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Acknowledgement

Firstly we would like to express our utmost gratitude to the Almighty Allah for helping us to

accomplice this industrial training successfully.

We are thankful to the Department of Mechanical Engineering, BUET for providing us this

unique opportunity of industrial training.

We are also very thankful to all the employees of Incepta Pharmaceuticals Ltd who were very

helpful and co-operative during our whole training schedule. Our special thanks go to Ms.

Zokhroof Yeasmin Khan (Training Coordinator), Mr. Shah Sharfin (Associate Senior Officer,

QC), Mr. Mizanur Rahman Chowdhury (Manager, Engineering), Mr. Mohammad Mamunur

Rashid (Senior Executive Officer, Engineering) for helping us with valuable information and

cooperation during the whole training program.

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1. Introduction

Purpose:

The fundamental objective of Industrial Training is to prepare students for future employment

in their chosen engineering discipline. Industrial Training enhances the academic material

studied at University by allowing students to practice what they have learned and to develop

key professional attributes. Industrial training provides an opportunity for us to:

Experience the discipline of working in a professional engineering organization.

Develop understanding of the functioning and organization of a business.

Interact with other professional and non-professional groups.

Apply engineering methods such as design and problem solving.

Develop technical, interpersonal and communication skills, both oral and written.

Industrial training gives students an opportunity to evaluate future employers as well as

enabling informed decisions about the discipline and career paths to follow.

Training Duration:

Start Date End Date Duration

05 April, 2015 18 April, 2015 2 Weeks

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Industry at a glance

Incepta Pharmaceuticals Ltd. is a leading pharmaceutical company in Bangladesh established

in the year 1999. The company has a very big manufacturing facility located at Savar, 35

kilometer away from the center of the capital city Dhaka.

Incepta Pharmaceuticals Ltd. is now the 2nd largest company of the country and recognized

as the fastest growing of the top five manufacturing company in the country. Established in

the year 1999, the company has come a long way.

The company has a clear vision to become a leading research based dosage form

manufacturing company with global presence within a short period of time. With this view in

mind the company started to expand its business in overseas markets. Currently Incepta

exports to 40 different countries around the world. With hundreds of brands registered in

different countries, and many more in the pipeline, Incepta is gradually expanding its global

footprint across all the continents.

Main products:

The company produces various types of dosage forms which include tablets, capsules, oral

liquids, ampoules, dry powder vials, powder for suspension, nasal sprays, eye drops, creams,

ointments, lotions, gels, prefilled syringes, liquid filled hard gelatin capsules, lyophilized

injections, human vaccine etc.

Production Capacity:

It manufactures more than 650 products from 30 therapeutic classes. The products of Incepta

is sold in 44 countries along with the local market.

Total Area: The Zirabo manufacturing plant covers an area of land about 15,000 m2. The

total built up production area is about 300,000 square feet.

Yearly Turnover:

The sales turnover of Incepta in 2014 was more than 7.4 Billion Taka (US$ 92.71 million)

with about 9.21% market share having a growth rate of about 15.64%.

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No. of Production Facilities:

There are total 3 production facilities in Zirabo factory. These are:

Incepta Pharmaceutical Ltd.

Incepta Vaccines Ltd.

Bio-Derived Product Facility (BDPF)

Power requirement:

Pharmaceutical unit: 3.2- 3.4 MW

Bio-Derived Product Facility (BDPF): 0.8-1.2 MW

Vaccine plant: 1.2- 1.4 MW

No of Engineers: 53 engineers.

Raw materials used and their source:

Pharmaceutical raw materials are essential to producing pharmaceutical drugs and include

active pharmaceutical ingredients (API). Different type of chemicals such as ethanol, Liquid

Glucose, Lactic Acid, Manitol, Citric Acid, Glycerine are used as raw materials. All the raw

materials are purchased from foreign countries. Incepta has no facilities for the production of

API or ingredient for the production of medicines.

