Effective Date: 1 May 2017

Transcription

1

2 4.0 PURPOSE / OBJECTIVE ICH GCP requires BaCT to implement and maintain quality assurance and quality control systems with written SOPs to ensure that trials are conducted and data are generated, documented and reported in compliance with the protocol, GCP and any applicable regulatory requirements. The objective of this SOP is to describe the procedures for the management and control, including the writing, issue, filing, use and archiving of BaCT SOPs and other controlled documents. This SOP does not cover the development and control of the following document types: instructions (for the despatch of product for clinical trial use), Processing Instruction, Material Specifications, Test Methods, Validation Documents. 5.0 PROCEDURE RESPONSIBILITIES It is the responsibility of all BaCT employees to ensure they have read, understood and adhere to the currently authorised version of each SOP. It is the responsibility of the document author to write the document according to this SOP. The document author should be a member of BaCT (or delegate) with a functional knowledge of the procedure and appropriate knowledge of guidelines and regulations controlling procedure. It is the responsibility of the document reviewer(s) to verify the procedure as appropriate and also to verify compliance with all necessary ICH Guidelines, Directives and/or Local Regulations and Codes of Practice. It is the responsibility of the document controller to review the document for readability, spelling or grammatical errors and compliance with BaCT_SOP-01_Preparation, Approval, Review and Issue of SOPs. The document controller should be an appropriately trained member of BaCT (or delegate). It is the responsibility of the document authoriser/approver to approve the document and any regulatory/gcp and codes of practice positional statements as formal BaCT policy. 5.1 IDENTIFYING THE NEED FOR A SOP OR SOP REVISION The process for SOP management explained below is applicable to BaCT. All employees should be aware of the purpose and importance of SOPs. All employees should be vigilant for procedures which require standardisation in performance, and take the initiative to address the need for a new SOP or SOP revision. The need for an SOP revision may arise from a number of circumstances, for example; Updates to National / International clinical research guidelines or regulations Changes to BaCT process A response to SOP deviations reports BaCT_GN_SOP-02_V2.0_; Effective Page 2 of 17

3 5.1.1 BaCT Document Review and Approval Form The BaCT Document Review and Approval Form (DRAF) should be used to document proposed controlled document (e.g. SOP, Protocol) or document revision requirements and submitted to the BaCT document controller. The DRAF will be used to record the details of the author, reviewers, and authoriser of the procedure, as well as document the employees training needs for implementation of the new/revised document. Should the need arise, the DRAF is also used to record paper copies of controlled document (e.g. SOP) issued to or retrieved from any party external to BaCT. 5.2 DESIGNATION OF SOP 5.3 AUTHOR, REVIEWER & AUTHORISER Where the SOP author has appropriate expertise, it may not be necessary to appoint a reviewer. However, it is recommended that a reviewer(s) is appointed to verify the process described is appropriate and compliant with guideline/regulatory requirements, as well as clear and understandable to other readers. The SOP reviewer(s) may be asked to review all or part of the SOP dependent on their expertise. Consideration should also be given to SOPs which overlap responsibilities of another division, and a reviewer should also be appointed from that area to ensure the process does not impact adversely on their process e.g. PCCTU or other clinical trials unit. The SOP Author will use the DRAF from the BaCT intranet site; fill in the relevant information and request the SOP number and/or revision version number from the document controller. Should the revision of an SOP be driven by documented deviations from the SOP necessitating revision, the author should ensure that copies of the deviation documentation are appended to the DRAF. All SOPs in draft form are to be saved in F:\BaCT Work Processes\SOPs\Drafts. 5.4 DRAFTING THE SOP OR SOP REVISION In order to achieve consistency in formatting, the SOP Author must use the SOP template to draft (or revise) the procedure. Obtain the template from the BaCT intranet site. Where the revisions of an SOP already formatted in compliance with the SOP template, it is permitted that the SOP Author request a copy of the word document for drafting the revision. It is suggested that the track change function is used when marking revision to current SOP to facilitate review. 5.5 REVIEW OF THE DRAFT SOP / REVISION The SOP Author will circulate the draft SOP / SOP revisions to the appointed reviewers. Reviewers will provide any comments to the SOP author. Once all review comments have been received the SOP author will update the SOP draft / revision accordingly. It is suggested that the track changes function, and draft versioning be used to assist with review. BaCT_GN_SOP-02_V2.0_; Effective Page 3 of 17

