Industrial Training Report on RENATA LIMITED INTRODUCTION RENATA Limited (formerly Pfizer Laboratories (Bangladesh) Limited), also known as RENATA, is one of the top ten (in terms of revenue) pharmaceutical manufacturers in Bangladesh. RENATA is engaged in the manufacture and marketing of human pharmaceutical and animal health products. The company also manufactures animal therapeutics and nutrition products. RENATA currently employs about 2300 people in its head office in Mirpur, Dhaka and its two production facilities in Mirpur, Dhaka and Rajendrapur, Dhaka.
BRIEF HISTORY OF RENATA LIMITED The company began its operations as Pfizer (Bangladesh) Limited in 1972. For the next two decades it continued as a subsidiary of Pfizer Corporation. However, by the late 1990s the focus of Pfizer had shifted from formulations to research. In accordance with this transformation, Pfizer divested its interests in many countries, including Bangladesh. Specifically, in 1993 Pfizer transferred the ownership of its Bangladesh operations to local shareholders, and the name of the company was changed to RENATA Limited. At present, RENATA manufactures about 300 generic pharmaceutical products including hormones, contraceptives, anti-cancer drugs, oral preparations, cephalosporins, parenteral preparations as well as other conventional drugs. In addition, they also offer about 95 animal therapeutics and nutrition products. In a gesture of corporate charity, Pfizer donated shares so that, along with a partial payment from the SAJIDA Foundation, 51% ownership of RENATA Limited would be held by the Foundation. Today SAJIDA’s microfinance and micro-insurance programs support over 107,120 members and their families; thus far cumulative loan disbursement totals BDT 5,750 million. Currently, SAJIDA’s health program covers over 1 million beneficiaries by delivering services through two 70 bed hospitals, panel doctors in SAJIDA’s micro finance branches, and mobile health teams. To date, the SAJIDA Foundation holds the majority ownership in RENATA Limited.
COMPANY AT A GLANCE LOCATION: Section-7, Mirpur, Dhaka-1216. TYPE: Pharmaceutical Company. PRODUCT TYPES: Tablet Capsule
Dry sirup Injection Products in sachet Soft Gelatin etc. FACTORIES: One at Mirpur,Dhaka Another one at Rajendrapur, Gazipur. PROJECTS UNDER DEVELOPMENT: Hormone-2 2.6MW Power Plant Herbal Product Factory OTHER INFORMATION: Market volume- 520-536 Crore (2011 end) 5Th largest among Pharmaceutical Companies of Bangladesh Entirely designed by internal engineers, not dependent on external consultants.
BOARD MEMBERS The Honorable Board Members of RENATA Ltd are•
Syed Humayun Kabir Chairman of Board of Directors since 1972
•
Syed S. Kaiser Kabir Managing Director since 2002
•
Dr. Sarwar Ali Board Member since 1994
•
Sajida Humayun Kabir Board Member since 2000
•
Hasanat Khan Board Member since 2000
•
Manzoor Hasan Board Member
•
Md. Fayekuzzaman
Board Member •
Md. Jubayer Alam Company Secretary Since 2011
MANAGEMENT TEAM The Management Team of RENATA Ltd. is driven by the active contribution of following personnel: •
Syed S Kaiser Kabir CEO & Managing Director
•
M. Alamgir Hossain General Manager, Operations
•
Khalil Musaddeq General Manager, Sales (Pharmaceutical)
•
Md. Jubayer Alam Company Secretary
•
Dr. Sayma Ali Head of Manufacturing
•
Monowarul Islam Marketing Manager, Pharmaceutical
•
Misha Ali International Business Manager
•
Khokan Chandra Das Head of Finance
•
Md. Sirajul Hoque National Sales Manager, Animal Health
•
Safina Hasan Human Resources Manager
ORGANOGRAM The ORGANOGRAM of RENATA Ltd. is as follows: Managing Director
Plant Manager
Departmental Head Senior officer
Officer
DEPARTMENTS RENATA Ltd. has two major departments. These departments are•
Project Department
•
Maintenance Department
Both the departments are working effectively for the benefits of the company. The Project department is mainly concerned with the planning and international dealings. The Maintenance department generally involves ensuring proper operation and control of engineering aspects.
CORE TEAMS OF RENATA Ltd. The following are regarded as the core teams of the running company: •
Production Department: This department determines the market demand and ensures that product is manufacture accordingly.
•
Quality Assurance: The function of this department is cross checking. The department also ensures quality of every product by quality control. It runs the laboratory for this purpose. QA is a batch process; rather than a continuous one.
•
Engineering Department: This department maintains the factory. It falls within the Maintenance Department.
FACILITIES AT A GLANCE General Facility (Mirpur, Dhaka) Area: 196,730 SFT or 18,277 m2
Manufacturing Capabilities: Tablet, Capsule, Soft Gel, Effervescent Tablet, Dry Syrup, Sterile Dry Fill, Sterile Liquid Fill, Large Volume Parenteral (Pilot), Lyophilisation (Pilot), and Premix
Packaging Capabilities: Blister pack, bottle dry-fill, pot-fill, and strip packaging
Potent Product Facility (Mirpur, Dhaka) Area: 22,500 SFT or 2,090 m2 Manufacturing Capabilities: Tablet Packaging Capabilities: Blister pack and pot-fill
Cephalosporin Facility (Rajendrapur, Gazipur) Area: 50,500 SFT or 4,692 m2
Manufacturing Capabilities: Tablet, Capsule, Dry Syrup, and Sterile Dry Fill Packaging Capabilities: Blister pack
Penicillin Facility (Rajendrapur, Gazipur) Area: 27,500 SFT or 2,555 m2 Manufacturing Capabilities: Tablet, Capsule, Dry Syrup, and Sterile Dry Fill Packaging Capabilities: Blister pack
Sachet Filling Facility (Mirpur, Dhaka) Area: 11,300 SFT or 1,090 m2
Manufacturing Capabilities: Powder Packaging Capabilities: Sachet (Dry Fill)
SERIVICES AND PRODUCTS Services Groups Anti-bacterial preparations Cephalosporins
Fluoroquinolones Macrolides Broad Spectrum Penicillin Trimethoprim Tetracyclines Carbapenemes Anti-ulcerant preparations
Products Polycef Cefticlor Furocef Cefazid Cefotax Orcef Levoking Flontin Azithromycin Zithrin Erythromycin Erythrox Ampicillin Pen-A Amoxicillin Co-trmoxazole Bactipront Doxycycline Renamycin Iropen Meropenem Pantoprazole Esomeprazole
Anti-hemorrhoidal preparations NSAID preparations Anti-allergic preparations
Cardiovascular preparations
Hemostatics preparation Expectorant preparation Vita min &Hematinic preparations
Calcium Supplement preparation Laxative preparation Steroid preparation Anti-spasmodic preparation Anti-protozoal preparation Anti-pyretic preparation Anti-diabetic preparation
Gastro-prokinetic
Omeprazole Ranitidine Diosmin & Hesperidin Naproxen Acelofenac Ketorolac Allermine Fenadin Tiramin Ostan plus Valzide Pendoril plus Pendoril Metaloc Ostanal Alphapress Cardioin plus Cardipin Xamic Honycol Kiddi E-Gel Mazic Chewrol Neurobest Beconex Becosules Bcosules Gold Calcin-D Titolax Dexatab Deltasone Algin MEZ IV Xanita Rapidol Pyra p;us Pyralgin Pioglin Mepid Glicron CR Glicron Domiren
preparation C.N.S preparation
Norry Carbretol Renxit Gaba Regmen Bredicon Medrogest Criptine Nandron 50 Emcon Thyrox Ovulet Menorest Giane Normens Letrol Desolon Cartilage Plus
Hormone preparation
Ortho-musculoskeletal preparation Anti-fungal preparation
Lucan-R Conasyd
ANIMAL HEALTH PRODUCTS: Poultry Animal health
Products Anrosin Renamycin
Imported Aqua
Bionix Renaquine 10% Rena Fish Renamycin soluble powder
GENERAL FACILITY PLANT-1(Mirpur, Dhaka) AREA: 196,730 SFT or 18,277 m2
MANUFACTURING CAPABILITIES: •
Tablet,
•
Capsule,
•
Soft Gel,
•
Effervescent Tablet,
•
Dry Syrup,
•
Sterile Dry Fill,
•
Sterile Liquid Fill,
•
Large Volume Parental (Pilot),
•
Lyophilisation (Pilot), and
•
Premix.
PACKAGING CAPABILITIES: •
Blister pack,
•
Bottle dry-fill,
•
Pot-fill, and
•
Strip packaging
FACTORY BUILDING: •
The bottom floor is the ‘Commercial Floor’. All the production under General Plant-1 is carried out here. This building also accommodates the PPF-1.5 Facility. The generators and the majority of the electrical power distribution system are located here. This floor also has a small workshop.
•
The upper floor is called ‘Service Floor’. The entire utility section is on this floor. The HVAC system including the ducts, water treatment plant and pipelines, boiler, air compressor electrical sub distribution boards etc. all are to be found on this floor.
•
The laboratory under QA is on the second floor.
•
The QA office is on the third floor.
•
The cooling tower is on the roof of the General Plant building.
MACHINES USED IN GENERAL PLANT -1: Serial #
Type of machinery
Numbers
1 2
Sealing Machine Labeling Machine
9 5
3
Tablet Press
13
4
Blender
4
5
Dry powder Filling
4
6
2
7
Capsule Filling Machine Powder Dryer
8
Bottle Wrapping
1
9
Bottle Dryer
2
10
Compactor
3
11
Granulator
5
12
Vibrator Shifter
1
13
Fitzmill
2
14
Dehumidifier
8
15
3
16
Bottle Inspecting Machine Coating
17
Fluid Blade Dryer
2
18
Stirrer
2
19
Blister Packing
11
20
1
23
Film Sealing Machine Auto Capsule Filling Machine Capsule Polishing Machine Washing Machine
24
Sterilizer
2
25
Powder Filling
3
26
Ampoule Filling Machine Mixing Vessel
3
2
29
Ampoule Inspecting Machine Vacuum Cleaner
10
30
Gelatin Melting Tank
2
21 22
27 28
2
5
2 2 7
3
PRODUCTION: The basic production procedure of the important products in the general plant was studied. The procedures can be divided into four major groups. These are: •
Tablet Production
•
Capsules Production
•
Dry Sirup Production
•
Production of Injectable etc.
MANUFACTURING PROCEDURE OF TABLETS: Tablets of a variety of groups and types and sizes are produced in the general plant. This is done on a number of tablet compression stations. The overall Tablet making process can be divided into four stages. These stages are: •
Granulation or Preparation of Material
•
Compression
•
Coating
•
Blistering etc.
