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Cadila
Pharmaceutical
Limited
Anas Haruna Indabawa
BARCHALOR OF PHARMACY
ADDRESS: Naini, Allahabad, U.P, INDIA. 211007.
ID NUMBER: 13BPH053
JUNE- 2016
This is to certify that Mr. Anas Haruna Indabawa, a student from the Department of
Pharmaceutical Sciences, Sam Higginbottom Institute of Agriculture, Technology & Sciences
Allahabad has Completed his Industrial Training from
to
at Cadila
Pharmaceuticals Limited, Samba, State of Jammu & Kashmir in integration of B.Pharm
degree Course.
Place:
Date:
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PAGE
5-7
8-15
Production Section
- General Instructions and Precautions
- Granulation
- Compression
- Coating
- Packaging and Labelling
- Encapsulation
Soft Gelatin and Hospicon Section
- Soft gelatin
- Hospicon
Quality Control & Quality Assurance Section
- Size and Shape
- Organoleptic Property
- Hardness and friability
- Weight Variation
Microbiology Section
- Microbiological Testing of Non-sterile product
- Sterility Testing
- Validation
Engineering Section
- Electricity Unit
- Water Treatment System
- Water Softening Unit
- Chilling/Steam Unit
- Air Handling Unit (AHU)
- Effluent Treatment Plant (ETP)
Raw Material and Finished Goods Section
16
17-19
20-23
24-27
28-30
Page4
- Raw material
Receiving
Sampling
Storing
Dispensing
- Finished goods
Conclusion
31
Bibliography
32
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Page6
APPROVED PATENTS
Page7
FORMULATIONS
Our extensive range of finished dosage formulations covers every aspect of human life.
Our basket of formulations contain more than 850 products in several forms belonging to 45
therapeutic segments and 12 specialities including cardiovascular, gastrointestinal, analgesics,
haematinics, anti-infectives and antibiotics, respiratory agents, antidiabetics, immunogicals and
oncology. The manufacturing expertise is available for almost all dosage forms including sterile
as well as non-sterile products. Formulations have three manufacturing facility in the state of
Gujarat, Jammu (India) and Ethiopia. All of which are approved by all prominent international
regulatory bodies, including USFDA
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Ensure area and equipment cleanliness before starting the manufacturing operations.
Check and ensure that all manufacturing equipment and other required accessories are
clean ready for use.
Wear gloves and nose mask during all manufacturing process.
Counter check the weights of all ingredients before using in the batch
Get line clearance from QA for manufacturing.
Air handling unit (AHU) system should be kept ON throughout the manufacturing
process.
Temperature should be kept between 25C 2C and relative humidity should be kept
between 5010%.
Ensure that only QC approval purified water is being used for manufacturing purpose
Always transfer solution to the manufacturing vessels through 20 meshes.
During the preparation of this product, no other product processing should be done in the
same area.
Whenever sifting through SS mesh is involved; check the mesh integrity before and after
use.
All critical aspects during manufacturing like temperature, duration of mixing, weight,
etc. must be checked and recorded by the supervisor.
Supervisor to ensure completion of all in-process records during various stages of
manufacturing operations till completion of the batch.
Release from QA should be taken from all in-process tests mentioned in batch
manufacturing record
No over writing is allowed in batch manufacturing record. If initial data is wrong entered,
cancel the data by single stroke arrow and put initials. Record reasons for change as footnote on the same page.
All the details whatever is necessary should be recorded in batch manufacturing record
(BMR).
Send a test request form to QC after manufacturing is completed
Check all polyethylene bags before and after material loading for black particles and
sealing.
Check calibration of respective equipment/machine before use.
Page9
GRANULATION
Departments
Unit Operation
There are three methods of preparing Tablets. These are:
Wet granulation
Dry granulation (also called slugging) and
Direct compression
Each of these methods has its advantages and disadvantages. The first two step of milling
and mixing of the formulation are identical, but thereafter the processes differ, Each
individual operations of the process is known as unit operation.
Step in different methods of manufacture
WET GRANULATION
o
o
o
o
o
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DRY GRANULATION
o
o
o
o
o
o
DIRECT COMPRESSION
o Milling of drugs and excipients
o Mixing of ingredients
o Tablet compression
Equipments
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Conta Blender
The Conta blender gives better efficiency as compared to conventional blenders.
Tumbling principle in partial void enables the homogeneous mixing of active ingredients,
additives and raw materials. The rotation of bunker in a diagonally eccentric plane ensures
efficient blending.