Contribution to Bangladeshs economy:

Incepta plays an important role in the economy of Bangladesh. It sells products not only in

local market but also in international market. It has become the second largest pharmaceutical

company in Bangladesh. It has been creating a wide job opportunities for a lots of people.

Besides, Incepta not only supplies the local market but also it exports its products in about 44

countries. In this way they bring a lots of foreign currency in Bangladesh and enhance the

reputation of the pharmaceutical industries of Bangladesh.

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Organogram

Managing Director

Director

Administration

section

Manager

(Admin)

Deputy Manager

Senior Officer

Officer

Assistant Officer

Junior Officer

Production section

Director Operator

Plant Manager

Production

Manager

Deputy

Production

Manager

Senior Officer

Officer

Assistant

Officer

Junior Officer

Engineering

section

Manager

(Engineer)

Deputy/Senior

Engineer

Assistant

Engineer

Sub Assistant

Engineer

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Production Line

The following product forms are manufactured on site:

A. Sterile Products:

Liquid dosage forms (LVP & SVP, Terminally sterilized and aseptically filled

ampoule)

Eye Drops

Solid dosage forms (Solid fill, Dry vials and Freeze-Dried Products)

B. Non Sterile Products:

Liquid dosage forms (Oral Liquid, Nasal Solution, Nasal Spray)

Semisolid dosage forms (Creams, Ointments, Gels)

Solid dosage forms (Tablets, Capsules, Powders, Granules)

C. Biological Products:

Aseptically prepared injectables: Erythropoetin, Enoxaparin, Insulin, Insulin Glargine

(rDNA), Filgrastim

D. Cephalosporins:

Solid dosage forms (Tablets, Capsules, Powder)

Sterile Powders (Aseptically filled vials)

The production area is serviced with HVAC system comprising of multiple AHU that

virtually divides the production area in different zones to implement effectively the latest

concept of GMP. All production activities including primary packaging are operated in the

controlled area where as operations like secondary packaging are conducted in the optical

clean area. To avoid cross contamination, the pressure of production area is kept lower than

that of the passage and to avoid micro-organism the pressure of production area is kept higher

than that of the passage.

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Flow chart of medicine production:

Tablet:

Capsule:

Raw material

collection Raw material sieving Blending or

Mixing

Encapsulation Stripping by strip

packing machine Packing

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Syrup:

Packing Section:

After completing production every product needs to be packed. It is done in the packing

section.

Flow Chart:

Product Clarity Checking Labeling Packing

Sucrose solution

preparation

Dissolving API in

Specific solvent Buffering agent

Coloring

agent

Flavoring

agent

Final volume and

mixing Filling Sealing

Clarity checking Labeling Packing

Final product analysis

and inspection F.G. Store

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Quality Control & Quality Assurance

The (Quality Management System) QMS of Incepta Pharmaceuticals Limited is established

in a frame to describe its operations in different documents and practices which is based on

the principles of PICS and WHO guidelines. The Quality Manual describes the Quality

Policy of Incepta Pharmaceuticals Limited.

The responsibilities for the technical aspects of Quality Assurance are defined in the Quality

Manual. It encompasses all activities necessary to generate, maintain and verify the quality of

drugs.

The Quality Assurance of Zirabo Plant consists of Quality Control, Quality Compliance and

Quality Surveillance. The main tasks and duties of Quality Control have been described in

the Quality Manual and relevant SOPs. The Head of Quality Assurance or his delegates are

responsible for releasing drug substances, excipients, dosage forms and packaging materials.

Quality Compliance is responsible for IPC, GMP co-ordination and training. Performances of

routine GMP checks are done as per need. Monitors to respect GMP regulation in the

manufacturing by instant checks of Batch Record completion, visual checks of cleaning of

working place, line clearance, performance checks of balance & other equipment.

Quality Surveillance is responsible for the implementation of the Quality Management

System in different areas in collaboration with different departments. Quality Surveillance

play active role in conducting external and internal audits with their follow-ups.

