This document provides a concept design for a DNA vaccine production facility. It describes the process, which includes fermentation, cell harvesting, lysis, clarification, concentration, and purification. It also outlines the raw materials, equipment, staffing needs, and proposed layout of the facility. The layout places production and utilities buildings around the site, with water intake from a nearby river. The production building layout separates areas by cleanroom classification. The document concludes with cost estimates and a proposed timeline for developing the facility.

1. 09/03/2017
CONCEPT DESIGN FOR DNA
VACCINE PRODUCTION
Plant design and manufacturing principles in (bio)
pharmaceuticalproduction
Marcin Wiktor Konarski
ID Number:1735729;Word Count:4971
Summary
This paper describes conceptdesign of the pharmaceutical facility focused on production of
DNA vaccines.Itfocuses on general layoutof proposed facility as well as flows which will be
present duringthe manufacturing,equipment required for production,costingand validation
of project.
First,the production was presented alongwith the media needed and scaleof production
assumed for this projectand staff involved to run this facility.Further, layoutwas shown and
described with argumentation. Utilities were proposed for cleaning,waste removal,heat
production,air purification systems,etc.
Project was concluded with costingof such facility,validation and timetableto develop this
facility and opinions of author regardingpossibledifficulties alongthe way.

2. 1

3. 2
Introduction
Manufacturing DNA plasmids is vital activity. These vaccinations are used for gene therapy &
vaccination. They trigger immune responses in responsible way. This facility allows the company to
take on the demand of the product as well as reduce the costs of the production & transport.
Thisproject’saim istodesignthefacility,describingeachof the processstepsinthe productionhouse.
Utilities and manufacturing flows were added to the layout and proposed existing systems to
implement as example.
Duringthe designing,thereare regulationsfromagenciesoverseeingthepharmaceutical industrysuch
as FDA inUnitedStatesof Americaaswell asregulationsof the specificcountrythe facilitywillbe built
on. Additionally, the facility must be built with accordance of cGMP (current Good Manufacturing
Practice).
The assumptions must be made when designing. First, maximum budget must be established for the
facility.Inthiscase,the budgetisset in £ 6 000 000. It isaverage numberforsuch a facility.Lastyear,
Big DNA started a facility of similar magnitude and the budget is set for £ 1,5 mil. Also, there is river
whichcan be usedas a source of wateras well as no needforterrain smoothingandlogisticsare not
a problem.
Otherassumptionisthatthe terrainobtainedisideal topresentedspecificationandthatthe reactions
are stechiometric. The specificlengthanddesignof the piping& valvesare unknownon thisstage of
design. Cost were evaluated to make approximations on the cost of the whole facility.
Followingreportwill make anattemptto designandcharacterize the facilityincludingrealizationthe
cost of it and presenting possible obstacles, which might be ahead.

4. 3
Table of Contents
Introduction ................................................................................................................................. 2
Details of the process.................................................................................................................... 4
Process Description................................................................................................................... 4
Production................................................................................................................................ 4
Raw Materials Required............................................................................................................. 5
Equipment required .................................................................................................................. 6
Staff Involved............................................................................................................................ 7
Design of manufacturingfacility..................................................................................................... 7
Plant Location........................................................................................................................... 7
Plant Layout.............................................................................................................................. 8
Layout Description................................................................................................................. 8
Layout of the production site.................................................................................................11
Manufacturing flow..................................................................................................................12
Material...............................................................................................................................12
Personnel.............................................................................................................................12
Waste Materials ...................................................................................................................12
Room Data Sheet Specification..............................................................................................13
Plant Services, Systems and Utilities..........................................................................................17
Heating, Ventilation and air-conditioning(HVAC) system ........................................................17
Water...................................................................................................................................17
Clean Steam.........................................................................................................................19
Heat and Power....................................................................................................................19
Cleaning-in-Place/Sterilizing-in-place (CIP/SIP)........................................................................19
Process Control & Instrumentation........................................................................................20
Cleanrooms..........................................................................................................................21
Process Validation, cGMP .........................................................................................................21
Gantt Chart..............................................................................................................................21
Costing....................................................................................................................................22
Capital Costs.........................................................................................................................22
Operating Costs....................................................................................................................23
Conclusion...............................................................................................................................25
Reference................................................................................................................................25

