NATIONAL MODEL COLLEGE FOR ADVANCE LEARNING

(NMCAL)
Nayabazar, Khusibu, Kathmandu

A Report On
In- plant training on CTL PHARMACEUTICAL Pvt. Ltd.
In partial fulfillment of the requirement for the degree of
Bachelor in Pharmacy
Submitted by:
Arjun Ghimire
4thBatch
Submitted to:
CTL PHARMACEUTICAL Pvt. Ltd.
Bhaktapur

ACKNOWLEDGEMENT
We take this opportunity to express our profound gratitude and deep regards to our program chief Dr. Madhav
Prasad Baral, program Director Mr. Prajwal Jung Pandey, our respected program coordinator Ms. Savyata
Gautam and faculty members Mrs. Junu Khatri Silwal, Mr. Anil Sah for their exemplary guidance, constant
support and encouragement through entire B. Pharm program, to undergo an In-plant training.
I would like to express my first and foremost gratitude to chairman Mr. Rabi krishna shrestha,
General manager Mr. Dipendra pradhan for providing me with an oppurtunity to train at CTL. I take my
pride to complete my in-plant training at CTL pharmaceuticals pvt. ltd., one of the most reputed
pharmaceutical companies of Nepal. I would like to express my special gratitude to factory manager Mr.
Amir bade for his support and guidance. I would like to express my most cordial and humble thanks to QA
manager , Mr. Ravi Maharjan for his support, motivation and guidance throughout my in-plant training at
CTL. I would like to offer my sincere gratitude to Mrs. Archana Pradhan QC manager, Mr. Dipesh
Shrestha QA officer, production head Rajendra Khadka , Rukesh Machamasi and Abhishek Shrestha for
their kind co-operation, support, guidance and constant supervision as well as for providing necessary
information during my training even in their busy schedule.I am highly indebted to all supervisors, analyst,
all the pharmacists of respective departments for giving me attention and time.I would like to give my
heartiest thanks to all the industrial staffs of CTL for their hospitality and encouragement and making my
stay at CTL a memorable time.

Arjun Ghimire

ABSTRACT
The in-plant training is required for the partial fulfillment of degree of Bachelor in Pharmacy under
Institute of Medicine and consists of in-plant training for 3 weeks at Pharmaceutical industry. The training
program consists of brief training in the different departments of the pharmaceutical industry. In the course
of training at CTL, I was exposed to the departments of CTL namely Production, Quality Assurance,
Quality Control, Store, Primary and secondary packaging. During the training period, I gained practical
knowledge on handling of raw materials, manufacturing process, operation of equipment, packaging of
product, quality testing of raw materials, intermediate products, finished products, and assurance of quality
through monitoring, controlling, documentation and other activities performed for achievement of quality
products. Moreover, I have also been aware of importance of quality in manufacturing of medicines and its
documentation. This training helped me in applying my theoretical knowledge to practical approach and to
use my theoretical knowledge to choose the specific department of my interest for my career.
Thus, this training has been very productive for me in my aim to be a competent pharmacist and to uplift
my profession.

ACRONYMS
AHU

Air Handling Unit

BMR

Batch manufacturing record

BPR

Batch Packaging Record

HEPA

High Efficiency Particulate Air

HPLC

High Performance Liquid Chromatography

HVAC

Heating, Ventilation and Air Conditioning

GMP

Good Manufacturing Practice

IPQC

In-Process Quality Control

KF

Karls Fischer

MFR
NMT

Master File Record

Not More than

NLT

Not Less than

PVC

Polyvinyl Chloride

PVDC

Polyvinyl Dichloride

QA

Quality Assurance

QC

Quality Control

RH

Relative Humidity

RM

Raw Material

RMG

Rapid Mass Granulator

RO

Reverse Osmosis

R&D

Research and Development

SOP

Standard Operating Procedure

UV

Ultraviolet

GRN

Goods Received Note

TABLE OF CONTENT

IN PLANT BRIEFING
With the aim of developing ability to translate theory into practice, the curriculum of Bachelor of
Pharmacy places students for in plant training in pharmaceutical manufacturing units for the duration of 3
weeks at the end of fourth year.
Area covered and duration : CTL Pharmaceutical Pvt. Ltd.
S.
N

Date

Concerned
department

06TH March13th March

Quality control

14th
Marchrd
23 March

Production

24th
Marchth
25 March

Quality assurance

1. BACKGROUND AND OBJECTIVES

For the partial fulfillment of degree of Bachelor in Pharmacy program of National Model College of
Advance Learning, Tribhuvan University, I have completed my 3 weeks in plant training at CTL
pharmaceutical Pvt. Ltd., one of the well established pharmaceutical industry of Nepal.

Training period: 6 March 25 March

Reporting time: 10 am to 3 pm

The objectives of the training were:

General objectives:
To know the organizational structure and functions of different departments in the industry and
also the overall manufacturing process of different products along with their quality control and
management and role of pharmacist in all these aspects.

Specific objectives:
To be familiar with the manufacturing of the pharmaceutical products in the industry so as to
gain
practical knowledge and experience.
To get detailed information regarding receipt of material, storage, dispensing of raw and
packaging materials.
To be familiar with various equipments and instruments used for the manufacturing of the drugs
in pharmaceutical industries.
To get overall ideas regarding operation, maintenance, assemblence and standardization of
water treatment plant, HVAC and other utilities.
To have idea about the flow of men and materials during manufacturing.
To know the different process of Quality Control and In-process Control of raw materials &
finished products.
To develop confidence and gain professional tips to work as capable pharmacist in near future.
To get idea regarding the waste disposal system.

2. COMPANY PROFILE
2

CTL Pharmaceutical Pvt. Ltd. established in 1990 is founded on a deep sense of National pride and
conviction to make a contribution to our countrys self reliance in the field of pharmaceutical formulation
and to ensure health and happiness for all by manufacturing the range of medicines of the highest quality at
affordable price and reaching out even to marginalized people of Nepal. It was established in 1994 as
Kathmandu Medical Hall, later in 1995, it is transformed to BR pharmaceuticals. All the activities are
carried out in dedicated areas with controlled environment as per GMP. Salient features of CTL
Pharmaceutical is committed to implement and maintain GMP norms, Quality assurance , quality and
environment policy at every stage from procurement, manufacture, packaging, storage, sales and
distribution to waste management. It is dedicated to manufacture and market pharmaceutical formulation of
requisite standard to cater customer need enhance the customer satisfaction and ensure better health care by
assuring continual and dynamic improvements in quality of its products and services. CTL Pharmaceuticals
is committed to create excellent working environments by improving its environmental performance
through continual improvement in environmental conditions, prevention of pollution and optimum
utilization of energy and resources. CTL ensures the occupational health and safety of its workers by
conducting regular health check-up. CTL produces a products which includes quality non-sterile
products among tablets, capsules.

1.1 Organizational chart of CTL pharmaceuticals

General Manager
Factory Manager
Quality Assurance Manager

QC Head

QA Officer

HR Department

Maintenance Officer

R&D Officer

Assistant QA Officer

Microbiologist
QC officer

Production Head

Assistant QC officer

Production Pharmacist

4. OPERATIONAL PROCEDURE
Vendor (Supplier)
De dusting
4

Store incharge

Receiving of starting and packaging materials

Cleaning
Quarantine in store
Sampling by QA and analysis by QC
Sampled material (Yellow label- Under test)
Fail (Red label)

Pass (Green label)

Storage of passed material

Dispensing
(As
per
cross check by production)

BMR

in

presence

of

store,

Manufacturing
Intermediate (IPQC)
Finished product
Analysis by QC
QC release
QA documentation and Review
Fail (Hold and needs recommendation

Pass (Release for Distribution)

for further processing)

Storage of finished product

5. VARIOUS DEPARTMENTS
1. Store department (raw material and packaging material store)

QA

and

This department receives, records, stores and dispenses the raw materials and packaging
materials to the various departments.