Research & Development is responsible for formulation development and method

development, implementing technical transfer to Production and Quality Control, and also

covers process validation, cleaning validation, method validation and follow up stability.

The Quality Manual describes how testing instructions are established and used. The testing

instructions include the specifications and testing methods. The testing instructions are

binding for release testing and for follow-up stability testing.

A routine inspection is being done in the name of "Self Inspection" mainly concerned with

safety, sanitation and infra-structural facilities leading to GMP including documentation.

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Supply of raw materials are mainly obtained from approved suppliers. We select and evaluate

the supplier as per procedures. This procedure is also applicable in case of supply of Primary

and Secondary Packaging Materials.

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Technical Features

Main Utilities:

Power or Electricity

Pharmaceutical Water

Steam

HVAC system

Compressed air

Effluent Treatment Plant

WTP = Water Treatment Plant

ETP = Effluent Treatment Plant

Utilities

Power or

Electricity

WTP Boiler Compre

ssed Air

HVAC

System

ETP

Potable Water Purified Water

(PW)

Water for

Injection (WFI)

Chilled water

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Power Generation

The total power of Incepta is generated from two units. One is situated at Pharmaceuticals

facility and the other is situated at BDPF.

Incepta Pharmaceuticals Facility

The total power generation capacity of Incepta Pharmaceuticals Ltd. Is about 8 MW. The

power is generated from gas and diesel generators. There are 4 gas generators and 6 diesel

generators.

4 Gas Generators-

One generator of 2 MW capacity

Three generators of 1 MW capacity each

6 Diesel generators-

One of 800 KW capacity,

One of 256 KW capacity and

Four of 500 KW capacity each.

Besides, a part of the required power is supplied from Rural Electrification Board (REB) as

per requirement.

The average power requirement ofInceptaPharmaceuticals Ltd. is about 3.2 MW.

Bio-Derived Product Facility (BDPF);

This facility has its own power generation system. It consists of

One gas generator of 2MW capacity

Two diesel generators of 800 KW and 830 KW capacity

So the total generation capacity of BDPF is about 3.6 MW. This facility receives about 200

KW power from REB.

The other facility i.e. Incepta Vaccines Ltd. has no power generation system. This facility

receives its power from both the above mentioned power generation units.

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GENERATOR SETS SPECIFICATION (2 MW)

UNITS: US METRIC

Maximum Continuous Rating: 2027 kW

Fuel Type: Natural Gas

Maximum Electrical Efficiency 44.7%

Maximum Standby Rating 2027

Frequency: 50/60Hz

Rpm: 1500rpm

ENGINE SPECIFICATION

Engine Model: G3516H

Bore: 6.7 in

Stroke: 8.5 in

Displacement: 4765.0 in3

Aspiration: TA

Fig. 1: Caterpillar G3516E Gas Generator

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GENERATOR SET DIMENSION

Length: 291.0 in

Width: 84.0 in

Height: 95.0 in

Dry weight genset: 40384.0 lb

G3516H STANDARD EQUIPMENT

AIR INLET

Package Mounted Air Cleaner with service indicator

COOLING

Engine driven water pumps for jacket water and after-cooler

EXHAUST

Center section cooled turbocharger with Cat flanged outlet

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Waste Heat Recovery System (Cogeneration)

At Incepta waste heat recovery system is in operation. A boiler is operated by means of the

exhaust of the 2 MW and 1 MW generators. On the other hand a chiller is run by means of

hot jacket water.

Fig. 2: Waste Heat Recovery System (Trigeneration)

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HVAC System

The acronym HVAC stands for Heating, Ventilation and Air-Conditioning.

It is the technology of indoor and vehicular environmental comfort. Its goal is to provide

thermal comfort and acceptable indoor air quality.

HVAC system design is a sub-discipline of mechanical engineering, based on the principles

of thermodynamics, fluid mechanics, and heat transfer.