These processes are described below:
GRANULATION: Before tablet compression, the raw materials are passed either in the wet granulation or dry mass process. For wet granulation, the raw materials are initially mixed for about 20 minutes and then a binder is applied in the mixer and a lump is obtained thereby. Common binding agents are: •
Mild Starch paste
•
Probiton-K
The lump or crystallized raw material is then passed through the “Fitz Mill” for sieving and then to the dryer. Drying is done for about 20 -30 min at 60-70˚C. Some lubricants are used such as: •
Sodium Lauryl Sulphate
•
Talcom Powder
•
Magnesium Stearate
Dry mass production is done on the oscillating granulator, and the product is obtained directly. PROCESS FLOW CHART: Raw Material Mixing
Preheating
Binder Adding
Lump Created
Dispensing
Drying
Sieving
Figure: Flow chart for Granulation
COMPRESSION: There are different tablet compression machines of varying capacities. The method incorporated by the machines is forming using die and punch. The machines available for this purpose are listed below: •
Cadmach 12
•
Cadmach 25
•
Cadmach 49
•
Sejong 37(1)
•
Sejong 37(2)
•
Sejong 51
•
Adept 25
•
Adept 23 etc.
The number written after the manufacturer’s name indicates the number of dies or stations available in the machine. The more this number is the more is the production rate. One sample specification of a SEJONG 37 machine given below: SPECIFICATION: o Electrical specifications: 400V / 50Hz / 3Phase o Number of station: 37 o Rpm of disk: 3-60 rpm o Power of main motor: 15Hp (11KW) o Machine floor space: 1150 * 1550 mm o Weight of machine: 4000 kg PROCESS FLOW CHART: Powder Inlet to Hopper
Filling
Compression by Die Punch
Product Output
Figure: Flow chart for Compression.
COATING: These machines are designed for tablets, pillets, granule type object coating. It is done by compressed air fundamentally. Some machines are; •
Sejong(2 guns)
•
Sejong(4 guns)
•
Glatt(6 guns)
One sample specification of a SEJONG 37 machine given below: •
Pump Specification: o Speed: 220 rpm o Voltage: 100-120 V o Frequency: 50 Hz o Current: 1.25 A
•
Spray gun Specification: o Mach 1A HVL o Air nozzle:
Inlet: 2 psi
Atomizing: 3 psi
o Fluid nozzle:
Inlet: 5 psi
Atomizing: 2 psi
o Control: PLC, touch screen. o Power supply: 100 - 150 W
BLISTERING: There are blistering machines of various capacities, models and control systems. Some are fully automatic, some requires human intervention. Al-Al blistering and Al-PVC blistering is of same principle, but in case of PVC it needs two additional heating stations for sealing. This is due to the fact that two metal strips of Aluminum under sufficient pressure and machining process can get sealed without any additional high temperature provision.
For Blistering, at first PVC or Aluminum Sheet is taken which is then heated by a heater, known as a pre heater. An air pocket is created by injection of compressed air. The tablets are fed into the created packet, either manually or by an automatic process. After this operation, another strip of Aluminum comes from the other end and sequentially sealing, slitting, cutting etc are done by different heaters with appropriate temperature. This is the basic principle of operation, which may vary from machine to machine to a certain extent. Some blistering machines are: •
Ulmann (2 pcs)
•
Pampac
•
Langnan
•
Buchon
One sample specification of a BUCHON machine given below: •
Specification: o Manufacturer: BUCHON Machinery Co. o Model: WDER-A1V o Type: UPS 300 o Electric: 415 V, 50 Hz, 3 phase o Rated Current:9 A o Main motor power: 1.1 kW o Gross power for head: 2 kW o Punching frequency: 10-30 times/min o Stroke adjusting range: 40-110 min o Preheat Temperature: 130.5˚C Strip Preheating o PVC/Al Preheat Temperature: 130.5˚C
Air Injection
Intake
o Sealing Temperature: 145.5˚C o Slitting Temperature: 100.2˚C Heating
Al strip input
Tablet Filling
Sealing
Embossing
Slitting
Secondary Packaging
Primary Packaging
Sealing
PROCESS FLOW CHART:
Figure: Flow chart for Blister Machine. Good Receiving
Labeling (2)
Quarantine (3)
(1)
Dispensing (6)
Stored for use (5)
Accepted
Rejected Hold for decisi on
QC Chec k (4)
Wet Mass Preparation (7)
•
Primary Milling + Sieving (8)
Flow chart for tablet manufacturing Coating (14)
Drying (9)
Hold for fromdecisi the on
Final Milling + Sieving (10)
Rejected
Batch Manufacturing Record (BMR):
Compression (13) Accepted
QC Chec
Blending (11)
k (12) Accepted
Rejected QC Chec
Primary Packaging (16)
Secondary Packaging (17)
k (15) Rejected Hold for decisi on
Hold for decisi on
QC Chec k (18) Accepted
Transfer to FG Store (19)
Process under controlled humidity and temp [40-60%] Process under ambient humidity and temp [25°C ± 2°C]
Figure: Overall Procedure including QC check and others of Tablet production
MANUFACTURING PROCEDURE OF CAPSULES: The capsule making process has both similarity and dissimilarity compared to that of tablet from many aspects. The process is same up to dispensing stage. The rest of the process can be sub-divided into three main stages. These can listed as below: •
Sieving and Blending (material preparation)
•
Encapsulation
•
Blistering etc.
The entire granulation step required for tablet making is replaced by sieving and blending only. The final stage or blistering is similar to that of tablets. The intermediate stage or encapsulation is described below: The mixed powder for capsules is taken into the encapsulation station which similarly produces capsules. The shells of all the capsules are not manufactured in the factory; rather they are bought from outside reliable sources as raw materials. PROCESS FLOW CHART:
Shell intake at Rake
Shell Disintegration
Raceway
Product Output and Rejection
Filler
Pusher
Figure: Flow chart for Encapsulation There are several capsule processing machines. Some of these machines are automatic, rests are manual. Such as: •
PTAM SA9, India
•
HUADA, China etc.
Good Receiving
Labeling (2)
Quarantine (3)
(1)
Rejected Hold for decisi on
QC Chec k (4) Accept
Sieving (7)
Dispensing (6)
Stored for use (5)
•
Rejected
Blending (8)
Hold
QC Flow chart for capsule manufacturing from the Batch Manufacturing Record (BMR): for Chec
decisi on
k (9) Accept
Rejected
Encapsulation (10)
k (11)
Secondary Packaging (13)
QC Chec
Rejected
k (14) Hold for
Accept
Transfer to FG Store
Hold for decisi on
QC Chec
Accept
Primary Packaging (12)
Process under controlled humidity and temp [40-60%] Process under ambient humidity and temp [25°C ± 2°C]
Figure: Overall Procedure including QC check and others of Capsule production
MANUFACTURING PROCEDURE OF DRY SIRUP: Production is done according to the market demand. A fully automatic machine (CVC, Taiwan) is used in this purpose. PROCESS FLOW CHART: Bottle installing
Conveyor
Filling station
Photo sensor sensor
Air injection
Final sealing
Capping
Manual Check
Labeling
Output
Gasket sealing
Figure: Flow chart for Dry Sirup Production PROCESS IN DETAILS:
The glass bottles are fed manually into the machine first. Also the metallic cap and plastic gaskets are fed into separate stations. The dry syrup powder is fed into the machine by creating a vacuum. The bottles are taken into the line automatically at six stations simultaneously. Desired amount of dry powder is filled into each bottle in an automatic process. The bottles also vibrate here to avoid any lump creation. Little amount of Air is sprayed to move away the outside and dry powder dust from the outer periphery of the bottles. After filling the bottles pass on a conveyor belt for the next process. There are sensors on the belt to avoid jamming. The filled bottles then move to be sealed with plastic gaskets. The gaskets fell from top and seal each bottle automatically and sequentially move to the next station, which is Capping. After capping is done by twisting and sealing the bottle completely, they move through the conveyor belt for next stages as labeling, primary and secondary packaging etc. This is to be noted that there are a number of sensors at each stations, each important points on the machine to ensure that the process is running properly and if not it can reject the individual item and in fact in some cases of severe errors, the machine stops by itself to ensure highest accuracy and quality. •
Maximum of 6 bottles are operated simultaneously.
•
Capacity of bottles: 130, 70, 35 ml
•
Each filling station has separate sensors.
•
Powder is lifted by vacuum.
•
There are a number of dampers, vacuum pumps and sensors.
•
The machine is made in Taiwan, by the CVC Technology Co Limited. But it uses an overall USA technological aspects and standards.
MANUFACTURING PROCEDURE OF INJECTABLE:
The products of injections are: •
Liquid ampoule
•
Liquid vial
•
Dry vial
These injectables are produced with maximum precaution in the sterile area. Various ampoule washer, cleaner, sterilizer and inspection machines are used in this process. Due to entry restrictions, we could not enter them thoroughly, but yet got an overall clear idea of the entire process. PROCESS FLOW CHART: Ampoule Washing
Sterilization
Good Receiving
Mixing of base product
Labeling (2)
Quarantine (3)
(1)
Sealing
Filling
Dispensing (6)
Stored for use (5)
Filtration Accepted
Rejected Hold for decisi on
QC Chec k (4)
Leak Test
Visual Inspection
Ampoule Washing by WFI
Sterilization of Ampoule
Final product to Filling + Sealing the Packaging (10)
Figure: Flow chart for Injection production. Rejected Hold for decisi on
IPQC Check
Warehouse
(11) Accepted
•
Flow chart for tablet manufacturing from the Batch ManufacturingRejected Record (BMR): Rejected Defected Ampoules Destroyed
Leak Test (12)
Visual Inspection (13)
Accepted
Accepted Rejected
IPQC Check
Packaging (15)
Accepted
QC Chec k (14)
(16)
Hold for decisi on
Accepted
Transfer to FG Store (17)
Rejected
Holdi ng decisi
Process under controlled humidity and temp [40-50%] Process under ambient humidity and temp [25°C ± 2°C]
Figure: Overall Procedure including QC check and others of Injection production
UTILITY: POWER DISTRIBUTION SYSTEM In pharmaceutical industry an essential utility is the electric power distribution to the whole industry. Electric power is distributed from the service floor according to the demand. In Reneta Limited the main power source is either from the generators or Dhaka Electric Supply Company (DESCO). It has two generators. The power capacity of smaller one is 0.7MW and the bigger one is 1.2MW. The ON/OFF process of small generator and DESCO IS done with a separate control
board. The controlling system is manual with hand lever. When the DESCO line is ON the small generator is OFF and vice versa. The big generator is controlled directly by the switch. When the DESCO line is ON then current is passed from the transformer it goes to the main distribution board (MDB) through Low Tension Panel (LTP). If the generator is ON, the current will be passed through circuit breaker to the LTP. At last reaches the MDB from where the power requirement for the industry is maintained.
Power Source DESCO FLOW DIAGRAM: DESCO
Switch
Transformer
LTP
Sub-Distribution Board
MDB
Figure: Flow Chart showing Power distribution from DESCO source.
DESCO: DESCO supplies current to the different parts in the Dhaka city. The voltage of DESCO current is 11KV. But in industry the voltage requirement is 380-400V.
