Part4
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MCC PRESENTATION - GMP MANUFACTURING ENVIRONMENTS Module 4 Presented by : Deryck Smith Consulting Engineers 1 GMP Manufacturing Environments Air Handling Systems HVAC Systems Heating Ventilation Air Conditioning Module 4: Pressure Cascades & Building Layouts 2 GMP Manufacturing Environments Topics for this Module: 1. 2. 3. 4. The integration of air conditioning systems and building layouts. The requirements for pressure cascades and how to achieve them. How building finishes and plant components affect facility cleanliness. Pharmaceutical Equipment 3 Inter-dependence of Air Handling Systems & Buildings •Building layouts, Pressure cascades, Air handling systems and Pharmaceutical equipment are all inter-related. •No one can exist without the other. 4 What is a Pressure Cascade? Pressure Cascade A process whereby air flows from the cleanest area, which is maintained at the highest pressure to a less clean area at a lower pressure. 5 What Is the Purpose of a Pressure Cascade? • Helps prevent cross-contamination between adjacent areas. •Helps prevent ingress of contaminants from outside. •Is used to enhance separation between areas of different cleanliness. The unit of measurement for pressure is the PASCAL (Pa) 6 Air Pressure Cascade Cleanest Environment Highest Room Pressure 15Pa Pressure Differential Less Clean Environment Lower Pressure 15Pa Pressure Differential Dirty Environment Ambient Pressure 7 Measuring the Air Pressure Cascade The pressure differential over the doorway is measured with a portable magnahelic gauge or micro manometer. Permanently installed gauges are preferred. 8 Room Pressure & Air Movement • A room pressure cascade system forces air to flow from clean areas to less-clean areas. Air movement, such as laminar flow (UDAF) over the product, protects the product. (aseptic packing / filling) Directional air movement helps carry contaminants away from a critical process. 9 Typical OSD Plant : Cross-contamination Protection TABLETS COMPR. 15Pa TABLETS COMPR. ENCAPSULATION 15Pa 15Pa AIR LOCK 30Pa PRODUCTION CORRIDOR 15Pa What should the room pressures be ? 10 Dispensary Layout WEIGH BOOTH 1 WEIGH BOOTH 2 STAGING AREA MATEREALS FROM WAREHOUS Is this a good layout ? WEIGHED MATEREALS TO PRODUCTION PIC/S PH 1/97 (Rev.3) #3.3 & 3.12 11 Improved Dispensary Layout WEIGH BOOTH 1 PRE-WEIGH STAGING MATEREALS FROM WAREHOUSE 20Pa 3 POST-WEIGH STAGING UNI-DIRECTIONAL Airflow direction AIRFLOW WEIGHED MATERIALS TO PRODUCTION UNI-DIRECTIONAL AIRFLOW 10Pa 2 20Pa 3 30Pa 4 WEIGH BOOTH 2 What should the room pressures be ? 12 Sampling Booth Layout (1) EXTRACT HOOD SAMPLING BOOTH WAREHOUSE 13 Poor Design Extract System Extract air EA Hood Door Grille SAMPLING CUBICLE or WEIGH BOOTH Section Through Sampling Booth 14 Sampling Booth Layout (2) UDAF HOOD SAMPLING BOOTH AIR AIR LOCK LOCK CHANGE Step-over-bench 15 Typical Section Through Sampling Boooth Supply air Return air Laminar flow distributor 16 What to Qualify in the Sampling Booth Suite • Cleanroom class – ISO 8 • HEPA filter integrity test • Airflow rates • UDAF velocity • Room pressures • Containment – smoke tests • Temperatures (< 25°C) 17 Ablution Layout 1 Production Staff Toilets Plant