Presented by Rosemarie Bell 24 April 2014

Transcription

1 Global Good Manufacturing Practice A Comparability Study to Link Good Manufacturing Practice Standards for World Wide Compliance Within the Cellular Therapy Industry Presented by Rosemarie Bell 24 April 2014

2 Overview Importance of GMP Standards Studied Standard Comparisons Common Points Main Differences Stumbling Points Other Considerations Wish List QIMR Berghofer Medical Research Institute 2

3 Importance of GMP

4 In a nutshell. Safety to Patient Safety of Product Consistency Continuous Improvement QIMR Berghofer Medical Research Institute 4

5 Different Standards Reviewed QIMR Berghofer Medical Research Institute 5

6 Different Standards Standards/ Codes/ Guidelines Reviewed So Far Pic/s Guide to GMP Australian Code of Good Manufacturing Practice- Human Blood and Blood Components, Human Tissues and Human Cellular Therapy Trials Therapeutic Goods Administration (TGA) Australian Regulatory Guidelines for Biologicals (TGA) Unapproved Therapeutic Goods TGA In Vitro Diagnostic Medical Devices TGA Standards/ Codes/ Guidelines under Review Ongoing International Conference on Harmonization Guidelines (ICH) European Medicines Agency (EMEA) Guidelines Committee for Proprietary Medicinal Product (CPMP) Federal Drug Administration (FDA) Guidelines Clinical Trial Handbook TGA References ICH Guidelines EMEA Guidelines QIMR Berghofer Medical Research Institute 6

7 Results

8 LEGEND # Standard QMS Applied ** Based on Annex 13 of the PIC/S Required X Not Required * Optional QIMR Berghofer Medical Research Institute 8

9 Requirement Organisational Structure Management Review Documentation Change Control Document Control Document Storage and Retention/ Confidentiality Good Manufacturing Practice Standards Comparison Performed to Date PIC/S Guide to Good Manufacturing Practice Australian Code of GMP for Blood, Tissues and Human CTPs (TGA) Clinical Trial Handbook/ GCP Guidance /ICH /EMEA Guidelines Standard Australian Regulatory Guidelines for Biologicals Unapproved Therapeutic Goods - TGA In Vitro Diagnostic Medical Devices Quality System Requirements Written accounts of Clinical Trial Products required Written accounts of Clinical Trial Products required # (STD QMS applied) Protocol Protocol # Amendment Amendment # # QIMR Berghofer Medical Research Institute 9

10 Requirement Good Manufacturing Practice Standards Comparison Performed to Date PIC/S Guide to Good Manufacturing Practice Australian Code of GMP for Blood, Tissues and Human CTPs (TGA) Clinical Trial Handbook/ GCP Guidance /ICH /EMEA Guidelines Standard Australian Regulatory Guidelines for Biologicals Unapproved Therapeutic Goods - TGA In Vitro Diagnostic Medical Devices Monitoring Systems Internal Auditable Auditable # Audits Corrective # Actions Customer ** ** # Complaints Annex 13 PICS Recall ** ** # Security # Computer Records # QIMR Berghofer Medical Research Institute 10

11 Requirement Good Manufacturing Practice Standards Comparison Performed to Date PIC/S Guide to Good Manufacturing Practice Australian Code of GMP for Blood, Tissues and Human CTPs (TGA) Clinical Trial Handbook/ GCP Guidance /ICH /EMEA Guidelines Standard Australian Regulatory Guidelines for Biologicals Unapproved Therapeutic Goods - TGA In Vitro Diagnostic Medical Devices Personnel and Training Training # Records Donor Records # Informed Consent # Collection Records # Retrieval Records # Processing # Records Final Product # Storage/Retention and Archiving # QIMR Berghofer Medical Research Institute 11

