The document describes the trainees' in-plant training report submitted to Beximco Pharmaceuticals Ltd, thanking the company for the opportunity and providing an overview of the aims and objectives of their training, as well as summaries of their experiences in each department.

1. Crossponding by Md. Mehdi Hasan & Mizanur Rahman;Email:mehdinub@yahoo.com
In-plant Training
Repot
On the basis of
Observation
Beximco Pharmaceuticals Ltd.
Submitted to:
Brig. Gen. Md. Mehboobul Haque (Retd.)
GM, HR & Admin.(Factory)
Beximco Pharmaceuticals Ltd.
Submitted by
Md.Mehdi Hasan Northern University Bangladesh
Kallol Banik Stamford University Bangladesh
Md.Mizanur Rahman Stamford University Bangladesh
Mahbub Hasan Stamford University Bangladesh
Ajoy Kumar Ghosh Stamford University Bangladesh
Rozi Hasna Stamford University Bangladesh
Ms.Sumaiya Mahmud University of Development Alternative
Training Duration
1st
June 2016 to 13th
June 2016
Date of submission
14th
June 2016

2. 2
14th
June, 2016
The General Manager,
Brig. Gen. Md Mehboobul Hoque (Retd.)
GM, HR & Admin (Factory) Beximco Pharmaceuticals Ltd.
126, Kathaldia, Nishatnagar,Tongi- 1711,
Gazipur, Bangladesh.
Subject: Submission of In-Plant training report.
Dear Sir,
At first, we the trainees of Northern University Bangladesh(NUB), Stamford University Bangladesh,
and University of Development Alternative(UODA) would like to relay our deepest gratitude to you
for providing us with the opportunity to attend in our in-plant training program from 1st June 2016
to 14th June 2016 in your renowned company as per our academic requirement. We take great
pleasure in informing you that we have successfully completed the training program and as a part of
it we have tried to prepare a comprehensive report on various aspects of Beximco Pharmaceuticals
Ltd.
We therefore will be much obliged to you if you will be kind enough to accept the report and also
would be kind enough to forgive our mistakes that might have taken place unintentionally.
Yours sincerely,
Md.Mehdi Hasan , Northern University Bangladesh
Kallol Banik , Stamford University Bangladesh
Md.Mizanur Rahman,Stamford University Bangladesh
Mahbub Hasan, Stamford University Bangladesh
Ajoy Kumar Ghosh,,Stamford University Bangladesh
Rozi Hasna,Stamford University Bangladesh
Ms.Sumaiya Mahmud,University of Development Alternative

3. 3
Aim & Objectives
For the last four years, we went through several courses of pharmacy to complete our
graduation. We studied many topics theoretically and also done our practical classes with
some basic equipments and machines but could not see their implementation in
pharmaceutical industries. So far the enrichment of our theoretical knowledge we are here
in your pharmaceutical industry and our objectives are,
1. For the development of our practical skills and techniques which are directly
applicable to our careers.
2. To realize and know how a pharmaceutical company runs.
3. To know how its departments are interlinked and work together.
4. To identify how GMP or cGMP is applied in the plant.
5. To have an idea about Standard Operating Procedure (SOPs).
6. To get information about how a product runs smoothly and be a quality based
product.
7. To understand how pharmacists manage the manufacturing problems.
8. To see how quality is assured as well as controlled.
9. To learn about the documentation record practices.
10. To get general ideas about corporate environment and activities of an organization.

4. 4
Acknowledgement
Internship program or In-plant training in any pharmaceutical company is an important part for the
partial fulfilment of Bachelor of Pharmacy Course (B. Pharm). We are fortunate enough to have a
chance to complete our In-plant training in Beximco Pharmaceuticals Ltd (BPL).
We would like to express our gratitude to Beximco Pharmaceuticals Authority especially to Brig. Gen.
Md. Mehboobul Haque (Retd), GM, HR, Admin (factory) and Mr. Lutfur Rahman,Director,
Manufacturers all other officers & members of Beximco Group for their cooperation and valuable
guideline.
We wish to express our deepest sense of gratitude thank to Mr. Alim Russell ,officer, HRA Factory,
who was the main coordinator of our training program specially for his friendly & affectionate
behavior.
We are extremely indebted to
1. Mr. Animesh Bhowmik (Senior Assistant Manager, Production Planning)
2. Mr. Partha Pratim Barua (Senior Manager, Warehouse)
3. Mr. Md. Ashraful Alam (Senior Manager, Solid Dosage Formulation)
4. Mr. Subodh Charndra Das (GM, Research & development)
5. Mr. Md. Abdul Mannan Miah (Senior Manager, Liquid dosage formulation)
6. Mr. Salim Hossain (DGM, Quality Control Department)
7. Mr. Md. Sazzad Hossain (Manager, Quality Assurance Department)
8. Ms. Soomna Lohani (DGM, Infusion Unit LVP formulations)
9. Mr. Yusuf Hossain (GM, Engineering Services & Utilities)
10. Ms. Saima Sultana (Senior Manager, Training Department)
11. Mr. Zakir Hossain (Manager, EHS), for their valuable instructions & information.
During our three weeks of training in Beximco Pharmaceuticals Ltd, we have got lots ofgenerous
cooperation from every people at every sector. We are really thankful to all the officers and workers
of the factory for treating us as family and helping us to widen our knowledge.

5. Index
HRA 13
Production Planning 18
Warehouse 22
Solid Dosage Formulation 27
Research and Development 52
Liquid Dosage Formulation 61
Quality Control Department 64
Quality Assurance Department 73
Infusion Unit: Large Volume Parenteral
Fromulations
78
Engineering Services & Utilities 84
EHS 91
Training Department 94
Findings 98

6. Introduction
Medicine is directly related to human life and therefore, its manufacturers
have massive social responsibility of providing safe and effective medication.
From its very initiation, Beximco Pharmaceuticals has always highlighted the
need for rigid quality. Beximco‘s commitment to quality is clear from its
progressive use of state of the skilled manufacturing technology.
Beximco strictly follows WHO guidelines at every stage of manufacturing and
procures its raw materials from the very best sources. But what makes Beximco
a success story is its people. Beximco‘s team of highly skilled and motivated
professionals work around the clock to guarantee the safety and efficacy
ultimately the qualities of its products
In plant training is a golden opportunity for a student to transform his/her
theoretical knowledge into practical experience. That having been said,
successful interns will have a fantastic experience, one that will be most
enjoyable & rewarding .our experience at ―BEXIMCO PHARMACEUTICAL
LTD‖ was quite amazing & it is one that we will certainly never forget.
A successful in plant training is the first step towards a successful professional
life. From this point of view we can certainly say that,we have had an
interesting & educational in plant training. This internship helps us to get an
insight into procedural aspect of a pharmaceutical company & to prepare
ourselves for the existing job field.

7. COMPANY PROFILE
―BEXIMCO PHARMACEUTICALS LTD‖ is one of the well renowned manufacturers of
pharmaceutical products as well as Active Pharmaceutical Ingredients (APIs) in Bangladesh
and also in the global market
―BEXIMCO PHARMACEUTICAL LTD‖ is a dynamic, progressive company engaged in the
science of mankind. It proudly stands today as one of the most reputed pharmaceutical
company of Bangladesh.
―BEXIMCO PHARMACEUTICAL LTD‖ is a private limited company established in the
end of 1976 & started production in the end of 1980 with the view of formulate & supply
quality pharmaceutical products to the people of Bangladesh.
―BEXIMCO PHARMACEUTICALS LTD‖ is the first pharmaceutical company who got the
most sophisticated and sensitive approval of USFDA which brings enormous proud for
Bangladesh.
―BEXIMCO PHARMACEUTICAL LTD‖ believes quality is first & to ensure quality they
have excellent facility & number of experience 7 skilled personnel who are contributing for
that.
BEXIMCO Group is the largest private sector industrial conglomerate in Bangladesh
engaged in diverse business areas. The Group turnover in 2008 was BDT 18.5 billion.
BEXIMCO employs 35,000 people and has 230,000 shareholders. BEXIMCO‘s shares
constitute 4.73% of the market capitalization of DSE.
We have successfully completed our training in ―BEXIMCO PHARMACEUTICAL LTD‖.
We took the notes during our visit to different departments. This report will only represent
what we have seen, what we have learnt & what we have been taught during our training. We
hope this report will help us to implement our experience in our working field.

8. KEY COMPANY INFORMATION:
Year of Establishment : 1976
Country of Incorporation : Bangladesh
Commercial Production : 1980
Status : Public Limited Company
Business Lines : Manufacturing and marketing of pharmaceutical Finished
Formulation Products, Large Volume Parenterals and Active
Pharmaceutical Ingredients (APIs)
Main Country of operation : Bangladesh
Corporate Headquarter &
Registered Address
: 17 Dhanmondi R/A, Road No. 2, Dhaka- 1205, Bangladesh
Phone: +880-2-58611891
Fax: +880-2-58613470
Email : beximchq@bol-online.com
Operational Headquarters : 19 Dhanmondi R/A, Road No. 7, Dhaka- 1205, Bangladesh
Phone : +880-2-58611001-7
Fax : +880-2-58613888, +880-2-58614601
Email : info@bpl.net
Website : www.beximcopharma.com
Overseas Offices & Associates : Australia, Bhutan, Cambodia, Chile, Ghana, Hong Kong,
Indonesia, Jordan, Kenya, Kuwait, Malaysia, Myanmar,
Nepal, Pakistan, Philippines, Saudi Arabia, Singapore, Sri
Lanka, Vietnam and Yemen
Authorized Capital (Taka) : 9,100 million
Paid-up Capital (Taka) : 3,862.4 million
Number of Shareholders : Around 90,000
: Dhaka and Chittagong Stock Exchanges of Bangladesh and
Stock Exchange Listings AIM of London Stock Exchange
Number of Employees : Upper 3,063
TIDM: (Tradable Instrument
Display Mnemonic)
Date shares were admitted to
trading
: BXP
: Dhaka Stock Exchange : 3 July, 1985
Chittagong Stock Exchange : 11 June, 1995
AIM ( Alternative Investment 21 October,
Market)
:
2005
ISIN : US0885792061

9. MILESTONES ARCHIVED BY BEXIMCO:
1976 Registration of the company.
1980
Started manufacturing and marketing of licensee products of Bayer AG of
Germany and Upjohn Inc. of USA.
1983 Launching of BeximcoPharma‘s own brands.
1985
Listing in the Dhaka Stock Exchange (DSE) as a Public Limited Company
(PLC).
1990 Commissioning of Basic Chemical (APIs) unit.
1992 Started export operation with Active Pharmaceutical Ingredients (APIs).
1993 First export market operation with finished formulations.
1996 Introduction of Sustained Release Dosage form.
1997
Introduction of Suppository Dosage form; Commissioning of Metered Dose
Inhaler (MDI) plant; Introduction of Metered Dose Nasal Spray.
1998
First pharmaceutical company of the country achieving ‗National Export
Trophy (Gold)‘ for 1994-95.
1999 UNICEF approval of BeximcoPharma as an enlisted supplier.
2000
Agreement to manufacture Metered Dose Inhaler (MDI) for
GlaxoSmithKline.
2001
Introduction of Small Volume Parenteral (SVP) products; establishment of
Analgesic Anti-inflammatory bulk drug plant.
9

