LocationLocation

Engineering of Building and PipingEngineering of Building and Piping

Utilities and PipingUtilities and Piping

cGMP Facility

Adequate space for future expansion.Adequate space for future expansion. Zoning laws to allow anticipated development Zoning laws to allow anticipated development

while restricting undesirable Development in while restricting undesirable Development in the vicinity.the vicinity.

Availability of water (quality and quantity), Availability of water (quality and quantity), power, fuel and sewage system.power, fuel and sewage system.

Ease of accessibility for Employee, customers, Ease of accessibility for Employee, customers, suppliers, visitors.suppliers, visitors.

Environmental issues: site history, soil, water, Environmental issues: site history, soil, water, AIR QUALITY, topological issues (potential AIR QUALITY, topological issues (potential Earth quakes, flooding, etc..)Earth quakes, flooding, etc..)

General Considerations before Purchase, Construct or Renovate existing facility

Continue….Continue….

Proximity of undesirable activities likely to Proximity of undesirable activities likely to pollute or act source of insects, odor or pollute or act source of insects, odor or microorganisms (based on the hygienic and microorganisms (based on the hygienic and industrial activities in area)industrial activities in area)

Availability of a suitable labor force (skilled Availability of a suitable labor force (skilled worker, labor relations and attitudes) worker, labor relations and attitudes)

Availability of research institutes and activities Availability of research institutes and activities to cove part of production chain.to cove part of production chain.

Ability to provide adequate security Ability to provide adequate security arrangements.arrangements.

Political situation-government stability, trade Political situation-government stability, trade policies, taxation, financial incentives.policies, taxation, financial incentives.

Site Preparation and Plant Design

Site arrangement and over-all layout Site arrangement and over-all layout design (green space parking, traffic, design (green space parking, traffic, Recreation area, tanks, site utilities, etc..)Recreation area, tanks, site utilities, etc..)

Water supply and waste management area Water supply and waste management area (waste contractors)(waste contractors)

Site security and access (fences, guard, Site security and access (fences, guard, cameras, etc..)cameras, etc..)

Utilities design, layout, backup (critical Utilities design, layout, backup (critical utilities backup)utilities backup)

Equipment-design, LAYOUT, spares, Equipment-design, LAYOUT, spares, capacitycapacity..

Continue….Continue….Safety (Personnel and Equipment), Safety (Personnel and Equipment),

emergency services access.emergency services access.External architecture should take in account External architecture should take in account

the local environment (temperature, the local environment (temperature, humidity, wind, etc..)humidity, wind, etc..)

Ease of maintenance (services ducts, cat Ease of maintenance (services ducts, cat floor, etc..)floor, etc..)

Project management (Managers, Project management (Managers, consultants, etc..)consultants, etc..)

Validation Plans and an effective change Validation Plans and an effective change control procedures. Provision of design and control procedures. Provision of design and (as built) drawings.(as built) drawings.

CONTRACTOR (Experience contractor)CONTRACTOR (Experience contractor)

Utilities

Waste Treatment

Complex Area

Stores

Waste Treatment Complex

Area

Production Area II

(Future Plan)

Production Area I

Utilities

Stores

• Less Engineering work and ease for new facility Less Engineering work and ease for new facility buildingbuilding

• Less Cost if it the facility was designed from the Less Cost if it the facility was designed from the beginning to have extra-capacity for the stores, beginning to have extra-capacity for the stores, utility and waste management systemutility and waste management system

• System Uniformity for utilities (Equipment in System Uniformity for utilities (Equipment in Piping)Piping)

• Higher assess value factoryHigher assess value factory

Design from the beginning tanking the extension plan in account will gives your factory the following advantages!

Engineering and Design LifecycleEngineering and Design Lifecycle

Pre-conceptual DesignPre-conceptual Design

Conceptual DesignConceptual Design

Basic DesignBasic Design

Detail DesignDetail Design

Layout Options (Single floor vs. Multi Layout Options (Single floor vs. Multi floor, Different options of facility floor, Different options of facility design)design)

Room Classification (Area and Room Classification (Area and Classes)Classes)

Commissioning and Qualification Commissioning and Qualification ApproachApproach

Equipment ListEquipment ListTime Schedule Time Schedule Price EstimationPrice Estimation

Pre-conceptual DesignPre-conceptual Design

Layout Layout Room ClassificationRoom ClassificationMaterial, product & Personnel flowsMaterial, product & Personnel flowsProcess Automation systemProcess Automation systemDraft Equipment requirement Draft Equipment requirement

specificationsspecificationsDraft qualification Master PlanDraft qualification Master PlanProcess/clean utilities/ flow diagramsProcess/clean utilities/ flow diagramsHVAC zoningHVAC zoningDetailed time scheduleDetailed time scheduleDetailed price estimateDetailed price estimate