HVAC is important in the design of medium to large industrial and office buildings such as

skyscrapers and in marine environments such as aquariums, where safe and healthy building

conditions are regulated with respect to temperature and humidity, using fresh air from

outdoors.

Purposes of HVAC System In Pharmaceutical Industries

- Maintaining temperature and humidity in a definite range.

- Maintaining pressure.

- Filtration.

- Avoiding contamination.

- Effective airlock system.

Components of HVAC System

Air conditioner

AHUs

Dehumidifier / Heater

Filters (Pre & HEPA)

Dust Extractors

Ducting (For supply & return of conditioned air)

Supply Fans

Dampers

Humidity / Temperature / Pressure sensors

Bag Filters

Heating / Cooling Coils

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Air Handling Unit (AHU)

An air handler or air handling unit (AHU) is a device used to regulate and circulate air as part

of a heating, ventilating, and air-conditioning (HVAC) system. An air handler is usually a

large metal box containing a blower, heating or cooling elements, filter racks or chambers,

sound attenuators, and dampers. Air handlers usually connect to a ductwork ventilation

system that distributes the conditioned air through the building and returns it to the AHU.

Components of Air Handling Unit

1 Supply duct

2 Fan compartment

3 Vibration isolator ('flex joint')

4 Heating and/or cooling coil

5 Filter compartment

6 Mixed (recirculated + outside) air duct

Fig. 3: Components of AHU

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Filters

Air filtration provides clean dust-free air to the building occupants. It may be via simple

filtering media, HEPA, electrostatic, or a combination of techniques. Gas-phase and

ultraviolet air treatments may be employed as well.

Filtration is typically placed first in the AHU in order to keep all the downstream components

clean. Depending upon the grade of filtration required, typically filters will be arranged in

two (or more) successive banks with a coarse-grade panel filter provided in front of a fine-

grade bag filter, or other final filtration medium.

The life of a filter may be assessed by monitoring the pressure drop through the filter medium

at design air volume flow rate. This may be done by means of a visual display using a

pressure gauge, or by a pressure switch linked to an alarm point on the building control

system. Failure to replace a filter may eventually lead to its collapse and thus contamination

of the air handler and downstream ductwork.

Fig. 4: Schematic diagram of an AHU

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Heating and Cooling Elements

Air handlers may need to provide heating, cooling, or both to change the supply air

temperature, and humidity level depending on the location and the application.

Such conditioning is provided by heat exchanger coil(s) within the AHU air stream, such

coils may be direct or indirect in relation to the medium providing the heating or cooling

effect.

Coils are typically manufactured from copper for the tubes, with copper or aluminum fins to

aid heat transfer.

If dehumidification is required, then the cooling coil is employed to over-cool, so

condensation occurs. A heater coil placed after the cooling coil re-heats the air to the desired

supply temperature. This has the effect of reducing the relative humidity level of the supply

air.

Heat recovery device

A heat recovery device i.e. heat exchanger of many types, may be fitted to the air handler

between supply and extract airstreams for energy savings and increasing capacity. Commonly

used heat recovery devices include Recuperator or Plate Heat exchanger, thermal wheel etc.

Thermal wheel or Rotary heat exchanger: A slowly rotating matrix of finely corrugated

metal, operating in both opposing airstreams.

Fig. 5: Different types of filters used in pharmaceutical industries

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When the AHU is in heating mode, heat is absorbed as air passes through the matrix in the

exhaust airstream, during one half rotation, and released during the second half rotation into

the supply airstream.

When the AHU is in cooling mode, heat is released as air passes through the matrix in the

exhaust airstream, during one half rotation, and absorbed during the second half rotation into

the supply airstream. Heat recovery efficiency up to 85%.

Fig. 6: A thermal wheel

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Clean Room

A cleanroom or clean room is an environment, typically used in manufacturing or scientific

research, with a low level of environmental pollutants such as dust, airborne microbes,

aerosol particles, and chemical vapors. More accurately, a cleanroom has a controlled level of

contamination that is specified by the number of particles per cubic meter at a specified

particle size.