COMPRESSION:
This step involves consistent flow of an adequately lubricated, uniform blend, into dies
where the granules are being compressed into tablets. Compression is to be carried out as per
batch manufacturing record. Collect the samples at various stages i.e. at start up, high RPM, low
RPM, low weight at target speed, high weight at target speed, initial, middle and end of
compression and carry out the testing of content uniformity and physical parameters such as
hardness, thickness, friability etc.In compression stage three batches i.e. Batch No I, II and III
shall be considered for validation. Compression results of all the batches are well within the
acceptance criteria results of the compression at different speed, low weight at target speed, high
weight at target speed, initial, middle and end of the compression.
Page12
COATING
Tablets may be coated for a variety of reasons, including protection of the ingredients
from air, moisture, or light. Tablets are also coated to protect the drug against decomposition or
to disguise or minimize the unpleasant taste of certain medicaments. Coating also enhances the
appearance of tablets and makes them more readily identifiable. In addition, coatings can be
resistant to gastric juices but readily dissolve in the small intestine. These enteric coatings can
protect drugs against decomposition in the acid environment of the stomach.
Coating is to be carried out as per batch manufacturing record. Samples are collected at
the end of coating stage and carried out the testing of content uniformity and identification tests,
related substances, individual impurities, and physical parameters such as hardness, thickness,
friability, etc. In coating stage three batches i.e. Batch No I, II and III shall be considered for
validation. Coating results of all the batches are well within the acceptance criteria.
Types of coating include:
Sugar coating
Film coating
Modified coating
Sugar Coating:- The sugarcoating process involves building up layers of coating material on the
tablet cores as they are tumbled in a revolving pan by repetitively applying a coating solution or
suspension and drying off the solvent. Before sugarcoating, the core is coated with a sealing coat
of shellac, PVP*-stabilized types of shellac, or other polymeric materials, such as cellulose
acetate phthalate and polyvinyl acetate phthalate. The next stage is to build up a sub coat that
will provide a good bridge between the main coating and the sealed core, as well as round off
any sharp corners. This step is followed by smoothing or grossing. The finishing stage is
accomplished by again applying one or two layers of clear syrup. The tablets are then left for
Sam Higginbottom Institute of Agriculture, Technology & Sciences (SHIATS) Allahabad.
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ENCAPSULATION
Encapsulation is the process of manufacture of capsules. Capsules are solid dosage forms
in which the drug substance is enclosed in either hard or soft, soluble form of gelatin.
TYPES OF CAPSULES
Hard gelatin capsule
Soft gelatin capsule
HARD GELATINE CAPSULE
It is referred to as dry filled capsule; consist of two sections, one slipping over the other,
thus completely surrounding the drug formulation.
SOFT GELATING CAPSULE
It is a soft, globular, gelatin shell, somewhat thicker than that of hard gelatin capsules.
The gelation is plasticized by the addition of glycerin, sorbitol, or a similar polyol.
The hard capsule is also called two pieces as it consists of two pieces in the form of
small cylinders closed at one end, the shorter piece is called the cap which fits over the open
end of the longer piece, called the body. The soft gelatin capsule is also called as one piece.
Capsules are available in many sizes to provide dosing flexibility. Unpleasant drug tastes and
odors can be masked by the tasteless gelatin shell. The administration of liquid and solid drugs
enclosed in hard gelatin capsules is one of the most frequently utilized dosage forms.
Filling of hard gelatin capsules:
a) Removal of caps
b) Filling of the bodies,
c) Replacement of caps, and
d) Ejection of filled capsules
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based
shell
surrounding
liquid
fill.
Softgel
shells
are
combination
of gelatin, water, opacifier and a plasticiser such as glycerin or sorbitol. Softgels are produced in
a process known as encapsulation using the Rotary Die Encapsulation process invented by
Robert Pauli Scherer. The encapsulation process has been described as a form/fill/seal process.
Two flat ribbons of shell material are manufactured on the machine and brought together on a
twin set of rotating dies.
Cadilapharmaceuticals commissioned a modern sophisticated manufacturing facility for
soft gelatin capsules at jammu complex. Designed to meet the most stringent international
standards, all operations in this plants from encapsulation to packaging, are carried out under
class 100,000. All systems are validated to meet international FDA standards, and the present
capacity of one million capsules per day can be doubled with marginal investments.
Sam Higginbottom Institute of Agriculture, Technology & Sciences (SHIATS) Allahabad.