10. ®
2003
Received ―National Export Trophy (Gold)‖ for consecutive 2 years .
(1998-99, 1999-2000)
Won the Silver prize of ICAB National Awards 2003 for ‗Best Published
Accounts and Reports‘ in Non-Financial Sector Category.
Introduced Anti-HIV drugs for the first time in Bangladesh.
Diversification into Anti-Cancer therapeutic class.
2004
Signed contract with Novartis to manufacture their liquid, cream, ointment
and suppository products under ―Toll Manufacturing‖ agreement.
Merger of Beximco Infusions Ltd. with Beximco Pharmaceuticals Ltd.
2005
Admission to Alternative Investment Market (AIM) of London Stock
Exchange (LSE)
2006
New USFDA standard Oral Solid Dosage (OSD) Plant Commissioned
Successfully relocated/outsourced penicillin and cephalosporin
manufacturing facilities as per cGMP guidelines Introduced generic
oseltamivir in Bangladesh Launched CFC free ozone benign HFA inhalers
as the first company in Bangladesh
2007 Launches Microincapsulation
2008
Become the first Bangladeshi company to achieve GMP Clearance from
TGA Australia. Also become the first Bangladeshi company to receive
export approval to Gulf countries.
2009 Only Bangladeshi company to receive GMP approval from ANVISA, Brazil
2010
The only pharmaceutical company in Bangladesh to enter the US market
through acquisition of an Abbreviated New Drug Application (ANDA).
Received GMP accreditation from AGES, Austria (for European Union);
2011 only pharmaceutical company to win ‗National Export Trophy (Gold)‘ for
the fourth time.
2012
First Bangladeshi company to launch Salbutamol HFA inhaler (Azmasol )
in Singapore
2013 First Bangladeshi company to export ophthalmic products to Europe
2014
First Bangladeshi company to receive GMP approval from Health Canada
and Taiwan Food and Drug Administration (TFDA)
2015 Become the first Bangladeshi company to achieve USFDA approval.
10

11. BEXIMCO consists of the following units:
TRACK - 1
 Solid Dosage Formulation
 QA & QC
 LCO & Suppository Unit
 Infusion Unit
 ION( injectable, ophthalmic & Nebulizer) Unit
 Power Plant
TRACK - 2
 Solid Dosage Formulation
 QA & QC
 MDI (Under construction)
WAREHOUSE
 Warehouse for LCO & Solid Dosage Form
 Infusion Warehouse.
There is a Liquid Nitrogen Plant in BEXIMCO on the other side of main area.
The employees are broadly divided into two groups-
1. Management (e. g. AGM, Manager, Senior Executive, Executive)
2. Non-management (e. g. workers); however, there are some employees who work on
daily basis & some work on a contract.
In this plant, there are several departments such as-
1. HRD (Human Resource Department)
2. PPIC (Production Planning & Inventory Control)
3. Warehouse
4. Production

12. 12
5. Quality Assurance & Control department
6. Engineering Department
7. Quality Assurance & Control department
8. Accounts, Finance & Informatics etc.
REGULATORY APPROVALS
The manufacturing facilities of Beximco Pharmaceuticals have been audited and approved
by:
 Food and drug administration (USFDA)
 National Health Surveillance Agency (ANVISA),Brazil (MDI)
 Therapeutic Goods Administration (TGA), Australia (OSD, MDI and Spray)
 Gulf Central Committee for Drug Registration (for GCC member states)(OSD &
MDI)
 Health Canada(Canada)
 TFDA(Taiwan)
 AGES (EU)
 Qualified by UNICEF (MDI & OSD)
 Qualified by Global GlaxoSmithKline (MDI)
 Qualified by Asthma Drug Facility (ADF), France (MDI)
 Qualified by Global F Hoff Mann La Roche (OSD)

13. 13

14. 14
HUMAN RESOURCES DEPARTMENT:
A human resources department is a critical component of employee well-being in any
business, no matter how small. A company‗s human resources department is responsible for
creating, implementing and/or overseeing policies governing employee behavior of company
toward its employees. The human resource function serves to make sure that the company
mission, vision, values or guiding principles, the company metrics, and the factors that keep
the company guided toward success are optimized.
Beximco Pharmaceuticals Limited is one of the leading corporate houses of the country and
has a handsome amount of workforce led by the HRD.
DUTIES & RESPONSIBILITIES
 Organizing & controlling of routine activity in the factory.
 Prepare & maintain ISO-9001 documentation.
 Supervise shift wise sectional activities.
 Shift wise manpower distribution.
No institution or workstation can run without people. BEXIMCO Pharmaceutical LTD. is one
of the leading industry of the country has a generous amount of work force led by the Human

15. 15
Resource Department (HRD). Many jobs are done by this department for smooth running.
Like,
1. Recruitment of Personal:
Daily labors (DL) with appropriate qualification & experience to fill all positions that have
an effect upon quality. Different standards are considered for different positions.
2. Preparation of Monthly Manpower Statement:
HRD prepare monthly manpower statement of the plant that includes DL to Director of the
industry and also prepares the daily manpower statement.
3. Maintain & Update Personal Files:
Detailed information of each and every employee are taken and updated monthly.
Conformations of job, increment, promotion, transfer etc. are built- in the file.
4. Deal with Industrial Related Issues:
They negotiate with employees union and ensure the labor right etc.
5. Disciplinary Action:
Disciplinary action including suspension, punishment & termination are done by HRD.
6. Inform Manager & Employee:
Personnel politics & procedures of the company are informed to the Managers and
employee by HRD
7. Coordination & Monitor Performance Appraisal:
HRD evaluate the performance of the plant employees in many ways:
a) Descriptive method
b) Questioner method
c) 360º appraisal etc.
8. Assess the training
HRD assess the training needs of personnel in light with cGMP& others related to HRD
issues. The training includes:
a) GMP
b) Safety
c) Training on performance appraisal management
d) SOP for HR & Administration
e) Labor standard & work place environment in pharmaceutical industry.
9. To arrange Induction Training Program:

16. 16
HRD organize orientation program for new employees.
10.Ensure proper implementation of labor Laws:
HRD ensure proper implementation of labor Laws applicable to factory workers &
employees.
10. Prepare and arrange In-plant training program:
Arrange training program for the students of different Universities. Coordinators handle
all matters related to In-plant training program.
11. Ensure Health labor-management relationship:
Ensure Health labor-management relationship for smooth & uninterrupted production.
12. Maintain liaison with Government Regulatory bodies
HRD collaborate with the following bodies for legal aid which help in any accident or for
medical aid:
a) Ministry of industry
b) Office of Director of labor
c) Explosive department
d) Tongi Pouroshova
e) Director of fire and Tongi fire station
f) Custom & VAT, Tongi circle
g) DC office, Gazipur
h) SP office, Gazipur
i) Civil surgeon, Gazipur.
13. Supervise & Monitor employee attendance, job cards regularly & prepare monthly
summary, daily absent report etc.
14. Monitor leaves of plant employees. Each employee has a leave file which integrate the all
kinds of leaves like-
 AL (Annual leave)
 ML (Medical leave)
 CL (Causal leave)
 Other leaves-
 Special leave
 Maternity leave
 Leave without pay etc.
15. Ensure safety of all employees and company assets.
16. Ensure proper securely management of the plant.
17. Handle external visitors & arrange necessary uniform and other accessories.

17. 17
18. Supervise overall cleaning service of the plant (housekeeping, gardening etc.)
19. Supervise washing facility to provide proper clean dress as per departmental daily
requirement.
20. Supervise transport pool (Distribution, repair, maintenance).
21. Supervise canteen management.
Others:
1. Picnic, cultural program, medical checkup, eye checkup.
2. Inform managers and employees regarding personnel policies and procedures of the company.
3. Assess the training needs of personnel in light with current GMP.
5. Daily labor recruitment, Transportation, Housekeeping and gardening

18. Product Planning and Inventory Control
18

19. 19
PRODUCT PLANNING AND INVENTORY CONTROL:
PPIC stands for product planning and inventory control. In PPIC all raw and bulk materials
first comes and stored. These materials are collected by invoice. After supplying by the
traders the PPIC checks the appearance, sealing, marking etc parameters and receives by
fixing a mark of Under Test Goods Receive Tag.
Production planning has two broad subtypes:
1. Factory based planning.
2. Planning and inventory control.
Production planning has some functions to operate in factory based planning:
Issuing BMR and BPR: Both Batch Packaging Record and Batch Manufacturing Record are
issued by the Production Planning Department. Should it consider the need to make
amendments to any of these documents, it consults with Product Development. BPR is issued
only once whilst BMR is issued for every batch.
Maintaining Monthly Plans: According to market demand, Production Planning suggests
whether or not the company should continue the manufacture of a particular product.
Ensuring The Availability of Raw and Packaging Materials: Production planning gathers
all types of raw and packaging materials under consultation of head office.
Arranging physician samples: Production unit separates physician samples from the bulk
production according to the Production planning Department. These samples are prepared at
least one month prior to dispensing and in special packages called ―Catch Covers‖.
Arranging Products for International Marketing: Having receiver information by email,
Production Planning takes necessary actions as per requirement of the buyer to meet their
demand for purpose of export.
Coordination among all sectors: Planning department aims for the highest production with
minimal costs which requires proper co-ordination among the various departments with
appropriate calculation of every aspects ranging from dispensing to final product.
Compare man hour and achievements: Production planning department determines the
actual efficiency of man and machine to give the highest production within minimum cost
and time.
Keeping daily production report and documents: Production Planning keeps all sorts of
daily production reports and it also maintains major documentation.
Submission of monthly report: Production planning department submits production reports
to Executive departments on a daily basis and maintains documents including:

20. 20
Acceptance/Rejection of raw and packaging materials.
 Order paper
 Delivery report
 BPR
 Other invoices
Production planning has some functions to operate in planning and inventory control:
Inventory control is the processes employed to maximize a company's use of inventory. The
goal of inventory control is to generate the maximum profit from the least amount
of inventory investment without intruding upon customer satisfaction levels.
Then they send samples to Q.A. Department. If the Q.A. Department approves they keep the
materials in Released area or if doesn‘t approve they keep the materials in Rejected area.
In Released Area it maintains dry and cool environment. For sensitive materials it ensures
below 8o
c temperature. Explosive materials such as Methylene Chloride are preserved in
Separate Area. Narcotics such as Pseudoephedrine are saved in Safe Lock at Liquid, Flavors,
and Lab Chemical Room. The temperature of these rooms is daily recorded.
The PPIC releases the raw and bulk materials under the requisition form from Production
department. After all type of calculation Such as Final potency, Amount after drying etc they
supply necessary amounts to the production department

21. 21
Flow Chart of Working Procedure in PPIC
Requisition from production department to PM
store
Checking for availability of required material
Preparation of Formulation Order and sending it to RM store
Packaging Materials
Checking availability of materials in RM store
Dispensing of required materials to production unit
Production of drugs
Packaging of the product
Sending the finished product to FG store

