## Quality Control System of Beximco Pharmaceuticals Limited

Subject: Pharmacy | Topics:

Executive Summary:

To assure the quality of the products we have to use different types of measurements or numerical mathematics. Sometimes ensuring quality of the products by numerical mathematics is impossible because this process takes lengthy time there has much more possibility to make mistake. That is why we use some statically method, which is called control charts.

When the quality controls have to focus on a quality characteristic hard or expensive to measure on a numerical scale, the control chart for attributes are a useful alternative.

Attributes concern quality characteristics which are able to be classified in two types, conform and not conform to specifications. What is called nonconforming means that the unit controlled is not conformed to standard on one or more of examined quality characteristics.

The goal of control charts for variable is still to control mean and variability of a process but here, we focus of number of nonconforming units or nonconformities in a population. Three types of charts exist. Their use depends on the production (which quality characteristic to control, how many to examine), the characteristic of controls (constant or variable sample size):

• The p-chart: it is a control chart for fraction nonconforming
• The c-chart: it is a control chart for number of defects or nonconformities
• The u-chart: it is a control chart for number of nonconformities per unit

INTRODUCTION

Subject like Pharmacy demands practical knowledge in the own field. Thus industrial training program is one of the most important parts of a students studying in a dynamic subject like Pharmacy. For gathering complete knowledge about pharmacy there is no alternative for In-plant or industrial training program which has to be accomplished by every student of pharmacy after his/her final year (B.Pharm.) examination. This training is conducted by the pharmaceutical industries in our country. By this training, each pharmacy student can achieve vast experience; can correlate the theoretical knowledge with the practical experience. Thus he/she can develop him/herself completely for pharmacy related job. To take part in such type of training program I have been selected for The Beximco Pharmaceuticals Ltd.

The Beximco Pharmaceuticals Ltd. is the leading pharmaceutical company of Bangladesh. This company manufactures product not only for the market of Bangladesh but also for the international market because they manufacture products having higher quality. They maintain cGMA in the production area and also they have well developed SOP. Besides they do IPC properly that is very important thing for manufacturing quality products.

Beximco Pharmaceuticals manufactures a range of dosage forms including tablets, capsules, dry syrup, powder, cream, ointment, suppositories, large volume intravenous fluids, metered dose inhalers etc. in several world-class manufacturing plants, ensuring high quality standards complying with the World Health Organization (WHO) approved current Good Manufacturing Practices (cGMP).

My training program was from 18th July to 2nd August,2010. During this period I have visited & worked in every section under the direct supervision of related officers.

HUMAN RESOURCE DEPARTMENT

The Human Resource Department of the Beximco Pharmaceuticals ltd. does different kinds of jobs for the frequent running of the industry. Among all these some of the important jobs that are done by the department are discussed below:

• Recruitment of personnel: one of the most important jobs of the HR department is to appoint personnel having appropriate qualification as well as experience to fill the position that have an effect upon the quality. In so doing, different kinds of standards are considered for different positions.
• Prepare monthly manpower statement: The HR department has to prepare the monthly manpower statement of the plant by the 5th of every month. It includes DL to the Director. To add to this, it also prepares the daily manpower statement.
• To maintain and update personal files: One of the outstanding jobs the HR department is to maintain and update personal files of all employees of the industry. Confirmations of jobs, promotion, transfer etc. are included in this file.
• Informing policies: The HR department generally informs the managers and employees regarding personal policies and procedures of the company.
• Coordination of performance appraisal: This department coordinates and monitors performance appraisals of plant employees. The process of evaluating of performances is happened in many methods.
• Asses training: The HR department generally asses the training needs of personnel in light with cGMP (current goods manufacturing practice) and others related HRD issues. The training also includes- GMP, Safety, and Laboratory standard and workplace environment in the pharmaceutical industry.
• To arrange induction training programme: To arrange the orientation program that is arranging induction training program for the new employees of the industry is the job of the HR department. As soon as each employee joins, she or he is introduced with the entire department and he is also taught the functions about the operations of the company.
• Preparing and arranging in plant program: The HR department prepares and arranges the in plant training programs for the students of different universities. This is an extra typed job of the department and to do this all kind of coordination is done by the department itself.
• Dealing with industrial related issues: Generally the industrial related issues such as negotiation with employees union, ensuring the labor rights etc are done by this department.
• Ensuring proper implementation of Labor Law: This department one of the main jobs is to ensure the proper and exact implementation of the Labor Law that is applicable to the factory workers and the employees.
• Taking Disciplinary action: This department has the right to take any kind of disciplinary action including punishment, suspensions and termination from the job.
• Maintaining liaison with Government Regulatory bodies: HRD keeps relation with the following Government regulatory bodies for the legal aid. Or helps in any accident or medical aid:
1. Ministry of Health, PeoplesRepublic of Bangladesh
2. Office of Directors of Labor
3. Explosive departments
4. Director of fire and the fire station of Tongi
5. Toni thana, NSI, DB and SB
6. The Pourosova of Tongi
7. Customs and Vat, Tongi circle
8. Office of the Deputy Commissioner, Gazipur
9. Office of the Superintendent of Police, gazipur
10. Civil Surgeon, gazipur.
• Supervise official works: To supervise and monitor the attendance of the employees, job cards regularly and prepare monthly summary and daily absent reports etc are the jobs of the HRD.
• To monitor leaves: The HRD monitors leaves of plant employees. Each employee has a leave file that integrate all kinds of leaves like-
1. Annual leave
2. Medical leave
3. Casual leave
4. Special leave
5. Maternity leave
6. Leave without pay etc.
• Ensuring safety: To ensure the safety of all employees and company assets as well as ensuring proper security management of the plant are the jobs of the HR department.
• Handling visitors: The work of handling external visitors and arranging all necessary uniforms and other accessories is done by the HRD.
• Supervising: The HR has to do several supervising jobs as follows:
1. To supervise transport tools (distribution, repair and maintenance)
2. To supervise canteen management.
3. Supervise of all cleaning services of the plant (House keeping and gardening etc.)

SAFETY

DEPARTMENT

Aim of this department is to create awareness to the working personnel of the factory through training, SOPs, and carrying out inspection or audit to observe the implementation of training and Sops. Activities of safety department are as follows-

• Induction of training for safety
• Collection of Material Safety Data Sheet (MSDS)
• Taking preventive action for fire
• Identification of hazardous area and taking preventive measures
• Preparation of SOPs for handling chemicals
• Identification of criticalities of machineries and providing awareness & safety
• Providing Personnel protective Equipment (PPE)
• Providing First Aid & its using procedure
• Arranging  yearly Medical Check up program
• Identification of pipelines by using different colors on them according to the standards
• Identification of dangerous goods by using different symbols on them according to the         standards
• Providing Automatic Fire Alarming System with smoke & heat detector
• Providing training for using alternative exit way in case of any type of emergencies.

TRAINING

DEPARTMENT

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 they want to promote. Accordingly, training programs are regularly undertaken for the staff to seek opportunities for skills improvement.

Employees of BPL are participated in various training programs both external & internal. There are six induction training for the field force, four in-house training & two external training for employees of the Head Office during this period. Factory personnel also attended in-house training programs of total 206 hours duration.

Training Procedure:

Training needs analysis

Select resource person

Prepare training calendar

Conducting training session

Evaluation of training, trainee

Documentation

Retraining

Training type:

Classroom training

Audio-visual training

Interactive training

On the job training

Group exercise

Training applies to:

All persons engaged in manufacturing directly and indirectly.

Manager

Officer

Workman

Covered area:

Solid manufacturing plant

Metered dose inhaler plant

Liquid, cream, ointment and suppositories plant

Antibiotic formulation plant

Pharmatek plant

Infusion unit

Quality control

Quality assurance

Product development

Engineering, BPL

Production planning

Project

Training topics:

For new employees:

Induction training is conducted for new employees on

Basic GMP

Safety overview

On-the job

For existing employees:

Train the trainers

GMP

Safety

Utility system

General self development training

On the job training

SOP’s

PRODUCTION PLANNING DEPARTMENT

A Pharmacist who works in the Production Planning department has to do multipurpose jobs. The works that the Production Planning Department generally do have been quoted below:

• Issuing of BMR & BPR: The department of Production Planning generally issues BMR and BPR. If planning finds that change is essential or needed in BMR and BPR, it would do consultation with the Product Development for its desired change.
• Ensuring the availability of raw and packaging materials: For the smooth and favorable production, the planning has to arrange all kinds of raw and packaging materials by doing discussion with the Head office of the company.
• Arranging Sample for Physician: The physician sample will be separated from the bulk production by the department of Production as the order of the Planning department.
• Arranging products for the foreign market: one pf the important job of the planning department is to arrange supply the products to the foreign market.
• Co-ordinate all departments for smooth production: Planning also co-ordinate different section of the company to have highest production level within lower total cost and minimum time.
• Comparing man-hour and achievement: Planning also compares man hour and achievement, and by this they know the real efficiency and effectiveness of man and machine.
• Keeping reports and other documents of daily production: The department of Planning also keeps all kinds of every days production reports. Besides, they also maintain the major documents.
• Submitting the monthly reports: It is the duty of the panning department to submit the monthly production report to the ED, works at the end of the month.
• 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.

From the above discussion it is visible that a Pharmacist who works in the Production Planning Department of the company has to such kind of multistructured works that require proper sincerity, care and effectiveness.
WAREHOUSE

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. This warehouse has three units. They are as followes-

• BPL Warehouse
• BIL Ware-house (Infusion Unit)
• Pharmatek Ware-house

There are different segments of the warehouse. They are:

In the Quarantine area raw and packaging materials are preserved for the approval of the Quality Assurance Department.

In the Released area 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.

Raw materials, packaging material and finished products that fail to get approval from the QA are retained with a lot of security in the Rejected area.

In the Finished product area generally finished products are installed here for distribution in the market.

In the Cold Storage area those products are kept that are heat sensitive and flammable materials.

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

• Routine works
• Periodic works

Routine works done by warehouse:

• Arrival of materials: Raw & packaging materials 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.

The handling of finished goods is also a routine work of the warehouse. After getting finished goods transfer note from manufacturing department, the works that are done by the warehouse are projected below:

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

• Export Order: Having information from international marketing department with Invoice, packing list and export permission issued by Drug Administration.
• 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.

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, (Ön+1) containers are sampled (where n = total number of the containers).

Dispensing areas of Warehouse:

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).

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.

SOLID

DOSAGE

FORMULATION

Beximco Pharma’s biggest unit is the Solid department which is also the most important department of any company. From this unit most of the returns on investment come for the company. Different units of the Solid department have been projected below in the flow chart:

• Granulation Unit: Granulation is the process in which powder particles of raw materials are made to adhere to form larger particles called granules. Granulation done for-
• To improve the flow of powdered materials by forming sphere like or regularly shaped aggregates and
• To improve the compression characteristics of the mix (blend.)
• To prevent segregation of the constituents in the powder mix.

In this unit two types of granulation processes are performed:

1. Dry Granulation
2. Wet Granulation

Flow Chart of Granulation

 Machineries used in Granulation Unit(Unit I, II, III,VI) Name of the machine Purpose Manufacturer Features Planetary mixer To form wet granules Gansons, India Unit I : 60 kgUnit II: 120 kg High Speed Mixer Granulator To form wet granules Pharmaceutical and Medical Supply LTD. Thailand 150Kg Multimill Size reduction & sieving Gansons, IndiaMerk industries, Bangladesh. Screen size:9.35mmrpm:1500Screen size:2.4mmrpm:3000 Fluid bed dryer (Electric heater) Granules drying Sapphire, IndiaGansons, India Unit I : 60 kgUnit II: 120 kgUnit III: 150 kg (2N) Vac-U-Max Granules transfer into Tote Bin Belle-ville, U.S.A – Tote Bin Granules blending with lubricants Kurri-Kurri N.S.W., Australia 500 Kg
• Compression unit: After granulation, the granules are compressed to form tablets of specific weight, hardness and thickness. Compression unit consists of six compression rooms.
 Machineries used in Compression unit Unit Machine name Source No. of station Channel Speed(tab/hr) 1 ManestyD3B England 16 Single hopper Max.35,000 2 ManestyBB4 England 35 Double hopper 70,000-210,000 3 ManestyBB4 England 35 Double hopper 70,000-290,000 4 SejongFETTE1200 Germany 30 Single  hopper Max. 200,000 5 SejongFETTE P3100 Korea 55 Double hopper Max. 300,000 6 SejongM45 Korea 45 Double hopper 378000 7 Sejong Korea 18 Single 16000 – 64000 8 Sejong Korea 49 Double 8800 – 420000

Coating unit:  Some reasons are responsible for coating tablets. Those are-

• To improve the pharmaceutical elegance of the product by use of special colors.
• To mask the unpleasant taste, odor, or color of the drug.
• To control the release of the drug from the tablet.
• To protect physical and chemical protection for the drug.
• To control dust of the tablet.