12 Requirement PIC/S Guide to Good Manufacturing Practice Australian Code of GMP for Blood, Tissues and Human CTPs (TGA) Clinical Trial Handbook/ GCP Guidance /ICH /EMEA Guidelines Standard Australian Regulatory Guidelines for Biologicals Unapproved Therapeutic Goods - TGA In Vitro Diagnostic Medical Devices Buildings and Facilities Environmental ** ** # Control Floors, Walls and ** ** # Ceilings Cleaning ** ** # Goods Receipt ** ** # Storage Areas ** ** # Manufacturing ** ** # Areas Donor Areas ** ** # Despatch ** ** # QIMR Berghofer Medical Research Institute 12

13 Requirement Qualification and Validation Preventative Maintenance Calibration and Validation Refrigeration Equipment Cleaning of Equipment Good Manufacturing Practice Standards Comparison Performed to Date PIC/S Guide to Good Manufacturing Practice Australian Code of GMP for Blood, Tissues and Human CTPs (TGA) Clinical Trial Handbook/ GCP Guidance /with reference to ICH /EMEA Guidelines Equipment Not specifically mentioned put falls under GMP principles statement outlined in Annex 13 of the PIC/S Standard Australian Regulatory Guidelines for Biologicals Unapproved Therapeutic Goods - TGA Not specifically mentioned put falls under GMP principles statement in Annex 13 of the PIC/S In Vitro Diagnostic Medical Devices # # # # QIMR Berghofer Medical Research Institute 13

14 Requirement Good Manufacturing Practice Standards Comparison Performed to Date PIC/S Guide to Good Manufacturing Practice Australian Code of GMP for Blood, Tissues and Human CTPs (TGA) Clinical Trial Handbook/ GCP Guidance /ICH /EMEA Guidelines Standard Australian Regulatory Guidelines for Biologicals Unapproved Therapeutic Goods - TGA In Vitro Diagnostic Medical Devices Control of Material Suppliers # Contractors Contract Contract # research organisations research organisations Reagents # Collection collection # Packs kits Labels ** ** # In process # and critical material Non conforming Material # QIMR Berghofer Medical Research Institute 14

15 Requirement Good Manufacturing Practice Standards Comparison Performed to Date Standard PIC/S Guide to Australian Good Regulatory Manufacturing Guidelines for Practice Biologicals Australian Code of GMP for Blood, Tissues and Human CTPs (TGA) Clinical Trial Handbook/ GCP Guidance /ICH /EMEA Guidelines Unapproved Therapeutic Goods - TGA In Vitro Diagnostic Medical Devices Donor Selection, Donation and Testing Pre Donation Select Select # donors on suitability donors on suitability Donation # Post Donation # Testing of Donor Samples Not specifically mentioned Not specifically mentioned # Medical Director involvement Process Control Validation Based on GMP principles of the PIC/S Not specifically mentioned Based on GMP principles of the PIC/S Monitoring # Release # QIMR Berghofer Medical Research Institute 15

16 Requirement Good Manufacturing Practice Standards Comparison Performed to Date Standard PIC/S Guide to Australian Unapproved Good Regulatory Therapeutic Manufacturing Guidelines for Goods - TGA Practice Biologicals Australian Code of GMP for Blood, Tissues and Human CTPs (TGA) Clinical Trial Handbook/ GCP Guidance /ICH /EMEA Guidelines In Vitro Diagnostic Medical Devices Storage Labelling # Quarantine Not specifically mentioned Not specifically mentioned # Discard Not specifically mentioned Not specifically mentioned Packaging Labelling # Records # # QIMR Berghofer Medical Research Institute 16

17 Requirement Transport Procedure Release Procedures Adverse Events Procedures HREC Committee Master Files PIC/S Guide to Good Manufacturing Practice Good Manufacturing Practice Standards Comparison Performed to Date Standard Australian Code of Clinical Trial Australian GMP for Blood, Handbook/ GCP Regulatory Tissues and Human Guidance /ICH Guidelines for CTPs (TGA) /EMEA Guidelines Biologicals Unapproved Therapeutic Goods - TGA In Vitro Diagnostic Medical Devices Transport # Release Documentation Release criteria Documentation # requirements required as well requirements and PIC/S Annex and PIC/S Annex # Site Master File Technical Master File Other Considerations Trial Master File Technical Master File under GMP Trial Master File TMF as part of QMS STD the detail is determined by the Class of IVD. Not mentioned QIMR Berghofer Medical Research Institute 17

