SummaryBeximco Pharmaceuticals Ltd. or BPL, the leading pharmaceutical company of Bangladesh and a member of the BEXIMCO Group was founded in 1976. Since then it has been producing produces pharmaceutical specialties of uncompromising quality in its several world-class pharmaceutical production units following current Good Manufacturing Practice (cGMP) as required by the World Health Organization (WHO). Beximco Pharmaceuticals Ltd. has products of different therapeutic classes, each of which occupies a prominent position in the market and the heart of people. Life seems static without Napa and Neoceptin, the prime products of BPL. More than 10% of country’s total medicine need is supplied by Beximco Pharma where separate solid production unit and Liquid/Cream/Ointment Production unit manufactures comprehensive range of formulations, which come in tablet, capsule, powder, liquid, cream, suppository, nasal spray and others covering all the major therapeutic groups.

BEXIMCO allays maintains GMP and cGMP over production areas. They have validated SOP, Process validation system, equipped Microbiology section, and cleaning procedure. They also have air lock system laundry for cleaning cloths and waste disposal system.

BEXIMCO have Quality Control and Quality Assurance Department that are responsible for the quality of the product in every step of production phenomena. And their documentation is excellent.

BEXIMCO Pharmaceuticals have Human Resources & Training Department, devoted to make skilled employee while engineering department is ensuring proper operations of machineries, electric and electronic equipment during production. Its safety measure for the employees is excellent.

IntroductionThe pharmaceutical sector is one of the most developed & leading sectors which

contributes in our national economy as well as creates lot of job opportunities. Before the

promulgation of drug ordinance- 1982, different Bangladeshi companies like Beximco were

involved in packaging & distributing formulated drugs throughout the country. The development

of this sector was accelerated after the promulgation of Drug Control Ordinance – 1982. Skilled

pharmacists, innovative ideas, huge investment & research are the key factors for tremendous

development. Bangladesh now exports drugs worldwide. This sector is also providing 99% of the

total medicine requirement of the local market.

According to the training schedule we visited all the sections and that Beximco

Pharmaceutical Ltd. Beximco Pharmaceutical Ltd. never compares with quality & this policy

drives all people to maintain their quality. To ensure good quality products the Quality

Assurance, Quality control, highs process control system have been developed.

During our training, we observed the process of manufacturing and maintaining quality

according to GMP (Good Manufacturing Practice) guidelines. As a result of visiting in such a

well organized and well-reputed company like Beximco Pharmaceutical Ltd. our theoretical

concept has become developed of the basis of practical view.

Company profile

Beximco Pharma is a leading edge pharmaceutical company which produces 447 drugs

including 268 solid, 53 oral liquids & 24 intravenous dosage forms. They produce and market

'branded generics' for almost all diseases from AIDS to cancer, from infection to asthma, from

hypertension to diabetes, for both national and international markets. They also manufacture

active pharmaceutical ingredients and intravenous fluids and contract manufacture for major

international brands of leading multinational companies. They partner our activities to the

humanities quest for longer, healthier, and happier life.

The company was incorporated in 1976 and commenced operations in 1980 with the

manufacturing and marketing of products of Bayer AG, Germany and Upjohn Inc., USA under

licensing arrangements. In 1983, the company started manufacturing its own formulations and it

launched export operation in 1992. In 2005 Beximco Infusions Ltd, the company that produces

intravenous fluids was amalgamated with the parent company. In the same year it completed the

state-of-the-art oral solid dosage plant in compliance with the US FDA and UK MHRA

standards, which has been approved by major global regulatory bodies.

It has now grown to become a leading pharmaceutical company in Bangladesh, and it supplies

more than 10% of country's total medicinal needs. Beximco Pharma does not reach in its

position in a day. Their development was the result of their quality and efficiency. A table is

given below showing their transformation to a pharma giant of Bangladesh.

Year Event

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 Beximco Pharma’s own brands

1985 Listing in the Dhaka Stock Exchange (DSE)

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 Beximco Pharma 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-Antiinflammatory bulk drug plant

2002 Won the first prize of ICAB National Awards 2000 for 'Best Published

Accounts and Reports' in Non-Financial Sector Category The first

Bangladeshi company to supply pharmaceuticals to Raffles Hospital- the

most prestigious hospital in Singapore

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

Won a tender to supply Neoceptin R and Neofloxin to Raffles Hospital of

Singapore for whole year's consumption 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

2005 Merger of Beximco Infusions Ltd. with Beximco Pharmaceuticals Ltd.

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 Enlargement of warehouse

2009 New plant of opthalmic prepration

Human Resources Management

IntroductionHuman resources is the set of individuals who make up the workforce of an organization,

business sector or an economy. The professional discipline and business function that oversees

an organization's human resources is called human resource management (HRM, or simply HR).

It is the management of an organization's workforce, or human resources. It is responsible for the

attraction, selection, training, assessment, and rewarding of employees, while also overseeing

organizational leadership and culture, and ensuring compliance with employment and labor laws.

Core Functions of Human Resource Management:-

Recruitment

Recruitment is the process of attracting, screening, and selecting employees for an organization.

The different stages of recruitment are: job analysis, sourcing, screening and selection, and

onboarding.

SelectionSelection is the process of selecting a qualified person who can successfully do a job and deliver

valuable contributions to the organization.

Orientation

Employee orientation, also commonly referred to as onboarding or organizational socialization,

is the process by which an employee acquires the necessary skills, knowledge, behaviors, and

contacts to effectively transition into a new organization (or role within the organization).

Development

For overall organizational success, it is crucial to develop employees through training, education,

and development.

Performance Evaluation

Performance evaluation is the process of assessing an employee’s job performance and

productivity, usually for a specified period of time.

Career Path Management

Career path management requires HRM to plan and then actively manage employee skills in the

pursuit of successful professional careers.

Beximco Pharmaceutical Limited is one of the leading corporate house of the country. It has a

handsome amount of workforce lead by the Human Resources Department (HRD). Different

activities are performed by this department for smooth running of the Industry. Some important

activities are discussed below:

Recruitment of personnel (worker) with appropriate qualifications as well as experience

to fill all the position that has an effect upon quality. Different standards are considered

for different positions.

Assist new employees to complete their joining activities and ensure placement of new

comers.

To arrenge induction training program ( orientation program) for new employees. After

joining each employee is introduced with all of their departmants and their particular

functions.

Prepare and coordinate internship program for the students of different university.

Internship is a method of externel recruitment program.

Prepare monthly human resources inventory report. In includes all information of daily

labor of the employees.

Maintain, update and store personal information’s of all employees which includes

confirmation of job, incentives, promotion, transfer and personal letters etc.

Supervise and monitor employee attendance, job card regulation and prepare monthly

summary and daily absent reports.

Monitor and store leave information in a leave file that integrates all kinds of leaves.

Prepare and coordinate performance appraisals of factory employees.

Coordinate training of personnel in light with cGMP and other related HR issues.

Ensure proper implementation of labor laws with negotiation with employees union and

ensure the labor rights.

Take disciplinary actions such as suspension, punishment, transfer and termination.

Ensure healthy labor management.

Maintaining liaison with different Government Regulatory bodies. HRD collaborates

with the following bodies,

Ministry of Industry.

Office of Director of Labor.

Customs and vat, Tongi circle.

Office of Deputy Commissioner, Gazipur.

Office of Superintended of Police, Gazipur.

Civil Surgeon, Gazipur.

Explosive Department.

Director of fire and fire station of Tongi

Tongi Thana, NSI, DB and SB.

Ensure safety of all employees and company assets.

Ensure proper security management of the plant.

Handle audit of external visitors and all accessories about this.

Supervise transport pool (distribution, repair, maintenance etc.)

Supervise overall cleaning and beatification services such as gardening.

Arrange and supervise canteen facilities.

Production PlanningIntroductionProduction planning means to fix the production goals and to estimate the resources which are required to achieve these goals. It prepares a detailed plan for achieving the production goals economically, efficiently and in time. A well defined production plan is the pre-requisite for a established & modern pharmaceutical industry, to achieve the following objectives. BPL possesses a organized Production Planning Department that ensures the desired excellence of quality.

Objectives of Production Planning

A typical large manufacturing business engaging in production planning will aim to maximize profitability while maintaining a satisfied consumer base. The objectives of Production Planning includes-

1. Effective utilization of resources

Production planning results in effective utilization of resources, plant capacity and equipments. This results in low-cost and high returns for the organization.

2. Steady flow of production

Production planning ensures a regular and steady flow of production. Here, all the machines are put to maximum use. This results in a regular production, which helps to give a routine supply to customers.

3. Estimate the resources

Production planning helps to estimate the resources like men, materials, etc. The estimate is made based on sales forecast. So production is planned to meet sales requirements.

