A Practical Exposure On An In-Plant Trai PDF

A practical Exposure On
An In-plant Training Programme
On
The Acme Laboratories Limited
Training Period: 1st February to 12th February, 2016
The Acme Laboratories Limited Page 1

A Report
On
AN IN-PlANT TRAINING PROGRAMME
ON
The Acme Laboratories Limited
Submitted To:
Head OF QOD, Head of HR, Head of HR & Admin (Factory)
The Acme Laboratories LTD.
Submitted By:
Name ID Institute
Khandaker Anzuman Akter 121-29-383 Daffodil International University
Ms.Rotna Akter 121-29-402 Daffodil International University
Ms.Fatima Tuz Zohra 121-29-369 Daffodil International University

Mr.Rasel Al-din 121-29-378 Daffodil International University
Mr. Parvez Alam 121-29-386 Daffodil International University

ACKNOWLEDGEMENT
Alhamdulillah
First of all thanks to Almighty Allah as we have got chance to complete the industrial training
at The ACME Laboratories Ltd. Industrial training program is one of the most essential
parts of a student studying in a dynamic subject like Pharmacy.
For gathering complete knowledge there is no alternative for In-plant or industrial training
program which has to be accomplished by every student. This training is conducted by the
pharmaceutical industries in our country.
We are very grateful to our respected chairmen of our universities and Head of the
Department and of course our cordial thanks to Mr. S.A.B.M. Shahadat Ali, Head of QOD,
and Mr.Shamim Ahmed, In charge of QOD. The ACME Laboratories Ltd.Dhamrai, for
allowing us to have our in-plant training.
We would like to give our cordial thanks to the designated personnel and Mr. Khondaker
Amirul Islam to whom we reported during the training.
We would like to give special thanks to our in-plant training co-ordinator, to coordinate us
with different divisions of the plant and with their respective Head In-charge.
We would like to give our warmly thanks to the organization named CDC (Career
Development Center) who has arranged this training.
We would like to give our cordial thanks to the designated personnel Mr. Tushar Kanti
Kundu who arranged this training.
During this in-plant training in The ACME Laboratories Ltd. Dhamrai, we have got lots of
friendly co-operation from every people in every section starting from the Executive to the
workers. Thanks to all for their every friendly co-operation.
We are very happy to get a chance for intern in renowned The ACME Laboratories Ltd.
Name Signature
Khandaker Anzuman Akter
Ms.Rotna Akter
Ms.Fatima Tuz Zohra
Mr.Rasel Al-din
Mr. Parvez Alam

Table of contents
Sl.No. Topic Name PageNo.

1. Introduction 5
2. Company Profile 6
3. Quality Policy 7
4. Organogram 8-9
5. Quality Control 10-12
6. Finished Product Testing Section, QOD 13-15
7. Raw Materials Testing Section, QOD 16
8. Packaging Materials Testing Section, QOD 17-19
9. In-Process Quality Assurance Section, QOD 20-27
10. Process Validation and Specimen sample testing Section, QOD 28-30
11. Method Development & stability study Section, QOD 31
12. Microbiology Section, QOD 32-37
13. R & D Department, QOD 38-45
14. Tablet Section 46-65
15. Oral Liquid Section 66-71
16. Capsule, Dry Syrup, Cream & Ointment Section 72-80
17. Injection Section 81-83
18. Inhaler and Suppositories Section 84-88
19. Marketing and Sales Section 89-91
20. Ware House section 92-99
21. Conclusion 100
22. References 101

INTRODUCTION
A pharmacist is the person of drugs or the expert on drugs. He is the only expert on drugs, for
expertise regarding drugs requires knowledge in depth in all the facts of pharmacy. It is his
professional responsibility to know all about the drugs. No educational program other than
that in pharmacy provides the background to understand completely all about drugs. Among
the professions of pharmacists like community pharmacy, institutional pharmacy, whole sale
pharmacy, industrial pharmacy, government service, pharmaceutical education,
organizational management, in our country industrial pharmacy offers great opportunity to
the pharmacists. Industrial pharmacy is a profession of unique hybrid of business and
profession.
So an industrial pharmacist should have proper knowledge about drugs and also about
medical progress, commence marketing and technology. To be a self-sufficient pharmacist
beside academic knowledge practical knowledge is essential. This is why after appearing the
Bachelor of Pharmacy examination in-plant training was arranged by the department of
Pharmacy of Daffodil International University in renowned pharmaceuticals industry. This
training has sharpened our academic knowledge what we learnt in the last four years .We
have completed our training in The ACME Laboratories Ltd, a rich pharmaceutical
company in Bangladesh. By this training, each pharmacy student can achieve vast
experience; can correlate the theoretical knowledge with the practical experience. Thus
he/she can develop him/herself completely for pharmacy related job.
To take part in such type of training program we have been selected for The ACME
Laboratories Ltd. We have taken our training in The ACME Laboratories Ltd. which
ensures manufacturing & marketing of essential medicines with highest quality by following
GMP, GLP, CGMP, and ISO-9001 by all the modern technologies. The main dosage form
manufacturing by the respective company are solid as tablet & capsule, powdered as dry
syrup and liquid as syrup, suspension & eye drop. Semi solid as ointment, cream &
suppositories. Others are antiseptic cream, sterile products & Inhaler. In order to maintain
GMP, every procedure & equipment have its own STANDARD OPERATION
PROCEDURE. Our training program was from 1st February to 12th February, 2016. During
this period we have visited & worked in every section under the direct supervision of related
officers.

COMPANY PROFILE
The ACME Laboratories Ltd. is one of the premier pharmaceutical companies of Bangladesh
with a proven track record for manufacturing marketing branded generic pharmaceutical
products. The history of The ACME Laboratories Ltd. dates back to 1954 when a
proprietorship firm was founded to manufacture ethical drugs. It started with the modest
introduction of a few oral liquid products. The late Hamidur Rahman Sinha was the founder
of the firm and was the main visionary of the organization until his sad demise in 1994.
The firm was converted into a private Limited company in the year 1976. Commercial
operation at the modernized plant equipped with sophisticated and advanced facilities began
toward the end of 1983. Many challenges were overcome successfully to transform the
company from a small unit to what it is today. ACME celebrated its Golden Jubilee in 1995.
ACME has also endeavoured to strengthen its network in international marketing operations
to export its products abroad. We are optimistic about our continued growth and success.
The facilities includes-
Sophisticated manufacturing facilities in a state-of-the-art factory

Committed to provide quality medicine at affordable price
Strict adherence to WHO cGMP regulations
An ISO 9001:2008 certified company
Wide range of dosage forms & products
Opened office in Pakistan
Exporting successfully to 11 countries World-Wide
Separate QC Lab equipped with modern machineries like FTIR, TOC analyzer,
HPLC, GC, Atomic absorption spectroscopy etc.

QUALITY POLICY
1. Quality slogan of The ACME Laboratories Ltd. is Perpetual Quest For

Excellence
2. The ACME Laboratories Ltd. is committed to maintain state of art manufacturing
facilities for ensuring best quality products to the customers.
3. The company is devoted to
Increase sales growth

Increase productivity
Increase profit margin
Improve company image and customer satisfaction
Ensure continual improvement
4. ACME is committed to achieve excellence by proper execution of
ISO 9001-2008 Standard

WHO, cGMP Standard
Best practices that are proven effective

ORGANOGRAM OF QUALITY OPERATION DIVISION
BoD
Quality Operation Division
Quality Control Quality

R&D
Department Assurance
Department
Department
Microbiology Research Section I.P.Q.A Section
Specimen Sample & Product Qualification &

Raw Materials Department Validation
Section Section
Product Testing Method

Section Development & Compliance &
Validation Documentation
Section Section
Packaging Materials
Section Stability Testing
Section
Calibration. WS &
Inventory Section
Figure: Organogram of Quality Operation Division

Organogram of Manufacturing Division
Manufacturing Division
Tablet Liquid Dry Syrup Cream and Inhaler & Capsule Injection
Ointment Suppository
Figure: Organogram of Manufacturing Division

QUALITY CONTROL DEPARTMENT
Quality control may be defined as an effective system for coordinating the quality
maintenance and quality improvement efforts of the various groups in an organization so as
to enable production at the most economical levels which allows for customer satisfaction.
While quality is generally concerned with setting standards, appraising conformance to these
standards, acting when the standards are exceeded and planning for improvement in the
standard. A quality control program for pharmaceuticals is concerned with the batch-to-batch
uniformity of a product, as well as insuring that the final uniformity, safety, efficacy &
stability within established levels, which meet all legal, professional & company standards.
Quality control department of Acme Laboratories Ltd. is responsible for the day by day
control of the quality within the company. This department is supported with trained
analytical staffs i.e pharmacists, chemists & other technicians who asses and assure that
entire production process has been completed satisfactorily & satisfied all aspects of GMP
through preserving the purity & quality of the product.
STEPS OF QC:
Raw material sampling Testing Release of raw materials

mmmaterials
Production Sampling from granulation

Sampling after blending
gggranulation granulation
Passed for compression Testing after compression Passed for coating
Packaging Checking Passed for commercial release
Figure: Steps of QC

QUALITY CONTROL ACTIVITIES:
RAW
CALIBRATION
FINISHED
PRODUCTS
QC
MICROBIOLOGICAL
TESTS
WATER AND
EFFLUENT
PACKAGING
Figure: Diagrammatic Representation of Q.C Activities
In The ACME Laboratories Ltd. the quality control division is categorized

by the following:
Product Testing
Raw materials Testing
Packaging Materials
Microbiology Testing

INSTRUMENTATION OF QUALITY CONTROL SECTION
Table: Instrument used in quality control section
INSTRUMENTS ORIGIN FUNCTION
HPLC
Waters, USA
HPLCSystem-
Shimadzu, Japan For separation, identification & assay.
1,2,3,4,5,6,7,8,9
Dionex, Germany
GLC
Shimadzu, Japan Product identification, separation & assay.
(Gas Liquid
Chromatogram)
UV Visible Shimadzu, Japan Product identification & assay.
Spectrophotometer
Atomic Absorption Shimadzu, Japan For identification/ detection of metal (elemental
Spectrophotometer (AAS) analysis).
Dissolution Testing
Erweka, Germany Dissolution rate determination.
Apparatus 1,2,3
Disintegration Testing
Erweka, Germany Disintegration time determination.
Apparatus 1,2
Melting Temperature
Optical activity Melting point determination.
Testing Apparatus
pH Meter Mettler Determination of pH.

Toledo, Switzerland
Moisture Analyzer OHAUS Determination of moisture & bound water.
Switzerland
Potentiometer Mettler Toledo Used for titration & voltage change, pH change.
Viscometer Brookfied Determination of viscosity.
Leakage Tester ERWEKA, Germany Determination of Leakage.

Potentiometric Titrator METROHM, Determination of potency.
Switzerland
Conductivity meter HACH,USA Determination of conductivity in solution.
Dissolution Tester ERWEKA, Germany Determination of dissolution time.

