Baxter New Filling Complex. May 2013 Geoffrey Pot PMO & Operational Excellence Manager

Transcription

1 Baxter New Filling Complex May 2013 Geoffrey Pot PMO & Operational Excellence Manager

2 Agenda Project Description Building Filling area Washing machine Depyrogenisation tunnel Filling line Isolator Paletizing robot Conclusion 2

3 Agenda Project Description Building Filling area Washing machine Depyrogenisation tunnel Filling line Isolator Paletizing robot Conclusion 3

4 Manufacturing sites Lessines, Belgium [IG purification, Fill and Finish] Vienna, Austria [Fractionation] Los Angeles, [Fractionation] Rieti, Italy [Fractionation] 4

5 Project Description Scope Upgrade the Gammagard Liquid/Kiovig filling capabilities at the Lessines plant to ensure that the product is filled under state-of-the-art conditions and provide adequate back-up capacity: Significantly increase the robustness of aseptic processing of one of the most important product for the Company using the latest technologies (Isolator) in order to respect current and future cgmp requirements and to face the current forecast for Gammagard Liquid/Kiovig. 5

6 Project Description Key assumptions Complete new Filling Complex with Filling line and Set-up equipments Isolator technology (new for Lessines plant) Lean manufacturing Compliance target 2030 Multi-format glass vials ( ml) Production in campaign (~ up to 5 batches) Electronic Batch Management 6

7 Project Description Overall Timeline Jan 2009 May 2009 Conceptual design study July 2009 CPA Approval Sep 2009 Nov 2010 Equipment Construction Jan 2010 Dec 2010 Building Construction Jan 2011 Feb 2012 Building Finalisation Mar 2011 Jan 2013 Equipment Validation Feb 2013 Oct 2013 PQ & stability studies July 2013 FDA submission Jan 2014 Routine Manufacturing 7

8 Agenda Project Description Building Filling area Washing machine Depyrogenisation tunnel Filling line Isolator Paletizing robot Conclusion 8

9 Building Ground floor Surface:1800 m² Filling Line under isolator Set Up areas with equipment Maintenance: tool shop, spare parts and offices Cold Room & production office First floor Black & Clean Utilities Electrical Supply HVAC Units Gowning room Second floor Offices 9

10 Building - Flow Segregated Material and Personnel flow Filling Area Set-up Area People Material 10

11 Building - Flow Segregated Material and Personnel flow Filling Area Set-up Area People Material 11

12 Building - Flow Segregated Material and Personnel flow Filling Area Set-up Area People Material 12

13 Building - Flow Segregated Material and Personnel flow Filling Area Set-up Area People Material 13

14 Building - Flow Segregated cleaned an uncleaned material flow Filling Area Set-up Area Uncleaned Mobile Tank Cleaned Mobile Tank Uncleaned Material Cleaned Material 14

15 Building - Flow Segregated cleaned an uncleaned material flow Filling Area Set-up Area Uncleaned Mobile Tank Cleaned Mobile Tank Uncleaned Material Cleaned Material 15

16 Building - Flow Segregated cleaned an uncleaned material flow Filling Area Set-up Area Uncleaned Mobile Tank Cleaned Mobile Tank Uncleaned Material Cleaned Material 16

17 Building - Classification Building - classification Grade D Grade C Grade A 17

18 Building - Classification Building - classification Grade D Grade C Grade A 18

19 Building - Classification Building - classification Grade D Grade C Grade A 19

20 Building - Classification Building - classification Grade D Grade C Grade A 20

21 Agenda Project Description Building Filling area Washing machine Depyrogenisation tunnel Filling line Isolator Paletizing robot Conclusion 21

22 Filling area Vial washing machine Depyrogenation tunnel Filling isolator Capping isolator Coding station Paletizing unit Vials are manually loaded in the vial washing machine. The remaining operations (from vial washing to paletizing) occurs in a fully automated way. The whole filling operations are further controlled by EBM (Electronic Batch Management), avoiding any human error during filling operations. 22

23 Washing machine 23

24 Washing machine Characteristics Supplier Optima 5505 vials washed / hour (10 ml) 1200 vials washed / hour (300 ml) 8 stations for cleaning and drying Challenges Mutliformat - 2 kind of spare parts for all formats Qualification issue with a single WFI pressure while the vials format are strongly different Timing: Q Q