In the pharmaceutical industry, clean rooms play a crucial role in the manufacturing of

pharmaceutical products which are required to be free from microbial and particulate

contamination and protected from moisture. Such pharmaceutical products are manufactured

and manipulated in cleanrooms, which are fitted with HEPA(High-Efficiency particulate

Arrestance) and, if required, ULPA (Ultra-Low Particulate Air) filters as well as dehumidifier

systems.

Fig. 7: A clean room corridor

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Cleanroom zoning

There are four types of clean zones in manufacturing sterilized pharmaceutical products. The

grade is defined by the type of product and a part of process which needs to be protected from

contamination.

A local zone. For operations that affords high risk for product quality, e.g. filling, closing,

ampoule and bottle opening zones. Usually in such zones is used laminar air flow which

provides similar velocity 0.36-0.54 m/s.

B zone, which is circled A-zone, is used for an aseptic preparation and fulfill

C and D is a clean zones for less responsible stages of manufacturing sterilized products.

etc.

X Filling for aseptic process

X Filling for terminal sterilization

X Depyrogenisation of containers

X X X Preparation of solutions for aseptic filling

X Preparation of solution for terminal sterilization

X Washing of containers

D C B A

Fig. 8: Level of protection for Cleanrooms

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Pressure Cascade

Controlling room pressure is only one aspect of cleanroom facility design when creating

segregated zones of different class. Specifying room overpressure in cleanroom design is a

common contamination control concept. To achieve this the HVAC needs to be designed to

control the room pressure by some means. Most commonly this is achieved using pressure

controlled actuated dampers in the return ducting. These dampers have to be designed to

modulate within a certain airflow range and with a specific accuracy and speed of reaction.

Fig. 9: Pressure Cascade (sterile production)

(Protection from Micro-organisms and Particles)

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Fig. 10: Pressure Cascade (Solid Production)

(Protection from Cross-Contamination)

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Boiler:

There are total 7 boilers present in different plants of Incepta. Only 2 of the boilers are run by

the exhaust of generators. The rest of the boilers are run by natural gas or diesel. The use of

fuel depends on the availability of natural gas. 2 boilers have capacity of 5 tons each, 3

boilers have capacity of 2.5 tons and the exhaust run boilers have capacity of 2 tons.

Potable water is used as feedwater of boiler thereby preventing corrosion of boiler. The steam

produced is known as industrial steam. It has several applications e.g. laundry, production of

pure steam, in HVAC system etc.

Fig. 11: Boiler

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Boiler Mountings:

These are different fittings and devices necessary for the operation and safety of a boiler.

Boiler mountings are generally mounted over the boiler shell. The following mountings are

usually installed on a boiler-

Water level indicator

Pressure gauges

Pressure relief valves

Steam stop valve

Feed check valve

Blow down valve

Low water alarms

Fusible plug

Man and mud holes covers, etc.

Boiler Accessories:

These are auxiliary plants and devices required for the proper and efficient operation of

boilers. Commonly used accessories are-

Air pre-heater,

Economizer,

Super heater,

Feed pump,

Injector, etc.

Application of boiler in Incepta

Production of pure steam

Heating purpose

Autoclave and sterilization

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Chiller

In Incepta Pharmaceuticals Ltd both absorption chiller and compression chillers are present.

The absorption chillers use LiBr-H2O system. The temperature of chilled water is kept

between 7-8 C.

There are 8 chillers in Incepta. 5 of them are absorption chiller and 3 of them are compression

chiller. 1 of the absorption chillers is run by the hot jacket water from gas generator, and

another chiller is run from the exhaust of a boiler. The other absorption chillers use either

natural gas or diesel as fuel.

Fig. 12: Chiller

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Cooling Tower:

Cooling towers are used to reject heat from generators, condenser water of chillers etc. The

cooling towers in Incepta are evaporative type.

