DURATION OF TRAINING:

21 DAYS
FROM AUGUST 24 TO SEPTEMBER 11, 2003.

SUBMITTED TO:

FACULTY OF PHARMACY
UNIVERSITY OF DHAKA
DHAKA.

SUBMITTED BY:

ROLL NO- 42
REGISTRATION NO- HA 2074 (1996-’97)
B. PHARM (HONOURS) EXAM-2000
UNIVERSITY OF DHAKA
DHAKA.
 Acknowledgements

My thanks to Novartis (Bangladesh) Limited for giving me the opportunity to

complete my in plant training. I am deeply grateful to all those who have, with their
good grace, given me their valuable time and energy to express their rich full
experience about the instrumental terms, conditions and working procedures. I
particularly want to acknowledge the tremendously helpful, supportive, creative
contributions of Mr. Mostafizur Rahman, Mr. Abdus Samad, Mr. Asrafuzzaman Khan,
Mr. Wahiduzzaman, Mr. Asadudzaman, Mr. Sumon Doha, Mr. Mahfuj Alam, Mr.
Ahsan A Chowdhury, Mr. Khurshid Alam, Mr. Masud Rana, Mr. Aminul Haque, Mr.
Mehraj Hamid. I owe a special thanks to my training coordinator Mr. A.K.M. Faisal
Ahmed for his contribution and polite behavior. My most warm thanks to the director
technical operations Mr. Mahbubul Karim especially for his unfailing personal and
professional support for this in plant training. Finally, my thanks to my teachers, who
has arranged such type of profession related training to gather professional
experience.

Other acknowledgements are made in the proper places.

 Company History

Novartis (Bangladesh) Limited (NBL) came into existence with the global merger
of Ciba-Geigy and Sandoz, two Swiss health care concerns in 1997. From early
1970, Novartis - then known as Ciba-Geigy - engaged in trading with various
chemical and healthcare products in Bangladesh. The Bangladesh group
company was incorporated in 1973 with the 40% participation of Bangladesh
Chemical Industries Corporation (BCIC). In a first joint venture agreement of both
partners in 1980 the investment in a crop protection formulation plant in
Chittagong was implemented. In a second joint venture agreement in 1988 NBL
and BCIC invested in a pharmaceuticals production plant in Tongi, which
operated as from 1990 with life-saving products fitting the needs of the country. In
2000 Novartis decided on a global basis to spin-off the agro business and
henceforth to concentrate on healthcare. This affected also Bangladesh group
company. The former crop production business of NBL will continue, also with the
business partner BCIC, under Syngenta as a separate legal entity. In January
2003 the Generics sector of NBL has undergone a substantial expansion of its
production capacity to strengthen the export business of pharmaceuticals, which
already go to many countries in Asia Pacific and Latin America and soon also to
Europe. In May 21, 2003 Novartis Generics officially changed its name to
Sandoz.

In-plant training report. Page 1 of 40

 Observations

Orientation and Departments of the Industry:

The company complies of the following departments in pharmaceutical sectors and I have
visited all the departments as trainees. The departments’ are-
• Production area (Area-A, Area-B).
a. Dispensing.
b. Granulation.
c. Compression.
d. Encapsulation.
e. Coating.
f. Filling and sealing.
g. Packaging.
• Quality assurance department.
a. Quality control.
b. In-process control.
• Product development department.
• Supply chain management department.
a. Material management.
b. Purchase department.
• Production planning and co-ordination department.
• Technical service department.
• Information technology department.
• Human resource department.

In-plant training report. Page 2 of 40

 Production

Dispensing:
The process by which active ingredient and excipients are received from ware house into the
production area and weighing materials according to dispensing order sheet (DOS) is called
dispensing.
In case of different batch of same product, excipients of both batches are weighted first then
active ingredients are weighted. There is no need of change over of instrument used in
production area. This process reduces the possibility of contamination.

Instruments available:
◊ Balance.
Name: Metler Toledo (area B)
Capacity: 150kg; 6kg.
◊ Plastic Platform (reduces particle formation than wooden platform)
◊ Exhaust system.

Limitations and solutions:

☻ According to Good Manufacturing Practice (GMP) the balance should not be replaced from
their original place, but balances are frequently replaced for various reason. This may cause
weight variation from batch to batch. More sophisticated balance may be used.
☺ Solution:
Balance built in floor may be used in place of replaceable balance.
☻ Exhaust duct used in dispensing area is not sufficient to remove dust particle that
generated inside it.
☺ Solution:
Exhaust system with large opening may be used as in production area A.

☻ Lighting system in the dispensing area suitable for the deposition of dust particles.
☺ Solution:

In-plant training report. Page 3 of 40

Lighting systems should be such type that the dust particle could not be deposited on light;
which are also difficult to clean.