Polarimeter OPTICAL ACTIVITY Determination of optical rotation.
LTD.
England

FINISHED PRODUCT TESTING, QOD
The product testing is a vital system to ensure the quality of product. The following
parameters are done for product testing-
(a) Solid Preparation

Description
Dissolution & Disintegration time
Weight Variation
Assay
Content uniformity
Hardness
Thickness
Friability test
Average weight
(b) Liquid Preparation

Appearance
Suspendibility
Potency
Weight per ml
Microbiological Limit Test
pH
(c) Semi-solid Preparation

Microscopic Examination
Assay
(d) Nasal Spray
pH
Identification
Assay
Total no. of spray per container
Uniformity of delivered dose
Particle size

Deposited amount size
Leak test
(e) Tests for Gel/Dry syrup/pediatric drop:

Identification of active ingredient
Microbial contamination (satisfactory/unsatisfactory)
pH value
Water per ml at 20C, gm.
Viscosity
Sedimentation test
Total solid
Color content
Alcohol content
Assay (Spectrophotometric /Titrimetric/HPLC)
(f) Tests for WFI:
Contents of vial/bottle
Sterility test
pH value test
Ammonia test
Nitrates test
Chlorides test
Sulphate test
Acidity/alkalinity test
Oxydizable substances test
Heavy metals test
Ca & Mg test
Residue on evaporation
Conductivity test
Water content

(g) For Packaging Materials
Description
Text
Color
Dimension
Weight (gm/m2)
Visual inspection for defects
Opacity & chemical test glass pack
Adaptability
(h) Control of Bulk Products
Each lot of bulk product is tested to ensure
Identity
Quality
Potency
Purity
Bulk products are tested following their MCP. Some products require compendia (BP/USP)
procedures for testing.

RAW MATERIAL TESTING, QOD
RAW MATERIAL is the basic material from which a good product is manufactured or made,
frequently used with an extended meaning in the primary production or manufacturing of a
good.
From different suppliers raw materials are stored in warehouse, and then they are sampled for
QC test. No production is carried out approval of QC.
There are raw materials suspension and paste for semisolid preparation, parental preparation,
END, MDI, DPI, suppository.
(a) Solid Raw materials

Identification
% of LOD
Sulfated Ash
Bulk density
Heavy Metal testing
Impurities
Melting point
Bulk density
Specific Optical Rotation
Water content test
(b) Liquid Raw Materials
Maximum tests for solid
Refractive Index
pH
Weight per ml
Viscosity

PACKAGING MATERIAL TESTING SECTION, QOD
PHARMACEUTICAL PACKAGING has to be carried out for the purpose of the safety of
the pharmaceutical preparations in order to keep them:
free from contamination,

hinder microbial growth, and
Ensure product safety through the intended shelf life for the pharmaceuticals.
Packaging is a critical tool in the pharmaceutical industry for product delivery and regulatory
compliance; many pharmaceutical companies will do all their packaging within a
contamination free environment or Clean room.
SOME COMMON PHARMACEUTICAL PACKAGING TECHNIQUES INCLUDE:
Foil and heat sealing;

Polyester and olefin package printing;
Polyethylene and polypropylene printing; and
Flatbed die cutting.
In The ACME Laboratories Ltd, for primary packaging the materials that are used are
as follows-
Poly vinyl chloride (PVC)
Aluminum foil
Poly vinylidene chloride (PVDC)
Glass vials and ampoules (USP type- 1 and 2, borosilicate and treated soda
lime respectively)
For secondary packaging material the following are used-

1. Carton There are three types ---
Swedish (tearing gives yellow color)
Cromolex (tearing gives white color)
Duplex (tearing gives brown color)
2. Shipment carton
3. Outer
4. Liner
5. Labels
6. Leaflets
7. Printed tape
THE FOLLOWING FORMS OF PACKS AVAILABLE IN THIS COMPANY
1. Strip pack
2. Blister pack
ANALYSIS OF PACKAGING MATERIALS
In this section, following parameters of a packaging material are checked & evaluated:
Description
1. Size
2. Inscription
3. Color
Text
1. Name
2. Label Claim
3. Price
4. Indication
5. Manufacturing Date
6. Expiry Date
7. Batch No.
8. Companys Name & Address
Color
Weight (gm/m2)
Adaptability
Visual Inspection of Defects
Opacity & Chemical Test for Glass vial
Identification Test for PVC & PVDC Blister Foil

DIFFERENT TYPES OF PACKAGING MATERIALS & THEIR TESTS:
Table: Types of packaging materials & tests
Packaging Materials Tests

PVC and PVDC Color, width, thickness, weight per unit area etc.
Carton Appearance, weight, moisture content (NMT 2%)
Shipping Carton Appearance, dimension, thickness & weight
Plastic Cap Appearance, weight, length, diameter, volume, capacity.
Dropper Appearance, weight, length, diameter, volume, capacity,
adaptability with bottle carton & plastic container.
Water Measuring Flask Appearance, weight, length, diameter, volume, capacity.
5ml Plastic Spoon Appearance, weight, length, diameter, volume, capacity

Bottle Height, neck diameter, body diameter, weight, machine
acceptance.

IN-PROCESS QUALITY CONTROL
IN-PROCESS QUALITY CONTROL SYSTEM lays emphasis on the responsibility of

manufacturers processors in ensuring consistency in quality during all stages of production
by adopting quality control drills and exercising control on raw materials and bought-out
components, manufacturing process, packing and final testing.
EVALUATION OF DOSAGE FORMS:
TABLETS
(a) General appearance: Size & shape, unique identification markings, Organoleptic
properties
(b) Content uniformity test: The content uniformity test is used to ensure that every
tablet contains the amount of drug substance intended with little variation among
tablets within a batch.
30 Tablets are kept aside. 10 tablets are assayed. 9 Tablets should have %limit of 85-
115% If more than 1 Tablet has 85-115% then, 20 Tablets are assayed Not more than
1 Tablet should have 75-125%.
(c) Hardness test or tablet crushing strength: It is defined as the force required
breaking a tablet in a diametric compression test. Tablet requires a certain amount of
strength or hardness and resistance to friability to withstand mechanical shakes of
handling in manufacture, packaging and shipping.
(d) Friability test: Speed 25 rpm for 4min. Acceptable range: 0.5-1 %.
(e) Weight variation: 20 tablets are taken and weigh individually to determine the
average weight of 20 tablets. Then it is compared with individual tablet weight to
average weight not more than 2 of the individual weights deviate from the average
weight by more than the percentage deviation and none deviates by more than twice
that percentage. U.S.P LIMITS, I.P LIMITS.

(f) Disintegration test: For most tablets, the first important step towards formation of
solution is breakdown of the tablet into smaller particles or granules, this process is
known as disintegration. -Disintegration apparatus: 6 glass tubes- 3inch length 10
mesh screen at the bottom. Temperature: 372C, Speed: 28-32 rpm.
(g) Dissolution test: Different types of dissolution apparatus:

Basket type
Paddle type.
Reciprocating paddle.
Flow through cell.
Paddle over disc.
Cylinder with membrane.
Reciprocating cylinder
Temperature: 370.5 C Speed: 25-150 rpm
Procedure:
Total tablets taken = 24, S1: 6 tablets taken Acceptable: If all of the tablets are not
less than (NLT) the monograph tolerance limit (Q) = 5%. If S1 fails S2: Another 6
tables are taken Acceptable: If average of 12 tablets is Q & no tablet is less than Q-
15% If S2 fails S3: 12 tablets taken Acceptable: No tablet less than Q & not more
than 2 tablets = Q-15%. USP limit for dissolution: NLT 75% of tablet dissolves in 45
min.

CAPSULE
(a) Raw materials: The gelatin of the capsule shells should be assayed for various
physical properties like bloom strength, viscosity, etc.
(b) Moisture permeation test: The degree & rate of moisture penetration is determined
by packaging the dosage unit together with a color revealing desiccant pellet. Expose
the packaged unit to known relative humidity over a specified time and observe the
desiccant pellet for color change. Any change in color indicates absorption of
moisture. By measuring pre-test weight & protest weight of pellet, amount can be
calculated.
(c) Content uniformity: 10 capsules are taken and subjected to assay. 9 of 10 capsules
should be in the range of 15 %( 85-115%) and 10th Capsule in the range of 75-
125%. If 2 Capsules are beyond 15% range. Then, 20 tablets are assayed. All
capsules should be in the range of 25 %( 75%-125 %.)
(d) Weight variation: for hard capsules: Weigh 20 capsules individually, and
determine the average weight. The individual weights should be within the limits of
90%and 110%of the average weight. If not all of the capsules fall within the limits,
weigh the 20capsules individually remove the contents of each capsule with the aid of
a small brush. Weigh the emptied shells individually.
Net weight of contents (individual) = the weight of shell -respective gross
weight.
Determine the average net content from the sum of the individual net weights.
Then determine the difference between each individual net content and the
average net content
Limits: Not more than 2 of the differences are greater than 10%of the
average net content No case is the difference greater than 25% wt range.
Limits: Not more than 6 of the 60capsules does the difference exceed 10%of the
average net content No case does the difference exceed 25%.

INJECTABLE
(a) Environmental control

(b) pH measurement
(c) Viscosity: Viscosity and consistency directly relates with stability of solutions.
Viscosity is measured by viscometer.
(d) Control on volume filled: The personnel working in the filling area should have
complete control on filling equipments.
(e) Osmolality (Occasionally): Osmolality is a count of the number of particles in a fluid
sample. The osmolality of a solution can be measured using an osmometer. The most
commonly used instrument in modern laboratories is a freezing point depression
osmometer.
(f) Conductivity measurement: Measured by using conductometer. It is also necessary
measure the conductivity of the vehicle used in sterile preparations. The conductivity
of the pure water is 0.055 S/cm (micro-Siemens/cm).
(g) Temperature for heat sterilized products: It is important to maintain the constant
temperature during heat sterilization of products. The temperature changes may cause
some undesirable changes like change in potency, change in isotonicity etc. The
temperature can be determined by normal thermometer, digital thermometer.
(h) Leakage test: Leakage test is employed to test the package integrity. This is done by
three Methods:
a) Visual inspection
b) Bubble point test
c) Dye test
(i) Clarity testing: Clarity testing is carried out to check the particulate matter in the
sample. It is practically impossible that every unit of lot is perfectly free from visible
particulate matter, that is, from particles that are 30 to 40 m and larger in size.
USP limits for large volume infusions:
Particle Size Particles limit

10m and larger/ml 50
25m and larger/ml 5

Visual inspection by naked eye each injectable is inspected visually against white
and black backgrounds. The white background aids in detection of dark colored
particles. The light or reflective particles will appear against the black back ground.
Instrumental methods also called as the particles count method. Particles counting
may be based on any one of the following principles
change in electrical resistance
light absorption
Light scattering.
(j) Sterility test: The test method for sterility of the product :
Membrane filtration
Direct inoculation of the culture medium
Membrane filtration Solutions to be examined must be introduced and filtered under
aseptic conditions all steps of this procedure are performed aseptically in a Class 100
Laminar Flow.
Hood pore size of 0.45 m
effectiveness established in the retention of micro-organisms
the size of filter discs is about 50 mm in diameter
(k) Pyrogen test:

LAL test Limulus amebocyte lysate (LAL) test to detect or quantify endotoxins of
gram-negative bacterial origin reagent: amoebocyte lysate from horseshoe crab
(Limuluspolyphemus). LAL reacts with bacterial endotoxin. It involves 3 methods
Gel clot method
Turbidimetric method
Chromogenic method

LIQUIDS
These are of two types
1. Monophasic liquids Ex : Solutions, Syrups, Elixirs, etc.

