STANDARD OPERATING PROCEDURE (SOP) CS06 …

1 :TF5) it's all about trust STANDARD OPERATING PROCEDURE (SOP) cs06 close Out Visit, version 04 Author: TFS Authorised by: Alistair Bone, Executive Vice President Global Quality Assurance ire`. 20 , Date of authorisation Approved by: Daniel Spasic, CEO / /Y,(2/( )0/./ Approval Date Effective Date The contents of this document are confidential. Unauthorised use, disclosure or reproduction without prior written permission from TFS is prohibited. Unofficial copy not valid close Out Visit STANDARD OPERATING PROCEDURE Version: 04 Number: cs06 Effective date: 24 March 2014 Page 2 (8) The contents of this document are confidential. Unauthorised use, disclosure or reproduction without prior written permission from TFS prohibited. CONTENTS 1. PURPOSE .. 3 2. DEFINITIONS .. 3 3. RESPONSIBILITY .. 3 4. PREPARING FOR THE VISIT.

2 3 5. CONDUCTING THE VISIT .. 3 Case Report Forms and Data Collection Forms .. 3 Informed Consent Forms .. 4 Unused Study Materials .. 4 Investigational Product Accountability .. 4 Code Envelopes .. 4 Investigator s File .. 4 Adverse Events .. 5 Audits and Inspections .. 5 Laboratory Reference Values .. 5 Finances .. 5 EC and Competent authority .. 5 Study Report and Publication .. 5 6. DOCUMENTING THE VISIT .. 6 close -Out Report .. 6 Issues .. 6 Review .. 6 Follow up with the Investigator .. 6 Filing .. 6 7. PREMATURE TERMINATION OR SUSPENSION OF A TRIAL .. 7 Unofficial copy not valid Unofficial copy not valid close Out Visit STANDARD OPERATING PROCEDURE Version: 04 Number: cs06 Effective date: 24 March 2014 Page 3 (8) The contents of this document are confidential. Unauthorised use, disclosure or reproduction without prior written permission from TFS prohibited.

3 1. PURPOSE This STANDARD OPERATING PROCEDURE (SOP) defines company policy and procedures to be followed after the completion of the clinical phase of a study or if a study has been discontinued prematurely. This SOP is valid for all clinical trials performed in accordance with TFS SOPs. 2. DEFINITIONS close Out Visit The close Out Visit is the last monitoring visit at the study site. The purpose of the visit is to discuss with the investigator the procedures following the termination of the study, to ensure that all activities required for trial close -out are completed, and that copies of essential documents are stored in the appropriate files, and that all study materials (eg Investigational Product, unused lab kits, unused CRFs) are collected from the site or otherwise arranged to be returned to the Sponsor or to TFS, as appropriate.

4 close out visits are normally conducted after database lock (in order that all queries are resolved) but can be conducted before. 3. RESPONSIBILITY The Monitor Preparing, conducting and documenting the Study close Out Visit 4. PREPARING FOR THE VISIT The Principal Investigator should be contacted to determine who will attend the meeting and to agree on date, time, length and location for the meeting. If the hospital pharmacy, laboratory or other service provider at the investigational site has performed study specific tasks then they should be visited as well, if appropriate. The monitor should prepare a list of all unresolved questions or issues to be discussed at the meeting, follow-up information on Adverse Events, missing or incorrect Case Report Form (CRF) data, missing documents, final payment etc.

5 5. CONDUCTING THE VISIT The close Out Visit Report should be used as a basis for what is to be performed during the visit. All the following items should be addressed/checked: Case Report Forms and Data Collection Forms Review all Case Report Forms (CRFs) that have been completed since the last visit (SOP, Study Monitoring). Follow-up any unresolved issues. Unofficial copy not valid Unofficial copy not valid close Out Visit STANDARD OPERATING PROCEDURE Version: 04 Number: cs06 Effective date: 24 March 2014 Page 4 (8) The contents of this document are confidential. Unauthorised use, disclosure or reproduction without prior written permission from TFS prohibited. Ensure that completed CRFs, Patient Diaries and Data Clarification Forms (DCFs) have been received and collected for all subjects and that the investigator s copies are available on site and filed appropriately Ensure that the randomisation numbers have been used in a consecutive order.