☻ Tiles are used in walls which causes dust particle deposition that is also difficult to clean.
Fungal growth may occur in the floor during damp season.

☺ Solution:
PVC walls and terrazzo (cement and crushed marble) floor may be used which is easy to
clean, repair and relatively cheap. To reduce fungal growth up to 1% of a fungi static such as 8-
hydroxyquinoline, pentachlorophenol may be added to the paint.

☻ Some ingredients are moisture sensitive. For their stability humidity control (dry syrup-
relative humidity below 30%) is essential in every step of manufacture. In dispensing area B
has no humidity control system.

☺ Solution:
It is essential to control humidity to increase stability.

Granulations:
Granulation is the process in which powder particles are made to adhere to form larger
particles called granules. Granules are usually used in the production of tablets or capsules.

Purpose of granulation:
™ Granulation prevents segregation of the constituents in the powder mix.
™ It improves the flow properties of the powder mix.
™ It improves compression nature of powder.

Machines available:
Machines Production area
A B
Solid mixer T.K. Mixer. Artofex 3

In-plant training report. Page 4 of 40

 (capacity 100kg) (capacity 320kg )

Fluid bed dryer Aeromatic Solace

Final mixer BHOLE mixer Not present
Solace multimill. Only one available for production
Russel shifter. Only one available for production

Types of granulation:
Three types of granulation techniques are used-
• Dry granulation
• Wet granulations
• Spray granulation

Dry granulation:
This method is applied for drugs which do not compress well after wet granulation or those
which are sensitive to moisture. It may be performed following two ways-

In-plant training report. Page 5 of 40

Process one: Process two:
1. Weighing. 1. Weighing.
2. Shifting. 2. Shifting.
3. Dry mixing. 3. Dry mixing.
4. Addition of disintegrants. 4. compression to form slug.
5. Lubrication. 5. Addition of disintegrants.
6. Lubrication.

Wet granulation:
Wet granulation involves the massing of the powder mix using a solvent. The solvents used must
be volatile, so that they can be removed by drying, and nontoxic.
Steps involved:
1) Weighing. 5) Drying.
2) Shifting. 6) Crushing.
3) Dry mixing. 7) Addition of disintegrants.
4) Wet mixing. 8) Lubrication.

Spray granulation:
This technique utilizes the technology of fluid bed drier. Heated air is blown through a bed of
unmixed powders and mixes the powders. Granulating liquid is pumped through a spray nozzle
over the particle.

Limitations and solutions:

☻ Multimill and shifter frequently used in granulation technique. Production A and production B
use these two instruments by shifting. It reduces productivity.

☺ Solution:
To increase productivity these instruments are essential in both areas.
In-plant training report. Page 6 of 40
☻ No final mixer (e.g. BHOLE MIXER) present in production area B; which is essential for quality
product.

☺ Solution:
It is essential to install a final mixer.

Compression:
Compression of powder means reduction in bulk volume of a material as a result of displacement
of the gaseous phase. Compression technique used for the manufacture of tablet.

Machines available:
◊ Manestry (unipress): single rotary, 20 punch.
◊ Clit machine: double rotary, 29 punch.
◊ Se-Jong tablet machine: single rotary, 30 punch.

Tablet machine parts:

Hopper. Main compression roller.
Fed frame. Compression sration.
Feed paddles. Ejection cam.
Draw down cam. Take off blade.
Weight controller Fill station. Ejection station.
Pre-compression roller. Take off chute.

Stages of compression:
1. Feed frame over die. 4. Feed shoe pull back.
2. Fill. 5. Compression.
3. Scrapping. 6. Ejection

In-plant training report. Page 7 of 40

Tablet manufacture problem:
Θ Punch filming and sticking. Θ High friability.
Θ Weight variation. Θ Low hardness.
Θ Capping/lamination. Θ Variable hardness.
Θ Mottling. Θ Bisection or embossing.

Limitations and solution:

☻ Vacuum system used in both Clit and Se-Jong tablet machine to introduce granules, that
reduce the requirement of manpower & increase productivity – but it produce dust particle which
contaminate environment. Manestry tablet machine has no such problem.

☺ Solution:
Automatic hopper as Manestry may be used or protective covering my use to prevent dust
formation.

☻weight of tablet digitally controlled in both Manestry and Se-Jong tablet machine that reduce
weight variation and also easy to control than clit machine which is manually controlled.

☺ Solution:
Establishment of digitally control system for Clit machine, granules that have better flowing
property may be compressed without any weight variation.

☻ Pre-compression roller reduce the air inside the granules, that reduce cracking problem –
absent in clit machine.

☺ Solution:
Granules with better compressibility can be easily compressed. If problem (Cracking) arises with
this machine direct compression (Ludipress LCE) agent may be used.