22. Warehouse
22

23. 23
Warehouse:
A warehouse is a large commercial building where raw materials or manufactured goods may
be stored prior to their distribution for sale or for sending it to the production department for
manufacturing purpose.Warehouses are used by manufacturers, importers, exporters,
wholesalers, transport businesses, customs, etc .
The warehouse of Beximco Pharmaceutical Ltd is an enclosed building and protects the
stored goods from environment influences. They are secured against fire by the special design
of the buildings and technical facilities. The fire brigade facility also has access to enable
appropriate firefighting.
There are 4 types of warehouse in Beximco Pharmaceutical Ltd:
1. Central warehouse: Central warehouse houses about 1000 types of raw materials such as
paracetamol, ranitidine HCI etc. and 7000-8000 types of packaging materials such as Blister
foil, PVC film, Inner carton. It also stores shipping carton, Alu-Alu foil. It has product
receiving area, approved area, and quarantine area. Materials enter from the log in area &
release from the log out area. It has a platform balance in the dispensing area & its capacity is
up to 300 kg. This area is also called weighing area.
It maintains-
Temperature: 22°C Humidity 48%
2. Infusion warehouse:100 types of packaging materials, 16 types of raw materials
(Calcium chloride, Calcium carbonate, Calcitrol) and some finished products
(Dexaque-100ml, Irigon – 100ml, Lactoride-1000ml) are stored.
3. Pharmatek warehouse
4. Track-2 warehouse-
There is a Liquid Nitrogen Plant in BEXIMCO beside the warehouse.
AREAS OF WAREHOSE:
1. Quarantine Area
After receiving, raw materials and packaging materials are kept for QC approval in a yellow
marked area
a. Materials come through a covered van and unloaded and cleaned to make it dust free.
b. Then these materials are checked individually and information like name,
manufacturer, manufacturing date, expiry date, quantity and etc are recorded in the
checklist.
c. They are weighed and crosschecked whether they contain the same material and
quantity as mentioned in the container or not.

24. 24
d. If it is found to be up to standard then MMR (material receiving report) is prepared
and materials are kept in the quarantine area for QC (Quality Assurance Department)
approval.
2. Released Area
QC approved raw materials and packaging is generally stored in the central place of
warehouse with great safety and with controlled temperature and humidity.
a. MMR is sent to the Quality Control Department; officer comes for sampling after
receiving the MMR and sampled sticker are sealed. [If the receiving material is an
active ingredient then 100% sampling is necessary but if it is, an excipients then (n+1)
is done.
b. If the sample is found to be standard by the Quality Assurance department then
released sticker is sealed and stored in the central place of the warehouse with great
safety.
3. Dispensing Area
One dispensing officer always responsible for dispensing the materials to the production and
packaging materials to the packaging areas, following things must be checked by the
dispensing officer
a. Only released (green tag) materials are brought to the dispensing area.
b. The dispensing area is completely free from materials of other products.
c. Correct quantity and approved qualities of materials are being dispensed as per
requisition.
d. Materials that expired first are being dispensed first i.e. to follow FIFO.
e. Documentation of dispensing
4. Finished Product Area
a. Finished products are also stored here for delivery.
b. Warehouse deliver the finished products as per asked by the planning department.
5. Rejected Area
a. If the materials fail to pass QC test, QA give rejected tag (red tag) on each and
individual container or box.
b. Rejected materials are placed in the rejected area until further decision for final
disposition is made (official letter is sent to respective department).
6. Packaging Products Area
Imported packaging products are stored in a separate room beside the raw material storing
room in the warehouse with great care.
7. Special Area:

25. 25
This is a special room or area for stored light & heat sensitive materials like colors, flavors,
vitamins poisonous materials, flammable materials etc. in maintaining temperature in
between 20-25ºC.
8. QC Sampling Room:
In this separated and lab- based room, when a new material arrives in the warehouse QC
officer comes here for sampling test.
9. Change Room for Warehouse Officers & Workers:
When any officer or worker works in the warehouse, before entering in the warehouse, he or
she change his/her cloths here & wears apron, shoe cover and head cover.
10. Change Room for QC Officers:
When any QC officer comes warehouse for sampling a material, he or she change his/her
cloths here and wears apron, shoe cover and head cover before entering into sampling room.
The main functions of warehouse are given below:
 Receiving in-voice and purchase order from material management
 Receiving materials
 Cleaning of received materials
 Weighing of received materials and compare with purchase order
 Dispensing of materials according to DOS for production
 Receiving of finished goods from production
 Inventory of tool manufacture also maintains by warehouse

26. 26
ACTIVITY OF WAREHOUSE
Arrival of Materials In Voice Checking
Quarantine Storage
Physical Inspection &
Receipt
LOG Book Entry
MRR for Inspection &
Receipt
QC for Analysis & Report
Q.A. Sampling
QA Release QA Reject
MRR Failed MRR
Disposition Released
Materials
Disposition Rejected
Materials
Distribution Dispensing
Computer Entry of
Requisition
Monthly Inventory Report

27. SOLID DOSAGE FORM
27

28. 28
TABLET:
Tablets are solid single unit pharmaceutical dosage forms containing one or more active
ingredients with or without auxiliary substances and prepared either by molding or by
compression.
Types of tablet according to BP
 Conventional/Uncoated tablet
 Coated tablet
 Effervescent tablet
 Soluble tablet
 Gastro-resistant tablet
 Modified-release tablet
 Tablet for using in the mouth
Production department has the following units:
 Dispensing
 Granulation
 Compression
 Coating
 Encapsulation
DISPENSING OF MATERIAL FOR PRODUCTION
One of the most vital steps in pharmaceutical manufacturing is dispensing. This is the first
step that needs to be done during the process of manufacturing. Dispensing area dispenses
only those materials which are released or approved by the QC. After dispensing, products
should be used within 7 days as stated in the SOP. Here, the appropriate weight of each
ingredient is measured according to the dose present in the BMR. Then it is kept in the
desired pallet and a tag is added to it which contains different information. Throughout the
process a log book is maintained.
Manual Dispensing:
 By hand scooping from primary containers and weighing each ingredient by hand on
a weigh scale
 By manual weighing with material lifting assistance like vacuum transfer and Bag
lifters.
Criteria of dispensing:
 Record the reading from the booth magnehelic gauges in the logbook before
commencing dispensing.
 Do not start dispensing if readings are in orange zone-report to executive.

29. 29
 Verify that the balances to be the used are clean and within their calibration period.
 Record the temperature and relative humidity of the area before dispensing using
hygrometer.
 Weighing area also contains HEPA filter and Dual filter.
 Dispense the RM in the order standard on dispensing page.
 Dispense each material of one batch at the same time.
 Bring only one raw material into the booth at one
 Dispense each material into sealed containers or polythene bags. Seal the polythene
bag properly with plastic wire ties. Complete and attach a dispersed label to each
container or polythene bag
 When batch is fully dispensed, transfer the packets cage trolley to the holding area for
further processing.
There are two dispensing booths in solid dosage form of BeximcoPharma
 one for weighing under 5 kgs
 another for weighing above 5 kgs
Cleaning Specifications in the Dispensing Area:
In the dispensing area, the operator and his helper is cleans the balances and cleaners cleans
the floors, corridors and other areas. These operators and cleaners have their training records
documented.
Dispensing area contains two booths which are facilitated with –
 Avery Balance.
 Sartorius Balance.
 Temperature & humidity detector.
 Different filters:
 Pre filter
 Fine dust filter
 HEPA filter
 Dual filter
A negative pressure is always maintained inside the booth. In addition, there is a vertical
laminar air flow inside the booth to prevent the entry of dust.
Equipment and Reagents Used For Cleaning In Dispensing Area
 Vacuum cleaner
 Clothes
 Water (hot, purified)
 Isopropyl Alcohol (70%) solution as disinfectant.
 Virocid (as disinfectant for floor cleaning only)
Savlon antiseptic lotion.

30. 30
Process of dispensing:
Receive the raw material issue requisition and record the serial number, material code and
date of receipt
Check for the batch size, batch no., R no. and signatures for requisite by and authorizes by
From raw material stock register, check the quantities of material available and quantities
requested for.
Issue the materials that are approved by QC
Check the tare weight of the empty container and note down on the dispensed label
Select the bulk raw material container of appropriate R no.
Carefully transfer the material into the dispensing area and then transfer the required
quantity into the container
Calculate the net weight and record on dispensing label and sign for issued by
Close the bulk raw material container and transfer back the bulk raw material container to
the original space
Repeat the steps for remaining raw materials needed for the specific drug formulation

31. 31
GRANULATION
In the pharmaceutical industry, granulation refers to the act or process in which primary
powderparticles are made to adhere to form larger, multiparticle entities called granules. It is
the process of collecting particles together by creating bonds between them. Bonds are
formed by compression or by using a binding agent. Granulation is extensively used in the
manufacturing of tablets and pellets (or spheroids).The granulation process combines one or
more powder particles and forms a granule that will allow tableting or the spheronization
process to be within required limits. This way predictable and repeatable process is possible
and quality tablets or pellets can be produced using tabletting or spheronization equipment.
The pharmaceutical granules regularly have a size reach between 0.2 to 4.0mm, contingent
upon their ensuing user.
Necessity of granulation
 Improve flow
 Densify materials
 Improve content uniformity
 Improve compression characteristics
 Control the rate of drug release
 Facilitate metering or volume dispensing
 Decrease dust generation and reduce employee exposure to drug product
 Improve the appearance of the tablet
Granule properties
 Controlled Size Distribution
 Specific Granule Voidage-Intragranular Porosity
 Specific Bulk Density
 Suitable Structural Stability and Physical Strength
Types of granulation performed in this unit are:
 Dry Granulation
 Wet Granulation
 Direct compression

32. 32
Wet Granulation:
In wet granulation, granules are formed by the addition of a granulation liquid onto a powder
bed which is under the influence of an impeller (in a high-shear granulator), screws (in a twin
screw granulator) or air (in a fluidized bed granulator). The agitation resulting in the system
along with the wetting of the components within the formulation results in the aggregation of
the primary powder particles to produce wet granules. The granulation liquid (fluid) contains
a solvent which must be volatile so that it can be removed by drying, and be non-toxic.
Typical liquids include water, ethanol and isopropanol either alone or in combination. The
liquid solution can be either aqueous based or solvent-based. Aqueous solutions have the
advantage of being safer to deal with than solvents.
During wet granulation, liquid binders or adhesives are added to the lactose and active
mixture, usually by blending. The mixture is then dried and sized, and compressed into
tablets. There by producing a dust free formula plus improving flowability, eliminating poor
content uniformity and the ability to encapsulate a poorly soluble API.
Mechanisms of wet granulation by Fluid Bed:

33. 33
Steps of wet granulation:
Key process stages include blending the dry powder mix, wet granulation with water or
another binder solution, adding any additional components, further lubrication and final
compaction. Excipients used in wet granulation typically include diluent, binder, disintegrant
and lubricant, while other stabilizing agents and pigments may also be included.
Process parameters
 Impeller Speed
 Chopper Speed
 Water Addition Rate and Method
 Massing Time
 Load of the Mixer

