STANDARD OPERATING PROCEDURE (SOP) QA02 …

1 Alistair Bone, Executive Vice President Quality Assurance ke, Date of authorisation Daniel Spasic, ca? Approval Dale , 0010 44()ti 0/5 fe/e)/10/f7 TFS Et's aIl about trust STANDARD OPERATING PROCEDURE (SOP) QA02 handling of suspected fraud or misconduct , version 04 Approved by: TFS Effective Date Author: Authorised by: The contents of this document are confidential. Unauthorised use, disclosure or reproduction without prior written permission from TFS is prohibited. Unofficial copy not valid handling of suspected fraud or misconduct STANDARD OPERATING PROCEDURE Version: 04 Number: QA02 Effective date: 5 October 2015 Page 2 (8) The contents of this document are confidential. Unauthorised use, disclosure or reproduction without prior written permission from TFS is prohibited. CONTENTS 1. PURPOSE .. 3 2. DEFINITIONS .. 3 3. RESPONSIBILITY .. 3 4. procedures .. 4 Initial action when fraud or misconduct is suspected .. 4 Initial action in case of suspected fraud .

2 4 Initial action in case of suspected misconduct .. 4 Internal meeting to assess the initial report of suspected fraud or misconduct .. 4 Internal meeting in case of suspected fraud .. 5 Internal meeting in case of suspected misconduct .. 5 Actions to be taken after the internal meeting .. 5 5. POSSIBLE INDICATORS OF fraud AND / OR misconduct .. 6 6. ARCHIVING .. 7 Unofficial copy not valid handling of suspected fraud or misconduct STANDARD OPERATING PROCEDURE Version: 04 Number: QA02 Effective date: 5 October 2015 Page 3 (8) The contents of this document are confidential. Unauthorised use, disclosure or reproduction without prior written permission from TFS is prohibited. 1. PURPOSE The purpose of this STANDARD OPERATING PROCEDURE (SOP) is to describe the procedures to be followed when there is suspicion of fraud or misconduct . 2. DEFINITIONS fraud The intentional creation of fictitious or falsified data or results including selective omission of data without scientific justification for the purpose of personal (or group) gain.

3 misconduct The systematic non-compliance which results in altered data, data errors or missing data to the extent that there is a serious breach of ethical and scientific principles. Deficiencies which are the result of lack of attention to detail, pressure of work, inadequate or over complex processes and procedures , or carelessness, and not from malice aforethought are not considered to be fraud or misconduct . 3. RESPONSIBILITY TFS Employees All TFS employees should be aware of the possibility of fraud or misconduct Any employee who suspects fraud or misconduct is responsible for reporting observations to their Line Manager and the Executive Vice President Quality Assurance immediately TFS Management Facilitate and support the reporting and investigation of suspected fraud or misconduct Provide guidance to TFS employees on the handling of the investigation of suspected fraud or misconduct Take appropriate action necessary to ensure the integrity and quality of a trial and the trial data Executive Vice President (EVP) Quality Assurance Contacting the sponsor to inform them of the incident EVP Quality Assurance is responsible for following up suspected fraud or misconduct Unofficial copy not valid handling of suspected fraud or misconduct STANDARD OPERATING PROCEDURE Version: 04 Number.

4 QA02 Effective date: 5 October 2015 Page 4 (8) The contents of this document are confidential. Unauthorised use, disclosure or reproduction without prior written permission from TFS is prohibited. 4. procedures All information regarding suspected fraud or misconduct is to be treated strictly confidentialy. Initial action when fraud or misconduct is suspected Initial action in case of suspected fraud TFS employees who observe possible fraud must contact their Line Manager, Project Leader and the EVP Quality Assurance and verbally report their findings immediately Alternatively, when there is suspicion of internal (involving TFS staff) fraud , immediate notification should be made to EVP Quality Assurance and/or CEO as appropriate Any TFS employee suspecting fraud should: Document the specific evidence of any suspicion of fraud When possible, obtain photocopies or photographs of the actual information / data Collect any associated documentation that supports the suspicion The initial notification should be followed by a written report (within 24 hours) including the areas of concern and the specific supporting documentation and collected evidence The EVP Quality Assurance should contact.

5 The CEO immediately The sponsor immediately if there is clear evidence of fraud Initial action in case of suspected misconduct The actions to be performed are the same as for fraud , only the timelines are different. TFS employees who observe possible misconduct must report the suspected misconduct as soon as possible (preferably on the same working day, but in any event within 2 working days). The initial contact should be followed by a written report (within 3 working days after the initial report) including the areas of concern and the specific supporting documentation and collected evidence. Internal meeting to assess the initial report of suspected fraud or misconduct A conclusion that fraud or misconduct has occurred will normally only be possible if it is clear that: There is a significant departure from accepted practices and regulations The fraud or misconduct was committed intentionally, knowingly or recklessly The allegation is supported by documentary evidence Unofficial copy not valid handling of suspected fraud or misconduct STANDARD OPERATING PROCEDURE Version: 04 Number: QA02 Effective date: 5 October 2015 Page 5 (8) The contents of this document are confidential.