Tablet coating
In-plant training report. Page 8 of 40
It is the process by which a layer of polymer or sugar applied on core tablet for various reasons is
called coating.
Types:
o Sugar coating.
o Film coating.
o Powder coating.
o Enteric coating.

Coating machines:

◊ Manestry accela cota (capacity 150kg)

◊ Se-Jong (capacity 150kg)

◊ NR-cota (capacity 30kg)

Sugar coating:
Sugar coating is the traditional method of coating tablet. It involves the successive application of
sucrose-based solutions to tablet cores in suitable coating equipment.

Steps:

Actual steps Used steps

1. Sealing of the tablet cores. 1. Application of liquor solution.
2. Sub-coating. 2. Application of talc solution.
3. Smoothing. 3. Coloring.
4. Coloring. 4. Polishing.
5. Polishing.
6. Printing.

Limitations and solutions:

In-plant training report. Page 9 of 40

☻ Here coating is performed by only four steps; which may cause stability problem of drug and
may not fill the purpose of coating.
☺ Solution:
If there is no reduction of productivity, all referred steps may be followed. It may improve the quality
of coated product. Product development may improve the process.
☻ Coating solution is applied manually- that may cause serious damage of core.
☺ Solution:
It is essential to use spray system for accuracy of coating and stability of drug.

Film coating:
Film coating is a modern technique of coating procedure requires very small time compared to
sugar coating. It involves less steps and coating problem.

Steps:
o Introduction of liquor solution.
o Coloring.
o Polishing.

Factors considered during coating procedure:

Following factors have to be considered during coating procedure-
I. Rotation of coating pan.
II. Inlet air velocity.
III. Pressure of air inside coating pan.
IV. Inlet air temperature.
V. Outlet air temperature.

Coating problems:
Logo-briging. Cracking.
Edge chipping./ Erosion. Twining.
Picking and Sticking. Tablet to tablet color variation.

In-plant training report. Page 10 of 40

Blocking. Peeling.
Orange pill/ roughness. Erosion.
Loss of logo definition.

Steps to reduce coating problems:

a. Coat tablet should not be flat, it should be convexed.
b. Granules should be properly dried.
c. Color solution should be added slowly.
d. Sugar coated tablet should not have logo.

Encapsulation
Encapsulation is the process of manufacture of capsule. Capsules are solid dosage forms in which
the drug substance is enclosed in either a hard or soft, soluble container or shell of a suitable form
of gelatin.
Types of capsule:

Θ Hard gelatin capsule.

Θ Soft gelatin capsule.

Hard gelatin capsule:

It is referred to as the dry filled capsule; consist of two sections, one slipping over the other, thus
completely surrounding the drug formulation.
Soft gelatin capsule:
It is a soft, globular, gelatin shell, somewhat thicker than that of hard gelatin capsules. The gelation
is plasticized by the addition of glecerin, sorbitol or a similar polyol.

Machines available:

◊ Machine: BOSH (for hard gelatin capsule)

In-plant training report. Page 11 of 40
Channel: Single.
CPM: 300; CPH: 18,000.
Output: 36 (per-rotation)

Machines criteria:
In a tablet machine one die fill with granules at a time from a hopper, but in a capsule machine
shell fill from hopper through different channel and thus final weight adjusted by trial and error
method.

Limitations and solutions:

☻ Weight of capsule adjusted by trial and error method; it is a time consuming process and there
is possibility of weight variation.
☺ Solution:
Replacement of old machine by newer one.

Packaging
Packaging can be defined as an economical means of providing, presentation, protection,
identification/information, containment, convenience and compliance for a product during storage,
carriage, display and use until such time as the product is used or administered.

Packaging materials provide protection to the product in following ways:

Mechanical hazards: Puncture. Pressure.

Shock or impact damage. Light.

Compression. Atmospheric gas.

Climatic hazards:
Vibration. Moisture.
Biological hazards:
Abrasion. Temperature.

In-plant training report. Page 12 of 40

Microbiological.
Pilferage.
Other infections.
Types of packaging:
Packaging can be divided into two ways:
☼ Primary packaging.
ƒ Blister packaging.
ƒ Strip packaging.
ƒ Bottle filling and sealing.
☼ Secondary packaging.
☼ Primary packaging:
In case of primary packaging, packaging material comes to the direct contact of the finished goods.
So its quality should be strictly maintained.

Blister packaging:
Blister packaging involves forming heat softened plastic film or around a deep-drawn pocketed
mold to make a plastic tray (thermoforming), filling with a solid dosage form product and sealing
with push through or peel able covering.

