Incepta Intern Paper

Report On In-Plant Training At Incepta Pharmaceuticals Ltd.
1. Introduction
Incepta Pharmaceuticals Ltd. is a leading pharmaceutical company in Bangladesh established
in the year 1999. The company has a very big manufacturing facility located at Savar, 35
kilometers away from the center of the capital city Dhaka. The company produces various
types of dosage forms which include tablets, capsules, oral liquids, ampoules, dry powder
vials, powder for suspension, nasal sprays, eye drops, creams, ointments, lotions, gels,
prefilled syringes, liquid filled hard gelatin capsules, lyophilized injections, human vaccine
etc. Since its inception, Incepta has been launching new and innovative products in order to
fulfill unmet demand of the medical community.
Since 1999, the name “Incepta” has been synonymous with trust and reliability inherent with
the word quality. Quality is ingrained with the work of the colleagues here and all their
values. They are dedicated to the delivery of quality healthcare throughout the nation. Their
business practices and processes are designed to achieve quality results that meet the
expectations of patients, customers, business partners, and regulators. Incepta has a relentless
passion for quality in everything they do.
Everyone in Incepta strives for continuous improvement in their performance measuring
results carefully and ensuring that respect for people are never compromised
Table 1: Address of Incepta Pharmaceuticals Limited.

Corporate Head Office Plant
Incepta Pharmaceuticals Limited
Ahmed Mansion (1st floor) Incepta Pharmaceuticals Ltd.
24, Chamelibagh, Shantinagar Dewan Idris Road, Bara Rangamatia
Dhaka-1217 Zirabo, Savar,
Bangladesh Dhaka
Phone: +880-2-8316402 Bangladesh
Fax: +880-2-9350684 Phone: +880-2-7708502-5
Email: [email protected] Fax: +880-2-7708507
[email protected]
Web: www.incepta pharma.com
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1.1. Values of Incepta
Figure 1: Quality
Figure 2: Teamwork
Figure 3: Performance
Figure 4: Community
Figure 5: Clients
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1.2. About Incepta Pharmaceuticals Limited

Incepta Pharmaceuticals Ltd. is a leading pharmaceutical company in Bangladesh established
in the year 1999. The company has a very big manufacturing facility located at Savar, 35
kilometers away from the center of the capital city Dhaka. The company produces various
types of dosage forms which include tablets, capsules, oral liquids, ampoules, dry powder
vials, powder for suspension, nasal sprays, eye drops, creams, ointments, lotions, gels,
prefilled syringes, liquid filled hard gelatin capsules, lyophilized injections, human vaccine
etc. Since its inception, Incepta has been launching new and innovative products in order to
fulfill unmet demand of the medical community. The focus has been to bring newer
technologically advanced molecules to this country.
The company specializes in value added high technology dosage forms like sustained release
tablets, quick mouth dissolving tablets, effervescent tablets, barrier coated delayed release
tablets, prefilled syringe products, Insulin and Insulin analogue and biological products,
among others. It has established a modern research and development laboratory for the
development of new, advanced dosage forms for various drugs and devices like poorly
soluble drugs, dry powder inhalers, coated pellets, modified release products, taste masked
preparation etc.
Incepta has a very competent sales team, which promotes the specialties throughout the
country. The company virtually covers every single corner of the rural as well as urban area
of Bangladesh. It has its own large distribution network having 18 depots all over the
country. The company has a clear vision to become a leading research-based dosage form
manufacturing company with global presence within a short period of time. With this view in
mind the company started to expand its business in overseas markets. Currently Incepta
exports to 40 different countries around the world. With hundreds of brands registered in
different countries, and many more in the pipeline, Incepta is gradually expanding its global
footprint across all the continents.
Company's state-of-the-Art R&D lab employs sophisticated and advanced technology to
bring newer products through research hitherto unknown in this country. Such activities will
not only benefit the company but also the total pharmaceutical sector of the country. In the
post 2005 era, the company also intends to embark into the production of Active
Pharmaceutical Ingredient (API). Plans are underway to get into reverse engineering and
analogue research in order to produce new API.
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Incepta Vaccines Limited, a sister concern of Incepta Pharmaceuticals, has already

established a State-of-the-Art Human Vaccine production facility. Incepta Vaccines is
planning to launched human vaccines in the Bangladesh market in September 2011. Incepta
emerges as the first Bangladeshi company to acquire the technology to produce Human
Vaccine. The larger production capacity will allow the company to supply its vaccines
globally.
On 15th January 2011, Incepta implemented globally acclaimed ERP software system - SAP.
Incepta is the first Bangladeshi company to implement SAP to manage resources throughout
the company operation. This world class resource management system will allow the
company to become more efficient and effective in its day to day operation.
The company is continuously expanding its activities beyond the geographical boundary of
Bangladesh. The company is open to collaborate with interested and relevant parties in
various countries Incepta will continue to strive to provide high quality medicine at
affordable prices to the people here in Bangladesh and other parts of the globe.
1.3. Vision and Mission

1.3.1. Vision
We want to become a research based global pharmaceutical company in addition to being a
highly efficient generic manufacturer. To discover and develop innovative, value-added
products that improve the quality of life of people around the world. And contribute towards
the growth of our Nation.
1.3.2. Mission
Provide people globally with high quality health care products at affordable prices in order to
improve access to medicine and to provide employees an enabling environment that
facilitates realization of their full potential.
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1.4. History of Incepta

Incepta began its operation with a handful of highly skilled and dedicated professionals
guided by an able leadership. Proper strategic planning, technical excellence, swift and timely
decisions helped us achieve our objectives leading to much faster growth. Incepta was able to
anticipate the need of the market and provide the right product at the right time. High focus
on R&D investment from the very beginning made possible the introduction of quality
products ahead of its competitors in most cases.
Incepta Pharmaceuticals Ltd. is now the 2nd largest company of the country and recognized
as the fastest growing of the top five manufacturing company in the country. Established in
the year 1999, the company has come a long way. Currently the Zirabo plant consists of
several buildings with state-of-the-art technology. Dedicated cephalosporin manufacturing
building, a specialized manufacturing building for the production of lyophilized products,
insulin and amino acids and newly built liquid and semisolid manufacturing building and
large warehouse is also in operation.
Incepta now has one of the largest and competent sales force and large distribution network
of its own, operated from 19 different locations throughout the country. A most dynamic
skilled and dedicated marketing team comprising of pharmacists and doctors are at the core
of the marketing operation. These highly skilled professionals play a crucial role in providing
the necessary strategic guideline for the promotion of its product.
1.5. Chronology of Events

The chronologies of events that take place in Incepta Pharmaceuticals Limited are given
below;
 December 16th 1998, the construction of the factory began.

 August 1999, office operations began.
 December 1999, first batch of product Neodin S 150 (Ranitidine 150 mg tablet) was
produced.
 January 2000, sales began formally.
 February 2000, training of the first batch of medical representatives began.
 April 2000, with the launching of Osartil (Losartan Potassium) the first prescription
product of Incepta was launched in the market. The company started off in a new
direction.
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 Several other first ever product, Celenta (Celecoxib), Rofenta (Rofecoxib) and
Omidon (Domperidone) followed in the footsteps of Osartil.
 A total of 23 new generics with 35 presentations were launched this year. 4 of these
generics were first ever in Bangladesh.
 By the end of 2000 Incepta was the number 31st company of the country.
 There was massive restructuring throughout the company. Sales, Distribution,
Marketing Strategy Department, and Factory; all were reorganized.
 A total of 18 new generics with 37 presentations were launched this year. 11 of these
 By the end of the year Incepta was ranked the 12th company of the country. The
company had a phenomenal growth of 448% over the previous year (IMS).
 A total of 32 new generics with 49 presentations were launched. 14 of these generics
were first ever in Bangladesh.
 Massive expansion project of the factory was envisioned. New office for the sales and
distribution operation was also taking shape.
 The company registered an excellent growth of 55.85% over the previous year. By the
end of the year Incepta was ranked the 10th company of the country (IMS).
 Incepta kept on introducing innovative and newer molecules to the local market. A
total of 32 new generics with 48 presentations were launched. 18 of these generics
 The new office (Dhanmondi) for the sales and distribution operation was inaugurated.
 The company registered an excellent growth of 28.5% over the previous year (IMS).
 By the end of the year Incepta was ranked the 8th company of the country (IMS).
 A total of 17 new generics with 32 presentations have been launched. 6 of these
 The company maintained an excellent growth of 48.2% over the previous year (IMS).
 The ranking went up again and the company was ranked the 5th largest company of
the country with the highest growth rate among the top five (IMS).
 We thrived under challenge and excelled in venturing into unexplored grounds and
continued to satisfy our customers. Incepta was audited and accepted as a supplier for
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UNICEF & UNDP. We started to supply life saving drugs to UNICEF from March,
2005.
were introduced first time ever in Bangladesh.
 The company maintained an excellent growth of 34.8% over the previous year (IMS).
 The company was ranked 3rd largest with the highest growth among the top five
(IMS).
 By 2006 Incepta had positioned itself as an innovative research oriented and
knowledge based pharmaceutical company specializing in analysis, design and
development of new products.
 Incepta successfully started overseas marketing operation from May 2006.
 The company maintained an excellent growth of 31.26% over the previous year
(IMS).
 The company maintained the ranking of 3rd largest (IMS).
 Incepta pioneered the introduction of biotech products (Human Insulin) and
lyophilized products (Pantoprazole injection) in the Bangladesh pharmaceutical
market. This was the first time a local pharmaceutical company produced such highly
sophisticated technology product in the country.
 Marketing, Sales, Distribution and Administration departments shifted to the fully
owned new office premises in Tejgaon, Dhaka. The international standard head office
of Incepta started operation in the new office premises on 1st October, 2007.
 A marketing and sales team was setup in Myanmar headed by a country manager
from the Marketing Strategy Team to promote the 35 products registered with the
Myanmar FDA.
 The company maintained a growth of 12.93% over the previous year (IMS).
 The company held the 3rd largest ranking (IMS) among the companies.
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 Continued investment in our core strength that is our manufacturing plant led to
recognition from European authorities and on January 11, 2008 Incepta attained
European "Certificate of GMP Compliance".
 40 new products with 86 presentations were introduced of which 10 were first ever in
Bangladesh.
 The plant received GMP certification (General formulations and Cephalosporins)
from Kenyan Ministry of Health on January 21, 2008.
 Incepta was also awarded GMP (Cephalosporins) from Ethiopian Ministry of Health
on July 22, 2008.
 Incepta registered 51 products in Mongolia on September 26, 2008 (As first
Bangladeshi Company).
 Incepta registered 3 products in Georgia on October 13, 2008 (As first Bangladeshi
Company).
 In 2008 significant number of products got registration in different countries. 19
products from Democratic Republic of Congo, 20 products from Sri Lanka, 22
products from Togo, 8 products from Hong Kong, 20 products from Mauritania, 6
products from Vietnam, 1 product in Cambodia.
 The company maintained a growth of 12.10% over the previous year (IMS).
 The company became the 2nd largest (IMS) among the companies operating in
Bangladesh.
 Incepta started venturing in the field of human vaccines and hormonal products.
Construction of the Vaccine & Hormones facilities started on 1st January 2009 and
8th November 2009 respectively.
 Incepta became the first Bangladeshi Company to get GMP Compliance Certificate
from Turkey (Tablets, Capsules and Lyophilized products) on January 08, 2009.
 Incepta achieved GMP certification from the Ministry of Health, Yemen on May 25,
2009 (Sterile and Non-sterile products).
 Incepta launched 51 new products in 2009. 4 of these were first ever in Bangladesh
pharmaceutical market.
 The company maintained an excellent growth of 27.71% over the previous year
(IMS).
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 The company maintained the 2nd largest (IMS) position in 2009.