2. Biphasic liquids Ex : Emulsions, Suspensions
1. Monophasic liquids
(a) Clean and purified vehicle (water): Quality control technicians test the water
frequently to ensure that it is clean and pure before the syrup is made. The syrup is
also thoroughly filtered before filling in bottles.
(b) Light transmittance test: A light transmittance meter is a newer tool that is used to
check syrup color. In a light transmittance meter, a syrup sample is checked for
color by passing light through the sample. The percent of light transmission is
compared to light transmission rates set for different grades.
(c) Visual inspection: The ingredients and the final products are carefully examined
for purity and for appearance. Physical appearance of products for patient adherence
and compliance is critical so it should be Good looking, Elegant in appearance.
(d) PH measurement: The measurement and maintenance of pH is also very important
step in the Quality control testing. Generally there are 2 different types of methods
used in the measurement of pH. The simplest and cheapest is to dip a piece of pH
paper into the sample. And the other one is by using pH meter (for greater
accuracy).
(e) Leak test
2. Biphasic liquids
(a) Determination of viscosity: Determination of viscosity is done to assess the

changes that might take place during aging.
(b) Determination of particle size: It is performed by optical microscopy and Coulter

counter apparatus.
(c) Determination of phase separation (for emulsions): Phase separation may be

observed visually or by measuring the volume of the separated phases. Or by

subjecting the emulsions to various stress conditions like boiling, temperature
variations etc.
(d) Stability of suspensions
Sedimentation method: The measurement of sedimentation volume is the

most important parameter in the evaluation of stability of suspensions.
Rheological method: The viscosity of the suspension is studied at different

time intervals by using a good quality of viscometer.
Electro kinetic method: The determination of surface electric charge or zeta

potential of suspension is helpful to find out the stability of suspension.
Micromeritic method: The stability of a suspension depends on the particle

size of the dispense phase. A change in particle size distribution & crystal habit
may be studied by microscopy & counter coulter method.
POWDER FOR SUSPENSION

a. Bulk Appearance, odor, color
b. Filling: Room condition, fill weight, reconstituted volume, sealing of cap
PACKAGING
For Bottle/ Vial
Batch no. on Label
MFG date on Label
EXP. Date on Label, MRP
Quantity of product
Print & colour of Product
Cap Sealing/ security overprinting
PVC & PVDC for Blister & Strip Packaging
Color, Width
Thickness

Weight/10 cm
Inner Carton
Product Name & Label Claim
Batch no
MFG date, EXP. Date, MRP
Print & color
Spoon/ cap/ actuator
Leaflet
Shipping Carton
Product Name & Label Claim
Batch no
MFG date, EXP. Date
No. of packs per shipping carton
Size no. & adaptability

PROCESS VALIDATION AND SPECIMEN SAMPLE TESTING SECTION
PROCESS : Process is the manufacturing procedure of a product.
VALIDATION: Validation of a process is the demonstration the controlling the critical steps
of a process results in products of repeatable attributes (e.g. content uniformity) or causes a
reproducible event (e.g. sterilization).
A validated manufacturing process is one that has been proven to do what it purports or is
represented to do. The proof of validation is obtained through collection and evaluation of
data, preferably beginning from the process development phase and continuing through the
production phase. Validation necessarily includes process qualification (the qualification of
materials, equipment, systems, buildings, and personnel), but it also includes the control of
the entire processes for repeated batches or runs.
CLASSIFICATION OF VALIDATION:
Validation In pharmaceutical is classified as follows:
1. Cleaning Validation
2. Process Validation
3. Analytical method validation
1. Cleaning Validation
Cleaning validation is carried out to ascertain the procedure and method adapted for
cleaning of equipments, area, and is capable of giving desired cleanliness of
equipment can be ascertained by caring out trace analysis of active ingredient of
previous products active ingredient trace analysis.
2. Process Validation
Process validation is carried out on the manufacturing process or steps, which are
adapted during pharmaceutical manufacturing. The process adapted in pharmaceutical
manufacturing, should yield consistent results with respect to quality of product. The
laid down process is crosschecked for evidence of efficacy, and the results are
documented for each steps.

Types of Process Validation
a. Prospective process validation (also called premarket validation),
b. Concurrent process validation,
c. Retrospective process validation,
d. Revalidation.
a. Prospective Process Validation
Prospective process validation is process of gathering of data and documentary
evidence about a product and its process before it is sent to market or for distribution,
a new product validation or a validation after making a change in the master formula,
to determine if the product meet its predetermined standards.
b. Concurrent validation
It is a validation process where current production batches are used to confirm the
compliance of processing parameters and standards. Concurrent validation is the set
of validation procedures following prospective validation
c. Retrospective Validation
Retrospective Validation is a type of validation where the product is already
established. Process of such batches of products which are being sent to market are
studied to gather documentary evidence about the efficacy of the process or any
change in process tests and the product itself, such type of validation can be adapted
to validate product and the process even if the product and process is not validated
earlier.
d. Re-validation
Almost all GMP texts recommend that whenever there are significant changes in the
facility, equipment or process, revalidation should be carried out.
The FDA process validation guidelines refer to a quality assurance system, in place
that requires revalidation, whenever there are changes in formulation, equipment,
processes.

SPECIMEN SAMPLE TESTING:
SPECIMEN SAMPLES come from various manufacturer companies at PPIC division and
PPIC send to factory at validation & documentation section. Validation & documentation
section firstly sampling the specimen sample and then do the other test according to
compendia (BP/USP) or In-house Specification. Finally if found all parameters are ok then
validation section given approval the sample and the manufacturer name are included in
approved vendor list. PPIC division purchase raw material from which manufacturer
company those are selected as vendor.
SPECIMEN SAMPLE TESTING INCLUDES THE FOLLOWING TEST OF SAMPLE:
Appearance of solution
Heavy metal
LOD
Sulphated Ash
Appearance : Color of the sample.
Identification : By IR or HPLC, alternative method- Titration.
Related substance : According to specification.
Assay : According to specification.
Long term stability : According to ICH Guidline.
Solubility :
Very soluble : 1 gm sample dissolve in 1 ml solvent.
Freely soluble : 1 gm sample dissolve in 10 ml solvent.
Soluble : 1 gm sample dissolve in 10-30 ml solvent.
Sparingly soluble : 1 gm sample dissolve in 30-100 ml solvent.
Slightly soluble : 1 gm sample dissolve in 100-1000 ml solvent.
Very slightly soluble : 1 gm sample dissolve in 1000-10000 ml solvent.
Particularly in soluble : 1 gm in more than 10,000 ml solvent.

METHOD DEVELOPMENT & STABILITY STUDY SECTION
Method development is a part of R & D department. For analysis, methods those are
described in compendia, i.e., BP, USP, are followed. But in case of non-described raw
materials, the methods supplied by raw materials suppliers are followed. But, in many
instances, the supplied methods dont work. In those cases, a better & compatible method is
developed. Following steps are involved in new method development:
Development protocol, method trial, recording in the book, selection of the

method, opening of a new file.
Method writing, checking & correction.
Method verification by analyst.
Method approval.
After method development, it is validated. Then it is used as standard analytical procedure.
Stability Study:
There are two methods by which stability is tested: Real-time stability study, and Accelerated
stability study.Products are kept in the stability chamber at three different conditions
A) Real time stability Tempatature-30C 2C
Relative humidity (RH)-65% 5%
B) Accelerated Stability three conditions are maintained here
Accelerated condition: Temperature (40 2)C and RH (75 5) %
The product stays in the stability chamber and test perform at first after initial month then
after 3 month and then after 6 month. If after 6 months the degradation of the product is less
than 5% in 6 months then the shelf life is 2 years is determined.
The Analytical method development requires demonstration of suitable
Accuracy Linearity
Precision System Suitability
Specificity
Sensitivity

MICROBIOLOGY SECTION
This unit of study provides information of micro-organisms with particular reference to the
importance of micro-organisms in pharmacy and the pharmaceutical sciences and the
application of basic microbiological principles to the production of clean and sterile
pharmaceutical products in both community and hospital pharmacy and in industrial
manufacture.
Microbiology section is one of the vital sections of any pharmaceutical to ensure quality
product. The microbiology section of QC department in ACME Laboratories Ltd is a well-
decorated and segregated area that evaluates microbial load and particulate matter of both
raw materials and finished product particularly sterile products.
EQUIPMENT USED IN MICROBIOLOGY:
Airborne Particle Counter

Incubator
Microscope
Refrigerator
Shen stream sterilizer
Liquid particle analyzer
THE MICROBIOLOGY LABORATORY PERFORMS THE FOLLOWING TESTS:
In parenteral products
Bacterial endotoxin test.

Sterility test.
Liquid particle count test.
Air velocity measurement of laminar air flow and HEPA filter.
Non-parenteral products
Limit test
Microbiological Limit Test of raw materials & finished products.
Total aerobic bacterial & fungal count.
Detection of 4 pathogens, which are Escherichia coli, Pseuodomonas
aeroginosa, Salmonella species & Staphylococcus aureus.

Bioassay of raw materials & finished products
Bioassay is mainly performed to determine the potency of antibiotics.
ENVIRONMENTAL MONITORING:
Environmental monitoring by settle plat.
Monitoring Surfaces.
Contact Plate Method
Swab Test
Monitoring of Airborne Microorganisms.

Air Sampling by RCS Sampler
WATER ANALYSIS :
Rinse water of manufacturing vessel of Liquid, Cream, ointment (LCO) section & other used
water analyzed for total bacterial count & presence of pathogens like Coliforms &
Pseuodomonas aeroginosa.
METHOD FOR WATER TEST:
R2A media is the only media used to test the water. Three method involved here-
1. Pour plate method

Water sample (1 ml sample) collection
Placed in Petri plat, then poured R2A media (20ml) on plate
Incubation at 37C for 24-72 hours and 5 days
Count the bacteria and fungi
Figure: Process of Pour plate method

2. Filtration method
Sample water passed through a filter paper
Keep filter paper in R2A media
Incubation at 32.5C for 24-72 hours and 5 days
Count the bacteria and fungi
Figure: Process of Filtration method
LABORATORY TEST:
a. Sterility test
It is done for sterile raw materials and product of materials. 14 days observation are
requiring for sterility test. Two types
1. Direct method.
2. Membrane Filtration method.
Reagents are
Fluid thioglycolate media
Soyabeen casein digest broth
Types of filter used in Membrane filtration are;

Cellulose Nitrate filter
Hydrophobic filter

b. Limit test/Contamination test
Process of limit test
Prepare sample solution at desired conc.
Placed in sterile Petridish
Poured in suitable media
Allowed to grow the micro-organism by placing (into incubation for 2-5 days)
Count colony number
Approved or reject considering the specification
Figure: Process of limit test
Purpose: To measure the products containing tolerable quantity of micro-

organism.
c. Endotoxin test/LAL test

It is an in-vitro test method for pyrogen, LAL test means Limulus Amebocyte lysate
test. Limulus amebocyte lysate (LAL) is an aqueous extract of blood cells
amoebocyte from the Horseshoe crabe Limuluspolyphemus. LAL reacts with bacterial
endotoxin and lipopolysecharide (LPS), which is a membrane component of Gram
Negative Bacteria This reaction is the basis of the LAL test, which is used for the
detection and quantification of bacterial endotoxins.
Single test
0.25 ml in LAL and dissolve
Incubation at 37 C for 1 hr
Gel formation
Indicate presence of endotoxins
Figure: Process of LAL test

Purpose: To detect the presence of pyrogen in parenteral preparations.
The total testing process can be as follows
Sample collection Media preparation Sample preparation
Incubation Colony count Identification
Final result
Figure: Total testing process of preparations.
MEDIA USED FOR LABORATORY TEST:
Nitriunt Agar : Agar means solid.