Composition:
Heat softened plastic film:
Chemically films used are polymer in nature. Polymers used are polyethylene (PE), poly vinyl
chloride (PVC), poly vinyl di-chloride (PVDC) etc. Films used may be of one, two or three layered;
depending on nature (moisture sensitivity) of finished product. Its thickness may vary from 250-300
micrometer.
Covering materials:
Covering material is usually preprinted or plane aluminum. Its standard thickness is about 25
micrometer. The covering material has a printing primer on one side and a heat sealing lacquer on
the other, which faces the product and forming film.

Machines:
Packaging machine:

In-plant training report. Page 13 of 40

Name: CAM, OTTO HANSEL, ULHMANN.
Printing machine:
Name: Hapamatic.

Operating temperature:
Heating temperature: 130° C (formation of pocket).
Sealing temperature: 160° C (sealing of film and cover).

Steps of packaging procedure:

• Formation of pocket for product (tablet or capsule) using heat softened plastic film.
• Introduction of product into pocket (manually or mechanically).
• Sealing of product by covering material (printed or without printed).
• Cutting.
• Conveying to packaging section by conveying belt.

Strip packaging:
A strip package is formed by feeding two webs of a heat sealable flexible film through a heated
roller. The product is dropped into the pocket formed prior to forming the final set of seals.

Machines:
◊ Packaging machine:
Name: Gansons (Capacity 1600 capsule/hr).
◊ Printing machine:
Name: Image (to print batch no and expiry date).

Associates have to observe:

o Vacant capsule shell. o Printing of batch no and expiry date.
o Chute flow of capsule. o Cutting of strip.

Limitations and solutions:

In-plant training report. Page 14 of 40

☻ In case of strip packaging machine voltage up and down may change temperature of heated
roller, which may cause leakage problem.
☺ Solution:
A voltage stabilizer may set for strip packaging machine.
☻ Conveying belt is not using to convey strips to packaging area that cause deformation of strips
before packaging.
☺ Solution:
To set a conveying belt for prevention of deformation of strips.

Filling and sealing:

Steps and instruments:

™ Bottle wash (Machine: Anchor mark).
™ Bottle drying (Machine: Anchor mark; Temp- 110º C for 2 hr).
™ Tablet filling (Chinese machine)/Powder filling (Machine: Anchor mark).
™ Airtight sealing (Machine: Anchor mark).
™ Packaging.
Precaution:
Humidity is strictly maintained during filling of dry syrup. Here dehumidifier is used to maintain RH
below 30%.

☼ Secondary packaging:
Secondary packaging mainly used for the following purposes:
♦ To improve handling property of large amount products.
♦ To facilitate transport of product.
♦ To withheld shock during shipment.
♦ To prevent the product from environmental hazards (moisture, temperature etc.).

In-plant training report. Page 15 of 40

 Quality assurance

Quality assurance department co-ordinate the functions of following four departments:

• In process control department.
• Quality control department.
• Good manufacturing practice (GMP) department.
• Quality compliance department.

In process control department

Instruments available:

◊ Friabilator:
Name: Pharma Test.
It is used to determine the capacity of tablet to withstand shock during coating, packaging and
shipment. It is expressed as percentage.

⎛ W ⎞
Friability (%) = ⎜⎜1 − 2 ⎟⎟100
⎝ W1 ⎠
Here,
W2=weight after friabilation.
W1=weight before friabilation.

◊ Hardness tester:
Name: Pharmatron.
Tablet hardness is the important measurement of IPC; as it control the disintegration time of the
tablet and also size of tablet.

◊ Disintegrator:
Name: Sotax DT3.
In-plant training report. Page 16 of 40
Disintegration is the process of conversion of tablet into smaller particle. Core tablet disintegration
performed in deionized water (temp-37.4°C). Enteric coated tablet disintegration time determined
in 0.1% HCl solution.

◊ Leak test apparatus:

Name: Ketan
It is used to determine packaging accuracy. Some time colored solution used to find leak in
packaged product.
◊ Loss on drying apparatus:
Name: Metler
It is used to determine moisture content of material, usually during drying, before compression and
during coating. IR radiation is used in this instrument. Moisture content expressed as percentage. It
is an important factor as weight of tablet compensate according to moisture of granule.

◊ Weight variation:
Name: Metler.
It is an automatic machine by which we can determine weight variation of core and coat tablet.

Tablet Weight variation (%)

18 tablets 2 tablets
Below 80mg. 10 20
80 – 250mg 7.5 15
Above 250mg 5 10

◊ Length, thickness and diameter tester:

Name: Absolute digimatic.
It is a digital instrument used to determine the length, thickness and diameter of tablet and capsule.

In-plant training report. Page 17 of 40

Responsibilities:
Receiving of materials from ware-house:
ƒ Right materials supplied or not (according to DOS).
ƒ Amount of materials supplied (according to DOS).
ƒ Condition of the container.