34. 34
Dry Granulation:
The dry granulation process is used to form granules without using a liquid solution because
the product granulated may be sensitive to moisture and heat. Forming granules without
moisture requires compacting and densifying the powders. In this process the primary powder
particles are aggregated under high pressure.
Dry granulation can be conducted under two processes; either a large tablet (slug) is produced
in a heavy duty tabletting press or the powder is squeezed between two counter-rotating
rollers to produce a continuous sheet or ribbon of material
Steps in Dry Granulation:
Direct Compression
This is another method of tablet manufacturing. The materials are directly compressed to
form tablets.Direct compression is a popular choice because it provides the shortest, most
effective and least complex way to produce tablets. The manufacturer can blend an API with
the excipient and the lubricant, followed by compression, which makes the product easy to
process. No additional processing steps are required

35. 35
Machines used for granulation:
Granulation Unit #1
Sl. Name of Instrument Manufacturer/
Supplier
Origin Capacity
1 High Speed Mixer Granulator
(HSMG)
Thailnd 60 Kg
2 Fluid Bed Dryer Saphire India 60 Kg
3 Multi Mill Gansons India 100 Kg/h
4 Vac-U-Max Belleville USA 2000
Kg/h
Granulation Unit #2
Sl. Name of Instrument Manufacturer/
Supplier
Origin Capacity
5 High Speed Mixer Granulator
(HSMG)
India 120 Kg
6 Fluid Bed Dryer Saphire India 120 Kg
7 Multi Mill Gansons India 100 Kg/h
8 Vac-U-Max Belleville USA 2000
Kg/h
Granulation Unit #3
Sl. Name of Instrument Manufacturer/
Supplier
Origin Capacity
9 High Speed Mixer Granulator
(HSMG)
Thailand 250 Kg
10 Fluid Bed Dryer Saphire India 150 Kg
11 Fluid Bed Dryer Saphire India 150 Kg
12 Multi Mill Mark Bangladesh
13 Vac-U-Max Belleville USA 2000
Kg/h
14 Lift Lever (Stacker) Toyota Tuscho
Corp.
Japan 650 Kg

36. 36
Granulation Unit #4
Sl. Name of Instrument Manufacturer/
Supplier
Origin Capacity
15 Solace Aero Dryer Solace India 120 Kg
16 High Speed Mixer Granulator
(HSMG)
Thailand 250 Kg
17 Multi Mill Gansons India 100 Kg/h
18 Vac-U-Max Belleville USA 2000
Kg/h
Blending:
Blending, one of the most basic of pharmaceutical unit operations, can also be one of the
most challenging to control. Solid formulations contain multiple ingredients beyond the
active pharmaceutical ingredients: fillers, tableting agents, disintegrants, and absorption
enhancers or agents that slow down and control absorption. Ingredients from different
vendors may behave differently due to their particle size and shape and other factors, and
their tendency to form aggregates.
Materials must be chosen to ensure the desired flow characteristics, potency, proper
dissolution profile, and absorption of specific formulations. Proper particle size grades of the
ingredients must be selected to produce an optimum blend for capsule filling.
For granules containing active ingredient/s the following procedure is used in the blending
units of BEXIMCO Pharmaceutical Limited;
 Remove the blender cleaned label & update the logbook with product detail.
 Display a product identification label at the display board.
 Verify that the instruments to be used are within their calibration period Matcon
IBC blender process timer. Blend Speed Indicator.
 Check that the lid is securely fitted to the IBC.

37. 37
 Blend the IBC for 20 minutes at 15 rpm
 Include the blender printout in the batch wallet.
 Verify that the balances used for the IBC weighing are within their calibration
period.
 Weigh the IBC to determine the granules yield.
 The weight of granules should be between 309.054 kg to 312.176 kg (99-
100%).Notify Executive if the yield is outside the limits. Executive to investigate
and provide a reason.
Blending critical parameters
 Blending time
 RPM (Rotation Per Minute)
Sieving:
A sieve, or sifter, is a device for separating wanted elements from unwanted material or for
characterizing the particle size distribution of a sample, typically using a woven screen such
as a mesh or net
Steps for sieving:
 Record temperature and relative humidity of the area before sieving.
 Remove the equipment-Cleaned label. Update the log book with product details
and display a product identification label at the room entrance.
 Check that the raw materials are correctly labeled and sealed and have been
weighted.
 Transfer the following raw material into 1000 L IBC
 Sieve the following raw materials through the Russell Finex Sieve fitted with 630
μm pore size screen into a labeled poly bags.
Compression:
Following granulation is compression where the granules are compressed to form tablets of
distinct shape, size, hardness, weight & thickness. BEXIMCO Pharmaceutical has 8
compression machines in the compression unit of the solid department in which the highest
punches station is 55 and the lowest is 18.

38. 38
Compression is the method where force or pressure is applied 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.
There are two types of compressions as seen in the tablet press units of the factory. These
includes:-
1. General Compression (Of previously made granules)
2. Direct Compression
Criteria to be followed in the compression process:
 Verify that the machine is properly cleaned
 Verify that no previous materials are present in the compression unit.
 Remove the equipment cleaned label and set up the compression machine.
 Update the logbook with details of the product and display a product identification label
at the production display board.
 Fit new flat tubing to the IBC discharge cone.
 Verify that the instrument to be used is within their calibration period.
 Ensure the compression machine is set up with the following tooling

39. 39
General Compression:
Granules (previously made)
Transfer granules in the hopper from intermediate bulk container on the
MATCON discharge station
Rising of upper punch & dropping of lower
Filling of die cavity through feed
Removal of extra granules by scrape off
Coming down of upper punch for Compression to produce
Raising of both upper & lower punches to certain
Pre-turret punch
Main compression
Ejection of tablet with the help of take out
Inner chop to outer chop and then pass through the de-duster
and metal detector
Obtain conventional Uncoated Tablets of desired shape and size

40. 40
DIRECT COMPRESSION:
Milling & Screening of active ingredients & the excipients
Mixing of the active ingredients along with excipients including lubricants &
disintegrates in the IBC
Transfer mixture in the hopper from intermediate bulk container on the MATCON
discharge station
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
Pre-turret punch compression and main compression
Ejection of tablet with the help of take out plate
Inner chop to outer chop and then pass through the de-duster and metal
detector
Obtain conventional Uncoated Tablets of desired shape and size

41. Compression machines:
Seri
al
Name of the
machine
Machine ID Producer No. of
station
No. of
channel
Capacity Model
of
punch
1. Bosch
xpress300
Sld-M-EQ -13-
51
MANESTY
Machineries
Ltd.
Liverpool,
England.
30 1(with
deduster)
200000
tablets/hou
r
D type
2 MANESTY
BB4
Sld-M-EQ-93-
018
MANESTY
Machineries
Ltd.
Liverpool,
England
35 2(with
deduster)
240000tab
lets /hour
B type
3 Fette-1200 Sld-M-EQ-
97025
Germany 30 1(with
deduster)
220000
tablets
/hour
BB
type
4 Fette-
3100(most
high speed
machine)
Sld-M-EQ-
97026
Germany 55 2(with
deduster)
594000
tablets /
hour
BB
type
5 Sejong 45 Sld-M-EQ-
06034
South Korea 45 2(with
deduster
400000
tablets /
hour
BB
type
6 Sejong -18 Sld –M-EQ-
09637
southkorea. 18 1(with
deduster
30000
tablets /
hour
B type
7 SEJONG-49 Sld-M-EQ-
09038
South Korea 49 2(with
deduster
150000
tablets
/hour
B type
8 IMA active
kilian
Sld-M-EQ-
011062
Germany 37 1(with
deduster
200000tab
lets/hour
B type
41

42. 42
COATING:
A coating is a covering that is applied to the surface of an object, usually referred to as the
substrate. The purpose of applying the coating may be decorative, functional, or both. The
coating itself may be an all-over coating, completely covering the substrate, or it may only
cover parts of the substrate
Reasons for coating:
 To mask the taste, odor or color of the drug
 To provides physical and chemical protection for the drug
 To control the release of drug from the tablet
 To protect the drug from the gastric environment of the stomach with an acid resistant
enteric coating
 To incorporate another drug or formula adjuvant in the coating to avoid chemical
incompatibilities
 To improve the pharmaceutical elegances by use of special colors and contrasting
printing
CLASSIFICATION OF COATING:
Coating is of two types:
1. Film Coating
o Aqueous coating
o Organic coating
o Enteric coating
2. Sugar Coating
In BEXIMCO Pharmaceutical Limited only film and enteric coating are done. Sugar coating
is not performed in the coating units of the factory. For enteric coating, the coating solution is
sprayed into 2 parts.
Part-I is sprayed to form a film on the surface of the tablet
Part-II solution is sprayed on the previously formed film so that the enteric coat can retain of
the film coat.
CRITICAL PARAMETERS OF COATING
Atomization pressure
Steam pressure
Spray pattern
Gun to bed distance
Spray rate
Pan depression
Program parameter
Height of core sample after pre-jag drying cycle.

43. 43
STEPS OF COATING:
Suspension making for about 45-60
Compress tablet core in feeding
Pre jag warm up for about 30 min at 40®C
Drying + Spraying
Drying
Cooling
Unloading of coated tablet
Film coating Defects
Sticking & Picking
-It is defect where isolated areas of film are pulled away from the surface when the tablet
sticks together and then apart.
-Insufficient drying and higher rate of application of coating are the main causes.
Remedies:
-Use optimum and efficient drying conditions or increase the inlet air temperature
-Decrease the rate of application of coating solution by increasing viscosity of coating
solution.
Roughness
It is the defect of spray coating process, where some of the droplets dry too rapidly before
reaching the tablet bed, resulting in deposits on the tablet surface of ‘spray dried’ particles
instead of finely divided droplets of coating solution.

44. 44
Higher distance of nozzle from tablet bed or increase polymer concentration /pigment
concentration are the main cause.
Remedies:
-Moving the nozzle closer to the tablet bed or reducing the degree of automization of
spraying
-Decrease the polymer concentration
Orange peel effects
It is related to the inadequate spreading of the coating solution before drying. Appearance
similar to orange feel.
Rapid drying and high solution viscosity are the causes.
Use mild drying conditions and use additional solvents to decrease viscosity of solution can
remedy
Bridging and filling
It is defect that renders the monogram or bisect indistinctness.
During drying the film shrink and pull away from the sharp corner of a bisect, resulting in a
bridging of the surface depression. This mainly represent a problem with formulation.
Increasing the plasticizer or changing the plasticizer can decrease the incidence of bridging.
Filling is caused by applying too much solution or too fast solution, resulting in a thick film
that fills and narrows the monogram or bisect.
Carefully monitoring of the fluid application rate and through mixing of the tablets in the pan
prevent filling
Blooming
It is defect where coating becomes dull immediately or after prolonged storage at high
temperature.
Blooming or dull film is generally because of higher concentration and lower molecular
weight of plasticizer. So use lower conc. And higher mol.wt grades of plasticizer.
Blistering
It is local detachment of film from the substrate forming blister.
It is related to entrapment of gases in or underneath the film due to overheating.
Too rapid evaporation of solvent from the core and the effect of high temperature on the
strength, elasticity and adhesion of the film may result in blistering.
Milder drying conditions are way of elimination.