4. Ensures optimum inventory

Production planning ensures optimum inventory. It prevents over-stocking and under-stocking. Necessary stocks are maintained. Stock of raw material is maintained at a proper level in order to meet the production demands. Stock of finished goods is also maintained to meet regular demands from customers.

5. Co-ordinates activities of departments

Production planning helps to co-ordinate the activities of different departments. For e.g. the marketing department co-ordinates with production department to sell the goods. This results in profit to the organization.

6. Minimize wastage of raw materials

Production planning minimizes wastage of raw materials. It ensures proper inventory of raw materials and materials handling. This helps to minimize wastages of raw material. It also ensures production of quality goods. This results in a minimum rejects. So proper production planning and control results in minimum wastage.

7. Improves the labour productivity

Production planning improves the labour productivity. Here, there is maximum utilization of manpower. Training is provided to the workers. The profits are shared with the workers in form of increased wages and other incentives. Workers are motivated to perform their best. This results in improved labour efficiency.

8. Helps to capture the market

Production planning helps to give delivery of goods to customers in time. This is because of regular flow of quality production. So the company can face competition effectively, and it can capture the market.

9. Provides a better work environment

Production planning provides a better work environment to the workers. Workers get improved working conditions, proper working hours, leave and holidays, increased wages and other incentives. This is because the company is working very efficiently.

10. Facilitates quality improvement

Production planning facilitates quality improvement because the production is checked regularly. Quality consciousness is developed among the employees through training, suggestion schemes, quality circles, etc.

11. Results in consumer satisfaction

Production planning helps to give a regular supply of goods and services to the consumers at far prices. It results in consumer satisfaction.

12. Reduces the production costs

Production planning makes optimum utilization of resources, and it minimizes wastage. It also maintains optimum size of inventories. All this reduces the production costs.

Function of production planning

Maintaining the monthly planAccording to the monthly plan based on the demand of the market, production planning department suggest production department to manufacture the product.

Issuing of B.P.R and B.M.R:Production planning department issue the B.P.R. and B.M.R. according to the production plan. When there is need of changing the B.P.R. planning department consult with the product development for its correction.

Maintaining Buffer Stock for raw and packaging materials Planning department arrange all types of raw and packaging materials by consulting with the head office for smooth production.

Optimization and Co-ordinate all sections Planning department optimizes and co-ordinates all sections to give highest production within minimum cost and time.

Keep daily production report and documentsPlanning department keeps all types of daily production reports from all departments and maintain major documentation.

Day wise machine utilization:

The planning department has to create daily machine utilization statement. If any complexity arises in the machine utilization, they have to immediately in form the higher authority.

Submission of monthly reportPlanning department submits monthly production report to ED. Production planning department deals with every paper of any production including-

Acceptance/ Rejection papers of raw and packaging materials Order paper Delivery report Other invoices

Arranging physician sample

Production department will separate physician sample from bulk production according to the order of the planning department. In this case, samples are prepared at least one month prior to dispense. These samples are dispensed in catch cover. From manufacturing to packaging production planning department have to pay extra concern for this type of product.

Arranging product for international marketPlanning department will arrange and supply the products to the international market. After receiving information from email, they take necessary action to meet the demand for export purpose.

Figure : Functions of Production Planning Department

Compare man-hour and achievement Planning department compares man-hour and achievement to know the actual efficiency of man and machine.

Production Planning Department

Physician Sample

Aggangement Product Arrangment for

International Market

Co-ordination of all Sections

Comparison of Man-hour & Achivement

Documentaion

Production Report

Keeping

Ensuring Availability of Raw

& Packaging Material

Monthly Report

BPR & BMR issue

Warehouse

Introduction Warehouse is the place where materials for the production are stored for further use and distribution. The Beximco Pharmaceutical Ltd. has a striking warehouse where raw, packaging and finished products are stored with great care.On the 1st day of our training we went to visit the BPL warehouse. We found that the chief difference between a normal warehouse and a pharmaceutical warehouse is that the latter stores raw material, packaging material and finished goods for human consumption and sorequire specified preservation techniques, place of storage, temperature, atmosphere, humidity etc. A BPL warehouse with about 1300 types of packaging materials and 500 types of raw materials has strictly maintained SOPs and is strongly guided by GMP.

Different Segments of Ware house

There are different segments of the warehouse. They are:

Quarantine area : After receiving raw and packaging materials are kept here for QA approval.

QC sampling area: This basically consists of sampling booths where the environment (temperature, humidity and pressure) is strictly controlled and the sampling is done by QC officer under laminar air flow and HEPA filter

Released area: This area is the considered as the heart of the ware-house. Raw and packaging materials are preserved here with great safety and care which are approved by the QA. This area is the heart of the ware-house.

Rejected area: Rejected raw and packaging materials and finished products are stored here with great care. The rejected area is located at one corner of the warehouse in a separate room, where entry is strictly regulated.

In–process area: Materials dispensed for manufacturing are kept in this area.

Finished products area: Finished product that are ready to release for market are stored here until delivery.

Return Good Store: If a product is returned from market then it is kept in Return Good Store

Special area: Area or room for storing heat and light sensitive materials like colors, vitamins, poisonous materials and flammable materials. There are 3 special areas.

Cool room : Temperature 8-150 C. Cold room : Temperature 2-8 0 C.

Area for narcotic and controlled drug : There is another specific area in the ware house where narcotics and controlled drugs are stored under lock and key.

Types of job done in the warehouse

The work of warehouse is differentiated into two categories. They are:

Routine works Periodic works

Routine works: Receiving of materials: Raw & packaging materials are received after arrive at the

factory premises by different Supplier with two copies of delivery challan & invoice.

Invoice checking: The concerned authorities of the warehouse verify the invoice &

accordingly they will check whether the shipping mark is logged on the container or not.

Physical inspection and receipt/Discrepancy report: After completing the physical inspection of the raw materials, the materials are received on the basis of SOP if there is no discrepancy.

Quarantine storage: Raw and packaging materials are stored in this stage before the checking by the QC and approval from the QA.

Log book entry: To entry the actual received quantity of materials into the log book and copy to MIS Department, Shipping Department, Production Planning (Factory), Warehouse.

MRR for imported items: After receipt of materials, MRR is completed & the quantity of materials undergoes computer entry to the final stock. Three copies of MRR send to Shipping Dept, A/C Dept, and Warehouse.

QC sampling: Warehouse authority will inform the QC for sampling and after doing sampling and analyzing the QC will send the report to the QA.

QA release / reject: On the basis of QC analysis & pass report QA give ‘released tag’ on each & individual container or box. If the material fails to pass QC test, QA give rejected tag on each and individual container or box.

MRR / Failed MRR: Send copy to A/C Department, Shipping Department, and Warehouse.

Disposition Of released / rejected materials: Released materials are placed in the released area for dispensing and Rejected materials are placed in the rejected area until further decision for final disposition is made.

Dispensing: Only the released materials are dispensed as per requisition of production department following respective SOP.

Distribution: Most of the dispensed materials are carried and supplied to respective department by Warehouse personnel.

Computer entry of requisition: Inventory updating is done by computer entry of issued requisition and copy to e-mail for users.

Monthly inventory report: Monthly updated inventory report is sent to MIS Department, A/C Department, and Purchase Department.

Periodic works

Periodic works done by warehouse: (Export in the foreign market)

1. Export Order: The ware house is responsible for obtaining Export Permission (EP) order for products that are to be exported. It is also considered as the final check point where the containers are weighed and matched with the invoices before exporting so that any discrepancies can be discovered

Apply to custom: To apply for export to customs office with Export from duly filled by Warehouse invoice, packing list and export permission issued by Drug Administration.

Delivery to C&F agent: In presence of custom inspector materials delivered to C & F agent.

Receipt of airway bill: International marketing department send airway bill for necessary information & action.

Submission to custom: Paying the air way bill to custom office with monthly return. Pricing: Incase of a change in price the warehouse is responsible for obtaining approvals

from customs. The appropriate documents are sent with samples of the product. Audits: To successfully face an audit, it is necessary for the warehouse to maintain the

logbooks (for weighing, cleaning, temperature, sampling booth, daily calibrations, etc) as a proof that SOPs are followed within the warehouse premises.

Inventory management: The BPL warehouse is responsible for continuously updating its inventory. The total inventory of materials is checked periodically and quantities of materials are either written on or off depending on whether it is excess or short respectively.

Operational Scheme of warehouse:

This scheme is maintained for both raw and finished products.

