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Standard operating procedure Title: Review and revision of effective standard operating procedures Status: PUBLIC Document no.: SOP/EMA/0013 Approver Effective date: 10-Jul-13 Name: Mario Benetti Name: Guido Rasi Review date: 10-Jul-16 Signature: On file Signature: On file Supersedes: SOP/EMA/0013 (08-JUL-10) Date: 10-Jul-13 Date: 10-Jul-13 TrackWise record no.: 3882 1. Purpose To describe the procedure for reviewing and revising or withdrawing standard operating procedures. 2. Scope This SOP applies to all lead authors involved in SOP/WIN drafting and to all Heads of Sector and Section Heads. 3. Responsibilities Each Head of Unit, Head of Sector and Section Head under the responsibility of the Executive Director must ensure that this procedure is adhered to within their own unit, sector or section. The responsibility for the execution of a particular part of this procedure is identified in the right-hand column of section 9. 4. Changes since last revision Revision of step 9 to adapt the instruction to the use of a MS Word SOP template instead of a template provided by TrackWise. Revision of step 12 to adapt the instruction with the use of MS Visio instead of MS Power Point to revise flowcharts. Replacement of references to EDMS by DREAM and updating of instructions to reflect DREAM. 7 Westferry Circus Canary Wharf London E14 4HB United Kingdom Telephone +44 (0)20 7418 8400 Facsimile +44 (0)20 7418 8416 E-mail info@ema.europa.eu Website www.ema.europa.eu An agency of the European Union European Medicines Agency, 2013. Reproduction is authorised provided the source is acknowledged.

5. Documents needed for this SOP SOP template in MS Word (provided solely by the ). Flow chart template in MS Visio (provided solely by the ). SOP_WIN transmission slip (provided solely by the ). 6. Related documents SOP/EMA/0001: Preparation and approval of new standard operating procedures SOP/EMA/0037: Publication of, and training on standard operating procedures and work instructions WIN/EMA/0036: Creating flow charts for standard operating procedures and work instructions WIN/EMA/0053: Use of TrackWise software for SOP/WIN recording and tracking 7. Definitions DREAM: Document records electronic archive management system EMA bodies: Management Board, scientific committees, working parties, scientific advisory groups, etc. of the European Medicines Agency HoS/SH: Head of Sector/Section Head : Unit IQM co-ordinator or delegate ManualCo: IQM manual co-ordinator or delegate SOP: Standard operating procedure - Detailed, written instructions to achieve uniformity of the performance of a specific procedure; the instructions usually cover more than one task or area within the Agency, Unit or Sector SOP Review: To critically examine a SOP in due time before its review date to determine whether the written procedure and related forms/templates accurately describe and reflect the procedure followed in practice or not SOP Revision: To modify a SOP and/or related forms/templates to accurately describe the procedure followed in practice as a result of a review or a change to the procedure at any time before the review date TrackWise: Software for the tracking of processes and the creation and archiving of related records and associated documents. The SOP/WIN Management module is intended for the recording and tracking of SOPs and WIN WIN: Work instructions Detailed descriptions of how to perform and record tasks; they may be, for example, detailed written descriptions, flow charts, checklists, pictures, or combinations thereof SOP/EMA/0013, 10-Jul-13 Page 2/8

8. Process map(s)/ flow chart(s) START 1. Is SOP due for review or requires revision? For revision For review 2. Prepare list of Unit SOPs Forward to HoS/SH/ interested persons 3. Review list in Unit/ Sectors/Sections 4. Approve review of SOP Reconfirm/appoint lead author, review team & approver Define consultation status and publication status 5. Inform 6. Update SOP status Create TrackWise record (WIN/EMA/ 0053) Send e-mail to lead author 7. Review SOP and related forms/templates 8. Is SOP obsolete? Yes 9. Inform No To 26. 10. Is revision required? No 11. Finalise SOP Yes 12. Revise flow chart (WIN/EMA/0036) To 23. 13. Revise SOP and forms/templates 14. Inform To 15. SOP/EMA/0013, 10-Jul-13 Page 3/8

From 14. 15. Check SOP format Update SOP status Update TrackWise record (WIN/EMEA/ 0053) 16. Is consultation with EMA bodies required? Yes No 17. Refer SOP to EMA bodies 18. Publish on IQM web page on intranet Inform intranet news editors 19. Announce on intranet news page 20. Evaluate and implement comments Check and finalise flow chart, SOP and related forms/templates Inform 21. Carry out QC check 22. Implement corrections, if required 23. Update SOP status Print hard copy Update TrackWise record (WIN/EMA/ 0053) Generate transmission slip Categorise in activity area/type From 11. 24. Sign SOP (lead author) 25. Read and sign SOP (approver) 26. Go to SOP/EMA/ 0037 From 9. END SOP/EMA/0013, 10-Jul-13 Page 4/8