Mainly three types of coating are performed in the solid section. They are as follows-

 Machineries used in Coating unit Unit Machine name Source Capacity(Kg) Speed (rpm) No. of nozzle/Gun 1 Manesty Accela Cota 150A England 150 5-8 2 Guns 2 Manesty Accela Cota 350A England 150 3-8 12 Nozzlesor2 Guns 3 Manesty Accela Cota 350B England 350 3-8 12 Nozzlesor2 Guns 4 Sejong Pharmatech Korea 350 3-8 12 Nozzlesor2 Guns

Coating problem: General coating problems that may occur during manufacturing. Those problems are-

• Logo bridging
• Logo infilling
• Picking/Sticking
• Twinning
• Cracking
• EDGE Chipping/ Erosion
• Core erosion
• Peeling
• Orange peel/roughness

The above problems can be overcome by following one or more of the following solutions:

• Select suitable coating material
• Change spray rate
• Change drying rate.
• Change distance between spray guns and surface of tablet bed.
• Change atomizing air pressure.
• Change inlet air temperature/air flow
• Moreover working experience may help to get quick salvation.
• Capsule filling unit:
 Machine Name Source Stations Feature Automatic Capsule Filling Machine MG-2 (MG Futura) Italy 16 Max. 50,000 Capsules/Hour.

Packaging Area:

Packing can be defined as an economical means of providing, presentation, protection, identification/information, containment, convenience, and compliance for a product during storage, carriage, display and use until such time as the product is used or administered. After compression of tablets and coating [if required], the tablets are packed either in blister pack or in the strip.

Primary packaging materials are (source Korea, India):

• Polyvinyl Chloride [PVC], (PVC/PVC)
• Polyvinyl dichloride [PVDC], (PVC/PVDC)
• Blister Foil,
• Alu-Alu Foil etc.
• Conventional strip foil

Blister Packing Machineries

### Maximum capacity

Pam pac

India

70 strip/min

Klockner Hansel, 085

Germany

84 strip/min

Klockner Hansel, 074

Germany

84 strip/min

OttoHansel,042

Germany

180 strip/min

Otto Hansel, 043

Germany

180 strip/min

Hoong- A

Korea

180 strip/min  (5 tracks)

Hemson 073

India

100Strip/min

Stage in Blister packing

Some common Problem in Blister Machine:

• Preheating problem – malleability
• Forming problem
• Sealing problem
• Slitting problem – perforation
• Air pressure
• Scanner problem
• Emboss problem
• Heat exchanger
• Feeding  problem –Chute channel, Gate transfer, Spiral, Brush
• Strip Packing and Bottle Filling Machineries:

### Maximum capacity

Strpping Machine(Ganson)

India

34 strip/min

Bottle filling machine 063

Taiwan

50 Bottles/ min

Cap sealing machine, 064

India

60 Bottles/ min

• Ø Machineries of printing room:
 Machine Name Type Origin Prontophot-Hapa. AG Auto Switzerland Sami Auto Printing Machine Semi-auto India KK & KK-2 Printing machine Auto Taiwan

RESEARCH AND DEVLOPMENT

Research and Development Department plays an important and innovative role in every step to establish a new formulation, new dosage form, coating system and their development etc. Product Development also prepare recipe for the product, formulation order, manufacturing process, Batch Production on Record (BPR), and data, and development in commercial scale of a new product. This section always tried to give higher quality product with minimum cost.

Marketing Department

Operation Department

Plant Manager

Research Development Department

Research

Establishment of new Product

Marketing Department

Regulatory Affair Department for approval of the new product by the Drug   Administration

Starting of Commercial Production

This department has tow part-

Function of Research Development Department:

Research development department deals with the following functions:

1)     Formulation of new product

2)     Reformulation of existing product

3)     Problem solving related to manufacturing

4)     Preparation of BMR and BPR for a new product

5)     Development of existing products.