 Incepta was accepted and became enlisted with the Copenhagen office of UNICEF,
UNDP and UNESCO as global supplier of medicine.
 Incepta was awarded GMP certificate from Uganda, National Drug Authority on 5th
August 2010 (Sterile Products, Non-sterile products and Cephalosporins).
 Incepta launched 56 product presentations. 10 of which were first ever in Bangladesh
market.
 Incepta maintained the 2nd largest (IMS) position in Bangladesh pharmaceutical
market in 2010. The company showed the strongest growth among the top 10
companies with a growth rate of 34.97% (IMS).
 Incepta introduced Human Vaccines to the market and become the first Bangladeshi
vaccine manufacturing company.
 Export has emerged as a focus area for Incepta. With over 300 products registered in
different countries export is now set to play more important role in the growth of the
company. Currently the company exports to 37 countries of the world with many
more in the pipeline.
 Since starting supply of medicine to UNICEF in Bangladesh, Incepta has remained
the largest supplier till today.
 In 2011 the company has launched 55 products, 9 of which are first ever in
Bangladesh market.
 In 2012 the company has launched 52 products, 7 of which are first ever in Bangladesh
market.
 In 2013 the company has launched 40 products, 7 of which are first ever in Bangladesh
market.
 Up to June, 2014 the company has launched 9 products, 1 of which is first ever in Bangladesh
market.
1.6. Growth in Incepta Comparison with Local Pharma Market
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Figure 6: Growth in Incepta Comparison with Local Pharma Market
Beginning in 2000, Incepta has been launching new and innovative products at a faster pace than its
competitors.
Up to June 2014 it has already launched 390 generics with a total of 696 presentations. The company
produces a wide variety of dosage forms covering nearly all the major therapeutic classes.
During the last 14 years of operation Incepta launched as many as 139 new generics for the first time
ever in Bangladesh. High focus on quality and timely introduction of much needed essential
medications previously unavailable in the country has enabled Incepta to become the second largest
pharmaceutical company of the country.
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Table 2: Growth In Comparison With Local Pharma Market

Year No. of Products First Ever Product IMS Rank*
2014 696 1 2nd
2013 686 7 2nd
2012 631 7 2nd
2011 632 9 2nd
2010 594 10 2nd
2009 585 4 2nd
2008 532 10 2nd
2007 451 17 3rd
2006 368 9 3rd
2005 288 12 3rd
2004 198 6 5th
2003 154 18 8th
2002 119 14 10th
2001 78 11 12th
2000 35 4 31st
* Intercontinental Marketing Services (IMS)
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2. Departments in Incepta Pharmaceuticals Limited

 Marketing Strategy Department
 Medical Service Department
 Human Resource Department.
 Administrative Department
 Engineering
 Sales Department
 Distribution Department
 Regulatory Affairs Department
 Finance & Accounts Department
 Management Information Department
 Production Department
 Quality Assurance Department
 Product Development Department
 International Marketing Department

However our training covers the following departments-
 Warehouse
 Production
 Quality Assurance
 Engineering
These departments are described in the upcoming section of this report.
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3. Warehouse
The warehouse of Incepta is an enclosed building and protects the stored goods from
environmental influences. They are secured against fire by the design of the buildings and
technical facilities. They are secured against fire by the design of the buildings and technical
facilities. The fire brigade facility has access to enable appropriate firefighting. The locking
system of the stored goods ensures that the access to the building is controlled.
Our warehouse is equipped with four different storage conditions; a) 2 oC – 8oC, b) 8oC –
15oC, c) 15oC -25oC, and d) ambient condition. There is specific quarantine and sampling
areas with dedicated separate storage location for cephalosporin, and steroids. Temperature
sensing is equipped with remote sensor technology.
There are controlled rooms with HVAC for specific materials and the conditions are
monitored to confirm compliance with the requirements. Also there is retention sample room.
The materials are stored in the warehouse by pallet racking. The status of materials and
products is controlled by colored status sticker.
The transaction of materials is done according to "first in first out" system. Accounting and
storage is maintained through SAP.
The area of warehouse includes-
1. Dispensing booth
2. Storage area for
a. Raw materials
b. Finished products
c. Packaging materials
3. Quarantine area for
a. Raw materials
b. Finished products
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3.1. Storage Area for Raw materials

 Raw material store: Goods kept when released by QC
 Cool room: 2-8 °C
 Dispensing room: for dispensing of ingredient.
 Quarantine area: After receiving of raw material they are stored first in the
quarantine area. If Q.C sampling and checking is approved then shifted to the store.
3.2. Storage Area for Finished Product

 Quarantine area: At first finished products are stored in this area for about 14 days,
checked by Q.A.D, if problem arises the product should be rejected and reprocessed if
possible.
 Product ready for marketing: After “pass” from the Q.A.D finished products are
shifted for marketing.
3.3. Storage Area for Packaging Materials

In this area packing materials are stored in normal condition and in control environment. The
store has well defined are for different packing materials. First the goods are kept in
Quarantine area for packing materials. Some materials like aluminum foil are kept in AC
store.
3.4. The major activities of Warehouse

a. Ensure the reception of right materials.
b. Issue required materials for production within the limit.
c. Reception of Finished Goods from production & timely distribution.
d. Monitoring of temperature & relative humidity.
e. Overall cleanliness of both materials & areas.
f. Materials management (Segregation, QC formalities, Disposition, etc.)
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Figure 7: Warehouse Department of Incepta Pharmaceuticals Ltd.
3.5. The duties of Ware House is sequentially- (Raw Materials Receive)
Checking of vehicle with Receiving chalan/Invoice (Exact product, volume/amount)
Unloading vehicles, sorting and palletization
Cleaning of incoming materials
Checking for damage/loss/excess
Information entry in “Systemic Application product in data Processing” (SAP)
Preparation of “Goods Receive Information” (GRI) & Quarantined Label
Affixing of “Quarantined Label” & transfer of materials to the quarantine area of

warehouse.
Sending out of GRI to QC department
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Result: Released Result: Reject
Affixing of release label, transfer of Affixing of reject label & transfer of

material to released area & sotware entry material to reject store
Informing PPIC about rejection of

materials.
3.6. The duties of Ware House is sequentially- Raw Materials issue to production
Receiving of “Batch Manufacturing Record” (BMR) from Production
Checking of materials “Process Order”
Information entry in the required field of BMR
Arranging of required released materials as per FIFO/FEFO system
Information entry in Bin Card
Issuing materials to the materials dispensing both
Dispensing of Raw Materials & issue to production
Returning the access materials to Warehouse & information entry in “Inventory software”
Storing of returned excess materials in the respictive location/area of warehouse.
3.7. The duties of Ware House is sequentially- Finished goods dispatch
Receiving of “Requisition of Finished Goods” from Central Sales Centre.
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Checking of availability of Finished Goods
Sending request to Quality Assurance for release (if required)
Arranging covered van for loading Finished goods
Preparation of Delivery Challan, Issue voucher & gate pass
Information entry in finished Goods register as well as inventory Software.
Exit of Finished Goods Vehicle from Warehouse
3.8. Different Units of Warehouse