5. 4
Details of the process
Process Description
Large-scale production of pharmaceutical-grade plasmid DNA is designed for production of large amount
of material with specific purity, potency, efficiency for therapeutic use.
The process consists of several steps:
 Fermentation
 Cell Harvest
 Cellular Lysis
 Clarification & Concentration
 Purification
Process starts with upstream processing. There is construction/selection of specific vectors as well as
choosing the host. Plasmid pUC19 is used as a starting vector because of its high copy number, as well as
temperature influence copy number. Next, the host is chosen to minimize the fraction of impurities –
Eschericha Coli strain HB101was chosen with low levels of nucleases production. Other reason for choosing
E.coli is popularity of this bacteria and large amount of information about it. (Prazeres et al., 1999)
Production
Fed-batch fermentation is used to grow cells. It must possess the extensive control system to monitor the
essential parameters. Nutrient, oxygen, heat, broth and electricity are delivered directly to fermentator. It
must be optimized in terms of low aeration, heat transfer and low shear affecting cells. Fermentation can
result in yield 230 [
𝜇𝑚
𝑚𝑙
] at temperature 30℃. (Prazeres et al., 1999)
After the fermentation, it is time for downstream processing. Their purpose is to eliminate the cellular
wastes from the solution of the host. First is the removal of cells from the broth in way of centrifugation.
After, the cells arere-suspended and buffer (such as EDTA)is used to disrupt cells and release the plasmids.
Usually it disrupts hydrogen bonds between lipids. (Prazeres et al., 1999)
Next is the alkaline lysis. The suspended solution is under Sodium Hydroxide and SDS treatment for
complete lysis of cells. Then, salt-neutralizing solution is added to achieve the formation of aggregates of
gDNA and SDS-protein complexes and is removed through filtration (solid-liquid separation). Finally, the
isopropanol is added for precipitation.
After lysis, clarification and concentration takes place to remove E.coli proteins and nucleic acids as well as
reducing the process stream via ammonium-acetate precipitation of proteins.
Last step is purification, where ion-exchange column chromatography is used and gel filtration. In ion
exchange electrostatic attraction between solute and cluster of charged particles is used for separation.
During filtration aggregates, whichare larger in size then others areremoved. They are sieved in stationary
beads. (Prazeres et al., 1999) To further polish product size exclusion column is added for endotoxin
removal. Figure 1. shows the whole process.

6. 5
Figure 1. Scheme of production process (c.) (Ferreira et al., 2000)
Raw Materials Required
There are many components needed to enter the process in order to createthe final product. They can be
divided into three main groups: Basic, Chemical, Biological. For pharmaceutical industry purity is essential,
there are requirements for purification upon entering the process.
Basic Media are substances used by wide rangeof apparatus and in largequantities. All of these arepresent
in number of critical appliances, directly linked to process or in utilities:
Table 1. Basic Media.
Basic Media
Water
Heat
Gas
Clean Steam
CompressedAir
Chemical Components are substances directly required in main process for reactions & treatment &
separation. They are not used in side processes or utility.
Table 2. Chemical Components.
Chemical Components
Oxygen
Nitrogen
Sodium Hydroxide
Salt-NeutralizingSolution
SDS
SodiumDodecyl Sulphate
Sodium Glycine
Tri-sodium Citrate
Sodium Chloride
Potassium Acetate
EDTA
Isopropanol
Biological Components have similar role in theprocess aschemical one but the waste createdis much more
difficult to remove. Additionally, it is imperative to modify these materials for maximum performance.