TRANSFORMER: A transformer is a device that transfers electrical energy from one circuit to another through inductively coupled conductors –the transformer’s coil. A varying current in the primary winding creates a varying magnetic flux in the transformers are and thus a varying magnetic field through the secondary winding. If a load is connected to the secondary an electric current will flow in the secondary winding and electrical energy will be transferred from primary circuit through the transformer to the load. In an ideal transformer the induced voltage in the secondary is proportional to the primary voltage and is given by the ratio of no. of turns in the secondary (N s) to the no. of turns in the primary (Np) as follows •
Specification of Transformer: Input : 11KV Output : 440V Primary winding : Del -connection Secondary winding : Y- connection Vector Group : DYn11
LOW TENSION PANEL:
The transformer steeped down the voltage. The low voltage is distributed from low tension panel. The bus-bars are used in RENATA limited to meet the continuous current rating and short circuit levels desired. The three phase vertical bus-bars provided are of highconductivity, electrolytic grade copper as standard. These vertical droppers provided with round edges for ease of contact insertion. They are provided in an enclosed chamber which is located behind the feeder compartment. The chamber is totally enclosed to prevent the entry of dust and vermin. The vertical busbars are accessible only after the removal of the feeder trolley and the front guard. The vertical bus-bars are free of bolts, holes etc. For connection and hence are maintenance free.FRP vertical bus-bar support are provided within the bus chamber at a distance of 100mm from each other.
Figure: Low Tension Panel
MAIN DISTRIBUTION BOARD: It is a board from which the power is distributed to the whole industry. The location of MDB is selected very carefully. It should be located in the dry place. The main distribution board LVMD is the central switch cabinet within a hospital. In it the basic network structure for the general supply (GS) and the safety power supply (SS) are established. Due to their great importance, there are strict requirements on the operational reliability and person and system protection. Accordingly, the system must be configured as a type-tested low-voltage switchgear and control gear assembly (TTA) according to DIN VDE 0660 Part 500, IEC 604391 and DIN EN 60439-1. •
The solution:
The main distribution boards consist of: o Incoming/Outgoing feeders general supply (GS) o Incoming/Outgoing feeders safety power supply (SS) •
Benefits: o Modular design of distribution, function systems and devices o Individual planning, project management and execution for every individual situation o Arc-fault safe insulation between common rail space, device space and connection space o High operational reliability, personal safety, and availability o Construction upon request, type-tested according to DIN VDE 0660 Part 500, IEC 60439-1 and DIN EN 60439-1 o Secure separation between the systems (GS and SS)
Figure: Main Distribution Board
Power Source Generator FLOW DIAGRAM: Generator
Switch gear
Low Tension Panel (LTP)
Main Distribution Boards
Sub Distribution Boards
Figure: Flow Chart showing Power distribution from GENERATOR source.
ELECTRIC GENERATOR: Electricity generation is the process of generating electric energy from other forms of energy. For electric utilities, it is the first process in the delivery of electricity to consumers. The other processes, electricity transmission, distribution, and electrical power storage and recovery using pumped storage methods are normally carried out by the electric power industry. In electricity generation, an electric generator is a device that converts mechanical energy to electrical energy. A generator forces electrons in the windings to flow through the external electrical circuit. It is somewhat analogous to a water pump, which creates a flow of water but does not create the water inside. The source of mechanical energy may be a reciprocating or turbine steam engine, water falling through a turbine or waterwheel, an internal combustion engine, a wind turbine, a hand crank, compressed air or any other source of mechanical energy. Before the connection between magnetism and electricity was discovered, electrostatic generators were invented that used electrostatic principles. These generated very high voltages and low currents. They operated by using moving electrically charged belts, plates and disks to carry charge to a high potential electrode. The charge was generated using either of two mechanisms: o Electrostatic induction o The triboelectric effect, where the contact between two insulators leaves them charged. Because of their inefficiency and the difficulty of insulating machines producing very high voltages, electrostatic generators had low power ratings and were never used for generation of commercially significant quantities of electric power. The Wimshurst machine and Van de Graff generator are examples of these machines that have survived. An engine-generator is the combination of an electrical generator and an engine (prime mover) mounted together to form a single piece of self-contained equipment. The engines used are usually piston engines, but gas turbines can also be used. Synchronous Generators are the primary source of all electrical energy and commonly used to convert the mechanical power output of steam turbines, gas turbines, reciprocating engines, hydro turbines and wind turbines into electrical power for the grid. They are known as synchronous generators because they operate at synchronous speed, which is the same principle of operation as a synchronous motor. The speed of the rotor with a constant magnetic field always matches supply frequency of the stationary winding. The constant magnetic field of the rotor is produced by the persistent magnetic field of a rotor
permanent magnet assembly or by controlling direct current to a rotor field winding (i.e., electromagnet) fed through a slip-ring assembly or a brushless means. Two synchronous generators are used in RENATA Limited. They are combined with engine. Generators run by diesel fuel. It has 12 V-cylinder and cooling system is provided with a radiator o The rotor is mounted on a shaft driven by mechanical prime mover o A field winding (rotating or stationary) carries a DC current to produce a constant magnetic field. o An AC voltage is induced in the 3- phase armature winding (stationary or rotating) to produce electrical power. o The electrical frequency of the 3-phase output depends upon the mechanical speed and the number of poles • Specifications of Synchronous Generator: Manufacturer
North Ireland/UK
Model
P800
Serial No.
GACL000390
Year of Manufacture
2001
Rated Power continuous: Rated voltage
800 KV 640 KW 0.8 cosφ 400/230 V
Phase
3
Rated frequency
50 Hz
Rated current
1154.7 A
Rated RPM
1500
Maximum Altitude
152.4 m
Maximum Ambient Temperature
27˚C
Sensor
PT100 (Thermal)
SWITCH GEAR: Circuit breaker is used as switchgear in this industry. The term switchgear, used in association with the electric power system, or grid, refers to the combination of electrical disconnects, fuses and/or circuit breakers used to isolate electrical equipment. Switchgear is used both to de-energize equipment to allow work to be done and to clear faults
downstream. This type of equipment is important because it is directly linked to the reliability of the electricity supply. The very earliest central power stations used simple open knife switches, mounted on insulating panels of marble or asbestos. Power levels and voltages rapidly escalated, making open manually-operated switches too dangerous to use for anything other than isolation of a de-energized circuit. Oil-filled equipment allowed arc energy to be contained and safely controlled. By the early 20th century, a switchgear line-up would be a metal-enclosed structure with electrically-operated switching elements, using oil circuit breakers. Today, oil-filled equipment has largely been replaced by air-blast, vacuum, or SF6 equipment, allowing large currents and power levels to be safely controlled by automatic equipment incorporating digital controls, protection, metering and communications. High voltage switchgear was invented at the end of the 19th century for operating motors and other electric machines. The technology has been improved over time and can be used with voltages up to 1,100 kV. Typically, switchgear in substations is located on both the high voltage and the low voltage side of large power transformers. The switchgear located on the low voltage side of the transformers in distribution type substations, now are typically located in what is called a Power Distribution Center (PDC). Inside this building are typically smaller, medium-voltage (~15kV) circuit breakers feeding the distribution system. Also contained inside these Power Control Centers are various relays, meters, and other communication equipment allowing for intelligent control of the substation. For industrial applications, a transformer and switchgear (Load Breaking Switch Fuse Unit) line-up may be combined in one housing, called a unitized substation or USS. Different switchgear equipments are given below o Circuit breaker o Isolator o Earthing switch o Lighting arrestor o Current transformer o Voltage transformer
•
Functions One of the basic functions of switchgear is protection, which is interruption of shortcircuit and overload fault currents while maintaining service to unaffected circuits. Switchgear also provides isolation of circuits from power supplies. Switchgear is also used to enhance system availability by allowing more than one source to feed a load.
•
Safety To help ensure safe operation sequences of switchgear, trapped key interlocking provides predefined scenarios of operation. For example, if only one of two sources of supply are permitted to be connected at a given time, the interlock scheme may require that the first switch must be opened to release a key that will allow closing the second switch. Complex schemes are possible. Indoor switchgear can also be type tested for internal arc containment. This test is important for user safety as modern switchgear is capable of switching large currents. Switchgear is often inspected using thermal imaging to assess the state of the system and predict failures before they occur.
The working process of low tension panel and main distribution boards is same as previously discussed when the power source is DESCO
WIRE (CABLE) SIZE SELECTION: A wire is a single, usually cylindrical, flexible strand or rod of metal. Wires are used to bear mechanical loads and to carry electricity and telecommunications signals. Wire is commonly formed by drawing the metal through a hole in a die or draw plate. Standard sizes are determined by various wire gauges. The term wire is also used more loosely to refer to a bundle of such strands, as in 'multi-stranded wire', which is more correctly termed a wire rope in mechanics, or a cable in electricity. Although usually circular in cross-section, wire is also made in square or flattened rectangular cross-section, either for decorative purposes, or for technical purposes. In industry cable size selection is the most essential task. If the material from which wires are made had zero resistance, then any size wire could carry any amount of current. Considering the formula of power
……(1)
…......(2) From equation (1) the current is determined. The value of ecal and length is obtained from cable selection chart. Using the value of current from equation (1) permissible voltage is
calculated. The maximum allowable voltage drop is 5%. If the voltage drop is below or equal to 5% then the design is ok.
ENERGY CONSUPTION: The daily energy consumption of this industry is approximately 1.6 MW. Energy consumption is dependent on the production capacity. The production process is continuous. So the monthly energy consumption is 48 MW.
COST OF ENERGY (MONTHLY CALCULATION): The cost of electricity generated by different sources measures the cost of generating electricity including initial capital, return on investment, as well as the costs of continuous operation, fuel, and maintenance. Source of energy
Cost (lakhs)
DESCO
26
Boiler (gas)
26
Generator (diesel)
12.5 Total = 64.5
ENERGY COST REDUCTION: Following steps can be taken to reduce the cost of energy: •
Bus-bar trunking system Busbar trunking system (BBT) performs the function of transporting current form one point to the other. Traditionally cables were used for this function. BBT goes beyond what cables do. BBT can tap off power to switchgear for further distribution using tap of boxes. In comparison to cables, BBT can thus serve as distribution panels at different stages (at floors of a building). BBT thus continues as a single system to replace cables as well as distribution boards at floor level for building.
•
Effective lighting Many LED lamps can become available as replacements for screw-in incandescent or compact fluorescent light bulbs, ranging from low-power 5–40 watt incandescent bulbs, through conventional replacement bulbs for 60 watt incandescent bulbs (typically requiring about 7 watts of power), and as of 2010 a few lamps were available to replace higher wattage bulbs, e.g., a 16-watt LED bulb which is claimed to be as bright as a 150W halogen lamp. A standard general-purpose incandescent bulb emits light at an efficiency of about 14 to 17 lumens/W depending on its size
and voltage. According to the European Union standard, an energy-efficient bulb that claims to be the equivalent of a 60W tungsten bulb must have a minimum light output of 806 lumens. •
Rearranging wire system Heavy industries have more demanding wiring requirements, such as very large currents and higher voltages, frequent changes of equipment layout, corrosive, or wet or explosive atmospheres. In facilities that handle flammable gases or liquids, special rules may govern the installation and wiring of electrical equipment in hazardous areas.