45. 45
Cracking /splitting
It is defect in which the film either cracks across the crown of the tablet(cracking) or splits
around the edges of the tablet (splitting)
Cracking occurs if internal stress in the film exceed the tensile strength of the film.
The tensile strength of the film can be increased by using high mol.wt. polymers or polymer
blends.
Colour variation.
This can be caused by processing conditions or the formulation. Improper mixing, uneven
spray pattern, and insufficient coating may result in colour varistion.. The migration of soluble
dyes, plasticizers, other additives during drying may give the coating mottled or spotted
appearance
Encapsulation:
In the manufacture of pharmaceuticals, encapsulation refers to a range of
dosage forms—techniques used to enclose medicines—in a relatively stable
shell known as a capsule, allowing them to, for example, be taken orally or be
used as suppositories.
According to World Health Organization, capsules are solid dosage forms with
hard or soft shells. They are of various shapes and sizes and contain a single
dose of one or more active ingredients. They are intended for oral
administration.
When excipients are used it is necessary to ensure that they do not adversely
affect the stability, dissolution rate, bioavailability, safety or efficacy of the active
ingredient(s); there must be no incompatibility between any of the components of the dosage
form.

46. 46
The different categories of capsule include:
 Hard capsules;
 Soft capsules;
 Modified-release capsules
The active is filled in the empty the hard gelatin capsule shell in the form of
 Powder
 Pellets
There are 4 different sizes of empty hard gelatin capsule shells used in
BEXIMCO Pharmaceuticals Ltd. for general production, which include-
 Capsule shell size 0
 Capsule shell size 1
 Capsule shell size 2
 Capsule shell size 4
BEXIMCO Pharmaceuticals Limited encapsulated only hard gelatin capsules.
Process of encapsulation:
Polishing of capsules, when needed, is done first by Capsule Polishing machine which
removes dust, adherent powder and gives a shiny appearance.
Machine used for encapsulation
Encapsulation Unit Name Capacity Supplier
01. MG-2 Futura 50000 capsules/hour MG America

47. 47
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. A
product is packaged for its safe delivery to the target customers. It should be safe, compatible
to the product contained and robust enough to resist the hazards met during the overall
transaction and shell-life. 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.
Packaging materials are of two types:
Primary Packaging materials (PVC, Aluminum foil, PVDC)
Secondary Packaging Materials (Printed cartoon, Liner, Labels, Leaflet, Printed tape)
Primary Packaging
Packing Forms
The following forms of packs available in this company:
 Blister pack, used for tablet, capsule,
 Strip pack, used for tablet and capsule
Primary Packaging Machine
Packaging unit Machine Supplier/origin
Blister 085 Klockner Hansel Germany
Blister 042 Otto Hansel Germany
Blister 043 Otto Hansel Germany
Blister 074 Klockner Hansel Germany
Blister Elmac Elmac India
Blister Pampac Pampac India
Blister Hoong A Hoong A Korea
Strip Packaging Gansons Strip Packaging India
Machine 1
Gansons Strip Packaging India
Machine 2

48. 48
Blister Packaging
The primary component of a blister pack is a cavity or pocket made from a formable web,
usually a thermoformed plastic. This usually has a backing of paperboard or a lidding seal of
aluminum foil or plastic. A blister that folds onto itself is often called a clamshell. After
packaging the strips is tested I leak Test apparatus and then passed on to the secondary
packaging area through conveyor belt
Blister packs are useful for protecting products against external factors, such as humidity and
contamination for extended periods of time. Opaque blisters also protect light-sensitive
products against UV rays.
Steps of Blister Packaging
Strip Packaging
The tablets formed by compression are enclosed in strip packages. The strip utilizes the rolls
of aluminum foils which are scaled together tablet with little application of heat, the coding is
done stereotypically. After the strip packing the strips are checked for leak in leak test
apparatus. The strips are then passed on to the secondary packaging area through conveyor
belt. Roller heating temperature limits -1200c-1400c.

49. 49
IPC for packaging
Leak test
Coding
Appearance
Stoppages/Adjustments
color
flavor
Bottle filling area for solid product:
Bottle filling machine
Producer:Tiwan
ID:SLd-P-EQ-89011
Cap sealing o2
ID:Sld-p-EQ-03012
Station :6
Bottle Washing machine
Name :pharmalab
Producer :India
Channel-64
Water spray station:28

50. 50
Bottle dryer
Name: Kilburn oven
ID;SLd-P-EQ-78023
Temp.-150c
Capacity :7200
Labelling machine
Name:Autolabelling
ID:Sld-P-EQ-95014
Producer:England
Secondary Packaging
Secondary packaging is the middle layer of packaging
Here different packaging line area assigned differently i.e. one packaging line comes from
each strip packaging area, one from blister packaging and one from bottle packaging area. All
materials received through conveyor from the primary packing area are suitably checked and
boxed which are packed in cartons and cooled sealed. Then operate the machine for
packaging.
Roller forming temperature – 140 ⁰CSealing roller temperature – 220 ⁰C
Perform leak test on 10 strips at a time
Final packaging
The stripped capsule arrived at the secondary packaging area through the conveyor belt from
primary packaging area. Stripped capsules undergo manual inspection for any irregular
printing or sealing or any damage. Then they are packed in cartoon which are subsequently
packed in specified corrugated boxes and sealed. The boxes are then to the finished goods
storeroom.

51. 51
Problems that may arise during packaging are:-
1. Empty pocket
2. No pocket
3. Damage of tablet/capsule
4. Printing mistake
5. Unclear printing

52. 52
RESEARCH
&
DEVELOPMENT

53. 53
Pharmaceutical companies generate innovation in health care by inventing and developing
new treatments for previously untreated health problems (radical innovation) and also
developing improved versions of existing medicines or new indications for them e.g. to treat
diseases other than those for which the medicines were originally invented (incremental
innovation). Often underestimated, these incremental innovations significantly improve
health and quality of life, by providing patients with more choice, better risk tolerance, easier
dosing and administration.
R & D deals with the following functions
a. Formulation of new product
b. Reformulation (where required)
c. Reprocessing (if required)
d. Problem solving related to manufacturing/formulation when required (Trouble
shooting )
e.
f.
Preparation of B.P.R/B.M.R for a new product.
Development of existing products.
g. Development of manufacturing procedure.
h. Analytical method development
i. Selection of packaging mood.
j. Stability study and determination of product shelf life.
Development of new product
Product development department is responsible for the establishment of formulation and for
the preparation of technical part of recipe of drugs. Steps involved in new product
development
Step-1: Product information from marketing department along with necessary attributes such
as
 Dosage form
 Strength
Step- 2: Pre formulation study of the active drug and excipients
 Chemical activity
 Function
 Interaction
 Boiling point
 Contraindication
 Moisture content, etc.
Step-3: Preparation of technical part of recipe for registration which include,

54. 54
 Formulation
 Manufacturing procedure
 Product specification &
 Acceptance criteria
Step-4: Requisition to purchase department for new material to give laboratory trial.
Step-5: Collection of raw material of active and excipients with necessary documents. (COA,
MOA, MSDS, stability report etc.)
Step-6: Product development (PD) laboratory trial batch production.
Step-7: Checking of physical and chemical parameters of PD lab trial batch.
Step-8: Selection for trial batch for stability study and prepare at least three batches for
stability study.
Step-9: Conduction for stability at three conditions,
 Room temperature
 300
C ± 20
C, RH 65% ± 5%.
 400
C ± 20
C, RH 75% ± 5%.
Step-10: Preparation for stability study report and determination for product shelf
Step-11: Preparation for provisional product data sheet.
Step-12: BPR/BMR preparation for pilot come commercial batch if every aspect is satisfied
which include -
 Product name
 Code
 Batch no
 Theoretical yield
 Batch size
Step-13: Production of at least three successful pilot come commercial batches.
Step-14: Finalization for formulation.
Step-15: Preparation for final BPR/BM for commercial production.
REFORMULATION
It is done for three reasons:
 For farther improvement for product quality.
 For increase productivity (by working on process).
 For more cost effective formulation maintaining quality.

55. 55
DEVELOPMENT OF EXISTING PRODUCTS
Product development department also deals with the development of existing product
formulation.
Objective
 Increasing the equality of the product.
 Prevention of any type for problem exiting in the product.
 To save time and cost.
 Increasing the patient acceptance.
STABILITY TESTING (AST)
Stability testing is done in following conditions:
 400
C ± 20
C, RH 75% ± 5%.
 300
C ± 20
C, RH 65% ± 5%.
 At room temperature
TROUBLE SHOOTING
During manufacturing of a new product in pilot come commercial batch many problems may arise. In
that case personnel from product development department (PDD) investigate the problems and take
necessary steps and remedies to minimize those problems and carry the manufacturing process
successfully.
Such as sudden capping of tablet or denting incase of capsule or may be pH imbalance in case of
liquid may occur. These types of problems are investigated by PD personnel and take necessary
actions to solve these problems immediately.
STABILITY
Stability test is done for a finish product to predict whether the product be stable for sufficient time to
ease marketing of the product. For stability test ICH guideline (International Conference on
Harmonization) is followed. 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.
PURPOSE OF STABILITY TESTING
1) For the required condition of the product
2) Increase the Shelf-life
3) Retention sample analysis
4) Fixation of expiry date
There are two type of stability testing,
A) Long term/ Real time stability test
B) Accelerated stability test

56. 56
A) Long term/ 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: 30 ± 2o
C
 Relative humidity: 60 ±5o
C
B) Accelerated stability test
In accelerated stability products are kept for short life (3or 6 month) in accelerated condition.
Upon the stability over this condition, shelf life is predicted.
 Temperature: 40 ± 2o
C
 Relative humidity: 75 ±5o
C
STORAGE CONDITION AND SAMPLING INTERVAL
Study Storage Condition Sampling intervals
Long term 300
C  20
C &
65% RH  5% RH
3,6,9,12,18,24,& 36
Month
Accelerated 400
C  20
C &
75% RH  5% RH
0,1,2,3,8,6 Month
PREDICTION OF SHELF LIFE
 If a product is stable over 1 year real time stability test, then 2 year of shelf life can be predicted
for the product.
 If a product is stable over 3 months accelerated stability test, then 2 year 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 product. Accelerated stability test can‘t be done for suppository, as it tends to
melt on body temperature.
MICROBIOLOGY
Microbiology division of QC performs microbiological tests. A microbiological test
determines the potency of products as well as the presence or absence of microbes in
products Microbiological tests relates to potency determination includes the following
products of Beximco: Azithromycine, Azithrocine capsule, etrocine dry suspension, etrocine
tablet, Gentocep cream, Anustant ointment, Genlomycin, Neomycin, Nystatin.
The microbiology department of BEXIMCO pharmaceutical Limited works with the QA
department. For implementation of GMP microbiology department is very important.
Microbiology section will just determine the microbial contamination monitoring.