 Quarantine area: After receiving of raw materials they are stored first in the
quarantine area. Then Q.C. sampling and checking is approved and then shifted to the
main storage area. Purpose of Quarantine area-
a) To receive the raw materials
b) To store the material before it passed the QA test
c) To manage the materials properly and systemically.
 Sampling area: Sampling means the process of taking a small portion from a lot for
test and analysis to show the quality of the whole lot. The purpose of sampling and
subsequent testing is to provide an effective check on the quality of the product or
substances being processed.
 Main storage area: Here raw materials are stored. There is another isolated storage
area for sophisticated materials maintaining temperature and humidity inside the main
storage area. The storage department performs some important functions such as
a) Specific raw materials are stored in specific mentioned area with proper
documentation. Cool area: 15-24°C & Humidity: 45-55%.
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b) According to monthly program, this department has the responsibilities to

get final Q.C. approval for raw materials.
c) According to plan and recovery maintenance, the raw materials are
supplied to the production area for required batch size.
 Dispensing area: Here raw materials are weighing under a laminar air flow cabinet
and supplied to the production areas by weighing according to the proper document
and release it from the RM store. The area from where raw materials and packing
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.
 Released area: Here raw materials are stored, those only passed the tests performed
by QC and QC provides released tag. Purpose of released area-
a) To store the approved materials
b) To store the approved materials in different conditions as
specified by the manufacture.
 Not released area: Here raw materials are stored, those tests not yet performed by
QC and QC provides not released tag.
 Rejected area: Rejected materials are stored here those failed the tests performed by
QC and QC provides rejected tag and the local raw materials are returned to the
suppliers. Imported raw materials are destroyed.
 Special area: It includes Cold room (Temp. 2-8, e.g. Cephradine, Cephalosporine);
Cool room (Temp. 8-15); Controlled room (Temp. 15-25); Ambient room
(surrounding room temp.).
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 Preservation of products: Due to some physicochemical changes medicines are

sensitive products. So, to protect the most sensitive ones, manufacturers use different
techniques and adjutants. In addition, each product goes with its own preservation
instructions. In the warehouse, it is essential to preserve the pharmaceutical products
from the factors of degradation to guarantee their stability up to their expiration date.
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4. Production Departments
4.1. Solid Dosage forms
4.1.1. Tablets
Tablets are the solid preparations each containing a single dose of one or more active
ingredients and obtained by compressing uniform volume of particles.
According to British Pharmacopoeia, “Tablets are solid dosage forms circular in shape with
either flat or convex faces and prepared by the compression or compaction of suitably
prepared medicament by means the tablet machine”.
Tablets are intended for oral administration. Some are swallowed whole, some after being
chewed; some are dissolved or dispersed in water before being administered and some are
retained in the mouth where the active ingredient is liberated.
Being the most common, convenient and inexpensive dosage form, tablet formulation and
design is the most important consideration in solid dosage form production in the
pharmaceuticals, which may be described as the process whereby the formulator ensures that
the correct amount of drug in the right form is delivered at or over the proper time at the
proper rate and in the desired location, while having its chemical integrity protected to that
point.
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4.1.1.1. Steps involved in the Manufacturing of Tablets

Granulation (wet or dry)
¯ Blending
Blending
¯ ¯
Compression Direct Compression
Conventional Uncoated Tablets
¯
Coating of Uncoated Tablets
¯
Coated Tablets
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4.1.1.2. Granulation
Granulation is the process in which the primary powder particles are made to adhere to form
larger, multiparticle entities called granules. In other words, granulation may be considered as
a size enlargement process during which small particles are formed into larger, are physically
strong agglomerates in which the original particles can still be identified.
The pharmaceutical granulations are used primarily to prepare material for tableting. Some
granulations are dispensed as packets or capsules.
The pharmaceutical granules typically have a size range between 0.2 to 4.0mm, depending on
their subsequent use.
4.1.1.2.1. Processes of Granulation

Granulation Processes Which Are Performed In the Incepta Pharmaceuticals Limited Are
Following;
a) Wet granulation
b) Dry granulation
Figure 8: Granulation unit of Incepta Pharmaceuticals Ltd.
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4.1.1.2.1.1. Wet granulation

In Incepta Pharmaceuticals Limited the wet granulation technique is used generally, which is
briefly described below with the help of a flow chart;
Weighing of active ingredient as well as excipients
¯
Dry mixing
¯
Wet mixing (in case of wet granulation) by addition of demineralized (DM) water or Maize
starch paste in Rapid Mixer Granulator (RMG) for a certain time period specified in the
Batch Production Record (BPR)
¯
Initial Phase drying in Fluid Bed Dryer (FBD)
¯
Milling in the Multimill
¯
Partial drying in FBD
¯
¯
Terminal/Final drying in the FBD
¯
Sieving in the Vibratory Sifter according to the required particle/granule size
¯
Measurement of Loss on Drying (LOD)
¯
Granules of desired size ready for blending.
Following the above process, 2 types of granules are produced in the four-granulation units of
the industry, which include;
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 Granules with active ingredient/s

 Placebo granules without any active ingredient/s for moisture sensitive active/s or
drug/s
4.1.1.2.1.2. Dry Granulation
Besides the wet granulation process, dry granulation process is also followed for certain
cephalosporin products in the cephalosporin building. The granulation process is carried out
following the steps given below;
Weighing of active ingredient as well as excipients
¯
Dry mixing
¯
Compression of the powder mixture into a slug on a heavy-duty rotatory tablet machine or
passing of powder through two rollers to produce a sheet of material by the process of roller
compaction
¯
¯
Granules with desired size ready for blending.
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4.1.1.2.2. Machines used in the Granulation unit for the purpose of Granulation
In each granulation unit, the following machines are present for granulation;
Table 3: Machines used in the Granulation unit for the purpose of Granulation
Name of the Machine Function Capacity
300-350 Kg (large) &

Rapid Mixer Granulator (RMG) Mixing
100-150 Kg (small)
Paste Kettle Preparation of slurry 600 Liter
Fluid Bed Dryer (FBD) Drying 200 Kg
Multimill Milling -
Vibratory Shifter Sieving -
4.1.1.2.3. Condition for manufacturing of Granules

 Relative Humidity: Not more than 55%.
 Temperature: Below 250C.
4.1.1.2.4. Common Problems That Arise During Granulation & Their Remedies
Table 4: Common Problems That Arise During Granulation & Their Remedies
Problems Remedies
Addition of more demineralized (DM)

Over dried granules
water or solution of binder
Increase in drying time or addition of less

Less dried granules demineralized (DM) water or solution of
binder
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4.1.1.3. Blending
Blending is the process of mixing lubricants, glidants and colorants with the granules prior to
compression (in case of granules containing the active ingredient/s) or mixing of active
ingredient/s along with lubricants, glidants and colorants with the placebo granules (in case
of granules without the moisture sensitive active ingredient/s) prior to compression. So, the
process in often-called lubrication or remixing.
4.1.1.3.1. Blending Procedure

For granules containing active ingredient/s the following procedure is used in the blending
units of Incepta Pharmaceutical Limited;
Granules containing active ingredient/s in the Drum or Double Cone Blender
¯
Transfer of glidants into the blender by passing through a sieve of mesh size 20 & Colorants
through 200 mesh screen
¯
Blending of the ingredients in the Drum (30 rpm) or Double Cone Blender (16 or 22 rpm) for
2-3 minutes as specified in the Batch Production Record (BPR) for a certain product
¯
Transfer of lubricants into the blender by passing through a sieve of mesh size 20
¯
Blending with the other ingredients in the same manner as stated above for 1 minute
¯
Granules are ready for compression
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Again, for placebo granules without any active ingredient/s the following procedure is used
in the blending units of Incepta Pharmaceutical Limited;
Placebo granules in the Drum or Double Cone Blender
¯
Transfer of Active ingredients & Glidants into the blender by passing through a sieve of mesh
size 20 & Colorants through 200 mesh screen
¯
Blending of the ingredients in the Drum (30 rpm) or
Double Cone Blender (16 or 22 rpm) for 2-3 minutes as specified in the Batch Production
Record (BPR) for a certain product
¯
¯
Blending with the other ingredients in the same manner for 1 minute
¯
Granules are ready for compression
4.1.1.3.2. Machines Used in the Blending Units for the Purpose of Blending
The following machines are used in the blending units for blending;
Table 5: Machines Used in the Blending Units for the Purpose of Blending
Name of the Machine Function Capacity Speed (rpm)
Double Cone Blender 300-350 Kg (large) 16 rpm

Blending
(DCB) 150-200 Kg (small) 22rpm
65 Kg (large)
Drum Blender Blending -
35Kg (small)
FITZ mill Milling - 4000
27
4.1.1.3.3. Condition Required During Blending