7. 6
Table 3. Biological Components
Biological Components
E.coli strains
VectorpUC19
Medium
Other Materials:
 Gel matrices for filtration
Equipment required
Each of unit operation requires utility apparatus and auxiliary appliances for proper functioning. Pumps
used for reagent input usually have capacity of 0,2 [
𝑙𝑖𝑡𝑟𝑒
𝑚𝑖𝑛
] and the reagent tanks – 10 [𝑙𝑖𝑡𝑟𝑒], while main
product pumps have capacity of approximately 1000 [ 𝑙𝑖𝑡𝑟𝑒
ℎ𝑜𝑢𝑟
].
Table 4. Equipment List
Main Equipment Additional Equipment
Seed Vessel (𝟎. 𝟎𝟏𝟓 & 𝟎. 𝟏𝟓 [ 𝒎 𝟑])
o Acid Tank
o Acid Pump
o Base Tank
o Base Pump
o Antifoam Tank
o Antifoam Pump
o Air Compressor
o Main Pump
Large scale fermentator (1500 [litre])
o Acid Tank
o Acid Pump
o Base Tank
o Base Pump
o Antifoam Tank
o Antifoam Pump
o Air Compressor
o Main Pump
o Inoculum Pump
Disc Centrifuge (1000 [l/h])
o Broth Pump
o Kill Tank Pump
Lysis reactor (4000 [litre])
o Reagent Tanks
o Lysate Tank
o Buffor Pump
o NaOH/SDS Pump
o Main Pump
Ammonium-acetate precipitator
o Reagent Tank
o Reagent Pump
o Main Pump
Ion-Exchange Chromatography column (42
[litre])
o Buffer Tanks
o Product Tank
o Waste Tank
o Sodium Glycine Pump
o Tri-sodium Citrate Pump
o Product Pump
Gel filtration (250 [litre])
o Product Tank
o Waste Tank

8. 7
o NaCl Tank
Size Exclusion Column
Boiler Unit
Cooling Unit
HVAC system (heating, ventilation & air
conditioning)
Control Equipment
Piping, Valves
Staff Involved
During the production, there will a staff needed, which oversight the production as well as load the
feedstock and react in random situations. Due the assumption made in the introduction – facility is
producing plasmid 24h a day, there must be 4 shift present across the day.
According to literature, to maintain production, 50 workers are required. Also 5 engineers to manage the
situation is needed. During the night, the staff should be shortened and it might be controlled from remote
place if accessible via internet.
Beside workers and engineers, in the facility there must be additional staff such as security guards,
controllers and other support staff working and maintaining facility.
Overall, number of workers employed in the whole plant can be estimated as approximately 500 people. It
is based on the similar facility of DNA vaccines being built in Scotland by the Iceni Pharmaceuticals.
Design of manufacturing facility
Plant Location
There are several factors which must be included when deciding the sitting of the facility. Most important
is the safetyof the nearby populated areasas wellas environment, keep thecost of the product tominimum
and easy access for workers to arrive.
There areseveral points which areimportant (Plant location: 11 factors that influence theselection of plant
location, 2014):
 Availability of Raw materials
 Proximity to Market
 Infrastructural Facilities
 Government Policy
 Availability of Manpower
 Local Laws, Regulations and Taxation
 Ecological and Enviromental Factors
 Competition
 Incentives, Land costs. Subsidies
 Climate Condition
It is important to know where the basic media will be provided from to lower the transportation costs.
Location close to this segment may influence the place to sell the final product – DNA plasmids. It will
increase transportation costs as well. The good location is next to the river, big enough to cover the needs
of the facility, close to gas storagefor electricity and heating purposes and near to the medium-sized
town for manpower. Transportation method for workers must be taken into account. Looking into local
laws is necessary to make sure the facility does not break any environmental laws established. (Plant
location:11 factors that influence the selection of plantlocation,2014)

9. 8
Next is the government approval and tax exemptions for clean energy etc. usage. Lastly, the geological
analysis of the area to ensure no dangerous scenarios and approval from Environment Agency of the
country where will be the facility. The location of the competition factory may increase the costs as well. In
the end the land cost is evaluated to receive as low price as possible – it is most direct way of lowering cost
of siting the factories. (Plant location: 11 factors that influence the selection of plant location, 2014)
Plant Layout
Layout Description
PlantLayout
Layout in Figure 2. present designed facility. From north, there is a river capable of sustaining water need
of the facility. Water (purple colour) is pumped into the purification processes. It is then send to rest of the
factory. Power (blue colour) and heat is produced in the CHP system next to water treatment, utilizing
natural gas (green colour) brought with pipeline. It is then distributed towards all buildings. Gas storage is
deliberately position in distance from other facilities in case of leakage or other incidents. Production
Building is placed in the middle. Other important infrastructure is placed around the facility. Waste (brown
colour) is directed to waste treatment building. Materials (red colour) is taken from storage and delivered
to production and then to product storage.
Production HouseLayout
Layout of production house’s main floor is shown in Fig. 4. Generally, building consist of basement level,
ground floor and first floor. On the first floor, there is HVAC system and technical area together with
distribution of services. As for the basement, there are located kill tanks for processes, shelters and
workshops. Entrance for the staff is located in the east as well as entrance for the components required
for project (gate G1). Then it travels west first for control, inoculum seed vessels, then to fermentation
and downstream processing. It is then storage next to southern wall and send out through gateG2.
Specific colors of is different cleanroom classification. Some processes require higher cleanness then
others with accordance to EU regulations (Grade C, Grade D, Grade A/E).

