My Definition of Deviation

Transcription

1 Development & Operation of a QA System for Deviations from SOPs in a Clinical Cell Therapy Laboratory PACT Webinar July 20, 2006 David H. McKenna, M.D. Clinical Cell Therapy Laboratory Molecular & Cellular Therapeutics University of Minnesota My Definition of Deviation True deviations, adverse reactions, complaints (per FDA), AND ALSO changes from SOPs and notable or noteworthy events.

2 Definitions Deviation: An event 1) that represents a deviation from applicable regulations in this part or from applicable standards or established specifications that relate to the prevention of communicable disease transmission or human cellular or tissue-based product (HCT/P) contamination; or 2) that is an unexpected or unforeseeable event that may relate to the transmission or potential transmission of a communicable disease or may lead to HCT/P contamination. Complaint: Any written, oral, or electronic communication about a distributed HCT/P that alleges: 1) that an HCT/P has transmitted or may have transmitted a communicable disease to the recipient of the HCT/P; or 2) any other problem with an HCT/P relating to the potential for transmission of communicable disease, such as the failure to comply with cgtp. Adverse reaction: A noxious and unintended response to any HCT/P for which there is a reasonable possibility that the HCT/P caused the response -Subpart A General Provisions (Sec ) Definitions (cont.) Notable/Noteworthy Event: An occurrence that may not fit into the previous definitions but still requires attention (medical, technical, etc.), as it may impact on patient and/or product outcome -In-house

3 Nuts and Bolts of a Deviation Management System Functions of the quality program must include: Investigating and documenting HCT/P deviations and trends of HCT/P deviations relating to core cgtp requirements... [Sec (b)(6)] Periodic review and analysis of all deviations, at least once a year (proposed GTPs) Reporting: You must report to FDA an adverse reaction involving a communicable disease if [Sec (a)] You must report HCT/P deviations (relating to the core cgtp requirements) related to a distributed HCT/P for which you performed a manufacturing step if deviation occurred in your facility or another facility under contract, agreement or arrangement [Sec (b)] Document Improve Deviation Management Investigate & Report Track & Trend Correct

4 Deviation Management System Tools Standardized Form User Friendly Database - Microsoft Access Graphs & Tables - Microsoft Access/Excel Reports

5 Why a deviation database? Flexible and powerful means of tracking deviations Identifying recurring and sentinel events Facilitates regulatory compliance Promotes continuous process improvement Deviation Database Design Easy to use Categorization of deviations Product/patient impact scoring Analysis and graphic display Report capabilities Pick-lists, description codes, clients, tech, equipment etc..

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8 Additional Features Security-compliant with FDA regulations (21CFR11) Requires usernames/passwords Access limited to dedicated staff Secured from unauthorized users Reviewed by Operations Manager Audit trails Username, original & added data, date/time of entry Complete tracking of data from initiation to modification to deletion Daily virus scanning Backed-up on server; in fire-proof safe; off-site Nuts and Bolts of a Deviation Management System Functions of the quality program must include: Investigating and documenting HCT/P deviations and trends of HCT/P deviations relating to core cgtp requirements... [Sec (b)(6)] Periodic review and analysis of all deviations, at least once a year (proposed GTPs) Reporting: You must report to FDA an adverse reaction involving a communicable disease if [Sec (a)] You must report HCT/P deviations (relating to the core cgtp requirements) related to a distributed HCT/P for which you performed a manufacturing step if deviation occurred in your facility or another facility under contract, agreement or arrangement [Sec (b)]

9 Document & Investigate Complete deviation form Investigate in real time Determine if need for Corrective Action/Preventative Action (CAPA) Root Cause Analysis/Investigation Investigational Report Reasons for Root Cause Investigation Examples Moderate Severe Risk to Patient Outcome CD34 Selection Failure Cord Blood Product Mix-up Adverse Reactions Engraftment Failure QA System Failures Equipment Monitoring Failure Impact upon Multiple Products/Patients Defective Freezing Bag

10 Investigational Report Description Description of event Data, test results, documents Identification of members of the review committee Patient impact, outcome analysis Review Committee Identify root cause Determine if reportable and to whom Identify corrective plan Corrective Plan Define with timeline Implement Monitor Nuts and Bolts of a Deviation Management System Functions of the quality program must include: Investigating and documenting HCT/P deviations and trends of HCT/P deviations relating to core cgtp requirements... [Sec (b)(6)] Periodic review and analysis of all deviations, at least once a year (proposed GTPs) Reporting: You must report to FDA an adverse reaction involving a communicable disease if [Sec (a)] You must report HCT/P deviations (relating to the core cgtp requirements) related to a distributed HCT/P for which you performed a manufacturing step if deviation occurred in your facility or another facility under contract, agreement or arrangement [Sec (b)]

11 Review & Analysis Quarterly basis Collectively and for each client Formally track/trend by product type, category, patient/product impact, equipment, etc.. Present and discuss with each client

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13 Nuts and Bolts of a Deviation Management System Functions of the quality program must include: Investigating and documenting HCT/P deviations and trends of HCT/P deviations relating to core cgtp requirements... [Sec (b)(6)] Periodic review and analysis of all deviations, at least once a year (proposed GTPs) Reporting: You must report to FDA an adverse reaction involving a communicable disease if [Sec (a)] You must report HCT/P deviations (relating to the core cgtp requirements) related to a distributed HCT/P for which you performed a manufacturing step if deviation occurred in your facility or another facility under contract, agreement or arrangement [Sec (b)]

14 Reporting Sec Focused on Product Contamination Transmission of communicable disease Failure of product function or integrity Final Thoughts Keep system practical, efficient, and dynamic Realize that deviations will occur Complexity of field & human nature Primary goal is quality improvement

15 Acknowledgements Diane Kadidlo Darin Sumstad Jeff McCullough McKenna D, Kadidlo D, Sumstad D, McCullough J. Development and operation of a quality assurance system for deviations from standard operating procedures in a clinical cell therapy laboratory. Cytotherapy 2003; 5(4):