After the approval by QA finished product come again to the ware house and stored until distribution

Quality of the finished product are tested by QC

Packaging

Manufactuaring

Approved materials goes to Production department according to requision

QC fixes 'Release' tag if materials passed in the tests

QC department takes sample

Quarantine

Material receive by primary checking

Rejected tag is given if materials failed to pass the

result

Sampling Booth of warehouse:

After reaching the raw material in the warehouse, the QC officer does the sampling of the raw materials in the sampling booth.

Sampling is done by a sampler that consists of three parts- upper, middle and bottom. The sampling is done on the basis of FIFO (First in First Out) system. For active ingredients, every container and for excipient, (√n+1) containers are sampled (where n = total number of the containers).

Dispensing areas:

A dispensing officer is responsible all the time for dispensing the raw materials to the production and packing materials to the packing areas. Following things should be checked by the dispensing officer in all phases:

To check that only those materials that are approved have been brought to the dispensing area.

To check that the area of dispensing is absolutely free from others materials. To check whether cleaning is done with IPA and savlon solution. To check that correct quantity and approved quality of materials are being dispensed as

per requisition. To heck that materials come first are being dispensed first, to follow FIFO (First In First

Out).

Some important informationSome important information about ware house:

Temperature is maintained not more than 25o C & humidity 30%.

Raw materials ready for Q.C. sampling are reserved by surrounding yellow color line for some

days.

Released finished products are reserved by surrounding green color line.

Two types of packaging-primary & secondary.

All data is reserved in the log book.

Special light is used to keep sage from insects..

Final products, ready for going to market, are kept in Finish Goods Area.

Miscellaneous things:

There are some other things that are maintained in warehouse. They are-

To keep warehouse free from attack of insects and rats, some insect or rat killer devices are being used.

To protect warehouse’s material from dust, the building is built in a systematic way such as the double door system.

Raw materials and finished products are easily identified here with the help of an index which includes different code for different area also.

Packaging materials in warehouse are kept or placed following Alphabetical order.

TabletIntroductionA tablet is the most common means of administering a medicine. Tablets are compressed powder, formulated so not to break up or chip before being taken, but to disintegrate in the digestive tract and release easily and in predictable manner. There are some basic steps which required to be fulfill during tablet formulation………………….

Characteristics of Tablet:-

Tablets are convenient to use and are an elegant dosage form.A wide range of tablet types is available, offering a range of drug release rates and

durations of clinical effect. Tablets may be formulated to offer rapid drug release or

controlled drug release, the latter reducing the number of daily doses required (and in so

doing increasing patient compliance).

Tablets may be formulated to release the therapeutic agent at a particular site within the

gastrointestinal tract to reduce sideeffects, promote absorption at that site and provide a

local effect (e.g. ulcerative colitis). This may not be easily achieved by other dosage

forms that are administered orally.

Dispensing

Granulation

Filling

Compression

Ejection

Tablet Coating

Packaging

Tablets may be formulated to contain more than one therapeutic agent (even if there is a

physical or chemical incompatibility between each active agent). Moreover, the release of

each therapeutic agent may be effectively controlled by the tablet formulation and design.

With the exception of proteins, all classes of therapeutic agents may be administered

orally in the form of tablets.

It is easier to mask the taste of bitter drugs using tablets than for other dosage forms, e.g.

liquids.

Tablets are generally an inexpensive dosage form.

Tablets may be easily manufactured to show product identification, e.g. exhibiting the

required markings on the surface.

The chemical, physical and microbiological stability of tablet dosage forms is superior to

other dosage forms.

Types of Tablets

Primarily there are two types of tablets. They are:1) Compressed tablet2) Molded tablet

Compressed tablets are subdivided into many tablets. They are described below:-

Oral tablet: These tablets are placed over the tongue and swallowed with a drink of water or any other suitable liquid. Most of them are formulated in such a way that they disintegrate in the stomach; some of the tablets are like enteric coated tablets are disintegrated in the intestine. Among the compressed tablets the oral tablets constitute a major group. Chewable tablets: These are the tablets which are required to be broken and chewed in between the teeth before ingestion. These tablets are given to the children who have difficulty in swallowing and to adults who dislike swallowing. For the preparation of chewable tablets mannitol is used as a base but since it is expensive, other substances like sorbitol lactose, chocolate powder, dextrose and glycine can be substituted in place of mannitol. These tablets don’t require any disintegrating agent to be present in the formulation. Buccal / Sublingual tablets: These tablets are required to be placed below the tongue or in the side of the cheek for the slow release of the medicament. Generally, these types of tablets contain those drugs which are destroyed, inactivated or not absorbed in the GIT but are directly absorbed through the mucosal tissue of the oral cavity.

Lozenge Tablets: These tablets should not disintegrate in the oral cavity but dissolve slowly in the mouth to produce continuous effect on the mucous membrane of the throat. Soluble Tablets: These tablets are required to dissolve completely in the liquid to produce solution of definite concentration. The solutions prepared by dissolving the soluble tablets may include mouthwashes, gargles, skin lotions, douches, antibiotics and certain antibiotics.Effervescent Tablets: Effervescent tablets are designed to produce a solution rapidly with the simultaneous release of carbon dioxide. The tablets are prepared by compressing the active ingredients with mixtures of organic acid—such as citric acid or tartaric acid and sodium bicarbonate. The most widely produced effervescent tablet is one that contains aspirin.Vaginal Tablets: Sometimes vaginal suppositories or pessaries are prepared by compression which are known as vaginal tablets. Antibiotics and steroids are prepared formulated in this way. They are generally ovoid or almond shaped for ease of insertion.Implants: Implants are small tablets meant for insertion under the skin by giving as small surgical cut into the skin which is stitched after the insertion of the tablet. As these tablets are inserted or implanted intramuscularly or subcutaneously they must be sterile. They must be produced under aseptic conditions and packed in unit dose sterile containers. Generally steroidal hormones like testosterone, stilbesterol etc. are formulated as implants.Enteric coated tablet: These are the tablets which are required to be disintegrated in the stomach. They are given coating which makes the tablets to pass the stomach as such but breaks in the alkaline medium of the intestines.Sustained action tablets: These are the tablets which after oral administration release drug at a desired time and prolong the effect of the medicament. The term ‘controlled release’ has associated with those systems from which therapeutic agents may be automatically delivered at predefined rates over a long period of time.Sugar coated tablets: These are the compressed tablets which are given a sugar coating to mask the objectionable taste and odor of the drug as well as to protect the substances from atmospheric conditions.Film coated tablet: These are the compressed tablets which are given a thin coating of the water soluble materials which protect tablets from the atmosphere. Various polymers are used for the film coating.Layered tablets: These are the compressed tablets in which the granules of incompatible substances are compressed into two or more layers successively in the same tablet.Press coated tablet: In these tablets the granules of incompatible ingredients are compressed around a previously compressed tablets.

ExcipientsAccording to the functions which these additives play in the preparation of tablets may be

classified as follows:----

Diluents: These are added to increase the bulk of powders to be easily compressed are known as diluents. Various diluents used are lactose, starch, mannitol, calcium carbonate etc.Binders: The agents used during granulation to impart cohesiveness to the powdered substances are known as binders. They keep the tablets compact after compression. Various commonly used binders are starch, acacia, tragacanth, gelatin, glucose, lactose etc.Granulating agent: These are the substances which are added to the powders during granulating process to convert fine powders into granules. Most commonly used granulating agents are water, mucilage of acacia, tragacanth.Disintegrating agent: These types of substances are added to tablets to facilitate their disintegration or breaking into small particles in GIT and thus facilitate their dissolution. Most popular and commonly used disintegrating agents are maize starch and potato starch. Others are methyl cellulose, agar, bentonite, carboxy methyl cellulose etc.Lubricants: Lubricants are the substances which are added to the granules before compression to improve the flow of granules. Generally, magnesium stearate, calcium stearate, talc are used as lubricants.Coloring agents: Coloring agents are used to impart elegance to the tablets. Only the approved colors are used. These are added in mixture before granulation.Flavoring agent: Flavoring agents are added to all types of lozenges, chewable tablets and effervescent tablets. For this purpose, volatile oils, volatile substances, fruit flavors are used.Sweetening agents: These are added to tablets which are required to be dissolved in the buccal cavity. The bases for their formulations are already sweet e.g. mannitol, lactose and sucrose. They impart sweetness in varying degree.

Primary

DiluentsBindersLubricanGlidant

Secondary

Granulating agentsDisintegrating agentSurfactantColoring agentFlavoring agentSweetening agent

Different Solid Manufacturing UnitSolid manufacturing unit consist of two main parts—

Dispensing Area Manufacturing Area

Dispensing Area:- Dispensing unit of Beximco Pharmaceutical Ltd consist of three rooms.1. Room for raw materials form warehouse,2. Weghing Area:- In this area raw materials for manufacturing unit is weighted.