6)     Analytical method development

7)     Stability study of new product according to stability study protocol.

8)      Preparation of sample for drug testing laboratories (DTL).

Analytical activities:

After production this unit responsible for following activities:

• Quality builds up and checks.
• Disintegration & dissolution test.
• Friability & thickness test.
• PH test.
• Stability test

Machineries used for RD department:

1. Compression machine

Source: Manesty, England(16 Station)

2. High speed mixture Granulator

Source: Thailand

3. Coating Pan

Accela cota,

Source: Thailand

4. Weighing balance

Source: Japan

5. Magnetic stirrer

Gallenkamp,

Source: England

7. Friability tester

Erweka,

Source: Germany

8. HPLC

Source: Japan.

9. Bulk/Tapped Density Tester

Electrolab

10. Magnetic Stirrer and Hot Plate

Gallenkamp

11. Multi-Mil

Source: MSC35 (INDIA)

12. HANNA PH Mixers (Romania)

13. ERWEKA Dissolution Tester

14. NEWTRONIC Stability Chamber

NEWTRONIC (INDIA)

15. MEMMERT Electric Oven (Germany)

16. SHARP Refrigerator

LIQUID DOSAGE FORMULATION

Oral Liquid and Topical Preparation Area is one of the most important area in Beximco Pharmaceuticals Limited. This section involved with the manufacturing of products like antacids, non-antacids and semisolids.

Manufacturing area of this section is divided into two Units as follows

1. Liquid Unit I
2. Liquid Unit II

Liquid Unit I

This section is divided into the following areas

• Area for antacid manufacturing, filling and Packaging.
• Area for non-antacid manufacturing, filling and packaging.
• Area for cream, ointment and gel manufacturing, filling and packaging area.
• Automatic washing room.
• Equipment washing room
• Bottle washing and autoclave room
• Printing room

Liquid Unit II

This section is divided into following sections

• Area for oral liquid products manufacturing.
• Area for oral liquid filling and packaging.
• Area for suppository manufacturing and packaging.

List of Machineries in liquid Section:

 Automat Filling & Sealing machine India 105-106 bottles/hr Greatide Ointment Filling & Sealing Machine Taiwan 2400 tubes/hr Weighing Balance, Satorious Germany Gansons Bottle Washing Machine India 240 bottles/hr Heracus Bottle Washing Machine India Memmert Cap Dryer Manufacturing & Storage Jacketed Vessel Australia 5000 litre Manufacturing & Storage Jacketed Vessel Australia 3000 litre Millipore Filter Germany 50 μ Manufacturing Vessel India 1000,500,200 L Avrey Weighing Machine, Gansons England 50 & 250 kg Planetary Mixer India Colloid Mill Germany 100 kg Manufacturing Vessel & Storage Tank Australia 3000 litre Dust Collector Italy Sarong Suppository Filling & Sealing Machine Italy Pharmalab Bottle Filling & Sealing Machine India 110 bottle/min Carton Sealing Machine Taiwan Automatic Printing Machine Taiwan 4000 peak/hr Semi automatic Printing Machine China

Flow Chart of L.C.O & Suppository Operation

Quality Control

Department

Quality control department makes all types of chemical assay and chemical analysis find the result in terms of potency, presence, identity, stability etc. The persons working here are responsible for the quality of the products. This is actually the analytical part of the plant.

Working Division of Quality Control Department

• Analytical section
• Microbiology section
• Packaging section

Analytical Section:

Analytical section of Quality Control Department performs analytical tests. Analytical tests are mainly of two types as follows:

• Quantitative
• Qualitative

Stability Study

Mainly for finished products, Quality Control Department performs stability study. Aim of this study is to ensure that all batches of the released products are maintaining within specification limits throughout their entire shelf life.

Stability study is performed according to International Conference on Harmonization (ICH).

 Type of Study Experimental condition Real time study for climate zone 3 & 4 30º C ± 2º C temperature65 ± 5% Relative Humidity Accelerated study 40º C ± 2º C temperature75 ± 5% Relative Humidity

An intermediate stability study is also performed at 30º C ± 2 º C temperatures and 65 ± 5% relative humidity. If 30ºC ± 2ºC temperature and 65 ± 5% is the long-term condition, there is no study required for intermediate condition.