UTILITY: Heating Ventilation Air Conditioning (HVAC) In pharmaceutical manufacturing, how space condition impacts the product being made is of primary importance. HVAC systems assists in ensuring the manufacture of quality products and also results in operator comfort. HVAC systems design influences architectural layouts, with regard to items such as airlock positions, doorways and lobbies. International guidelines are available which are approved by various organizations in the respective field. Every pharmaceutical company must choose and strictly follow any of these guidelines. Being a pharmaceutical company itself, RENATA Ltd is no exception.
FUNCTIONS OF HVAC SYSTEMS: HVAC systems perform the following four basic functions. •
Control airborne particles, dust and micro-organisms: Of all the design goals, it is the quality of air, cleanliness of the space and prevention of contamination which are of utmost importance. Externally generated particulates are prevented from entering the clean space through the use of proper air filtration.
•
Maintain room pressure (ΔP): Areas that must remain “cleaner” than surrounding areas must be kept under “positive” pressurization, meaning that air flow must be from “cleaner” area towards the adjoining space (through doors or other openings) to reduce the chance of airborne contamination. This is achieved by the HVAC system by providing more air into the “cleaner” space than is mechanically removed from the same space.
•
Maintain space moisture (relative humidity): Humidity is controlled by cooling air to dew point temperatures or by using desiccant dehumidifiers. Humidity can affect the efficacy and stability of drugs and is sometimes important to effectively mould the tablets. While most of the areas could have a RH of 50 ± 5%, facilities designed for handling hygroscopic powders need to be at 30 ± 5%.
•
Maintain space temperature (T): Temperature can affect production directly or indirectly by fostering the growth of microbial contaminants on workers. Yet this is the least critical parameter. Lower temperature may be required where workers are very heavily gowned and would be uncomfortable at “normal” conditions.
DESIGNING HVAC SYSTEM: The design of HVAC systems should be considered at the concept design level. The efficacy of the system design is based on the proper consideration of the following factors: •
Building construction and layout design
•
Defining the HVAC requirements system-wise and room-wise o Cleanliness level o Room temperature, relative humidity o Room pressure o Air flow pattern
•
Cooling load and air flow compilation
•
Selection of air flow pattern
•
Pressurization of rooms
•
Air handling system
•
Duct system design and construction
•
Selection, location and mounting of filtration system
•
Defumigation required
•
Commissioning, performance qualification and validation
•
Testing and validation
•
Documentation
HVAC SYSTEM IN RENATA LIMITED: The HVAC Utility in RENATA Ltd. is operated and maintained by the Engineering Department under Maintenance. It has an overall capacity of 700 tons and the whole HVAC utility is situated on the service floor (above production floor) except the cooling tower, which is placed on the roof of the general plant building. •
Guideline followed by RENATA ltd.: Currently RENATA Ltd. is following the ISO-14644 Cleanroom Classification Class 8 and BS 5295 for HVAC system design. The ISO 14644 Class 8 deals with the molecular contaminant restrictions. The ISO Classification of Cleanroom doesn’t include the operating condition of the room, i.e., “at rest” or “in operation”. Rather the criterion is the maximum concentration limits (particle/m3). The following table contains molecular contamination limits of ISO standard.
TABLE-1: ISO 14644-1 Cleanroom Standards Maximum concentration limits (particles/m3) for particles ≥ particle sizes shown Class 0.1 µm 0.2 µm 0.3 µm 0.5 µm 1 µm 5 µm ISO 1 10 2 ISO 2 100 24 10 4 ISO 3 1,000 237 102 35 8 ISO 4 10,000 2,370 1,020 352 83 ISO 5 100,000 23,700 10,200 3,520 832 29 ISO 6 1,000,000 237,000 102,000 35,200 8,320 293 ISO 7 352,000 83,200 2,930 ISO 8 3,520,000 832,000 29,300 ISO 9 35,200,00 8,320,000 293,000 0 • Cleanroom Zoning: There are four types of cleanroom 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. The zones are: o A – local zone: For operation that affords high risk of product quality, e.g. filling, closing, ampoule and bottle opening zones. Usually in such zones is used in laminar air flow which provides similar velocity 0.36-0.54 ms -1. o B zone: This is circled A zone and is used for an aseptic preparation and fulfillment. o C and D zones: These are clean zones for less responsible stages of manufacturing sterilized products. TABLE-2: Clean Zones Grades GRADE
AT REST
IN OPERATION
A
Maximum permitted number of particles per m3 equal to or above 0.5 micron 3,500
Maximum permitted number of particles per m3 equal to or above 5 micron 0
Maximum permitted number of particles per m3 equal to or above 0.5 micron 3500
Maximum permitted number of particles per m3 equal to or above 5 micron 0
B
35,000
0
35,000
2,000
C
350,000
2,000
350,000
20,000
D
3,500,000
20,000
Not defined
Not defined
From the table, it is visible that Grade-A classification is the most stringent of all. It requires air in the immediate proximity of exposed sterilized to be no more than 3500 particulates per cubic meter, in a size range of 0.5micron and larger. In the size range of 5micron the maximum allowable limit is zero. This is the HVAC requirement for the injective products. The solid dosage area is supplied with grade-D. These
products in this area require low relative humidity (<45%, best 35%, in case of sterile it is 50-60%). The contamination is of secondary importance for this grade. •
Types of HVAC Systems available at RENATA LTD.: There are two types of HVAC systems available at RENATA LTD. These are as follows: o Central type: General plant o Package type: Sachet filling, softgel etc.
COMPONENTS OF HVAC UTILITY: The main components of the HVAC system are as follows: •
Chiller
•
AHU
•
Dehumidifier
•
Cooling Tower
•
Pump
•
Ducts and pipelines etc.
FLOW PROCESS OF HVAC UTILITY: Condenser Water
Condenser
Cooling Tower
Freon
Compressor
Expansion device
Evaporator
Fresh Air
Cold Water
AHU
Cold Air
Return air
Chiller
Normal Water
Room Return air
Dehumidifier
Sensor Return air
Figure: Schematic Diagram of the HVAC System
DESCRIPTION OF THE FLOW PROCESS: The circuit on the left of the flow diagram is the refrigerant circuit of the chiller. This is a typical refrigeration cycle comprising of components like compressor, condenser, expansion valve and evaporator.
Normal water is cooled by passing it through the evaporator where the refrigerant evaporates by extracting heat from the normal water. The refrigerant is then compressed by compressor. The superheated refrigerant then condenses in the condenser. Water from cooling tower takes way the heat. The condensed refrigerant is then expanded as it comes across a expansion valve. The cold water from the evaporator is passed into the cooling coils of AHU. At the same time fresh air and return air is taken and mixed together at required rate. The air is then cooled as it flows over and around the cooling coils. The cold air the then supplied to the room at the required rate through ducts. The return air after passing through the return air filter and sensor is taken into the dehumidifier. There dehumidification occurs. Finally the air is directed to the mixing chamber of the AHU. From the diagram it is visible that the HVAC is of recirculation type, not once through air type. The advantages of this type of systems are as follows: o Lower air filter maintenance and energy cost o Opportunity of better air filtration o Better control of parameters (T, RH) o Less cooling or heating cost as the amount of throw-away air is less etc. This type of system also has some disadvantages like: o Return air ductwork to AHU may complicate the layout of service floor o There remains chance of cross-contamination etc.
Figure: Schematic of Return Air HVAC system.
CHILLER: There are two chillers in RENATA Ltd. The manufacturer is same. The chiller supplies cold water for the AHUsâ&#x20AC;&#x2122;. â&#x20AC;˘
Mechanical parts of a Chiller:
The Chiller consists of the following mechanical parts: o Compressor o Condenser o Evaporator o Expansion valve o Oil separator o Solenoid valve o Oil sump o Gas pump
•
Specification: The specification of the chillers is given below: o Manufacturer: TRANE o Capacity: 350 ton per chiller o Full Load Current: 275-375 Ampere o Voltage: 380-440V o Refrigerant: R-134a
•
The following diagram of a chiller is collected from the manufacturer’s catalogue available on internet:
•
A set of sample data of the chiller is given below: Compressor Data: o Starts: 1272 o Running time: 3187.42 o System differential pressure: 106.3 psid o Oil Pressure: 128.8 psig o Oil level sensor: Wet o Refrigerant discharge temperature: 134.4°F o Volts:
o Ampere:
o RLA:
AB
BC
CA
409
412
413 V
L1
L2
L3
250
255
256 Amp
85.3
87.2
88.5%n (the percent of rated load amps)
Condenser Data: o Inlet H2O temperature: 89°F
o Outlet H2O temperature: 92.4°F o Saturated refrigerant temperature: 108.3°F o Saturated refrigerant pressure: 142.7 psig o Approach temperature: 16.9°F Evaporator Data: o Inlet H2O temperature: 47.4°F o Outlet H2O temperature: 44.2°F o Saturated refrigerant temperature: 41.3°F o Saturated refrigerant pressure: 36.4 psig o Approach temperature: 3.3°F
AIR HANDLING UNIT OR AHU: Pharmaceutical air handling systems support clean aseptic environments, so the equipment is air tight. The air-handling unit is box-like equipment with a fan and a cooling coil inside. There are also Air Filters. The whole fan and motor assembly, comprising shaft, bearings, pulley, and belt is usually put inside the AHU. Typical the box is a metal casing, with an insulation liner applied to the inside of the casing. There are 30-35 AHUs’ in RENATA Ltd. The basic function of the AHU is to suck air from the rooms, let it pass through chilled water cooling coils and then discharging the cooled air back to the rooms. Normally, letting it pass through panel or bag filters also filters the air. A certain amount of fresh air (10-15% of return air) is introduced at the suction duct so that air in the rooms may be gradually replaced. Control valves are used to throttle chilled water through the chilled water coils. There is no reservoir for cooling water, the same water is circulated between chiller evaporator and AHU coils though make-up water may be added. There are also control damper to control the air supply. The fan and motor assembly is mounted on vibration dampers that absorb any vibrations generated. Removable panels are installed so that operator can enter into the AHU for maintenance. Maintenance is mostly changing or washing of air filters, greasing of bearings, changing of belts, and general inspection and cleaning work. An AHU has three types of filters. These are the Back filter, Pre-filter and HEPA ( HighEfficiency Particulate Air) filter etc. Among these filters, the HEPA filter is most efficient one. The pre-filters are used to prolong the service life of the HEPA filters. The 0.5 micron HEPA filters used in the AHUs’ of RENATA Ltd. are the box-types. These are able to prevent microorganisms of the size 1 micron from entering the room. Specification: The specification of the AHU motor is given below:
o
Power: 10Hp/7.5KW, 1450 rpm, 60Hz.
o
V-belt connects it to the runner of the fan.