57. 57
The function of microbiology laboratory can be presented as follows,
Microbial count
Water, raw materials, bulk
samples, finished products,
packing containers
LAL test sterility test
Water, indictable, raw
materials, other sterile
products
Environmental study
All manufacturing & filling
area including aseptic filling
room
Validation
Steam & dry heat sterilizer,
oven & cleaned equipment
Personal hygiene test
Aseptic production area
operators
Bio- assay
Antibiotic raw materials &
finished products
Major tests are performed by microbiology department
 Bioburden test (microbial count)
 Bioassay
 Sterility test
 Test for water
Microbial count
These tests are performed for
 Raw material (Active pharmaceutical ingredient & excipients)
 Water (PRW & WFI)
 Finished dosage form
 Pre-sterilized

58. 58
Required media
 TSA (Trypton soya agar)
 SDA (Sabourauds dextrose agar)
Flow chart for microbial count
For solid take 10mg & for liquid take 10ml of sample
Add 90ml of PBPS (Phosphate buffer peptone salt)
From these solution taken 1ml in to TSA media for bacterial growth & 1ml in SDA mediafor
fungal growth observation.
STERILITY TEST
Sterility test is an important test for sterile product. All product labels sterile must pass the
sterility test, having been subjected to an effective process of sterilization.
Media
 TSB
 TGM
Process
Collect sample according to sample volume and dissolve into a suitable solvent and passed
through the filter paper
This filter paper is cut into 2 pieces then one was taken into TSB media & another was taken
into TGM media
Incubation for 14 days then visual inspection done (if the microorganism present the media
will becomes turbid)

59. 59
LAL TEST
The meaning of LAL is LimulasAmoebocyte Lysate. This test is performed to identify the presence of
pyrogen. The procedure of the test involves taking 100 ml of product and 100 ml reagent in a small
tube. The mixer is then keeping into incubator for 1hr for incubation. After incubation the tube is
inverted to check whether the gel is formed or not. Generally 0.125EU/ml is present then gel is
formed. If gel is formed there is the presence of Pyrogen and if not the solution is liquid the product
satisfied the test and ready for use.
Machines/ Equipments present in R&D department:
In formulation sector:
 High speed mixing granulator made in Thailand.
 Film coating machine- NR cota, Thailand.
 Fluid bed dryer- Sapphire, India.
 16 station compression machine- Manestry, England.
 USP Dissolution tester- Erweka, Germany.
 Tap density tester (USP) - Electrolab.
 Moisture analyzer- Sartorius, Japan.
 Hardness tester- Erweka, Germany.
 Multimiller- India.
 Oven.
 Dehumidifier.
 Rapid dryer- Retsch.
 Weighting balances- Sartorius, Japan.
In Analytical sector:
 HPLCs
 USP Dissolution tester
 UV Spectrophotometer
 Potentiometer
 Balances
 Viscometer
 MP apparatus
 Shieve shaker
 Tap density tester
 DT machine
 Hardness tester

60. 60
 Fume hood
 Dryer
 FTIR
 Hot stage microscope
 Vacuum oven
 Moisture analyzer
 TOC analyzer
 Refrigerators
 AAS
 GC
 Malvern particle size analyzer
 Polarimeter
Climate zone:
To store a drug in suitable storage conditions and to export drugs to foreign countries, the
knowledge of climate zone is very important fact. According to ICH (International
Conference on Harmonization), the whole world is divided into five following climate zones
on the basis of environmental conditions:
Climatic Zone Temperature Relative Humidity
Zone I 21ºC ± 2ºC 45% ± 5%
Zone II 25ºC ± 2ºC 60% ± 5%
Zone III 30ºC ± 2ºC 35% ± 5%
Zone IV 30ºC ± 2ºC 65% ± 5%
Zone IVb 30ºC ± 2ºC 75% ± 5%
Bangladesh is in the Zone IVb. So the environmental factors must be considered to ensure
proper storages of drugs.

61. LIQUID DOSAGE FORMATION
61

62. 62
The production unit of BEXIMCO Pharmaceuticals Limited is highly maintained to minimize
the risk of serious medical hazard due to cross-contamination , dedicated and self contained
facilities are available for the production of Pharmaceuticals products ,
There are adequate working and in-process storage space to permit the orderly and logical
positioning of the equipments and materials to minimize the risk of confusion between
different pharmaceutical products and their components. To avoid cross-contamination and to
minimize the risk of omission or wrong application of any of the manufacturing or control
steps.
Pipe works, light fittings, ventilation points and other services are designed, and sited to
avoid the creation of recesses that difficult to clean.
The area is effectively ventilated, with air control facilities appropriate to the products
handled, to the operations undertaken and to the external environment. These areas are
regularly monitored during both production and non-production period to ensure compliance
with their design specification.
Premises for the packaging (Both primary and secondary) are specifically designed and laid
out to avoid mix-ups or cross contamination.
Production equipments are thoroughly cleaned on schedule basis they are cleaned as back to
back cleaning and complete cleaning.
Function:
 Commercial batch production
 Readjustment of instruments and facilities according to the instruction of QA department
 Small - scale experimental production of newly developed product according to the
instruction of PD department.
 Supervision of raw materials and packaging and final products in connection to QC
department
 Supervision of packaging process
 Calibration and maintenance of the production unit‘s machinery.
Objectives:
 Fulfill the market demand
 High productivity
 Reproducibility
 Quality production
The oral use of liquid pharmaceuticals has generally been justified on the basis of
administration to those who have difficulty in swallowing solid dosage form. A drug
administered in solution is immediately available for absorption & in most cases is more
rapid in action.

63. 63
LCO Department of Beximco Pharmaceuticals Limited produces about 84 products of
various dosages form including .
(i) Syrup (example: Napa, Aristoplex)
(ii) Suspension (example: Lactameal, Flatameal DS)
(iii) Nasal spray (example: Decomit)
(iv) Drops (Example: DefluxPed. Drop)
(v) Suppositories (example: Napa, Ultrafen)
(vi) Cream, Ointment, Gel (example: Neostin cream, Anustat ointment, Ultrafen gel)
LCO Department of BPL consists of following seven lines:
 Line I: Syrup, Suspension
 Line II: Antacid preparation
 Line III: Small volume oral liquid preparations
 Line IV: Cream, Ointment
 Line V: Suppository manufacturing, filling & packing
 Line Vl: syrup manufacturing
 Line Vll: export packaging
INSTRUMENTS USED IN LIQUID SECTION
Name of machine Manufacturer/supplier Capacity
Automat Filling & Sealing Machine India 5000 bottles/hr
GreatidOinment Filling & Sealing
Machine
Taiwan 2400 tubes/hr
Pharmalab Bottle Filling & Sealing
Machine
India 5000 bottles/hr
Gansons Bottle washing Machine India 240 bottles/hr
Manufacturing & storage jacketed vessel Australia 5000 liter
Manufacturing & storage jacketed vessel Australia 3000 liter
Manufacturing vessel India 1000, 500, 2000
liter

64. QUALITY CONTROL DEPARTMENT
64

65. 65
QUALITY CONTROL:
Quality control department is a set of procedure which is performed to ensure that the raw
materials , finished products and packaging materials adheres to defined set of quality
criteria or meets the requirements of the clients or customer at an economical level. ―Keep the
quality up‖ with that slogan Quality Control Department of BEXIMCOPHARMA performs
its day-to-day duties. This department is stuffed with pharmacist, chemist and microbiologist
who assess and assure that entire production process has been completed satisfactorily and
satisfied all the aspects of GMP.
Objectives,
 Ensuring quality and stability
 Reducing product loss
 Personnel train up
 Better interdepartmental and employee relation
 GMP practice
QC is responsible for,
1. Analytical testing of RM
2. Inspection of PM
3. In-process control (IPC)
4. Testing of finished products
Quality control units:
 Central quality control lab(Track-1)
 Quality control lab (Track -2)
 Quality control lab (infusion)
Requirements of Quality Control Department:
 Laboratory
 Manpower
 Machine
 Method
 Material
Quality control activities,
 Having equipped and supported with trained with analytical staff the QC laboratory
has to perform the following major responsibilities:
 Assessment of microbiological quality of raw material
 Assaying potency of antibiotic
 Assessment of the intermediate products for further processing
 Assessment of the bulk products for their release, Reprocess, reject, etc.
 Assessment of the finished products for their release, reject, etc,

66. 66
 Storing retention samples from each hatch
 LOT of raw materials
 Maintaining batch wise full duality control tests records, signature of the person who
performs the tests.
 Batch documentation and batch sentencing
 Ensuring precision and accuracy of all testing methods
 Performing environmental monitoring checks
 Calibration and standardization of laboratory equipment.
 Control of laboratory regents
 Testing of any return goods
 Analysis of complaint samples with their corresponding retained samples.
 Prepare QC related documents for DTL.
 Management of stability study program.
 Method development of new drug substances/products.
Good Manufacturing Practice (GMP) in QC:
GMP provides basic standards for the manufacture of drugs and from the basis on which each
company build its own system procedures to ensure the product quality. GMP ensures that
products consistently produced and controlled to the quality standards appropriate to their
intended use .There are number of national & international GMP regulatory boards
 WHO
 PIC
 FDA
 MHRA
 TGA
Types of assay done by quality control
1. GENERAL:
 Orientation of QC laboratory
 GMP and GLP
 Documentation
 Raw/packaging material and finished product sampling
 Packaging material
 Microbiology
 Stability study
2. ANALYTICAL
 Chemical and physical analysis
 Analytical development

67. 67
3. INSTRUMENTAL
A) High performance liquid chromatography(HPLC)
B) Gas chromatography(GC)
C) Fourier transform infrared spectrophotometer(FTIR)
D) Partical size analyzer(Malvern)
E) Atomic absorption spectrophotometer(AAS)
F) UV visible spectrophotometer
G) Dissolution tester
H) Disintegration tester
I) Suppository testing apparatus
 Disintegration tester
 Softening time determination apparatus
 Melting time determination apparatus
J) Karl Fischer titrator
K) Polarimeter
L) Potentiometric tritator
M) Other instruments
 pH meter
 Melting point testing apparatus
 Viscometer
 Refractometer
 Stampfvolumeter
 Table top centrifuge
 Muffle furnage
 Vaccum oven
 Sonicator
 Ultrasonic bath
 Water bath
 Centrifuge machine
 Microscope
Packaging material
 A,B,C class are classified according to vendors quality
 Highest rating vendor is selected
 But if source is changed then a new parameters are set for the new parameters

68. 68
Packaging materials Tests
Carton Appearance, weight, moisture content, sulphated
ash
Shipping carton Weight, dimension, thickness, appearance
Plastic cap Weight, appearance, length, diameter, volume,
capacity
Dropper Weight, appearance, length, diameter, volume,
capacity, adaptability with bottle, carton, and
plastic cover.
Musk tap Appearance, width, adhesiveness
Water measuring flask. Weight, appearance, length, diameter, capacity
5ml spoon (plastic). Weight, appearance, length, diameter, capacity
Blisters Height, neck diameter, body diameter, weight,
overflow capacity,
machine acceptance, and light transmission
Inert cartoon Height & level, description, weight, dimension
MICROBIOLOGY
 Microbiology division of QC performs microbiological tests.
 A microbiological test determines the potency of products as well as the presence or
absence of microbes in products.
 Microbiological tests relates to potency determination include the following products
of BEXIMCO Pharmaceutials –
1. Azithromycine
2. Azithrocine capsule
3. etrocine dry suspension
4. etrocine tablet
5. Gentocep cream
6. Amustant ointment
7. Gentomycine
8. Neomycine
9. Nystatin etc.