2. Engineering and utilities department

Heating, ventilation and air condition system (HVAC)

Water treatment plant
Steam generator/ boiler
Power supply / generator
Compressed air supply

3. Research and Development department

Developing new products

Stability studies
Process simplification
Dosage form development

1. Production department
Cephalosporin
Non-penicillin
Penicillin
2. Quality Control department
Instrument room
Controlled sample room
Stability chamber room
Microbiology laboratory
Room for analysis
Office room
3. Quality Assurance department
Material, processing and document control
Validation
Documentation
Method development
DISCUSSION ON VARIOUS DEPARTMENTS
5.1.
Store department:
Storage is the process of keeping or holding goods in a systematic way preserving its quality and store is
the place where goods are kept safely for future use. Store is the first point of entry of material into the
factory and the last point at which the factory still has control of its product before they leave to go to a
6

customer. Store should therefore be properly maintained to prevent deterioration, contamination of stored
goods.
Requirements of storage area:
Storage areas should be of sufficient capacity to allow the orderly storage of the various categories
of materials and products.
Storage areas should be designed or adapted to ensure good storage conditions.
Storage areas should be clean, and free from accumulated waste and vermin.
Materials and pharmaceutical products should be handled and stored in such a manner as to prevent
contamination, mix-ups and cross-contamination.
Materials and pharmaceutical products should be handled and distributed according to GMP as
defined in this document.
Rejected materials and pharmaceutical products should be identified and controlled under a
quarantine system designed to prevent their use until a final decision is taken on their fate.
Materials and pharmaceutical products should be stored in conditions which assure that their quality
is maintained, and stock should be appropriately rotated. The first expired first out (FEFO)
principle should be followed.
Storage areas should provide adequate lighting to enable all operations to be carried out accurately
and safely.
Different labels used in stores are as follows:

Yellow : Raw material under test

Green: Approved
Red: Rejected

CTL practices good storage and distribution practice. So the store scientifically designed to make it rodent
proof, adequate storage is maintained, and RH is adjusted to avoid the degradation of raw materials and
finished product. CTL has separate store room for RM/PM of non-penicillin, penicillin, cephalosporin, feed
supplement, and finished product. The store is very spacious and properly designed to ensure good storage
condition.

Store department of CTL formulation has following section:

Raw material store

Packaging material store
7

Finished product store

The goods when delivered are received and they are checked as per the purchase order. The data entry is
done via software programme. Afterwards the goods are cleaned and dedusted and stored in the quarantine
room. Sampling is performed by the QA officer in the sampling booth. The choice of a sampling plan
should always take into consideration the specific objectives of the sampling and the risks and
consequences associated with inherent decision errors. Sampling may be required for different purposes,
such as prequalification; acceptance of consignments; batch release testing; in-process control; special
controls; inspection for customs clearance, deterioration or adulteration; or for obtaining a retention
sample.
The tests to be applied to the sample may include:
verifying the identity;
performing complete pharmacopeial or analogous testing; and
performing special or specific tests.
In case of the active materials, all the containers need to be sampled whereas, for the excipients,
appropriate sampling plan needs to be carried out. Generally n-plan i.e. formula (n+1) is applied where
n is the number of containers to be sampled.
The sampled materials are sent to the QC lab for analysis and these products are tagged with yellow slip
notifying under test. The materials are stored in quarantine until QC approves for their further use. The
passed materials as per the specification are tagged with green slip whereas the failed ones are tagged with
red slip and are kept in the separate area. The rejected materials are either destroyed or returned to the
vendor.
5.1.1 Raw material store:
Active as well as excipients are stored in this store. RM store is separate for pharma product and veterinary
products. The approved products are stored in this store. RM is dispensed to production as per the
requisition following the BMR with the rule FIFO or FEFO. The amount of RM received and dispensed
each time is recorded in the register. The dispensing is done in the presence of QC personnel.

5.1.2 Packaging material store:

The PMs like Duplex box, Aluminum foil, PVC, Bottles and Tubes are stored in the PM store separately
and safely to avoid damage, deterioration and contamination. The rejected materials are quickly removed
from store to avoid mix up. This store receives PM from different vendors and informs QC for testing. The
8

passed materials are stored and dispense to production as per requisition. The packaging materials are
grouped into primary and secondary packaging materials.
5.1.3 Finished product store:
After passing all the tests, finished product is packed well and transferred from packaging section to
finished product store room from where these products are released to the market. Delivery of finished
product is done only upon request from sales department. Delivery of FG also follows FEFO and FIFO
system. FG store in-charge dispatch the FG goods as mentioned in issue register (Challan) received from
Head Office and write details about product and quantity being dispatched to Head office. Gate pass is
prepared for all quantities being dispatched which are verified by security personnel at the gate. Dispatch
FG goods are loaded in Delivery van and dispatched to the destination place viz. Distributors.
Finished Goods store also receives the returned and expired product from distributer which is segregated
into different area to avoid mix-up. In case of expired products, destruction note is prepared by store which
is approved by QC in-charge, management and QA in-charge. Then, in presence of QC, expired products
are destroyed as per company rule.

Following is the chart showing system and practice followed by store for handling of new
raw materials

Store department receives order from different departments and is forwarded

to logistic department

Logistic department procure the required raw materials from

vendor

Raw materials are delivered to factory along with invoice of

raw materials

Received goods are checked by security and details are entered in

register

Store department rechecks the materials as per invoice

(including quantity, batch number, MFG. date, EXP. Date
etc) and keep them in quarantine
Based on GRN, official label is prepared and attached to
respective container.

Store sends GRN & RM test request note to QC for sampling

and analysis

QC department sample the materials for analysis and label them as

under test [100%sampling is required for active materials whereas
sampling of excipients is don according to the formula ( n+1)]

QC analyzes raw materials as per specification and label the raw

material Approved (Green Sticker) or Rejected (Red Sticker) and
certificate of analyzes is forwarded to store.

Store department transfers the approved raw materials into the main
store and register details are enter in the stock register.

Store department transfers the approved raw materials into the main
store and register details are enter in the stock register.

The approved API are transferred to respective storage areas based

on the environment controlled condition

Dispensing of RM/PM for a batch is done in the dispensing booth by officer from
10
store, supervised by QC and counterchecked by production
on receiving RM/PM

requisition Slip from production which in turn is issued on release of BMR or BPR

Amount of RM and PM received and dispensed each time is entered in

RM and PM register book showing balance/ amount remained.

Fig: Flow chart of Raw Material Handling.

5.2 Engineering and Utilities:

Engineering department in the pharmaceutical industry is for assessing machineries, arranging services and
sanitation so as to facilitate smooth production and control environment. The major function of this
department is routine management of Air handling unit, water treatment plant, electricity supply, and
compressed air supply. Dedicated personnel and engineers have been allocated for these purposes. Besides,
maintenance and repairing are also carried out by this department.
The engineering department is well defined at CTL Pharmaceutical Pvt. Ltd. It works under QA department
and helps in preventive as well as emergency maintenance. They also carry out the repairing of electrical
wirings, pipelines, and the factory premises etc.
The units related to this department are:

Heating Ventilation and Air-conditioning system(HVAC)

Water treatment system
Power supply(operating generator)
Compressed air
Steam generator (boiler)

5.2.1 Heating Ventilation Air Condition System:

HVAC has important role during the designing and implementation of Clean room concept on the
Pharmaceutical premises. HVAC contains many air filters, heater and air conditioning unit to maintain a
correct temperature, moisture and pressure difference as required during operation in the production area,
microbiology laboratory and the office rooms. HVAC system design influences architectural layouts with
regard items such as airlock positions, doorways, and lobbies. The architectural components have an effect
11

on room pressure differentials cascades and cross contamination control. The prevention of contamination
and cross contamination is an essential design consideration of the HVAC.
It performs four basic functions:
Control airborne particles, dust and micro-organisms
Maintain pressure difference between two areas.
Maintain space moisture (Relative Humidity
Maintain space temperature.

