CHMP: CMDh: CMS: CTFG: D-CM: DCP: D-LS: DREAM: EC: EMA: H-QM: H-SE: INN: JAR: LoOI: LoQ: LoR: MAH: Assessment report Committee for Medicinal Products for Human Use Coordination Group for Mutual Recognition and Decentralised Procedures - Human Concerned Member State Clinical Trials Facilitation Group Communication Sector Decentralised procedure Legal service Document Records and Electronic Archive Management system European Commission European Medicines Agency Quality of Medicines Sector Safety and Efficacy Sector International non-proprietary name Joint assessment report List of outstanding issues List of questions Letter of representation Marketing authorisation holder SOP/H/3177, 04-SEP-12 Page 4/25

5 MMD: MRP: MS: NCA: OE: P-CI: PI: P-MI-PIN: P-R-CP: P-R-RA: PSM: : PTM: PTM-Q: PTM-RA: Q&A: QRD: r-mf: RMS: SAG: SC: SH: SOP: ToD: TT: V-PD-BUS: V-PD-DBM: V-PD-DIS: WIN: Management of Meeting Documents system Mutual recognition procedure Member State National competent authority Oral explanation Compliance and Inspections Sector Product information Public Information and Stakeholder Networking Section Community Procedures Section Regulatory Affairs Section Product shared mailbox Product team leader for the referral procedure Product team member Product team member from H-QM Product team member from P-R-RA Questions and Answers document Quality Review of Documents Referral master file Reference Member State Scientific Advisory Group Standing Committee Section Head Standard operating procedure Table of decisions Timetable Product and Application Business Support Section Product Database Management Section Document and Information Services Section Work instructions SOP/H/3177, 04-SEP-12 Page 5/25

6 8. Process map(s)/ flow chart(s) START 1. Receive referral notification from RMS. Create folder in DREAM. 2. Identify. Assign responsibilities to administrative assistant and. 3. Need for PTM-Q? Yes 3.1 Appoint PTM-Q. No 4. Request appointment of PTM-RA. 5. Appoint PTM-RA. 6. Allocate procedure reference number. Add to database. 7. Create PSM. 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. 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. 14. Attend internal pre-referral meeting. 15. Propose (co-)rapporteur and request agreement. 16. Receive annex I, LoR and dossier. 17. Circulate annex I to RMS and CMS for validation. Finalise annex I. 18. Verify LoR. 19. Generate draft LoQ, TT and cover letter. 20. Prepare scientific parts of draft LoQ. Table draft LoQ and TT inmmd. Continue with step 21. SOP/H/3177, 04-SEP-12 Page 6/25

7 Continue from step Attend CHMP. Ensure (co-)rapporteur appointment. 22. Identify and agree if PI is affected. 23. Type of workflow? Rapporteur-led Standard Go to step Finalise LoQ and TT and table in MMD. 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. 28. Receive repsonses to LoQ from MAH/applicant. 29. Save reponses in DREAM. Receive PI. 30. Receive AR on responses from (co-) rapporteur. Standard workflow 31. Save AR on responses in DREAM. 32. Forward AR to PTMs. 33. Redact AR. 34. Send redacted AR to MAH/applicant. Request updated PI. 35. Receive comments from CHMP members on AR on responses. 36. Did (co-) rapporteur receive same comments? No 36.1 Exchange comments. Yes 37. Save comments in DREAM. Compile comments. 38. Need for LoOI? No 39. Generate draft LoOI and cover letter. Update TT. Yes Go to step 89. Continue with step 40. SOP/H/3177, 04-SEP-12 Page 7/25

8 Continue from step 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. 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. 45. Organise ad hoc Expert meeting. Verify CHMP ToD and Minutes. 46. Update tracking table. Standard workflow 47. Receive responses to LoOI from MAH/applicant. 48. Save responses in DREAM. 49. Receive JAR on responses from (co-) rapporteur. 50. Save JAR in DREAM. 51. Forward JAR to PTMs. 52.Redact JAR. 53. Discuss need for oral explanation. 54. Send JAR to MAH/applicant. Request updated PI. 55. Receive comments from CHMP members on JAR. 56. Did (co-) rapporteur receive same comments? No 56.1 Exchange comments. Yes 57. Save comments in DREAM. Compile comments. 58. Attend SAG/ad hoc Expert meeting Send minutes of SAG/ad hoc Expert meeting to (co-)rapporteur. Continue with step 89. SOP/H/3177, 04-SEP-12 Page 8/25

