MCC PRESENTATION - GMP MANUFACTURING ENVIRONMENTS

MCC PRESENTATION - GMP MANUFACTURING ENVIRONMENTS Module 4 Presented by : Deryck Smith Consulting Engineers

GMP Manufacturing Environments Air Handling Systems HVAC Systems Heating Ventilation Air Conditioning Module 4: Pressure Cascades & Building Layouts

GMP Manufacturing Environments Topics for this Module: 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

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.

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.

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)

Air Pressure Cascade

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.

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. 

Typical OSD Plant : Cross-contamination Protection What should the room pressures be ?

Dispensary Layout Is this a good layout ? PIC/S PH 1/97 (Rev.3) #3.3 & 3.12

Improved Dispensary Layout Airflow direction What should the room pressures be ?

Sampling Booth Layout (1) EXTRACT HOOD SAMPLING BOOTH WAREHOUSE

Poor Design Extract System Section Through Sampling Booth

Sampling Booth Layout (2) UDAF HOOD SAMPLING BOOTH AIR LOCK AIR LOCK CHANGE Step-over-bench

Typical Section Through Sampling Boooth

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)

Ablution Layout 1 Production Plant Toilets Staff Change Room Staff

Ablution Layout 2 Production Plant Change Room Toilets Staff Staff

Change Room Layout

Protective Garments Outside ?? It is pointless having a change room if it is not used properly

STERILE CHANGE 5T A/L COMPONENT 5T PREP 6 STERILE STERILE 7 STAGING FILLING RM 6 5U 6 AUTO- CLAVES FILLING MACHINE FORMULATION ROOM 5T CHANGE A/L AUTO- 7 CLAVES 6/7 8 7 PERSONEL MAT. MAT. 9 A/L A/L A/L FINISHED PRODUCT STAGING 8 = Room Pressure 15Pa = ISO Cleanroom Class 8 T = Turbulent U = Uni-directional Sterile Suite Pressure Cascade

Product Flow Diagram Wood free zone RAW MAT. RECEIPT PACK. MAT. RECEIPT DISPENSARY PACK. MAT STORE MANUFACTURING PRIMARY PACK MAT. CLEAN DOWN PRIMARY PACKING GMP ZONE SECONDARY PACKING DISPATCH

Staff flow Diagram STAFF ENTRY CANTEEN RAW MAT. RECEIPT PACK. MAT. RECEIPT DISPENSARY CHANGE PACK. MAT STORE GMP CHANGE PRODUCTION PRIMARY PACK MAT. CLEAN DOWN PRIMARY PACKING GMP ZONE SECONDARY PACKING DISPATCH

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.

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.

Case Study – Penicillin Plant MALE ABLUT. Add room pressures, Cleanroom class and comment on layout LAUNDRY FINISH. GOODS

WASH TABLET -30Pa UP SYRUPS COMPRES- CAPSULE PREPARATION SION -40Pa FILLING -35Pa MIXING -35Pa STAGING DRY -30Pa GRANULATING SYRUPS POWDER FILLING -25Pa -25Pa -30Pa FILLING WEIGH ROOM -40Pa PRODUCTION PASSAGE -15Pa -20Pa PRODUCT -25Pa -30Pa STORE A/L -45Pa ABLUTIONS -25Pa PACKING PACKING -25Pa -45Pa MALE GOODS FEMALE MAT ABLUTIONS A/L -10Pa -35Pa SUPER- -35Pa VISOR MALE FEMALE CHANGE CHANGE -35Pa LEGEND -35Pa -35Pa ROOM PRESSURE RELATIVE -15Pa TO AMBIENT FINISHED -35Pa GOODS AIR LOCK AIR LEAKAGE DIRECTION -15Pa -25Pa Case Study – Penicillin Plant

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.

Building Finishes

Floors / drains Tiled Floor Epoxy Floor

Poor & Good Windows Bacteria City !!!

Paint Finish… • Not only building paintwork must be considered but also equipment Is there anything wrong with this Tablet Press?

Building & Equipment Finishes

Services Distribution Impossible to clean! Easy to clean!

Keep a Balance Don’t ignore building finishes… … and then go overboard on staff dress code.

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)

RETURN AIR SUPPLY AIR Split Unit Poor quality Air filter Cooling Coil Condensate drip tray Fan liberates dust into the air

Fluid Bed Drier • Is the quality of the • supply air to the FBD • correct? • What filtration is used? • Is the exhaust air filtered?

Group session Airlock

Modified Layout with Cascade MAL = Material Air Lock PAL = Personnel Air Lock

Work session: Connect the arrows between processes for Product Flow and Staff Flow Product Flow Diagram Raw Mat. Store Quarantine Released Materials Primary Change room Sampling A/L Sampling A/L GMP Change Room Sampling Booth Pack Mat. Store Dispensary Pre-Staging Dispensary Post-Staging Dispensary Weiigh Booth Primary Pack Mat. Clean Down Pharmaceutical Manufacturing Secondary Packing Primary Packing F/G Dispatch

MCC PRESENTATION - GMP MANUFACTURING ENVIRONMENTS