1. GMP for utilities and services
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2. Location Engineering of Building and Piping Utilities and Piping
cGMP Facility
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3. Adequate space for future expansion.
Zoning laws to allow anticipated development while restricting undesirable development in the vicinity.
Availability of water (quality and quantity), power, fuel and sewage system.
Ease of accessibility for employee, customers, suppliers, visitors.
Environmental issues: site history, soil, water, AIR QUALITY, topological issues (potential earth quakes, flooding, etc..)
General Considerations before Purchase, Construct or Renovate existing facility
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4. Continue….
Proximity of undesirable activities likely to pollute or act source of insects, odor or microorganisms (based on the hygienic and industrial activities in area)
Availability of a suitable labor force (skilled worker, labor relations and attitudes)
Availability of research institutes and activities to cove part of production chain.
Ability to provide adequate security arrangements.
Political situation-government stability, trade policies, taxation, financial incentives.
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5. Site Preparation and Plant Design
Site arrangement and over-all layout design (green space parking, traffic, recreation area, tanks, site utilities, etc..)
Water supply and waste management area (waste contractors)
Site security and access (fences, guard, cameras, etc..)
Utilities design, layout, backup (critical utilities backup)
Equipment-design, LAYOUT, spares, capacity.
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6. Safety (Personnel and Equipment), emergency services access.
Continue….
Safety (Personnel and Equipment), emergency services access.
External architecture should take in account the local environment (temperature, humidity, wind, etc..)
Ease of maintenance (services ducts, cat floor, etc..)
Project management (Managers, consultants, etc..)
Validation Plans and an effective change control procedures. Provision of design and (as built) drawings.
CONTRACTOR (Experience contractor)
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7. Administration Building Waste Treatment Complex Area
Stores
Administration Building
Production Area
Waste Treatment Complex Area
Utilities
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8. Administration Building Waste Treatment Complex Area
Stores
Administration Building
Waste Treatment Complex Area
Production Area II (Future Plan)
Production Area I
Utilities
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9. Less Engineering work and ease for new facility building
Design from the beginning tanking the extension plan in account will gives your factory the following advantages!
Less Engineering work and ease for new facility building
Less Cost if it the facility was designed from the beginning to have extra-capacity for the stores, utility and waste management system
System Uniformity for utilities (Equipment in Piping)
Higher assess value factory
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10. Engineering and Design Lifecycle
Pre-conceptual Design
Conceptual Design
Basic Design
Detail Design
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11. Pre-conceptual Design
Layout Options (Single floor vs. Multi floor, Different options of facility design)
Room Classification (Area and Classes)
Commissioning and Qualification Approach
Equipment List
Time Schedule
Price Estimation
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12. Conceptual Design Layout Room Classification
Material, product & Personnel flows
Process Automation system
Draft Equipment requirement specifications
Draft qualification Master Plan
Process/clean utilities/ flow diagrams
HVAC zoning
Detailed time schedule
Detailed price estimate
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13. Basic Design Final Layout with complete building specification
Room Classification (Final)
Material, product & Personnel flows (Final)
Process Automation system (Final)
Equipment requirement specifications
Draft qualification Master Plan
Process/clean utilities/ flow diagrams
Complete HVAC Design
Qualification Master Plan
Estimate price of the project (± 30 %)
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14. Detail Design Usually done by consultant engineering company
Complete 3D design of the facility including: Engineering, pipe work, HVAC ducting, Electrical Module and wiring
Complete specifications of all part of the project for
Building complete specifications
Equipment (size, capacity, utility requirements, net-working, etc..)
Final walk through model (material flow, personnel flow, etc..)
Possibly with complete operation model (Chem-CAD model)
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16. Integrated Concept for Engineering and Qualification
Customer requirements specification Planning and Design VMP+ Primary Risk Analysis Establishment of all Equipment plan, Design Qualification Specifications, tender, offer and order Secondary Risk Analysis - Plant testing - Controlled delivery of the Equipment - Equipment Installation (Positioning) - Utility Piping - Equipment check, primary testing - Installation of piping interconnections Installation Qualification - Testing of installation isometrics - Loop check - Calibration - Installation test - Pressure test - Mechanical final assembly (Equipment fixing) Starting IQ/OQ testing Functional testing with SOP IQ/OQ/PQ
Concept Eng.