9 Continue from step Finalise TT and table in MMD. 60. Prepare and send correspondence and documentation to MAH/applicant. 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 64. Receive AR from (co-)rapporteur. 65. Save AR in DREAM. 66. Forward AR to PTMs. Redact AR. 67. Send AR to MAH/applicant. Request updated PI. 68. Receive comments from CHMP members on AR. 69. Did (co-) rapporteur receive same comments? Yes 70. Save comments in DREAM. Compile comments. No 69.1 Exchange comments. Rapporteur led workflow 71. LoQ or Opinion? Opinion LoQ 72. Generate draft LoQ and cover letter. Update TT. Go to step Prepare scientific parts of LoQ. Table draft LoQ and TT in MMD. 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. Continue with step 76. SOP/H/3177, 04-SEP-12 Page 9/25

10 Continue from step 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. 82. Forward AR to PTMs. 83. Redact AR. 84. Discuss need for oral explanation. 85. Send redacted AR to MAH/applicant. Request updated PI. Attend SAH/ad hoc Expert meeting. Rapporteur led workflow 86. Receive comments from CHMP members on AR on responses. 87. Did (co-) rapporteur receive same comments? No 87.1 Exchange comments. Yes 88. Save comments in DREAM. Compile comments. 89. Update annex I. Continue from step 38, 58, Prepare oral explanation, if applicable. 91. Generate draft CHMP opinion and AR. 92. Prepare TT for translations and cover letters. 93. Prepare scientific parts of CHMP opinion and AR. Liaise internally and with (co-) rapporteur. 94. Inform V-PD-DIS on upcoming translations. 95. Inform P-MI of expected opinion. 96. Prepare draft Q&A. 97. Provide comments on draft Q&A. Continue with step 98. SOP/H/3177, 04-SEP-12 Page 10/25

11 Continue from step Table draft CHMP opinion, AR and Q&A in MMD. 99. Attend CHMP. Update CHMP opinion and AR accordingly. Request and verify updated PI. Table final documents in MMD Submit Opinion and cover letter for signature Prepare and send correspondence and documentation to MAH/applicant and EC Prepare sign-off folder for publication of Q&A in English and send it to Webteam Send annexes to V-PD-DIS and MAH/applicant for translation. Receive translations from V-PD-DIS and MAH/applicant Verify CHMP ToD and Minutes Update tracking table Re-examination? Yes Handle reexamination. No 107. Send final translations to EC, IS and NO and MAH/applicant Receive dates of SC consultation Save draft Commission Decision in DREAM Comments from SC? No Yes Send update to EC and MAH/ applicant InformEC that no comments were received Save final Commission Decision in DREAM Update Q&A and send to Webteam for publication. END SOP/H/3177, 04-SEP-12 Page 11/25

12 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. V-PD-BUS 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). 2 Identify a scientific administrator from P-R-CP to act as for the referral procedure and check possible conflicts of interest according to SOP/EMA/0101. SH P-R-CP Inform the appointed about the referral procedure and the appointment as for the referral procedure. Forward documents received to the. Assign responsibilities to an administrative assistant and secretary from P-R-CP and inform them accordingly. 3 Consider the need for involvement of a PTM-Q. SH P-R-CP 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 Appoint the PTM-Q and inform the PTM-Q and 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. 5 Appoint the PTM-RA and inform the PTM-RA and 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. 9 Request the consolidated report from the RMS (see template). Receive the report and save it in the procedure folder in DREAM. 10 Table the consolidated report in MMD for discussion at CHMP. Redact any confidential information in the consolidated report from SOP/H/3177, 04-SEP-12 Page 12/25

13 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. 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). 13 Organise an internal pre-referral meeting with the, secretary, Administrative assistant, PTMs, CMDh secretariat and D- LS if applicable. 14 Attend the internal pre-referral meeting to check the notification and to discuss the referral procedure. 15 Propose the (co-)rapporteur (based on RMS and objecting MS) and request agreement from the (co-)rapporteur by (see template). 16 Receive the draft annex I, LoR and dossier from the MAH/applicant and save them in the procedure folder in DREAM., PTMs, D-LS, CMDh secretariat, Administrative assistant, secretary Forward the draft annex I and LoR to the administrative assistant. 17 Circulate the draft annex I to the RMS and all involved CMSs contact points requesting validation of the list (see template). Administrative assistant 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). 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. 19 Generate the draft LoQ, TT and cover letter (see templates) and prepare the administrative parts of the draft LoQ and TT. Administrative assistant Save the documents in the procedure folder in DREAM. 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. Initial CHMP discussion and start of procedure 21 Attend the CHMP discussion on the referral procedure and ensure SOP/H/3177, 04-SEP-12 Page 13/25

14 confirmation of the (co-)rapporteur (see SOP/H/3176). 22 Identify and agree with the rapporteur on whether the PI is affected. 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. Standard workflow List of questions 24 Finalise the LoQ and TT taking into account the CHMP discussion. Inform the about the adoption of the LoQ and TT. Table the final documents in MMD for adoption by CHMP. 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. 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. 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. V-PD-BUS Forward the responses to the and PSM. 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. 30 Receive the (co-)rapporteur s assessment reports on the responses. V-PD-BUS Forward the reports to the and PSM. SOP/H/3177, 04-SEP-12 Page 14/25