Dispensing:
ƒ Cleanliness of dispensing area.
ƒ Presence of production officer.
ƒ Random weighing of material.
ƒ Accurate tag used or not.
ƒ Balance is calibrated or not.

Granulation:
ƒ Assure cleanliness of granulator, dryer ect. According to Standard Operating Procedure
(SOP) instrument cleaned before 15 days can be used in granulation procedure.
ƒ Temperature of inlet and outlet air.
ƒ Moisture content of dried granules.

Compression:
ƒ Cleanliness of compression area and instruments e.g. die, punch etc.
ƒ Right die, punch used.
ƒ Tablet size and shape.
ƒ Tablet color.
ƒ Tablet imprint.
ƒ Tablet hardness.
ƒ Tablet friability.
ƒ Disintegration time.
ƒ Weight variation.

Coating:
ƒ Cleanliness of coating area and instrument eg. Coating pan, spray system etc.
In-plant training report. Page 18 of 40
 ƒ Smoothness of coated tablet.
ƒ Pan rotation speed.
ƒ Inlet and outlet temperature.
ƒ Coating material addition speed.
ƒ Weighing after coating procedure.

Encapsulation:
ƒ Cleanliness of encapsulation area and instrument.
ƒ Length and radios of shell.
ƒ Length and radios of capsule.
ƒ Disintegration time.
ƒ Capsule shape and size.

Packaging:
ƒ Leakage of blister and strip package.
ƒ Package (blister and strip) imprint.
ƒ Visualization of tablet inside the package.
ƒ Cleanliness of packaging area and instrument.

Environment monitoring.
Sanitation and cleaning.
Machine validation assuring. Etc.
So the quality assurance personnel are always conscious about the quality of the product by taking
consideration into above factors. It requires large manpower to do all the functions accurately.

Quality control department

Quality control refers to the process of striving to produce a perfect product by a series of
measures to prevent or eliminate errors in production.

In-plant training report. Page 19 of 40

Functions:
Quality control department has functions in the following areas:
♦ Documentations.
♦ Raw materials.
♦ Finished products.
♦ Packaging materials.

Documentations: Raw materials: Finished products: Packaging

materials:
Validation of- Name of materials. Description. Packaging materials:
Sampling of materials. Identity. • Printing.
• DOS.
Descriptions. • UV absorption. • Color.
• POS. Solubility. • Chromatography. • Message.
Identity: Assay.
• SOP. • IR absorption. Dissolution. With product:
• BMR. • UV absorption. Impurities. • Batch no.
• Chromatography. Microbial limit. • Exp date.
Maintenance of log
• Melting point. • Printing.
book of instruments. Assay.
Purity and quality.
Data input of various
Microbial limit.
tests in BMR.

Instruments in Q.C. lab:

◊ High performance liquid chromatography (HPLC):

Name: Merk Name: Shimadju.
Name: Hitachi. Name: Perkinelmer.

◊ FTNIR- Genesis: ◊ Karl fischer machine:

Name: Buchi. Name: Metrohm.

◊ Particle size analyzer: ◊ Viscometer:

Name: Malvem mastersizer. Name: Brookfield.
In-plant training report. Page 20 of 40
◊ Melting point detector:
Name: Buchi.

N- content detecror:
Name: Buchi.

◊ Dissolution tester.
◊ PH meter.
◊Gaschromatography.

In-plant training report. Page 21 of 40

Microbiology laboratory:

Functions:
Microbiology laboratory is the part of quality control. It has following responsibilities-
• Microbial limit test (For bacteria and fungi).
• Antibiotic assay.
• Microbial content of environment.

Microbial limit test:

For the following materials microbial limit test is performed –
Packaging materials-
o Primary packaging materials(both blister and strip foils)
o Secondary packaging materials(polybag used in bulk supply )
Raw materials.
Finished materials.

Non-pathogenic micro-organism Acceptable limit Media used

Bacteria 103 CFT/gm TSA

Fungi 102 CFT/gm SDA

Pathogenic micro-organism Acceptable limit Media used

E. coli 0 MCA
Enterobacteriaceae 0 VRBGA
Salmonella 0 DCA
Pseudomonas aeruginosa 0 CA
Staphylococcus aureus 0 BPA

Microbial limit test performed for the validation batches (usually first 5 batches) then MLT
performed after a definite batch interval.

In-plant training report. Page 22 of 40

Microbial content of environment:
Environment of a pharmaceutical industry includes-
1. Air.
2. Water.
3. Personnel.
4. Machines.
Microbial content of the above determined after a definite time interval as all are the good
source of contamination.

Procedure:
Presence of microbial contamination performed by the following steps-
ƒ Media preparation.
ƒ Autoclaving.
ƒ Specific method for specific organism.
ƒ Incubation.
ƒ Colony count.

