Good Laboratory Practice Study plan Standard operating procedures Conduct and Reporting Dr. Wolf Burchard Bulling Federal Institute for Risk Assessment Thielallee 88-92  D-14195 Berlin Tel. +49 30-8412-3936  Fax +49 30-8412-3970 w.bulling@bfr.bund.de  www.bfr.bund.de

Course of GLP Study (example) Sponsor Request Approval TF Management SD appointment Agreement Archive Draft Study Plan Sponsor Study Director Preparation Approval QA Statement SD signature Study completion date Final report Quality Assurance GLP compliance study conduct Study Plan QA verification SD Signature Study initiation date Signatures Author, TFM QA verification SOPs

Study Plan Study plan means a document which defines the objectives and experimental design for the conduct of the study, and includes any amendments. (Definition OECD Principles) The GLP regulations require that each study have an approved study plan and specify the information that must be in the study plan in relation to the study conducted Study plans should conform to the GLP requirements Study plan is a vital document for the reconstruction of study

Study Plan sponsor agrees with study design management involved regarding personnel, facility and material resources study director responsible for scientific and technical conduct of the study quality assurance for GLP compliance and planning of monitoring activities serve as working tool for technical personnel who actually perform the activities Study plans should be written to address the study objectives and the users needs

Study Plan Study Plans should be Not overcrowded

Study Plan Study Plans should be Easy to follow

Study Plan alterations documented and acknowledged by SD unanticipated anticipated amendment SP + Amend- ment(s) deviation Raw data

Study Plan alterations Study plan amendment means an intended change to the study plan after the study initiation date. foreseen circumstances planned, permanent and deliberate systemic changes usually standardised study plan amendment form dated signature of study director test facility management should also sign study plan amendment in case of change of study director or termination of study maintained with study plan

Study Plan alterations Study plan deviation means an unintended departure from the study plan after the study initiation date. unforeseen circumstances any departure (positive or negative) from approved procedures study director must be informed in a timely manner deviations should be described, explained, acknowledged and dated by the study director maintained with raw data

Standard Operating Procedures (SOP) to avoid unnecessary repetitions in study plans, the routine activities common to a number of studies can be described in SOPs Standard Operating Procedures (SOPs) means documented procedures which describe how to perform tests or activities normally not specified in detail in study plans or test guidelines

Standard Operating Procedures General Format Preparation Authorization Review / Revisions Deviations Coverage of all relevant activities SOP List Distribution and Collection Availability Archiving SOP about

Standard Operating Procedures SOPs should be complete, concise and easy to follow without dispensible information

Study plan and SOPs form a single package Study Plan versus SOP Study plan and SOPs form a single package describing the scenario of the whole study. SOPs Study Plan High Variability Low Variability Study Plan SOPs Studies with high variability demand detailed study plans and less SOPs Standardised Studies demand many, detailed SOPs and shorter study plans

Conduct - Study Director - Role Single point of study control with ultimate responsibility for the overall scientific conduct of the study Coordinating input of management, scientific/technical staff and QAU Request and coordinate resources provided by management (e.g. personnel, equipment and facilities) for the proper conduct of the study Study plan design and approval Overseeing data collection, analysis and reporting Responsible for Final Report, scientific conclusions and compliance with GLP regulations

Conduct - Study Personnel - Role Study personnel should: have knowledge about GLP Principles applicable to their involvement in the study exercise health precautions to minimise risk to themselves and to ensure integrity of the study comply with the instructions given in study plan and appropriate Standard Operating Procedures and report deviations to the study director record raw data promptly , accurately and in compliance with GLP, and are responsible for the quality of their data

Study Personnel – Raw Data record of all study relevant activities (record of data: directly, promptly, accurately, and legibly, no pencil, signed/initialled and dated) corrections of raw data according to the GLP regulations changes in the raw data should: not obscure the previous entry indicate the reason for change signed/initialled and dated Wrong Correct

Final Report Final Report for each study Corrections and additions to a final report should be in form of amendments (justification and signature of SD) Reformating does not constitute a correction, addition or amendment Original Signed and dated by study director to indicate acceptance of responsibility for the validity of data and GLP compliance Reports of PI or scientists involved signed and dated by them QA Statement (specifies type, date and phase of inspections, reports to management), confirm that Final Report reflects the raw data

Final Report – Study Director Statement Reference to GLP Principles Exemptions clearly described General GLP compliance evaluation Not required by most countries Dated signature of Study Director Study Completion Date End of the GLP Study

Thank you for your attention! A N Y Q U E S T I O N S ? Wolf Burchard Bulling