10. 9
Figure 1. Facility Layout

11. 10
Figure 2. Personnel Flow Layout

12. 11
Layout of the production site
Figure 3. Production House Layout

13. 12
Manufacturing flow
Material
Fermenter
Input media is continuously sterilized and then send to fermenter. For the inoculum, there are two seed
vessels (small sizes), run one after another for maximum performance.
Air is delivered to fermenter after filtration (through compressor) to prevent contamination. Nutrients are
sterilized as well into fed-batch reactor. After the growth period (approx. 1 day), biomass is received and
the broth is harvested by way of pumping to centrifuge. Clean steam is delivered as well as cooling water.
Centrifuge
Broth is pumped into thecentrifuge (1000 [
𝑙
ℎ
]) for solid-liquid separation. Solid is removed and dewatered,
while concentrated broth is pumped to alkaline lysis reactor.
Lysis Reactor
Product is suspended in largeamount of EDTA. Then, thereis the spontaneous reaction with NaOH and SDS
in ratio 1:1 for cellular rapture. In the end, cell debris is precipitated with isopropanol, then neutralized in
1:1 ratio with potassium acetate.
Clarification & Concentration
To remove large quantity of proteins from degeneration there must be additional steps after lysis.
Clarification & Concentration is used to remove those, increasing yield of plasmid in the process. It is
important to remove RNA of high molecular weight. They are “salted out” with ammonium acetate. The,
plasmid DNA is concentrated using PEG precipitation. (Ferreira et al., 2000)
Ion Exchange Chromatography
Feedstock is pumped into the column (45 [litre]) at high speed (1000 [𝑙/ℎ]). Charged plasmids are bound
by ion exchange. Material which bounds on wall of column, is removed by sodium glycine (205 [litre]) and
plasmid is eluted by tri-sodium citrate (255 [litre]). Output flow of 250 litres is send towards filtration
column with fourth of the product lost.
Gel Filtration Column
Flowrate in the column is 2000 [𝑙𝑖𝑡𝑟𝑒/𝑚3
ℎ]. 0,1M NaCl is used as a buffer. Pharmacia Sephadex is used as
a fill of the column for final purification (99,5%). Approximately 30 liter of purified product is send further.
Rest of the buffer is send to the tank.
Personnel
One of the main flow which must be considered is personnel. When designing new pharmaceutical facility
to link the various parts of the facility including the personnel inside such as chemist, engineers, biologists
and other professions to complete task most efficiently. Flow of this personnel is shown on the Figure 3.
Personnel (pink colour) arrives in the south either by caror company bus. Materials and components arrive
via east gate or west depending on the destination. Product is then shipped through separate gate in the
south-west.
Waste Materials
Beside the basic media, product and people flow, there is one more, which
must be discussed. Waste materials is vital part of chemical facility design.
Waste must be treatedaccording to the regulations and standards (ISO etc.).
For treatment of wastewater, membrane system was used, due to high
efficiency and low cost. Example of such system might be GE Water ZeeWeed
MBR system, which combines membrane and biological treatment. When
dealing with solid waste, it must be first incinerated, then autoclaved.