Nitriunt Broth : Broth means Liquid.
FOR THE ENVIRONMENTAL INSPECTION FOLLOWING TEST ARE DONE -

Air particle count the air particle of the room of the total production area is
maintained not more than 100000.
Settle plate test in this test the plate is exposed to the environment for 4 hours using
TSA (Tripton Soya Agar) media is mainly used.
SWAB test the microbial count in the wall, floor and ceiling is monitored by this
method.
Table: Condition require for microorganism test given below
Type of Organism Duration Temperature

Bacteria 2-3 days 30C 37C (Optimum temp.
32.5C)
Fungus 5 days 20C 25C (Optimum temp.
22.5C)

Table: Air classification system for manufacture of sterile products
Grade Maximum number of Maximum number of viable

particles permitted per ft3 microorganisms per plate
0.5 m >5 m
A (Laminar air 100 0 less than 1
flow work station)
B 1000 7 5
C 10000 70 50

RESEARCH AND DEVELOPMENT DEPARTMENT
PRODUCT DEVELOPMENT (PD) is a wide concept in pharmaceutical area. Product

Development department is another vital part of any pharmaceutical which is responsible for
launching a new product in the market. From the pharmaceutical point of view it is part of
formulation, analysis and documentation of new invention of drug under this analytical work.
Product Development is divided into two parts according to the routine work. They are-
1) Formulation of a new product.
2) Analytical (Analysis and documentation of this formulated new product)
OBJECTIVES
Increasing the quality of product.
To save time & cost.
Increasing the patient acceptance.
Determine product validation
Determine product stability in market.
R &D DEPARTMENT D EALS WITH THE FOLLOWING FUNCTION:

New product formulation.
Reformulation
Reprocess
Trouble shooting
Preparation of BMR, BPR, Master formulation for a new product.
Development of existing product.
Source approval for API & excipients.
R&D also has to do process research to
Improve yield
Bulk scale-up
And finally from an experienced trial-and error method a formulation is developed.

NEW PRODUCT DEVELOPMENT
Steps of the development of a new product:
Step-1: Product information from marketing department along with necessary

attributes such as
Source
Sample
Q.C test (Characteristics, LOD/Water Content, PH, Potency etc.)
Step-2: Pre-formulation study of the active drug and excipients.

Chemical activity
Function
Compatibility studies
Boiling point, Melting point
Moisture content etc
Step-3: Collection of raw materials of active drug and excipients.
Step-4: Different trials for development of a stable, effective and active

formulation.
Step-5: Drug administration formalities include:

a) Submission of recipe to drugs administration which contains
Strength
Dosage form
Contraindication
Description
A Precaution
Side effect
M.R.P.
Indication
b) Sample admission (if INN product)
c) Approval of sample from drug administration and inclusion of price.
d) Drug Administration Registration number and license no.

e) Submission of Inclusion Dossier.
f) Final approval for commercial production.
Step-6: First stability study then Pilot batch trial.
Step-7: Readjustment If necessary.
Step-8: BPR preparation if every aspect is satisfied which contains

Product name
Code
Size
batch no
Theoretical yield
Batch size
Annexure etc.
Step-9: Transfer to production department for commercial production.

LAUNCHING A NEW PRODUCT INVOLVES A LOT OF WORK
Market study of Proposal from Product

the new product Management Department (PMD)
by PMD
Evaluation of existing facilities Feasibility study by PD
Consulting with the Engineering Department
Feasibility study by Cost Evaluation

PMD
Proposal Approved
Product File Open
Raw materials procurement requisition according to QA specifications
Lab batch produced by PD Stability testing
Pilot batch production (3 consecutive batches)
Galenical and Analytical method development and validation
Accelerated Stability testing (6 months)
Recipe sent to Drugs Regulatory Authority (DRA) for approval
Annexure approval
Commercial production
Figure: Process of launching a new product

REPROCESS
If the chemical assay for QC for a particular batch dont comply the standard then PD will
check the batch & take necessary action accordingly.
REFORMULATION
Selection of product for reformulation to improve the product quality, product stability,
manufacturing process, organoleptic properties of the product and to change elegance &
packaging mode of the product.
DOCUMENTATION
Preparation of product dossier for regulatory purpose.

Preparation of export document (e.g. manufacturing process, batch formula, and
stability data) as per requirement of respective countries.
AREAS
Formulation Section.
Tablet Compression room.

Coating room
Granulation, Drying & Milling Room.
Analytical Section
Stability study room

HPLC Room.
DT, Dissolution analysis room.
Documentation Room
Official Room

MACHINERIES PRESENT IN THE PRODUCT DEVELOPMENT DEPARTMENT IN
FORMULATION SECTION
Table: Machine used in the product development department
Machine Name Company Country of origin
Compression Machine Rimek India
Coating Machine Neo Cota Thailand
Tray Dryer Memmert Germany
Friability Tester Erweka Germany

Moisture Analyzer Sartorius Japan
Weighing Machine Sartorius Japan
LAB BATCH:
A lab batch is produced to see if the formulation is effective. The recipe of the lab batch is
sent to the DRA. It is also done for a feasibility study. The lab batch recipe undergoes various
corrections.
PILOT BATCH: The manufacturing procedure should be validated on at least three pilot lots
to identify the critical parameters in the product and process. Tentative limits fixed for the
critical variables may be modified from the data available by stability studies.
Prevention of any type of problem in existing product

Corrective and preventive action (CAPA, also called corrective action / preventive
action, or simply corrective action) are improvements to an organization's processes taken
to eliminate causes of non-conformities or other undesirable situations.CAPA is a concept
within good manufacturing practice (GMP), and numerous ISO business standards. It focuses
on the systematic investigation of the root causes of identified problems or identified risks in
an attempt to prevent their recurrence (for corrective action) or to prevent occurrence (for
preventive action).

Corrective actions are implemented in response to customer complaints, unacceptable levels
of product non-conformance, issues identified during an internal audit, or adverse or unstable
trends in product and process monitoring such as would be identified by statistical process
control (SPC). Preventive actions are implemented in response to the identification of
potential sources of non-conformity.
To ensure that corrective and preventive actions are effective, the systematic investigation of
the root causes of failure is pivotal. CAPA is part of the overall quality management
system (QMS).
Concepts
Clearly identified sources of data which identify problems that will be investigated.
Root cause analysis to identify the cause of a discrepancy or deviation and suggest
corrective actions of a problem which is identified.
A common misconception is that the purpose of preventive action is to avert the occurrence
of a similar potential problem. This process is all part of corrective action, because it is a
process of determining such similarities that should take place in the event of a discrepancy.
Preventive action is any proactive methodology used to determine potential discrepancies

before they occur and to ensure that they do not happen (thereby including, for example,
preventive maintenance, management review or other common forms of risk avoidance).
Corrective and preventive actions both include investigation, action, review, and further
action if so required. It can be seen that both fit into the PDCA (plan-do-check-act)
philosophy as determined by the Deming-Stewart cycle.
Investigations to root cause may conclude that no corrective or preventive actions are
required, and additionally may suggest simple corrections to a problem with no identified
systemic root cause. When multiple investigations end in no corrective action, a new problem
statement with expanded scope may be generated, and a more thorough investigation to root
cause performed.
Implementation of corrective and preventive actions is the path towards improvement and
effectiveness of Quality Management Systems. Corrective actions is nothing but the action/s
based on the problem identification. The problem or a non-conformance can be identified
internally through staff suggestions, management reviews, document reviews or internal
audits. Customer complaints / suggestions, customer rejections, non-conformities raised in
customer / third party audits and recommendations by the auditors are the external sources
which lead to find the root cause of the problem.
Root cause is the identification of the source of the problem where the person(s), system,
process or external factor is identified as the cause of the non-conformity.
Corrective action is the re-work / rectification activity of the non-conforming products as per
ISO 9001:2008 (8.5.2).
Preventive action is prediction of problem and trying to avoid the occurrence (fail safe)
through self-initiated actions and analysis related with processes/products. This can be
initiated with the help of active participation of staff members/workers through improvement
teams, improvement meetings, opportunities for improvement during internal audits,
management review, customer feedback and deciding own goals quantized in terms of
business growth, reducing rejections, utilizing the equipment effectively, etc.
Example of Corrective Actions
Error Proofing
Visible or Audible Alarms
Process Redesign
Product Redesign
Training or enhancement/ modification of existing training programmes
Improvements to maintenance schedules
Improvements to material handling or storage
In some cases a combination of such actions may be necessary to fully correct the problem.

TABLET SECTION
TABLET is a pharmaceutical dosage form. It comprises a mixture of active substances and

excipients, usually in powder form, pressed or compacted from a powder into a solid dose.
The excipients can include diluents, binders or granulating agents, glidants (flow aids) and
lubricants to ensure efficient tableting; disintegrates to promote tablet break-up in the
digestive tract; sweeteners or flavors to enhance taste; and pigments to make the tablets
visually attractive. A polymer coating is often applied to make the tablet smoother and easier
to swallow, to control the release rate of the active ingredient, to make it more resistant to the
environment (extending its shelf life), or to enhance the tablet's appearance. The compressed
tablet is the most popular dosage form in use today.
MATERIALS RECEIVING SYSTEM FOR TABLET :
Materials for production are received by following way-
Requisition for RM & PM by production department according to

BMR & BPR
Requisition for BMR & BPR by the production department to QA

department
Approved by production manager
Issued by warehouse manager
Dispensing by dispensing pharmacist
Checked by QA officer
Approved by QA department
Received by production officer

Observed Product:
Brand name Generic name Drug Class Therpeutic class
V-PLEX Vitamin-B Vitamin-B Specific Vitamin

complex preparations Preparations
FEROCIT Ferrous fumerate Iron & Vitamin Iron Deficiency

+ folic acid Combined Anaemias
preparations
MIZOLAM Midazolam Benzodiazepine Sedation &

hypnotics Hypnosis
V-PLEX (film coated) Vitamin-B Vitamin-B Specific Vitamin

complex preparations Preparations
STERON Dexamethasone Glucocorticoids Corticosteroid

hormones
Product Change Over:
Product change over means the changing and cleaning process of production machineries
parts, production room & other equipments after production of every batch or every products.
Example: In case of tablet compression, product change over includes the cleaning and
changing process of tablet compression machine such as die, punch and all of the contact
surface. This function is very important to prevent product to product cross contamination
Commonly used exipients in tablet manufacturing:
Agents Examples
Diluents Maize starch, Calcium hydrogen phosphate, lactose.
Binding agent Starch paste, Povidone etc.
Lubricants Polyethylene glycol, purified talc, Mg-stearate, Aerosil-200.
Glidants Colloidal silicon dioxide, talc.
Disintegrants Starch-1500, Aerosil-200

Coloring agents Allura red lake.
Sweetening agents Granulated sucrose, saccharine-Na.

Flavoring agents Orange flavor, Anise oil, vanilla, perfume rosa.
Humectants: Glycerin, sorbitol, ethylene glycol.
Shining agents: Tritanium dioxide, Mg-stearate

Preservatives Methyl paraben, propyl paraben
Dissolution rate Na-lauryl sulfate, Corsecarmelose Na.
enhancer:
Surfactants: Cremephor , colloidal silicon dioxide, tween-80, span etc.
Machineries used for granulation:

Name of machine Manufacturer Purpose
Planetary mixture -3 Ganson - India To mix the ingredients.

High speed mixture-2 Sainath & Saizoner To mix the ingredients.
mixture- India
Multi mill Ganson - India To reduce the size of granules.
Drum Mixture-1 Bangladesh To blend.