4.1.1.4. Compression
Compression can be defined as the technique of applying force or pressure to the granules or
powders (in case of direct compression) to produce tablets of desired shape and size with the
help of tablet press machine.
Two types of compressions are seen in the tablet press units of the factory; they are-
 Compression of previously made granules
 Direct Compression
4.1.1.4.1. Process of General Compression

Granules (previously made)
¯
Transfer of granules in the hooper of tablet press machine by hand or auto powder/granules
loader
¯
Rising of upper punch & dropping of lower punch
¯
Filling of die cavity through feed frame
¯
Removal of extra granules by scrape off plate
¯
Coming down of upper punch for compression to produce tablet
¯
Raising of both upper & lower punches to certain extent
¯
Ejection of tablet with the help of takeout plate
28
Conventional Uncoated Tablets of desired shape and size

4.1.1.4.2. Process of Direct Compression
Direct compression is the preferred method when the active ingredient shows inherently good
compression behavior. The direct compression process assumes that all materials can be
purchased or manufactured to specifications that allow for simple blending & tableting. The
process is described below through a flow chart;
Milling & Screening of active ingredient/s
& the excipients
¯
Mixing of the active ingredient/s along with excipients including lubricants & disintegrants
¯
Transfer of mixer in the hooper of tablet press machine by hand or auto powder loader
¯
Rising of upper punch & dropping of lower punch
¯
Filling of die cavity through feed frame
¯
Removal of extra granules by scrape off plate
¯
Coming down of upper punch for compression to produce tablet
¯
Raising of both upper & lower punches to certain extent
¯
Ejection of tablet with the help of takeout plate
¯
Conventional Uncoated Tablets of desired shape and size
4.1.1.4.3. Machines Used in the Tablet Press Unit for The Purpose of Compression
In each tablet press unit, the following machines are present;
29
Table 6: Machines Used in the Tablet Press Unit for The Purpose of Compression
Name of the Machine Function
Loading of powder or granules to

Automatic Powder Loader
the hooper of the tablet press
Tablet press machine (B-tooling/

Compression
D-tooling)
Dust Collector Removal of dust
Weighing of tablets in regular

Electronic balance
intervals to maintain equal weight
4.1.1.4.4. Condition Required During Compression

4.1.1.4.5. Common Problems That Arise During Compression

Common Problems that generally arise during compression are-
 Capping
 Chipping
 Sticking
 Weight variation
 Mottling
 Hardness problem
30
4.1.1.5. Coating
Tablet coating is the application of a coating composition to a moving bed of tablets with the
intention of conferring benefits and properties to the dosage form over the uncoated variety.
The distribution of the coating is accomplished by the movement of the tablets either
perpendicular (coating pan) or vertical (air suspension) to the application of the coating
composition.
There are three primary components involved in tablet coating. They are;
 Tablet properties
 Coating process
- Coating equipment
- Parameters of coating process
- Facility & ancillary equipment
- Automation in coating process
 Coating composition
4.1.1.5.1. Reasons of Coating

Coating is an additional step in the tablet manufacturing process, which increases the cost of
the product, therefore so the decision to coat a tablet is usually based on one or more of the
following objectives;
 To mask the test, odor or color of the drug

 To provide physical and chemical protection for the drug
 To control the release of the drug from the tablet
 To protect the drug from the gastric environment of the stomach with an acid-resistant
enteric coating
 To facilitate product identification specially for distinguishing of different strength of
a drug
31
4.1.1.5.2. Types of Coatings

Generally, there are 3 types of coatings that can be done over tablets, but in the coating units
of Incepta Pharmaceutical Limited, 2 types of coating are performed;
Figure 9: Solace Auto-coater of Incepta Pharmaceuticals Ltd.

4.1.1.5.3. Coating Composition
For both cases of film coating & enteric coating, the following ingredients are used for
coating;
 Polymers
 Plasticizers
 Solvent system
 Colorant
32
4.1.1.5.4. Commonly Used Polymers in Film Coating & Enteric Coating

Table 7: Commonly Used Polymers in Film Coating & Enteric Coating
P Film Coating Enteric Coating
O Cellulosic (e.g. HPMC) Cellulosic (e.g. CAP)
L Glycols (e.g. PEG) Phthalate (e.g. HPMCP)
Y Acrylic acid derv. (e.g.Eudragit Acrylic acid derv. (e.g.EudragitL100)
M E100)
E Vinyls (e.g. PVP) Succinates (e.g. HPMCAS)
R
S
4.1.1.5.5. Film Coating

 Organic solvent-based
 Aqueous solvent-based
a) Enteric Coating
b) Sugar coating is not performed in the coating units of the factory.
4.1.1.5.5.1. Process of Film Coating
For film coating the following procedure is used in the coating units of Incepta
Pharmaceutical Limited;
Mixing of polymer/s with the solvent system by the aid of a mechanical stirrer
¯
Transfer of colorant/s containing solution (previously prepared with the help of a
homogenizer) into the coating solution manufacturing vessel & mixing with the polymeric
solution
¯
Loading of uncoated tablets in the circulating coating pan for dedusting for 2-3 minutes with
a speed of 15rpm
¯
Spaying of coating solution onto the tablets for a certain period as specified in the Batch
Production Record (BPR) & subsequent drying by adjusting inlet and outlet air temperature
33
Drying of coating over the tablets for 15minutes with same pan speed of 15rpm
¯
Film coated tablets
4.1.1.5.5.2. Process of Enteric Coating
For enteric coating the following procedure is used in the coating units of Incepta
Pharmaceutical Limited:
Mixing of polymer/s with the solvent system by the aid of a mechanical stirrer
¯
Transfer of colorant/s containing solution (previously prepared with the help of a
homogenizer) into the coating solution manufacturing vessel & mixing with the polymeric
solution
¯
Loading of uncoated tablets in the circulating coating panfor dedusting for 2-3 minutes with a
speed of15rpm
¯
Spaying of coating solution onto the tablets for the purpose of sub coating for some time as
specified in the Batch Production Record (BPR) & subsequent drying by adjusting inlet and
outlet air temperature
¯
Spaying of another coating solution onto the tablets for the purpose of enteric coating for
some time as specified in the Batch Production Record (BPR) & Subsequent drying by
adjusting inlet and outlet air temperature
¯
Drying of coating over the tablets for 15minutes with same pan speed of 15rpm
¯
Enteric-coated tablets
34
4.1.1.5.5.3. Machines Used in the Coating Unit for the Purpose of Both Film & Enteric
Coating
In each coating unit, the following machines are present;
Table 8: Machines Used in the Coating Unit
Perforated Coating Pan System Loading of Tablets
Spray Gun Spraying of coating solution
Coating Solution Manufacturing

Manufacturing of Coating Solution
Vessel
Manufacturing of Homogenous
Homogenizer
Solution of Colorants
4.1.1.5.6. Condition Required During Coating

4.1.1.5.7. Common Problems That Arise During Coating

Common Problems that arise during coating are-
 Film cracking
 Chipping
 Orange peel
 Picking
35
4.1.1.6. Coated Granules

Granulation may be considered as a size enlargement process during which small particles
are formed into larger, are physically strong agglomerates in which the original particles can
still be identified.
Some granulations are dispensed as coated in packets or sachet usually intended for single
dose as the pharmaceutical granulations are used primarily to prepare material for tableting.
4.1.1.6.1. Process of Manufacturing Coated Granules

Flavored Placebo granules
¯
Transfer of granules in the Drum or Double Cone Blender
¯
Transfer of Active ingredients & Glidants into the blender by passing through a sieve of mesh
size 20 & Colorants through 200 mesh screen
¯
Blending of the ingredients in the Drum (30 rpm) or Double Cone Blender (16 or 22 rpm) for
2-3 minutes as specified in the Batch Production Record (BPR) for a certain product
¯
¯
Blending with the other ingredients in the same manner for 1 minute
¯
Uncoated Granules
¯
Coating
¯
Coated Granules
4.1.2. Capsule
Capsule is the solid unit dosage form of medication with a separate body & cap (Both are
gelatin shells). There are two types of capsules-Capsule with hard gelatin shell & Capsule
36
with soft gelatin shell. Hard capsules are filled with powders & pellets, whereas soft capsules
are filled with liquid or semisolid product.
According to British Pharmacopoeia,” Capsules are the solid dosage form in which the drug
is enclosed either in a hard or soft, soluble container or shell of a suitable form of gelatin”.
In this pharmaceutical industry filling (encapsulation), sealing and polishing (if required) of
capsules of hard gelatin shell are done during manufacturing, as the industry does not
manufacture any capsule shell.
The active is filled in the empty the hard gelatin capsule shell in the form of-
 Powder
 Pellets
There are 5 different sizes of empty hard gelatin capsule shells used in Incepta
Pharmaceuticals Ltd. for general production, which include-
 Capsule shell size 00

The Encapsulation is done by either
 Automatic Capsule Filling Machine

Or
 Manual Capsule Filling Machine by Hand
37
4.1.2.1. Encapsulation Process by Automatic Capsule Filling Machine

For encapsulation of pellets the following procedure is done with the help of Automatic
Capsule Filling Machine in the capsule filling units of Incepta Pharmaceutical Limited;
Blend Pellets with NPS
¯
Encapsulation
For encapsulation of powder the following procedure is done with the help of Automatic
Capsule Filling Machine in the capsule filling units of the industry:
Blending
¯
Slugging
¯
Granulation
¯
Sieving
¯
Encapsulation
4.1.2.2. Encapsulation Process by Manual Capsule Filling Machine by Hand