Fig. 13: Cooling tower

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Air Compressor

A sterile environment is essential in the pharmaceutical industry. So when it comes to

compressed air, only oil-free will do.

Any contaminates in compressed air, such as oil, can cause process disruptions, production

shutdowns, and expensive product recalls and company reputation.

Use of Compressed Air

Process air air used in direct contact with products for cleaning, aeration and

product moving

Control valves & cylinders to control equipment used in the manufacturing process

Material handling Fluid pumping systems are operated by compressed air in

volatile environments without the risk of explosion

Nitrogen generation air is filtered via a membrane to produce nitrogen

Air curtains air is used as a curtain to create a safe and clean area

Product drying air is mixed with products to accelerate the drying process.

Fig. 14: Srew Compressor

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Water Treatment Plant

Water is the most widely used substance, raw material or starting material in the production,

processing and formulation of pharmaceutical products.Control of the quality of water

throughout the production, storage and distribution processes, including microbiological and

chemical quality, is a major concern.

Types of Water in Pharmaceuticals Industries:

Drinking or potable water

Purified Water (PW)

Water for Injection (WFI)

Potable Water

Typical processes employed include:

Desalinization;

Filtration;

Softening;

Disinfection or sanitization (by sodium hypochlorite (chlorine) injection);

Iron (ferrous) removal;

Precipitation;

Reduction of concentration of specific inorganic and/or organic materials.

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Purified Water (PW)

Fig. 16: Schematic diagram of Purified Water (PW) production

Fig. 15: A Water Treatment Plant

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Water for Injection (WFI):

Fig. 17: Schematic diagram of WFI production

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Effluent Treatment Plant

Generally three types of waste are generated from pharmaceutical industries:

Process waste water,

Utility waste water and

Domestic waste water.

The combine waste from different areas of the pharmaceutical industries were subjected to

consecutive three stages of treatment-

Physical treatment,

Chemical treatment, and

Biological treatment.

Fig. 18: Effluent Treatment Plant at Incepta

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Physical Treatment

Physical treatments are used primarily to remove the unwanted solid substances from the

waste stream. Raw waste stream is passed through the bar racks for screening followed by

grit chamber and sedimentation tank. The waste sludge, collected from the sedimentation

tank, is then sent to the solid waste treatment plant for combustion and then the effluent is

passed to the chemical treatment plant.

Chemical Treatment

The effluents, collected from the physical treatment plant, are neutralized with lime in the

neutralization tank and then alum is added to the flash mixing tank. After that the effluents

are taken to the flocculation tank. After flocculation the heavy solids are removed from the

sedimentation tank and sent to the solid waste treatment plant and the decant solution were

further treated in the equalization tank.

Biological Treatment

Biological treatments again can be subdivided into two types:

Anaerobic and

Aerobic biological treatment.

Fig. 19: Chemical treatment of waste water

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From the equalization tank, the effluents are subjected to two steps biological treatment. In

the first step, anaerobic digestion was carried out by acidogenesis and volatile organic acids

are formed. Then they are converted to acetic acid and methane through acetogenesis and

methanogenesis respectively.

After anaerobic treatmentthe effluents are again treated by two stages aerobic digestion after

settling in the hopper bottom settling tank.

Fig. 20: Flow diagram of the biological treatment of waste water.

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Conclusion:

This industrial training was a great learning curve for all of us. Through this industrial

training we have learnt a lot about pharmaceutical industry. We learnt about pharmaceutical

water, clean room technology, pressure cascade, effluent treatment plant and many other

things which were unknown to us before. Moreover, we have got practical knowledge about

HVAC system and its different components. We got a very practical knowledge about

generator, boiler, chiller, cooling tower etc. We have learnt how an industry operates and

earned basic knowledge about Operational and Technical Management of Engineering,

Production, Quality Assurance, Warehouse Department etc.

Finally, we can conclude that this training program was a great experience for us. It helped us

to take a closer look at an industry and taught us professionalism. The knowledge and

experience gathered from this training program is invaluable to us.