Roller compactor CLIT- India For slugging.
Fluid bed dryer-6 Alliance and Ganson - To dry the granules.
India
Tray dryers-3 Bangladesh To dry the exicipent.
Blister For primary packaging
packing machine
Strip packaging For primary packaging
machine
Dehumidifier For room temperature &
humidity control

Methods of tablet manufacturing:
Pharmaceutical tablets are prepared with active ingredient and suitable excipientsby the
following method-
Method of tablet manufacturing
Wet granulation Dry granulation Direct compression
Granulation: Granulation is the process in which the powder particles of raw materials are
made to form larger particles in order to facilitate compression for the production of tablet.
All the materials are received from the dispensing unit and granulation is performed. For
suitable granulation, it is required to have 30-40% powder and 60-70% granules and also 1-
5% moisture in compressing particles
Granulation is done;
To improve the flow properties of powder materials.

To get better the compression characteristics of the mix (blend).
To prevent segregation of the constitution of the powder mix
Two types of granulation processes are performed in The Acme Laboratories Ltd
1. Dry granulation:
Substances, which are heat and moisture sensitive and do not compress well after wet
granulation are formulated by Dry granulation.
2. Wet Granulation:
The substances, which are not water sensitive and cannot be made by direct compression and
dry granulation, are formulated by wet granulation.

General Procedure of Wet Granulation
Dispensing / Weighing
Dry mixing of API & diluents
Dry mixing of API & diluents
Adding binding solution into RMG
Drying (using Fluid Bed dryer)
Milling & Sieving (using Multimiller)
Final drying by FBD
Lubrication & Blending
Compression
Core Tablet formed

Dry granulation process
It is possible to form granulates without the addition of a granulating fluid, by techniques

generically referred to as dry granulation. These methods are useful for materials that are
sensitive to heat and moisture but which may not be suitable for direct compression.
General Procedure of Dry Granulation
Dispensing
API + Excipients + Lubricants
Mixing With Double Cone Blender
Slugging
Size reduction with Multimiller
Granules + lubricants
Mixing + Sieving
Transferred into Compression

Direct compression
Direct compression is the term used to define the process where powder blends of the drug
substance and excipients are compressed on a tablet machine.
Flowchart of Direct Compression
Dispensing and Weighing of raw materials
Sieving
Blending
QC test for Yield %
Direct compression

TABLET MANUFACTURING PROCESS
Wet
Dispensing
Dry Granulation Granulation
API &
Dry mixing of API &
Excipients Excipients by RMG
Binder preparation: Wet mixing: By

Sieving
Paste or solution form RMG/PLM
Mixing: Drum Mixing is continued until a

mixing Paste or solution form lump formation is observed
Slugging: By Wet milling: by Cone Mill

compression discharge of wet Granules by
Machine using appropriate mesh
(generally 8mm)
Lubrication
Direct compression Drying: By fluidized
Bed Dryer (FBD)
Crashing: By Multi
Sieving
Mill
Sizing or crushing: According
to the - specification by BMR
Blending: Bin mixer
Tablet compression Lubrication
Primary Packing
Coating
Core Tablet Packaging Coated Tablet
Warehouse

Compression:
After obtaining the approval from Quality Assurance department, the granules are
compressed to form tablets of specified weight, hardness and thickness, the process of
compression is performed in eight (8) separate rooms, each room equipped with compression
machine, weighing machine, batch production record sheet, hygrometer, a de-duster and de-
humidifier.
The compression pressure, shape and size of dies and punches are adjusted according to the
need. Time to time lubrication and cleaning of compression is done.
Flowchart of compression:
Particle rearrangement / inter-particle slippage / transitional repacking
Deformation at Points of Contact
Fragmentation and Deformation
Bonding
Deformation of the solid body
Decompression
Ejection
Compressor: It consists of:
Hopper
Feed frame
Dies
Dies table
Pineum
Upper Turret & Lower turret
Upper punch
Lower punch
Cam track-Upper cam track, Lower cam track
Upper roller
Lower roller
Wheel
Channel ( Outlet)
Each Tablet is formed by a tooling set; the tooling must meet many requirements to
satisfy the needs of dosage uniformly, production efficacy and esthetic appearance.Dies,
Punches & their setup is known as tooling system.
Two type of tooling usually used.
a. B-tooling
b. D-tooling
D tooling is thicker than B-tooling

D tooling is used for both large & small tablets but B-tooling is used only for small
tablets.
Machineries used for Compression

No. of compression machines-9
Two types of machines: D-tooling-3
B-tooling-6
Name No. of station Manufactured By
CADMACH-1 35 CADMACH MACHINARY LTD.

INDIA
CLIT-2 37 INDIA
CLIT-3 29 INDIA
CLIT-4 29 INDIA
CLIT-5 29 INDIA
CADMACH 55 Cadmach, Machinery Ltd.-INDIA
CADMACH 37 Cadmach, Machinery Ltd.-INDIA

GZP 32 Cadmach, Machinery Ltd.-INDIA
Chinise Company
During and after compression, following tests are preformed:
Hardness
Relative humidity
Thickness and diameter
Moisture content of tablet
Friability Temperature
Disintegration time
TABLET COATING:
Coated tablets are tablets covered with one or more layers of mixtures of various substances
such as natural or synthetic resins, gums, gelatin, inactive and insoluble fillers, sugars,
plasticizers, polyols, waxes, coloring matter authorized by the competent authority and
sometimes flavoring substances and active substances. The substances used as coatings are
usually applied as a solution or suspension in conditions in which evaporation of the vehicle
occurs. When the coating is a very thin polymeric coating, the tablets are known as film-
coated tablets.
Coated tablets have a smooth surface which is often colored and may be polished; a broken
section, when examined under a lens, shows a core surrounded by one or more continuous
layers with a different texture.
OBJECTIVES OF TABLET COATING:
1. To protect against deterioration by environmental factors like sunlight, temperature

variations, moisture, environmental gases etc.
2. To facilitate swallowing.
3. To mask taste and odor.
4. To increase shelf-life.
5. To enhance aesthetic appeal and brand image.

6. To facilitate product identification during manufacture and prevent wastage during
packing and handling.
7. To provide enteric release properties for release in the intestinal tract.
8. To facilitate identification of oncological drugs.
MACHINES USED FOR COATING:
Name Manufacturer
Rama cota Thailand
Neo cota India
Gans cota India
CLASSIFICATION OF C OATING:
Mainly three types of coating are performed in the solid section. They are as follows:
Coating
Sugar coating Film coating Enteric coating
Aqueous coating Organic coating
Two types coating are observed in the ACME Laboratories Ltd. This are
1. Film coating
2. Enteric Coating
1. Film coating: Film coating is the process, which involves the deposition of a
membrane, consisting of polymer, plasticizer, colorant and possibly other additives on
to the surface of a pharmaceutical dosage form, typically a tablet or granule.

Following materials are used for film coating
a) Hydroxy propyl methyl cellulose

b) Polyethylene glycol
c) Methylene chloride
2. Enteric Coating: An enteric coating is a barrier applied to oral medication that
controls the location in the digestive system where it is absorbed. Enteric refers to the
small intestine; therefore enteric coatings prevent release of medication before it

reaches the small intestine.
Following materials are used for enteric coating:
a) Cellulose acetate phthalate.

b) Hydroxy propyl methyl cellulose phthalate
c) Diethyl phthalate
d) Polyvinyl acetate phthalate (PVAP)
Factors affecting the quality of film coatings:
1. Interaction between the core material (substrate) and the applied coating
2. The drying process.
3. The uniformity of distribution of the coating.
4. Distance between tablet and sprary gum.
Observed coating tablet:
Film coating: A-ZYME tablet
V-PLEX tablet
Enteric coating: A-ZYME tablet
Coating Factors
Distance
Pan speed
Spray Rate
Inlet & Outlet Temperature
Dosing Speed
Pan Press
Atomic Air Pressure
Appearance
PREPARATION OF COATING SOLUTION AND PROCESS OF COATING:
(Coating agent+solvent)mixing the solution properly by propeller
Coating solution
Setting the inlet & outlet temperature, pan speed air pressure &distance of gun to tablet
bed
Charging tablet in the caoting solution by the nozzle
Spraying the coating solution by the nozzle(spray gun)
Turning off the exhaust fan & blower
Spaying of the pollishing agent & rolling the tablets
Coating is complete,after down the temperature (40c) tablets are ready for removing
from the coating bed
Figure: Flow chart of Coating process

COMMON PROBLEMS ASSOCIATED WITH TABLET COATING:
Following problems develop either during the coating process or once the process has been
completed.
LOGO BRIDGING
Cause:
1. Surface characteristics of the product being coated
2. Inadequate adhesion of film coating
3. Inadequate design of logo (e.g. too detail/fine logo)
Remedy:
1. Modify core formulation to include more hydrophilic ingredients
2. Increase core porosity
3. Using formulation with increased adhesion property.
4. Increase area within the debussing and modified angles.
CORE EROSION
Cause:
1. Inherent softness or high friability of core.
2. Excessive pan speed in coating process.
3. Spray rate too low.
4. High sensitivity of core to moisture as coating is applied.
Remedy:
1. Increase mechanical strength of core.
2. Decrease pan speed.
3. Increase spray rate.
EDGE CHIPPING/EROSION
Cause:
1. Low mechanical strength of coating
2. Excessive pan speed
3. Low solid content in coating liquid

4. Low spray rate
5. Sharp edges on tablets
6. Worn tablet punches
Remedy:
1. Using formulation with increased mechanical strength
2. Decreased pan speed
3. Increase solid content in coating liquid
4. Decrease spray rate
5. Use modified punch design
PICKING/STICKING:
Cause:
1. Spray rate too high
2. Inadequate drying condition
3. Pan speed too low
4. Inadequate atomization of coating liquid
5. Poor distribution of coating liquid
Remedy:
1. Decrease spray rate.
2. Increase drying condition.
3. Increase pan speed.
4. Increase atomizing air pressure/volume.
5. Increase number of spray gun
CRACKING:
Cause:
1. Low mechanical strength of coating, exacerbated by inadequate plasticization,
excessive pigmentation.
2. Core has significantly different thermal expansion characteristics than coating.
3. Extended strain relaxation of core after compaction.

Remedy:
1. Selecting formulation with increased mechanical strength and elasticity properties.
2. Avoid use of mineral type fillers (e.g. CaCO3, CaSO4, MgCO3 etc.)
3. Extend holding period of tablets prior to submitting them to coating process.
PEELING:
Cause:
1. Low mechanical strength of coating
2. Poor adhesion of coating to tablet surface
Remedy:
1. Using ingredients of improved mechanical strength.
2. Using ingredients with improved adhesion properties.
ORANGE PEEL /ROUGHNESS :
Cause:
1. Viscosity of coating liquid is too high
2. Poor atomization of coating liquid
3. Excessive drying condition
4. Over wetting (causing coating too rub)
Remedy:
1. Decrease solid content of coating liquid
2. Increase atomizing air pressure/volume
3. Decrease inlet air temperature/flow rate
TWINNING:
Cause:
1. Spray rate too high
2. Pan speed too low
3. Inappropriate tablet shape

Remedy:
2. Increase atomizing efficiency
3. Increase pan speed
4. Select new tablet shape that decrease chances of flat surfaces coming into contact
during application of coating liquid. (e.g. avoid capsule shape tablet with thick side
wall)
TABLET-TO-TABLET COLOR VARIATION
Cause:
1. Too little coating applied
2. Inadequate mixing of tablet during coating
3. Poor opacity (or hiding power)
4. Solid content of coating liquid too high
5. Insufficient number of spray gun
Remedy:
1. Increase quantity of coating applied
2. Increase pan speed/increase improve baffle system
3. Reformulate coating with respect to colored ingredients or use a pacified white pre-
coat.
4. Decrease solid contents of coating liquid.
5. Increase number of spray gun.