Components of HVAC system

Weather Louver : To prevent insects, birds dirt, rain etc. from entering
Silencer : To reduce noise caused by air circulation
Flow rate controller : Automated adjustment of volume of air (night & day Pressure control)
Control Damper : Fixed adjustment of volume of air
Heating Unit : To heat the air to the proper temperature
Cooling unit/De-humidifier :
Humidifier : To bring the air to the proper humidity, if too low
Filters : To eliminate particles of predetermined dimensions or micro-organisms
Ducts: To transport the air
Glass wool fiber: To insulate the temperature of the flowing air inside the duct.

5.2.2 Air Handling Unit (AHU):

AHU is the heart of the HVAC system which is intended to provide unidirectional flow of fresh air. AHU is
a special air treatment plant installed in CTL Pharmaceutical to maintain clean room condition based on
WHO GMP requirements. There are separate AHU and is made in such a way to permit effective cleaning
and maintenance in order to avoid cross contamination and build of dust.
Settings of AHU:
Air velocity: 20-25 Cycles/hr
Pressure difference: 15 6 Pa (Corridor-Positive with 30 Pa and Room- Negative with 15 Pa)
It maintains the D-CLASS requirement of particle count of industry as per GMP requirements

12

Production department: class 1, 00000,

Dispensing booth: class 100.
In AHU unit 75% recalculated air and 25%fresh air is supplied in combination.
The different parts of AHU includes
1. Filter section
2. Coil section(Heating coil and conditioning coil)
3. Blower section
Filter section:
Four types of filters are used in AHU with different sizes and location.

Pre- filter: Pore size 10 and it is washable.

Bag filter: Pore size 5 and is disposable.
Supply filter: Contains HEPA filter of pore size 0.3 is disposable.
Coarse/Return filter: Pore size of 20 and are washable

Coil section
It consist heating and cooling coils. It maintains temperature and Relative Humidity of air.
Blower section
Sends air to supply duct according to the required CFM (Cubic feet/ min). The air change/hour in the
operating room has been maintained to be at least 20 changes / hour depending upon the volume of room,
products and personnel involved as per WHO-GMP Guideline.

13

Process flow of AHU with components:

Fig: Flow chart of Air Handling Unit

5.2.3 Water Treatment Plant:

Water is one of the raw material most frequently used in Pharmaceutical Industry. It used in the production,
processing and formulation of pharmaceutical products. Different grades of water quality are required for
different dosage forms or for different stages in washing, preparation, synthesis, manufacturing or
formulation.

14

The water should be free from unacceptable microbial, chemical or physical contamination.the water in the
factory comes from water supplier. After removing iron by aeration, the water is then pumped to the storage
tank kept on top floor. Then, it is subjected to treatment as follows:

Aeration
Chemical
system

Removes iron from water by oxidation and then

sedimentation of iron.
dosing

CDS1 (Alum), CDS2 (Chlorine) which removes

odour, maintain pH and acts as disinfectant.

Degasser

Removes dissolved gases.

Sand filter

Comprises of 3 layers viz. gravels, pebbles and

sand; removes metals and organic materials.

Carbon filter

Removes colour, odour, organics and free chlorine.

Softener

Decrease the pH of water and converts hard water

into soft water.

Reverse osmosis

Removes total dissolved solids (TDS) upto 9095%

UV treatment

For disinfection of water.

Water types used in Industry:

Potable water: Drinking , Washing

Soft water: Boiler
Purified water: Production and Rinsing of instruments

Specifications of PW:

Conductivity: less than 1 S/cm at 200oC (BP)

PH: 5.0 - 7.0
Total organic carbon ppb (TOC): 500g/l
Bacterial count: 100 CFU/ml
Total dissolved solids ppm less than 1
Coliform CFU/ml = 0

15

Water treatment process flow chart:

Fig: Water treatment process

16

5.2.4 Steam generator (Boiler):

Husk pack based Steam supply system is well maintained at CTL Pharmaceutical to supply the heat
required for the different instruments during the various processing steps of the tablets, semisolid dosage,
and capsule section of the production department. Steam is required for the FBD, paste vessel, ointment
vessel, wax vessel etc. Steam at CTL Pharmaceutical is supplied by the steam boiler plant installed
separately.
5.2.5 Air Compression Unit:
There is air compressor system at CTL Pharmaceutical through which air is distributed all the production
rooms. They are used according to the need. Compressed air is passed through a pipe. By filtering the
compressed air it is supplied to production rooms. Before using, the air is again filtered. The compressed
air is used to remove dust, in mixing, in drying etc. Compressed air is necessary in granulation room,
Fluidized Bed Drier, compression, capsule separation and polishing, primary packing, coating, RMG, dedusting, ointment filling, etc. The compressed air supplying machine consists of a double piston system
which takes the environment air, filters it and supplies it under high pressure.

5.3 Production Department:

Production department of CTL Pharmaceutical is constructed, maintained and operated according to WHO
GMP guidelines. As per the WHO GMP guidelines it has three separate production blocks for
cephalosporin, non- penicillin and penicillin products. The non- penicillin block comprises tablet, capsule,
and ointment section, cephalosporin section comprises Tablet, and Dry syrup whereas penicillin block
comprises Tablet.
Tablets and Capsules Production area is maintained under class 1, 00,000 i.e. number of particles of size of
less than 0.5 micron should not exceed 1, 00,000 per cubic feet while topical and liquid is maintained under
class 10,000. Corridor must be positive of 15 Pascal than that of the room. The walls and ceilings are
painted with epoxy emulsion to avoid retention of any particulate matters. Standard Magnehelic pressure
Gauge is installed in every door to monitor the pressure difference. Rooms are cleaned periodically by
disinfectants like Phenol, Savlon and Dettol to prevent resistance to microorganisms. Before entering into
production area one has to pass through change room, which consist of cross over bench. All
manufacturing and primary packaging room is equipped with Dry/wet thermometer (Hygrometer) to
measure the temperature and humidity. Production is strictly controlled under the plan of production
manager and production is done as per BMR provided by QA. Before any manufacturing process begins,
the Line Clearance is done to ensure that the working areas and equipments are free from any other
previous products, so that cross contamination is prevented. There are clearly written SOPS for each
instrument and the SOPS are reviewed in specific interval.
17

Production department is divided into 3 sections:

Non-penicillin section
Cephalosporin section
Penicillin section

5.3.1 Non penicillin section:

There is separate block for non-penicillin products in the CTL Pharmaceutical. Non-penicillin section
produces tablet, capsule and ointments of non-penicillin class of drugs.
5.3.1.1 Tablet Section
Tablets are solid, oral dosage forms each containing a single dose of one or more active ingredients and are
obtained by compressing a uniform volume of particles (granules) by applying high pressure and using
punch and dies. Tablet section of CTL Pharmaceutical produces different coated and uncoated tablets with
varying shape and size as per the respective BPPR. Tablet produced in CTL Pharmaceutical consist:
Cephalosporin, Non Penicillin, penicillin.
Method of Tablet Production:
Direct Compression
Dry Granulation
Wet Granulation
In CTL Pharmaceutical tablet is produced by wet granulation method.
This section consists following areas:
S.
N

Areas

S.
N

Areas

Raw
Material
Dispensing Area

Tablet
area

Mixing,
Granulating
and
Drying Room

IPQC Room

Tablet
Compression
Room

Quarantine Store

Tablet
Room

Coating

18

Packing

 Raw Material dispensing room:

Dispensing booth is the area designed to dispense the starting materials for production. There are HEPA
filter, intermediate filter and negative pressure in dispensing booth. The air flow is vertical laminar air flow.
The dispensing and sampling procedure is carried out in presence of a QA Officer, representative from
store and a production department and is done inside safe zone. Weighing balance should be well calibrated
and properly cleaned. Light sensitive raw materials are dispensed protecting from light. During dispensing,
excipients should be dispensed first and then the active ingredients to prevent cross contamination.
Equipments used:

