WHAT IS TO BE EXPECTED IN GMP INSPECTION OF CELL & TISSUEBASED THERAPEUTIC (CTT) PRODUCTS Goh Choon Wee Health Products Regulatory Group Health Sciences Authority 19 June 2014 OUTLINE  HEALTH PRODUCTS REGULATION GROUP  CELL & TISSUE-BASED THERAPEUTIC (CTT) PRODUCTS  GMP STANDARD & INSPECTION PROCESS  EXAMPLES OF DEFICIENCIES  SHARING & GROWING Health Products Regulation Group  Medicines Act & Health Products Act  Regulatory framework for health products  295 staff – 17 qualified GMP inspectors 9,800+ 5,300+ 12,000+  CTT Product Definition  Autologous, allogeneic  Medicinal purposes  Exclude organ for transplantation  Exempt whole blood & blood component  Regulate those products  Substantially manipulated (GMP Requirements)  Non-homologous use  Combination products  Licensing controls of CTT products  Product Licence  Manufacturer’s Licence  Clinical Trial Certificate  Supporting the manufacture of CTT products  GMP Certificate for clinical trial products  Review layout of manufacturing premises STATUS UPDATES WHAT IS GMP STANDARD?  Pharmaceutical manufacturers  Products produced and controlled consistently - fit for its intended purpose - meet the Marketing/Clinical Trial Authorization requirements or product specification  Applied throughout product lifecycle Product GMP Complaint Material Recall Process QUALITY SYSTEM Equipment Personnel Premises HVAC Documentation PURPOSE  To promote uniformity in licensing and regulatory decision  Remove trade barriers between countries  Maintenance of high quality standard in development, manufacture and control of medicinal products STRUCTURE  PIC/S GUIDE To GMP For Medicinal Products (Part I)  basic requirements - intermediate/finished products  PIC/S GUIDE To GMP For Medicinal Products (Part II)  basic requirements – active pharmaceutical ingredients  PIC/S Guide To GMP For Medicinal Products (Annexes)  Annex 1  Annex 2  Annex 13  Annex 14  Annex 15 * - sterile medicinal products - biological medicinal substances & products* - investigational medicinal products - products derived from human blood/plasma* - qualification and validation Effective 1 Mar 2014 REVISION IN-PROGRESS  Chapter 3: Premises & Equipment  Chapter 5: Production  Chapter 6: Quality Control  Chapter 7: Outsourced Activities  Chapter 8: Complaints & Product Recall  Annex 15: Qualification & Validation WHAT IS THE GMP INSPECTION PROCESS? PRE-GMP INSPECTION DURING GMP INSPECTION POST-GMP INSPECTION PRE-GMP INSPECTION Application submitted Form inspection team Confirm date & scope Submit Site Master File & CMC DURING GMP INSPECTION Opening meeting Visit Store & HVAC Visit Processing/Lab Area Review Documentation Closing Meeting POST GMP INSPECTION Post inspection letter Submit and review CAPA Seek clarification/further actions required Close-out inspection Issue GMP Certificate KEY AREA OF FOCUS CONTAMINATION WRONG MAT/PROCESS/ PRODUCT QUALITY DETEORIATION LOSS OF TRACEABILITY DEFICIENCIES SHARING & GROWING KEEPING OUR SOCIETY HEALTHY IS OUR COMMON GOAL SUMMARY HPRG & CTT PRODUCTS PIC/S & GMP STANDARD GMP INSPECTION PROCESS KEY FOCUS IN INSPECTION EXAMPLES OF DEFICIENCIES AFTER THOUGHTS ACKNOWLEDGEMENT CTT WORKING GROUP ACKNOWLEDGEMENT GMP INSPECTORATE