Packaging Area:
The area is situated in the first floor. After compression of tablets and coating (if required)
the tablets are packed either in blister pack or in the strip pack.
Blister package:
Blistering materials: Following materials are used in blister packaging
1. PVC (Polyvinyl chloride)

2. Polyethylene laminated aluminum foil.
3. PVDC
4. Alu-Alu foil.
Machineries used for Blister Packaging
Total blister Machine-12

Automatic-6
Semi-automatic-6
Name Manufacturer Speed(tab/hr)
Horn noack West germany 70,000
Strip package:
A strip package is a form of unit dose packaging which is commonly used for the packing of
tablets and capsules.
Striping materials:
Polyethylene laminated aluminium foil.

Machineries used for Strip Packaging
Total machine-5
Name Manufacturer
Strip sealing machine-1 India

Ganson

Ganson
NIMCO

Ganson
Responsibilities of Tablet Section:
After the recommendation for the production of a batch, at first the requisition of
required raw materials is sent to ware house department.
QC & QA approved required raw materials of specific amount is then sent to the
dispensing unit.
Accurate weighing of materials.
Rechecking of the dispensing materials.
Mixing and granulation
Lubrication
Compression
Coating (if necessary)
Packaging and packing
Each step is carried out according to Standard Operating Procedure

ORAL LIQUID SECTION
The oral use of liquid pharmaceuticals has generally been justified on the bases of ease of
administration to those who have difficulty swallowing solid dosage forms. A drug
administrated in solution is immediately available for absorption and in most case, is more
rapidly and efficiently absorbed than the same amount of drug administered in a tablet or
capsules.
Liquid Department of ACME Laboratories Ltd. is as follows-
Liquid Department
Antacids Others liquid
Suspensions Emulsion Syrups Suspensions
Observed products:
Brand name Generic name Therapeutic Class
PROFEN Ibuprofen Inflammation and

Rheumatic Diseases
Equipments used in Liquid Department:
Compounding Vat.
Stainless steel vessel
Silversion stirrer
Water pump
Liquid transfer pump.
Utensils
Stock vessel

Auto filling and sealing machine.
In cleaning process the following materials are used:
Tape water, Purified water,UV treated water
JET powder
70% IPA (Iso-propyl alcohol).
FUMIGATION:
Na-Nitrite 100 ml (6.9%W/V). It is given to the pipe line.
250 ml formalin sprayed in the whole room for whole night.
ROOM CONDITION:
0
Double door system, positive pressure in the room, temp28 C.
Preparation of Antacid Charge Room:
It is essential to prepare the room after Antacid production. The room must be prepared
before 02 hours of Antacid production. Following steps are taken in preparing the room
Cleaning the room

Fumigation (Formalin & sodium nitrate)
Temperature control ( Not more than 28C )
Excipients used:
Agents Name
Sweetening agents Sodium saccharine, Aspartame, Neotaml etc.
Suspending agents Na-CMC, Hydroxy propyl methyl cellulose etc.
Thickening agents Aerosil
Preservatives Methyl paraben, Propyl paraben
Surfactants Tween-80
Buffering agents Citric acid, Sodium citrate
Colouring agents Orange red colour
Flavouring agents Lemon essence

GENERAL MANUFACTURING PROCESS OF ORAL LIQUIDS:
The general manufacturing of oral liquids in the liquid section of ACME Laboratories Ltd is
briefly described below with a flowchart -
Weighing of active ingredient/s along with excipients

Mixing of excipients with certain amount of Demineralized (DM) water as specified in the
batch Production Record (BPR) by the aid of a mechanical stirrer

Addition of active ingredients

Passing through a pump to the storage vessel

Transfer of the solution to the filling vessel through 0.2 Cartridge filter.

MANUFACTURING FLOW CHART OF SUSPENSION:
In liquid section oral suspension, syrup etc. are manufactured. During our visit, we have
observed the manufacturing of Oxycone Suspension which is given below-
Al, Mg dried gel are taken into the charge vat for Hydration
Addition of sweetening agent
Addition of Aluminum hydroxide compressed gel
Continuously stirring by silverson stirrer
Addition of suspending agent
Addition of preservatives
Addition of coloring, flavoring, buffering agent
Addition of monochloramine water to get10ppm for prevention of microbial growth.

Stirring continuously
Volume adjustment
Sample-1 Send to microbial section Sample-2 Send to QC dept.
If the result is ok
Then the product sends to Filling and sealing unit
Labeling
Packaging
Figure: Manufacturing process of suspension

MANUFACTURING FLOW CHART OF SYRUP:
Collection required amount of water & sugar.
When temp. Goes to 100 0 C
Adding preservatives
After 20 min, cooling start
Addition wetting agent when temp. Below 450 C
Addition of active ingredient
Addition of co-solvent, buffering agent
Addition of sweating agent
Addition of color & flavor
Volume adjustment
Filling
Sealing
Packing
Figure: Manufacturing process of syrup

MACHINERIES USED FOR COMPOUNDING (FOR SYRUP AND FOR ANTACID):
The machineries and utensils that are used for compounding are listed below:
1. Compounding vessels (capacity: 500L, 250L,210L,1000 L,2500L,3000L)
2. Silverson stirrer
3. Filter press pump
4. Colloid mill
5. Transfer pump and
6. Storage vessels
BOTTLE WASHING AND DRYING:

The bottle are washed both internally and externally with DM water. The washed bottles are
dried at 140oC for 120 min. For antacid preparation, bottles passed through CL-water.
Table: Machine used in bottle washing and drying
Name Capacity Manufacturer

Bottle washing machine 100-1 20 bottle/min India
Automatic filling, sealing & 6 channels,100 bottles/min India
labeling machine
OBSERVATION:
1. Cleanliness and environmental are strictly maintained.

2. Temperature, humidity, aqurately maintained.
3. Water purity aqurately maintained.
4. Purified water is used.
5. Microbial contaminations are maintained.
6. Separate bottle washing & drying room.
7. All machines are operated according to standard operating procedure.
8. Machines are calibrated timely.

Capsule, dry syrup, Cream & Ointment section
Capsule Section
Capsule may be defined as solid pharmaceutical dosage form in which medicinal and/or non-
medicinal inert substances are enclosed within a tasteless, hard or soft soluble small shell or
container made up of a suitable gelatin.
The ACME Laboratories Ltd. produces almost 32 types of capsules, most of them are
antibiotics, and others are hematinic vitamins, antidiarrheal etc. The ACME Laboratories
Ltd. use only hard gelatin capsule for their production.
TYPE OF CAPSULES BASED ON CONSISTENCY :

Hard-capsule and soft-capsule:
The size and capacity of hard gelatin capsule Shell:
1. For human : 000, 00, 0, 1, 2, 3, 4, 5

2. For animals : 10, 11, and 12
Hard gelatin capsule shell consisting of:
1. Basic ingredients : Gelatin, Sugar, and Water.

2. Other ingredients : Dyes, preservatives (e.g. SO2), Blur agent (e.g. TiO2),
flavoring agent''
Soft capsules shell consisting of:
1. The basic ingredients : Gelatin, tenderizer (poly-ol), Sugar, Water (6-13%)

2. Other Materials : Dyes, preservatives, blur agent, flavoring agent, enteric
coating (for a capacity of 1-480 Minims (1 minim = 0.06ml)
3. OBSERVED PRODUCT:
In my training period I observed various capsule productions. These are:
1. Lopamid capsule (Loperamide Hydrochloride), Antibacterial,

2. A-flox 500mg (Flufloxacillin Sodium), Antibacterial.

CAPSULE SHELL SIZE :
Capsule shells are supplied as a number of sizes. The number varies from 000 to 5, the
former being largest and later the smallest. The exact amount of medicament which can be
filled in a particular size of capsule shell depends upon the density of the materials to be
filled in. Generally capacity varies from 600mg to 30mg.
We know that, Capsule filled weight = Tapped bulk density capsule volume.
Then, Capsule volume = Tapped bulk density/weight of capsule.
Most widely used capsule sizes are 1 and 2. The largest capsule shell 000 is used for
veterinary purpose.
CAPSULE FILLING AREAS:
There are three distinct areas for encapsulation in The ACME Laboratories Ltd.
1. Penicillin area
2. Cephalosporin area
3. Non-penicillin and non-Cephalosporin area
FILLING ROOM CONDITION

1. Temperature : must kept at 20 to 25oC
2. Relative Humidity : not exceed 50%
FILLING THE CAPSULE SHELL

First, the weighed amount of active ingredients and additives filling operation. Now the
empty capsule shell are taken to separate them into cap and body. The body is taken filled
with the prepared powder mixer or granules. Now the cap is pressed in the body to close it.
Finally the filled capsule shells are ejected for cleaning and polishing.

MANUFACTURING FLOW CHART
Weight of raw materials
Sieving of all raw materials
All Ingredients blending (Drum mixing)
Capsule shell filling
Checking
Polishing
Blister/Strip Sealing Checking
Packing
Figure: Manufacturing process of capsule
MACHINERIES USED:
Table: Machine used for capsule preparation
Name of the machine Manufacturer Purpose
Drum mixer Bombay To mix the active ingredients

with excipients
Semi-automatic capsule India To fill capsule shell with
filling machine SCORPIO medicaments
Strip sealing machine India To seal

GANSONS
Blister sealing machine Germany To seal
HORN NOACK

DRY SYRUP DEPARTMENT
Dry syrup is the preparation that is formulated as dry powder but administered orally as
liquid dosage form. They are prone to hydrolysis during extended exposure of moisture. they
are to be reformulated by mixing with certain amount of cooled boiled water and should be
used up within certain periods(generally 5 to7 days at normal tempature.
The ACME Laboratories Ltd. produces three different formulations for Dry Syrup
1 Powder for suspension

2 Powder for syrup
3 Powder for paediatric drops.
Physical plant design
It is divided into two areas
1) Manufacturing area (blending or mixing area)

2) Filling and Sealing area
Ingredients Used
Ingredients Justification
Cefradine (micronized powder) Active ingredient
Dried sucrose powder Sweetening agent
Raspberry red color Coloring agent
Aerosil-200 Absorbs moisture Increase flow properly Suspending
agent
Sodium benzoate Preservative
Banana/Raspberry trusil flavors Flavoring agent
Observed product
Sefril (Cefradine) powder for suspension 100 ml

In process control
1 Manufacturing: Relative Humidity should not exceed 50% and temperature should be
in between 25-28oC.
2 Filling/Sealing: Weight variation, relative humidity, temperature and sealing check.

Manufacturing Flow Chart
Weighing of all ingredients
Sieving of ingredients
With different sieve size
All ingredients Blending/mixing

Bottle washing and
Drying at 130oC
Filling of dry syrup in bottle
Sealing of Bottles
Checking
Packing
PRECAUTION:
1. Manufacturing area, utensils, sieve must be cleaned according to SOPs.
2. Room temp. is about to 28oC and RH not exceeds 50%.
3. Workers must healthy and must wearing clean dressing, head cover, and face cover.

CREAM SECTION
PHARMACEUTICAL CREAMS are semi-solid preparations containing one or more

medicinal agents dissolved or dispersed in either water-in-oil or an oil-in-water emulsion or
in another type of water washable base. After application of the cream, the water evaporates,
leaving behind a thin residue film of stearic acid or other oleaginous component.
In The ACME Laboratories Ltd. there are two adjacent rooms for the manufacture of
ointments and creams.
Eye ointment (aseptic)

Skin ointment and cream (non-aseptic)
Machineries Observed in cream section:
Jacketed S.S Planetary Italy To mix the active ingredients with

mixer/vat MONITA excipients
Homogenizer/colloid mill India To prepare homogenize mixture.