DEHUMIDIFIER: Dehumidifiers are used to control the relative humidity (RH) to lower levels. RH of 50±5% can be achieved by cooling the air to the appropriate dew-point temperature. When chilled water is supplied at 42-44°F to the cooling coils, a minimum dew-point of about 50-52°F can be obtained. This results in a minimum RH of 50% at 70°F. Spaces with high moisture content, it is important to use a cooling coil that is deeper i.e. with higher number of rows. This will lead to lowering of supply air temperatures downstream the cooling coil, which is reheated by hot water coil or electric strip heaters before dumped into the space. In some cases where hygroscopic (product sensitive to moisture) materials are handled, the room RH requirement may be as low as 30 to 35% and may require the use of chemical dehumidifiers. Both dry and wet chemical dehumidifiers are available for commercial use. Lithium salt solutions are examples of wet dehumidifiers while silica gel and activated alumna are generally used as dry dehumidifiers. The dehumidifiers used in RENATA Ltd. uses the dry ones. The dehumidifiers in RENATA Ltd. are also metal box-like structures similar to AHUs’, but smaller. Inside the dehumidifier there is an electric heater, Silicas coil (silica being the chemical dehumidifier) and two fans. The fans are used to draw air inside.
COOLING TOWER: There is only one cooling tower in RENATA Ltd. The cooling tower is located on the roof of the general plant building. It is a Counter-flow, Induced type cooling tower. Counter flow cooling towers have the air passage flowing directly against the flow of the water. Water is allowed to spread out with the help of air inlet louvers. Their bottle like shape characterizes this type of cooling towers. There is only one single fan at the center. Fitted below the fan is a rotating water pipe distributor. The pipes of the water distributor shoot water only from one side. The action of the water pressure shooting from one side rotates the distributor. The water is thus dropped evenly over the air inlet louvers. The water dropping by gravity meets head on with the up moving air current sucked in by the fan. The air cools the water. The water collected at the bottom of the cooling tower is pumped to the chiller, becomes heated up again, and is then returned back to the cooling tower for cooling. The following schematic diagram of a cooling tower:
Figure: Schematic Diagram of a Counter Flow Induced Draft Cooling Tower.
UTILITY: WATER TREATMENT PLANT The purity of water used in pharmaceutical industries is a crucial factor that must be ensured. To provide the water of desired quality (as approved by various international guidelines such as United States Pharmacopeia or British Pharmacopeia) water treatment is carried out. The objective is to produce water keeping the following factors within the recommended limit and also to supply the required quantity: •
pH
•
Conductivity
•
Micro Organism Content
There are two basic types of pharmaceutical water; water for typical use or cleaning (sterile purified water, or PW), or water for injection (WFI). The pH (5-7) and conductivity (0.6–4.7 µSiemens/cm) value are same for both types of water. The quality differs when Micro Organism Content is taken into account. The preferred values of MOC are 100cfu/ml for PW and 10cfu/100ml for WFI (USP guidelines). The WFI water is passed through some higher stages of purification and the distribution of these two types of water is also kept separated.
PURIFIED WATER (PW): In RENATA Limited, there are two plants for supplying PW. These are: •
The Manual plant
â&#x20AC;˘
The Automatic plant
THE MANUAL PLANT FOR PURIFIED WATER: It utilizes the method of Ion Exchange using ion exchange resin. These resins are polymers that are capable of exchanging particular ions within the polymer with ions in a solution that is passed through them. Synthetic resins are usually used for water purification. In water purification the aim is usually either to soften the water or to remove the mineral content all together. If the water needs to have the mineral content completely removed then it is passed through a resin containing H + (which replaces all the cations) and then through a second resin containing OH - (which replaces all the anions). The H + and OH- then react together to give more water. It supplies PW at a rate of 1000liters/hour. The manufacturing company is Ion Exchange Ltd. (India).
The flow of PW through the Manual Purifier: Deep Tube Well
ANION Bed
Overhead Reservoir
3.2pH water
(Synthetic Resin: FFIP)
5-7pH water Conductivity <2
CATION Bed
Flow Meter (Rotameter)
Storage Tank for PW
Figure: Flow chart for Manual Water Purifier Description of flow process:
varying sizes)
(Synthetic Resin: 225H)
7.5-9.8pH water
MIXED Bed
Filter (Layers of rock of
The source of water is the underground water which is collected by using a deep tube well and then into an overhead reservoir. The water is filtered by passing it through a vessel filled with layers rocks of varying sizes. This is a gravel type filter. At the exit a Rotameter is placed to measure the flow rate of water. Then for the chemical process the water is passed through a set of three vessels, namely Cation Bed, Anion Bed and the Mixed Bed. In the Cation Bed the resin used is 225H which adds to H+ content of the water by replacing all other cations. Thus the pH value decreases to 3.2 and so the water out of Cation bed is acidic. As the water passes through Anion Bed it comes into contact with the resin FFIP, which adds OH- to the water, makes it basic and increased value of pH is within the range 7.5-9.8. In the Mixed Bed, the mixing of these two types of water occurs and the final pH value drops down to the range of 5-7. The conductivity is ensured to be below 2ÎźSiemens/cm. The PW is then collected in the Storage tank for PW. The Cation and Anion Beds require regeneration after a certain time period of operation. HCl is used to regenerate Cation Bed and NaOH for Anion Bed. The regeneration takes 6-8 hours. During this time this plant doesnâ&#x20AC;&#x2122;t supply PW.
THE AUTOMATIC PLANT FOR PURIFIED WATER: Most of the modern water purifier utilizes the method of Reverse Osmosis combined with EDI cell. The Automatic Plant in RENATA Ltd. also falls in this category. Reverse osmosis, also known as hyper-filtration, is the finest filtration available today. Reverse osmosis will allow the removal of particles as small as individual ions. The pores in a reverse osmosis membrane areTube onlyWell approximately 0.0005 micron in size (bacteria are to 1 micron Deep Overhead Iron0.2 Remover (Silica + & Resin, holds iron primarily) viruses are 0.02 to 0.4 microns). Reservoir The water flow rate is 1500Liter/hour. The Filter flow (Layers of PWof through the AutomaticBooster Purifier:Pump rock of
Reservoir
varying sizes)
Softener 1 &2 (Brine solution, removes hardness)
Activated Carbon Filter-140
Micron Filter
Dosing System 3
Dosing System 2
(Silica Stabilizer)
(Caustic Soda, pH control)
Heat Exchanger (to control temperature)
Storage Tank for PW
Dosing System 1 (Sodium bisulphate, hardness removal)
Recirculation Tank
Booster Pump
EDI Cell (removal of
RO (reverse osmosis) Membrane (Filter)
Pyroxene)
Figure: Flow chart for Automatic Water Purifier Description of flow process: The source remains same for both the plants, i.e., underground water collected into an overhead reservoir using a deep tube well. The subsequent steps are described below: o Iron Remover: It helps to hold iron primarily. Silica and resin is used for this purpose. It cannot completely remove iron but restrains a considerable amount. This is necessary because Fe 2+ iron is likely to form harmful fouls or scales later in the process. o Reservoir: This reservoir collects the apparently iron free water. o Booster Pump 1: There are two booster pumps used in the automatic plant. From the flow chart is can be easily noticed that both the pumps are placed after reservoirs. The function is to smooth out the water pressure in case the flow is variable. o Filter: This is also a gravel filter, one similar with that from the manual plant. It consists of a large vessel filled up with layers of rocks varying in size. o Softner 1 & 2: The softening is done is two stages or in two vessels. Softening means removing the hardness of water, in chemical terms to remove cations like Ca2+ and Mg2+ etc. For this purpose Brine solution is used which is actually NaCl (Soduim Chloride) solution. The Brine Solution is added to the water at a controlled rate from separate tank. o Activated Carbon Filter-140: It is used as a pre-treatment as part of a reverse osmosis system to reduce many organic contaminants, chlorine, and other items that could foul the Reverse Osmosis Membrane. Carbon filters are NOT generally successful at removing dissolved inorganic contaminants or metals.
There are two principle mechanisms by which activated carbon removes contaminants from water; adsorption, and catalytic reduction, a process involving the attraction of negatively-charged contaminant ions to the positively-charged activated carbon. Organic compounds are removed by adsorption and residual disinfectants such as chlorine and chloramines are removed by catalytic reduction. o Dosing System 1, 2 & 3: The chemical dosing is done in three stages. At each stage different chemical is dosed at fixed rate and the purpose is also different. At the first stage Sodium Bisulphate is added to remove the remaining hardness. Caustic Soda is added at the second stage and the purpose is to control the desired pH value. Finally Silica Stabilizer is used. It separates silica by coagulation method. o Micron Filter: After chemical dosing is done water is passed through a micron filter. It filters micro organisms like bacteria or virus. o Heat Exchanger: Then there is a heat exchanger to regulate the temperature of the water. It cools down the water to 21째C. o Recirculation Tank: The water from the heat exchanger is collected in a recirculation tank. This is nothing but a simply reservoir. o Booster Pump 2: The second booster pump then again directs water after smoothing the pressure to the RO Membrane. o Reverse Osmosis Membrane (ROM): Reverse osmosis uses a membrane that is semi-permeable, allowing pure water to pass through it, while rejecting the contaminants that are too large to pass through the tiny pores in the membrane. Quality reverse osmosis systems use a process known as crossflow to allow the membrane to continually clean itself. As some of the fluid passes through the membrane the rest continues downstream, sweeping the rejected contaminants away from the membrane and down the drain. The process of reverse osmosis requires a driving force to push the fluid through the membrane. The booster pump upstream fulfills the purpose.
Figure: Working of a RO Membrane.
An RO membrane system can remove as much as 98â&#x20AC;&#x201C;99% or more of all dissolved contaminants and can remove essentially all suspended (particulate) contaminants. However, RO units require pretreatment to prevent scaling, fouling with living and nonliving particulate materials, and chemical attack, commonly by oxidizing agents. o EDI (Electrodeionization) Cell: EDI is a continuous electro-chemical process of water purification where ion specific membranes, mixed bed resin and a DC voltage across them, replace the standard acid-caustic chemical regeneration process. The EDI Cell consists of a series of thin chambers that alternately contain mixed bed resin for water purification and concentrate water flow to carry away impurities. Ion-specific membranes, cationic on one side and anionic on the other, separate the chambers. A cationic-specific membrane will only allow positively charged ions to pass, while blocking the passage of negatively charged ions. An Anionic-specific membrane does just the reverse. Neither membrane will allow water to pass. High-voltage DC electrodes are located on the either side of the sandwiched resin/concentrate chambers. As water begins to flow through the cell, the charged ions in the water in a resin chamber are captured by the ion exchange resin. When a voltage is applied across the cell, the captured cationic and anionic impurities begin to migrate across the resin bed in the direction of the appropriate electrode. The ions then pass through the ion-specific membranes into the concentrate chamber.