There are two types of balance:-

Name of Equipment Capacity

Sartorious Balance 4.2 Kg

Sartorious Balance 300kg

Manufacturing Area:-

Granulation:-

Types of Granulation:- There are three types of granulation-a) Wet & b) Dry.

Wet granulation process:-

Dry granulation process:

Critical Parameters in Granulation:- Moisture content Heating temperature Air flow Ration of powder and granules.

Machines used in Granulation Unit:-

Name of Machines Type Producer Capacity

Ganson Planetary Mixture IndiaFB-600 Fluid Bed Drier 250KgMark Inds Multi-mill Bangladesh 100MG-60-2SX High-speed Mixing

granulatorThailand 250

Observation:- Napa 500mg

Compression:- Types of Punch:-

i. D-typeii. B-type

iii. BB-typeiv. Special BB-typev. Special D-type

Compression Process:- The granules are compressed in the die cavity by the upper punch after filling the cavity with the granules coming from hopper. It involves a few steps—

Machine used in Compression Unit:-

1. Compression unit # 1:Name of the machine: MANESTYModel of the punch: D typeName of the producer: MANESTY Machineries Ltd. Liverpool, England.No of stations: 16Capacity: 1500 tablets/hourObservation: During visit, this machine was stopped.This is very old model tablet compression machine but it is the first machine by which Beximco started.

2. Compression unit # 2:Name of the machine: MANESTYModel of the punch: B typeName of the producer: MANESTY Machineries Ltd. Liverpool, England.No. of stations: 35Capacity: 240000tablets /hourObservation: Frensit

3. Compression unit # 3:

Lowering of the lower punch.

Filling of the feed shoe with granules from

hopper

Removal of the feed shoes other

the die

Filling the die cavity with

granules

Removal of excess granules

by feed shoe retraction

Lowering of upper punch

compression of the materials in

the

Cavity to form tablet and

retraction of upper punch

Rising of lower punch to eject

tablet

Removal of the tablet by feed show

movement to continue the process.

Ejection of tablets into a barrel or other suitable

container.Packaging

Name of the machine: MANESTYModel of the punch: B typeName of the producer: MANESTY Machineries Ltd. Liverpool, England.No. of stations: 35Capacity: 240000 tablets /hour

4. Compression unit # 4:Name of the machine: Fette-1200Model of the punch: BB typeName of the producer: GermanyNo. of stations: 30Capacity: 220000 tablets /hour

5. Compression unit # 5:Name of the machine: Fette-3100Model of the punch: BB typeName of the producer: GermanyNo. of stations: 55Capacity: 594000 tablets / hourObservation: Aristovit –B

6. Compression unit # 6:Name of the machine: MANESTYModel of the punch: B typeName of the producer: MANESTY Machineries Ltd. Liverpool, England.No. of stations: 35Capacity: 70000 tablets / hour

7. Compression unit #7:Name of the machine: SEJONG-49Model of the punch: B typeName of the producer: South KoreaNo. of stations: 45Capacity: 494000 tablets /hourObservation: Aristovit –B

Coating:-

Purified water is heated in electric jacket vessel and stirring is started

Sugar is added and boild for 2hr

Description of Sugar Coating:-

There are two primary steps of sugar coating. Those are---i. Coating solution preparation

ii. Sugar Coating stages.

Coating solution preparation consist of three steps. Those are given below----

a) Sub-coating Solution Preparation Process:-

Purified water is loaded in electric heated jacket vessel and stirring is started

Gelatin and accacia is added and boiled

Then sugar is added and stirred

Then talc is added and stirred for 30min

Then titanium dioxide is added and stirred

Total time requires is 3.5 hours.b) Sugar syrup Preparation Process:

Total time spent: 2 hour.

c) Color Solution Preparation Process:-

Color blend is added to sugar syrup and stirred for 30minutes.

Sugar Coating stages are multi stage process. Those are given below---

Film Coating Process

• Modern approach to coating tablets, capsules, or pellets by surrounding them with a thin layer of polymeric material. 

• Description of tablets: Shape dictated by contour of original core.

• Process: Single stage process, which involves spraying a coating solution . Film coating solution may be aqueous or non-aqueous . An aqueous solution contains the following;

1. Polymer

2. Solvent

3. Plasticizer

4. Colorant

The solution is sprayed onto a rotating tablet bed followed by drying, which facilitates the removal of the solvent leaving behind the deposition of thin film of coating materials around each tablet.

Types of film coating:-

A. Immediate release

B. Modified release

General Problems in Tableting:-

During the production of tablets many defects arise with the finished tablet, those problems are given below:

Capping : It is the partial or complete separation of a layer from the main body of the tablet.

Causes:1. Lack of sufficient moisture content during compression.2. Incorrect adjustment of scrapper blade.3. Improper flashing of lower punch to eject the tablets.4. Insufficient time of compression.5. If the granules do not follow the normal distribution curve.

Remedy : Have sufficient moisture content during compression. Correct adjustment of scrapper blade. Proper flashing of lower punch to eject the tablets. Sufficient time of compression.

Picking:- It is the removal of surface materials from the tablets by the punch due to cohesiveness or sticking of materials with the surface of the punch.

Cause : More moisture content over normal / optimum. Improper use of lubricants and adherents. Broken edges of the punch and dyes. If the surface of the punch and die cavity id not sufficient smooth. If the engraved symbol is itself abrasive.

Remedy : Should maintain optimum moisture content Proper lubrication Washing the die and punch Die cavity should be smooth Use of colloidal silica to prevent adhesiveness.

Sticking : It is the adhering of the materials to the die wall.

Cause :1. More moisture content over normal / optimum.2. Improper use of lubricants and adherents.3. Broken edges of the punch and dyes.4. If the surface of the punch and die cavity id not sufficient smooth.5. If the engraved symbol is itself abrasive.

Remedy : Should maintain optimum moisture content Proper lubrication Washing the die and punch Die cavity should be smooth Use of colloidal silica to prevent adhesiveness.

Lamination : Lamination is the separation of the tablets into two or more distinct layers.

Cause :1. Improper adjustment of scrapper blade2. Improper flashing of lower punch to eject tablet3. Improper setting of punch4. Improper binder and lubricants5. Much more moisture contents6. Air entrapped

Remedy: Proper adjustment of scrapper blade Proper flashing of lower punch to eject tablet Proper setting of punch Proper binder and lubricants.

Chipping : It is the broken of the edge of the tablets.

Cause :1. Improper adjustment of scrapper blade2. Improper flashing of lower punch to eject tablet3. Improper setting of punch4. Improper binder and lubricants5. Much more moisture contents

Remedy: Proper adjustment of scrapper blade Proper flashing of lower punch to eject tablet Proper setting of punch Proper binder and lubricants.

Mottling : It’s an unequal distribution of color of a tablet with light or dark areas comparing to the area of surface.

Cause :1. If the color of drugs differ from other excipients2. If addition color is used and not distribute properly

3. Using of water soluble colorantsRemedy :

No color and excipients If colored excipients are must then additional color should be used to mask it. Lake color should be used Uniform drying Proper solvent should be used

Weight variation: With a tablet design to contain a specific amount of drug in a specific amount of tablet formula, the weight of tablet being made is routinely measured to help ensure that a tablet contains the proper amount of drug.

Cause:1. Variation of the vibration of machine2. Improper fitting of punch3. Size variation of granules4. Inadequate flow property

Remedy: By adjusting punch Uniform size distribution By adjusting the volume of dye

Hardness variation: Tablet hardness is usually expressed as the load required crushing a tablet placed on its edge. Hardness is thus sometimes termed as the tablet crushing strength.The hardness of a tablet is a function of the compressive force, the granule of crystal hardness and ability to deform under load, the binder used and their concentration, the granulation method, and other factors. Tablet hardness, in turn, influences tablet density and porosity. It may affect tablet friability and disintegration time. It usually affects drug dissolution and release, and it may affect bioavailability.

Cause :1. Variation of the vibration of machine2. Improper fitting of punch3. Size variation of granules4. Inadequate flow property5. Improper amount of binders and diluents6. Much compression

Remedy: Adequate flow property Proper amount of binders and diluents By reducing moisture content Adjusting the fitting of dyes and punch Double impression.

Double impression:- This problem occurs when the punch has engraved symbol and monogram during compression the tablet receive the quality of punch.

Machine used in Coating Unit:-

Unit Machine name Origin Capacity (Kg) No.of guns

1 Manesty Accela Cota 150 England 150 2

2 Manesty Accela Cota 350 A England 350 2

3 Manesty Accela Cota 350 B England 350 2

4 Sejong Pharmatech(Sugar coating)

Korea 350 2

CapsuleIntroduction:-

Capsules are solid-dosage forms that are most commonly composed of gelatin and are designed to contain a drug-containing formulation. Two types of capsule are available – hard and soft gelatin capsules. These differ in both their mechanical properties and in capsule design.