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Mass mixer
Bandage making machine
Bandage cutting machine
Bandage coating machine
Dryer / Dehumidifier
Pulling machine
Slitting machine
Conveyor
The working standard are those obtained from reliable source and whose purity and
strength have been optimized through test, generally compared with the reference
standard. The quality control section performs different control measure and test
Sam Higginbottom Institute of Agriculture, Technology & Sciences (SHIATS) Allahabad.
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EVALUATION
Page19
%
10%
7.5%
5%
USP
Weighing 130mg or less
Weighing 130-324mg
Weighing 324mg or more
DISINTEGRATION
6 test tube and 3 inch long
10 mesh screen
1L beaker of water (0.1N HCL) simulated gastric fluid or simulated intestinal
fluid
Temperature 372C
Up and Down from 5-6 cm
Frequency 28-32 cycle/min
Tablet should remain 2.5cm below the surface of liquid on their upward movement and
same for downward movement. The potency of tablet is expressed in mg ,g, g. Official
range is not less than 95%. Majority of tablets has their disintegration time of 30 min.
Instruments and Devices seen in QA/QC
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Ultrasonic Bath.
UV Cabinet.
Bursting Strength Test Apparatus.
UV-VIS Spectrophotometer. (Ultra Violet Visible)
FT-IR Spectrophotometer.(Fourier Transform Infrared).
Karl Fisher Titration.
HPLC system
Polarimeter
Digital pH meter
MICROBIOLOGY SECTION
The Guide to the Inspection of Pharmaceutical Quality Control Laboratories provided
very limited guidance on the matter of inspection of microbiological laboratories. While that
guide addresses many of the issues associated with the chemical aspect of laboratory analysis of
pharmaceuticals, this document will serve as a guide to the inspection of the microbiology
analytical process. As with any laboratory inspection, it is recommended that an analyst
(microbiologist) who is familiar with the tests being inspected participate in these inspections.
Following processes are carried out in microbiology laboratory:
Sterility Testing
Bioburden Determination
Water Analysis
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provides a high degree of assurance that a specific process will consistently produce a product
meeting its pre-determined specifications and quality characteristics.
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Analytical balance
Incubator
Refrigerator
Biosafety cabinet / Laminar Air Flow
Magnetic stirrer
Deef freezer
Light microscope
PH meter
Autoclave
Hot air oven
Analytical Balance
They are used in precise weighing of small amounts (upto miligrams) of samples and chemicals
used for preparing media and stock solutions.
Biosafety Cabinet
It is used in microbial inoculation and isolation studies as well as sterile storage of materials. In
addition, it is utilized for protection of user, samples and the environment from hazardous
contamination.
Refrigerator
The device is used for the storage of the stock solutions, chemicals, kits and nutrient media that
should be maintained at certain temperatures.
Shaker Incubator
In the microbiology laboratories it is among the leading devices which are based on the principle
of shaking at different temperatures according to the purpose and the work load of the laboratory.
Sam Higginbottom Institute of Agriculture, Technology & Sciences (SHIATS) Allahabad.
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Electricity unit
Water treatment system
Water softening unit
Chilling/ steam unit
Air Handling Unit (AHU)
Effluent Treatment Plant
ELECTRICITY UNIT:
Generation of electricity in cadila is from three sub-station red, yellow and blue (RYB)
Light arrester: -A lightning arrester is a device used on electrical power systems and
systems to protect the insulation and conductors of the system from the damaging effects
of lightning. The typical lightning arrester has a high-voltage terminal and a ground
terminal.
Transformer:-Step-down unit, this transformer converts high-voltage, low-current
power into low-voltage, high-current power. The larger-gauge wire used in the secondary
winding is necessary due to the increase in current. The primary winding, which doesnt
have to conduct as much current, may be made of smaller-gauge wire.
Cadila has two step-down transformers, one which convert voltage from 66kv to
11kv and the other one which convert the voltage from 11kv to 440 volt for the industrial
use.
Vacuum
Circuit
Breaker:-A circuit
breaker is
an
automatically
operated electrical switch designed to protect an electrical circuit from damage caused
by over current or overload or short circuit. Its basic function is to interrupt current flow
after protective relays detect a fault.
Water treatment is used to optimize most water-based industrial processes, such as:
heating, cooling, processing, cleaning, and rinsing so that operating costs and risks are reduced.
Poor water treatment lets water interact with the surfaces of pipes and vessels which contain it.