Dispensing Booth for particulate filtration

Electronic Balance-Electronic

Mixing, granulation and drying room

All the dispensed materials required for tablet manufacturing are first sieved to avoid the unnecessary
particles. These are passed through vibro sifter having different mesh sizes. Usually, mesh size of 80, 60
and 20 are used. Then mixing is performed in RMG. The wet granulation method is preferred for the
processing of tablet.
Granulation
It is the process in which dry primary powder particles (i.e., single, discrete powder particles) are processed
to adhere to form larger multiparticle entities called granules. Pharmaceutical granules typically have a size
range between 0.2 and 4.0 mm, depending on the subsequent use of the granules.
Reasons for granulation

To prevent segregation of the constituents of the powder mix

To improve the flow properties of the mix
To improve the compaction characteristics of the mix
To reduce dust generation, capping tendencies and sticking
Granules being denser than parent powder mix, occupies less volume per unit

General steps of wet granulation are outlined below:

19

Granulating
Drug +
Diluent
(Pulverizati

Wet
mixing

Dry
mixing

Agent

Water/solvent

Dry
sieving

Wet
sieving

Drying

Blending

Compressi
on

Coating

Packaging
Disintegrant
+ Glidant +
Lubricant

Fig: Steps of wet granulation

Wet granulation is further of two types: Aqueous (water is used) and Non-aqueous (organic solvents are
used). Generally, starch paste and PVP are used as binding agents. These are kneaded for sometime
carefully. As longer the kneading time, longer will be the disintegration time and thus the rate of dissolution
will be decreased. Temperature is the critical parameter while preparing starch paste. Granulation can be
inspected by:

Breaking the clumps in order to see the clumps formed

Feeling the heavier damp mass

20

Mixing and granulation is performed in RMG. RMG has a stainless steel mixing bowl containing a three
bladed main impeller, which revolves in the horizontal plane, and a three-bladed auxiliary chopper, which
revolves either in the vertical or the horizontal plane. The unmixed dry powders are placed in the bowl and
mixed by rotating impeller for a few minutes. Granulating liquid is then added via a charging port in the lid
of the granulator while the impeller is turning. The granulating fluid is mixed into the powder by the
impeller. The chopper is usually switched on when the moist mass is formed so as to break up the wet mass
to produce a bed of granular material. Once the satisfactory granule has been produced, the granular
product is discharged, passing through a wire mesh, which breaks up any large aggregates. The major
benefit of this process is that mixing, massing and granulation are all performed within few minutes in the
same piece of equipment.
Another equipment used for the granulation is mass-mixer. It is used for making large quantity of
granules.
Drying
FBD is used for the drying of materials to get the desired moisture content in the tablet manufacturing
granules. It is the well known and widely used equipment in pharmaceutical manufacturing.
Principle of FBD: If air is allowed to flow through a bed of solid powdered material in upward direction
with the velocity greater than the settling rate of the particles, the solid particles will be blown up and
become suspended in the air stream. At the stage solid bed looks like the boiling liquid, therefore this stage
is called as fluidized. Use of hot air to fluidizing the bed will increase the drying rate of the material.
Components
Material container (material to be dried are placed)
Air suction fan (generate airflow necessary for fluidization of the powders)
Steam of hot air (for fluidization to the desired temperature)
Inlet air(filters the air used for fluidization of powders filter)
Exhaust air (filters to retain dust and fine particles)
Filter or FBD bag (increase surface area for drying)

21

Working
The material to be dried is placed in the material or product container. Air is introduced from the bottom of
the container and heated at required temperatures by the heaters. This air is filtered through the filtered and
then passes through the bed of the material. This air flow is generated by the fans fitted at the top of the
equipment. The flow rate and the operating temperature are adjusted by control panel. As the flow of air
increases, the bed known as FBD bag expands and the particles of powder starts a turbulent motion. Due to
the regular contact with air, material gets dry. The air leaving the FBD passes through the filter to collect
the fine particles of the material. FBD has a high drying rate and the material is dried in a very short time
i.e., about 15 min. Material remains free flowing and uniform. FBD bags are finger like in structure to
increase the surface area of the drying bed.
Blending or Lubrication room
After drying, dry screening of the material is carried out. Then it is send for lubrication. Various lubricating
agents like magnesium stearate, talc, colloidal silicon dioxide (aerosil) are used. These help in reducing
friction by interposing an intermediate layer between tablet constituents and the die wall during
compression and ejection. The equipment used for drying is double cone blender.
Compression room
Compression is done just after lubrication of granules. For this purpose, tablet compression machines of
various stations are used.
In CTL, 27D or 16D rotary compression machines are used in T ablet section and 10 station rotary
compression machines is used in R&D department. Humidity and temperature should be controlled in this
room by dehumidifier because excess moisture can affect the flow of granules causing weight variation and
various other problems like sticking, picking or chipping.
All the tablet presses employ the same basic principle: they compact the granular or powdered mixture of
ingredients in a die between two punches. Different shapes and sizes of dies and punches are available
according to the need. During compression, the ratio of granules and fine should also be maintained i.e.,
70:30. If the granules are more than fine, weight variation may occur. Likewise, if the ratio of fine exceeds
then improper flow property may exist. Other parameters like weight, hardness, thickness, speed have to be
equally considered during compression.

Components of Tablet press

Hopper
22

Feed frame
Turret
Punches
Die table
Die
Cam track
Pressure roll
Chute

Things to be considered during compression

1-2 mm gap should be kept between Turret and Feed frame to avoid friction and maintain proper
spread of granules within feed frame compartments.
Weight and Hardness Adjustment- weight is adjusted first followed by hardness. Hardness should
be adjusted in such a way that tablet should pass Friability (NMT 1%) and DT (NMT 15 min for
uncoated tabs) but at the same time tablets should be of desired thickness, because variation in
thickness, can cause problem during packing. Weight variation, Hardness and Disintegration time
should be checked every hourly or so by the operator and IPQC to adjust variation if it has
occurred.

Visual defects seen in tablets

Defects related to tableting process

Defects related to excipients
Defects related to more than one factor
Defect related to machine

capping, lamination, cracking

chipping, sticking, picking, binding
mottling (color variation)
double impression

Coating room
Coating process is the last critical step in the tablet production cycle. Tablet coating is the application of a
coating composition to a moving bed of tablets with the concurrent use of heated air to facilitate
evaporation of solvent. The distribution of the coating is accomplished by the movement of the tablets
either perpendicular (coating pan) or vertical (air suspension coater) to the application of coating
composition. The successful application of the coating solution formula to a tablet provides the visual
characteristics for the product; thus, the quality of the product may be judged on this final production step.

23

In CTL, coating machine of perforated pan system i.e., semi automatic coater is used. Depending upon the
nature of drugs, tablets are either enteric or film coated.

Coating objectives

To improve aesthetic qualities of the product

To mask unpleasant taste and odor
To enable the product to be more easily swallowed by the patient
To facilitate handling. particularly in high-speed filling packaging lines
To improve product stability
To modify drug-release characteristics

Types of coating
I.

II.

III.

Film coating
Addition of polymer film to the surface of tablet
Adds up to 2-3% weight to final tablet
Retains contour of original core and usually not shiny
Coating time 2-3 hrs
Prevents from moisture, mask bitterness, elegance and identity.
Sugar coating
Application of sucrose based solution to tablet core
Adds up to 30-50% weight to final tablet
Rounded with high degree of polish
Coating time more than 8 hrs
Masks bitter taste
Enteric coating
Polymer barrier applied on tablet core
Adds up to 9-10% weight to final tablet
For acid labile drugs, to deliver drugs with high bioavailability in basic medium to their primary
absorption site i.e. intestine and to prevent gastric irritation.