For encapsulation of powder the following procedure is done with the help of Manual
Capsule Filling Machine by hand in the capsule filling units of the industry:
Loading of capsule in the loading plate
¯
Removal of caps of the shells
¯
Filling of powder
¯
Rejoining of caps of the shells
38
Encapsulation
¯
Sorting of Capsules
¯
Polishing of Capsules
4.1.2.3. Polishing of Capsules after Encapsulation

Not all but most capsules need polishing specially those are filled with powder. Polishing is
done first by Capsule Polishing machine which removes dust, adherent powder and gives a
shiny appearance.
Figure 10: Capsule polishing and inspection of Incepta Pharmaceuticals Ltd.
39
4.1.2.4. Machines Used in the Capsule Manufacturing Unit

In each Capsule Manufacturing unit, the following machines are present;
Table 9: Machines Used in the Capsule Manufacturing Unit
Automatic Capsule Filling Filling of empty Capsule shell

Machine
Capsule Sorting Machine Removal of defected capsules
Capsule Polishing Machine Polishing of Capsules after powder

filling
4.1.2.5. Condition Required During Manufacturing of Capsule

4.1.3. Dry Syrup

A dry pharmaceutical syrup may be defined as a finely divided insoluble particle ranging
from 0.5-5 μ, which is to be distributed in a suitable vehicle Dry syrups are the solid dosage
form that can be reconstituted by the addition of water to administer by the oral route. Mostly
antibiotics are available in dry syrup form. Besides, some moisture sensitive and pediatric
drugs are also available in the form of dry syrup .Dry syrup at Incepta Pharmaceutical
Limited is manufactured in a method namely, Direct Mixing.
4.1.3.1. Flow Chart for Direct Mixing for the Manufacturing of Dry Syrup
Crushing the sucrose in FITZ mill at 3000 rpm
¯
Transfer of half portion of sucrose from step-1 into a double cone blender by passing through
a 20 mesh screen
¯
Transfer of all other excipients in the blender to blend for 30 minute
¯
Transfer the mix from the double cone blender by Passing through a 20 mash screen
4.1.3.2. Machines Used in the Dry Syrup Manufacturing Unit

In the Dry Syrup Manufacturing, the following machines are used;
40
Table 10: Machines Used in the Dry Syrup Manufacturing Unit

Double cone Blender Blending/Mixing
FITZ Mill Crushing/ Milling
Bottle Filling Machine Filling of Dry Syrup
Bottle Sealing Machine Sealing of Dry Syrup Bottle
4.1.3.3. Condition for Manufacturing Dry Syrup

 Temperature: Below 250
4.2. Liquids and Semisolids Dosage Forms

Although tablets and capsules are more widely used than liquid preparations for oral
administration, the oral use of liquid pharmaceuticals has generally been justified on the basis
of administration to those individuals who have difficulty swallowing solid dosage forms.
Drugs that have difficulty in swallowing solid dosage form are administered in solution. A
drug administered 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 tablet or
capsules.
Liquids and semisolids preparations include-
 Oral Syrup  Emulsion

 Suspension
41
4.2.1. Areas of Liquid Section
Antacid area Other Liquid Area
Syrups Suspension
42
4.2.2. Manufacturing Flow Chart of Syrup

Preparation of syrup (hot water + sucrose)
↓
Clear red solution was made
↓
Addition of preservatives.
↓
Cooling at 400 C
↓
Addition of wetting agent
↓
Transfer the sucrose solution into the vat by transfer pump
↓
Addition of active ingredient
↓
Addition of co-solvent, buffering agent
↓
Addition of color/flavor
↓
Volume adjustment
↓
Filling
↓
Sealing
↓
Labeling
↓
Packing
4.2.3. Machineries used for Compounding (For Syrup and For Antacid)
The machineries and utensils that are used for compounding are listed below:
43
 Compounding vessels (capacity: 3000L, 2500L, 1000L and 500L)

 Silverson stirrer
 Filter press pump
 Colloid mill
 Transfer pump and
 Storage vessels
4.2.4. Bottle Washing and Drying

The bottle are washed both internally and externally with DM water. The washed bottles are
dried at 140oC for 2 hours. For antacid preparation, bottles are first passed through Cl-water
Table 11: Machines Used in Bottle Washing
Name of machine Capacity Manufacturer
Bottle washing 100-120 bottle/min India

machine
Bottle filling & Cap 6 channels,100 bottles\ India

sealing machine min
Figure 11: Bottle Washing Machine of Incepta Pharmaceuticals Ltd.
44
4.2.5. Machines Used in the Oral Liquid Manufacturing Unit

In the Oral Liquid Manufacturing, the following machines are used;
Table 12: Machineries of Oral Liquid Manufacturing Unit
Steam Jacketed Vessel Mixing 1000 Liter
Charge Vessel Manufacturing 2000 Liter
Storage Vessel Storage 2000 Liter
Cartridge Filter Filtration -
Bottle Filling & Sealing Filling & Sealing of Oral

2500 bottles /hour
Machine Liquid Bottles
4.2.6. Problems Associated With Oral Liquid Dosage Form

 Microbial contamination
 Sedimentation
 Phase separation
 Cake formation
 Color may be changed
4.2.7. Observation
 Cleanliness & environment are strictly maintained.
 Temperatures are quarterly maintained.
 Water purity quarterly maintained
 Purified water is used.
 Microbial contamination is maintained.
 Separate bottle washing and drying room.
 All machines are operated according to standard operating procedure (SOP).
 Machines are calibrated timely.
45
4.3. Sterile Products

Sterile products are dosage forms of therapeutic agents that are free of viable
microorganisms. Principally these include parenteral, ophthalmic and irrigating preparations.
Of these, parenteral products are unique among dosage forms of drugs because they are
injected through the skin or mucous membrane to the internal body compartments.
Commonly the small volume parenteral or injectable products are filled in-
 Ampoules
 Vials
4.3.1. Injectable Products in Ampoule

Injectable Products are dispensed in ampoules following the procedure given below-
Ampoule Deboxing
¯
Ampoule washing
¯
Sterilization (in case of aseptically filled ampoules)
¯
Ampoule Filling (under laminar air flow)
¯
Ampoule Sealing
¯
Terminal Sterilization
¯
Ampoule Inspection
¯
Sealed Ampoules
46
4.3.1.1. Ampoule Filling & Sealing (Under Laminar Air Flow)

Ampoule on the filling belt
N2 flush ® Filling ® N2 flush ® Sealing by flame ® Ejection
Figure 12: Ampoule Washing Machine of Incepta Pharmaceuticals Ltd.
4.3.1.2. Ampoule Inspection
 The white zone detects visually the black particles,
 The black zone detects the white particles.
 The volume is measured visually by taking 4 ampoules at a time in hand
47
Particle Count
Table 13: Particle Cunt
Particle count at rest Particle count at operation Microbial growth
Class
(/m³) (/m³) (cfu)
0.5µ 5µ 0.5µ 5µ
A 3500 0 3500 0 <1
B 3500 0 350000 2000 <5
C 350000 2000 3500000 200000 <50
D 3500000 20000 Not defined Not defined -
Different Sterilization Techniques & Their Uses

Table 14: Sterilization Techniques
Sterilization Temperature Exposure Time Pressure
Uses
Technique (0C) (hrs) (Bar)
180 3 1.1
Dry Heat Sterilization
220 2.5 1.1 Vials
(DHS)
260 1 1.1
Ampoules,
Steam Sterilization
121 0.5 1.1 Gloves, Filters,
/Autoclave
Gourmets
48
Zonal Classification of Clean Rooms & Respective Air pressure

Table 15: Classification of Clean Rooms
Air pressure
Zone Class of Environmental Cleanliness
(Pascal)
Under Laminar Airflow A NLT 40
Filling zone A 40
Sealing zone B 40
Filtration room B 30
Change Rooms C 15-30
Ampoule cooling room C 20
Ampoule storing room D 10
Machines Used in the Manufacturing of Injections (Ampoules)

Table 16: Machine Used in the Manufacturing of Injections
Ampoule washing Washing 12000ampoule (0.2ml)/hr

machine
Ampoule Filling & Filling & Sealing 7000ampoule (0.2ml)/hr

Sealing Machine,
Storage Vessel Storage 50 Liter
Cartridge Filter (0.2μm) Filtration -
4.3.2. Vial Sterilization Process

Washing by hot WFI
↓
49
Sterilized by sterilization chamber at 3300 C temperatures for 7-8 min.

