Jingwang Zheng_EN 2011.10上海ISPE

ISPE-CCPIE CHINA CONFERENCE 2011 October 25-28 2011 Shanghai 1 Systematic practise within sterile core area and compliance Jinwang Zheng Shanghai Tofflon Science and Technology Co., Ltd. ISPE-CCPIE CHINA CONFERENCE 2011 1. Risk identification of traditional freeze- drying production line 2. Classification of freeze-drying auto loading and unloading system 3. Summary Content ISPE-CCPIE CHINA CONFERENCE 2011 3 Aseptically Processed Products （ISPE Baseline） ISPE-CCPIE CHINA CONFERENCE 2011 4 Nested Manufacturing Zones （ISPE Baseline) ISPE-CCPIE CHINA CONFERENCE 2011 Traditional Stopper Transport ISPE-CCPIE CHINA CONFERENCE 2011 Manual Unscrambling ISPE-CCPIE CHINA CONFERENCE 2011 Manual Loading/Unloaing ISPE-CCPIE CHINA CONFERENCE 2011 • Operator puts the trays with vials into the freeze dryer or the trolley manually, then put the trays on the shelves of the freeze dryer, the open angle of the freeze dryer’s door is wide, the whole chamber is exposed in the external environment. • During the transport of the vials, the operator is very close to vials. People is the main contamination source to the sterile product . It is very difficult to verification the sterile protection of the process. • The contamination risk is very high when transfer the vials into the freeze dryer after filling as well as take the vails to the capping machine after freeze dried。 Lyophilization Risk ISPE-CCPIE CHINA CONFERENCE 2011 A major pharmaceutical company has determined the average percentage of risk distribution of each aseptic process stage, base on media fill results, as follows:  Aseptic Compounding Risk 10%  Aseptic Set-up Risk 10%  Aseptic Filling Risk 50%  Lyophilization Risk 30% • Risk Source :Personnel A gowned operator may release as many as 10.000CFU/hour。 • Risk Route: Airborne。 Freeze-dried Product Manual Loading and Unloading ISPE 2007 Tampa Conference ISPE-CCPIE CHINA CONFERENCE 2011 1. Small-bore , high speed filling with low risk ,except the vials is easy to fall。 2. Big-bore ,low speed filling with high risk。 3. Isolated transport to reduce the risk。 4. It is high risk when the product is exposed in the external environment ,even the product under the grade A。 5. Isolation and automation can reduce the risk。 6. Operate the aseptic equipment manually need high skills and it is high risk。 Risk Analysis of Traditional Freeze Drying Production Line ISPE-CCPIE CHINA CONFERENCE 2011 1. Risk Identification of traditional freeze- drying production line 2. Classification of freeze-drying auto loading and unloading system 3. Summary Content ISPE-CCPIE CHINA CONFERENCE 2011 Washer Depyro Tunnel Filling Automatic Loading and Unloading Freeze Drying Capping Outside Washer Inspect Packing Stopper Raw material Dispensing Compounding Water water equipment Steam Vials HVAC Systematically Designed Production Line ISPE-CCPIE CHINA CONFERENCE 2011 Definition of Systematically Designed Production Line • Systematic Production Line : The whole freeze drying production line is automatic, isolated and process continued。 • Automation ：in the core area, all the operation is automatic to reduce the human intervention。 • Isolation ： the product and the operator will be separated by using the barriers or isolator technology to protect both the product and operator。 • Process continue: all the equipments , process of the production line are continued。 ISPE-CCPIE CHINA CONFERENCE 2011 • Reduce the human interventions in the grade A area Reduction in bio-burden and the probability of contamination Greater assurance of product sterility Reduce operating cost • Protection of operators Potent products • Verified ,Good Repeatability • Reduce the air conditioning cost • Achieved unmanned operation, improved the practical applicability The Advantage of the Systematically Designed Production Line ISPE-CCPIE CHINA CONFERENCE 2011 • Higher reliability of equipments required。 • Higher cost of initial facility。 • The validation is complicated(Software validation and process validation)。 • The more advanced production technology should be adopted, more reliable quality monitoring and quality monitoring device should be adopted during the whole production process。 Disadvantage of Systematically Designed Production Line ISPE-CCPIE CHINA CONFERENCE 2011 • Flexible systems • Fixed systems • Mixed systems The Classification of The Auto loading and Unloading System ISPE-CCPIE CHINA CONFERENCE 2011 Flexible Systems • Consists of IS, AGV and OS 。 • one shelf one time for finishing the loading and unloading • Suitable for 2 sets or more freeze dryers。 • Unilateral loading and unloading or one side loading while the other side is unloading。 • Suitable for LAF ,RABS 。 • The space between the lyophilizer can be more compact。 • The door of the lyophilizer is in the clean room。 ISPE-CCPIE CHINA CONFERENCE 2011 Flexible Systems Sketch Map ISPE-CCPIE CHINA CONFERENCE 2011 Automatic Guided Vehicle ISPE-CCPIE CHINA CONFERENCE 2011 Infeed Systems(IS) ISPE-CCPIE CHINA CONFERENCE 2011 Outfeed System（OS) ISPE-CCPIE CHINA CONFERENCE 2011 Fixed Systems • As we called “Row by Row” • loading and unloading row by row 。 • Suitable for one or two lyophilizers 。 • Suitable for toxic product 。 • Suitable for low temperature loading process 。 • Suitable for LAF、RABS、cRABS、ISOLATOR。 • The chamber door is in the mechanical room , while the pizza door is in the clean room。 ISPE-CCPIE CHINA CONFERENCE 2011 Fixed Systems Sketch Map ISPE-CCPIE CHINA CONFERENCE 2011 Fixed Systems ISPE-CCPIE CHINA CONFERENCE 2011 Fixed Systems Workshop Layout ISPE-CCPIE CHINA CONFERENCE 2011 Picture of Fixed Systems with cRABS ISPE-CCPIE CHINA CONFERENCE 2011 Picture of Fixed Systems with cRABS ISPE-CCPIE CHINA CONFERENCE 2011 Picture of Fixed Systems with RABS ISPE-CCPIE CHINA CONFERENCE 2011 Inside Picture of RABS ISPE-CCPIE CHINA CONFERENCE 2011 Picture of Fixed Systems with cRABS ISPE-CCPIE CHINA CONFERENCE 2011 Mixed Systems • Two separated clean room , one is for loading ,the other is for unloading。 • Front side loading , back side unloading 。 • The lyophilizer must be designed with two floor。 • Fixed loading ,flexible unloading 。 • Flexible loading ,flexible unloading 。 ISPE-CCPIE CHINA CONFERENCE 2011 Mixed System Workshop Sketch Map ISPE-CCPIE CHINA CONFERENCE 2011 Picture of Second Floor ISPE-CCPIE CHINA CONFERENCE 2011 Picture of Ground Floor ISPE-CCPIE CHINA CONFERENCE 2011 1. Numbers of freeze dryers to be operated 2. The speed requirement of production line (filling ,capping) 3. The size of vials 4. The size of clean room 5. Stability of the product 6. Clean room classification 7. The length of the freeze drying cycle 8. The space between the freeze dryer and the filling / capping machine 9. From single side or pass-through for loading and unloading •2009-6-16 The Factor for Choosing The Fixed or Flexible Auto loading and Unloading System ISPE-CCPIE CHINA CONFERENCE 2011 1. Risk Identification of traditional freeze- drying production line 2. Classification of freeze-drying auto loading and unloading system 3. Summary Content ISPE-CCPIE CHINA CONFERENCE 2011 Summary: The Trends of Lyophilizer Systems • Automation Lyophilizer system’s integration is becoming higher and higher. As the manual operation resulted in a number of risks and uncertainties, the future operation will be more automated, reducing manual operation during the production process , thereby reducing the associated risks。 • Isolation Loading : primarily to meet the requirements of GMP Unloading: Primarily concerns the safety of operator and meet the requirements of GMP 。 • The configuration of pass-through lyophilizer Can improve overall performance, especially shorten cycles of freeze- drying, freeze dryer with two or more connected to the filling line。 • Loading and unloading without Trays In order to avoid complicated washing, sterilization and transport for trays。 • Lyophilizer with two floors design The mechnical area and condenser are located below the chamber, in order to create a path leading to the maintenance area withour requirement of cleanliness classification。 ISPE-CCPIE CHINA CONFERENCE 2011 Many thanks! 38