Hard gelatin capsules are less flexible and are composed of two pieces, termed the capsule and the body, whereas soft gelatin capsules are more flexible and are composed of a one piece capsule shell. A wide range of formulation types may be included within the interior of the capsule. For example, powders, tablets, semisolids and non-aqueous liquids/gels may be filled into hard capsules, with powders being the most common formulation option. Beximco Pharmaceutical is not involed in soft gelatin capsule production.

Capacity of Empty Capsules:-

Hard gelatin capsule shells has average 65mg weight.Their capacity to hold powder is 234mg.

Process of Capsules Filling:-

There is a highly sophisticated capsule-filling machine in the solid department of BPL. During capsule filling, room temperature and humidity (<40%) must be strictly controlled, because capsule shells are highly sensitive to moisture as well as some drugs (e.g. Ranitidine). Even though, after filling of capsules by mainly granules or pellets, finished capsules are transferred from the filling room to the packaging room by plastic drums that are covered by silica gel that acts as moisture absorbents.

Machines:-

Name of the machine Source Stations FeatureAutomatic Capsule Filling MachineMG-2 (MG Futura)

Italy 16 Max. 50000Capsules/hr

Observation:-Automatic Capsule Filling of Proceptin-20

Packaging Introduction:-

A packaging system is equivalent to a container closure system. A package, or market

package, is the container closure system and labeling, associated components (e.g., dosing cups,

droppers, spoons), and external packaging (e.g., cartons or shrink-wrap). A market package is the

article provided to a pharmacist or retail customer on purchase and does not include packaging

used solely for the purpose of shipping such articles.

Types of Packaging:- Primary packaging:- A primary packaging components a packaging component that is or

may be in direct contact with the dosage form.

Secondary packaging:- A secondary packaging component is a packaging component that

is not and will not be in direct contact with the dosage form.

Raw material used for packagingPrimary packaging raw materials include-

Plastic

Stainless steel

Glass

Rubber

Paper

A container closure system is the sum of packaging components that together contain and protect

the dosage form. This includes primary packaging components and secondary packaging

components, if the latter are intended to provide additional protection to the drug product.

Primary packaging materials: ALU- ALU types ALU- PVC type ALU - PVDC type

Types of Primary Packaging: 1. Blister Packaging 2. Strip Packaging

Secondary Packaging Materials are: Inner carton Leaflet

Strip Packaging Area:

Strip Packaging

Gansons Strip Packaging machine-1 IndiaHamson Strip Packaging machine-2 India

Problems that may arise during packaging are:-1. Empty pocket2. No pocket3. Damage of tablet/capsule4. Printing mistake5. Unclear printing

Blister Packaging Machines:-

Packaging Unit Machine Supplier/Manufacturer Observed Product

Blister 085 Klockner Hansel

Germany Nurocal

Blister 042 Otto-Hansel Germany Napadol

Blister 043 Otto-Hansel Germany Aristofol

Blister 074 Klockner-Hansel

Germany

Blister Elmac Elmac India Napa Extended

Blister Pampac Pampac India

Blister Hoong A Hoong A Korea Napa

Packaging of Powder for Injection:-

Name:-Hauser MachineryOrigin:- CanadaParts:-

Powder-Filling Machine Cap Sealing Machine

Observation:- Azithrocin Powder

Research and Development Department

IntroductionResearch and development (R&D) department is responsible for the justification and

documentation of all activities scientifically to establish a new marketed dosage form. Countries

like Bangladesh are unable to synthesis new drug molecules as well as design new drugs because

of many lacking. So pharmaceutical companies try to develop a new formula of dosage form

design from an innovator formula regarding of the drug which is available in the market and then

send for the drug approval to the regulatory authority. This method of drug approval is known as

Abbreviated New Drug Application (ANDA). R&D department also prepare recipe for the Drug

Administration approval and Batch Manufacturing Record (BMR) and Batch Packaging Record

(BPR) which includes all the manufacturing and packaging information of a new drug. This

department is always tries to manufacture quality product within minimum possible cost.

Overall working procedure of R&D department at Beximco Pharmaceuticals:

1. Marketing department analysis the present situation of drug marketing and predict the future

market needs.

2. R&D department tries to gather more information about this drug from different sources such

as Pharmacopoeias, Drug Directory, published literature in different journals etc. to

manufacture the drug.

3. Preformulation study of the active and the required exipients such as

Physico-chemical Properties of API

Drug interaction

Melting point

Crystal characterizes

Solubility tests

Feasibility test

Packaging material design

Moisture and light effects

Study of manufacturing parameter such as types of dosage form, selection of punches

and dies etc.

4. Requisition for raw material.

5. Prototype trail batch in small scale.

6. Perform different tests such as Disintegration time (DT), Hardness, Stability etc.

7. BMR and BPR preparation.

8. Scale up batch (larger batch).

9. If scale up batch is ok then go for three successive commercial batches.

10. If these three batches produce reproducible result then everything is ok for further

commercial batches.

The R&D department of Beximco Pharmaceutical has two parts: Formulation and Analytical.

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, Ingland.

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

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 consider to ensure proper

storages of drugs.

Tests perform in R&D analytical sector:

Physical tests e.g. Appearances, textures, visual inspections etc.

Assays: two types e.g.

Comparison study with the standard. Methods include HPLC, IR, GC, UV etc.

Independent methods e.g. Titrimatric methods, Conductivity test etc.

Impurities tests:

Methods for detecting metals include AAS, reaction with sulfuric acid etc.

Methods for detecting organic impurities includes HPLC, GC, UV etc.

Methods for detecting residual solvent (e.g. alcohol) include GC.

Efficiency tests such as dissolution test, viscosity test, pH test etc.

Stability tests:

There are three types of stability tests such as stability test in

1. Intermediate condition :Temperature- 30O C and relative humidity- 65%

2. Accelerated condition: Temperature- 40O C and relative humidity- 75%

3. Room condition/ Real time condition: Temperature- 25O C and relative humidity-

50%

[Temperature may be ±2 and relative humidity may be ±5]

In accelerated condition, if the parameter such as dissolution, DT, potency etc are OK after six

months then the product self life is claimed at two years. In intermediate condition and room

condition, if all the parameters are OK after twelve months then the product self life is claimed at

two years.

LCO DepartmentIntroduction

LCO (Liquid Cream & Ointment) unit is one of the most important area in Beximco Pharmaceuticals Limited. We visited this section on This section mainly manufactures various types of syrups, suspensions, pediatric drops, nasal spray, cream, ointment, gels and suppositories etc. Beximco produces 87 liquids products (syrup, suspension and solution), 27 semisolids, 8 suppositories and 5 nasal sprays.

Syrup

Syrup a concentrated solution of a sugar, such as sucrose, in water or other aqueous liquid, sometimes with a medicinal agent added; usually used as a flavored vehicle for drugs. It is commonly expanded to include any liquid dosage form (e.g., oral suspension) in a sweet and viscid vehicle.

Manufacturing of syrup

Manufacturing Filtration Storage Bottle filling

SealingLabellingPackaging

The following steps are involved in the preparation -

Cream and Ointment Pharmaceutical cream or ointment is used as a means of delivering an active ingredient directly to the required area of the skin. Products can be either a water-in-oil (w/o) or oil-in-water (o/w) emulsion, consisting of waxes, emollients and lubricants dispersed in an oil phase, and a water phase containing emulsifying, stabilizing and thickening agents, preservatives and in some cases, colorant. Active ingredients are dispersed in either phase or added when the emulsion has been formed and allowed to cool.

Steps in cream/ ointment manufacturing

Excipient Melting (500C)

Addition of active ingredient

MixingFillingCongealing (20-220C)

Sealing

Packaging

Suppository A suppository is a drug delivery system that is inserted into the rectum (rectal suppository), vagina (vaginal suppository) or urethra (urethral suppository), where it dissolves or melts. They are used to deliver both systemically-acting and locally-acting medications. The alternative term for delivery of medicine via such routes is pharmaceutical pessary. The general principle is that the suppository is inserted as a solid, and will dissolve or melt inside the body to deliver the medicine pseudo received by the many blood vessels that follow the larger intestine.

Manufacturing of suppository

Areas in the LCO section

The LCO area is divided into 7 lines. These are-

Line 1: Non antacid syrup & suspension manufacturing area.

All types of syrup and suspension are prepared in this line.Room standard - clean room DEquipment - SS manufacturing vessel (5000L) SS Storage Vessel (3000L)

Sartorius Stedim filter (5µ)Product prepared- NAPA Syrup (Paracetamol)

Machines used

Name CapacityBottle Washing Machine 3000 bottle/hrMonopolo Filling Machine 3000 bottle/hr

Line 2: Antacid suspension manufacturing area.