4 Where there is disagreement between reviewers, the SOP Author should facilitate an SOP review meeting to establish agreement. Once the SOP author and reviewers are in agreement the final draft SOP will be prepared. It is recommended that minutes of the review meeting are taken, and attached to the DRAF. The SOP reviewer(s) is responsible to ensure any requested changes to the SOP have been made, and will sign/date the DRAF to confirm their review. The final draft SOP will include the effective date of the SOP. The effective date must allow sufficient time for checking, authorisation, distribution and training prior to implementation of the new/revised SOP (usually a minimum of 2 weeks). Effective date must be agreed by delegates of relevant departments and must be based on the provision of training of relevant employees (as indicated on the DRAF) in the SOP occurring prior to its implementation. 5.6 SOP VERSION CONTROL The SOP final draft will be submitted to the document controller for quality control procedures. Examples and Definitions of SOP Version Control Version Examples BaCT_GN_SOP-01_VDraft0.1.0 BaCT_GN_SOP-01_VDraft0.1.1 When approved BaCT_GN_SOP-01_V1.0 Definition Reads as first draft of General BaCT SOP-01 Reads as second draft of General BaCT SOP-01 Reads as approved General SOP 01, Version SOP QUALITY CONTROL PROCEDURES The document controller will review the final draft for compliance with the SOP Document Control Procedures for BaCT. The document controller will return any comments to the SOP Author for incorporation into the SOP Final Version. Once the SOP Final Version is ready for approval, the SOP author will inform the document controller and request a printed copy. The document controller will remove the electronic work copy from the Draft folder to the restricted folder in the BaCT intranet. 5.8 SOP APPROVAL The SOP Final version will be printed off by the document controller and forwarded to the SOP Author. The SOP author signs it and then presents the SOP to the SOP Authoriser for signature. Where the SOP Authoriser raises objections to the SOP, the SOP will return to draft status and drafting / revision steps (the document controller to return electronic copy of to Draft Folder and destroy printed copy) as per 5.4 until the draft is agreed. Therefore it is recommended that consideration is given to the SOP Authoriser in the SOP development process. The SOP author, reviewer and authoriser should be different people. BaCT_GN_SOP-02_V2.0_; Effective Page 4 of 17

5 If the SOP is unavoidably approved / authorised after the effective date, the effective date on both the master copy (on the front page only) and the electronic copy must be amended to reflect the later new effective date. 5.9 SOP FINALISATION When the final version has been signed by the SOP Author and SOP Authoriser, the original signed paper version of the SOP will be forwarded by the SOP Author to the document controller. The SOP Author will also ensure the relevant sections of the DRAF have been completed and any relevant attachments e.g. scanned signature pages, minutes of review are forwarded to the document controller. The Document controller will move the electronic copy to the restricted folder in the BaCT intranet directory and make a non-modifiable copy marked Training Only available in the BaCT intranet for training and reading DOCUMENT CONTROL Master Index of Controlled Documents. The document controller will maintain the BaCT Master Index of Controlled Documents (Master Index). This document lists each SOP, including SOP number, SOP title, SOP version, date of authorisation (sign off), effective date, reviewer(s) and date withdrawal. Controlled SOP paper copies issued will be access restricted. The Master Index may also be used to log SOP deviations BaCT Department Controlled Document Naming, Numbering and Version Control. Naming: Name and Title of Document should be relevant and appropriate, reflecting the type and use of the document. Numbering: SOPs will be allocated a number. The document controller will provide SOP authors with the appropriate SOP number and version and update the Master Index accordingly. Consecutive numbering will apply to all functional department SOPs. Version Control: Version Numbers form part of the document identification number and shall be contained in the footer and in the relevant history. Different versions of a document shall be treated as separate documents. For major amendments where there is a change in procedure, the version number should increase in sequential increments of 1 e.g. version 1.0, version 2.0, version 3.0. For minor amendments i.e. administrative changes, administrative errors etc., the version number should increase in sequential increments of 0.1 e.g. version 1.1, 1.2 or 3.1, 3.2. When drafting new SOPs, the version will be recorded as V0.1.0_Draft, until the SOP has been approved. DRAF shall be used to document changes and approval of the document. Once document is approved and under formal control, it shall not be altered. A new version of a document may be classified as a minor or major change and training requirements will be documents in the DRAF. BaCT_GN_SOP-02_V2.0_; Effective Page 5 of 17