18 Requirement Investigator Brochure Deviation from Statistical Plan Reference to other Codes / Standards Good Manufacturing Practice Standards Comparison Performed to Date PIC/S Guide to Good Manufacturing Practice Australian Code of GMP for Blood, Tissues and Human CTPs (TGA) Council of Europe Guidelines for the Selection of Donors Clinical Trial Handbook/ GCP Guidance /ICH /EMEA Guidelines Standard Australian Regulatory Guidelines for Biologicals Unapproved Therapeutic Goods - TGA In Vitro Diagnostic Medical Devices Other Considerations x X Exempt if not x included on x ARTG under CTN, CTX scheme x X X x x Reference to ISO, ICH, EMEA Annex 13 of Stds PIC/s CPMP/ICH/1 35/95 OSP 14155, Reference to Annex 13 of the PIC/S Therapeutic Goods Act 1989, Therapeutic Goods (Medical Devices) Regulations 2002 ISO ISO Designed to reflect the PIC/S QIMR Berghofer Medical Research Institute 18

19 Requirement Other Considerations PIC/S Guide to Good Manufacturing Practice Good Manufacturing Practice Standards Comparison Performed to Date Standard Australian Code Clinical Trial Australian of GMP for Blood, Handbook/ GCP Regulatory Tissues and Guidance /ICH Guidelines for Human CTPs /EMEA Guidelines Biologicals (TGA) Other Considerations CTN / CTX scheme allows non ARTG registered goods to be supplied to the public as part of Clinical Trial. Refers to CTN and CTX Schemes for Clinical Trials Generally based on a risk management approach Specific criteria for products fall under this Code Covers Infectious Disease screening in more detail Covers donor evaluation in more detail. Unapproved Therapeutic Goods - TGA CTN/CTX scheme allows non ARTG registered goods to be supplied to the public as part of a Clinical Trial Special Access Schemes In Vitro Diagnostic Medical Devices IVD Medical Devices are classified as Class 1,2,3,4 pending on the health risk to the public. Conformity Assessment includes a QMS and design, manufacturing, risk analysis, clinical evidence and ongoing monitoring documentation. QIMR Berghofer Medical Research Institute 19

20 Still Going With FDA Guidelines EMEA Guidelines ICH Guidelines Plus other guidelines The list is endless QIMR Berghofer Medical Research Institute 20

21 Common Points

22 Established Quality Management System Traceability Emphasis on patient and product safety BUT Can be open to interpretation QIMR Berghofer Medical Research Institute 22

23 Main Differences

24 Dependant on product type or clinical trial phase. Infectious Disease Screening Requirements (IDS either side of collection/ 180 day follow up for HBV, NAT ) Process Validation Requirements Risk Management QIMR Berghofer Medical Research Institute 24

25 Stumbling Blocks

26 Requirements to conduct Clinical Trials from Phase I differ between countries Release criteria may be different IDS may need to be performed by licensed Laboratories (i.e. TGA licensed) Validation of process prior to commencement of manufacture differs between manufactured product and clinical trial QIMR Berghofer Medical Research Institute 26

27 Obtaining sponsorship to manufacture Time taken to implement Standard and acquire licence - at least 1-2 years Cost factor- can be prohibitive starts at $100k + QIMR Berghofer Medical Research Institute 27

28 Other Considerations

29 Risk Management Perception of risk may differ between groups Access to unapproved biologics different requirements/legislations between countries QIMR Berghofer Medical Research Institute 29

30 Wish List

31 To achieve a global harmonization standard that is easy to understand, easy to follow, providing a progressive approach to achieving GMP compliance, while allowing room for continuous improvement. Recognition for Companies licensed by equivalent Standards. QIMR Berghofer Medical Research Institute 31

32 While there are differences between the Standards, GMP Standards are similar and a robust global Standard harmonisation is achievable if all have one common goal product safely produced in accordance with standardised good manufacturing practice. QIMR Berghofer Medical Research Institute 32

33 Thank you