Generally viscous products are manufactured here.Room standard - clean room CEquipment - SS Manufacturing Vessel (3000L)

SS Storage Vessel (3000L)Product prepared- Flatameal DS Suspension (Al Hydroxide, Mg Hydroxide and Simethicone)

Machines used

Name CapacityBottle Washing Machine 3000 bottle/hrMonopolo Filling Machine 3000 bottle/hr

Line 3 : Small Volume Liquid(SVL) preparation area.

Nasal Spray, Pediatric Drops are manufactured here.Room standard - clean room CEquipment - SS Manufacturing Vessel (200L)

SS Manufacturing Vessel (100L) SS Manufacturing Vessel (60L)Product prepared- Melphin Suspension ( Pyrantel Pamoate)

Machines used Name Capacity

Vertical Ultrasonic Cleaning Machine 50- 200 pcs/minFar IR sterilizing and drying machine 50- 300 pcs/minFilling and plugging machine 50-100 pcs/minCap sealing machine 40-120 pcs/minLabeling machine 60-180 pcs/min

Line 4 - Cream, ointment & gel manufacturing area.

Room standard - clean room DEquipment - SS Manufacturing Vessel (200kg)

SS Manufacturing Vessel (100kg)

Main Mixing Vessel (250kg) Silverson homogenizer

Machines used

Name Capacity

Cream Filling And Sealing Machine 1500tube/hr

Product prepared- Gentocep ( Gentamicin cream )

Line 5- Suppository Line

Room standard - clean room DEquipment – Jacketed vessel Product prepared- NAPA Suppository.

Machines used

Name Capacity

Sarong Suppository Sealing and Filling Machine

5000supposity/hr

Erweka Leak Testing Machine

Line 6- syrup preparation line

This line only for syrup manufacturing.

Line 7- Packaging line

This line is used for the packaging of export product.

Other Machineries in liquid Section:

Weighing Balance, Satorious Germany

Avrey Weighing Machine, Gansons EnglandDust Collector ItalyCarton Sealing Machine TaiwanAutomatic Printing Machine TaiwanSemi automatic Printing Machine China

Quality Control DepartmentIntroduction:-Total quality control refers to the process of producing a perfect product by a series of measures. BPL’s Q.C. lab is well equipped with most modern and sophisticated equipment and In every step, from the procurement of raw materials to the manufacturing of finished products, the latest World Health Organization (WHO) approved current Good Manufacturing Practices (cGMP) are being followed. There are written Standard Operating Procedures (SOPs) for every process and step involved which are being closely monitored to ensure that all concerned personnel are complying with these procedures.

Activities:-QC laboratory has to perform following activities:-

Assessment of microbiological study of raw materials.Assessment of potency of antibiotics.Assessment of intermediate products of further processing.Assessment of bulk products for their release, reject, reprocess etc.Assessment of the final products for release, reject etc.Storing retention sample of each products.Maintaining batch wise full quality control tests record, signature of the person who performed the tests.Batch documentation and batch sentencing.Ensuring precision and accuracy of all testing methods.Performing environmental monitoring checks.Calibration and standardization of laboratory equipments.Control of laboratory reagents.Testing of any return goods.Analysis of any compliant samples with their corresponding retained samples..Prepare QC related documents.Management of stability study.

Protocol of QC activities

Stage DescriptionReceiving sample A representative of QC receives sampleSupervising Assigning someone to analyze the sampleAnalysis and Reporting The analyst analyses the sample according to

the specifications and documents properly.Checking After the tests of analysts, someone checks the

report.Disposition The QC manager is available for disposition

from QC.

General Functions:-

1. GMP &GLP: Good manufacturing practice are organizations concerned with the production and control of drugs have developed rules for pharmaceutical industries.

2. Documentations: The information that describes the products to its users includes documents, detailed code comments, white papers etc.

3. Sampling of packaging and raw materials: Sampling is the process of removing appropriate number of items from a population in order to make interference to the entire population. Sampling of raw materials is as follows:

WAREHOUSED MMR √(n+1) ( according to SOP)

Packaging materials :Commonly 2 Types

Primary ( Direct Contact) Secondary (No Direct Contact)

Some common tests are Description Tests Color (identification Appearance) Weight Dimension ( Diameter, Volume, Length) Visual inspections for defects

4. Microbiology: Microbiology division of QC performs microbiology tests to determine potency as well as presence or absence of microbes to the products. Microbial test is performed for the oral solid , parenteral, production environment etc, of BEXIMCO Pharmaceuticals:

Following microbs must not be allowed:o Escherichia colio Pseudomonus aeroginoseaeo Staphylococcus aureouso Salmonella spp.

Machines used in microbiology lab:

Instruments Company/Source Function

Incubator Kotterman-2736, Japan Incubation

Autoclave Memmert-600, Germany Sterilization

Laminar Air Flow Air tech , Japan Sterile working Condition

Stability Testing: Purpose: Shelf life study

o New productso Raw materials

Condition; a) Real time studyb) Accelarated stability study

Real time study condition: Temperature: 25oC (+2o) Relative Humidity: 60% (+5%)

Accelerated Stability Testing Condition: 1st 6 months and 2nd 3 months Temperature: 40oC (+2o) Relative Humidity: 75% (+5%)

Intermediate stability testing condition: Temperature: 30oC (+2o) Relative Humidity: 60% (+5%)

Analitycal study for QC: Physical and chemical analysis

Physical Analysis includes appearance, odor, melting point , ph, weight/gm, LOD, Viscocity, Solubility etc.

Chemical analysis includes sulfate, chloride, Organic volatile matter, heavy metals, chemical assay etc.

Tests Done for Quality Control:Stage Tests

Raw Materials a. Assayb. Descriptionc. Solubilityd. Identificatione. Optical Rotationf. Purityg. Water content Determination etc.

In Process Quality a. Disintegration Time

b. Quantitative Assayc. PH

d. Identificatione. Weight variation Testf. Dissolution Test

Finished Products a. Assayb. Descriptionc. Identificationd. DTe. Weight variation test

Packaging Material a. Visual inspectionsb. Weightc. Size and Diameterd. Dimentione. Adaptabilityf. Adhesiveness

Instruments for analylical tests:

INSTRUMENTS COMPANY/SOURCE FUNCTIONKarl Fischer Titrator Menler Dl-18, Germany Determining the moisture of

the sampleDissolution Test Machine ERWEKA DT6, Germany Determining Dissolution ratePotentiometer Stirrer-72, Switzerland Determining potencyPH meter Beckman32 Determining PH

Melting point Apparatus BUCHI530, England Determing melting pointMagnetic Stirrer B 211 V, Germany StirringShaker Germany ShakingViscometer USA Determining ViscosityAutomatic polarimeter AP-100, Japan Determining Optical

RotationSeive Analyzer Determining wheather a

product crystal Granules, or powder

Microscope To magnifyHPLC Waters, USA Determining quality &

quantityUV- Visible Spectrophotometer

Shimadzu, Japan To determine quality & quantity

IR-Spectrophotometer SHIMADZU, Japan IdentifyGas Solid Chromatography SHIMADZU, Japan Determining quality &

quantity of volatile productsMelting point determination ERWEKA Determining melting point

Machine EST2,GERMANYSoftening time determination ERWEKA PM3, Germany Determining softening TimeSonicator Dhrawave, England To SonicateRefractometer Determining RIAAS Aurora Instrument, Canada Determining Qualitative

metallic elementDegasser SHIMADZU, Japan Removing gas

QA DepartmentIntroduction:-

Quality Assurance is the modern wide ranging concept which covers all the matters which individually or collectively affect the quality of the products in a pharmaceutical Industry. To ensure the required quality it deals with all the sections in the company. The activity of QA starts with the entrance of raw materials and upto release of finished products.The QA has the following Units:

i. Quality Controlii. Microbiology

iii. Documentationiv. In process quality control

The in process duty of QC are Monitoring Documentation Approval Auditing Self Inspection Corporate Audit

QA is an organizational element designed by the management of each step Of the manufacturing Operation.Major area of QA tasks are as follows

o Material checking in Warehouseo In process checking of all products & processo Documentationo Retention of sampleo Development works

Material Checking:-

a. When raw or packaging material appear at warehouse physical appearance observed by QA. It is sampled & sent to QC department for analysis.

b. On the basis of QC report & QA physical observation the materials are given release or rejected status.

Production Area

Cleaning of all production area and filling area are checked by QA. In process checking is performed throughout the total manufacturing process.