Instruments:
To conduct the above steps following instruments are used-
◊ Autoclave (Microbial media sterilized by using the condition temperature 121°C, pressure
15 Psi for 15-20 minutes).
◊ Incubator (Two types of incubator are available; one control temp. between 35-37°C other
between 20-25°C. Use of incubator depends upon microbial type).
◊ Horizontal laminar-flow workbench (Use to transfer MO to the media without external
contamination).
◊ Reuteri centrifugal air sampler (Used to find bacteria and fungal contamination).

The plant has only solid section, so there is less possibility of microbial hazard. But for the
safety of patient and also for stability of product it is essential to control and measure
contamination.

In-plant training report. Page 23 of 40

Good manufacturing practice (GMP) department:
This department overview/ inspect the function of total production system. This department has
no routine work but work in every where to inspect/ assure good manufacturing practice.

Quality compliance department:

This department deals with the problems arises in other production related department. Here
some people are always engage to solve the problem. It is absent in the plant, related
personnel solve their problem through discussion with proper personnel. It is essential for a
quality concern department, because the problem arises if not solve by proper hand may
reduce productivity.

Θ High performance liquid chromatography (HPLC):

High performance liquid chromatography (HPLC) is a powerful method for the separation of
complex mixture, especially when many of the components may have similar polarities.
Two types of analysis possible with HPLC-
• Isocratic analysis (to separate single compound).
• Gradient analysis (to separate mixture of compounds).

Reservoir Resorvoir Recorder

Gradient
Pump Controller Fraction
Collector Detecror

Mixing Analytical
Chamber Pump Column

Solvent conditioning Injector

Column Precoloum

Figure: Block diagram of a complete HPLC. Directly connected lines are necessary only for
gradient elution.

In-plant training report. Page 24 of 40

Analytical column:
Here the actual separation takes place. It is usually a stainless tube, usually 5 to 25 cm long
with 2 to 4.6 cm diameter. It is packed with the stationary phase. Silica gel is the material most
frequently employed for micro particulate column packing. It may be used as such for
absorption chromatography, but more often liquid phases for partition chromatography are
bonded chemically to its surface. These include alkyl groups with the chain length of 1, 2, 8 or
18 carbons, cyanopropyl groups, phenyl groups and ion exchanger. Chiral stationary phases
also used for the separation of optical isomers.

Detector:
Ultraviolet-visible spectrometer.
Fluorescence spectrotometer (sensitivity pictogram range)
Differential refractometer.
Based on electrochemical measurements:
¾ Amperometry.
¾ Columetry.
¾ Polarography.
¾ Photoconductivity.

Product development department

Functions:
Product development (PD) department has following functions:
Document development.
Galenical development.
Analytical development.
Packaging development.

In-plant training report. Page 25 of 40

Document development:
Product development department generate batch manufacturing record (BMR), dispensing
order sheet (DOS), packaging order sheet (POS) initially for a newly launched product and also
maintain the document of their functions.

Galenical development:
Galenical development involves the development of the functions of production area for the
production of a product. It develops the formulations by trial and error method.

Steps of development:
Trial batch
(if criteria fulfilled)
Validation batch.
(if criteria fulfilled)
Production batch.

Instrument used:

◊ Granulator: ◊ Compression machine:

Name: Solace. Name: Jaguar.
Capacity: 2 kg. Capacity: 6 station.
◊ Coating machine: ◊ Capsule filling machine.
Name: pan coater, accela cota. ◊ Particle size distribution.
Capacity: 2 kg.

Analytical development:
Analytical development involves the development of the functions of quality control department
for the production of a product.

In-plant training report. Page 26 of 40

Development work:
o Assay procedure of API.
o Assay procedure of impurities.
o Stability testing.
o Validation of instruments used.
Routine work:
o API analysis (if source changed).
o Stability testing (on going process).
o Process validation.
Stability testing:
Stability testing helps in the prediction of the shelf life of a product. It is based on the
application of the Arrhenious equation:
−E
k = Ze RT

Condition. Name of exp. Time of exp. Shelf life

Temp. %RH
40ºC 75% Accelerated stability test 6 month 1 year.
30ºC 70% Follow up stability. On going Stable period.
20ºC 60% Follow up stability. On going. Stable period.

Packaging development:
Packaging development involve the design of primary and secondary packaging for a particular
product or routine check of the packaging materials.
Development functions:
a. Types of packaging (strip/blister) selection.
b. Size of strip/blister.
c. Size of packet.
d. Design (color, message) of packet.
e. Literature of leaflet.

In-plant training report. Page 27 of 40

Limitations and solutions:
☻Product development department has no opportunity to test pharmacokinetic and
phamacodynamic parameters. It is essential to study bioavailability for a newly launched
product. As the accuracy of dissolution rate and potency not always explain bioavailability of
drug.
☺ Solution:
To develop a pharmacological assay department for better development.