6 If not, make notes of discrepancies and, if appropriate, make a list of numbers not used. Informed Consent Forms Check that signed and dated Informed Consent Forms are present for all subjects and that they have been filed in the investigator s file. If informed consent forms have been filed in another location in subject s CRF or medical record, this should be clearly documented in the investigator s file. Unused Study Materials Arrangements should be made for the collection/return of all unused study materials, CRFs, forms, labels, specimen containers and any hired equipment such as centrifuges or refrigerators etc. The process should be agreed with the sponsor. Investigational Product Accountability Ensure that Investigational Product Accountability Forms have been accurately completed and collected and that a copy of the Investigational Product Accountability Forms is included in the Investigator s File.

7 Collect or arrange for the transportation of any unused Investigational Products for return to the Sponsor or other, as appropriate. If the investigational product is to be destroyed at the trial site, ensure that this will be conducted in accordance with the Investigational Products SOP and the destruction has been approved in writing Code Envelopes All code envelopes must be collected and accounted for. Code envelopes must be checked to ensure that none have been opened. Any code envelopes that have been opened should have an explanation as to why they were opened, the date of opening and the investigator s signature. Investigator s File The Investigator s File should be checked to ensure that all the essential documents according to the SOP- Study Files, Document Handling and Archiving are present, and the investigator should be reminded of his obligations for filing study documents.

8 The investigator/institution should maintain all the trial documents as specified in ICH Guidelines for GCP Section 8 Essential Documents for the Conduct of a Clinical Trial and as Unofficial copy not valid Unofficial copy not valid close Out Visit STANDARD OPERATING PROCEDURE Version: 04 Number: cs06 Effective date: 24 March 2014 Page 5 (8) The contents of this document are confidential. Unauthorised use, disclosure or reproduction without prior written permission from TFS prohibited. required by the applicable regulatory requirement(s). The investigator/institution should take measures to prevent accidental or premature destruction of these documents. Essential documents should be retained until at least 2 years after the last approval of a marketing application in an ICH region and until there are no pending or contemplated marketing applications in an ICH region or at least 2 years have elapsed since the formal discontinuation of clinical development of the investigational product.

9 These documents should be retained for a longer period however if required by the applicable regulatory requirements or by an agreement with the sponsor. It is the responsibility of the sponsor to inform the investigator/institution as to when these documents no longer need to be retained. (Reference: ICH E6 GCP ) In practice, this means that the investigator should keep the documents until notified by the Sponsor, in writing, that they are no longer required. This should be explained to the investigator, and the monitor should satisfy themselves that archiving arrangements are adequate. Adverse Events Check that all Adverse Events (including Serious Adverse Events) have been adequately followed up and documented. Audits and Inspections Inform the investigator(s) of the possibility of inspections and audits by competent authorities, the sponsor and TFS.

10 Laboratory Reference Values Check if there have been any changes in the laboratory reference values during the course of the study and, if so, ensure that all versions have been collected and sent to project leader and data management. Finances Clarify final payment plans. EC and Competent authority Remind the Investigator of any obligations to report the end of the trial to Ethics committees and Competent Authorities as appropriate Study Report and Publication Discuss plans, including the time schedule, for the Final Study Report and clarify roles and responsibilities. Plans and procedures for publication and presentations should also be discussed, including roles and responsibilities. Unofficial copy not valid Unofficial copy not valid close Out Visit STANDARD OPERATING PROCEDURE Version: 04 Number: cs06 Effective date: 24 March 2014 Page 6 (8) The contents of this document are confidential.