6 Examples, Definitions and Explanation of Controlled Document Naming, Numbering and Versioning; including Protocol and Patient Information & Consent Forms. Term BaCT Department Examples of Types of Controlled Documents Definition BaCT is the designate for all Controlled documents developed by the Centre for Biostatistics and Clinical Trials (PeterMac) Controlled Document Type (may be e.g. SOP, Form, Template, Guidance document, Process Flow) Examples: BaCT_GN_SOP-01_V1.0 Reads as: BaCT General SOP-01 Version 1 BaCT_CLF_001_V1.0 Reads as: BaCT Clinical Form number 1 Version 1 Specific functional department. The designated functional department will be the one with main responsibility for the tasks described in the SOP. This will not preclude the SOP from applying to other functional departments. GN General CL Clinical Project Management DM Data Management ST Statistics PV Pharmacovigilance (Safety) QA Quality Assurance BaCT SOPs are distinguished from Peter Mac institution SOPs by the prefix BaCT. SOPs will be numbered sequentially according to the Master Index. Other various controlled documents will be listed as: Form = F Template = T Guideline = G (M = Management) CLF Clinical Form CLT Clinical Template CLG Clinical Guideline GNF General Form GNT General Template GNG General Guideline DMF Data M Form DMT- Data M Template DMG-Data M Guideline STF Stats Form STT Stats Template STG Stats Guideline PVF Safety Form PVT Safety Template PVG Safety Guideline QAF Quality A Form QAT Quality Template QAG Quality Guideline BaCT_GN_SOP-02_V2.0_; Effective Page 6 of 17

7 5.11 VERSION CONTROL OF CLINICAL TRIAL PROTOCOLS Process Flow See Appendix XXX Protocol Version Control Protocol Version Number and Date After a proper name has been assigned it is necessary to attribute a version number and date: A number is always assigned to the very first version of a document The version will always be accompanied by the date on which that document was created E.g. Study XXX Protocol_v 0.1_21 Jan 2017 Subsequent version numbers will be assigned during the development of the document (See Appendix 1 Version Process) Protocol Status The status describes the state of the document, and depending on the stage of the writing process the author will assign one of the three following status to the document in particular reference to clinical trial protocols: Draft: A protocol at the initial stage of the writing process, drawn up in preliminary form, which can still undergo several revisions and will be afterwards perfected. E.g.: Study XXX Protocol v 0.1_21 Jan 2017_Draft Study XXX Protocol v 0.1.1_02 Feb 2017_Draft Final for Submission: A protocol that has undergone a revision process and all the proposed changes have been accepted. The document is ready for Sponsor review and Ethics Committee submission for approval. Eg. Study XXX Protocol v 0.1.2_14 Feb 2017_Final Final for Approval: The cover letter (Appendix 2) to ethics submitted with the Final for Submission protocol must state: Protocol XXX is being submitted as: v 0.1.2_14 Feb 2017_Final. Prior to issue of study approval letter please inform BaCT as the approved protocol will be versioned as: Study XXX Protocol v 1.0_14 Feb 2017_Final Approved The Final for Approval versioned protocol will be submitted within 2 working days of notification by ethics of approval for their records and in order that the protocol documented on the ethics approval letter reflects the Final Approved version number. For Peter Mac Sponsored studies, a copy of the Final Approved protocol is sent to the Sponsorship Committee (OCR) for their records. BaCT_GN_SOP-02_V2.0_; Effective Page 7 of 17