Production planning & coordination department

Functional responsibility:
o Following are the functional responsibility of production department:
o Co-ordinate raw and packaging material flow with material management and export.
o Establish production planning window.
o Schedule the product requirements (local/export).
o React to emergencies/urgent order.
o Lead or participate in production planning.
o Delivery in full on time (DIFOT).

Delivery in full on time (DIFOT):

It comprises the activities involved in successful delivery of a customer according to
requirement(s) with in the time limit.

Planning process:
• Planned order for local or export from POFO-data analysis.
• Four month production planning following update on monthly basis.
• Confirm the materials.
• Capacity utilization.
• Monthly schedule (rolling update on weekly basis).
• Weakly evaluation.

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 Convention of planned order into process order:
• Process order of tree months for export.
• Process order of one month for local.
• Release of process order.
• Co-ordinate the order with related department.
• Reporting to plant director or mother organization.

Planning considerations:
• Various lead time. • Safety stock.
• Raw materials and packaging • Service level.
materials. • Ensure production continuity.
• Closing stock. • Production capability.
• Production capacity. • Production sequencing.

Production planning tools:

o System application program (SAP) for data processing.
o M.S. excels.
o M.S. word.

In short production planning department has the following functions:

a. Maximize plant output (production).
b. Maintain of material flow (raw materials, finished goods).
c. Optimum inventory (both plant and central ware house).

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 Supply chain management department

It has following three functional division:

♦ Material management department.
♦ Procurement department.
♦ Ware house.

Functions of supply chain management given by flow chart:

Production impulse from planning department
to material management (MM) department.

MM department give If materials available

order to purchase in ware house MM
department give order to supply
to purchase materials if materials for
not available. production.

Production Ware house receive

raw materials/ finished
goods and/or supply to
production area/MM
Product according to DOS.

Figure: Flowchart of functions of supply chain management.

In short functions are:

™ Purchase materials according to requirement.
™ Maintain proper inventory of both raw materials and finished goods.
™ Maintain inventory of tool manufacturer.

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Ware house:
Ware house is a store room to store raw materials, packaging materials and finished goods.

The main functions of ware house are given below:

a. Receiving in-voice and purchase order from material management.
b. Receiving materials.
c. Cleaning of received materials.
d. Weighing of received materials and compare with purchase order.
e. Dispensing of materials according to DOS for production.
f. Receiving of finished goods from production.
g. Inventory of tool manufacture also maintain by ware house.
h. Documentation.

Arrangement of ware house:

According to materials:
Finished goods Packaging materials Raw materials

For export. For export products. Same raw materials used

for the product of both
For local market. For local marker. export and local market.

According to Q.C. release:

a. Q.C. released materials (green marked).
b. Quarantine materials (not yet released by Q.C. department – yellow marked).

Limitations and solutions:

☻ Special storage environment (temperature and humidity) required for some product for
their stability, ware house has no such type of facility.

☺ Solution:
For better stability it is essential to establish an area that can provide special storage
environment.

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☻ Marking and card system used for ware house. It creates hazardous condition of ware
house. It is difficult to find the materials without the help of the system used.

☺ Solution:
It can be developed by using following tools:
a. Arrange the materials alphabetically and fix the sticker on self accordingly.
b. Separate store for raw, finished and packaging materials.
c. To maintain a completely separate quarantine area.

Special features:
¾ Presence of Q.C. sampling room inside the ware house.
¾ Presence of Q.C. sampling store inside the ware house.
¾ Flammable materials store at different area- not inside the ware house.
¾ Fire safety obtained by using temperature and smoke sensor.

Technical service department

This department is called power house of any type of plant. In a pharmaceutical plant it provide
following types of services for the continuation of productivity-

Maintenance support:
Following maintenance support given by technical service department-
• Protection of machineries.
• Preventive measures.
• Breakdown support.

Supply support:
Supply support maintains blood-stream of a plant. It provide following supply to the various part
of plant-
• Compressed air. • Electricity.
• De-ionized water. • Gas and
• Cold and hot water. • Steam.

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Lubrication:
Lubrication of machineries routinely to prevent friction and subsequent damage.

Incinerator:
To destroy waste material by using fire. Here materials used for once and have no more used
usually destroyed.

Service:
• Car workshop.
• Carpeting.
• Painting.

Maintaining heating, ventilation and air conditioning (HVAC) system.

Instruments used for the supply support:

◊ Electricity:
Required electricity mainly obtained from DESA, incase of load shedding heavy duty generator
provide electricity.
Generator:
Type: diesel operated.
Capacity: 1050 kilowatt.
Requirement: 450 kilowatt.

