Welcome to my graphical Knowledge summary

1. Welcome to my graphical Knowledge summary Dussex Jean-Charles Via pizzamiglio,9 CH-6833 Vacallo JEAN@bluewin.ch FROM IDEA TO APPLICATION

2. Summary of system actors TQMS-1

3. Presentation in Work breakdown structure style TQMS-1

4. Procedure deviation process according to deviation criticality TQMS-2

5. Process parameter design space TQMS-3

6. Validation workflow TQMS-4

7. Filter dryer Failure Mode Effect Analysis-01 Risk analysis

8. Cause Effect Diagram: sampling sys. no powder transferred Risk analysis

9. Process transfer and Equipment qualification Process transfer Equipment Qual. Some concepts

10. Example of Room layouts and symbols Personnel flow, room pressure and class

11. Factory entrance Personnel flow

12. Class D surrounding area Personnel flow

13. Specific workplace in qualified room Personnel flow

14. Water system 090320 Factory planning-P26

15. Chromatography system pre-layout Pre-URS discussion for project definition

16. Chromatography system Project pre-layout phase 1 Pre-URS discussion for project definition

17. Drawing symbols (CAD) P and ID symbols 110303

18. In order to develop new concepts/components to be applied in filtering/drying applications, we test, using a simple PE Bucket: • New discarding valve (SAV) • New filter sinter plate • Pneumatic conveying of dried product. • New discarding cyclone • Development and test of new drying concept/components Load slurry Dry Well Done. Move cake After results computing, we decide to proceed with integrations of the concept/components to the entire range of filters/dryers we are using or prototyping. Discard Filter dryer flow inversion static drying

19. Filter dryer-NEW study of critical contamination points Filter dryer flow inversion drying tray model

20. Filter dryer-NEW study of critical contamination points Filter dryer flow inversion static drying container

21. Schematic flow of drying operations Filter dryer flow inversion ancillary equipments

22. Filter 8 inch modified for integration in glove box model 2 Filter Dryer modules with sampling

23. Filter 8 inch modified for integration in glove box model 3ed2 Filter Dryer modules with sampling

24. Filter glass DN-150 with heating Layout of filter dryer with in line heater unit. Integrated mass flow controller and flash heating assembly Filter dryer DN150 based

25. Glass reactor units, skid mounted into glove boxes P-13 Containment glove box-P13

26. Reactor Skid and special vacuum line Containment glove box-P13

27. Filter 10 inches in glove box, pre-layout Containment for filtering/drying

28. Clostridium high contamination risk lab layout ed2 Containment area for biotech

29. Layout -1 with one outlet candle filter Automated micro powder dryer-P26

30. Layout -4 brainstorming with customer technical staff Automated micro powder dryer-P26

31. Final Head configuration layout (decisional to establish URS) Automated micro powder dryer-P26

32. Basic model used to develop process • Powder management under vacuum Model integrated in glove boxes, corrected after risk analysis FMEA Vortex Powder management

33. Inert material construction • No moving mechanical parts • temp range RT+10 to 300°C (for Glass Model) • Pressure range +0.5 to absolute vacuum • Product/°C contact 5-10 seconds for water equivalent viscosity • Typical use, separation of two fractions. • Can be series mounted for multi-fractions distillation. • Used to distillate thermo sensible products. • Liquid distillation model HELIX FLASH DISTILLATION

34. Melting solids distillation model • Adding the powder feeder and the in-line melting unit to the liquid distillation model; its possible to distillate melting solids wit the “Helix” • A proved application is purification of DTE. HELIX FLASH DISTILLATION

35. Final packaging of pharmaceutical / different rooms PASS BOX

36. RINSE STEP The separator tank (3) is filled trough one of the two separator tank waffer filling valves(1). The supply pump (2) draw the water from the tank (3) and deliver the solution to the process trough the discharge control valve (4) at the programmed flow rate. At the same time, solution is pumped trough the venturieductor (5) and back into the separator tank (3) inlet, thereby ceating a vacuum at the CIP return connection. The high turbulence created within the circuit prevents settling of any solid and provides self cleaning of the system. The rinse step is followed ba drain step. Tipically, a serie of 3-4 rinse/drain steps are utilised for the final rinse proven by low conductivity at the Cip return connection. CIP VENTURI BASED

37. DRAIN STEP The discharge control valve (4) is closed and solution from the separator tank (3) is pumped trough the venturieductor (5) and back into the separator tank (3) inlet, thereby ceeating a vacuum at the CIP return connection. Returning solution create a high-level condition in the separator tank (3) causing the drain control valve (6) to bleed solution to drain at the set flow rate until the process and the separator tank (3) are empty. CIP VENTURI BASED

38. WASH STEP The separator tank (3) Is filled trough one of the the two separator tank water fill valve (1). The supply pump (2) draws the water from the separator tank (3) and deliver the solution trough the process trough the discharge control valve (4) t the programmed flow rate. At the same time, solution is pumped trough the venturieductor (5) and back into the separator tank (3) inlet, thereby creating a vacuum at the CIP return connection. he high turbulence created within the circuit prevents settling of any solid and provides self cleaning of the system. CIP solution temperatures are elevated using the a heater (7) in the recirculation loop. Chemical solutions (8) are injected into the highly turbulent separator tank (3) and controlled trough conductivity.. CIP VENTURI BASED

39. 30 LITER BIOREACTOR Bioreactor P&ID

40. 7901 custom manufacturing, customer requirements for VMP A customer need to manufacture a new API for clinical trials Phase III. In order to fix the Validation requirements for this process, graphical representation was lay down Project management flows in API processing

41. 7901 graphical batch record test for presentation Project management flows in API processing

42. 7901 Graphical Equipment Configuration sheet After Process batch record was defined, a graphical representation of required equipment configuration was lay down Project management flows in API processing

43. 7901 Graphical micronisationexternal supplier control form-1 Crystalline API will be Micronised by an approved external supplier. The form on left details the Product shipment and receiving protocol page 1 Project management flows in API processing

44. 7901 Graphical micronisation external supplier control form-2 Crystalline API will be Micronised by an approved external supplier. The form on left details the Product micronisation and back receiving protocol page 2 Project management flows in API processing

45. 7901 Graphical example, yield sheet Process and Yield comparison between external suppliers performing micronisation Project management flows in API processing