Activities of Quality Control Department:

# Sampling

(A quality control officer does it when Raw materials arrive in Warehouse)

# Analysis

(The analyst analyses the sample according to the specification)

# Checking

(After the tests, the results are checked)

# Final approval

(The Q.C manager verifies the result)

# Collection

(A Q.A officer collects the results of the sample that was assigned previously)

Machineries of Analytical Section

 Equipment Name Origin HPLC System & Controller Shimadzu, Japan Karl-fisher titrator Mettler, Switzerland. Leica AR-600 Automatic Refratrometer Leica, U.S.A Brookfield Digital Viscometer Brookfield, U.S.A Atomic Absorption Spectrophotometer Aurora, Canada. IR Prestige 21 (FTIR Shimadzu, Japan PolarimeterGas Chromatography Atago, Japan Humidity Control Oven Newtronic Equipment Company, India. Humidity Oven Thermolab, India. Dissolution Tester 4 Erweka, Germany. Electronic Anal Precision Balance Sartorius AG, Germany Disintegration test Apparatus Erweka, GmbH, Germany. Apt-Line Kbf Humidity Oven WTB Binder, GmbH, Germany. Melting Point Apparatus Gallenkanp, England. Octagon Sieve Shaker UK pH meter Beckman Sonicator Ultrawave

Microbiology section:

Microbiology section of Q.C department is performed microbiological tests. Microbiological tests cover two types of test, one is microbial limit test and another is bioassay of antibiotics.

Activities of microbiological section

• Microbial limit test of raw materials and finished products
1. Total aerobic bacteria and fungal count.
2. Detection of pathogens like; Salmonella sp, Escherichia coli (E. coli),

Pseudomonas aeruginosa, Staphylococcus aureus.

• Microbial assay of raw materials and finished products.
• Environmental monitoring

Equipments in Microbiological Section

 Name of the Machine Origin Comments Laminar Air Flow (Bench) Airtech CompanyJapan 0.45μHEPA Filter porosity 0.22 μ Hot Air Oven Kottermann-2736Germany 180ºC temperaturefor 3 hours is used to sterilize Autoclave Apl, Naniwa Ikakgyo Company, Japan 121ºC temperature with 15 pound pressure for 15 minutes is used to sterilize the media Incubator Memmert md-600Germany 37ºC temperature to support optimal bacterial growth. Rotamixer Hook & Fucker Instruments, UK Proper mixing of Sample and preparation of Inoculums suspension

Packaging Section

Quality Control Department performs the following tests for packaging materials:

 Packaging Materials Tests Cotton Appearance, weight, moisture content, sulphated ash Shipping carton Weight, dimension, thickness, appearance Plastic cap Appearance, weight, length, diameter, volume, capacity Dropper Appearance, weight, length, diameter, volume, capacity, adaptability with bottle, carton and plastic cover Mask tape Appearance, width, adhesiveness Water measuring flask Appearance, weight, length, diameter, capacity 5 ml Spoon (Plastic) Appearance, weight, length, diameter, capacity Bottles Height, neck diameter, body diameter, weight, overflow capacity, machine acceptance, light transmission(10% allowed) Inner carton Height & level, description, weight dimension PVC/PVDC Color, width, thickness Label & Literature Product name, generic name, batch number,manufacturing date, expiry date, M.R.P,

QUALITY ASSURANCE

Quality Assurance is an organized department in Beximco Pharmaceuticals Ltd. which deals with ensuring the quality of the product up to the end user. In1980s the approach for assuring product quality extended the responsibilities of quality control far beyond the area of testing and compliance check, and the concept of Quality Assurance was developed:

QA=Product design + GMP + QC + Quality goal activities

The activities of Quality Assurance are as follows:

Approval of source

Checking of Dispensing operation

In process checking of all production area

Product sampling , release

Product complaint handling

Supplier’s performance review

Conducting quality audit

Perform all type of Validation activities

Document preparation, editing, control etc.

Retention sample collection, archiving, monitoring, retrieval etc.