◊Compressed air:
Compressed air is provided by oil free compressor. Air is passed through passed various grade
of filter to eliminate particle. These prevent contamination from oil and dust particle.
Name of compressor: Sullair.
Functional mechanism: air is passed through a screw system device.

◊ Steam:
A boiler is used to boil water to110ºC and produce steam for production area B. Heat is
generated by using gas. Generated steam is used in fluid bed dryer.

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◊ Cold water:
Chiller is used to produce cold water (6ºC) for HVAC system (to cool the air). After circulating
this cold water through close looped HVAC system temperature become 12ºC. This raised
temperature is released to environment through another closed loop system of water circulation
system. Here temperature of water changed from 37ºC to 30ºC and temperature released. So
there no loss of water.
Capacity of chiller: 250 ton.

◊ Hot water:
Boiler is used to produce hot water (110ºC) for HVAC system (to dry the air). After circulating
this hot water through close looped HVAC system temperature become 90ºC. This loosed
temperature is used to develop HVAC system. The hot water also flows through a close looped
system and thus no loss of water.

◊ Water supply:
Water is supplied to plant by using a deep tube well. It supplies water from 120m deep of soil.

◊ Waste water management:

Water used in plant released to environment after proper treatment. At first water is passed
through the various grade of filter to remove particle and bacteria cultivated in treatment plant
to engulf dissolve chemicals. It prevents water contamination.

◊ Deionized water plant:

In pharmaceutical plant deionized water used in place of normal water as the ion present in
water may produce some adverse reaction to product and also may alter chemical assay.

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Deionized water plant may represent in following way:

Raw water passed Filtered water passed

through 5µ filter. through a fine 2µ filter.

U.V. sterilization

Regeneration: Cation and anion Water collected

Anionic: NaOH 30% exchange resin and pH
Cationic: HCl 32% usually geolite. maintained
With water. between 6.5-8.5.

Mixed bed ion Released to

exchanger. environment.

Water passed through0.5µ

filter.

O3 treatment.

Reservoir tank Closed loop supply

of DI water.

Figure: flow chart of de-ionized water plant.

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Heating, ventilation and air conditioning (HVAC) system:
It system control temperature and relative humidity of production area A. It is a highly
developed system that can control the condition of individual room as per requirement.

HVAC may represent by following flow chart:

Supply:

Air, 20% inroduced

Recycled 80% Filter F8 Filter F9

Blower

Cold Hot
duct 12°C duct28°C

Room TMV mixing

22°C/55%RH Filter H11 box.

Return:
20% returned air
removed to
Room Filter F8 Filter F9 environment and
80% recycled.

Blower

Figure: flow chart of HVAC system.

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Advantages:
¾ Environment of individual room can be controlled.
¾ Recycled air contains less amount of dust particle than obtain from environment; it
reduces stress on filter used. But returned air from granulation room contain large
amount of dust hence air is not recycled here.
¾ Pneumatic system provides automatic control of environment.

Information technology

Novartis (Bangladesh) Limited has introduce network communication within Novartis and also
with the mother and sister concern all over the world through SAP in May 2000. It may call the
neuron of Novartis.
This software is developed by Germany. For installation it cost approximately 7-crore BDT.
Now using charge per year is 4500 Swiss frank. Now NOVARTIS (BANGLADESH) LIMITED
has 72 SAP users. Net communication is maintained by radio link and locally communication
with fiber optic. This program is based on advanced business application program (ABAP)
language.

Infra-structure:

Infra-structure

Networking Communication

LAN WAN MAN Lotus Voice over

notes phone

Figure: Flow chart of IT department infra-structure.

In-plant training report. Page 37 of 40

Application of SAP and flow of work:

Customer Sales/distri Central ware

relationship bution unit house
management

Finance
Ware
Material house
management
Controlling

Product
Purchase planning
order

Process Ware Quality Ware

industry house assurance house

Figure: Flow chart on application of SAP and flow of work.

Human resource department

Functions: Tools used:

o Employee allocation. o Payroll.
o Personnel management. o Employee relation and welfare.
o Maximize output from personnel. o Planning/counseling

Motivation of employee:
HR department motivate employee by using following factors-
o Leave.
o Salary.
o Provident fund.
o Gratuity.
o Medical.
o Leave fair assistance (LFA).
o Workers participation profit fund (WPPF).

In-plant training report. Page 38 of 40

 Conclusion

Pharmacy is a professional subject. As a student of pharmacy department, I need

to have theoretical as well as practical and industrial knowledge. In-plant training
helped me to acquire knowledge on drug manufacture and manufacture
management; and it will be very much useful in my professional life. I am
concluding my report by giving thanks to God and also those who has to face
hard work for me. Wish prosper of Novartis (Bangladesh) Limited day by day.

In-plant training report. Page 39 of 40

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