Figure: Schematic of an EDI Cell. o Storage Tank: The water is finally collected in the common PW storage tank.
COMPARISON BETWEEN TWO WATER TREATMENT PLANTS: The points of difference between the two water plants are given below. a) The manual plant occupies less space than the automatic one b) The manual plant has lower initial and operating cost. c) Periodic and manual regeneration has to be done for the manual plant. At this time the plant is out of order. But the automatic plant is self-regenerative. d) The efficiency and quantity of water supply is also comparable. COMMON PURIFIED WATER DISTRIBUTION FOR BOTH PURIFIERS: The PW is then sent for distribution from the storage tank. Two pumps are used to maintain continuous circulation. Because pyrogen is likely to form in stagnant water. Pyrogen is a substance that produces fever. The PW is passed through UV sterilizer. The function of UV sterilizer is that it neuters the pyrogen but cannot remove it from the water.
DISTRIBUTION PATH FOR PURIFIED WATER:
Storage Storage Tank Tank for for PW PW
Two pumps (to Multi Column maintain circulation)
Heat Exchanger
Pure Vapor
UV Sterilizer (sterilizes pyrogen but cannot remove)
Solids (pyroxene etc Points are User collected and drained)
Figure: Flow chart showing distribution path for Purified Water (PW) Cooling water (from PW tank)
Condenser
Cooling water (from external source)
WATER FOR INJECTION (WFI): PW contains dead bacteria which is undesirable for WFI. This dead bacteria or pyrogen is Storage Tank for removed from PW by incorporating higher stages of purification. The flow path of WFI:
WFI
Jacketed pipes
Pressurized Steam
(to maintain 80째C)
(for ampoule cleaning)
User Points
Autoclave (for ampoule cleaning)
Figure: Flow chart for WFI Description of flow process: From the flow chart it is apparent that the higher purification employed for WFI is nothing but a combination of heat exchanger and condenser. The water is at first taken from the PW storage tank. Then water is passed through a multi-column (five columns) heat exchanger. The multi-column heat exchanger receives five utility inputs. These are feed water, cooling water, air, steam and electricity. There is a PLC control system present. At this point the pyrogen gets separated from the water and drained. The remaining vapor is then cooled down again in the condenser. The condenser water is taken from two sources. One is from the PW storage tank and another source is external. The vapor and condenser water doesnâ&#x20AC;&#x2122;t come into direct contact. As the water gets condensed, it is collected into a storage tank for WFI. The temperature is maintained at 80°C by passing it through jacketed pipes for distribution. At this temperature no pyrogen can survive.
Some application may require pressurized steam such as Autoclave for ampoule cleaning. In such cases steam is pressurized (up to 4.5 bar) locally near the user point by using Pure Steam Generator.
UTILITY: STEAM GENERATION PLANT The steam generation utility is operated and maintained by the Engineering Department. The plant is on the service or utility floor.
APPLICATIONS OF STEAM IN PHARMACEUTICAL: There are several functions which require the steam of certain pressure and temperature. These are: o Water Treatment (to produce WFI, inside the multi-column heat exchanger) o Raw Material Drying o Coating Machine for Tablets o Medicine Mixing o Washing Purpose o Sterilization (ampoule washing, autoclave) etc.
COMPONENTS OF STEAM GENERATION PLANT: The equipments used are listed below: o Boilers o Pure Steam Generators o Pipelines
BOILER: There are two boilers in RENATA Ltd. which maintain the required steam supply. o Type of boilers: Both water-tube and fire-tube boilers are used. But at the time of training the watertube boiler was not operating. o Fuels for boiler: The fire-tube boiler running presently can utilize three types of fuels, i.e. natural gas, diesel and furnace oil. There is a diesel tank kept at a distance from the boiler so that diesel can be used without any delay when required. Usually diesel is used when the gas pressure is not sufficient. The use of furnace oil requires an additional heater. o Specification of boiler:
Manufacturer: Dennis Baldwin and Sons Ltd. Series type and serial no. MX2500-42 Design pressure and temperature: 165 psig / 250°C Hydraulic test pressure: 248 psig Maximum working pressure – 150 psig Rated output (maximum continuous rating): 55000LB/HR F&A
100°C
No. of British Standard and Class of Construction: BS2790 1992 CLASS 1 o Specification of Boiler Burner: Manufactured by: DUNPHY Combustion Ltd., ROCHDALE, England Type: THD 310 YHLLFVD Serial – 23005 Electrical specification: 400V/ 3phase/ 50Hz Gas Type: Natural, I2H Burner rating gas: 650-3050 KW Oil type: Heavy oil Burner motor rating: 6.6 KW o Boiler Mountings: Following is a list of boiler mountings:
Feed water pump: There are two pumps. One pumps runs alternately for seven days.
Water level indicator gage: It indicates the feed water input level. If the water level goes up a maximum level, it stops the pump.
Blower: The blower supplies air essential for combustion inside the boiler. Air supply in controlled by a damper. Purging time is 2-3 minutes. Purging means removal of exhaust gases remained from the previous operation period. The firing is done in two stages. At first low firing occurs. This procedure is ensured by a photocell sensor. Then the final firing occurs.
Safety valve: The working pressure of the boiler is 8-9 bars. The maximum pressure allowed is 10bars. But when the pressure reaches 9 bars, the safety valve opens automatically and the excessive pressure is released to ensure the safe operation of the boiler. It is situated at the top of the boiler.
Main valve: The main valve is also at the top. But its function is to supply the steam generated.
Chimney: The chimney is used for exhausting the flue gas. By analyzing the exhaust, it can be determined if any fuel is wasted or not. While running on diesel, if one notices smoke in the exhaust, then it can be assumed that fuel is not burned completely.
Pressure gages: There are several pressure gages. For example, the gas pressure gage, diesel pressure gage, exhaust pressure gage etc.
Blow down valve: As water evaporates inside the boiler, the metalic hardness of water remains within and is collected at the bottom of the boiler. It is necessary to remove it in order to prevent scale formation. Blow down is carried out by the operator manually. The blow down interval can range from 2-4 hours depending on the quality or amount of hardness present in the feed water.
o Boiler feed water treatment: The feed water before entering the boiler is treated chemically to prevent scale formation. Scales reduce boiler’s efficiency as it hinders heat transfer. Dosing is done for this purpose. Typical dosing agents are Sodium Sulphide, Sodium Hydroxide, Hydrogen or Phosphate etc. The dosing is done in the dosing tank, which is full of resin inside. The dosing agent charges the resin which ultimately treats the water. The feed water is available at ambient temperature. A little increase in temperature of feed water is desirable before entering the boiler. This increases boiler efficiency. So it is passed through a hot well. A portion of the steam from the boiler is used for this purpose. o Boiler Inspection: The boilers are inspected after every 1.5 years.
PURE STEAM GENERATOR: Pure steam generator is used to increase the pressure of WFI steam generated. This highly pure steam is used in the autoclave for ampoule washing. There are two pure steam generators.
o Specification of PSG: Manufactured by: DE LAMA, Italy Electric voltage: 400 volts Working pressure: 4.5 bars (psig)
DIFFERENCES BETWEEN BOILER AND PURE STEAM GENERATOR: Pure steam generator differs from boiler in two respects. These are:
•
Boiler extracts heat from gas or flue gases, whereas pure steam generator extracts heat from steam from the boiler.
•
Raw water is feed into the boiler after chemical treatment. On the other hand WFI is the feed for pure steam generator. This is because the application requires steam free from any microbiological contaminants.
UTILITY: COMPRESSED AIR SUPPLY Compressed air supply is an essential utility of pharmaceutical production procedure. Tablet press, capsule filling, dry sirup filling, coating, blistering all these processes require compressed air. The overall process of supplying compressed air in RENATA Ltd. is described below:
COMPONENTS OF COMPRESSED AIR SUPPLY PLANT: Following is the list of equipments required to supply the desired quantity of dry and compressed air: o Air Compressor: There are 4 compressors
Specification of one compressor KAESER KOMPRESSOREN GmbH, GERMANY Serial no. ASD-37 Maximum working pressure: 11bar Rated Power: 22KW Speed: 2945/min
o Water Filters o Eco Drains
Specification of one eco drain: KAESER Eco Drain 12 Made in Germany 0.8/16Bar (12/230 psig) 230VAC/50-60 Hz
o Air Receiver Tank: There are 2 Large tanks o Dryer: There are 4 dryers
Specification of one dryer: KAESER KOMPRESSOREN GmbH, GERMANY
Maximum working pressure: 18bar Refrigerant: R-134a Charge of refrigerant: 2.1 kg Electrical specification: 400 V/3 phase/50 Hz Rated Current: 4.3 Amp o Header
FLOW PROCESS OF COMPRESSED AIR SUPPLY PLANT: Air
Air Compressor
Water Filter
Air Receiver Tank
Water
Dryer
Eco Drain Water Filter Water
Air
Header for Distribution
Water
Figure: Flow chart for Compressed Air
DESCRIPTION OF THE FLOW PROCESS: The compressor intakes air from ambient. But ambient air contains moisture which is undesirable for various purposes. At first the air-moisture is compressed together. Then the air is passed through a water filter, where the air-water separation occurs. The separated water is passed through the eco drain. The purpose of the eco drain is to release the collected water without affecting the air pressure. It also thus restricts the outflow of air accompanied by water. Eco drain consists of a coil-type water level sensor contained within a little container made of Gk-Al, electronic circuit, solenoid valve and diaphragm. The working principle is rather simple. The condensed water falls through the pipe into the container. As the container is filled up to a certain level, the sensor activates the solenoid valve. The water thus goes out as the valve opens. The compressed air on the other hand is collected into a large receiver tank. This is done to ensure the constant flow at constant pressure. But the air is still hot. The temperature is 6070째C. it needs to be cooled down.
Dryer is used to cool the air and to further reduce moisture. The dryer operates on typical refrigerant cycle. The refrigerant is R-134a. As the air further cools down the rest of the moisture gets condensed, collected and drained out manually. Then finally after passing again through a water filter, the air reaches the header. From the header the compressed and dry air is supplied through pipeline to the required stations.
QUALITY MAINTENANCE Quality is a vital issue for a product. Quality of the product is maintained by the “Quality Assurance” department in this industry. This department is divided into two parts: •
Quality Compliance
•
Quality Control
QUALITY COMPLIANCE Quality compliance means maintaining the consistency of the overall procedure. It ensures that there will be no problem created in the production process by preventing all sorts of causes of errors. It checks different parameters of the production process which have already been set. For example, during mixing of ingredients the mixing proportion is checked. Moreover the sequence of the production is maintained or not – that is also checked. It also checks the physical parameters like – HVAC system, cleanliness, pressure, temperature etc.
QUALITY CONTROL Quality control means to maintain the quality of the raw materials, intermediate products and finished products. It also ensures the proper chemical formulation and the quality of the product. Quality control department works in different subgroups.