Solid sectiona) Granulation Area: Before Granulation the area and the machineries are checked whether

they are ready or not. This procedure is checked for SOP.

b) Compression Area: Total area and machineries are checked for cleaning before operation. Initially some tablets are compressed for general description, weight, hardness, thickness, friability, Weight variation, DT, organoleptic & relevant parameters. If all the parameters meet the specifications the batch operation starts. During operation all the parameters are checked time to time. Then the finished products are sent to QC while they are kept in Quarantine area. On the basis of QC report products are released.

c) Coating Area: Before coating area and machineries are checked for proper cleaning. After coating the products are sent to QC for analysis while they are kept in quarantine area. Then on basis of QC report they are sent for packaging.

d) Packaging Area: The machines and room are checked for proper cleaning before operation. Some strips are checked for leakage, batch& printing, slitting etc. During packaging time all parameters are checked time to time. Then they wait for distribution & documentation.

e) Raw materials, Finished products, BMR, BPR etc all documents are maintained & reserved by QA. Product compliant handling and corrective measures are recommended.

Liquid & Infusion SectionMost of the parameters like solid without Granulation or coating are strictly maintained in Liquid and Infusion area with additional large scale microbiological assay routinely. Test for bioassay and Aseptic condition are maintained & observed by QA.

Infusion Unit

IntroductionBeximco Pharma's intravenous (IV) fluid manufacturing plant may be regarded as one of the

most technologically advanced plants in the world. The plant was designed and installed in

collaboration with Pharma plan of Germany, a sister concern of Fresenius AG of Germany. The

plant is ISO 9001: 2000 certified.

Preparation of infusion

The infusion preparation involves two main operations:-1. Preparation of WFI.2. Preparation of solution

Followed by bottle preparation, autoclave & packaging

Preparation of WFI.Water for injection is a special type of distilled, sterile and de-ionized water that is usually

prepared by distillation in a still specifically designed to produce the high quality water required.

Criteria of WFI:

1) Must be distilled.

2) Must be sterile.

3) Must be de-ionized.

4) Solid dissolved particles should not > 10 ppm.

5) It should have USP or BP standard.

6) Must be gas free.

7) Must be pyrogen free.

8) Non-toxic; non-irritant.

9) WFI should not have conductivity > 1mmoh.

The process is performed by the following step—

Step-1: Natural Water Collection:

At first the normal water is collected by deep tube well from the ground core. The pump is 120 feet deep. It is situated at the outside of building. Then the water is supplied to the reservoir by pipe line.

Step-2: Removal of Iron:

Then the water is supplied to the Erosion chamber. Here the water is oxidized from soluble ferrous chloride to insoluble ferric chloride. Then the ferric chloride becomes separable from the water and removed.

OxidationFeO Fe2O3

Step-3: Chlorination:

Then the water is supplied to the organism water tank. Chlorination is performed by using bleaching powder to destroy the micro-organism.

Step-4: Removal of Bad Odor and Pyrogen:

The water is passed through the activated carbon filter. As it remove dead body microorganism, it also remove the bad odor of the water. Here two types of filter are used;

Pre-filter with the pore size 1.4μm Sterilized filter with the pore size 0.2μm.

Step-5: Removal of Minerals:

To remove minerals from the water, it is passed through three resin ion exchange columns. The three columns are:

1. Anionic column2. Cationic column3. Mixed ion column

Here, cations (Na+, K+) are exchanged for H+ and anions (Cl-, Br-, I-) are exchanged for OH-. A conductometer is attached to the column terminal to determine the amount of ion in water by measuring the conductivity of the water. The more conductivity of water, the more ions present in water.Now the water is free from minerals. It is called demineralized (DM) water. The DM water is preserved in a reservoir. DM water is used in oral preparation as it is not free from pyrogen.

Step-6: Removal of Pyrogen:

In Beximco Pharmaceuticals water is made free from pyrogen by distillation process. Here four distillation columns are available including DM water reservoir. The water is heated at 150o C Temperature and pure steam is prepared by fitting baffles in the path of vapors between the boiler and the condenser which prevent the entrainment of liquid droplets containing pyrogen. The distillation still or column is made up stainless steel fitted with the baffles. The condenser is also made up stainless steel. The reservoir is heat insulated. The pure steam (free from pyrogen) is converted to water in condenser and preserved in a reservoir at 50oC temperature.

Stap-7: Temperature Minimization:

Before using the WFI, is passed through a heat exchanger to minimize heat. The final temperature of water is 30±5oC temperatures.

Preparation of solution:

The infusion belongs to the larger volume parenteral its manufacturing needs highly controlled, sterile environment.

The various rooms working stations of Beximco Infusion Ltd. have been divided as general area and clean area both of which has got three classes. They are:

Area Classification LocationGeneral General class – 1/ G – 1 Warehouse

General class – 2/ G – 2General class – 3/ G – 3 Packaging hall, autoclave

area, duty officer rooms and visitor corridor

Class BILClassification

Location Specification0.5 µm 5.0 µm

Clean class

Grade D(Class 100000)

Personal air lock, material air lock, bottle pack area

100000 700

Grade C(Class 10000)

Injection, molding room, solution preparation room, clean corridor, weighing room

10000 70

Grade A(Class 100)

Under Laminar air flow 100 None

Preparation WFI

Aeration Chamber (Compressed air supply)

Sand & Gravel Filter

Over Head Tank (Capacity 5000L)

Chlorine dosingPre-filter 15µ

Raw water

Steps in Infusion preparation

Dispensing:

The main responsibilities of dispensing are to supply accurate material at accurate quantity. This is approved / controlled by Q.A. department. The dispensing process of Beximco is as follows-

Ware house

Charcoal bed

Filter

Filter

Filter

Filter

Raw Water Tank

(2000L)

Distillate Tank (6000L)

Temp. 80-900C

Raw material

Supplied for Q.C by Q.A

QC Test

Back to Q.A

If approved then for finally dispense

Material air lock

Weighting room.

Manufacturing

A weekly program is prepared and according to it raw materials are gathered. The manufacturing process is as follows-

Solution preparation room

Solution preparation unit

Cleaning with citric acid weekly

Flushing with DM and distilled water

Sterilization at 1200 c, 1.2 bar, for 15 / 30 minutes

Bubble point test to ensure the integrity of sterile filter

Drain the WFI(300 L) taken for bubble test

Collection of WFI for solution preparation, temperature must be 25 to 350c

Pouring the materials when WFI reach 1st propellen

Mixing

Pre-filter (2.5µ)

Final filter (0.2µ)

Re-circulation

Transfer into reservoir tank

Again re-circulation before transferring solution for filling

Solution for filling.

Bottle filling:

Bottle is instantly prepared from low density polyethylene granules. Above the temperature 1100c the granules are melt and a positive air flow make bottle. Then the bottles are filling with the solution. Then the bottle is sealing and cooling below 200c. The filling area is class-A (100). The sealing cap is a special cap which is air tight even after injection or remove of needle.

Autoclaving:

The bottled solution is then sterilized by autoclave. Five trolleys is loaded and placed in autoclave chamber. There they sterilized at 1060c with 1.1 bar pressure for 85 minutes. The heat of the entire place in the chamber is not equal. So this chamber is monitored digitally by a computer having specific software for this purpose. The area in the autoclave chamber where the temperature is lowest, samples are collected from there and send for QC test.

Packaging:

Before packaging some tests are performed. They are sequentially described below:

Sterilized bottleVisual inspection

Bottle under pressure belt (0.3-0.5 bar) for leakage test

Extensive visual inspection by passing light through bottle

Attachment of label

Over-bag wrapping for safety

Placed in carton and send to warehouse quarantine area

Manufacturing Process Of Infusion

Sterilization; 1210C, 30 minutes

Cleaning with citric acid

Flushing with DM water & distilled

water

TANK (capacity 4700L) TANK (capacity

4700L) Processing unit

After completion of filling

No PC

Warehouse Material Air-Lock

Dispensing AreaStore requisition by

PRD=Production DepartmentQAO= Quality Assurance OfficerPC= Product Change

Packaging:

PC

Cleaning

Filling (2-3 bar air pressure)

Cleaning sample to IPC WFI (300L) taken for Bubble

point test to ensure the integrity of sterile filter

QAO

Collection of WFI for solution preparation (Temp.