Components of semi automatic coating machine

Coating pan
Spray Gun (sprays coating solution which works on the principle of compressed air sent through
Air Compressor)
Hot air Blower adjusted to required temp to facilitate effective drying.
Dust extractor is fitted properly so that dusts produced during coating are carried away.

Colloid mill is used in the coating room to ensure particle size reduction and proper dispersion.
24

Problems
of
Coating

Causes

Sticking &
picking

Over wetting
Excessive film
Inefficient
drying

Fast drying
High pigment
concentration
and polymer
concentration
with coating
solution

Decrease degree of
atomization

Optimise
concentration

High solution
viscosity
Inadequate
spreading of
coating
solution
before drying

Thinning
of
solution with more
solvent

Roughnes
s

Orange
peel effect

Remedies

Decrease
liquid
application
Increase in drying
air temperature and
air volume

the

Blister
forming

Rapid drying
High
temperature

Milder
drying
concentration

Hazing/
Dull film

High
temperature,
humidity

Control
temperature
humidity

Color
variation

Migration of
soluble dye
Improper
mixing

25

use lake dye

and

Bridging
and filling

uneven spray
pattern
insufficient
coating
The
film
shrink
and
pull away the
sharp corner
of bisect and
form bridge

Increase
plasticizers
concentration

Sorting of tablets
Sorting is done before packaging process to minimize the risks and chances of packing the deviated
tablet. Different parameters like shape, size, color, logo, breakage, cracking etc are observed manually.

IPQC
In-process inspection and testing should be performed by monitoring the process or by actual sample
analysis at defined locations and times. The results should conform to established process parameters or
acceptable tolerances. Work instructions should delineate the procedure to follow and how to use the
inspection and test data to control the process.
The works of IPQC are related with production, store and Quality Control. It also checks different
parameters for solid preparations. The in-process quality control for solid dosage form i.e., tablet are:

Checking the weight variation of the tablets at pre-determined intervals during manufacturing

Checking disintegration, hardness, thickness and friability of the tablet repeatedly each hour of
production

Checking of moisture content in case of granules

Leak testing and overprinting of label for packaging product

26

Equipments used in IPQC

1. Weighing balance: for weight variation, 20 tablets are taken and this is done every hourly after the first
15 min. Minimum and maximum deviation is then calculated.

Specification

Standard Limit %

80 mg or less

10

>80 mg &<250
mg

7.5

250 mg or more

In house specification: 5% for min and max deviation

2. Hardness tester (breaking force): 10 tablets taken
3. Vernier caliper: for thickness, length, breadth, 10 tablets taken
4. Disintegration test apparatus: 6 tablets taken

Tablets

Limit

Uncoated

NMT 15 min

Coated

NMT 30 min

5. Moisture balance: less than 1.5%

6. Friability test apparatus: 10 tablets taken, limit: NMT 1%
7. Leak test apparatus
27

5.3.1.2 Capsule section:

Capsules are the solid unit dosage form of medicaments in which the drug(s) is enclosed in a practically
tasteless, hard or soft soluble container or shell made up of a suitable form of gelatin. Capsule shells are
smooth, slippery, can be easily swallowed and are tasteless, and are particularly beneficial for drugs having
an unpleasant taste or odor.
At high moisture capsules become soft/tacky and at low moisture they become brittle, so, temperature and
relative humidity should be maintained at 222C and 455% respectively. Temperature and humidity is
controlled in capsule section by dehumidifier. CTL pharmaceutical manufacture hard gelatin capsule of
sizes 0, 1 and 2. CTL has semiautomatic capsule filling machine.
Equipment used in capsule section:

Semi-automatic capsule filling machine

Manual capsule filling machine
Double cone blender
Dehumidifier
Weighing balance

Manual capsule filling machine:

Hand operated and electrically operated machines are in practice for filling the capsules but for small and
quick dispensing hand operated machines are quite economical. A hand operated hard gelatin capsule
filling machine consists of the following parts:

A bed with 200 to 300 holes.

A capsule loading tray.
A pin plate having 200 t0 300 pins corresponding to the number of holes in the bed and capsule
loading tray
A lever
A plate fitted with rubber top.

In CTL has operated capsule filling machine with 300 holes is used for manual filling of hard gelatin
capsule.
IPQC for Capsules
It includes:
28

Weight variation.
Physical appearance(shape, size, color, locking etc)
Locked capsule length
Fill Weight
Disintegration Time (DT apparatus)

5.3.1.3 Ointment section

Ointment is a viscous or semisolid preparation used on the skin as a cosmetic, emollient, or medicament. It
is rubbed on the skin for medicinal purposes or as a cosmetic. Ointments have an oily or greasy consistency
and can appear stiff as they are applied to the skin. Ointments contain drug that may act on the skin or be
absorbed through the skin for systemic action.
CTL manufacture basically three type of semisolid preparations for topical use such as
a. Ointment
b. Cream
c. Gel
The ointment section is equipped with:
a.
b.
c.
d.
e.

Wax vessel
Aqueous vessel
Anchor/ Manufacturing vessel
Ointment transfer tank
Semi-automatic ointment filling and crimping machine

29

Flow Chart for Overall Process of Ointment Production

RM

QC
analysis and
release

RM Requisition from
Production

In presence of
production. QC
and store
personnel

RM Dispensing
by Store

Preparation of Oil
phase (Planetary
Mixer)

Addition of active ingredients + Other

Ingredients (by dissolving in their
respective solvents)

Mixing & Cooling

Milling (Triple Roller Mill/Colloid

Mill)
QC release

Filling and Packaging

Fig: Process of ointment production

30

IPQC for ointment:

1. The weight variation test of ointment includes following process:
Sample of ten filled tubes are taken.
The tubes are emptied and the average weight is calculated.
Average net weight of content of 10 tubes should not be less than the labeled amount
NLT 91% and NMT 109% where the labeled amount is 10mg or less
NLT 94% and NMT 106% where the labeled amount is more than 10gm
If the test fails, 10 additional tubes are taken
2. Average weight
3. Proper crimping
4. Batch coding
5.3.2 Cephalosporin section:
CTL has separate floor for cephalosporin products with a separate AHU. Tablets and dry syrup are
manufactured in this section. Dry syrups are also called as reconstitution suspension. Cephalosporin
products are not manufactured in liquid dosage form because of hydrolytic degradation of the
formulation. . It has rooms for granulation, mixing, IPQC test, compression, coating, strip packing, labeling
and secondary packing, powder filling and sealing and quarantine. There is separate Store (RM/PM/Drums)
and separate dispensing booth.

Liquid manufacturing:
In liquid section, various veterinary syrup and suspension are manufactured. The Water used for the
preparation of liquid formulation is RO water. Liquid section has following rooms:

Liquid manufacturing room

Liquid filling/sealing room

The liquid section is equipped with:

Syrup preparation tank

Manufacturing/ Mixing tank with stirrer
Colloidal mill and homogenizer
Filter Press
Transfer Pump
Storage tank
Bottle washing machine
Automatic liquid filling and sealing machine

31

IPQC test for liquid

a.
b.
c.
d.

Fill volume
Leak test
pH test
Physical parameter

5.3.4 Packaging room

Packaging may be defined as the collection of different components (e.g. bottle, vial, closure, cap,
ampoule, and blister) which surround the pharmaceutical product from the time of production until its use.
Any material, including printed material, employed in the packaging of a pharmaceutical product,
excluding any outer packaging used for transportation or shipment is known as the packaging material.
Packaging material may be:
A primary packaging component means a packaging component that is or may be in direct contact with
the dosage form.
A secondary packaging component means a packaging component that is not and will not be in direct
contact with the dosage form.
Packaging room has two sections: Primary packaging and Secondary packaging rooms
Why packaging?
Packaging preserves the stability and quality of medicinal products.
Packaging protects them against all forms of spoilage and tampering.
Packaging provides comfort for patients on handling products.
Packaging provides certain level of elegance to the product to build brand image.
Packaging provides required safety mechanism to the consumers (e.g. Child proof covers, Tamperevident packaging).
Methods of primary packaging in CTL

Alu- alu packaging

Blister packaging
Strip packaging
32

I.