8 Protocol Rejected or Approved Subject to Change by Ethics Committee for Further Revision If the protocol submitted to the ethics committee is rejected and returned for further review the status of the protocol reverts to draft e.g. Study XXX Protocol v 0.1.3_20 Mar 2017_Draft On re-submission to the ethics committee becomes: Study XXX Protocol v0.1.3_21 Mar_2017_Final Protocol Footer The footer of the front page and all subsequent pages of any document will always include the following information. Project number or acronym Description of the document Current version number The date of the current version Current status Page in the format X of Y Eg: Study XXX Protocol v 1.0_14 Feb 2017_Final Approved 2 of Protocol Amendments A document that has been finalised and approved may be amended. There are 2 types of amendment: Major Amendment: If a substantial change or major review of the document is required. In this case the version number for a protocol undergoing revision will be numbered: - Study XXX Protocol v0.2_12 March 2017_Draft The process of submission to ethics and finalisation of the protocol will be followed as per Section On approval the finalised protocol will be: - Study XXX Protocol v2.0_14 March 2017_Final Approved Minor amendment: This is usually an administrative change e.g. contact address change. Version numbering will be as follows: - Study XXX Protocol v1.0_14 Feb 2017_ Final Approved - Study XXX Protocol v1.1_10 Mar 2017_ Final Approved (i.e.1 admin change) In both cases, while the amendments are being implemented the document will be labelled as Draft until the end of the revision process. BaCT_GN_SOP-02_V2.0_; Effective Page 8 of 17

9 Protocol Documentation Filing All documentation relating to the protocol is filed in the study Trial Master File (TMF) PATIENT INFORMATION AND CONSENT FORM (PICF) VERSIONING Process Flow Refer BaCT SOP-0X_Informed Consent and Recruitment Generic PICF All versions will be identified in the footer as Draft along with the version date, and tracked changes used to facilitate review. The document footer will be changed to reflect the Generic Approved version e.g. Study XXX_GN PICF v1.0_21 Jan Country Specific PICF The document footer will reflect the Country identity of the PICF and in watermark Generic version identity e.g. Study XXX_NZ PICF v1.0_24 Feb 2017 Study XXX_AU PICF v1.0_24 Feb 2017 (Based on Study XXX_GN PICF v1.0_21 Feb 2017) Site Specific PICF The document footer will reflect the specific identify of the site PICF and in watermark Country version identity e.g. Study XXX Site XXX Date XXX (Based on Study XXX_AU PICF v1.0_24 Feb 2017) PICF Documentation Filing All documentation relating to the PICF is filed in the study Trial Master File (TMF) and relevant Central Sites Files (CSF) SOP FILING SOP Master File (Paper) On receipt of the original signed paper version of the SOP, the document controller will scan the document into a PDF file (or equivalent). This PDF file will be the electronic copy used to publish the SOP on the BaCT intranet. This original signed paper format SOP is considered the SOP Master document. It will be filed in the SOP Master File as the current version of the SOP. There shall be a single definitive version of this SOP Master document. BaCT_GN_SOP-02_V2.0_; Effective Page 9 of 17