Change Room Staff 18 Ablution Layout 2 Production Plant Staff Change Room Toilets Staff 19 Change Room Layout FACTORY CHANGE ROOM AIR LOCK TOILETS CANTEEN 20 Protective Garments Outside ?? It is pointless having a change room if it is not used properly 21 Sterile Suite Pressure Cascade STERILE CHANGE 50Pa 40Pa COMPONENT PREP 20Pa 5T A/L 5T 30Pa STERILE STAGING 7 STERILE FILLING RM FILLING MACHINE AUTOCLAVES 5U 6 6 15Pa FORMULATION ROOM CHANGE 40Pa AUTOCLAVES 6 6 5T A/L 40Pa 60Pa 5T 25Pa 40Pa 6/7 7 8 7 MAT. A/L 9 MAT. A/L 15Pa 15Pa 20Pa 40Pa 5T 20Pa FINISHED PRODUCT STAGING 20Pa PERSONEL A/L 20Pa 10Pa 20Pa 8 15Pa 8 T U = Room Pressure = ISO Cleanroom Class = Turbulent = Uni-directional 8 20Pa Product Flow Diagram Wood free zone RAW MAT. RECEIPT PACK. MAT. RECEIPT DISPENSARY PACK. MAT STORE MANUFACTURING GMP ZONE PRIMARY PACKING PRIMARY PACK MAT. CLEAN DOWN SECONDARY PACKING DISPATCH 23 Staff flow Diagram RAW MAT. RECEIPT STAFF ENTRY DISPENSARY CANTEEN PACK. MAT. RECEIPT CHANGE PACK. MAT STORE GMP CHANGE PRODUCTION GMP ZONE PRIMARY PACKING PRIMARY PACK MAT. CLEAN DOWN SECONDARY PACKING DISPATCH 24 Negative Pressure Facilities • Required for facilities handling potent compounds such as penicillin & hormones. • Special precautions required to prevent product contamination from the atmosphere. • Exhaust air must be efficiently filtered and safe filter handling must be used. 25 Safe Change Filters Used for filtering hazardous materials: •Dirty filters are removed into a plastic bag •The bag is automatically sealed at the filter unit housing •A new filter is inserted via a plastic bag and the cover closed •At no time is the operator or the atmosphere exposed to the hazardous powder. 26 Case Study – Penicillin Plant WASH UP TABLET COMPRESSION SYRUPS PREPARATION CAPSULE FILLING MIXING SYRUPS FILLING GRANULATING STAGING DRY POWDER FILLING WEIGH ROOM PRODUCTION PASSAGE PRODUCT STORE MALE ABLUTIONS A/L MALE ABLUT. MAT A/L PACKING GOODS PACKING FEMALE ABLUTIONS SUPERVISOR FINISHED GOODS Add room pressures, Cleanroom class and comment on layout FEMALE CHANGE LAUNDRY MALE CHANGE FINISH. GOODS AIR LOCK 27 Case Study – Penicillin Plant WASH UP TABLET COMPRESSION -30Pa SYRUPS PREPARATION -40Pa CAPSULE FILLING -35Pa MIXING -35Pa -30Pa GRANULATING SYRUPS FILLING STAGING DRY POWDER FILLING -25Pa -25Pa -30Pa WEIGH ROOM -40Pa PRODUCTION PASSAGE PACKING GOODS -25Pa PACKING FEMALE ABLUTIONS -35Pa SUPERVISOR AIR LEAKAGE DIRECTION FINISHED GOODS ROOM PRESSURE RELATIVE TO AMBIENT -35Pa MALE CHANGE FEMALE CHANGE -35Pa LEGEND -15Pa -45Pa -25Pa -30Pa -45Pa MAT A/L -10Pa PRODUCT STORE MALE ABLUTIONS A/L -25Pa -20Pa -15Pa -35Pa -35Pa -35Pa AIR LOCK -15Pa -25Pa 28 Building Finishes: • In module 1 we discussed the need for all facility components to complement each other. • Therefore a good air handling system must be complemented by a building of good design and good finishes. • On the next slide we will be looking at some of the Acceptable and Un-acceptable building finishes. 