Alu- Alu packaging

This packaging is mostly done in CTL, which offers advantages like:

More protective
High light resistance
High moisture resistance

In this machine, two thin foils of aluminium are used for packing the tablets. One of the foils is printed in
which the batch no., mfg. date, exp.date and price are printed whereas other is plain. The printed foil
consists of heat seal lacquer which helps in sealing the two aluminium foils together. The air pressure is
required to run the machine which is supplied via the air compressor.
II.

Strip Packaging

Strip packing is done for moisture sensitive drugs as Aluminium foil is highly resistant to moisture
permeation.
Parts of a strip packing machine
1. Fixed parts: control panel, heater, felt bush roller
2. Changeable parts:
a) Washable: hopper, plate, chute
b) Non washable: roller, printing drum, gear

Hopper: for feeding

Plate: for guiding the tablets form the hopper into the chute.
Printing Assembly: consists of printing drum, felt brush roller and stereos of different types. They
are used to print the batch no. , mfg. date, exp. date, price, on the plain Al foil.
Chute: for passing the desired no. of tablets into the foils between the rollers.
Heater: heat the foil
Roller: For sealing the dose contained within the two heated foils.
Brush
Cutter: for cutting the required size strips.

33

Process of packaging
Two webs of materials being fed between two heated crimping rollers on which there are circumferential
cavities of a size and depth appropriate to the shape, size and thickness of the article being packed. The
material to be packed is fed from a hopper through channels to drop between the two webs where they meet
between the crimping rolls and the cavities there in. the webs are then sealed together by the activation of
the thermoplastic coating on their inner surface
and pockets formed around the contents. To check that the packaging material is not perforated around the
periphery of the pockets and the heat seals are efficient, sample strips are taken at regular intervals and
tested.

HOPPER

PLAIN Al.
HEAT
FOIL
ER

TABLET FILTER
SETTING
PLATE
COMPRESSOR

140
CUTTER
CSTRIP PACKED PRODUCT
O

Al.
HEAT FOILBATCH
PRINTI
ER
NG
140O
ROLLE
C
R

Fig 1.1 Process of strip packaging

I.

Blister packaging

Blister pack is a term for several types of pre-formed plastic packaging used for small consumer goods,
foods, and for pharmaceuticals. The primary component of a blister pack is a cavity or pocket made from a
formable web, usually a thermoformed plastic. This usually has a backing of paperboard or a lidding seal of

34

aluminium or plastic. Most commonly used thermoplastic are PVC and PVDC. PVDC provides more
protection against moisture than PVC.

Parts of blister packing machine

1. Washable parts: Hopper, feeder, feed track, guide track, vibrator
2. Non washable parts: PVC holder, forming roller, sealing roller, strip cutter, cutting gear, forming
heater, sealing heater, control panel, printing drum.

Changing parts: forming roller, sealing roller, forming heater, sealing heater and the cutting gear
Process of blister packing
A sheet of thermoplastic resin is heat softened and vacuum is drawn to the softened sheet of plastic into a
contoured mold. Heat-softening is done by passing thermoplastic through forming heater heated at
temperature of 1400C-1600C and is cooled by passing through chiller. After cooling, the sheet of plastic is
released from the mould preceding it to guide track of packaging machine. The semi rigid blister previously
formed is filled with the product and lidded with an aluminum foil. Sealing is done at temperature above
1500C-1800C. Cutter is available to cut the blister pack into the desired size by the blade. The cutting gear
is set according to the size of blister/strip to be cut. After they are carried to secondary packing room by
conveyor belt.

HOPPER
VIBRATOR + SENSOR
FILLING PLATE

PVC/PVD
Al.
SETTING
BLIST
BATC
SEAL
SEALIN
C FOIL
FOIL
PLATE
ER
H
ING
G
SEALING HEATER
PRINT
HEA
HEATER FORMI
CUTTER
NGBLISTER PACKED PRODUCT
ING
TER
160OC- ROLLE
ROLL
180O
170OC
R
ER
C

35

Fig1.2. Process of blister packaging

Secondary packaging room

Secondary packaging comes under Black Area as the PM doesnt come directly in contact with the drug. In
Secondary packaging, following activities are done:

Strip pack, Blister pack or Alu- alu packed tablets are packed in passed Printed Carton (Duplex
Box) and then in passed Corrugated Board Container.

Before secondary packing, following parameters are checked:

'On line rejects' such as strip, blister pack or alu- alu pack having printing mistakes, broken
tablets, unfilled pack etc are kept separately as Rejection.
Strip/ Blister pack/Alu- alu pack should pass the leak test.
5.4. Quality Control Department:
Quality control is a part of GMP concerned with sampling, specification, testing, and with the organization,
documentation and release procedures which ensures that the necessary and relevant tests are actually
carried out and that materials are not released for use nor products are released for sales or supply until
their quality has been judged to be satisfactory. QC lab is equipped with sophisticated equipments, various
chemicals, reagents and trained pharmacists and analysts. QC department performs analysis as per the
official pharmacopoeias and other validated procedures like In-House Specification to check if the tested
materials meet the specification or not. The major activities done in QC department are:
a.
b.
c.
d.
e.
f.
g.
h.
i.
j.
k.
l.

Raw material analysis

Intermediate product analysis
Finished product analysis
Packaging material analysis
Release or rejection of raw material, packaging material, intermediate products and finished
products
Stability studies(Maintaining proper RM and Finished product control sample and performing real
time stability study)
Reverse osmosis water testing
Calibration and standardization of laboratory equipments
Sampling and line clearance
Dispensing supervision
Microbial studies
Testing of returned goods
36

m. Maintaining quality control test records of all the analysis i.e. RM, PM, IPS.
Flow chart of QC activities

AA
nc
at
li
yv
si
it
si
e
s

37

Different Sections in QC lab

Document section
Microbiology section
HPLC section
Managers Office
Chemical reagents section
Heat generating room
Analysis area
Stability chamber sections
Instrumental section

QC is equipped with following instruments:

UV spectrophotometer
Karl Fischer Titrimeter
Dessicator
Weighing Balance
Hardness tester
Polarimeter
High performance liquid chromatography (HPLC)
Digital Ph meter
Sonicator
Centrifuge machine
pH meter
Water bath
Leak test apparatus
Autoclave
Vernier Calliper digital
Melting Point Apparatus
Distillation unit
Humidity chamber
Stability chamber
38

Magnetic Stirrer
Muffle furnace
Disintegration Test Apparatus
Dissolution Apparatus
Oven
Flame photometer
Potentiometer
Laminar Air Flow
Incubator
FTIR apparatus
Friability tester

Following activities are performed in QC:

Analysis of raw material (Active and Excepients); primary and secondary packaging material;
intermediate product for further processing; finished product for their release.
Calibration of instruments
Daily RO water analysis
Retaining the samples of starting material, intermediate, bulk products and finished products for
reference for all batches of products
Maintaining proper raw material and finished product control sample and performing real time
stability study and accelerated time stability study.
Keeping and maintaining the laboratory documents like:
specifications
procedures describing sampling, testing, records (including test worksheets and/or laboratory
notebooks), recording and verifying
procedures for and records of the calibration/qualification of instruments and maintenance of
equipment
a procedure for the investigation of Out of Specification and Out Of Trend results
testing reports and/or certificates of analysis
data from environmental (air, water and other utilities) monitoring, where required
validation records of test methods, where applicable
SOPs
records all the test/analysis performed
Investigations of complaints related to the quality of the products.
Establishing, validating and implementing QC procedures.
Evaluating, maintaining and storing the reference standards for substances.
Performing microbiological tests for water, raw materials, finished goods.