Conceptual DesignConceptual Design

Final Layout with complete building Final Layout with complete building specificationspecification

Room Classification (Final)Room Classification (Final)Material, product & Personnel flows (Final)Material, product & Personnel flows (Final)Process Automation system (Final)Process Automation system (Final)Equipment requirement specificationsEquipment requirement specificationsDraft qualification Master PlanDraft qualification Master PlanProcess/clean utilities/ flow diagramsProcess/clean utilities/ flow diagramsComplete HVAC DesignComplete HVAC DesignQualification Master Plan Qualification Master Plan Estimate price of the project (± 30 %)Estimate price of the project (± 30 %)

Basic DesignBasic Design

Usually done by consultant engineering Usually done by consultant engineering companycompany

Complete 3D design of the facility Complete 3D design of the facility including: Engineering, pipe work, HVAC including: Engineering, pipe work, HVAC ducting, Electrical Module and wiringducting, Electrical Module and wiring

Complete specifications of all part of the Complete specifications of all part of the project forproject for

Building complete specificationsBuilding complete specificationsEquipment (size, capacity, utility Equipment (size, capacity, utility

requirements, net-working, etc..)requirements, net-working, etc..)Final walk through model (material flow, Final walk through model (material flow,

personnel flow, etc..)personnel flow, etc..)Possibly with complete operation model Possibly with complete operation model

(Chem-CAD model)(Chem-CAD model)

Detail DesignDetail Design

Customer requirements specification Customer requirements specification

Planning and Design VMP+ Planning and Design VMP+ Primary Risk AnalysisPrimary Risk Analysis

Establishment of all Equipment plan, Design Establishment of all Equipment plan, Design

Qualification Qualification Specifications, tender, offer and order Secondary Specifications, tender, offer and order Secondary

Risk AnalysisRisk Analysis - Plant testing- Plant testing - Controlled delivery of the Equipment- Controlled delivery of the Equipment - Equipment Installation (Positioning) - Equipment Installation (Positioning) - Utility Piping- Utility Piping - Equipment check, primary testing- Equipment check, primary testing - Installation of piping interconnections Installation - Installation of piping interconnections Installation

Qualification Qualification - Testing of installation isometrics- Testing of installation isometrics - Loop check- Loop check - Calibration- Calibration - Installation test- Installation test - Pressure test- Pressure test - Mechanical final assembly (Equipment fixing) Starting IQ/OQ - Mechanical final assembly (Equipment fixing) Starting IQ/OQ

testingtesting

Functional testing with SOP IQ/OQ/PQ Functional testing with SOP IQ/OQ/PQ

Integrated Concept for Engineering and QualificationIntegrated Concept for Engineering and Qualification

Concept Eng.Concept Eng.

Basic Eng.Basic Eng.

Detail Eng.Detail Eng.

OperationOperation

InstallationInstallation

Utilities and Piping in Biopharmaceutical Facilities

Utilities and Piping in Biopharmaceutical Facilities

A - Basic Utilities for the production site A - Basic Utilities for the production site - Electricity (regular depends on the site of Electricity (regular depends on the site of

facility)facility)- Continuous supply, possibly with backup Continuous supply, possibly with backup

generator and UPS for lag-time between generator and UPS for lag-time between electricity cut-off and generator operationelectricity cut-off and generator operation

- Natural Gas supply (preferable source of Natural Gas supply (preferable source of clean energy) and/or Diesel tanksclean energy) and/or Diesel tanks

- Water supply (Tab water quality)Water supply (Tab water quality)

(in case of using water tanks, refer to water (in case of using water tanks, refer to water reservoir guidelines)reservoir guidelines)

UtilitiesUtilities

B - Piping network (Inside and outside the B - Piping network (Inside and outside the production area) production area)

(Steam IN, Steam OUT (condensate)) (Steam IN, Steam OUT (condensate)) IN / (OUT opt.)IN / (OUT opt.) (Clean/Dry steam)(Clean/Dry steam)

1) 1) Sterilization (equipment, transfer line) Sterilization (equipment, transfer line)

2) 2) Temperature control Temperature control

(Dust free, dry air) (Dust free, dry air) IN IN

1)1) Culture aeration Culture aeration 2) 2) Valve operation Valve operation (Pneumatic valves)(Pneumatic valves)

3) 3) Culture transfer Culture transfer 4) 4) Standard for out-gas Standard for out-gas analyzeranalyzer

1 - Steam1 - Steam

2 - Air2 - Air

- - Tap water (for non-production related activities and Tap water (for non-production related activities and cleaning) cleaning) ININ

-- Soft water (for operation of steam generator) Soft water (for operation of steam generator) ININ