14. 13
Room Data Sheet Specification

15. 14

16. 15

17. 16

18. 17
Plant Services, Systems and Utilities
Heating, Ventilation and air-conditioning (HVAC) system
In pharmaceutical industry, there is many concerns put into purity of the final product. There is GMP
concerning design of HVAC system, taking into account several variables such as building materials, flow of
equipment, and key parameters like temperature, humidity, pressure, filtration, airflow parameters and
classification of cleanroom. (Bhatia, 2008)
It performs basic functions such as control airborne particles, dust and microorganisms using HEPA filters.
Maintains room pressure to ensure positive pressure (flow of cleaner airtowards exits of the room). It also
ensures constant relative humidity which can be controlled via cooled air (might affect stability of product)
and monitors is space temperature. (Bhatia, 2008)
When designing the HVAC system, it is imperative to take into account those parametersfor GMP. It is also
desirable to keep similarly classified areas close to each other to allow connection to same air handling
system and organized in a way that people don’t disrupt the cleanness. Heat balance must be calculated
for heat-loss through walls and doors as well as psychometric analysis for full air sheet. Air handling units
should be placed in rooms which require cleanness. (Bhatia, 2008)
Recirculated HVAC was chosen due to easier control of parameters such as temperature, humidity,
pressure as well as lower cost of cooling and heating. It also ensures better air filtration.
Figure 5. Recirculated Air Schematic. (Bhatia, 2008)
Air Handling Unit is made of filters, fans and coils closed in the box (easy for cleaning and isolated with
insulation). If there is a need for heating or cooling there are heating/cooling coils installed. To control
humidity, there are de/-humidifiers installed.
Water
Water is used in multiple steps of production. Most direct use of water is as an input. Water as an input is
used in the production as a solvent and process fluid. It is also used in CIP and SIP systems, autoclave and
for rinsening. It’s used as well for temperature regulation as jacket fluid.
Due to wide range of applications of water for different purposes and requirements of each processes it is
imperative to minimize the contaminants present such as organics (petrochemical, plant, mammalian
matter), inorganics (ions such as calcium, magnesium, chloride, carbon dioxide etc.), matter,
microorganisms (bacteria)and pyrogens (might cause illness). It is regulatedby national agency tasked with
oversight of the facility. They state the conditions of the products must fulfill and it is required to meet
them no matter the process used.

19. 18
Figure 6. Proposed water treatment system with steam generation. (Pharmaceutical water purification systems,
2016)
This system proposed by the NGK Insulators is designed for pharmaceutical industry. It comprises of three
stages to ensure full contaminants removal. In addition, there is also module for steam generation which is
one of the needed media.
For first stage of water purification, water must be removed of big particles with pre-treatment (bag
filtration) and through softener units. Then, reverse osmosis is used followed by electro-deionisation to use
electrostatics to remove ions, lowering conductivity in addition. In the end, it is heated and treated with
ultraviolet to achieve purified water. It is used in CIP to clean processes.
Second stage focuses on use of the ultra-filtration for further contamination removal. In the last stage,
distillation process is combined with steam generation for production WFI (water for injection) used in drug
formulation, fermentation and rinsing after CIP. There are several columns to ensure complete
decontamination.

20. 19
Clean Steam
It is used when contact with materials is needed without causing contamination. Conventional boiler
produce steam which cannot be used in this case due to contamination avoidance. It is used for sterilization
in SIP.
It is generated to avoid droplet generation. There are several methods used but the best one is
thermosyphon, displayed below. (Latham, Eng, and Micheme, no date)
Figure 7. Clean Steam Generator. (Latham, Eng, and Micheme, no date)
Heat and Power
In order to supply the facility with energy and heat, Combined Heating and Power System was installed
(CHP). It is cogeneration system, fueled by natural gas, biofuel, biodiesel. SAV system CHP system is
proposed as a source. It has high efficiency and low cost of maintenance.
Figure 8. SAV Systems CHP system. (Andara, 2017)
Power unit is an engine producing power and heat. It is then stored and distributed towards designated
facilities.
Cleaning-in-Place/Sterilizing-in-place (CIP/SIP)
It is critical process for the pharmaceutical production in terms of hygiene and purity of the products.
Introduction of automatic control in cleaning process leads to shortening thetime of apparatusmaintaining
and limiting costs. It consist of tanks filled with cleaning substances and used ones, pumps & valves for

21. 20
circulation of this substance, and units for cleaning control. Filtration is then used to recycle the substance.
(Paper, 2013)
When designing, it is important to ensure elimination of fouling andbeing properly welded. When designing
such system there are several parameters, which must be taken into account including flow rate, op.
temperature, cleaning substance and pump selection. (Paper, 2013)
For this facility, Bosch’s CIP system was chosen. It was designed specifically for this purpose and according
to GMP, it has 10000 [litre] storage capacity. The cleaning substance is sodium hydroxide. (Bosch presents
CIP system for use in vaccine production, 2014)
Second system called sterilizing in place is used to sterilize the process apparatus. Sterilization is controlled
by installing thermocouples in the equipment. For tank sterilization, steam enters the tank as superheated
vapour from above, it condenses and is collected at the bottom. (Cappia, 2004)
Process Control & Instrumentation
Processes, apparatus and utilities are controlled via installed devices
on-line/off-line/in-line depending on the situation. Sensors areinstalled
on the process and signals go into the controller which regulate control
devices for example valves or motors. The sensor/control system works
in control feedback loop, which must be tuned to eliminate deviation.
Figure 9. CIP/SIP system (Bosch)
Parameters which are monitored are among others:
 Temperature
 Pressure
 Level
 Flow
 Quantity
 Moisture
 pH
These arebasic instrumentation but there aremore complicated measurements such as chromatographic,
UV etc. checking parameters important to the process.
For each component of the process there are several parameters to control:
 Fermenter
o Level Sonic Measurement
o Pressure Piezoelectric Measurement
o Thermocouple
o UV analysis
o pH probe
 Alkaline Lysis
o Level Sonic Measurement
o Pressure Piezoelectric Measurement