39

 Swab test
This test is performed to ensure that equipments and utensils are properly cleaned and does not cross
contaminate the active ingredients to next batch production. It is provided to determine compliance with
the requirements given in the individual monograph / specifications. Once this test is failed cleaning is
repeated and again swab test is performed to confirm the cleanliness.
Stability studies
This stability testing is to provide evidence on how the quality of an active substance or pharmaceutical
product varies with time under the influence of a variety of environmental factors such as temperature,
humidity and light. This enables recommended storage conditions, re-testing intervals and shelf-lives to be
established. Insufficient stability of a drug product can result in changes in physical (like hardness,
dissolution rate, phase separation, etc.) as well as in chemical characteristics (high risk of decomposition of
active substances).
In Florid, basically two types of stability studies are carried out :
a) Real time (long term) stability study: It is carried out every 3 months over the first year, every 6
months over the second year, and annually thereafter throughout the proposed shelf-life. i.e. 0, 3, 6, 12
months, for a 12 months study.
b) Accelerated stability study: A minimum of three time points, including the initial and final time points
(e.g., 0, 3, and 6 months), for 6-months study is recommended.

Stabilit
y Study

Real
time

Storage

Minim
um
time
period
covere
d
by
data at
the
time of
submis
sion

Condition
Tempera
ture

R
H

300 50C

65
%

5
%

12
months

40

400 50C

Acceler
ated

75
%

5
%

6
months

5.6 Quality Assurance:

Quality Assurance is a wide ranging concept covering all matters that individually or collectively influence
the quality of a product. It is the totality of the arrangements made with the object of ensuring that
pharmaceutical products are of the quality required for their intended use. Quality assurance therefore
incorporates GMP, ISO and other factors, including product design and development. The chain of quality
complies from the product design and product development stage up to the end user. The quality assurance
department is established to ensure compliance to the quality policy in every aspect of production and
quality control. The QA department ensures that the products are designed & developed in such way that
takes account of the requirements of GMP & GLP to guarantee the quality of the products till shelf life.
Principles of QA System
1.
2.
3.
4.
5.

Wide ranging concept.

Covers all matters that individually or collectively influence the quality of the product.
Totality of the arrangement.
To ensure that the drug is of right quality for the intended use.
Quality assurance incorporates GMP and also product design and development.

Activities of QA are as follows:

Documentation, records and its renewal of each and every aspect of the industry
Qualification
Product Recall Handling.
Self-inspection
Training Program
Validation
Retrospective
Prospective
Concurrent validation
Re-validation
41

Master Formula and Pacing Instruction

Log book maintenance
Site Master File
Deviation Log book etc.
Issuance of control documents( BMR,SOP,MFR, Site master file)
Dispensing of raw material
Specification of material, bulk, intermediate and finished products.
QC report handling
Batch release of finished products
Rejected Batch and rejected material Handling
Annual Product Review
Review of environmental and water quality analysis
Communication
Health and Hygiene
Problem identification and corrective action for the same.

In CTL Pharmaceutical, all the activities related to the product quality is handled by QA, QC and
production department.
5.6.1 Documentation:
Good documentation is a crucial part of Quality Assurance System. The rationale behind documentation is
to record important information with substantiation. Documentation is written proof/ evidence of any
activity. GMP requires that the manufacturing process be adequately documented throughout all stages of
operation. Before releasing the product for distribution, Quality Assurance should review the batch records
of all in-process tests and controls and of all test of final product to determine whether they conform to
specification so that they can be confident in the final product release. CTL Pharmaceutical has been
practiced good documentation practice to ensure their product quality.

Documents maintained in CTL Pharmaceutical are:

42

Site Mater File

Process Validation Records

BMR

Record of analysis of intermediate and

bulk products

Master File Record

BPR
SOP
IPQC test records
Product Specification
QC test records
Complaint record
Product recall record
Record Book of Packing Materials

Batch Entry Book

Sampling Log Book
In house training manual
Change control record
Internal audit record
Leave / ill record of employee
Finished product release slip
Validation record of AHU, RO plant
etc.

5.6.2 Validation:
Validation is defined as documented evidence which provides high degree of assurance that meets its
predetermined specifications and quality attributes. Validation is systematic approach to gathering and
analyzing sufficient data that will give reasonable assurance (documented evidence), based on scientific
judgment, that a process, when operating within specified parameters, will consistently produce results
within predetermined specifications.

Following are the different methods of Validation

1. Prospective validation:
Prospective validation shall be carried out before the process is commercialized. Minimum 3 consecutive
batches are to be considered. The important requirement for the validation is protocol preparation.
2. Retrospective validation:
The retrospective process validation is established documented evidence that a process what is intended to
be done is based on review and analysis of historical data.

43

3. Concurrent validation:
Concurrent validation is established documented evidence that a process is based on information generated
during actual implementation of the process.

4. Re-validation:
Repeated validation of an approved process to ensure continued compliance with established requirements.

5.6.3 Qualification:
Qualification proves that any premises, system and items of equipment work correctly and actually lead to
the expected results. New systems and equipment should pass through all stages of qualification including
design qualification (DQ), installation qualification (IQ), operational qualification (OQ) and performance
qualification (PQ) as appropriate.

Stages of qualification:

Design qualification

Installation qualification

Operational qualification

Performance qualification

Change control/Re-qualification

44

Products available in CTL Pharmaceuticals

S
.
N
.

Product
name

Generic
name

strength

Dosage
form

1
.

ACEAID

Aceclofenac

100 mg

Tablet

2
.

ALEXOF
EN

Fexofenadine
hydrochlorid
e

120/180
mg

Tablet

3
.

ALEXOF
EN 60 ml

Fexofenadine
hydrochlorid
e

30 mg

Liquid

ALFRAD

Cefadroxil

500 mg

Capsule

45

OX 500

5
.

ALTRIN

Cetrizine
hydrochlorid
e

5 mg

Liquid

6
.

AMD

Amlodipine

2.5/5/10
mg

Tablet

7
.

AMD-AT

Atenolol+
amlodipine

50/5 mg

Tablet

8
.

AMOX
CTL
60/90 ml

Amoxycillin

125 mg

Dry syrup

1
0
.

AMOX
CTL
250/500

Amoxycillin

250/500
mg

Capsule

1
1
.

AMP GEL
170

Alumunium
hydroxide+
magnesium
hydroxide+
methyl
polysiloxane

250/250/
50 mg

Liquid

1
2
.

AZITOP
500

Azithromyci
n

500 mg

Tablet

1
3
.

AZITOP
15

Azithromyci
n

200 mg

Liquid

BRONKO

Salbutamol+

2/4 mg

Liquid

46

4
.

MOL
EXPECT
ORANT

bromhexine
hydrochlorid
e

1
5
.

BRONKO
MOL 100
ml

salbutamol

2 mg

Liquid

1
6
.

BURNHE
AL PLUS
25g

Silver
sufadiazine+
chlorhexidine
gluconate

1%w/w/
0.20%
w/w

Ointment

1
7
.

C-TAB

Paracetamol
+
chlorphenir
amine
maleate+
phenyl
epherine
HCl

500/4/10
mg

Tablet

1
8
.

CALFER
OL

Calcium+
Vitamin D3

500
mg/250
IU

Tablet

1
9
.

CALFER
OL-CM

Calcium+
Vitamin D3

250
MG/200
IU

Tablet

2
0
.

CAREBO
MET
500/850

Metformin
HCl

500/850
mg

Tablet

47

2
1
.

CARBO
MET-ER
500/1000

Metformin
HCl

500/1000
mg

Tablet

2
2
.

CEPHA
D/S
60
ML

Cephalexin

125 mg

Dry syrup

2
3
.

CEPHA
CTL
250/500

Cephalexin

250/500
mg

Capsule

2
4
.

CHLORA
CTL60

Chloramphe
nicol

125 mg

Liquid

2
5
.

CHLORA
CTL
250/500

Chloramphe
nicol

250/500
mg

Capsule

2
6
.

