Design and Construction of Biocontainment Laboratories Commissioning and Validation Benjamin MABILE Director Global Validation, GSK Biologicals
GSK Biologicals Context - Vaccines Key elements of the Validation cycle Definitions How to combine cgmp & Biosafety in the context of Vaccines Manufacture?
GSK Biologicals Vaccines Manufacture Mammalian & Insect cells, Virus, Bacteria. BL -1 to BL-3 Worldwide registration, under cgmp regulations FDA 21 CFR Part 600: «All rooms and work area where products are manufactured or stored shall be kept orderly, clean, free of dirt,.precautions shall be taken to avoid clogging and backsiphonage of drainage systems. Precautions shall be taken to exclude extraneous infectious agents from manufacturing areas. Ventilation system shall be arranged to prevent dissemination of microorganisms method of operations must ensure destruction of contaminating microorganisms», and other regulations. GSK Bio has integrated Biocontainment in all GMP activities, including validation, for product Purity, Efficacy and Safety
Key elements of the Validation cycle Definitions URB - BOD VMP URS DQ File Consistency LOTS PQ Qualification Handover Construction Handover IQ-OQ COMMISSIONING FAT SAT
User requirements Brief Basis of Design Manufacturing process description Organisms BL classification Basic needs for Clean utilities Segregation requirements Preliminary layout for Material Personnel Product flows
Validation Master Plan A high-level document, defining the validation approach and scope, and which establishes an umbrella validation plan for the entire project. Equipment list validation requirements Pre-requisite: Systems Level Impact Assessment Evaluating the impact of the operating, controlling, alarming and failure conditions of a system on the quality of a product The objective is to provide a rationale for classifying all systems into Direct Impact, Indirect Impact or No Impact systems on the product quality. 7 questions: Product contact Produce an excipient / ingredient Used in cleaning & disinfection Preserves product status Generates data for batch release Process control system Biocontainment Results define the level of validation to be applied
Commissioning IQ OQ Includes all static inspections and dynamic tests that verify that the system & equipment are conform to URS, functional and technical specifications. Is the documented verification that all aspects of a facility, utility or equipment adhere to approved specifications (e.g. construction materials), and are correctly installed. (P&ID, drawings, Tech. Data sheets, Calibration, ) Is the documented verification that all aspects of a facility, utility or equipment operate as intended, meeting pre-determinned acceptance criteria. (instruments calibration, functional testing, )
Performance Qualification Is the documented verification that all aspects of a facility, utility or equipment perform as intended, meeting pre-determinned acceptance criteria. (consecutive test runs following operating method, including worst case approach)
How to combine GMP & Biosafety? cgmp practices represent the highest level of assurance for product Safety as well as Environment protection: Facility design: Dedicated AHU Segregation between manufacturing steps (Upstream, downstream, Secondary operations) Material flows EM program Personnel: Flows, incompatible operations Gowning and disinfection Product & Process: Space Closed systems Equipment design
From Validation perspective Cleaning Validation demonstrates targeted organism removal (Swabs) Known effect of cleaning solutions (hot WFI, NaOH 2%, ) Cleaning agents & disinfectants validated against USP/EP microorganisms and targeted Ag. Sterilization Decontamination Total kill approach Same mapping and criteria Change-over Validated (SOP, Swabs) Periodic monitoring Fogging (VHP) Large volumes containment, emergency procedures Training & hygiene programs Supervision
References ISPE Baseline Guide Vol 5 FDA 21 CFR Eudralex WHO Biosafety Guidelines