22. 21
o Thermocouple
o pH Measurement
 Clarification & Concentration
o Level Sonic Measurement
o Thermocouple
o Chromatographic
 Ion Exchange Column
o Flow Measurement
 Gel Filtration
o Pressure Piezoelectric Measurement
o Laser Particle Counter
o Electrophoresis
 Piping
o Flow Measurement
Cleanrooms
DNA Vaccines are produced in cleanrooms to keep one of the principles of GMP to prevent contamination,
dust. These cleanrooms are made according to specific ISO classification. Process rooms where special
equipment is needed including fermentation, storage and raw materials are equipped with Class 100
biosafety with HEPA filters (High Efficiency Particulate Air Filter) and HVAC. There is a requirement for
airlocks and separate rooms for staff, raw and waste materials. Inlet for air as well as exit with activated
carbon filter to purify is needed. Appropriate floor as well as electricity, light and HVAC system for safety
and free from contamination.
Cleanrooms present in the facility will be grade B, C, D situated in close proximity within the facility. Rooms
will be equipped with sensors to detect air flow, pressure etc. (McFadden, 2010)
Process Validation, cGMP
Process of validation is an imperative for the plant design. It allows to follow the cGMP – current Good
Manufacturing Practice. Validation evaluates logic of thedesign and exposes the weaknesses. Main reasons
for conducing validation is law procedures, quality assurance and lowering cost. (Bennett, Cole, 2003)
In the beginning, it starts with User Requirement Specifications (URS), created by design engineer. Next,
the objective is to write up the validation master plan which is a protocol for validation of how it should be
done. It takes into account expected outcomes and to show outside clients the regulations. Into this VMP
it is included:
 Design qualification (DQ) –confronting the pieces of equipment tomatch theregulations theymust
abide;
 Process Validation (PV)
 Installation qualification (IQ) – verify the layout as well as systems are built in accordance with
standards;
 Operational Qualification (OQ) – confront that the equipment work within the stated parameter,
testing alarms, switches etc.;
 Performance qualification (PQ) – performance tests of main apparatus;
Gantt Chart
In planning the facility, to organize the schedule for each of the steps and set deadline for people to meet,
Gantt chart is used.

23. 22
It is a common tool in project management showing the activities presented against the time. On the left
side, there are activities presented. On the X-axis, there is time presented in a suitable fashion. Bars
presented describe the activity but the duration and start and end date.
Figure 10. Gantt Chart for the current facility creation.
In this scenario, first design must be procured (simplified then detailed). During the same time as detailed
design, procurement must be done for most efficient use of time, since there are already directives for this
from first stage. Environmental Analysis should be then done before beginning of the building to avoid
surprises. After the finish of building there must be validation of the facility and bringing it to commission.
The process should take approximately 2-3 years to come into fruition.
Costing
In plant design, especially in pharmaceutical facility, it is important to createconditions to yield a net profit.
It is an income lowered by the costs of the project. To estimate the costs of the facility there are several
areas, which must be taken into account. A key one is capital cost estimating. It is a direct cost of the plant
including materials and equipment. There are also indirect expenses.
Capital Costs
Capital cost bases around the price of the design, equipment and the utilities. The equipment included
piping, process control instruments and:

24. 23
Table 5. Table of Equipment and cost
Fermentation
Equipment
Cost of
equipment
(taken from
producers’
sites) 𝒌 £
Downstream
Equipment
Cost of
equipment
(taken from
producers’ sites)
𝒌 £
Utility
Equipment
Cost of
equipment
(taken from
producers’ sites)
𝒌 £
2 x Small Seed
Reactors
40 Lysis Reactor 140 Boiler Unit 110
2 x Large Seed
Reactors
170 Disc Centrifuge 80 Chilling Unit 100
2 x Fermenters 200 Expanded Bed
Ion Exchange
Column
45 2 x Storage
Tanks
10
Gel Filtration
Device
30 CIP/SIP
system
60
2 x Buffer Tank 15 Automation 50
Broth Tank 10
5 x Waste Tank 10
3 x Reagent
Storage Tanks
100
Lysate Tank 60
To calculatethe factorialmethod of cost estimation is used. Precision of this method is linked with reliability
of used data and advance of the design. Uses a Lang factors to give a fixed capital cost. (Saeed, 2014)
𝐶 𝑓 = 𝑓𝐿 ∙ 𝐶 𝑒
Where
𝐶𝑓 - fixed capitalcost
𝑓𝐿 - Lang factor (3.6 for mixed liquid-solid processing)
𝐶 𝑒 - total cost of the equipment
𝐶 𝑓 = £ 1 340 000 ∙ 3,6 = £ 4 824 000
Into this amount should be also included the CHP system and water treatment. But because it is outside of
the main process it is not included.
Operating Costs
Next it is important to estimate the operating costs to evaluate the viability of the design. In these costs,
we can distinguish two groups.
Table 6. Types of Operating Costs
Fixed Operating Costs Variable Operating Costs
Maintenance Raw materials
Labour Utilities
Supervision
Insurance
Marketing and Distribution
Recruiting Cost
Training/ plant overhead

25. 24
Fixed Operating Costs
First of the operating cost is maintenance which includes work required, materials. Usually maintenance
costs are 7% of installation costs. (Sinnott, 1993) In this case, it is projected to be £ 600 000.
Next cost will be labour required for operation of the production. Total number of workers is as stated
before and is 55 including the engineers. This cost includes shifts and salary. The averagesalary is £ 35 000.
Training must be included to reduce number of incidents and teach workers the proper procedures in cases
of emergency. Plant overhead includes the medical staff, fire fighters and canteen costs. Usually it is half of
the labour cost. (Sinnott, 2016)
Insurance, marketing and distribution must be also included since it is significant fraction of the costs.
Insurance for the facility is paid as a small yield of capital costs. Also, cost of sales is included into the
operating costs for marketing and moving of the product. Usually it is 20% of the costs.
Variable Operating Costs
Most important fraction of these costs areraw materials. The price of each materialused is taken from the
catalogues available online (Sigma-Alrdrich). However, the quantities of the compounds for one batch of
product is known due to lack of mass balance it is impossible to know the exact cost of the materials, so it
will be approximate estimation (shown in Table 7.).
Table 7. Cost of compounds
Compound Cost per unit
Ammonium hydroxide 300
Sodium Hydroxide 0.1
SDS 1
Isopropanol 1.5
Salt-NeutralizingSolution 0.15
Antifoam 28
Glucose 0.5
Sodium Chloride 0.88
EDTA 5
Tri-sodium citrate 0.25
Ammonium acetate 0.25
Next are media & utilities vital for processes (taken from producers’ and Sigma catalogue and Gov.uk
website):
Table 8. Cost of ultilities
Utility Cost
Gas 2,18 (perkWh)
Gel filtration Matrix 50 000
Mediafor chromatography 100 000
Effluent Treatment 100 000
Overall, it can be concluded that the costs of this facility are:
 Capital Costs - £ 4 824 000
 Operating Costs - £ 750 000

26. 25
Conclusion
Aim of this assignment was to propose a concept design together with estimated costs and schedule.
Layout of both site and production facility was presented in this report with certain assumptions.
Main process was described along with required materials and utility equipment for constant production.
Number of personnel was estimated to employ as well as equipment required to start the production.
Next, detailed description of proposed layout was presented with specific flows of materials, people and
waste. Additionally, room data sheets for two exemplary rooms present in the facility were introduced.
The last part of engineering designing of the facility was to propose plant systems and utilities and show
advantages of chosen components such as efficiency, costing and durability.
Further ahead, costing of the facility was calculated, both capital and operating costs, to ensure the
reasonable budget required to build the facility. It was established that at least £ 5 million is needed,
which is below assumed budget. Validation was also established, to minimize the risks of the investment.
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