15 31 Save the (co-)rapporteur s assessment reports in the procedure folder in DREAM. 32 Forward the assessment reports to the PTMs as appropriate. 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. 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 and (co-)rapporteur, if applicable. 35 Receive comments on the (co-)rapporteur s assessment reports from other CHMP members. V-PD-BUS Forward the comments to the and PSM. 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 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. 37 Save the CHMP members comments in the procedure folder in DREAM. Forward compiled CHMP members comments to the PSM. 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. 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. 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, SOP/H/3177, 04-SEP-12 Page 15/25

16 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. 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. 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 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. 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. 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. 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. V-PD-BUS Forward the responses to the and PSM. SOP/H/3177, 04-SEP-12 Page 16/25

17 48 Save responses to the LoOI from the MAH/applicant in the procedure folder in DREAM. 49 Receive the JAR on the responses to the LoOI from the (co-) rapporteur. V-PD-BUS Forward the JAR to the and PSM. 50 Save the JAR in the procedure folder in DREAM. 51 Forward the JAR to the PTMs as appropriate. 52 Redact any confidential information in the JAR (see WIN/EMA/0070) and save the redacted version in the procedure folder in DREAM. 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. 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 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. 55 Receive comments on the JAR from other CHMP members. V-PD-BUS Forward the comments to the and PSM. 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 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. 57 Save CHMP members comments in the procedure folder in DREAM. Forward compiled CHMP members comments to the PSM. 58 Send the minutes of the SAG/ ad hoc Expert Meeting to the (co-) rapporteur, if applicable. SOP/H/3177, 04-SEP-12 Page 17/25

18 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 about the adoption of the TT. Table the final document in MMD for adoption by CHMP. 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. 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. 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. 64 Receive the (co-)rapporteur s assessment reports. V-PD-BUS Forward the reports to the and PSM. 65 Save the (co-)rapporteur s assessment reports in the procedure folder in DREAM. 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. 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 and (co-)rapporteur, if applicable. 68 Receive comments on the (co-)rapporteur s assessment reports from other CHMP members. V-PD-BUS Forward the comments to the and PSM. SOP/H/3177, 04-SEP-12 Page 18/25

19 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 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. 70 Save the CHMP member s comments in the procedure folder in DREAM. Forward compiled CHMP members comments to the PSM. 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). 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. 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. SOP/H/3177, 04-SEP-12 Page 19/25

20 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 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. 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. 76 Verify the CHMP ToD and CHMP minutes with regard to the procedure and provide comments to the CHMP secretariat if necessary. 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. V-PD-BUS Forward the responses to the and PSM. 79 Save responses to the LoQ from the MAH/applicant in the procedure folder in DREAM. 80 Receive (co-)rapporteur s assessment reports on the responses. V-PD-BUS Forward the reports to the and PSM. 81 Save the (co-)rapporteur s assessment reports in the procedure folder in DREAM. 82 Forward the assessment reports to the PTMs as appropriate. 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. 84 Discuss with the (co-)rapporteur whether there is a need for an oral explanation to the CHMP. Inform the CHMP secretariat about SOP/H/3177, 04-SEP-12 Page 20/25

21 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 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. 86 Receive comments on the (co-)rapporteur s assessment reports from other CHMP members. V-PD-BUS Forward the comments to the and PSM. 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 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. 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. 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. Administrative assistant Receive answers from the contact points. Update annex I with comments received, if necessary. 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. SOP/H/3177, 04-SEP-12 Page 21/25

22 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. 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, P-R-RA and D-LS (see templates and Action list for product secretaries). Save the documents in the procedure folder in DREAM. 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. 94 Inform V-PD-DIS (translation inbox - translationsrequests@ema.europa.eu) about up-coming translations (annex II and IV), if applicable. 95 Inform P-MI-PIN about the expected opinion. 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. 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. 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 SOP/H/3177, 04-SEP-12 Page 22/25

23 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. 100 Submit the sign-off folder with the adopted opinion to the, 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. 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. 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. 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. 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. 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 SOP/H/3177, 04-SEP-12 Page 23/25

24 If no, go to step 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 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. Standing Committee and Commission decision phase 108 Receive an 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. 109 Save the draft Commission Decision in the procedure folder in DREAM and forward the from the EC to the PSM. 110 At the end of the SC phase, verify with the if comments have been received. If yes, go to step If no, go to step 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 Inform the EC that no comments were received. 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. SOP/H/3177, 04-SEP-12 Page 24/25

25 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. 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. SOP/H/3177, 04-SEP-12 Page 25/25