-- Distilled water (Media preparation/ cleaning) Distilled water (Media preparation/ cleaning) ININ

-- Deionized water (Analysis and buffer preparation) Deionized water (Analysis and buffer preparation) IN IN

-- Water For Injection (Buffer preparation and Water For Injection (Buffer preparation and purification) purification) ININ

(WFI) (WFI)

- - Chilled water (For temperature control and cooling Chilled water (For temperature control and cooling purpose) purpose) ININ

3 - Water3 - Water

• Media Media

(liquid medium including: medium supplements,(liquid medium including: medium supplements,

Fed-batch medium Acid/Base for pH adjustment)Fed-batch medium Acid/Base for pH adjustment)• BufferBuffer• Water (of different quality, based on process Water (of different quality, based on process

stage)stage)• Piping for CIP systemPiping for CIP system• Steam for SIP system (for direct steam Steam for SIP system (for direct steam

injection)injection)• Sterile air for medium aeration and for broth Sterile air for medium aeration and for broth

and liquid transferand liquid transfer

4 - Non-utility piping(Directly in contact with product, byproduct or production vessel)

4 - Non-utility piping(Directly in contact with product, byproduct or production vessel)

• Point requirement (Flow, temperature, Point requirement (Flow, temperature, presssure)presssure)

• Valves (Type, specification, location)Valves (Type, specification, location)• Insulation requirements.Insulation requirements.• Piping (Material, Diameter (pressure drop))Piping (Material, Diameter (pressure drop))• Connections (Pressure gauge, FiltersConnections (Pressure gauge, Filters• Deadlegs - Slope - DrainabilityDeadlegs - Slope - Drainability• Steam trapsSteam traps• Flexible design for future extensionFlexible design for future extension• Maintenance - Maintenance - • Minimize the pipe lengthMinimize the pipe length

Piping Networking DesignPiping Networking Design

Piping, Filters and ValvesPiping, Filters and Valves

PipingOutside the production siteOutside the production site

Inside the production areaInside the production area

Piping network Design and Material requirementsPiping network Design and Material requirements

Not in contact with the productNot in contact with the product

In direct contact with the productIn direct contact with the product

Why Stainless Steel for Fixed piping Why Stainless Steel for Fixed piping system?system?

## Corrosion resistant Corrosion resistant

## Durable, long life Durable, long life

# # Low expansion coefficientLow expansion coefficient

## Easy for clean finishing Easy for clean finishing

Piping NetworkPiping Network

Stainless steel are more than 70 types Stainless steel are more than 70 types and many special alloys. and many special alloys.

The International Codes:The International Codes:

11 - AISI (American Iron and Steel Institute) - AISI (American Iron and Steel Institute)

22 - ACI (Alloy Casting Institute) - ACI (Alloy Casting Institute)

All stainless steel are iron bases, with All stainless steel are iron bases, with 12%-30% chromium, 0%-22% nickel, 12%-30% chromium, 0%-22% nickel, and minor amounts of carbon, and minor amounts of carbon, columbium, copper, molybdenum, columbium, copper, molybdenum, selenium, Tantalum and titanium.selenium, Tantalum and titanium.

Stainless Steel is not Standard word

1.1. Wall thicknessWall thickness

2.2. Surface finish / treatmentSurface finish / treatment

3.3. CleanlinessCleanliness

4.4. Material Test ReportMaterial Test Report

5.5. Chemical AnalysisChemical Analysis

6.6. Fitting ToleranceFitting Tolerance

7.7. Surface Anomalies Surface Anomalies

(Pits, porosity, scratches, tool (Pits, porosity, scratches, tool marks)marks)

Material characteristic (St.St. Pipes)

1.1. 304 and 316 stainless steels and their L 304 and 316 stainless steels and their L grades (non-magnetic), and not hadenable grades (non-magnetic), and not hadenable by heat treatment.by heat treatment.

2.2. Austenitic stainless steel with higher Mo Austenitic stainless steel with higher Mo contentcontent

3.3. Duplex stainless steel groupDuplex stainless steel group

4.4. Superaustenties in particular (6Mo)Superaustenties in particular (6Mo)

5.5. Alloy C family (Ni, Cr, Mo family)Alloy C family (Ni, Cr, Mo family)

6.6. Cobalt based alloy with high corrosion and Cobalt based alloy with high corrosion and wear-resistancewear-resistance

7.7. Titanium alloys, referred as chemically Titanium alloys, referred as chemically pure (CP)pure (CP)

Stainless Steel Types for Biotechnology factories

CompositioComposition (%)n (%)

304304 304L304L 316316 316L316L

CrCr 18.0 – 20.018.0 – 20.0 18.0 – 20.018.0 – 20.0 16.0 – 18.016.0 – 18.0 16.0 – 18.016.0 – 18.0