Basic Eng.
Detail Eng.
Installation
Operation
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17. Utilities and Piping in Biopharmaceutical Facilities
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18. Utilities A - Basic Utilities for the production site
Electricity (regular depends on the site of facility)
Continuous supply, possibly with backup generator and UPS for lag-time between electricity cut-off and generator operation
Natural Gas supply (preferable source of clean energy) and/or Diesel tanks
Water supply (Tab water quality)
(in case of using water tanks, refer to water reservoir guidelines)
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19. B - Piping network (Inside and outside the production area)
(Steam IN, Steam OUT (condensate)) IN / (OUT opt.)
(Clean/Dry steam)
1) Sterilization (equipment, transfer line)
2) Temperature control
(Dust free, dry air) IN
1) Culture aeration ) Valve operation (Pneumatic valves)
3) Culture transfer ) Standard for out-gas analyzer
1 - Steam
2 - Air
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20. - Tap water (for non-production related activities and cleaning) IN
- Soft water (for operation of steam generator) IN
- Distilled water (Media preparation/ cleaning) IN
- Deionized water (Analysis and buffer preparation) IN
- Water For Injection (Buffer preparation and purification) IN
(WFI)
- Chilled water (For temperature control and cooling purpose) IN
3 - Water
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21. (liquid medium including: medium supplements,
4 - Non-utility piping
(Directly in contact with product, byproduct or production vessel)
Media
(liquid medium including: medium supplements,
Fed-batch medium Acid/Base for pH adjustment)
Buffer
Water (of different quality, based on process stage)
Piping for CIP system
Steam for SIP system (for direct steam injection)
Sterile air for medium aeration and for broth and liquid transfer
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23. Piping Networking Design
Point requirement (Flow, temperature, presssure)
Valves (Type, specification, location)
Insulation requirements.
Piping (Material, Diameter (pressure drop))
Connections (Pressure gauge, Filters
Deadlegs Slope Drainability
Steam traps
Flexible design for future extension
Maintenance -
Minimize the pipe length
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24. Piping, Filters and Valves
Outside the production site
Piping
Inside the production area
Not in contact with the product
In direct contact with the product
Piping network Design and Material requirements
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25. Piping Network Why Stainless Steel for Fixed piping system?
# Corrosion resistant
# Durable, long life
# Low expansion coefficient
# Easy for clean finishing
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26. Stainless Steel is not Standard word
Stainless steel are more than 70 types and many special alloys.
The International Codes:
1 - AISI (American Iron and Steel Institute)
2 - ACI (Alloy Casting Institute)
All stainless steel are iron bases, with 12%-30% chromium, 0%-22% nickel, and minor amounts of carbon, columbium, copper, molybdenum, selenium, Tantalum and titanium.
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27. Material characteristic (St.St. Pipes)
Wall thickness
Surface finish / treatment
Cleanliness
Material Test Report
Chemical Analysis
Fitting Tolerance
Surface Anomalies
(Pits, porosity, scratches, tool marks)
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28. Stainless Steel Types for Biotechnology factories
304 and 316 stainless steels and their L grades (non-magnetic), and not hadenable by heat treatment.
Austenitic stainless steel with higher Mo content
Duplex stainless steel group
Superaustenties in particular (6Mo)
Alloy C family (Ni, Cr, Mo family)
Cobalt based alloy with high corrosion and wear-resistance
Titanium alloys, referred as chemically pure (CP)
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29. Chemical Comparison between different St.St. types
Composition (%)
304
304L
316
316L Cr
18.0 – 20.0
16.0 – 18.0 Ni
8.0 – 11.0
8.0 – 13.0
10.0 – 14.0 C
0.08 max
0.035 max
0.88 max
0.35 max Fe
Balance Mo -
2.0 – 3.0 Mn
2.0 max Si
0.75 max P
0.040 max S
0.030 max
0.005 to 0.017
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30. ASME Bioprocessing Equipment (BPE-1997/BPEa-2000)
Standards
ASME Bioprocessing Equipment (BPE-1997/BPEa-2000)
This American National Standard is covering: material, design, fabrication,
examination, inspection, testing, certification (for pressure system) and
pressure relief (for pressure system) of vessels and piping for bioprocessing
system, including sterility and cleanability (Part SD), dimensions and
tolerance (Part DT), surface finish requirement (Part SF), material joining
(Part MJ), and seals (Part SG)
This standard is applied to:
All parts that contact with product, raw material, and/or product intermediates during manufacturing, process developing or scaling up.
