2. should take into consideration the following points
allover the manufacturing steps from receiving raw
materials till releasing of finished products.
1.Personnel safety for all factory stuff.
2.Environmental safety.
3.Patient safety through following current GMP
requirements to minimize both contamination & cross
contamination risks.
3. FDA, Guidance for Industry, Sterile Drug Products Produced by Aseptic
Processing - Current Good Manufacturing Practice, 9 - 2004.
FDA, Compliance program guidance manual chapter 56 - Drug quality
assurance, sterile drug process inspections, 5-11-2012.
FDA, Guide to inspections of high purity water systems.
EMA – Note for Guidance on quality of water for pharmaceutical use, 5-2002.
WHO – TRS 929, Annex 3, Good Manufacturing Practices: water for
pharmaceutical use, 2005.
EMA – Eudralex – volume 4 – Annex 1, Manufacture of Sterile Medicinal
Products, 25-11-2008.
EMA – Eudralex – volume 4 – Part 1 – chapter 3, Premise and Equipment,
coming into operation on 1-3-2015.
EMA – Eudralex – volume 4 – Part 1 – chapter 5, Production, coming into
operation on 1-3-2015.
WHO – TRS 961, Annex 6, Good manufacturing practices for sterile
pharmaceutical products, 2011.
WHO – TRS 961, Annex 5, Good manufacturing practices for heating,
ventilation and air-conditioning systems for non-sterile pharmaceutical dosage
forms, 2011.
4. WHO – TRS 957, Annex 3, Good manufacturing practices for pharmaceutical
products containing hazardous substances, 2010.
ISO 146441- Part 1, 2, 3, 4, 5, 7.
ISO 8573, Part 1, 2010.
ISO 13408, Part 1, 2, 4, 5, 6.
BS EN 285:2006 + A1:2008, Sterilization – steam sterilizers – large sterilizers.
ANSI/AAMI/ISO TIR 17665 – Part 1 & 2: Sterilization of health care products -
Moist heat.
HTM 2010 – Part 1, 2, 3, 4 & 5.
UK – Department of health, Management & decontamination of surgical
instruments, Part C: Steam sterilization, 20-3-2013.
ASME BPE-2012, Bioprocessing Equipment.
ISPE - Sterile Product Manufacturing Facilities - Volume 3 - 2nd edition - Sept
2011
5. Risk assessment for all drug manufacturing processes in the factory.
- identify risk for spillage (Raw materials, in process bulk & finished products)
- identify risk sources for microbial contamination
- identify risk sources for cross contamination
Containment strategy.
- In equipment (Barrier & isolator systems – CIP/WIP)
- Personnel protective equipment (Face masks & full cover protective
suite with respiration)
- Safety exit showers
- HVAC design (Pressure cascading, full fresh air or recirculated air & safe
changing filters)
User requirements for:
- Facility (Store, Manufacturing, Laboratory……….)
- Process utilities
- Process support utilities
- Equipment (Store, Manufacturing & Laboratory)
Conceptual design
Detail design
Design review & Approval
6. HVAC System ( AHUs & duct work) with Building management system
(BMS).
- Full fresh & full exhaust (1st choice)
- Recirculated air and its requirements:
- recirculation to same area.
- Presence of double unit of safe changing Bag in bag out
HEPA filter units in return AHU & the return Fan to be
after these units.
- Gauges of AHU to be connected by stainless or copper connectors (
not plastic tubes)
Pure media system (PW, WFI & PS).
Compressed gas system (Air, Nitrogen………); come in contact directly
with product or in contact with manufacturing equipment surface.
7. Boilers for generating industrial steam
Oxygen generator for compressed oxygen
generation & distribution system.
Compressed air for equipment & utilities valves
operation.
Electricity generators & required UPS
Active effluent treatment plant.
Drain system.
Tape water, hot water & cold water.
Chiller.
Breathing air.
8. Certified contractor for developing pharmaceutical GMP layouts
will develop the following layouts:
Layout for Material & finished goods flow.
Layout for Personnel & safety exits flow.
Layout flow for Waste flow.
Layout for Room classification with Absolute, differential
pressure cascading & no of air changes.
Layout for HVAC ducts (Supply & returns), no of HEPA filters
and grills.
Layout for supplied utilities (Compressed air, nitrogen,
oxygen, pure & industrial steam, chilled water, purified
water, water for injection & city water points).
Layout for Drain openings & its pipelines.
9. Sampling / Dispensing & Preparation Isolators for active potent /
hazardous ingredients.
Sampling & Dispensing Booth for Non active ingredients.
Ampoule & vial washing machine connected to Depyrogenation Tunnel
connected to aseptic filling Machine (where filling machine integrated
with CIP & SIP system).
Vial capping machine.
Solid porous load double door sterilizing Autoclave.
Double door autoclave for terminal sterilizing of filled Ampoules & vials.
Ampoule & vial leakage tester.
Filled crimped vial washing machine.
Automatic loading / unloading Lyophilizer (for lyophilized products).
Preparation & Holding (Storage) tanks equipped with CIP & SIP systems.
10. Sampling / Dispensing & Preparation Isolators for active potent / hazardous ingredients.
Sampling & Dispensing Booth for Non active ingredients.
Movable dispensing drums & / or IBC bins (intermediate bulk containers bins) with
modular interlocked opening / connecting ports with hygienic quick release butterfly
valves.
Tanks, Drums & Bins washer with drying station.
Connected system of High shear mixer, fluid bed dryer & cone mill; Integrated all with
wash in place (WIP) & clean in place (CIP).
Bin blender and Movable modular height & arms bin lifter.
Containment WIP, CIP tablet press machine with tablet deduster, weight checker, metal
detector & wet type dust collector.
Coating solution preparation tank.
Coating machine with WIP, CIP and wet type dust collector.
Containment WIP, CIP capsule filling machine with deduster, weight checker & metal
detector & wet type dust collector.
Double door Washing machine for machine parts.
Containment tablet & capsule blistering machine.
Containment Suppository preparation tank and suppository filling machine integrated with
WIP & CIP.