9. Procedure Step Action Responsibility 1 For effective SOPs due for review, go to Step 2. If an effective SOP needs to be reviewed well before its review date due to a change in the procedure, go to Step 4. 2 On a regular basis as determined by each Unit, generate a list of SOPs falling under the responsibility of the respective Unit that are due for review within the next 3 months or that have expired and are pending review. HoS/SH/Lead author Forward list to HoS, SH and other concerned persons in the respective Unit. 3 Review the list in the respective Unit/Sectors/Sections and prioritise review of SOPs. 4 Approve review of SOP. HoS/SH HoS/SH Re-confirm or assign lead author of SOP. Appoint/re-appoint review team having a good knowledge of the procedure. If cross-section/sector/unit representation is necessary, consult with other SH/HoS to appoint team members. Re-assign consultation status, publication status and approver (refer to SOP/EMA/0001). 5 Inform by e-mail of SOP to be reviewed, consultation status, publication status, and lead author, review team and approver names. 6 Update status of SOP (refer to WIN/EMA/0035). Check in to DREAM. Create new record in TrackWise (refer to WIN/EMA/0053). When completed, send e-mail to lead author with the link to the SOPspecific folder in DREAM. 7 Review the SOP and related forms/templates, if applicable, to evaluate the need for a revision or otherwise. 8 If the procedure described in the SOP is obsolete, go to step 9. If the procedure described in the SOP is still valid, go to step 10. 9 Inform that the SOP is obsolete and should be withdrawn. Go to step 26. 10 If the procedure has not changed in any way and the SOP does not require revision, go to step 11. If the SOP needs to be revised, go to step 12. SOP/EMA/0013, 10-Jul-13 Page 5/8

Step Action Responsibility 11 Update the section Changes since last revision by replacing existing text with SOP reviewed and reissued without any changes. Inform that SOP can be re-issued without changes. Go to step 23. 12 Revise, if appropriate, the flow chart in MS Visio provided by the (refer to WIN/EMA/0036). Save all versions of the document in the SOP-specific folder provided. 13 Revise the SOP using the MS Word document provided by the. Update the section Changes since last revision by briefly listing the changes that have been made and are included in the revised version of the SOP. Changes from previous versions recorded under the heading should be replaced by the most recent changes. If extensive changes are made, type Extensive revision to rewrite SOP. Use the same approach described in SOP/EMA/0001 to describe the procedure steps. Verify if any related documents or forms, templates, etc need to be revised concurrently. Ensure that all functions identified as responsible for specific actions described in the SOP have been consulted and engaged in the review of the SOP. Paste the updated flow chart as a picture (enhanced metafile) in the SOP (refer to WIN/EMA/0036). Save all versions of the revised SOP in the SOP-specific folder provided. In case of difficulty with any part of this step, seek assistance of the. 14 When revision is complete, inform the. If other EMA bodies need to be consulted, discuss the length of consultation with the. Note: For a revised SOP, the length of consultation is 2 weeks; When other EMA bodies need to be consulted the length of consultation may be longer than the standard 2 weeks. 15 Check that SOP has been completed according to the instructions in the template and complete checklist in TrackWise (refer to WIN/EMA/0053). Update status of SOP to CONSULTATION (CONFIDENTIAL) in template and check in to DREAM. Update the TrackWise record (refer to WIN/EMA/0053) with the SOP/EMA/0013, 10-Jul-13 Page 6/8

Step Action Responsibility consultation details. Note: TrackWise sends automated notifications to lead author and ManualCo. 16 If the SOP requires consultation with EMA bodies, go to step 17. If the SOP does not require consultation with EMA bodies, go to step 18. 17 Refer SOP and forms/templates, if applicable, to secretariats of EMA bodies to initiate consultation. 18 Publish the SOP on the intranet IQM web page. ManualCo Inform the News Editors to advertise the SOP consultation on the intranet news page and provide the deadline for consultation. 19 Announce SOP consultation on the intranet news page. Intranet news editors 20 On receipt of comments from staff and, where applicable, from EMA bodies, acknowledge receipt by e-mail. Evaluate comments and implement appropriate suggested improvements in the SOP. Check and finalise flow chart, SOP and forms/templates, if applicable. Inform when ready. Note: TrackWise sends automated notifications to lead author and at the end of the consultation and when there are delays in finalising a SOP after consultation. 21 Carry out quality check (use checklist in WIN/EMA/0053) and request lead author to make corrections, if required. 22 Make necessary corrections to SOP and forms/templates, if required. 23 Update status of SOP to agreed publication status as informed in step 4. Print hard copy. Check in to DREAM. Open the SOP record in TrackWise, document quality check and update required fields (refer to WIN/EMA/0053). Prepare the SOP_WIN transmission slip. (Re-)Categorise the SOP in the relevant activity area and type for web publication, and document in the transmission slip. Forward SOP and transmission slip to lead Author. 24 Sign SOP and transmission slip. SOP/EMA/0013, 10-Jul-13 Page 7/8

Step Action Responsibility Forward to approver. 25 Read SOP and sign SOP and transmission slip. Approver Forward to. 26 Refer to SOP/EMA/0037. 10. Records Electronic records of SOPs are generated and saved in TrackWise. Electronic documents are filed in DREAM under: Cabinets/06. Corporate governance/06.2 Integrated Management System/2. IMS Manual/5. SOPs and WINs SOP/EMA/0013, 10-Jul-13 Page 8/8