QAO

Pouring the raw materials when WFI collection

completed

Pre-filter 2.0µ

Mixing; varies 30-60 minutes

Final filter 0.2µ

Recirculation (30

BFFS (Blow Form Fill &

Filled & welded bottles for terminal sterilization (1060C for 85 minutes by water spray

technique)

Approval for filling by QAO

Ready for packaging

Performed leak test at

every 30 minutes

interval by

Received bottles from autoclave

Bottles passed through a pressure belt at 0.3-.05 bar pressure. Defective bottles are deformed here

and are rejected

Hanger & top ring are checked visually when

Bottles are then transfer on fluorescence light for assuring the product is free of

Instrumentation of Production Section of Infusion Unit

Name Source CapacityManufacturing Vessel 1&2 Pharmaplan (Germany) 3800LManufacturing Vessel 3&4 Getinge (Sweden) 4000LBottle packing, filling & sealing machine

Pharmaplan (Germany)

Autoclave Getinge (Sweden)

Pressure conveyor belt Germany 0.3-0.5 Bar

Labeling machine Avery (Germany)

Sealing machine Impulse auto sealer (Taiwan)

Inkjet printer Jaine 1000 (France)

Labeling with product specific label which encode Batch No.Mfg. DateExp. Date

Labeled bottles are then wrapped with PE over bag

Wrapped bags are then sealed with heater (sealing machine)

Same information of batch identity encoded on label are

Insert the bottles into shipping carton (10 bottles /carton)

Filled shipping carton are then palletized for transfer to

QA of Infusion

The following tests are done to assure the quality of Infusion

Name TestPhysical test Dimensions of cartons

Weight of cartons, rubber disc Adaptability of cartons over bags

Chemical tests: For raw materials Characteristics Solubility Identification LOD Optical rotation

For packaging materials

Tests performed for PVC granules & rubber disc

Appearance of solution Density Acidity/alkalinity test

For WFI

Characteristics pH value Oxidizable substances Heavy metals

Finished products

Characteristics Identification Particulate materials

Microbiological tests: Microbial limit test of raw & packaging materials.

Monitoring of water. Environmental control monitoring of surface

for microbial contaminants in manufacturing area.

Environmental monitoring Monitoring of surfaces- Monitoring of air born microorganisms Monitoring of personnel Monitoring of water

Engineering Services & UtiltiesIntroductionWe had the opportunity to visit an important part of any industry i.e the Engineering Department. It is the driving force of the machineries and utilities and without the proper functioning of this department production would come to a stand-still.

Beximco Pharmaceuticals Ltd.has an independent engineering department for looking after production and utility machineries. Responsibilities of engineering department are to install, maintain, handle and solve all types of problems such as electrical, electronic and mechanical.

Utility support is very much important for smooth operation of all production machineries.

Major functions :1. Maintenance of production machineries

2. Operation & maintenance of utilities machineries3. Maintenance of QC machineries4. Technical supports to all department.5. Trouble shooting of all technical problems.6. Installation of new machinery.7. Calibration of all types of machinery.

Maintenance ca also be of two types:

a) Scheduled/Preventive maintenance:All the production machineries are checked periodically (weekly, monthly ets) for ensuring efficient operation and minimum breakdown.b) Breakdown maintenance:Breakdown maintenance is done when any machine is out of control due to mechanical, electronic or electrical problem.

Machineries of this department are of 2 types:Production MachineriesUtilities

Engineering Department is concerned for operation and maintenance of utility machines and provide-

1. Power Supply

2. Water System

3. Steam Supply

4. Gas Supply

5. Compressed Air Supply

6. Central Air conditioning System (HVAC).

1. Water pump:

AME                            MODEL                  MOTAR MODEL                  CAPACITY

Deep tube well             310b/9                    Siemens 40HP

Deep tube well             37B/10                        Siemens 10HP                         9000gal/hrs

2. Air compressor:

a) Model: Compressor 145-SR

Air end: single stage oil injected screw

Cooling: Air cooled

Oil capacity; 18.50usgal

Delivery air pressure: min bar (psig) -5(72)

                               max bar (psig) -13 (189)

Motor speed: 5000rpm

b) Model: Compressor –l: 30

Rotary Screw Compressor

Out put4.49cun/min at 9bar

c) Broom wade air compressor

Oil free air compressor

Capacity: 300cfm at 7 h

3. Fire tube boiler

Mfg: WHOSUNG

Origin: USA

Model: a)CIW700200150

           b) CIW7000125150

4. Chiller

DUNBUM-BOOL

Model: ACF×155-S

Capacity: 1,845,600 BTU/Hr.

5. Generator 11/4 KUA substation for electrical supply

Manufacturer Capacity Engine model

Generator model

Enginator model

Origin

G1 WAUKESHA

920KW 17042GSI

A248810001

VHP7100GSI USA

G2 WAUKESHA

1020KW

3516 USA

G3 WAUKESHA

900KW 15794GSI

VHP5904GSID

G4 WAUKESHA

900KW 15794GSI

VHP5904GSID

Central Air conditioning System (HVAC).

HVAC (heating, ventilation, and air conditioning) is the technology of indoor and vehicular environmental comfort. HVAC system design is a subdiscipline of mechanical engineering, based on the principles of thermodynamics, fluid mechanics, and heat transfer. Refrigeration is sometimes added to the field's abbreviation as HVAC&R or HVACR, or ventilating is dropped as in HACR (such as the designation of HACR-rated circuit breakers).

HVAC is important in the design of medium to large industrial and office buildings such as skyscrapers and in marine environments such as aquariums, where safe and healthy building conditions are regulated with respect to temperature and humidity, using fresh air from outdoors.

Training Department

Introduction The Training Department of BPL One of the agenda of the Human Resources Department is continuous development of the employees so that they can cope with the rapidly changing business environment. Innovation is a major priority that BPL wants to promote. Accordingly,training programs are regularly undertaken for the existing staff to seek opportunities for skills improvement. Beximco pharmaceuticals Ltd. arranges training also for new employees to introduce with job responsibilities and to comply with rules and regulation as well as to make them competent with their respective job in this company.

Objective of training

o Error free operation o Fulfillment of regulatory requirementso Business purpose

Purpose of Training

o To create skilled persons in BPLo To enhance efficacy of all walks of people of BPL

Beximco Provides Two Types Training Generally:

a) In-house Training b) External Training Training Procedure:

Training Need Analysis

Select “Resource Person”

Preparing Training Calendar

Conducting Training session

Evaluation

Documentation

Retraining

Training Type:

Classroom training

Audio-visual training

Interactive training

On the job training

Group exercise

Training Applies to:

Manager

Officer

Workman

For new Employees:

Basic GMP

Safety Overview

On the job

SOP

For Existing Employees:

GMP

Safety

Utility System

On the job

SOP

Covered Areas:

Solid Manufacturing Plant

Metered Dose Inhaler Plant

Liquid, Cream, Ointment & Suppositories Plant and Pharmatek Plant

Antibiotic Formulation Plant

Infusion unit

Quality Control Department

Quality Assurance Department

Product Development Department

Production Planning Department

Engineering Department

Human Resources Department

Environmental health and safety (EHS)

IntroductionEHS department of beximco pharmaceuticals Ltd. Aim to create awareness of the working personnel of the factory through training, SOPs and carrying out inspection or audits to observe the implementation of training and SOPs. EHS department ensures every process of production, storage and transport it also tries to prevent or minimize the impact on environment through appropriate design, manufacturing, distribution, use and disposal practices.

Safety

The last but not the least is the safety parameter that we came to know about from the TRACK-II unit of Beximco. There we saw that the management of BPL are continuously thriving to protect the environment and ensure the safety and health of their employees and communities where they operate. It is always monitored that concerned people wear appropriate and designated dresses like gowns, aprons, masks, helmets etc.

Activities of safety department are as follows:

Induction of training for safety Collection of Material Safety Data Sheet (MSDS) Taking preventive action for fire

Fire can be classified as-

Class A- Involve ordinary combustible material such as wood, paper etc.Class B- Involve flammable or combustible liquids & gases such as kerosene common organic solvents etc.Class C- Involve live electrical wires & equipments such as motors and appliances etc.Class D- Involve combustible metals such as Mg, Na etc.

Types of fire extinguishers are-o Water is used for Class A fires.o Dry chemical (multipurpose) extinguishers are used for Class B & C fires.o Chemical foam extinguishers are used for Class A & Class B fires.o Sand is used for Class D fires

In case of fire employees are instructed toKeep calmUse stair -not use liftFollow evacuation procedure

Health

This is concerned with the following Annual health checkup of the employee Checking the health the employee to set the correct person at the correct position. Eye checkup of the personnel who directly involved in the visual inspection of products.

Effluent treatment plant

BPL has a organized Effluent treatment plant. So, the waste of the product do not pollute the surround environment.

Collection pit

Equalization tank( air agitation)

Chemical treatment (addition of lime .FeSO4 or polyelectrolytes)

Fluctuation(upper portion is collected)

Transferred to aeration tank (retention time 3 days)

Settling tank(microbes settle down)

Filtration by activated carbon filter

Final treatment with chemicals

BOD, COD testing and release to environment