GANSONS
Semi auto tube filling and India For filling and sealing purpose.
sealing machine

PROCESS FLOW OF CREAM PRODUCTION PROCESS
Aqueous phase mixing at 700 C for 30 Oil phase melt in Stainless steel jacketed
min in a Stainless steel jacked vessel emulsifier at 300 c for 30 min
Stirring with stirrer
Oil phase is transfer to the content of

aqueous phase to vacuum emulsifier
Stirring with Silverson stirrer and cool down

at 450 c
Add the active ingredients directly to vacuum

emulsifier and mix the product for 30 min
Send the sample advice sheet to the QC for

sampling
Filling, sealing and Packing
Figure: Production process of cream
OBSERVED PRODUCT:
Table: Observed product
Brand Name Generic Name Therapeutic Class
PERMIN Cream 15gm Ibuprofen BP Inflammation and

Rheumatic Diseases

OINTMENT SECTION
OINTMENTS are semi-solid preparations in which active medicaments r solid phase dispersed
in oil phase. Ointments are intended for external application to the skin or mucous
membranes. Ointments may be medicated or not. Unmediated ointments are used for the
physical efforts they provide protestants, emollients, or lubricants.
PROCESS FLOW OF OINTMENT PRODUCTION PROCESS -
Oil phase melt in stainless still

jacketed planetary mixer by heat and Cool down to about 400C Add Active ingredients
raise the temp. at 1500C, keep for 1
hr.
Homogenizer Storage Vessel Send sample to QC and Packaging & send to

Filling in tube warehouse
Figure: Production process (Ointment)
SPECIAL CARE FOR EYE-OINTMENT:
Tubes for eye ointment are sterilized.

The room is sterilized with UV radiation and fumigation is performed with formalin.
Ointments must free from gritty particles.
pH viscosity and consistency is strictly maintained (Monitored by Q.C).

MACHINERIES FOR OINTMENT PREPARATION:
Table: Machine used for ointment preparation
Jacketed S.S Planetary Italy To mix the active ingredients with

mixer/vat MONITA excipients
Homogenizer/colloid mill India To prepare homogenize mixture.
GANSONS
Semi auto tube filling and India For filling and sealing purpose.
sealing machine
Observed Products:
Table: Observed products
Brand Name Generic name Therapeutic class

A-TETRA Tetracycline Ophthalmic preparations

INJECTABLE SECTION
INJECTABLE are sterile and pyrogens free products that intended to be administered in the
body with the help syringe and needles through various routes such as intravenous (IV),
intramuscular (IM), intrathecal (IT), intraperitoneal (IP) etc. The ACME Laboratories Ltd.
produces 39 categories injectables in vials and ampoules meant for administration in the body
through IV or IM routes and The ACME Laboratories Ltd. has separate for Injectables which
consists of several sub units:
Compounding area
Aseptic rooms for filling and sealing
Sterilization room (autoclaving and terminal sterilization)
Vials and ampoules washing and sterilizing room
Packaging and packing room.
The ACME Laboratories Ltd. produced three types of Injectables, they are:
Aseptic products
Terminally sterilized products
Powder for injection
EQUIPMENT USED FOR PARENTERAL PREPARATION SECTION:
Equipment Use
For washing area : 1. Washing of vial/ampoule.

1. Ampoule /Vial washing equipment. 2. Washing & rinsing.
2. Distilled water & holding tank. 3. Drying components.
3. Drying oven. 4. Components collecting & storage.
4. Laminar air flow system.
For sterilizing equipment : 1. Moist heat sterilization.

1. Autoclave. 2. Liquid sterilization by filtration.
2. Membrane filtration units. 3. Dry heat sterilization.
3. Oven.
For bulk preparation area :

1. Bubble point testing equipment. 1. Testing filter integrity.

2. Double distilled plant. 2. Liquid preparations.
3. Filtering device. 3. Filtration.
4. Measuring equipment. 4. Volume measurement.
5. Mixing vessels/glass jars. 5. Collecting filtrate.
For aseptic filling area : 1. Filling line.

Under positive pressure, supplied with HEPA 2. Filling & sealing of products.
filtered air, minimum 20 air-changes, 3. Clean air protection.
controlled environment etc. Entry with sterile
dress through changing room, limited number
of people working at a time.
1. Conveyor.
2. Filling & sealing machine.
3. Laminar work bench.
MANUFACTURING CONDITION:
Room condition:
Room temperature : 20-25oC
Room humidity : >50 5%
Pressure difference : 10-15pascle
Clothes, utensils and removable parts of the machine: autoclave at 121oC for
20 min.
Depending on particle count aseptic rooms are classified as follows:
Class-100 : Not more than 100 particles (0.5 p)/ft air
Class-10,000 : Not more than 10,000 particle (0.5 p)/ft air
Class- 100,000 : Not more than 100,000 particles (0.5 p)/ft air
The Laminar air flow chamber is a class-100. Ampoule and vial filling is done under the
laminar airflow system.

MANUFACTURING OF I NJECTABLE PRODUCT:
Empty ampoules washing, sterilization and cooling
Solution preparation
Filtration
Filling and sealing (class 100)
Terminal sterilization (if necessary)
Visual inspection
Blister sealing
Packing
Figure: Manufacturing process of liquid Injectable

INHALER SECTION
Among three MDI & DPI producer of Bangladesh, ACME is of them. Inhaler may be defined
as pressurized packaging system that depends on the power of a compressed or liquefied gas
or any other mechanical stress to expel the contents from the container.
The ACME Laboratories Ltd. produces two different types of Inhaler system
1. Metered Dose Inhaler (MDI)

2. Dry Powder Inhaler (DPI)
1. Metered Dose Inhaler (MDI)
Metered dose inhalers are a special type of drug delivery systems, by which, a
predetermined dose is released as a spray on actuation of a metering valve present in a
special type of device named inhaler, which makes possible of the administration of an
inhalant into the respiratory tract. In MDIs, drug is either dissolved or suspended in liquid
propellant mixture together with excipients, including surfactants & presented in a
pressurized canister fitted with metering valve. When released from the canister, the
formulation undergoes volume expansion in the passage within the valve & forms a
mixture of gas & liquid before discharge from the orifice. The high speed gas flow helps
to break up the liquid into a fine spray of droplets
Observed product: Salflu 250 Rotacap Dry Powder Inhaler (DPI)

Manufacturing process:
Active Drug: Salmetarol Xinafoate, Fluticasone Propionate.
Receiving raw materials
Acclimatization (for 3 hours)
Mix accurately inhalac and lactose sorbolac for 10 min in a container
Mix the API
Seiving (40 mesh)

Mix for 5 min
Seive it (40 mesh)
Mix 5 mins
Seive it (40 mesh)
Mix 15mins
Keep it Container
Send to QC for Sampling
Fill it
Container Fill
Package
Figure: Manufacturing process Dry Powder Inhaler (DPI)

SUPPOSITORIES
This dosages form especially designed for those patient who unable to take solid, liquid and
parental drug forms. This form also suggested for those patient who are in serious condition
and need immediate action. Suppository is as medicated solid dosage from generally
intended for use in the rectum, vagina and to a laser extended, the urethra. Rectal and
suppositories usually employ vehicle that melt or softened at body temperature, whereas the
vaginal suppositories, sometime called pessaries, are also made as compress tablets that
disintegrate in the body fluid.
Brand Name Generic name Therapeutic class

CIPRO-A Ciprofloxacin bacterial infections
Manufacture of suppositories
In The ACME Laboratories Ltd. an automatic machine is used for the manufacture of
rectal & vaginal suppositories. By this machine, mixing, pouring, cooling and ejection is
performed in a single preparation. The machine contains a rotary cooling chamber to cool and
solidify the suppository.
Machine observed:-Automatic suppository machine-SARONG (Italy)
Function: Suppository compounding, filling and sealing.

PROCESS FLOW OF SUPPOSITORY PRODUCTION PROCESS
50 C
Manufacturing Vessel Melting Cooling (40C)
Sieving 40 mesh Addition of active Machine storage

screen drug vessel (40C)
15
min
Filling pump (40C) Mouth sealing & batch Cutting
coding (120C)
Packaging & send to

warehouse
Figure: Manufacturing process of suppository
SECONDARY PACKAGING SECTION

This section deals with the checking of procured packaging and packing materials as well
monitors the proper packing of finished products for their correct label, batch number,
manufactured and expiry date. the tablets are packed either in blister pack or in the strip pack.
Blister package:
A blister package in excellent form of unit dose packaging .It provides excellent environment
protection, coupled with an esthetically pleasing and efficacious appearance. It also provides
user functionality in terms of convenience, child resistance and now temper resistance
Blistering materials: Following materials are used in blister packaging

PVC (Polyvinyl chloride)
Polyethylene laminated aluminum foil.
PVDC
Alu-Alu foil.

Strip package:
A strip package is a form of unit dose packaging which is commonly used for the
packing of tablets and capsules.
Striping materials:
Polyethylene laminated aluminum foil.

MARKETING AND SALES DIVISION DEPARTMENT
The pharmaceutical industry in Bangladesh is one of the most developed hi-tech sectors
within the country's economy. In 2000, there were 210 licensed allopathic drug-
manufacturing units in the country, out of which only 173 were in active production; others
were either closed down on their own or suspended by the licensing authority for drugs due to
noncompliance to good manufacturing practices or drug laws. The industry manufactured
about 5,600 brands of medicines in different dosage forms. There were, however, 1,495
wholesale drug license holders and about 37,700 retail drug license holders in Bangladesh.
After the promulgation of Drug Control Ordinance - 1982, the development of this sector was
accelerated. The professional knowledge, thoughts and innovative ideas of the
pharmaceutical professionals working in this sector are the key factors for these
developments. Due to recent development of this sector, the industry is exporting medicines
to global markets, including the European market. This sector is also providing 97% of the
total medicine requirement of the local market.
OVERVIEW OF NEW PRODUCT LAUNCHING

1. Line Extension
2. New Product
A. 1st time in ACME
B. Pioneer
1st Time in ACME
i. IMS DATA (Market Size, Growth, Share)
ii. 4P DATA
Pioneer
i. FDA Approval
ii. Mother Campus
iii. Indication
iv. Population
v. Clinical Study

A Flow Chart of New Product Launching:
MB (Marketing Brief) to PDD
Sale Forecast (Monthly, Per FP and Sale) to Costing Department reply to us

on Profit Grade (A+++,A++,A+,B+,B,C,D, E,F)
Management Approval Sheet
Recipe Submission Letter to PDD (Regulatory Affairs Drug (DGDA) Submit)
PDD Start Stability (6 month accelerate)
RM (Raw material purchase letter)
DML submit to DGDA
DGDA provide DAR no
Price approval received for DGDA
Production forecast to factory
Marketing Circular
OVERVIEW OF THE COMPANY
The ACME Laboratories Ltd. is a global pharmaceutical company committed to creating

value for patients, shareholders, employees and society by discovering and commercializing
innovative products that satisfy unmet medical needs and lower healthcare costs.
This division has mainly the following departments
National Sales Department
Marketing Department

Export Department
Training Department
Research Department
ACMES VALUES
The following are the views of the ACME on the Values:
Respect for people

Integrity
Sense of Urgency
Networking
Creativity
Empowerment
Courage
JOB RESPONSIBILITIES OF E XECUTIVES/SR. EXECUTIVES, PMD
Identification of new product

Marketing plan
Sales analysis
Promotion materials development
New product Launching work
Conducting of Training
Market Visit
Free Sample Allocation
Communication with Sales Personnel
Communication with Media
Government or other institute orders for medicine
ISO related work
Other Routine Work

WAREHOUSE SECTION
Warehouse is the area where the initially received incoming materials stored and issued for
production after necessary quality activities. Warehouse activities considered as one of the
major part of any manufacturing industry.
The Warehouse department of The ACME Laboratories Ltd. includes the following sections:
1. Raw materials Warehouse

2. Packaging materials Warehouse and
3. Finished goods Warehouse
Besides there are some common areas which are using by all the sections; like as-
I. Cold and Cool room

II. Rejected materials room
III. Non-conforming materials room
IV. Loading/unloading Area
The ACME laboratories Ltd. has a large warehouse. It is six storied building. Each storey
consists of different materials or product. Such as-
Ground Floor : For finished goods storage

1st Floor : For raw materials storage
2nd Floor : For packaging materials storage
3rd Floor : For packaging materials storage
4th Floor : For packaging materials storage
5th Floor : For packaging materials storage
The main working standards of Warehouse are as follows:
a. Receiving.
b. Production issuing.
c. Finished goods storage & Distribution
Here, FIFO principle is strictly followed- FIFO means First In First Out.
If required then FEFO principle is followed-FEFO means First Export First Out.