10 The SOP Master File will also contain the completed DRAF, and any SOP deviation forms. The Master File will be kept in a secure filing room SOP Superseded and Obsolete SOPs are reviewed and updated periodically. During this review process SOPs might become superseded or made obsolete. Decision / rationale for the review process will be recorded in the DRAF accordingly. Superseded versions of the SOP will be retained in the Superseded SOP Master File and marked superseded. Any SOP that has been made obsolete will be marked Obsolete and will also be retained in the Superseded SOP Master File. The Master Index will be updated as necessary SOP Electronic Records Both the Word and PDF electronic versions will be stored by the document controller in an access restricted folder of current SOPs. Both Word and PDF electronic versions of the SOP should be accessible only to the document controller and delegated back-up personnel. Access will be controlled via the IT administrator. The SOP will be made available to BaCT employees via BaCT Intranet as per section Publication of the SOP (Section 5.15). Superseded /Obsolete electronic version (both Word and PDF) of the SOP should be moved by the document controller to an access restricted folder of superseded SOPs in the BaCT directory. The Master Index will be updated by the document controller as necessary SOP TRAINING The DRAF will record how employees are to be trained in the SOP. Employees with responsibilities under the SOP should be trained in the SOP prior to the effective date but MUST be trained prior to commencing duties relevant to the SOP. SOP training will be documented in the employee training records. Prior to the effective date, the document controller will send an to all relevant BaCT employees (and to other employees as relevant) to notify about the new SOP. The new SOP in non-modifiable format marked Training Only will be made available within a training area of the BaCT intranet until the effective date at which point it will be removed from the training area and a pdf copy of the approved SOP will be published within the current SOP area. Prior to the effective date, the SOP author (or Line Manager as appropriate) should ensure the relevant employee training record is updated to indicate self-directed training is completed or if formal training is required, a copy of the completed training Attendance Record is forwarded to document controller by the effective date. A copy of the training Attendance Record should be provided to employees for their individual training file PUBLICATION OF THE SOP BaCT is responsible for ensuring all employees have access to the currently effective SOP. This will be achieved primarily via publication of the SOP on the BaCT intranet directory. BaCT_GN_SOP-02_V2.0_; Effective Page 10 of 17

11 In the unusual event of interruption to the BaCT intranet, temporary access to currently effective SOPs will be set up for SOP users via the BaCT F drive (temporary folder set up). The document controller is responsible for the publication and distribution of SOPs to ensure that only the currently effective version of documents are easily available to SOP users. On the effective date the document controller will ensure that the new version of the SOP is published on the intranet and the superseded version is removed. The version published should be in a nonmodifiable format. i.e. PDF. In order to minimise the risk of accidental change or misuse, documents will be uploaded to the website from a secure location, with access restricted. BaCT employees are permitted to make copies of the SOPs for personal reference only. However, it is the responsibility of all employees to ensure that any photocopies or print outs of expired SOPs are destroyed immediately a new version comes into effect. Where for the purpose of performing a process to BaCT standards, a party external to BaCT needs to be provided with a BaCT SOP, a controlled copy will be provided. The document controller will issue a controlled copy i.e. the copy will be allocated a copy number, and be initialled and dated by the document controller as a controlled issue. SOP controlled copies issued will be printed on coloured paper. The document controller will retain a log per SOP of controlled copies issued and will request an acknowledgment from recipients. On issue / withdrawal of an SOP, the document controller must ensure all copies of the superseded / withdrawn SOP are returned to the document controller for destruction or acknowledged as destroyed PERIODIC REVIEW AND RE-ISSUE OF SOPS SOPs must be reviewed and updated whenever there is any regulatory requirement change that would make the SOP non-compliant or if there is a requirement to amend a process described in the SOP. If no occasion arises for an SOP to be updated, the SOP can only have a non-review period of up to three (3) years. All SOPs will be reviewed at least every three years from the effective date. At three months prior to the review date, the document controller will initiate a BaCT DRAF and activate the process. If at the three year point, it is agreed (using the DRAF) that the SOP does not require any change, it may be reissued. The SOP Authoriser must sign and date in the SOP periodic review section and on the signature page of the original master copy. This extends the effectiveness of the SOP until the next SOP periodic review or until a SOP revision is required. The document controller will update the BaCT intranet and Master Index accordingly DOCUMENT CONTROL OF BACT CONTROLLED DOCUMENTS Document Control of BaCT Forms, Templates and Guidelines Documents with issued numbers (unique identifiers) referenced within SOPs are considered controlled documents, and employees are required to use only the currently approved controlled documents. BaCT_GN_SOP-02_V2.0_; Effective Page 11 of 17