29 Building Finishes Not Acceptable Acceptable PVA Paint L Epoxy or Enamel paint J Window sills L Flush glazed windows J Exposed pipes L Smooth surfaces J Horizontal pipes & services L Concealed services J Open floor drains L Hygienic drains J Floor cracks, flaking floor surfaces L Homogonous sealed floors – epoxy finish or welded vinyl J Ceiling cracks & joints L Smooth sealed ceilings J Exposed, open light fittings L Flush light fittings J Wooden furniture L S/Steel or Melamine furniture J 30 Floors / drains Tiled Floor Epoxy Floor 31 Poor & Good Windows 32 Paint Finish… • Not only building paintwork must be considered but also equipment Is there anything wrong with this Tablet Press? 33 Building & Equipment Finishes 34 Services Distribution Impossible to clean! Easy to clean! 35 Keep a Balance Don’t ignore building finishes… … and then go overboard on staff dress code. 36 Services Distribution •Where ever possible services should be located behind wall panels •Exposed services & pipes are very difficult to clean & sometimes impossible to clean •Equipment such as Film Coaters should be enclosed so that only the front face is in the GMP area. This makes cleaning much easier. •Make use of service corridors behind equipment (but must be under negative pressure) 37 Split Unit RETURN AIR Poor quality Air filter Cooling Coil Condensate drip tray SUPPLY AIR Fan liberates dust into the air 38 Fluid Bed Drier •Is the quality of the supply air to the FBD correct? •What filtration is used? •Is the exhaust air filtered? 39 Group session Sampling Rooom Service Corridor (contains Vacuum & RO water supply) Air Shower Airlock A/ Lock1 Air Lock2 Warehouse Weighing Tablet 1 Tablet 2 Liquids Mix Softgel Capsule Packing Clean Corridor Emergency Exit Air Lock 3 Equipment Wash Sterile eyedrops dispensing & aceptic filling 2 Stage personnel entry for eyedrops Male Change 2 Female Change 2 Packed Goods Quarantine Male Change 1 Female Change 1 Air Lock 4 Primary & Secondary Packing Service Room 40 Modified Layout with Cascade Sampling Rooom 20Pa 0Pa Service Corridor (contains Vacuum & RO water supply) 30Pa Air Shower 20Pa 10Pa MAL 2 Warehouse 0Pa Weigh Booth 30Pa Post Staging 20Pa Tablet 1 30Pa Tablet 2 15Pa Softgel Capsule Packing Liquids Mix 15Pa 30Pa MAL1 Air Lock 15Pa 30Pa Clean Corridor Emergency Exit PAL 40Pa MAL 3 40Pa Sterile eyedrops dispensing & asceptic filling 20Pa 20Pa Male Change 2 Female Change 2 10Pa 60Pa 15Pa Equipment Wash MAL 4 50Pa Change 50Pa 10Pa Male Change 1 Female Change 1 10Pa Packed Goods Quarantine Air Lock 4 0Pa Secondary Packing 20Pa Primary Packing 30Pa Service Room 0Pa 0Pa MAL = Material Air Lock PAL = Personnel Air Lock 41 Work session: Connect the arrows between processes for Product Flow and Staff Flow Product Flow Diagram Raw Mat. Store Sampling A/L Released Materials Quarantine Sampling A/L GMP Change Room Sampling Booth Pack Mat. Store Dispensary Pre-Staging Dispensary Post-Staging Dispensary Weiigh Booth Pharmaceutical Manufacturing Primary Change room Primary Packing Primary Pack Mat. Clean Down Secondary Packing F/G Dispatch 42 Work session: Connect the arrows between processes for Product Flow and Staff Flow Product Flow Diagram Raw Mat. Store Sampling A/L Released Materials Quarantine Sampling A/L GMP Change Room Sampling Booth Pack Mat. Store Dispensary Pre-Staging Dispensary Post-Staging Dispensary Weiigh Booth Pharmaceutical Manufacturing Primary Change room Primary Packing Primary Pack Mat. Clean Down Secondary Packing F/G Dispatch 43