6 Unauthorised use, disclosure or reproduction without prior written permission from TFS is prohibited. Internal meeting in case of suspected fraud TFS EVP Quality Assurance should inform the CEO (the same day) and convene a meeting with the reporter and Line Manager as soon as possible (within 24 hours of the initial notification). This meeting can be performed by video conference/telephone. In case of suspicion of internal (involving TFS staff) fraud , EVP Quality Assurance and/or CEO as appropriate should inform relevant management and convene a meeting with the reporter and management as soon as possible (within 24 hours after the initial notification). This meeting can be performed by video conference/telephone. To determine whether the allegations of fraud are justified, the following should be done: Conduct a review of the allegation Review and discuss the available documentation/evidence Determine if an investigation is justified Internal meeting in case of suspected misconduct The actions to be performed are the same as for fraud , only the timelines are different.

7 In case of suspected misconduct the meetings should be convened within 5 working days after the initial notification. Actions to be taken after the internal meeting If as a result of this meeting fraud or misconduct is no longer suspected a detailed file note should be created by EVP QA and filed in the QA department. If after the initial meeting fraud or misconduct is still suspected the following actions should be taken: A report in writing should be prepared by the EVP Quality Assurance and filed in the QA department. The Sponsor should be contacted as soon as possible and provided with full details of the suspected fraud or misconduct and the following should be discussed at a minimum: Who will be responsible for the follow up of the suspected fraud or misconduct The need to contact Competent Authorities and/or IEC/IRB Whether or not an audit or other investigation should be performed Other action ( closure of the investigational site, termination of vendor contract) If after the initial meeting the suspected fraud or misconduct concerns a TFS employee directly, the following actions should be taken by EVP Quality Assurance / CEO as appropriate: Unofficial copy not valid handling of suspected fraud or misconduct STANDARD OPERATING PROCEDURE Version: 04 Number: QA02 Effective date: 5 October 2015 Page 6 (8) The contents of this document are confidential.

8 Unauthorised use, disclosure or reproduction without prior written permission from TFS is prohibited. Deciding: Who will be responsible for the follow up of the suspected fraud or misconduct Whether or not there is a need to contact the sponsor, the Competent Authorities and/or the IEC/IRB Whether or not an audit or other investigation should be performed Other actions such as (formal warning, suspension, termination of contract of the employee). This must be documented. A written report should be prepared by the EVP Quality Assurance / CEO as appropriate and filed in the QA department / CEO s archive as applicable. 5. POSSIBLE INDICATORS OF fraud AND / OR misconduct Detecting fraud is not easy and many situations arise which could appear to indicate fraud and /or misconduct but have a logical and reasonable explanation. Some examples of evidence which could possibly indicate that fraud and/or misconduct might have occurred are given below.

9 A very much higher, than expected, number of subjects recruited Different subjects with large amounts of matching data ( clinical chemistry, haematology) Values of parameters which are not possible or are highly unlikely, even for seriously ill subjects Alteration in source data values that turn an ineligible subject into an eligible one Alteration in source data values which change the result of key efficacy parameters Extensive use of masking fluid on source documents Frequently obliterated subject identifiers, on ECG printouts, scans Handwriting similarities between documents such as diaries or questionnaires from different subjects Subject diary cards which are uncharacteristically neat and error free Similarities between investigator and subject signatures on consent forms Site staff very often absent during planned monitoring visits No source documentation for a subject Data collected at unusual times such as public holidays or at weekends Unusual or unexpected data at one site compared with all other sites in the same study for which there is no possible explanation, such as: o Absence of screen failures or adverse events common at other sites o Repeated values or number preference in data where variability is expected Unofficial copy not valid handling of suspected fraud or misconduct STANDARD OPERATING PROCEDURE Version: 04 Number: QA02 Effective date.

10 5 October 2015 Page 7 (8) The contents of this document are confidential. Unauthorised use, disclosure or reproduction without prior written permission from TFS is prohibited. 6. ARCHIVING All documentation pertaining to the evaluation of suspected or confirmed allegations will be archived in the Quality Assurance archive or in case that TFS employees are involved in the Quality Assurance archive or CEO s archives as copy not valid handling of suspected fraud or misconduct STANDARD OPERATING PROCEDURE Version: 04 Number: QA02 Effective date: 5 October 2015 Page 8 (8) The contents of this document are confidential. Unauthorised use, disclosure or reproduction without prior written permission from TFS is prohibited. DOCUMENT HISTORY Version No Effective Date Brief Description of Change New training required Yes No 01 1 February 2002 New SOP 02 1 October 2006 General update to harmonise TFS and CDC SOPs.