↓
Cooling to 400 C
↓
Turn table
↓
Filling
↓
Rubber stopper
↓
Sealing
4.3.3. Room Condition/Critical Parameter
 Temperature: Below 250 C.
 Relative humidity:
Below 60% (Manufacturing area).
Below 50% (Packaging area).
Pressure: Positive pressure in rooms and negative pressure in corridor and pressure
difference 12-15 Pa.
Figure 13: Vial Washing Machine of Incepta Pharmaceuticals Ltd.
50
4.3.4. Maintenance of Sterile Areas

Concentration
Area Cleaning solutions Time
(%)
IPA 70
Covers of Laminar air Before & after
Savlon 17.5
flow Production
Filling & Sealing machine IPA Before & after

70
Production
Walls IPA Once a week

70
Powder Dosing (a) 9/18
micro Machine Capping Cartoning
Ceiling 70 Machine
Washer
IPA Once a week
DepyrogenationTunnel
Hypochlorite
1 Once a week
solution
Floors Savlon 17.5 Every day
Dettol 2.5 Every day
4.3.5. Lyophilized Products

Lyophilization or freeze drying is a process that is playing an increasingly important role in
the Pharmaceutical industry today. The process is an optimal drying method under vacuum to
extend the lifetime of moisture and temperature sensitive medicine. It gives products
excellent solubility characteristics that allows for rapid reconstitution. In Bangladesh, Incepta
is the first manufacturer of lyophilized products. The whole facility is set up in clean room
environment in order to maintain high quality standard and aseptic processing. Sophisticated
equipment are used to meet the specialized requirements needed for the process.
4.3.6. Lyophilization Process
Precooling at -45ºC for 2 hours
↓
Primary Drying up to -25ºC (ramp duration)
↓
51
Wait for 250 minutes at -25ºC (soak duration)

↓
Apply vacuum at 0.2 milibar
↓
Allow temperature to rise up to 10ºC
↓
Secondary Drying at 30ºC for 30 minutes
↓
Wait for another 250 minutes at 30ºC
↓
Deicing by 85-90ºC pure steam
↓
Nitrogen gas is used to remove moisture
↓
Collect product at 25-30ºC
Figure 14: Lyophilized Filling Machine (Front) of Incepta Pharmaceuticals Ltd.
52
Lyophilized products manufactured by Incepta include

 Pantoprazole – Pantonix 40 injection
 Omeprazole – Omenix 40 injection
 Esomeprazole – Esonix 40 injection
 Vecuronium Bromide – Nor Q injection
 Azithromycin – Tridosil IV infusion
 Vitamin B Complex and Vitamin - C – Aritone IV
Figure 15: Lyophilized products of Incepta Pharmaceuticals Ltd.
4.3.7. Ophthalmic Preparation

With continuous effort to provide better products, Incepta established a state-of-the-art
ophthalmic facility. It is well-equipped with technologically advanced equipments and it
strictly maintains quality standards.
All eye drops are manufactured in a specially controlled aseptic environment, where it has the
highest precision in every area.
53
Figure 16: Ophthalmic products of Incepta Pharmaceuticals Ltd.

Self-filling a syringe can be a difficult process, which is not only slow but can also result in
incorrect dosages and spillage. The availability of prefilled syringes allows both convenience
and accuracy to self-administered drugs.
Incepta has built up an international standard, pre-filled syringe filling facility under aseptic
condition. The state-of-the-art machineries have all the latest technologies which can fill up
to 0.1 ml of product. It is a closed system with isolator technology which protects the
medication from contamination.
Some of the products manufactured in this facility are:
 Sodium Hyluronate – Hyronate
 Filgrastim (rDNA) – Filastin
 Erythropoietin (rDNA) – Epoetin
 Enoxaparin Sodium – Parinox
 Hydroxypropyl Methyl Cellulose – Lubric Gel
 PEG Interferon α-2A - Optipeg-A
54
Figure 17: Pre-filled Syringe Filling products of Incepta Pharmaceuticals Ltd.
4.3.8. Nasal Preparation

Nasal preparations are intended for application of drug to the systemic circulation via naso-
pharingeal route and so they posses a separate group of pharmaceutical preparations.
These pharmaceutical preparations are prepared with care because of their administration in
microbial infections.
At Incepta Pharmaceutical Limited, the nasal preparations are manufactured & dispensed in
two forms;
 Nasal Drop
 Nasal Spray
Supported by special controlled production facilities, Incepta has a strong line-up of nasal
sprays and drops. The production is done under condition which minimizes microbial and
particulate contamination.
We have wide spectrum presentation of nasal sprays and drops for effective and safe
treatment of allergic rhinitis and related complications.
Some of the products manufactured in this facility include:
 Oxymetazoline – Rynex Nasal Drops & Spray
 Mometasone Furoate – Momeson Nasal Spray
 Fluticasone Propionate – Lutisone Nasal Spray
 Budesonide – Budicord Nasal Spray
 Triamcinolone Acetonide – Cenolon Nasal Spray
 Olopatadine – Lopadine Nasal Spray
55
Figure 18: Nasal Sprays & Drops of Incepta Pharmaceuticals Ltd.
A
4.4. Cephalosporin Products
According to cGMP regulations separate facility for Cephalosporin is required to prevent
cross contamination with other penicillin products or non-beta-lactum products. Unintended
exposure with Cephalosporin products may cause health concern to patients sensitive to
Cephalosporins.
 Fully separated, well established and isolated manufacturing area only for
Cephalosporin.
 Highly sophisticated HVAC system and AHU are used to condition, monitor and
supply clean air to the working zone.
 Production floors and wall are covered with epoxy resin.
Incepta is the first national company in Bangladesh to build a dedicated state-of-the-art
Cephalosporin facility. Incepta currently produces tablets, capsules, powder for suspensions
and injectables in this facility.
Some of the high quality cephalosporin brands that are produced by this pioneer facility
include:
 Cefadroxil – Adora
 Cefepime – Ultrapime
 Cefixime – Emixef
 Cefpodoxime – Ximeprox
56
 Cefradine – Procef
 Cefetamet – Tenafet
 Ceftazidime – Sidobac
 Ceftriaxone – Exephin
 Cefuroxime – Kilbac
 Cefotaxime – Cefotim
57
Figure 19: Cephalosporin products of Incepta Pharmaceuticals Ltd.
4.4.1. Machineries Used in Cephalosporin Area

Serial
Name of Machine Brand Name Origin Capacity
No.
Vial Washing, Filling, Capping &

01 Macofar Italy 9000/hr
Packaging Machine
02 Tablet Compression Machine N.R Industries Thailand 13 station
03 Film Coating Machine N.R Industries Thailand 20 kg
04 Blister Machine Hoonga Thailand 6000/hr
05 Encapsulation Machine Sejong SF Korea 40000/hr
06 Powder Loader Korea
Powder for suspension Filling

07 Jih Cheng Taiwan 3000/hr
Machine
08 Bottle Washing Machine Taiwan
09 Sealing & Labeling Machine Italy
10 Dryer India
350 & 700

11 Blender Cosmec Italy
Kg
58
12 Multi Mill India
13 Autoclave Celestar Spain
59
5. Packaging
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 Cleanroom. Some common pharmaceutical packaging
techniques include foil and heat sealing; polyester and olefin package printing; polyethylene
and polypropylene printing; and flat bed die cutting.
The main purpose of using packaging material is to keep the pharmaceutical preparations safe
from any types of contamination.
Pharmaceutical products are mainly packed into two steps:
5.1. Primary Packaging
The packaging material with which the product always remains directly in contact is called
primary packaging. For example, blister packaging, bottle filling, foiling of capsule etc.
5.2. Secondary Packaging
After the primary packaging the products are packed with one or more packing material is
called secondary packing. For example, packing in outer carton or Shipper undergoes to
secondary packaging. Secondary packaging can be also classified into another two types.
These are:
a. Online Packaging
b. Offline Packaging
a. Online Packaging:
The packaging in which the primary packaging and secondary packaging are done
simultaneously is called online packaging.
b. Offline Packaging:
The packaging in which the primary packaging is done first and the secondary packaging is
done later, is called Offline Packaging.
The packaging materials are selected when they fulfill the following characteristics:
 They must protect the preparation from environmental conditions.

 They must not be reactive with the product
60
 They must not impart to the product tastes or odor

 They must be non-toxic
 They must be FDA approved
 They must applicable temper-resistance requirements
Figure 20: Honga Blister machine of Incepta Pharmaceuticals Ltd.
In Incepta Pharmaceutical Limited following packaging materials are used

In Primary Packaging
 Poly vinyl chloride (PVC)
 Poly vinyli di-chloride (PVDC)
 Aluminum foil
 Aluminum tubes
 Glass vials and ampoules
 Glass bottles
 Plastic bottles
 Plastic container
In Secondary Packaging
1. Paper packet :
2. Three types-
61
a. Swedish (gives yellow color when tearing)

b. Cromolex (gives white color when tearing)
c. Duplex (gives gray color when tearing)
3. Shipment carton
Following packs are available here:
 Strip pack
 Blister pack
Following materials are also included in packaging:
 Label
 Insert
 Tape
 Plastic cap
 Dropper
 plastic
62
6. Quality Assurance Department

Quality assurance (QA) is a wide-ranging concept covering all matters that individually or
collectively influence the quality of a product. With regard to pharmaceuticals, quality
assurance can be divided into major areas: development, quality control, production,
distribution, and inspections. Quality assurance is the heart and soul of quality control.
QA= Product Design + GMP + QC+ Quality goal activities
Quality is built-in. Only a quality raw material, under correct operation procedure and quality
production facilities, handled by qualified personnel, under controlled environment can result
a quality drug products. Deviation in any stage of manufacturing can affect the overall quality
of a drug product as a result Quality
Assurance is a wide-ranging concept, which covers all matters that individually and or
collectively influence the quality of a product. As whatever not written is not done,
documentation is a very important.
Quality Assurance (QA) department of Incepta Pharmaceuticals Limited is associated with-
 Quality Control
 Quality Compliance
 Quality Surveillance
The Quality Assurance department maintains product quality through cGMP & various
organized activities. This department is correlated with raw materials & packaging materials
sampling up to market compliance.
63
6.1. Functions of Quality Assurance