25 Depyrogenisation tunnel 25

26 Depyrogenisation tunnel Characteristics Supplier Optima Inlet zone for preheating Hot zone: Uniformity of temperature with IR and depyrogenation at 315 C 2 cold zones (22 C and 12 C) to prevent thermal shock Each format has a specific belt speed Challenges Meet filter integrity requirements: Protection filters vs temperature changes in start and end of production Timing: Q Q

27 Filling Line 27

28 Filling Line Characteristics Supplier Optima All vials are weighted: Filling 100% IPC Maximum speed: 100 vials/min Coding station to ensure a complete traceability of the vial Challenges Multi-format : ml 2 stopper sizes : mm Timing: Q Q

29 29 Filling Line - Needles Filling steps: 1. Empty vials are weighted 2. Vials are filled in time pressure by 4 filling needles (95% - 99,5% of setpoint) 3. Vials are weighted and the remaining volume is added (5% to 0,5% of setpoint) 4. Vials are weighted for a third time to allow release This manner of filling has two main advantages: Better filling accuracy and precision No risk for lower out of volume vials

30 30 Filling Line - Needles Filling of a 100ml vial is very precise: Set point : 104,30 g Average: 104,32 g Std Deviation : 0,08 g Accuracy was evaluated by QC >99% (average weight was 104,23 g) Note: First and last 30 vials not taken into account

31 31 Filling Line - Stoppering The stopper processor machine was manufactured at ATEC. Empty vessel is cleaned in place (CIP). After this cleaning, stoppers are loaded into the vessel and are Sterilized in Place (SIP). This happens in the set-up area, in parallel to the line set-up and takes 8 hours. One vessel can contain up to stoppers of 32mm or stoppers of 20mm, enough to fill 5 different Gammagard Liquid/Kiovig batches in one campaign.

32 32 Filling Line Coding station The datamatrix was installed to be able to have a full traceabiltiy of the batch. Therefore after capping, every cap is printed by an UV printer. The datamatrix contains the batch number, vial number and the information if the vial is conform or not. Vials are online checked with a camera and non-conform vials will be rejected. In case of microbial excursion, technical issue, or other manufacturing issue, vials good be segregated based on their filling sequence.

33 33 Isolator For the isolator design it was decided to initiate mock-up studies (model scale 1:1) Step 1 : at supplier site => for first mechanical concept/design Step 2 : at customer site => for mechanical concept/design optimization and training

34 34 Isolator The mock-up studies were used to: determine the size; use 1:1 drawings of all machines in the isolator simulate loading (tools, agar, probes ) determine positions for particle counting and viable air monitoring determine position for gloves carefully define interfaces for HVAC, media, computer-systems, supplier of filling-machine Simulate all operations in the isolator This helped to have the best design for manipulation and to define the EM testing places.

35 Isolator Characteristics Suplier SKAN Pressure cascade - 19 C +/-3 C - Humidity control (<30%) Laminar flow (0,36 m/s - 0,54 m/s) Hydrogen Peroxyde decontamination (Cycle VHP 2,5h - 35%H202) Challenges Time of decontamination Design : Ergonomy Decontamination of all surfaces Timing: Q Q

36 Palatizing robot 37

37 Paletizing robot Characteristics Supplier Sybermat Maximum speed 100 vials/min 2 robots Staublï (TX90 & TX 200L) Small robot : placing vials in the racks Big robot : placing racks on the pallets Challenges Incubation racks Old racks (manual and automatic use) Timing: Q Q

38 39 Agenda Project Description Building Filling area Washing machine Depyrogenisation tunnel Filling line Isolator Paletizing robot Conclusion

39 Conclusion A new filling complex was implemented and validated at Baxter BioScience Lessines within 4 years. This building has multiple benefits from a manufacturing and quality standpoint: 1. State of the art filling equipment reducing significantly the microbial excursions 2. Improved filling precision allowing a financial saving of multiple Million dollars 3. First In First Out: In case of investigation/issues every single vial can be fully traced Video 40

40 41 Acknowledgment Xavier Baert Engineering Manager Baxter BioSciene Lessines Henri Jacquemin Engineering Manager Baxter BioSciene Lessines Gareth Crothers Quality Engineering Manager Baxter BioSciene Lessines Antoine Damiens Aseptic Processing Manager Baxter BioSciene Lessines Karine Boscher Project Manager Baxter BioScience Lessines