NiNi 8.0 – 11.08.0 – 11.0 8.0 – 13.08.0 – 13.0 10.0 – 14.010.0 – 14.0 10.0 - 15.010.0 - 15.0

CC 0.08 max0.08 max 0.035 max0.035 max 0.88 max0.88 max 0.35 max0.35 max

FeFe BalanceBalance BalanceBalance BalanceBalance BalanceBalance

MoMo -- 2.0 – 3.02.0 – 3.0 -- 2.0 – 3.02.0 – 3.0

MnMn 2.0 max2.0 max 2.0 max2.0 max 2.0 max2.0 max 2.0 max2.0 max

SiSi 0.75 max0.75 max 0.75 max0.75 max 0.75 max0.75 max 0.75 max0.75 max

PP 0.040 max0.040 max 0.040 max0.040 max 0.040 max0.040 max 0.040 max0.040 max

SS 0.030 max0.030 max 0.030 max0.030 max 0.030 max0.030 max 0.005 to 0.005 to 0.0170.017

Chemical Comparison between different St.St. typesChemical Comparison between different St.St. types

This American National Standard is covering: material, design, This American National Standard is covering: material, design, fabrication,fabrication,

examination, inspection, testing, certification (for pressure system) andexamination, inspection, testing, certification (for pressure system) and

pressure relief (for pressure system) of vessels and piping for pressure relief (for pressure system) of vessels and piping for bioprocessingbioprocessing

system, including sterility and cleanability (Part SD), dimensions andsystem, including sterility and cleanability (Part SD), dimensions and

tolerance (Part DT), surface finish requirement (Part SF), material tolerance (Part DT), surface finish requirement (Part SF), material joiningjoining

(Part MJ), and seals (Part SG)(Part MJ), and seals (Part SG)

This standard is applied to:This standard is applied to:

1)1) All parts that contact with product, raw material, and/or product All parts that contact with product, raw material, and/or product intermediates during manufacturing, process developing or scaling intermediates during manufacturing, process developing or scaling up.up.

2)2) All equipments or systems that are critical part of product All equipments or systems that are critical part of product manufacture, such as Water for Injection (WFI), clean steam, manufacture, such as Water for Injection (WFI), clean steam, ultrafiltration, intermediate product storage and centrifuges. ultrafiltration, intermediate product storage and centrifuges.

Standards

ASME Bioprocessing Equipment (BPE-1997/BPEa-2000)

SD - 3.1.Cleanability SD - 3.1.Cleanability

SD - 3.2.SterilitySD - 3.2.Sterility

SD -3.3.Surface finish SD -3.3.Surface finish

SD - 3.4.Material of constructionSD - 3.4.Material of construction

SD-3.5. FabricationSD-3.5. Fabrication

SD-3.6. Static-O-ring, seals and gasketsSD-3.6. Static-O-ring, seals and gaskets

SD-3.7. Connections and FittingsSD-3.7. Connections and Fittings

SD-3.8. Exterior DesignSD-3.8. Exterior Design

SD-3.9. ContainmentSD-3.9. Containment

SD-3.10. Miscellaneous design detailsSD-3.10. Miscellaneous design details

SD-3.11. System designSD-3.11. System design

SD-3.12. DrainabilitySD-3.12. Drainability

ASME Design guidelines (BPE – Part SD - 3)

• SD-4.1 InstrumentationSD-4.1 Instrumentation• SD-4.2 Fittings and hosesSD-4.2 Fittings and hoses• SD-4.3 CentrifugesSD-4.3 Centrifuges• SD-4.4 Filtration equipmentSD-4.4 Filtration equipment• SD-4.5 PumpsSD-4.5 Pumps• SD-4.6 Pressure (hygienic) valveSD-4.6 Pressure (hygienic) valve• SD-4.7 Vessel designSD-4.7 Vessel design• SD-4.8 Agitators and mixersSD-4.8 Agitators and mixers• SD-4.9 Heat exchanger equipmentSD-4.9 Heat exchanger equipment• SD-4.10 Cell disruptersSD-4.10 Cell disrupters• SD-4.11 High purity water and steam systemsSD-4.11 High purity water and steam systems• SD-4.13 Generators and clean/ pure steam generatorsSD-4.13 Generators and clean/ pure steam generators• SD-4.14 Sterilizers/ autoclavesSD-4.14 Sterilizers/ autoclaves• SD-4.15 CIP systems and designSD-4.15 CIP systems and design

ASME Design guidelines (BPE – Part SD - 4)

WeldingWelding

Technique – orbital weldingTechnique – orbital welding - Automatic (preferable)- Automatic (preferable) - Argon (pure gas)- Argon (pure gas)

Practice – welder qualityPractice – welder quality - certificate- certificate

Test – x-rayTest – x-ray