12 The document controller will maintain a list of controlled SOPs, forms, templates, process guide / guidelines, process and policy documents that have been allocated unique identifiers by the document controller as part of the Master Index of Controlled Documents. Controlled documents such as SOPs, forms templates, guides and policy documents will be sequentially allocated a unique number. Versioning will also be used. The document number, version and effective date will be included in the footer and/or header in all controlled documents in order to verify that the current version of the document has been used. The document controller is responsible to ensure only current effective version is published and the superseded version is removed from circulation on the BaCT intranet. The document controller will maintain a Master File of the above types of controlled documents where current and superseded copies of the controlled documents are filed with the associated DRAFs. The document controller will also maintain the master electronic copies of the controlled documents and file them in an access restricted folder Approval of Controlled Documents Controlled documents will be approved by the Director of Division of Cancer Medicine (DCM) or delegate and such approval will be documented using the DRAF. The DRAF will document the circumstances / extent of modification permitted to the controlled document and this will be recorded by the document controller as part of the Master Index Publication of Controlled Documents Controlled documents will be published via the Intranet by the document controller. The format of publication will be determined via the DRAF. Where employees are not permitted to make any changes to the document, it will be published as a PDF or equivalent non-modifiable document. Where employees are permitted to customise the document for use in a specific study (e.g. in BaCT) it will be available as a template (or equivalent) so that the original document text/format is not changed, but study specific version can be saved to the study specific folders. It should be clear, via the format of the publication of the document which parameters of the document are permitted to be customised and which are mandated. It is suggested that nonmodifiable text format is used for mandatory text. Document completion guideline can also be used to provide user guidelines. The master approved and published document must always be used for generating a study specific document (e.g. in BaCT) and not a prior version of a study specific document. The document controller is responsible to ensure only the current document version is available and that the superseded version is removed from the BaCT Intranet. BaCT_GN_SOP-02_V2.0_; Effective Page 12 of 17

13 Guidelines for completion of Forms and Templates In order that a form or template is used correctly, guidelines for completion of form / template may be required. The guidelines will be named and versioned SOP DEVIATIONS Planned Deviations BaCT employees must comply with the SOPs. However, should circumstances arise where it not be possible to comply with the SOP (i.e. vendor procedure is non-compliant with BaCT procedures) the deviation from the BaCT SOP must be agreed by all parties. The employee should document the SOP deviation on the Deviation Form and submit to the document controller. The document controller will co-ordinate internal review with appropriate members of BaCT according to the SOP involved. The form will be used by the relevant vendor employee to document and determine the risks the SOP deviation present to BaCT and any necessary action required. The completed form will be kept in the SOP Master File, with a copy provided to the specific clinical trial Trial Master File (TMF) where necessary Unplanned SOP Deviation Where a deviation to an SOP is detected, the employee should fill in the Deviation Form stating the SOP Deviation, the reason for the deviation and action taken. The form should be submitted to the document controller to co-ordinate review and risk assessment by the appropriate members of BaCT according to the SOP involved. The form will be used to document the impact of the deviation and determine any corrective or preventative action required. The completed form will be kept in the SOP Master File with a copy provided to the specific clinical trial Trial Master File (where necessary) Periodic Review of SOP Deviations It is recommended that the document controller present a listing of SOP deviations to the BP & O Manager (or delegate) quarterly. However, where the deviation is considered significant by the employee involved in the review of the deviation, the Director of DCM should be notified promptly. Reasons for non-compliance should be considered and the need for training or revisions to the BaCT SOP considered. Where it is decided the SOP should be revised, the document controller will initiate the review process ensure a DRAF is completed. 6.0 DOCUMENT VERSION CONTROL Document version control will be managed by the BaCT. BaCT_GN_SOP-02_V2.0_; Effective Page 13 of 17