The main functions of Quality Assurance include-
 In-process Check/Control (IPC)
 Documentation
 Finished Goods Release
 Retention sample management
 GMP Training/ Coordination
 Market (Drug Product) complaint Handling
 Arranging quality audit visits to suppliers & self-inspection.
 To ensure implementation of GMP in routine operations.
 Establishing manufacturing methods & SOPs covering entire procedure.
 Identifying problems & positive actions for error cause removal.
 To ensure product quality & adequate training program
6.2. In-process Check/Control (IPC)
Table 17: In-process Check/Control (IPC) for
In-process Check/Control (IPC) for
Solid Liquid Semisolid
Blend uniformity
Loss on drying (LOD) Identity
Appearance Odor
Average weight Viscosity

Description
Dosages uniformity Fill variation weight
Assay
Hardness PH
Particle size
Thickness Screen
Foreign matter
Friability Average fill intent
Weight variation Specific gravity
Disintegration
Dissolution
Ampoule/vials Blisters after packing
64
Filling
Filling
Sealing
Sealing
Leak test
Weight variation
Presence of dust
Filled Volume
6.3. Documentation
Documentation of QA department includes the followings-
 Record of annual Batch Production Record (BPR)
 Record of LOG books
 Temperature & Humidity control record
 Goods destruction records
 BPR Archival
 Product Change Over Certificate
 Out of Specification Certificate
 Process Validation Record
65
Table 18: A Batch Production Record (BPR) Contains

A Batch Production Record (BPR) contains
Fill Label Pack (FLP) Order
Maximum Material Received (MMR)
Batch Printing Order sheet
Number
In-Process Checks
Analytical Report Sheet (ARS)
Report of Inspection (ROI)
Bulk or Raw material Scan Sheet
Label/Carton Sample
Quality Assurance Profile
Sterility Report
Wt./Vol.Chart
Pyrogen Report
Product Change Over Certificate
Toxicity Report
Lot Accountability
Finished Good Releases order
Label Accountability
Others, if any
6.4. Retention Sample Management

 Sampling of raw materials (Both actives & excipients) & packaging materials.
 Destruction of rejected or expired Products according to SOP.
6.5. GMP Training/ Coordination

Arrangement of Training for both
Officers & Workers.
6.6. Market complains Handling
 Collection of rejected goods & maintenance for at least 5years
 Problematic product handling
66
7. Quality Control Department

Quality Control Department is very important for a pharmaceutical industry to maintain
GMP. The concept of Total Quality Management refers to the process of striving to produce a
perfect product by a series of measures requiring an organized effort by the entire company to
prevent or eliminate errors at every stage in production.
The Quality control Department confirms the quality of a product not only during production
but also to its final stability in the market, its potency, physical and chemical parameters of
raw materials (both active & excipients). The Quality control department Maintain record
books or file of work done in the factory and others records.
The Quality control Department has the following functions
 General chemical analysis of-

--Raw materials
--Packaging materials
--Finished products
 Analytical method development

 Stability test
 Microbiological test
At Incepta Pharmaceutical Limited, Quality Control Department is subdivide into three

sections, namely-
 Raw materials & Packaging section

 Commercial section
 Method Development section
67
Figure 21: QC Laboratory of Incepta Pharmaceuticals Ltd.
7.1. Raw materials & Packaging Section

Raw materials & Packaging section of QC deals with all the analytical procedures required to
meet the specifications of raw materials & packaging. The tests performed by the section for
both raw materials & packaging are as follows:
Table 19: Raw Materials
Raw materials
Solid raw materials Liquid raw materials
Identification Maximum tests for solid

LOD Refractive index
Residue on ignition PH
Bulk density Weight per ml
Heavy metal testing Viscosity
Impurities
Melting point
Screen test
68
Assay
Table 20: Packaging Material

Packaging Material
Label Cartoon Catch cover
Text Color & Text Same test as done for

Color Proper gumming or gluing cartons.
Size Proper locking Contains no MRP.
Bottles Vials Foils
Body diameter Alkalinity Color

Neck finish & Height Thickness Thickness
External/ Internal diameter Diameter Width
Opacity Leak test
Percentage of Aluminium
& Resin
Rubber closure Ampoules Cap
PH Alkalinity Printing
Stickiness Thickness Color
Toxicity Height Diameter
Density Breaking point Height
Alkalinity Volume
69
7.2. Commercial Section

Commercial section of QC deals with all the analytical procedures required to meet the
specifications of finished Products. The tests performed by the section for Finished Products
are as follows:
Finished product
Solid preparation Liquid preparation Dry syrup
Description Description Description

Disintegration time Weight per ml Assay
Dissolution time Assay Reconstitution rate
Weight variation PH Dispersion
Assay Microbiological limit test
Stability Testing
7.3. Method Development Section

Method Development Section of QC performs the following functions-
 Standardization of Standard Operating Procedure (SOP)

 In house analytical method development
 Development of Standard Testing Procedure (STP)
 Equipment verification/ calibration,
 Process Validation
7.4. Stability Test

Stability test is done for a finished product to predict whether the product be stable for
sufficient time to ease marketing of the product according to ICH guideline (International
Conference on Harmonization) Stability test is done for any new drug, change in the
formulation, change in primary packaging material, for change in the source of raw material
and for registration purpose
70
7.5. Conditions of Stability Test

Real time stability test: In real time stability test, the product is kept up to one year more
than predicted expiry date i.e. shelf life. The storage condition is-
Temperature: RT ± 20C
Relative humidity: 60 ± 5%
Accelerated stability test (AST): In accelerated stability products are kept for short life (3 or
6 months) in accelerated condition. Upon the stability over this condition, shelf life is
predicted.
Temperature: 40 ± 20C
Relative humidity: 75 ± 5%
Prediction of Shelf Life
 If a product is stable over 1 year real time stability test, then 2 years of shelf life can be
predicted for the product.
 If a product is stable over 3 months accelerated stability test, then 2 years of shelf life
can be predicted for the product.
 If suppository is stable over 1 year real time stability test, then 1.5 years of shelf life
can be predicted for the products. Accelerated stability test can’t be done for
suppository, as it tends to melt on body temperature.

Stability Testing Parameters
 Description  Disintegration
 Assay  Dissolution
 Viscosity  Friability
 pH  Hardness
71
Figure 22: HPLC Machine of Incepta Pharmaceuticals Ltd.
7.6. Instruments Available in the QC Department & IPC

 PH meter,  HPLC machine
 Dissolution tester  Magnetic stirrer
 Disintegration tester,  Ultrasonic bath
 Friability Testing Apparatus,  UV spectrophotometer
 Tablet Hardness Tester  FTIR spectrophotometer
 Melting point apparatus,  GC machine,
 Potentiometric titrimeter  Heating Mantle
 Atomic Absorption  Dehumidifier
Spectrophotometer (AAS)  Vacuum Filter
 Leak test apparatus  Polarimeter,
 Halogern-moisture analyzer,  Karl-Fischer Titrator,
 Electronic balance  Shaker
72
8. Microbiology Department
Microbiology is the study of microorganism. It is concerned with their form, structure,
reproduction, physiology, metabolism and classification. It includes the study of their
distribution in nature, their relationship to each other and to other living organisms, their
effects on human beings and on other animals and plants.
The Microbiology department at Incepta Pharmaceutical Limited works in association with
the QC department. The areas its analysis and different analytical methods are given below:
Table 21: The areas its analysis and different analytical methods
Tests Required for Tests
Microbial limit test
Pyrogen test (LAL test)

Raw materials
Sterility test (in case of sterile RM)
Sensitivity (potency) test for antibiotics
Packaging materials Microbial limit test
Pyrogen test (LAL test) (for WFI)

Water
Conductivity
(Raw, DM, WFI)
PH
Environment Microbial limit test by settle plate
Microbial test
Filters
Sterility test
Personnel Microbial limit test
73
Figure 23: Microbial activities of Incepta Pharmaceuticals Ltd.
8.1. Common Microbiological Tests

Table 22: Different Microbiological Tests
Temperature Incubation period
Microbiological tests Required media
(0C) (Days)
TSB 37 7
TGM 22 14
Limulus
Pyrogen test (LAL test) Amebocyte Lysate 37 14
(LAL) reagent
TSB 37 7
Sterility test
TGM 22 14
Sensitivity test TSB 37 3
74
Figure 24: Kinetic LAL test of Incepta Pharmaceuticals Ltd.
8.2. Instruments available in the Microbiology Laboratory