All equipments or systems that are critical part of product manufacture, such as Water for Injection (WFI), clean steam, ultrafiltration, intermediate product storage and centrifuges.
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31. ASME Design guidelines (BPE – Part SD - 3)
SD Cleanability SD Sterility SD -3.3.Surface finish SD Material of construction SD-3.5. Fabrication SD-3.6. Static-O-ring, seals and gaskets SD-3.7. Connections and Fittings SD-3.8. Exterior Design SD-3.9. Containment SD Miscellaneous design details SD System design SD Drainability
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32. ASME Design guidelines (BPE – Part SD - 4)
SD-4.1 Instrumentation
SD-4.2 Fittings and hoses
SD-4.3 Centrifuges
SD-4.4 Filtration equipment
SD-4.5 Pumps
SD-4.6 Pressure (hygienic) valve
SD-4.7 Vessel design
SD-4.8 Agitators and mixers
SD-4.9 Heat exchanger equipment
SD-4.10 Cell disrupters
SD-4.11 High purity water and steam systems
SD-4.13 Generators and clean/ pure steam generators
SD-4.14 Sterilizers/ autoclaves
SD-4.15 CIP systems and design
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33. Surface characterization
Surface finishes are all interior surface finishes accessible and inaccessible, that directly or indirectly come in contact with the designated product in bioprocessing equipment and distribution system components.
Reference should be made to ASME BPE standard, Part SF,
“Stainless Steel and Higher Alloy Interior Surface Finishes”
Surface finishes quantified by different measuring Units:
Gritt Number (USA Finish Number)
Ra (Micron)
Rmax (Micron)
ISO Number
Ra (Micron inch)
Rmax (Micron inch)
Japanese standard
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34. Arithmetic Average Roughness (Ra)
The arithmetic average height of roughness component irregularities from the mean line measured within the sample length (L)
Surface Measurement Comparison
Ra (Micro inch)
Ra (Micron)
Grit (Size) 71
1.80 80 52
1.32
120 42
1.06
150 30
0.76
180 15
0.38
240 12
0.30
320 10
400
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35. Electropolishing
The technique: it carried out using mixed acid solution sometimes with organic additives (electrolyte), and a cathode that is pulled through the inside of the tube. The tube becomes the anode, so it preferentially dissolves, removing metal from the peaks and not form the valley.
Advantages:
Improve the metal appearance
Produce extremely smooth surface, which minimize adherence to surface.
An increased chromium to iron ratio on the electropolished surface to improve corrosion resistance.
Creation of a passive layer that is free from iron contamination.
Improved ability to visually detect surface defects.
Improved mechanical property performance through minimization of stress risers.
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36. Welding Technique – orbital welding - Automatic (preferable)
- Argon (pure gas)
Practice – welder quality
- certificate
Test – x-ray
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37. Valves
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38. Main Criteria for Valve Selection
Media to be handled: this will affect both types of valve and material choice for valve constructions
Functional requirements: mainly affecting choice of type of valve.
Operating conditions: affecting both choices of valve type and construction materials.
Flow characteristics and frictional loss: setting additional specification
Valve size: this may affect choice of valve selection (very large size are only available in a limited range of types).
Special requirements: such as quick opening, etc…
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39. Valve types for specific applications in Biotech facility
1ry . Choice
2ry. Choice
Gases
Butterfly valve
Check valve
Diaphragm valves
Pressure-controlled valves
Pressure-relief valves
Safety valve
Pressure-reducing valves
Liquid, clear up to sludge and sewage
Screw-down stop valve
Pinch valve
Slurries and liquids heavily contaminated with solids
Gate valve
Steam
Safety and relief valves
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