The subgroups are shown below: Quality Control
PD Development
Routine Commercial
Raw material And Intermediate Product
Finished product
Source approval
Packaging product
Packaging material check
Pilot batch finished product
• Routine Commercial Quality control checks the following properties of the raw material: •
Appearance
•
Solubility
•
Moisture content
•
Impurity
•
Assay
•
Potency etc
Raw material of newly developed product
These properties are checked according to the United State Pharmacopoeia (USP) grade or British Pharmacopoeia (BP) grade. After checking all these things then the raw materials are accepted. In between the production process the checking is done also. After every process like mixing, blending, granulating the quality of the intermediate products is checked. It checks the uniformity of the product after every stage of production process. If the standard deviation is less than three then the products are accepted. This department also checks the following properties of the finished product: •
Hardness
•
Thickness
•
Friability
•
Disintegration time
•
Volatility
•
Impurity etc.
Before packaging the packaging materials are checked. Packaging materials should be not harmful for the product. The packaging should be of such that the air cannot pass through it. Otherwise air can damage the desired properties of the product.
• PD development PD development means product development. This is also known as “Analytical Team”. This department is concern about the development issue of the product. It always tries to increase the quality of the product. In doing so this department may change the source of the raw material. It may change the process of making the medicine (USP or BP grade). But this is done only after proper analysis. This department also checks the packaging material and to improve its quality it takes necessary steps. It also searches for new product. For newly developed products it analyzes the raw materials.
Stability of the product is also checked under the quality control department. It determines the time period up to which the product will not lose its desired properties. To do this extra temperature, pressure, humidity is applied to the product for testing. A guideline is followed for that. It is “International Center for Standard “. There is a quality control lab equipped with modern machineries, tools and instruments to check the quality of the product in different stages of the production process. Every instrument is fully computer controlled. These machines show the standard deviation automatically. Many pharmacist and chemist are work together here.
QUALITY MANAGEMENT SYSTEM: There is another group working in the quality department Known as “Quality Management System” (QMS).They are responsible for •
Market complain handling
•
Change control
•
Deviation Check
•
Corrective and preventive action (CAPA)
This department checks the demand of the market. It also faces the buyers. It also listens to their complains. Then this department brings change in the quality control system to improve the quality of the product according to the market demand. It finds out the problems or wrong action in between the production process. Then if the standard deviation is too much necessary preventive and corrective actions are taken. So the function of this department is to take a market feedback. The brochure team is working under QMS. Its function is the documentation of overall process in details.
SACHET FILLING FACILITY (Mirpur, Dhaka)
Sachet Filling is a minor facility of RENATA Ltd. All products manufactured under this facility have the similar procedure. The HVAC requirements are same as the products from the general plant.
THE PRODUCTS: The Soft Gel facility manufactures mainly two types of products. The second product has three brands. These are as follows: o Saline-R o Vitamin and Minerals
Pustikona
Sprinkle
Monimix etc.
Fifteen ingredients are used for Pustikona. For Sprinkle and Monimix five ingredients are used. Goods Receiving (1)
MACHINES USED:
Rejected
Following is a list of machines used in Sachet Filling Facility:
Hold for decision
o Vibratory Sifter
Quarantine RM Store (2o Multi-Mill 1)
QC Check
o Blender
Accepted
o Filling Machines Released RM Store (2-2) PRODUCTION PROCESS:
o Automatic Carton Machine etc.
• The general flow process of products under Sachet Filling Facility from the Batch Dispensing (3) (BMR): Manufacturing Record Rejected
Mixing (4)
QC Check
Hold for decision
Rejected Hold for decision
Accepted
Filling (5) QC Check
Packing (6) Accepted
FG Store (7)
Process under controlled humidity and temp [40-60%] Process under ambient humidity and temp [25°C ± 2°C]
Figure: Overall Procedure including QC check and others of Sachet production
DESCRIPTION OF THE FLOW PROCESS: Description of the process of Sachet Filling product manufacturing is given below: o Storage: All the raw materials are stored in the store room. For saline raw material is sodium, sodium citrate, potassium, anhydrous, dextrose etc .For vitamin dry vitamin is the raw material. At first the raw materials are kept in the quarantine area for checking. Then sampling is done in a sampling booth. After that the raw materials are released for dispensing. o Dispensing: The purpose of dispensing booth is to release the correct amount of raw material. There is a weighing machine that can measure up to 60 kg. And for measuring the light weight there is another machine that can measure not more than 200 grams. o Mixing:
After dispensing raw materials are shifted to blending room. Here the raw materials are mixed properly. At first the raw materials are placed into the Vibratory Sifter. Then these are shifted to Multi-Mill for crushing. Again these are moved to the Vibratory Sifter. Then the material is taken into Blender for proper mixing. Vibratory Sifter
Multi-Mill
Blender
Figure: Flow process for mixing There are separate blending room for saline and vitamin. Vibratory Sifter has 20 mesh for saline and 50 mesh for vitamin. Sieve diameter is one millimeter. For saline preparation mixing time is one hour. For vitamin it is 45 minutes. o Filling: After filling the products are ready for filling. Following is the list of machines used in the Soft Gel Facility for filling purpose:
GREATIDE: There are three GREATIDE (model no. F, G, H) machines available at RENATA Ltd. Each machine is provided with manual photo electric control system. Each machine can produce 40 – 42 sachets per minute. But these machines are not being used due to lower productivity.
SOLPAC: There are three SOLPAC (model no. J, K, L) machines available. Each machine is provided with PLC control system. These machines are used for filling vitamin & minerals. Each machine can produce 250 – 300 packets per minute. The working process of these machines is given below: Foil
Powder
Vertical Sealing at both sides (2 heaters, 127°C)
Batch Print
Horizontal Sealing at the bottom (2 heaters, 127°C)
Slitting
Cutting
Upper Sealing
Figure: Flow process in SOLPAC Machine
Figure: SOLPAC Machine Foil comes from two ways for front portion and rear portion. Then the powder i.e. mixed ingredients pass through small conical shaped ducts which vibrates always. Vibratory motion helps powder to flow below. Then upper sealing and lower sealing are done by heating. Upper sealing temperature is 127°C and the lower sealing temperature is 130 C. Then the batch number, manufacturing date and expired date are printed which is called batch print. After slitting and cutting the sachet filling is completed and the product is ready for packaging.
BOSSAR: PLC control The number of BOSSAR (model no. A, B, C) machines available is three. Each machine is provided with PLC control system. These machines are used for filling saline. Each machine can produce 95 – 100 packets per minute. The working process of this machine differs from SOLPAC machine. The working process of this machine is given below: Foil
Bottom Sealing
Side Sealing
Side Cutting
Packet opening
Cutting
Eye Mark Sensor
Batch Print
Powder filling
Upper sealing
Figure: BOSSAR Machine
Foil is bended first to insert into the machine. Then lower sealing and side sealing are done. Sealing temperature is 140 C. Then the batch print is done. After that the packet is cut. There is a photo cell which actually a sensor to help cutting in right place. Then the sachet is opened for filling powder into it. After filling the powder upper sealing is done. And the product is ready for packaging. o Leak test: Leak test is done before packaging. It is done in the IPC room. Saline is tested by water and pustikona is tested by isopropyl alcohol. o Packaging: Packing system is not fully automatic. At first ten sachets are picked up manually by the workers. Then they put it into the automatic packing machine. This machine puts the 10 sachets into a packet made of paper. Then the packets are placed into a carton manually.
SOFT GEL FACILITY (Mirpur, Dhaka) Soft Gel or Soft Gelatin is a minor facility of RENATA Ltd. considering not only the size of the plant but also the number of products manufactured under this facility. The products under this facility are intended for children.
THE PRODUCTS: The Soft Gel facility manufactures three products. These are as follows:
o E-Gel-200 o E-Gel-400 o Lucent- 0.25mcg The first two products are Vitamin E and the last one is Calcium (mineral).
MACHINES USED: Following is the list of machines used in the Soft Gel Facility: o Colloid Mill GEq-193 o Medicine Service Tank o Vacuum Homogeneous Mixer Good ReceivingSky Softgel, Co. Labeling LTD. (2)
Quarantine (3)
(1)
o Triple Roller o Gelatin Melting Tank
Dispensing (6)
Stored for use (5)
Accepted
Rejected Hold for decisi on
o Softgel Encapsulation Machine and Tumbling Dryer QC
Chec k (4)
Made: SS-100 415 Volt, 50Hz, 4 Phase.
Medicine Preparation (7)
Serial: 5B0652F 77 Sky Softgel Co. LTD Gelatin Melting (8)
Rejected Hold for decisi on
QC Chec k (9)
PRODUCTION PROCESS: Hold
• The generalfor flow process of products under Soft Gel Facility from the Batch Accepted decisi
Manufacturing Record (BMR): on Rejected
QC Chec
Drying (11)
Encapsulation (10)
k (12) Accepted
Primary Packaging (13)
Rejected
Secondary Packaging (14)
QC Chec k (15) Accepted
Process under controlled humidity and temp [40-60%] Process under ambient humidity and temp [15°C ± 2°C]
Transfer to FG Store (16)
Hold for decisi on
Figure: Overall Procedure including QC check and others of Softgel production
DESCRIPTION OF THE FLOW PROCESS: The first six stages of manufacturing process are similar to any other products starting from good receiving to dispensing. The principal process is comprised of four stages. These are given below: o Medicine preparation: The medicine refers to the liquid within the shell or capsule of the product. In other words this is what is encapsulated. The process is mainly grinding and mixing carried out in a series of machines. At first multi vitamin and multi mineral are taken into the Colloid Mill for grinding purpose. The mixed material is then taken into the Medicine Service Tank. After that, mixing is done in the Vacuum Homogeneous Mixer. Finally the mixture is passed through a manual machine, the Triple Roller. In it all the processes mentioned above are carried out, namely, the grinding, colloid milling and final mixing.
o Gelatin Melting: In this stage of the process the shell making is carried out. The process is nothing but just melting of gelatin occurs in a large drum or tank called Gelatin Service Tank. There are two tanks available for this purpose. As the melting takes place, the tank also rotates. There are electric motors provided for this purpose. The process flow is shown below: Heat Generation
Addition of Raw Material Gelatin Service Tank
Figure: Flow Chart for Gelatin Melting o
Encapsulation and Drying: The final stages are the encapsulation and drying. These are carried out in a single machine, Soft Gel Encapsulation Machine and Tumbling Dryer. The medicine is added through a hopper which incorporates a pump. The medicine being liquid justifies the use of a pump. On the other hand gelatin is passed through a service pipe by creating a pressure difference. For this pupose pressurized air is used. The gelatin is also heated to soften it in order to facilitate the shell formation process. To ensure optimum softening it is passed over a cooling drum after heating. The gelatin sheet is then passed over a set of rollers. The rollers convey the gelatin sheet to pass over a drum on which there are impressed dies. At this point heated injection of medicine occurs and this pushes the gelatin to set inside the die, forming the shell. This machine is a symmetric one. In other words same process occurs from opposite direction on the same machine. This means two parts of the shell are made at the same time and seal immediately as injection of medicine occurs. The Tumbling dryer is a blower. There are 8 vessels in it. The total drying is carried out for 40 minutes. The whole structure is made inclined so that the capsules come out of the machine automatically. If required the capsules are then again dried in a separate room using dryer.