 Refrigerator  Shaking Bath
 Hot Air Oven
 Dry Heat Sterilizer
 Moist Heat
Sterilizer/autoclave
 Antibiotic Zone reader
 Laminar Air flow unit
 Particle counter
 Incubator (Warmed)
 Incubator (Cooled)
 Microscope
 Micropipettes
 PH Meter
 Conductivity Meter
75
9. Engineering Department
The Engineering Department guarantees proper production environment. The manufacturing
area of a Pharmaceutical plant demands different grades of cleanliness. Apart from particles,
moisture and temperature should also be within specification. Pharmaceutical plant also uses
different grades of water, steam lines, vacuum system and so on. All these utilities are
maintained by the Engineering Department.
9.1. Facilities
9.1.1. Electricity
The electricity supplies from 2 gas Generators of capacity 805 KW & 523 KW. the plant has
an electricity supply from Rural Electrification Board (REB) The plant has its own back up
secondary power system with 2 stand by Diesel generators, which provide 350KW &
252KW.
9.1.2. Central Air-conditioning System
The plant is fully air conditioned by central Fan Cooling Unit (FCU) system using 2 chillers
of capacity 350 tons and 250 tons, where ‘air compression’ ® ‘condensation’®
‘expansion’® ‘evaporation’®then again compression cycle is maintained
9.1.3. Air Handling Unit
There are 17 air-handling units including laminar airflow system. The individual air
conditioning unit is provided for separate section of the plants as per requirement, for
example, separate air handling units for sterile area, cooling area, washing area, production
area, administration area, Cephalosporin Building etc.
9.1.4. Air filtration System
This system is mainly used for sterile air for sterile area (Injection and Ointment) and
Cephalosporin Building.
9.1.5. Compressed Air
Compressed air is provided by central system with Two-compressor with speed of
6.98m3/min.
9.1.6. Boiler (Steam Generator)
The boiler or steam generator is of Shellmax Company. It has a capacity of 2.00 tons and
supply capacity of 3000 LBS/hr. Although the maximum used now about 2200 LBS/hr.
76
9.1.7. Water Supply

The plant has its own water supply from deep tube-well with a capacity of 17000 Liter/hr and
treated by RO Plant with a capacity of 2000Liter/hr to get purified water and DIP plant with a
capacity of 1500Liter/hr for getting de-mineralized (DM) water. This water goes to the distil
water plant section and after that it goes to multicolumn plant for getting WFI. Finally its
goes to the different section. There are two distil water storage tank of 1500 liter capacity
which maintain water at 800C continuously to avoid the growth of the microorganism and the
water is always remain in circulation which called loop system.
9.1.7.1. Types of water
 Well water
 Hot water
 Purified water
 DM water
 Water For Injection

(WFI)
77
9.1.7.2. Schematic Diagram of Purified Water Plant

Portable Automatic Break
water Multimedia
filter Reverse Osmosis
Automatic Softener Automated Carbon Filter

Coreless
(absorbs Cl and organic
filter
molecules)
(10µ)
Soften Water tank Heat exchanger Cartridge

filter
Circulation Booster
pump pump
Storage tank
(600L) Continuous
Purified Electro deionizer
Water
Loop
circulation Heat
pump exchanger
User Point
(25
78
Figure 25: STILMAS Water for Injection Plant

9.1.8. HVAC System
HVAC (heating, ventilation, and air conditioning) refers to technology of indoor or
automotive environmental comfort. HVAC system design is a major subdiscipline of
mechanical engineering, based on the principles of thermodynamics, fluid mechanics, and
heat transfer.
HVAC is important in the design of medium to large industrial and office buildings such as
skyscrapers and in marine environments such as aquariums, where safe and healthy building
conditions are regulated with temperature and humidity, as well as "fresh air" from outdoors.
79
Figure 26: Schematic Diagram of Air Handling Unit (AHU)
9.1.9. Effluent Treatment Plant

The purpose of an Effluent Treatment Plant (ETP) is to reduce Biological Oxygen Demand
(BOD) & Chemical Oxygen Demand (COD) of pharmaceutical unused chemicals, powders
and waste materials which may cause severe harmful effect on environment as well as human
health.
Effluent management in Incepta Pharmaceutical Limited is carried out through biological
and chemical treatment process.
80
Process Flow Chart of Effluent Treatment Plant (ETP)
Collection Tank
↓
Storage Tank
↓
Mixing & Cooling
↓
Neutralization
↓
Chemical Coagulation
↓
Biological Oxidation Tank
↓
Sedimentation & Separation of Sludge
↓
Sludge Thickener
↓
Filtration
↓
Discharge to Drain
Collection Tank: Commencing part, waste from different section enter here.
Storage Tank: Several blower pipes in this chamber. Mixing properties are different with
temp. as well.
Mixing & Cooling: Cooling tower is on paddle mixer used for mixing.
Neutralization: PH is controlled here.
Chemical Coagulation: Fe₂ (SO₄)₃, Al₂(SO₄)₃ etc use for coagulation.
Biological Oxidation Tank: Artificially Eco-system established. Blowing air helps to live
micro-organism.
Sedimentation & Separation of Sludge: The blanket of precipitations is skimmed off to
another tank and remaining solution is removed to pressure filter.
Sludge Thickener: After exceeding the required level of recycling, sludge passed through
thickening chamber.
Filtration: Filtration layer consists of sand rock which filters wet sludge to extract water rest
in it.
Discharge to Drain: Release to environment with the check of final load of effluent in it.
81
10. Conclusion
I feel very much proud on the completion of our in-plant training in The Incepta
Pharmaceuticals Ltd. as it is the leading pharmaceutical industry in Bangladesh. Its
contribution for the development of national economy is well known. I have gained cast
knowledge during this training period that will be definitely helping me in future.
Our academic curriculum would be insufficient if I was not here. But why I feel proud, the
cause is, first of all this is the fast-growing pharmaceutical industry in Bangladesh that
maintains “quality” first. Most important is that the company is assuring quality of all its
products and its company is doing its best to make medical development of human resources
of our country.
I would like to say that I have achieved my best knowledge here by having the opportunity to
have my training here. So, I am very much thankful to the Authority of Incepta
Pharmaceuticals Ltd.
I have learned many others thing from here, one of them was discipline. The Incepta
Pharmaceuticals Ltd. strictly follows the discipline, which is the key to their success and also
important in any organizational level. The officers here try heart and soul to lead the
company forward.
The two weeks in plant training has been completed successfully by the help of all the people
The Incepta Pharmaceuticals Ltd. My achievement during this training will eventually help
me in my professional life.
On behalf of our department and on my own behalf, I would like to express my hearties
thanks to Incepta Pharmaceuticals Ltd. I hope that such cooperation between the authority of
Incepta Pharmaceuticals Ltd. and the department of Pharmacy, Southeast University
Bangladesh will be strengthened day by day and will remain everlasting.
Finally, all best wishes to Incepta Pharmaceuticals Ltd.
82
11. References
 www.inceptapharma.com
 The Theory and practice of Industrial Pharmacy- Leon Lachman
 http://en.wikipedia.org/wiki/Incepta_Pharmaceuticals
 Assurance of Quality Pharmaceuticals- Dr.M. Shah Nawaz Khan
83

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Report On In-Plant Training At Incepta Pharmaceuticals Ltd.

Table 1: Address of Incepta Pharmaceuticals Limited.

1.1. Values of Incepta

1.2. About Incepta Pharmaceuticals Limited

Incepta Vaccines Limited, a sister concern of Incepta Pharmaceuticals, has already

1.3. Vision and Mission

1.4. History of Incepta

1.5. Chronology of Events

 December 16th 1998, the construction of the factory began.

 The company maintained the 2nd largest (IMS) position in 2009.

1.6. Growth in Incepta Comparison with Local Pharma Market

Figure 6: Growth in Incepta Comparison with Local Pharma Market

Table 2: Growth In Comparison With Local Pharma Market

2014 696 1 2nd

2013 686 7 2nd

2012 631 7 2nd

2011 632 9 2nd

2010 594 10 2nd

2009 585 4 2nd

2008 532 10 2nd

2007 451 17 3rd

2006 368 9 3rd

2005 288 12 3rd

2004 198 6 5th

2003 154 18 8th

2002 119 14 10th

* Intercontinental Marketing Services (IMS)

2. Departments in Incepta Pharmaceuticals Limited

 Medical Service Department

 Human Resource Department.

 Regulatory Affairs Department

 Finance & Accounts Department

 Management Information Department

 Quality Assurance Department

 Product Development Department

 International Marketing Department

3.1. Storage Area for Raw materials

 Cool room: 2-8 °C

 Dispensing room: for dispensing of ingredient.

3.2. Storage Area for Finished Product

3.3. Storage Area for Packaging Materials

3.4. The major activities of Warehouse

Figure 7: Warehouse Department of Incepta Pharmaceuticals Ltd.

3.5. The duties of Ware House is sequentially- (Raw Materials Receive)

Checking of vehicle with Receiving chalan/Invoice (Exact product, volume/amount)

Unloading vehicles, sorting and palletization

Cleaning of incoming materials

Checking for damage/loss/excess

Information entry in “Systemic Application product in data Processing” (SAP)

Preparation of “Goods Receive Information” (GRI) & Quarantined Label

Affixing of “Quarantined Label” & transfer of materials to the quarantine area of

Sending out of GRI to QC department

Result: Released Result: Reject

Affixing of release label, transfer of Affixing of reject label & transfer of

Informing PPIC about rejection of

Checking of materials “Process Order”

Information entry in the required field of BMR

Arranging of required released materials as per FIFO/FEFO system

Information entry in Bin Card