Product quality review(Annual/Periodic)

Artwork preparation, checking, finalization for packaging material

Preparation of certificate of analysis for finished formulation and finished API.

Establishing manufacturing methods and SOPs covering entire operations and their regular up-dating.

Communication of every aspects relating to quality to all relevant persons for early positive action.

Ensuring product Stability

INFUSION UNIT (LARGE VOLUME PARENTERAL)

WATER TREATMENT PLANT

Sterile products are very sensitive one and should be free from any viable microorganisms. As water is used as large volume raw materials in infusion preparation and this is directly inject to blood so purification of water for preparing Water For Injection (WFI) is very important. For this water treatment plant is a mandatory part of Infusion Unit.

Machineries used in water treatment plant are as follows:

• Boiler
• Chiller
• Air Compressor
• Cooling Tower

Rests of the machineries which are used in water treatment plant are given in the following flow chart:

FLOW CHART OF WATER TREATMENT PLANT

Submersible pump (collection of water from 110-120ft below from earth level)

Erosion Chamber

Multimedia Filter

Cl2 Dozing

15micron filter

Reservoir

Activated Carbon Filter

micron filter

micron filter

Ion Exchanger

Mixed Bed

micron filter

micron filter

DM Water Tank

Distillation Plant

Condenser

Distilled Water Tank

Heat Exchanger

Water For Injection (WFI)

Solution preparation area: Functions of solution preparation area are given with a   flow chart-

DM water              Cleaning & sterilization of tank               pouring water in tank for

Preparing solution

Sample for QA approval                     Stirring                        Addition of raw material

Filtration at pall filter              Filtration at pall filter             sending to buffer tank for filling                                          (0.22micron)

(2.5 micron)

Bottle Packing: Activities in bottle packing area are-

Polyethylene             Extrude               Mould                                  Blowing & Filling

Sealing                         Cap welding                       Punching

Autoclave:  Autoclave is one of the most important area in manufacturing sterile dosage forms. In autoclave, sterilization is done at 106°C temperature at chamber pressure 2.1 bar and steam pressure 1 bar for 85 minutes.

Packaging: Activities of packaging area are-

a) Visual inspection (cap spot, body spot, mechanical stress, deformation)

b) Bottle checking in pressing belt & manual sorting of defective bottles

c) Labeling on bottles

d) Over bagging & printing through jet printer on over bag

e) Over bag sealing

f) Master cartooning

Machineries Used in BPL

 EQUIPMENT ORIGIN FEATURE Injection Moulding machine( Superjack ) Germany Capacity : 12 ounce( 180 PC ) Electronic balance( Rhewa ) Taiwan Vessel-1 ( solution Vessel ) Germany Capacity : 3000 liter Vessel-2  ( Gentinge ) Germany Capacity : 3000 litre Muller device Germany Bottle Packing, Filling & Sealing machine( Bottle Pack Type 302 ) Germany Capacity :  785 pcs 1000ml bottle / hr. Bottle Packing, Filling & Sealing machine( Schuma ) Germany Filter Checking Machine( Paltronic ) Germany Assembling Machine( Rubber Filling ) Autoclave( Sauter-Sulgen ; Gentinge ) Germany Blue Bath Tester Used for leakage testing of bottle Pressure/ conveyer Belt Germany Pressure used :  0.3– 0.5 Bar Labelling Machine( Avery ) Germany Air Sealing Machine( Impulse Autosealer ) Taiwan Inkjet Printer( Jaine 1000 ) Germany

QUALITY ASSURANCE IN INFUSION UNIT:

QA department plays a vital role in infusion area. QA tests are performed in each and every step in manufacturing infusions. Providing quality, safe products is the main responsibility of QA department.

Activities of QA department in infusion unit are given below with a flowchart.

Receiving of MRI

Visual inspection of RM & PM

Sampling of RM & PM

Q.C., chemical & microbiological testing of RM & PM

After preparation of solution assay and pH checking of sample

ENGINEERING

SERVICES & UTILTIES

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.

CONCERNED AREA OF ENGINEERING DEPARTMENT

• 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

• Engineering Department is also concerned for maintenance of all production machineries. Maintenance can be classified into two different categories-

a) Schedule/ Preventive maintenance:

All the all production machineries are checked routinely (weekly, monthly etc) 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.