69. 69
Function of microbiology section
 Microbial count- Water, raw materials, bulk samples, finished products, packing
containers.
 LAL test/sterility test- Water, raw materials, parenteral products, other sterile
products.
 Environmental study- All manufacturing &filling area including aseptic filling room.
 Validation- Steam &dry heat sterilizer, oven & cleaned equipment.
 Personnel hygiene area- Aseptic production area operators.
 Bio-Assay- Antibiotic raw materials &finished products.
Activities of microbiological section
 Microbial limit test of raw materials and finished products-
 Total aerobic bacterial and fungal count
 Detection of pathogens like E.coli, Salmonella sp, Staphylococcus, Pseudomonas
aeruginosa.
 Microbial assay of raw materials and finished products
 Environmental monitoring
 Test for water
 Bioassay.
Equipment in Microbiological section
 Laminar air flow
 Hot air Oven
 Autoclave
 Incubator
 Rota mixer
STABILITY STUDY
Climatic zone
According to ICH (International conference on Harmonization), whole world is divided into
following climatic zones in considering the environmental conditions.
Zone-1 (cool & cold country, 8-15 0
C)
Zone-2 (cold country)
Zone-3 (hot country)
Zone-4 (Hot &humid country)
According to ICH guideline our country fall in zone 3&4. Stability study is performed
according to ICH

70. 70
Stage Tests
Raw Materials a. Assay
b. Description
c. Solubility
d. Identification
e. Optical Rotation
f. Purity
g. Water content Determination etc.
In Process Quality a. Disintegration Time
b. Quantitative Assay
c. PH
d. Identification
e. Weight variation Test
f. Dissolution Test
Finished Products a. Assay
b. Description
c. Identification
d. DT
e. Weight variation test
Packaging Material a. Visual inspections
b. Weight
c.
d. Size and Diameter
e. Dimention
f. Adaptability
g. Adhesiveness
Types of study Experimental condition Testing frequency
Long term 25⁰c temperature , Done in every 3 months for
60%relative humidity 1st year
Intermediate 30⁰c temperature , Done in every 6 months for
65%relative humidity 2nd year
Done only once for 3rd year
Accelerated 40⁰c temperature , Done initially.
75%relative humidity Then in 3rd month and 6th
Month
ANALYTICAL ANALYSIS
Tests Done for Quality Control:

71. Instruments which are in use in QC departments
Name of instrument Model Manufacturer Origin Use
Electronic analytical BP 210s Sartorious AG Germany Analytical weighing
precision balance
Electronic balance PT 310 Sartorious AG Germany Weighing
Electronic balance EL300 Shimadzu Japan weighing
Electronic BD 120L Mettle tiedo AG USA Do
balance(Top balance)
IR Moisture analyzer MA 30 Sartorious AG Germany Moisture
determination
Disintegration test ZT3/6 Erweka,GmbH Germany Disintegration testing
apparatus
Dissolution tester DT 6L Erweka,GmbH Germany Determination of
dissolution
Dissolution tester DT 700 Erweke, gmbh germeny Determination of
dissolution
Rotating bottle none Fabricated in Germany Do
disintegration tester BPL
Suppository ST 30 Erweka,GmbH Germany DT of suppository
disintegration tester
Suppository melting SSP Erweka,GmbH Germany Determination
point apparatus of melting point
Suppository softening PM3 Erweka,GmbH USA Determination
time tester of softening time
Humidity control NEC-234R Newtronic India Drying
oven equipment
Incubators Kottermann Germany Incubation
Jolting Stan PF STAV2003 Karl-Kolb Germany Tapping
volumeter Scientific
Supplies
Atomic absorption Ice 3000 Thermo scientific USA Metal detection
spectrophotometer(AAS) series
Gas chromatography 2010 Shimadzu Japan Volatile compounds
potency
HPLC(high performance
liquid chromatography)
E 2695 Water USA Sample potency
71

72. HPLC SPD-20 A Prominence, Japan Sample potency
Shimadzu determined
HPLC Ultimate Dionex Germeny do
3000
autosampler
UPLC(ultra Waters Usa Detect the unknown
performanceliquid material in short time
chromatography)
UV spectrophotometer UV 1800 Shimadzu Japan UV spectrum
Potentiometer 888 titrando Metrohm UAE Potentiometric titration
Karl fisher 890 titrando Metrohm UAE Water content
determination
Karl fisher DL 18 Mettler Water content
determination
Particle size analyzer AP2000 Malvern UK Particle size
determination
Polarimeter H 532 Schmidt+ Optical rotation
halensch
Refractometer AR 600 Leica Refractive index
Infrared spectro Prestige - 21 Shimadzu Japan Identification of raw
photometer material
FTIR Prestige-21 Shimadzu Japan do
Tap density tester Tap21 LOGAN USA Determine bulk density
instruments corp of raw material
Viscometer DV–I Brookfield USA Viscosity determination
PRIME
72

73. 73

74. 74
QUALITY ASSURANCE DEPARTMENT:
Quality assurance is the heart of the pharmaceutical company because in this section quality
of the production is assured. To maintain cGMP quality assurance department is the most
important sector for any company. The system of QA appropriate for the manufacture of
medicinal products should ensure that medicinal products are designed & developed in a way
that takes the account of requirements of GMP &GLP (good laboratory practice). The quality
measured physically, chemically or microbiologically. The quality assurance ensure the
quality of the product this department inspected the quality is maintained or not. A
pharmaceutical product must satisfy certain standards to claim its quality. The main
characteristics of any drug, in dosage form are- safety, potency, Efficiency, stability,
Acceptance, regulatory compliance. To produce quality drug product, quality must be
ensured in:
 Every step in the production
 In maintaining environment
 Personnel
 Equipment
 Operating procedure
Quality Assurance (Definition according to DIN ISO 8402)
All planned and systematic actions necessary to provide adequate confidence that a product
or service will satisfy given requirements for quality.
The impact of total quality maintenance is-
 Improved operating procedure.
 Greater customer satisfaction.
 Increased financial performance.
Quality Assurance- Its importance creates its need. Quality assurance is a broader concept
ranging from development, quality control, production, distribution, and inspections that
individually or collectively influence the quality of a product. Quality assurance department
does hold an important responsibility of making sure effective quality control tests are
included at right stages and executed perfectly at proper stages of product life cycle. Quality
Assurance applies for both drug substances (APIs) and medicinal products, and includes
current Good Manufacturing Practices (cGMPs), as well as any necessary analytical testing
and stability studies. Quality assurance (QA) is a vital as well as a very organized department
in Beximco pharmaceuticals. It helps in ensuring the quality of a product till the hands of
consumers.

75. 75
Quality assurance activities:
 Validation of three consecutive batches.
 Training of GMP and SOP
 Audit - vendor audit and
 Internal audit i.e. self inspection
 Stability testing
 IPC
 QC
 Quality incident report - corrective action, preventive action (CAPA)
 Change Control Request
 Out of specification
 Customer complain handling
 Regulatory activities
 Certificate of Analysis (CO A) generation
 Release for sale certificate.
 Orientation
 Product recall
 Product quality review etc.

76. 76
Functions of QA department
1. Warehouse:
 Visual Inspection of incoming raw materials and packaging materials
 Sampling of raw and packaging materials for Amoy, Microbial and Retention
test.
On the basis of the analytical results, release or rejection of raw and packaging materials are
done.
2. Dispensing area:
The QA dispensing officer monitors dispensing process thoroughly and attaches dispensing
cards to materials.
3. In- process checking
Solid Department
 Granulation area
a) Machine cleanliness and room conditions are checked and line clearance is permitted
b) LOD (loss on drying) of granules measured
c) Compression Area
Machine cleanliness and room conditions are checked and line clearance is permitte
 Qurantine area
On the basis of QC reports tablets are released for packaging.
 Packaging area
Before packaging starts, the room and machines are checked for cleanliness.
LCO department
 Before starting a new batch production room‘s cleanliness, manufacturing tank
cleanliness, room temperature and %RH are checked.
 After preparation of the product in manufacturing tank, the following are checked by
QA department.
 PH of preparation
 Viscosity
 Assay
 Filling and sealing:
During filling and sealing, the following parameter are checked

77. 77
o Proper weight
o Proper volume
o Cleanliness
o Microbial test of sealing preparation
o In case of suppository teak test is done
 In packaging area:
QA officer checks the following-
o Batch printing
o Inner and shipping carbon at regular time interval
 In Suppository section
 Before start up of manufacturing or filling machines/rooms are checked for
proper cleaning and good house keeping.
 During manufacturing room temperature, vessel temperature, pump
temperature, congealing temperature, room humidity, hardness, weight etc.
are checked.
 In Inhalation section
 The manufacturing vessel and area are checked properly before start up of
manufacturing.
 During manufacturing weight of the ingredients, mixing time, temperature,
rpm etc. are checked.
 During packaging the containers are checked for leak, total actuation no.,
dose/actuation, batch printing etc.
 Sampling and approval/disapproval is done like other section.
Documentation:
The basic rules in any good manufacturing practice (GMP) regulations specify that the
pharmaceutical manufacturer must maintain proper documentation and records.
Documentation is most important task of the quality assurance department. The purpose of
documentation is to record import information with evidence. GMP requires that a complete
and accurate records of all raw/packaging materials, finished product, BMR, BPR, have to
maintain for any necessary forcing back of any time.