CLAMPI
CTL

Ampicillin+
cloxacillin

250/250
mg

Capsule

2
7
.

CLOTIF
15g

Clotrimazol
e

1% w/w

Ointment

2
8
.

CLOTIFB 15g

Clotrimazol
e+
beclomethas
one

1% w/w /
0.025%
w/w

Ointment

48

dipripionate
2
9
.

CLOVAT
E

Clobetasol
propionate

0.05%
w/w

Ointment

3
0
.

CLOVAT
E-S

Clobetasol
propionate+
salicylic acid

0.05
w/w /3%
w/w

Ointment

3
1

CLOVIR
5g

Aciclovir

5% w/w

Ointment

3
2
.

CLOVIR
200/400/8
00

Aciclovir

200/400/
800 mg

Tablet

3
3
.

CLOX
CTL
250/500

Cloxacillin

250/500
mg

Capsule

3
4
.

CODMIN

Codiene
phosphate

15 mg

Tablet

49

3
5
.

COPAR

Paracetamol
+
codiene
phosphate

500/10
mg

Tablet

S
.
N
o

Product
name

Generic
name

strength

Dosage
form

3
6
.

CUFSUP
100ml

Levodropro
pizine

30 mg

Liquid

3
7
.

CYCLOD
ON

Dicyclomine
HCl+
simethicone

10/40 mg

Liquid

3
8
.

DICONA
C 30g

Diclofenac
sodium

1% w/w

Gel

3
9
.

DICONA
C PLUS
30g

Diclofenac
diethylamin
e+
methyl
salicylate+
oleum lini+
menthol

1.16%w/
w
/
10%w/w/
3%w/w /
5% w/w

Gel

4
0
.

DOX
CTL 100

Doxycycline

100 mg

Capsule

50

4
1
.

DOXOFI
L

Doxofyline

400 mg

Tablet

4
2
.

DYSPAM
80

Drotaverine
HCl

80 mg

Tablet

4
3
.

ETHRO
CTL 60ml

Erythromyci
n

125 mg

Liquid

4
4
.

ETHRO
CTL
250/500

Erythromyci
n

250/500
mg

Tablet

4
5
.

EXPULI
N 100ml

Ammonium
chloride+
pheniramine
maleate+
menthol

120/12.5/
1.14 mg

Liquid

4
6
.

F-CLOX
250/500

Flucloxacilli
n

250/500
mg

Capsule

4
7
.

FERON

Elemental
iron+ folic
acid+ zinc

120/0.5/2
0 mg

Capsule

FERON-

Elemental

100/1.5

Tablet

51

8
.

XT

iron+
acid

folic

mg

4
9
.

GERMO
LIN

Chlorhexidi
ne gluconate

0.2% w/v

Liquid

5
0
.

GABANE
T 100/300

Gabapentin

100/300
mg

Capsule

5
1
.

GLOSA
500

Glucosamin
e sulphate
potassium
chloride

500 mg

Capsule

5
2
.

HALVAT
E 15g

Halobetasol
propionate

0.05%
w/w

Ointment

5
3
.

HALVAT
E-S 15g

Halobetasol
propionate+
salicyclic
acid

0.05%
w/w/ 3%
w/w

Ointment

5
4
.

INDOMO
D 25/50

Indomethaci
n

25/50 mg

Capsule

S
.
N
o

Product
name

Generic
name

strength

Dosage
form

52

5
5
.

Isolax

Isapgol husk

49% w/w

Powder

5
6
.

KEPODE
X 200

Cefpodoxim
e

200 mg

Tablet

5
7
.

KEPODE
X
dry
syrup
30ml

Cefpodoxim
e

50 mg

Powder

5
8
.

KEPODE
X
dry
syrup 60
ml

Cefpodoxim
e

50 mg

Dry syrup

5
9
.

LANSOP
AZ

lansoprazol

30 mg

Capsule

6
0
.

LIPILAG
E 10/20

Atorvastin

10/20 mg

Tablet

6
1
.

LOTACE
25/50

Losartan
potassium

25/50 mg

Tablet

6
2

LOTACE
A

Losartan+
amlodipine

50/5 mg

Tablet

53

6
3
.

LOTACE
H

Losartan+
hydrochloro
thiazide

50/12.5
mg

Tablet

6
4
.

METHE
X

Mecobalami
n

500/1500
mcg

Tablet

6
5
.

METOR
ATE
25/50

Metoprolol
tartrate

25/50 mg

Tablet

6
6
.

MEZOR
AX

Paracetamol
+
chlorzoxazo
ne

500/250
mg

Tablet

6
7
.

MUROB
AN 5g

Mupirocin

2% w/w

Ointment

6
8
.

MYPRID
E 1/2

Glimipiride

1/2 mg

Tablet

6
9

NIBUCID

Nimesulide

100 MG

Tablet

54

7
0
.

PENISOL
VK

Phenoxy
methyl
penicillin

250 mg

Tablet

7
1
.

7PLEX
syrup 200
ml

Thiamine
hydrochlori
de+
riboflavin+
nicotinamid
e+
cynacobala
mine+
Dpantheol+
pyridoxine
hydrochlori
de

2/2.5/20/
2/3/0.75
mg

Liquid

7
2
.

7 PLEX
capsule

Elemental
zinc+
thiamine+
riboflavin+
pyridoxine
HCl+
cynacobala
mine+
nicotinamid
e+ folic acid

15/10/10/
2/7.5/75/
1 mg

Capsule

7
3
.

PRAZOL

Omeprazol

20 mg

Capsule

7
4

PROFIX
dry syrup

Cefixime

50/100
mg

Dry syrup

55

60ml

7
5

PROFIX
200/400

Cefixime

200/400
mg

Tablet

7
6
.

P-ROXI
20

Piroxicam

20 mg

Tablet

7
7
.

ROSEMI
DE 40

Frusemide

40 mg

Tablet

7
8
.

ROSEMI
DE-A

Frusemide+
amiloride

40/5 mg

Tablet

7
9
.

ROSEMI
DE-S

Frusemide+
spironolacto
ne

20/50 mg

Tablet

8
0
.

ROUTIN
5/10/20/40

Rosuvastin

5/10/20/4
0 mg

Tablet

8
1
.

SHAKTIJ
AL

Sodium
chloride+
sodium

2.6/2.9/1.
5/13.5 g

Powder

56

citrate+pota
ssium
chloride+
glucose
anhydrous
8
2
.

TERBIN
A 10g

Terbinafine
HCl

1% w/w

Ointment

8
3
.

TETRA
CTL
250/500

Tetracycline
hydrochlori
de

250/500
mg

Capsule

8
4
.

TRICON

Itraconazole
(enteric
coated
granules)

100 mg

Capsule

8
5
.

WINMO
L

Paracetamol

125 mg

Liquid

8
6
.

WINMO
L PLUS

Paracetamol
+ ibuprofen

125/100
mg

Liquid

8
7
.

XORPIC
500

Ciprofloxaci
n

500 mg

Tablet

8
8
.

ZINCOV
A 20

Elemental
zinc

20 mg

Tablet

57

Conclusion
The 18 days In-plant training at CTL Pharmaceutical Pvt. Ltd. was very informative, fruitful and
productive for me. It was a great opportunity for me to complete my in-plant training at CTL
Pharmaceuticals Pvt. Ltd. I feel very glad to spend my short period of time at CTL with friendly, cooperative, helpful and supportive staffs. Their throughout guidance and support have really helped me to
understand and learn many fundamental and practical things of pharmaceutical manufacturing and its
regulation within a very short period of time , for which I am very grateful to all the CTL Pharmaceuticals
team. I am sure that knowledge and skills I gained here will help me to boost up my career.
In this training period I got the knowledge about different departments of pharmaceutical industry
like Production, Quality Control, Storage, Quality Assurance etc and various manufacturing processes of
medicines.
Lastly I would like to convey my best wishes to CTL for its success in upcoming days.

58

59