AREAS OF WAREHOUSE :
Quarantine area: Purpose of Quarantine area

To receive the raw materials
To store the material before it passed the QA test
To manage the materials properly and systemically.
Released area: Purpose of released area
To store the approved materials
To store the approved materials in different conditions as specified by the
manufacture.
Dispensing area
The area from where raw materials and packaging materials are dispensed according
to the requisition sheet for the production. Raw materials, packing materials and
finished products kept in different places should be labeled properly. Only the
approved (green tagged) materials are brought to the dispensing area. Materials that
come first are dispensed first according to the FIFO (first in first out) rule.
Finished product area
This is the area where the finished products are stored after the total manufacturing
process.
Working Procedure
The standard operating procedure are available in ACME Laboratories Ltd. At present
there are 19 standard operating procedures and the warehouse personnel maintain
strict adherence which the standard operating procedures during performing their job.
As per company policy the ware house material management following Periodic
Inventory Method by using both software and manual documentation.
Company goals, Quality Objectives and Role Profiles are available and well
described.
Flow chart of all major activities that is describes in the working methods and ISO
9001:2008 guidelines.
Some important and major activities are:
Ensure the reception of right materials.
Issue require materials for production within time limit.
Finished goods receive from production and distribute timely.
Monitoring of temperature and humidity.
Clean both materials and areas.
Materials management.

Storage Areas of Warehouse
Raw Materials Area:
Location: Level 02 (1st floor) of warehouse building.
Facilities: Quarantine Area, Release Area, Sampling Booth, Dispensing Booth, Separate area
for cephalosporin materials, Penicillin materials and Narcotic materials.
Storage Temperature: Below 25 C and ambient.
Activities: Receiving of raw materials and issue of raw materials to production.
Raw Materials Receive System:
Checking of vehicle with related document
Unloading
Cleaning of incoming materials
Checking for damage/excess/loss
Information entry Material Receiving Register
Preparation of GRI and Quarantine Label
Transfer of the materials to the quarantine area of warehouse with Quarantine Label
Sending GRI to Quality Control Department
If release then attach release label and transfer to release area and software entry and
If reject then attach reject label and send to reject store
Informing PPIC about the rejection of materials

Raw Material Issue to Production:
Receiving BMR from production
Checking of Bin Card
Information entry in the BMR
Arranging of required released materials as per FIFO/FEFO system
Information entry in Bin Card
Issuing materials to the dispensing booth
Dispensing of raw materials and issue to production
Returning excess materials to the warehouse and information entry in inventory software
Storing of the returned excess materials in a separate location of Warehouse
Packaging Materials Area:
Location: Level 03 (2nd floor to 5th floor) of warehouse building.
Facilities: Quarantine Area, Release Area, Separate area for primary and secondary
packaging materials, under lock and key facilities for printed labels and dedicated area for
exportable items.
Storage Temperature: Below 25 C and ambient.
Activities: Receiving of packaging materials and issue of packaging materials to production.

Packaging Materials Receive System:
Checking of vehicle with related document
Unloading and storing
Cleaning of incoming materials
Checking for damage/excess/loss
Information entry in Material Receiving Register
Preparation of GRI and Quarantine Label
Transfer of the materials to the quarantine area of warehouse with Quarantine Label
Sending GRI to Quality Control Department
Informing PPIC about the rejection of materials

Packaging Material Issue to Production:
Receiving BPR from production
Checking of Bin Card
Information entry in BPR
Arranging of required released materials as per FIFO/FEFO system
Information entry in Bin Card
Issuing materials to the production and information entry in Inventory software
Storing of the returned excess materials in a separate location of Warehouse and information
entry in inventory software
Finished Goods Area:
Location: Level 01 to Level 03 (Ground floor to 2nd floor) of warehouse building.
Facilities: Quarantine Area, Release Area, separate area for products need to be stored under
controlled temperature.
Storage Temperature: 15 C to 20 C and ambient.
Activities: Receiving of finished goods and distribution as FIFO & FEFO policy.

Finish Goods Receive System:
Delivery of Finished goods from Production to Warehouse with Goods Receiving Note
Checking of quality and quantity according to Goods Receiving Note
Transfer of Finished Goods to the quarantine area of warehouse with Quarantine Label
Information entry in the Finished Goods Receiving Register
Informing PPIC about the rejection of Finished Goods
Finished Goods Dispatch:
Receiving of Requisition of Finished Goods from Central Sales Center
Checking of availability Finished Goods
Sending request to quality Assurance for release (if required)
Preparation of Delivery challan, Issue voucher and gate pass
Arranging covered van for loading Finished Goods
Information entry in Finished Goods register as well as Inventory software
Exit of Finished Goods Vehicle from Warehouse

Observed Product:
Area Temperature Product

Raw Material Area Controlled Temperature 15 C to 20 IBUPROFEN, SUCROSE,
C VILDAGLIPTIN
Cool Temperature 2 C to 8 C MIFEPRISTONE,
VITAMIN D3
Ambient SORBITOL, PROPYLENE
GLYCOL
Packaging Area Controlled Temperature 15 C to 20 ALUMINUM FOIL, GUM
C
Ambient MOST OF THE PRODUCT
Finished Goods Area Controlled Temperature 20 C to 25 INHALER,
C SUPPOSITORIES,
INJECTION
Quarantine Area 15 C to 20 C V-PLEX, PHOTOCID,
RANIDIN
PHARMACEUTICAL WAREHOUSE should be well situated, well laid out, clean and well
secured. This enables:
Easy and efficient management.
Good preservation of drugs
Safety for staff and stocked goods.
COMMENTS:
All materials are properly labeled.

Documentation system is excellent.
Here first in first out principle is strictly followed.

CONCLUSION
After completing our In-Plant training in The ACME Laboratories Ltd, We are fully satisfied
because it is a company with superior ethical culture. We got full freedom to observe all of
the activities & functions of The ACME Laboratories Ltd.
The objective of the In-plant training was the partial fulfillment of our B.Pharm Courses and
for the achievement of practical experience about manufacturing of quality drugs. During the
In-plant training the process of manufacturing and maintaining quality according to GMP
guideline were observed. The function and performance of quality assurance and production
department are unique and appreciable. By the overall performance of all sections, The
ACME Laboratories Ltd. is producing quality products and thus serving the nation. Under
all circumstances ACME Laboratories Ltd. meets the local regulatory quality standard, which
even is higher or more rigorous. Always its journey is to excellent.
ACME Laboratories Ltd. besides providing local pharmaceuticals need has been exporting its
product to various countries. Again the fact, The ACME Laboratories Ltd is recognized as
an ISO-9001: 2008 certified company.
Two weeks in In-plant training has been completed successfully by the help of all the
employee of The ACME Laboratories Ltd. Our achievement during this training will
eventually help us in our professional life.
Hopefully One day The ACME Laboratories Ltd will be the top one companies in our
country.

REFERRENCES:
1. http://acmeglobal.en.gongchang.com/
2. http://www.acmeglobal.com/AcmeLabs/Products/Human/prod_human1100.htm
3. Briefings obtained from different department of ACME.
4. www.pharmacybd.com
5. Pharmaceutical Excipients - Raymond C Rowe.
6. Cooper & Gunn, 11 editions, Dispensing for Pharmaceutical Students.
7. Remington- The Science & Practice of Pharmacy (Vol I & II).
8. British Pharmacopoeia BP.
9. United State Pharmacopoeia USP.
10. http://www.bddrugs.com/search.php
11. http://acmeglobal.com
12. https://en.wikipedia.org/wiki/Corrective_and_preventive_action
-----------The End------------

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A practical Exposure On

An In-plant Training Programme

The Acme Laboratories Limited

Training Period: 1st February to 12th February, 2016

The Acme Laboratories Limited Page 1

The Acme Laboratories Limited

Ms.Rotna Akter 121-29-402 Daffodil International University

Ms.Fatima Tuz Zohra 121-29-369 Daffodil International University

Mr. Parvez Alam 121-29-386 Daffodil International University

The Acme Laboratories Limited Page 2

The Acme Laboratories Limited Page 3

Sl.No. Topic Name PageNo.

The Acme Laboratories Limited Page 4

The Acme Laboratories Limited Page 5

The facilities includes-

Sophisticated manufacturing facilities in a state-of-the-art factory

The Acme Laboratories Limited Page 6

1. Quality slogan of The ACME Laboratories Ltd. is Perpetual Quest For

Increase sales growth

4. ACME is committed to achieve excellence by proper execution of

ISO 9001-2008 Standard

The Acme Laboratories Limited Page 7

Quality Operation Division

Quality Control Quality

Microbiology Research Section I.P.Q.A Section

Specimen Sample & Product Qualification &

Product Testing Method

Figure: Organogram of Quality Operation Division

The Acme Laboratories Limited Page 8

Figure: Organogram of Manufacturing Division

The Acme Laboratories Limited Page 9

Raw material sampling Testing Release of raw materials

Production Sampling from granulation

Passed for compression Testing after compression Passed for coating

Packaging Checking Passed for commercial release

The Acme Laboratories Limited Page 10

Figure: Diagrammatic Representation of Q.C Activities

In The ACME Laboratories Ltd. the quality control division is categorized

The Acme Laboratories Limited Page 11

Table: Instrument used in quality control section

INSTRUMENTS ORIGIN FUNCTION

pH Meter Mettler Determination of pH.

Viscometer Brookfied Determination of viscosity.

Leakage Tester ERWEKA, Germany Determination of Leakage.

Dissolution Tester ERWEKA, Germany Determination of dissolution time.

The Acme Laboratories Limited Page 12

(a) Solid Preparation

(b) Liquid Preparation

(c) Semi-solid Preparation

The Acme Laboratories Limited Page 13

(e) Tests for Gel/Dry syrup/pediatric drop:

The Acme Laboratories Limited Page 14

(h) Control of Bulk Products

Each lot of bulk product is tested to ensure

The Acme Laboratories Limited Page 15

(a) Solid Raw materials

The Acme Laboratories Limited Page 16

free from contamination,

SOME COMMON PHARMACEUTICAL PACKAGING TECHNIQUES INCLUDE:

Foil and heat sealing;

For secondary packaging material the following are used-

THE FOLLOWING FORMS OF PACKS AVAILABLE IN THIS COMPANY

ANALYSIS OF PACKAGING MATERIALS