78. 78
.
INFUSIONS UNIT

79. 79
INFUSIONS UNI:
Infusion is a very sophisticated product where highest purity & quality is maintained because
this is introduced into patient‘s systemic circulation. A micro corruption may lead to death. In
BEXIMCO Pharmaceuticals the quality & purity of infusions products are maintained
strictly. They mainly produce dextrose saline.
The infusion preparation involves 2 main operations-
1. Preparation of WFI
2. Preparation of solution.
Followed by 2 operations like-
I. Bottle preparation & Autoclave
II. Packaging.
A. Preparation of WFI:
WFI means water for injection. It is used for injectables. It has some specific criteria like-
 Totally pyrogen free.
 Free from all ions & minerals.
Steps of preparing WFI in BEXIMCO-
Step 1: Natural water collection
Step 2: Removal of iron
Step 3: Chlorination
Step 4: Removal of bad odor &pyrogen
Step 5: Removal of minerals.
Step 6: Removal of Pyrogen
Step 7: Temperature minimizatio

80. Process of Preparation:
80
Aeration Chamber (Compressed
air supply)
Sand & Gravel Filter
Raw water Over Head Tank (Capacity 5000L)
Pre-filter 15µ
Charcoal bed
Chlorine dosing
Filter
Raw
Water
Tank
(2000L)
2.5
µ
Filter
.22
µ
C A C A
A N A N
T I T I
Filter
MULTI
BED
Distillate Tank
(6000L)
Temp. 80-900
C
Steam distillation &
Condensation
DM Water
storage
Tank(4000L
)
.22
µ
2.5
µ
Filter
Heat Exchanger
WFI for Consume

81. 81
AREA CLASSIFICATION
Class BIL
Classification
Location Specification
0.5 µm 5.0 µm
Clean Grade D Class Personal air lock, 100000 700
class 100000 material air lock,
bottle pack area.
Grade C Class Injection, molding 10000 70
10000 room, solution
preparation room,
clean corridor,
weighing room
Grade A Class Under laminar air 100 None
100 flow
Manufacturing and Packaging Steps for LVPF:

82. 82
Different section of infusion unit:
 Production: Solution preparation and packaging
 Engineering: Bottle pack, injection moulding, autoclave, utility.
 QA and QC: Quality of the product.
 Warehouse: Quarantine approval and reject materials.
Quality Control Department
QC performs physical, chemical and microbiological test
Physical test
This is mainly done for packaging materials
o Dimensions
o Weight
o Adaptability
Chemical test
This is done for raw materials, finished product and wfi
o pH value
o Density
o Solubility
o LOD
o Optical rotation
o Acidity/Alkalinity
Quality Assurance Department
The following activities are performed by QA
Inspection
 Raw materials
 Packaging materials
 Minerals status
 Label
Sampling
 Raw materials
 Packaging materials
 Bulk solution minerals
 Cleaning sampling
 Finished product

83. 83
In process control
 IPC of raw materials
 IPC of bulk solution
 IPC during bottle pack
Microbiology Department
Microbiology test perform an important role to ensure the quality of the parenteral products
in the various steps ranging from raw materials to finished product.
In microbiology laboratory contains the following rooms
o Testing and incubation
o Media preparation room
The total testing procedure can be summarized as follows
o Sample collection
o Media preparation
o Culture preparation
o Incubation
o Colony count
The microbiological test procedure includes
o Test of raw materials and packaging materials
o Test of finished products
o Environmental control
o Purified wateriest
o Monitoring of surfaces
o Personnel hygiene

84. ENGINEERING SERVICE & UTILITIES
84

85. 85
ENGINEERING SERVICE & UTILITIES:
BEXIMCO pharmaceutical Ltd. has a complete and sound Engineering department for
supporting the frequent production. The engineering department provide production
environment. The manufacturing of various products require cleanliness, machine in order.
Different type of water supply, the controls of air, ventilation of the company, control of the
temperature, control of the RH test of the new machine, repairing machines etc are most
important concern for the pharmaceutical industry. All of those are maintain by the
engineering department.
Function of Engineering Department
The function of the department is divided into two types
1. Maintenance or Utility service
2. Process
3. Power supply
Maintenance of existing system
The function of this section is to separate the utilities and services in the plant. They also
perform maintenance function. The utilities and service handled by this section are given
below-
 Electricity
 Boiler
 Compressed Air
 HVAC system
 Potable / drinking water and purified water
 Central vacuum system
 Hot water
 Cold water
 Chill water
Maintenance of production machinery
Engineering department is also responsible for proper maintenance of production machinery.
This function is performed by the following two ways:
a) Scheduled maintenance
b) Troubleshooting or Breakdown maintenance
Compressed Air System
Compressed air is provided by compression unit. Compressed air required for
 Driving portable tools, driving machinery, transmitting control signals and actuating
pneumatic control devices and is not expected to have an impact on product quality.
 Terminal filters are also used before the user points of the machines where the products
come in direct contact with the compressed air.

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 Capacity is 10000 lit/min.
Chiller system
This system is involved in the production of chilled water which supplied through pipe to
produce air conditioning system. BEIMCO Pharmaceuticals has both compression &
absorption type chiller of which one in new solid & another is in old solid area.
Power supply
BEXIMCO Pharmaceutical Ltd. has its own complete power supply plant, which is
considered as the heart of the factory. They do not use PDB electricity. This power plant is
divided into two sections Low Tension (LT) & High Tension (HT). About 4000 kw power is
produced from LT sector & 1950 kw power is produced from HT sector.
QUALITY OF COMPRESSED AIR
 The quality of clean compressed air is monitored and required to meet the clean
com air specifications.
 GPF (General Purpose Filter) and DRF (Dust Removal Filter) are used to remove
particle size down to 1µm.
 OVF (Oil Vapor Filter) are used to removal of particle size down to 0.01µm.
 Mirror test performed to check whether any water or oil exists in the compressed
air. Maximum oil remaining 0.01ppm.
HVAC SYSTEM
The simultaneous control of various parameters of air to the specific limit as required for the
manufacturing of quality medicine is known as air conditioning. BEXIMCO dedicated Air
Handling Units and other building service systems installed in the mezzanine floor with a
focus to prevent cross contamination.
HVAC system is required for
 To maintain specified temperature (Here 240
C)
 To maintain specific relative humidity ( Less than 40% for some hygroscopic material
like ranitidine)
 To remove dust particle from production area
 To maintain proper airflow to the rooms ensuring that cross contamination does not
occur.
 To prevent microbial contamination in some area by maintaining particle size within the
tolerance range (using HEPA Filters etc).

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Laboratory
Manufacture
HVAC
Primary
Production
area
DIFFERENT HVAC SYSTEM
HVAC
Systems
Production
Area
Warehouse
Secondary
Production
Area
Dust
Collect
Microbiology
Lab
AN &Inst
Lab
Raw material
HVAC
PG
HVAC
WATER TREATMENT PLANT
In BEXIMCO pharmaceuticals, raw water is treated in different stages to meet criteria
specified for various applications. Process water should meet USP pacification for purified
water. Besides soft water is used for boiler feed water and generator cooling tower. Pre-
treated water is used for drinking, sanitary, washing applications etc.
Water Treatment
Plant
Iron removal
plant
Pre-treatment
plant
Soft water
plant
Purified water
plant
Iron Removal Plant
Bore whole water is passed through deep tube well to Iron removal plant. Iron is removed
here with the help of sand filter. Alum is dosed to the raw water prior to entrance to the sand
filter. Required iron concentration is less than 0.1 ppm.

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Pre-treatment Plant
This consists of tank, pumps, sand filters, activated carbon filters and dosing systems. Raw
water pump takes water from the tank and force through the filtration media of the
Omnifiltration system. Flocculants such as alum is dosed to destabilize the colloidal particles
and to give rise to insoluble compounds before entry to the filtration media. Omnifiltration
system consists of two filters installed in series and controlled by diaphragm valves. Water
passes downwards through the filtering layers in the two units and flows out of system free of
particulate material or undesirable elements. Sodium hypochlorite is dosed for oxidization as
well as for minimizing microbiological contamination. Activated carbon filters remove color,
odor and free chlorine.
Softened water plant
Water from the pretreatment plant is stored in a 8000 liter storage tank from where it is
pumped through the treatment stages. Firstly water is pumped through a sand filter which
removes suspended solids. Sodium Metabisulphate is dosed into the filtered water to
neutralize any residual chlorine that could be harmful to the softener resin. Water is then
passed through a duplex softener to remove most of the calcium and magnesium, ions. The
softening system is operated in duty/standby mode. Regeneration of the water softener is
initiated automatically after a preset volume of softened water has been produced. Then
softened water is passed through a 10 micron cartridge filter to remove any resin particles.
The softened water is split to a 12500 liter soft water tank and a 2000 liter softened water
tank. The 2000 liter softened water tank provides a buffer for the soft water that is fed to the
purified water plant. Water from this tank passes through a UV sterilizer to control
microbiological contamination. An anti-scalent chemical compound is dosed into the
softened water to remove any excess dissolved silica that could damage the reverse osmosis
membranes. Caustic is dosed to increase the PH
of the softened water. This plant produces
soft water with hardness less than 5 ppm.

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PURIFIED WATER PLANT
5 micron filter
Duplex softener
Activated carbon filter
Buffer tank
PUMP (Reverse osmosis)
Pure water
CDI
Anode
Cathode
Feeding water system (<0.2 u filter)
UV sterilizer
Purified water tank (10,000 liter)
1st
& 2nd
Heating and cooling exchanger
Final UV sterilizer (254 nm Intensity)
User points
Recycle to purified water tank
Flow 11.4 m3/hr
Calibration section
This section is responsible to calibrated all the instrument and machines to ensure
performance & effectiveness. The general process is to calibrate the instruments and
machines against a standard which is also standardized against international standards.
Waste chemicals cause environmental pollution by decreasing dissolved oxygen by oxidation

90. The oxygen demand is maintained by the following method-
Waste Chemical in
ETP
Add nitrifying bacteria that
cause breakdown of
chemical
Oxygen penetration in
water from outside
Urea supply in ETPfor
nitrifying bacteria
Maintaining normal limit
of dissolved oxygen
No environmental
pollution
FLOW CHART OF CHEMICAL WASTE MANAGEMENT
Chemical waste
Liquid waste Solid waste
Treatment
Effluent treatment plant Alkali/ ammonia treatment in case
of antibiotics
Disposed outside Incineration
90

91. TRAINNG DEPARTMENT
91

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BEXIMCO Pharmaceutical Ltd. arranges training for new employees to introduce with job
responsibilities & to comply with rules and regulations as well as to make them competent
with their respective job in the company. BEXIMCO also arranges training for existing
employees to update information to the point.
BEXIMCO provides 2 types of training generally-
a) In house training
b) External training.
In house Training: Beximco Pharmaceutical Ltd.
 Training Procedure:
 Training Need Analysis
 Select ‗Resource Person‘.
 Preparing training calendar.
 Conducting training session.
 Evaluation.
 Documentation.
 Re-training.
 Training Type:
 Class room training.
 Audio visual training.
 Interactive training.
 On the job training.
 Group exercise.

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 Training Applies To:
 Manager
 Officer
 Workmen
 Training for new employees:
 Basic GMP
 Safety overview.
 On the job training
 SOP
 For existing employees:
 GMP
 Safety
 Utility system
 On the job training
 SOP

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The EHS department of Beximco Pharmaceuticals Limited (BPL) is concerned with the
disposal of waste in a way that does not damage the environment, safety of the personnel as
well as their health, for instance by arranging annual checkup for the existing employees and
pre medical check-up for the newly joined employees
Water pollution can be controlled by:
Physical treatment:Methods employed are-
 Sedimentation and gravity settling methods
 Adsorption process using activated carbon
Chemical treatment:Such a treatment is generally brought out by-
 Coagulation,
 Flocculation,
 Emulsion Breaking,
 Precipitation And
 Neutralization.
Biological treatment:
This is another treatment process which consumes oxygen dissolved in water.
Dust explosions
In pharmaceutical industries, a large number of grinding operations is employed. If iron
or stone pieces get into the disintegrator or other similar girding mills, sparks are emitted
which might bring about explosion with some easily combustible materials.
It has been found that in pharmaceutical and ancillary factories, dust of starch and dextrin
besides organic substances are extremely hazardous.
Suitable precautions against accumulation of dust should be taken.
The methods used for controlling dust in pharmaceutical industries are-
 Filtration
 Inertial separation
 Electrostatic precipitation
Activities of Safety Department:
First Aid Measures (Chemical):
Eye Contact:
 Flush eyes with plenty of water for at least 15min, lifting lower and upper eyelids
occasionally.
 Do not rub eyes