FLOW CHART OF MAINTENANCE PROCEDURE OF ENGINEERING DEPARTMENT

Planning for maintenance

Requirement of skilled and trainer manpower (Personnel)

Availability of required materials (Parts of machines)

Execution of work

1. Water pump:

NAME                            MODEL                  MOTAR MODEL                  CAPACITY

Deep tube well     310b/9                    Siemens 40HP

Deep tube well37B/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

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.

They perform maintenance works by two ways

Routine/preventive/schedule maintenance : check weekly which include

1. Cleaning

2. Greasing and oiling

3. Change bearing

4. Checking

5. Inspection

Breakdown

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

RECOMMENDATIONS

We all know that Beximco pharmaceuticals Ltd. never compromise regarding the quality of the product. BPL follows the guidelines of the cGMP and maintenance the standards from the very beginning of the production procedure to distribution in the market & keeps record of all documents. That is why there is hardly any scope of rendering any suggestion for its further modification.

But some recommendations can be given-

• Effluent Treatment Plant may be set up as early as possible though BEXIMCO Pharma already ensured the destruction of hazardous wastes safely in contract basis with icddrb.
• Opportunities for the trainee may be given to visit TRACK-II and MDI.
• Capsule polishing machine is needed to reduce manufacturing time.
• We hope Beximco Pharmaceuticals Ltd. will  Manufacture Soft gelatin capsule.

FINDINGS AND ANALYSIS

During our training program in Beximco Pharmaeuticals Ltd. we have found the following findings:

• Beximco Pharmaeuticals Ltd. strictly follows the rules and regulations of cGMP.
• Beximco Pharmaeuticals Ltd. has got the TGA approval of Australia this year.
• Beximco Pharmaeuticals Ltd. is going to introduce small volume parenterals(SVP).
• Enough paste control device is available inside the plant.
• A separated Sampling Booth is available in warehouse where temperature, humidity, and pressure is controlled.
• Rejected materials are kept locked to reduce the possibility of mix-up with the released material.
• Hazardous wastes are destructed safely by the collaboration with icddrb.
• Beximco Pharmaeuticals Ltd. has a separated training department.
• Central Warehouse of Beximco Pharmaeuticals Ltd.  is very large and well arranged.
• Quality Control department is well equipped.
• RD department is self sufficient for the development of new product.

EXECUTIVE SUMMERY

BEXIMCO Pharmaceuticals is the second largest company in Bangladesh. Though Beximco is a local company but they follow multinational culture. They also maintain a chain of command. After the 1982 drug policy, they go their own formulation and in a short period they acquired crown of success. In case of coating Beximco is the pioneer. They believe quality is first. And to ensure quality they have excellent facility and no. of experience & skilled personnel who are contributing for that. It has a wide range of product line such as solid, semisolid, liquid, ointment, cream, suppository etc.  BEXIMCO Infusions and MDI have the best facilities and utilities than that of other production areas. These areas are highly specified and maintaining aseptic technique. MDI of BEXIMCO undergoes contact manufacturing with Glaxo Smith Kline (GSK).BEXIMCO Infusions operating a well organized water treatment plant “Pharmaplan” imported from Germany, which makes BEXIMCO one step ahead of other infusion plants in Bangladesh.

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.

CONCLUSION

I had a strong desire to gather practical knowledge during my in-plant training from BEXIMCO Pharmaceuticals Ltd. is the leading pharmaceutical industry in Bangladesh. Its contribution for the development of national economy is well known. BEXIMCO Pharma having a pioneering role in exporting pharmaceuticals from Bangladesh. The plant layout of the Beximco pharma. Ltd. is excellent and well organized. They have large area and they can easily extension of plant if it is necessary.

The 2 weeks in-plant training helps us to understand the steps of tablet coating, method of granulation, compression, Liquid filling, aseptic condition and much difficult topics of pharmaceuticals.

During in-plant training, we got lots of co-operation from every people of every section and we delighted for their friendly approach. We satisfied and produto have the modern knowledge and practical experience from a well reputed factory like Beximco Pharmaceuticals Ltd. This practical knowledge will help us in my future professional life.

BIBLIOGRAPY

1.     All Department of Beximco pharmaceuticals Ltd.

2.     Half yearly Report

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