Document Revision History Version Effective date Changes 01 New SOP Writing, Reviewing and Layout of Standard Operating Procedures
1.0 Scope This Standard Operating Procedure (SOP) has been written in order to conduct clinical studies according to the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use Good Clinical Practice (ICH-GCP) guidelines. This SOP describes in particular the procedure for writing and reviewing as well as the layout of SOPs. This procedure applies to all SOPs of the Clinical Trial Offices (CTOs) of the European Group for Blood and Marrow Transplantation. 2.0 Abbreviations CTO GCP ICH SF SOP WI Clinical Trial Office Good Clinical Practice International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use Standard Form Standard Operating Procedure Working Instruction 3.0 Responsibilities Director Clinical Trials The director must ensure that every employee is trained to use and adheres to this SOP to produce new or revised SOPs. It is the judgement of the director if an amendment of a SOP is deemed necessary after working page 2 of 8
procedures have been changed or whether an amendment is mandated by a change in legislation. CTO personnel Each employee must have knowledge of and adhere to this SOP. 4.0 Introduction To perform clinical research in multiple hospitals, cities, or countries it is imperative that working methods are standardized in order to ensure that all are adhering to set standards and work practices are comparable across the organisation.. To standardize procedures across the different locations of the EBMT in Europe the need for written SOPs is evident. 5.0 Procedure SOPs are very carefully written, but for readability purposes they are written in the male context. Anywhere he or his is typed, the equivalent she or her is also meant. 5.1 Format All SOPs have an equal layout. For an example of the standard layout: see appendix A (SF 1.1 Layout of SOPs template). 5.1.1 Font type Times New Roman page 3 of 8
5.1.2 Font size - (sub)sectiontitles: bold 14 point - Text: plain 12 point - Header/footer: plain 10 point 5.1.3 Line spacing Line spacing is 1.5 lines. Two lines between sections and one line between subsections. 5.1.4 Format of dates Format of all dates is dd-mm-yyyy. 5.1.5 Page numbering Page numbering starts on the front page of SOPs and the number is positioned at the bottom right of the footer. 5.2 Section order All SOPs have the same order of sections: 1.0 Scope, 2.0 Abbreviations, 3.0 Responsibilities, 4.0 Introduction, 5.0 Procedure, 6.0 References, and 7.0 Appendices. Each section can be divided in subsections, sub- subsections and subsub- subsections (e.g. 5.1, 5.2.1 or 5.2.1.1). page 4 of 8
5.3 Author The author of a new or revised SOP is an employee with practical or sound theoretical knowledge on the subject of the SOP. He produces a draft SOP with the word DRAFT in the title, on the front page, and in the header before the SOP xxx.xx number. 5.4 Numbering of SOPs and SFs The SOPs are numbered and the numbers are assigned in Leiden. The numbers 001-099 are reserved for general SOPs, 101-199 for Quality Control, 201-299 for Information Technology and 301-399 for Clinical Trial Management. Standard forms (SFs) that are mentioned in SOPs gain sequential digits added to the SOP number (SF sop number.sequential number). E.g. SF 211.1 is the first standardized form of SOP 211. The SFs are in the appendix of each SOP with the word Sample as a watermark. This word is deleted if SFs are used. SFs must be available on the clinical trials portal, where everybody has access to the most recent version. 5.5 Version control If a new or revised SOP is being written, it has the word DRAFT in the title. When the review process has been completed this word disappears. If the SOP is being revised, the word is added to the title again. Example: DRAFT SOP 001.01 SOP 001.01 DRAFT SOP 001.02 SOP 001.02 DRA... etc. If an amended SOP version is issued the main number remains the same, the version number is augmented by one. (For example) SOP page 5 of 8
001.01 becomes SOP 001.02, SOP 102.23 becomes SOP 102.24. Each amended SOP version SOP must have the main changes from the prior version briefly noted on the front page of the SOP. It will have the differences with the prior version highlighted. Current CTO staff must read the SOP before its effective date and sign their SOP Reading Log (SF 1.2). They will also put their initials on the version with highlighted differences. As soon as all personnel in a location have read the changes, the Leiden office shall be notified and the final version (without highlights) is distributed to be kept in the CTO s SOP binder. 5.6 SOP training If an SOP is new or revised all personnel must receive proper training and document this on their SOP Training Log (SF 1.4) before its effective date and before he actually performs the tasks described in the SOP. New employees joining the CTOs must read the SOP and must be trained against it. For more detailed information about training see SOP 002.xx Training. If an SOP does not have a direct application to the job description of any CTO personnel, then that person will be required to read it for information purposes only. 5.7 Reviewer The reviewer of a DRAFT SOP is generally a co-worker of the author with more or less the same level of expertise. He reads and reviews the DRAFT SOP and provides the author with comments, adjustments, additions or deletions. After discussion and/or implementation of the issues the reviewer starts the review process again until he is satisfied with the outcome. Next, the two parenthesis around RED INK ORIGINAL in the footer are removed and the DRAFT SOP is ready for approval. page 6 of 8
5.8 SOP review Each SOP will be reviewed periodically at least once every two years. If change is mandatory due to any change in legislation or if working methods do change before the two year limit, a new SOP is compulsory within 3 months after change in legislation or change of the procedure described in the SOP. The review date is in that case automatically reset to two years thereafter. 5.9 Approval The director of clinical trials operations of the EBMT or his designee then reads and reviews the DRAFT SOP. After completing this process the word DRAFT is omitted from the title, front page, and header. The SOP is subsequently printed and signed, first by the author and then by the approver. 5.10 SOP availability The signed originals of all SOPs are kept centrally in a separate binder in Leiden. Each (new) SOP is distributed to the clinical trials office (CTO) of the EBMT. There must be (at least) one SOP binder per CTO. The originals of the SOPs are digitally saved as a PDF file and kept in a separate folder and are made available on the prospective trials portal. page 7 of 8
5.11 Archiving If a newer version of an SOP becomes available or an SOP becomes obsolete, the original version of an old/obsolete SOP must be archived in a separate binder in Leiden. 5.12 Work Instructions Working Instructions (WI) can be written to describe in more detail how a specific task must be executed. They can also consist of protocol specific procedures. 6.0 References - ICH Harmonised Tripartite Guideline for Good Clinical Practice 1996 - EU Clinical Trials Directives2001/20/EC and 2004/28/EC - SOP 002.xx Training 7.0 Appendices Appendix A: SF 1.1 Layout of SOPs template Appendix B: SF 1.2 SOP Reading Log Appendix C: SF 1.3 SOP Training Log page 8 of 8