Steam boilers can scale up or corrode, and these deposits will mean more fuel is needed to heat
the same amount of water. Cooling towers can also scale up and corrode, but left untreated, the
warm, dirty water they can contain will encourage bacteria to grow, and Legionnaires Disease
can be the fatal consequence. Also, water treatment is used to improve the quality of water
contacting the manufactured product e.g. semiconductors, and/or can be part of the product e.g.
beverages, pharmaceuticals, etc. In these instances, poor water treatment can cause defective
products. Domestic water can become unsafe to drink if proper hygiene measures are neglected.
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Water softening: - Water softening is the removal of calcium, magnesium, and certain
other metal cat ionsin hard water. The resulting soft water is more compatible with soap
and extends the lifetime of plumbing. Water softening is usually achieved using lime
softening or ion-exchange resins.
Chilling/Steam unit:
Chiller
A chiller is a machine that removes heat from a liquid via a vaporcompressionor absorption refrigeration cycle. This liquid can then be circulated
through a heat exchanger to cool equipment, or another process stream (such as
air or process water). As a necessary byproduct, refrigeration creates waste heat
that must be exhausted to ambient or, for greater efficiency, recovered for heating
purposes. Concerns in design and selection of chillers include performance,
efficiency, maintenance, and product life cycle environmental impact. In
industrial application, chilled water or other liquid from the chiller is pumped
through process or laboratory equipment. Industrial chillers are used for
controlled cooling of products, mechanisms and factory machinery in a wide
range of industries.
Boiler
A boiler or steam generator is a device used to create steam by
applying heat energy to water. A boiler or steam generator is used wherever a
source of steam is required. The form and size depends on the application:
mobile steam engines such as steam locomotives, portable engines and steampowered road vehicles typically use a smaller boiler that forms an integral part of
the vehicle; stationary steam engines, industrial installations and power stations
will usually have a larger separate steam generating facility connected to the
point-of-use by piping.
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Oil Separation
It is a process in which Floatables, namely non-emulsified oil and organics separates from
wastewater. The design of the separator is based on the specific gravity difference between the
oil and the wastewater and between the suspended solids and wastewater. In general, this
separator can handle very large flow. However, its disadvantage is the long retention time
required for efficient oil separation.
Flow Equalization
Flow equalization is used to overcome the operational problems caused by flow variations, to
improve the performance of the downstream processes, and is also used as an emergency tank to
equalize wastewater effluent in case of any process failure in the treatment process.The design
must provide for sufficient mixing to prevent solids deposition and concentration variations and
also to provide aeration to prevent odor problems.
Sedimentation
Sedimentation is the separation from water, by gravitational settling, of suspended particles
that are heavier than water.Sedimentation is used for separation of grit and particulate matter in
the primary settling basin, separation of biological-floc in the activated-sludge settling basin, and
separation of chemical-floc when the chemical coagulation process is used. It is also used for
solids concentration in sludge thickeners.
Sam Higginbottom Institute of Agriculture, Technology & Sciences (SHIATS) Allahabad.
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receiving
sampling
storing
dispensing
RECEIVING
raw material is supplied by vendors by placing order
after receiving the raw material check the observation on pack
segregate the raw material according to batch number
pre entry cleaning of raw material by vacuum cleaner
weighing of the raw material
Sam Higginbottom Institute of Agriculture, Technology & Sciences (SHIATS) Allahabad.
Page29
Temperaturepoint:
It is the point where the temperature is checked by placing digital thermometer on daily basis
DISPENSING
Raw material is picked for dispensing according to materialpicklist for process order
and dispensed according to BMR prepared by QA personnel
Selection of raw material is done according to firstexpiryfirstdispense
Raw material is dispensed from dispensing booth under LAF to the production area
FINISHED GOODS
Finished goods are goods that have completed the manufacturing process but have not
yet been sold or distributed to the end user. A good purchased as a "raw material" goes into the
manufacture of a product. A good only partially completed during the manufacturing process is
called "work in process". When the good is completed as to manufacturing but not yet sold or
distributed to the end-user, it is called a "finished good". This is the last stage for the processing
of goods. The goods are ready to be consumed or distributed. There is no processing required in
term of the goods after this stage by the seller.
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Receive the finished good transfer ticket from production duly authorized by
production supervisor and checked by QA
Following are to be made in finished good transfer ticket after received from
production
Name of product
Batch No.
Manufacturing date
Expiry date
Quantity (No of box x per pack)
Date of transfer tickets
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Wikipedia
www.slideshare.net
GPAT Cracker
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