The rest of the process is again similar to any other product manufactured in RENATA Ltd. The remaining stages include primary packaging in a blister machine, secondary packaging which is done manually in this facility, quality control and finally transfer to the finished goods store.
OTHER FACILITIES ANIMAL HEALTH:
RENATA Limited is worldwide known for animal health products. They produce some highly quality products to serve animal health needs in the country as well as have some export ventures also in this project. The products are used in poultry farms and such other areas for hens, chickens, and cows mainly. • • •
Animal Health products are o Tablet o Capsule The production is done inside the general plant facility, but in a special separate zone with required machineries and settlements. Raw materials for Animal Health Products are purchased, stored and preserved totally separately than the other general products.
HORMONE: •
•
Hormone Products are produced under three sections basically: o PPF-1.5(inside the general plant) o PPF-1(separate facility at the Mirpur site) o PPF-2 (under construction at the Rajendrapur site; also known as Hormone-2) Hormonal products are produced under special safety precautions as they might be detrimental to public health if inhaled or be openly in contact with regularly.
GENERAL PLANT-2: • • •
This project is under construction at the Rajendrapur, Gazipur site. This is even larger than the existing General Plant-1 facility. It is expected to start commercial production from the June-July, 2012.
CEPHALOSPORINE AND PENICILLIN: • • •
The products under these facilities cannot be manufactured with others. The factory site in entirely at Rajendrapur site. Products are mainly antibiotics.
• •
RENATA is supposed to start a herbal product plant very soon. Project is currently in the design phase.
HERBAL PRODUCTS:
ETP (EFFLUENT TREATMENT PLANT) Industrial waste-water treatment covers the mechanisms and processes used to treat waters that have been contaminated in some way by anthropogenic industrial or commercial activities prior to its release into the environment or its re-use.
Most industries produce some wet waste although recent trends in the developed world have been to minimize such production or recycle such waste within the production process. However, many industries remain dependent on processes that produce wastewaters.
THE BASIC PROCESS FLOW DIAGRAM: Effluent Water from Production
Equalization Tank
Gravity Settling Tank
Tube Settler
Flocculation Tank
Coagulation Tank
Collecting Tank
Activated Carbon Tank
Final Treated Water Tank
Inland River
Drainage system
Figure: Basic process flow of ETP
DESCRIPTION OF THE FLOW PREOCESS: • •
Effluent water: Contains mainly chemical contents, no micro organisms present. Equalization Tank: Water from production is collected for a certain time at a certain rate, the time is known as Retention Time. It is required to obtain certain desired general parameters of the collected water as it comes from very different sources. Here occurs aeration: a) Natural b) Compressed Air (Forced) Advantages of aeration:
•
a) Mixing of water b) Solidification of Ionized particles Gravity settling: Solid particles fall as precipitates due to gravity.
• • • • • •
Coagulation Tank: Here Alum (Al2SO4) dosing is done. But beforehand the pH of water is checked. If it is less than 8, then lime dosing is done. Flocculation Tank: Flocculation is a process where colloids come out of suspension in the form of flakes. The action differs from precipitation in that, prior to flocculation, colloids are merely suspended in a liquid and not actually dissolved in a solution. Tube Settler: Water is collected from the mid level, because upper level contains colloidal suspended particles and lower one is filled with heavy precipitates. The tubes are designed to maintain a laminar flow of water. Activated Carbon: It purifies water by adsorbing different micro organisms. But at the same time it takes away some oxygen, which is detrimental to treatment process. Final Treated water Tank: In this final tank, forced aeration is done to treat the water and compensate for the O2 loss in the activated carbon portion. Drainage: Purified water is drained out to municipal drainage system, which eventually goes to the inland rivers.
INCINERATOR:
Incineration is a waste treatment process that involves the combustion of organic substances contained in waste materials.[1] Incineration and other high temperature waste treatment systems are described as "thermal treatment". Incineration of waste materials converts the waste into ash, flue gas, and heat. The ash is mostly formed by the inorganic constituents of the waste, and may take the form of solid lumps or particulates carried by the flue gas. The flue gases must be cleaned of gaseous and particulate pollutants before they are dispersed into the atmosphere. In some cases, the heat generated by incineration can be used to generate electric power. Scum is collected to the sand bed filter. Then after drying by natural heating, the solid slug is taken to the incinerator. Here along with all the solid wastes, they are burnt at minimum 800˚C and released to atmosphere as CO2, no CO is present at that much high temperature.
FACTORS TO BE MEASURED: To check if any industry is completely environment friendly or not, some parameters are to be measured of the water which is let out in the open environment. They are about 40 in numbers. Among them which are essentially important are: •
BOD: Biological Oxygen Demand Biochemical oxygen demand or B.O.D. is the amount of dissolved oxygen needed by aerobic biological organisms in a body of water to break down organic material present in a given water sample at certain temperature over a specific time period. The term also refers to a chemical procedure for determining this amount. This is not a precise quantitative test, although it is widely used as an indication of the organic quality of water.[1] The BOD value is most commonly expressed in milligrams of
oxygen consumed per litre of sample during 5 days of incubation at 20 °C and is often used as a robust surrogate of the degree of organic pollution of water. •
COD: Chemical Oxygen Demand In environmental chemistry, the chemical oxygen demand (COD) test is commonly used to indirectly measure the amount of organic compounds in water. Most applications of COD determine the amount of organic pollutants found in surface water (e.g. lakes and rivers), making COD a useful measure of water quality. It is expressed in milligrams per liter (mg/L), which indicates the mass of oxygen consumed per liter of solution. Older references may express the units as parts per million (ppm). Many governments impose strict regulations regarding the maximum chemical oxygen demand allowed in wastewater before they can be returned to the environment. For example, in Switzerland, a maximum oxygen demand between 200 and 1000 mg/L must be reached before wastewater or industrial water can be returned to the environment
•
pH: In chemistry, pH is a measure of the acidity or basicity of an aqueous solution.[1] Pure water is said to be neutral, with a pH close to 7.0 at 25 °C (77 °F). Solutions with a pH less than 7 are said to be acidic and solutions with a pH greater than 7 are basic or alkaline. pH measurements are important in medicine, biology, chemistry, agriculture, forestry, food science, environmental science, oceanography, civil engineering and many other applications. In a solution pH approximates but is not equal to p[H], the negative logarithm (base 10) of the molar concentration of dissolved hydronium ions (H3O+); a low pH indicates a high concentration of hydronium ions, while a high pH indicates a low concentration. This negative of the logarithm matches the number of places behind the decimal point, so, for example, 0.1 molar hydrochloric acid should be near pH 1 and 0.0001 molar HCl should be near pH 4 (the base 10 logarithms of 0.1 and 0.0001 being −1, and −4, respectively). Pure (de-ionized) water is neutral, and can be considered either a very weak acid or a very weak base, giving it a pH of 7 (at 25 °C (77 °F)), or 0.0000001 M H+.[2] The pH scale has no upper or lower limit and can therefore be lower than 0 or higher than 14 [3]For an aqueous solution to have a higher pH, a base must be dissolved in it, which binds away many of these rare hydrogen ions. Hydrogen ions in water can be written simply as H + or as hydronium (H3O+) or higher species (e.g., H9O4+) to account for solvation, but all describe the same entity. Most of the Earth's freshwater bodies surface are slightly acidic due to the abundance and absorption of carbon dioxide; [4] in fact, for millennia in the past, most fresh water bodies have long existed at a slightly acidic pH level.
•
DO: Dissolved Oxygen
Oxygen saturation or dissolved oxygen (DO) is a relative measure of the amount of oxygen that is dissolved or carried in a given medium. It can be measured with a dissolved oxygen probe such as an oxygen sensor or an optode in liquid media, usually water. It has particular significance in medicine and environmental science. â&#x20AC;˘
TDS: Total Dissolved Solid Total Dissolved Solids (often abbreviated TDS) is a measure of the combined content of all inorganic and organic substances contained in a liquid in: molecular, ionized or micro-granular (colloidal sol) suspended form. Generally the operational definition is that the solids must be small enough to survive filtration through a sieve the size of two micrometer. Total dissolved solids are normally discussed only for freshwater systems, as salinity comprises some of the ions constituting the definition of TDS. The principal application of TDS is in the study of water quality for streams, rivers and lakes, although TDS is not generally considered a primary pollutant (e.g. it is not deemed to be associated with health effects) it is used as an indication of aesthetic characteristics of drinking water and as an aggregate indicator of the presence of a broad array of chemical contaminants. Primary sources for TDS in receiving waters are agricultural and residential runoff, leaching of soil contamination and point source water pollution discharge from industrial or sewage treatment plants. The most common chemical constituents are calcium, phosphates, nitrates, sodium, potassium and chloride, which are found in nutrient runoff, general stormwater runoff and runoff from snowy climates where road de-icing salts are applied. The chemicals may be cations, anions, molecules or agglomerations on the order of one thousand or fewer molecules, so long as a soluble micro-granule is formed. More exotic and harmful elements of TDS are pesticides arising from surface runoff. Certain naturally occurring total dissolved solids arise from the weathering and dissolution of rocks and soils. The United States has established a secondary water quality standard of 500 mg/l to provide for palatability of drinking water.
â&#x20AC;˘
TSS: Total Suspended Solid Total suspended solids is a water quality measurement usually abbreviated TSS. It is listed as a conventional pollutant in the U.S. Clean Water Act. This parameter was at one time called non-filterable residue (NFR), a term that refers to the identical measurement: the dry-weight of particles trapped by a filter, typically of a specified pore size. However, the term "non-filterable" suffered from an odd (for science) condition of usage: in some circles (Oceanography, for example) "filterable" meant the material retained on a filter, so non-filterable would be the water and particulates that passed through the filter. In other disciplines (Chemistry and Microbiology for examples) and dictionary definitions, "filterable" means just the opposite: the material passed by a filter, usually called "Total dissolved solids" or
TDS. Thus in chemistry the non-filterable solids are the retained material called the residue.
CONCLUSION The visit to such a well known factory for our industrial training was quite a lot beneficial to us in many respects. It was a well-equipped factory from which we could gather firsthand knowledge about mechanical engineering, how different machines work and their trouble shooting process, Practical issues over there, Staff management, labor control, Quality issues, co-operation of different departments, business dealing etc. The authority provided us with intense scope and facilities to learn so many different things in a very short time period. People over there were friendly and helpful. But, due to time constraints, we could not visit their under construction Rajendrapur Factory, where we could enhance our knowledge about the basic steps to start a factory, working procedure and project management etc. Yet, the industrial tour really taught us how to behave, manage and work properly in practical job life. Our sincere thanks and gratitude goes to each and every person who made this possible, both at RENATA Limited and Mechanical Department of Bangladesh University of Engineering and Technology.