14 7.0 DISSEMINATION AND IMPLEMENTATION This SOP will be disseminated by The Centre for Biostatistics and Clinical Trials (BaCT). Updates will be made available with details of planned dates of implementation. 8.0 REVIEW AND UPDATING This SOP will be reviewed every three years, or whenever there are changes to legislation or working practices that impact upon the content of this document. This SOP may be merged with another SOP if appropriate or removed entirely if it becomes redundant. 9.0 DEFINITIONS Term BaCT ICH GCP Controlled Documents Document Controller Form Template Process PG (Guideline) SOP SOP Draft Effective Date Superseded SOP Obsolete SOP Definition Biostatistics and Clinical Trials. International Conference on Harmonisation of Good Clinical Practice. Documents that are named and versioned that are tracked by BaCT. These include SOPs and forms. The Document Controller is responsible for controlling the numbering, filing, sorting and retrieval of electronically stored or hard copy documentation produced by technical teams, projects or departments in a timely, accurate and efficient manner. Paper or electronic document used to collect information or data. A document with the preferred format where relevant information can be inputted prior to print. Systematic series of actions directed to some task. Process Guide / Guideline Instruction/explanation direction that help ensure correct intended use of a document. Standard Operating Procedure Detailed written instruction to achieve uniformity of the performance of a specific function (GCP1.55) SOP that is currently being written or reviewed, but has not yet gained authorisation. The date which the controlled document (SOP) is implemented as the current BaCT procedure. An SOP version that has been updated i.e. BaCT_SOP-01_V1.0 is superseded by BaCT_SOP-01_V2.0 An SOP that is no longer in use BaCT_GN_SOP-02_V2.0_; Effective Page 14 of 17

15 Term Definition SOP Periodic Review DRAF CRO TMF CSF and ISF A review of the SOP 3 years from the effective date where no change was required BaCT Document Review and Approval form. The form used in BaCT to document reviewing and approving of controlled documents Clinical Research Organisation Trial Master File Central Site File and Investigator Site File 10.0 LEGISLATION/REFERENCES/SUPPORTING DOCUMENTS It is important to ensure all relevant literature, legislation, standards and/or journal articles used to develop your procedure are referenced. This avoids plagiarism and offences relevant to copyright laws. Peter Mac recommends the Harvard Reference Style that is located on line.e.g. The University of Melbourne Library AMENDMENT HISTORY Version Date Amended by Details of amendment 12.0 APPENDICES Appendix 1: Version Control New Protocol Appendix 2: Version Control Protocol Amendment BaCT_GN_SOP-02_V2.0_; Effective Page 15 of 17

16 Appendix 1: Version Control New Protocol CLINICAL TRIAL PROTOCOLS Final For Approval of first release Final for Submission Development of first release new document START Example - Study XXX Protocol v 0.1_21 Jan 2017_Draft Example - Study XXX Protocol v 0.1.1_02 Feb 2017_Draft Example - Study XXX Protocol v 0.1.2_10 Feb 2017_Draft Example - Study XXX Protocol v 0.1.2_14 Feb 2017_Final HREC approved? yes Study XXX Protocol v 1.0_14 Feb 2017_Final Approved FINISH HREC approves the Protocol and versions is as final approved The version n. becomes 1.0 The HREC reports this final approved version in the approval letter no * The DRAFT document can still undergo several revisions and will be afterwards finalised. Start from 0.1 The zero before the number reminds you that this is a draft version Keep adding 0.01 to every next draft version and change the date All the proposed changes have been accepted. The document is ready for Sponsorship and Ethics Committee submission for approval. The submission letter to ethics will mention this version. If the protocol is approvable, ethics will notify the applicant so that the version number can be changed and document returned to ethics with the correct footer amendment before the approval letter issued. If not approved, draft re- enters the development stage with the next sequential draft version and new date i.e. Study XXX Protocol v.0.1.3_18 Feb 2017 Draft (will become final when all changes accepted and ready for resubmission.) BaCT_GN_SOP-02_V2.0_; Effective Page 16 of 17

17 Appendix 2: Version Control Protocol Amendment Start from previous approved version* Assign a subsequent version number that will start with 0.x while in draft START Previous approved version Study XXX Protocol v 1.0_14 Feb 2017_Final Approved * Study XXX Protocol v 0.2_12 March 2017_Draft Major Revision needed? Minor Study XXX Protocol v1.1_14 Feb 2017_ Draft Study XXX Protocol v 0.2.1_13 March 2017_Draft HREC ACKNOWLEDGEMENT Study XXX Protocol v1.1_14 Feb 2017_ Final Approved HREC approved? yes no Study XXX Protocol v2.0_14 March 2017_Final Approved If not approved, draft reenters the revision stage with the next sequential draft version and new date i.e. Study XXX Protocol v.0.2.2_18 Mar 2017 Draft BaCT_GN_SOP-02_V2.0_; Effective Page 17 of 17