REPORT ON

IN-PLANT TRAINING

AT

BIOPHARMA LABORATORIES LIMITED

TRAINING SESSION:

20 January, 2011 to 01 February, 2011.

Submitted to:

Md. Saiful Amin

Director plant,

Biopharma Laboratories Limited.

Submitted by:

1. Fahad Hussain ID # ASH 0603014

.

DEPARTMENT OF PHARMACYNOAKHALI SCIENCE & TECHNOLOGY UNIVERSITYSONAPUR ,NOAKHALI -3802. BANGLADESH website: www.nstu.edu.bd

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Contents

No Subject Page

1 Preface 3

2 Acknowledgement 4

3 Introduction 5

4 Product list 6-15

5 Administration 16

6 Quality Control Department 17-20

7 Microbiology Section 21-22

8 Tablet Department 23-33

9 Capsule Department 34-37

10 Dry Syrup Department 38-41

11 Liquid Department 42-47

12 Semi-solid Department 47-50

13 Packaging Department 51-53

14 Quality Assurance Department 54-56

15 Research & Development 57-60

16 Warehouse 61-65

17 Product Management Department (PMD) 65-66

18 Current Good Manufacturing Practice (cGMP) 67-70

19 About NSTU Pharmacy Department 71

20 Conclusion 72

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Preface

It is the ultimate task to submit a report after industrial tour. But when we sit for preparing this report we face a number of problems, because we have visited different manufacturing units within a very short time. Though we have tried my best to observe different manufacturing process and equipments carefully and try to keep documents about them with the help of concerned supervisor, we have failed to do that properly. However, with the cordial help of my respectable concerned supervisors finally we able to complete this report.

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ACKNOWLEDGEMENT

All praise to Al-mighty Allah who has given us the opportunity to undertake and complete this in-plant training and finally write up the report. We would like to express our gratitude to our parents for their endless love, admiration and encouragement throughout our life.

We are very grateful to our teachers. Specially our advisor A.F.M Shahid-ud-Doula, our training advisor Mr. Bishwajit Kumar Biswas and our Head of Department Mohammed Anwarul Basher.

We would also like to express our deepest sense of gratitude and sincere thanks to Md. Saiful Amin, Plant Director; Md. Masudur Rahman, PMD Manager; for his support and sincere regards.

We also like to express our special thanks to all the staffs and personnel of Biopharma Laboratories Limited for their continuous support and welcoming assistance through our training program.

Our cordial thanks to all of our classmates, friends and some other special people for their continuous inspiration.

We, the students of Pharmacy Department, The Noakhali Science and Technology University have the honor to express our cordial thanks to the authority of Biopharma Laboratories Limited. They are very much helpful and their co-operation and suggestion regarding to this training program always encouraged us to achieve our goal.

Introduction

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Training is the most important key facts for all professional subjects. Where as, in Pharmacy

education, In-Plant Training are must for justifying the education achievements, also for

make connection between practical and theory. It’s also important to know in details the

application mode of modern scientific and management issues aiming to familiar them

correctly. In another point of view In Plant Training is the bond between pharmacy education

institution and commercial pharmaceutical organization.

ABOUT BIOPHARMA LABORATORY LTD:

BIOPHARMA is always committed to assure the best quality pharmaceutical products and

best services to the customers. Our mission is to serve the mankind, especially the distressed

and poor ailing people and our vision is to be regarded globally as a Quality pharmaceutical

manufacturer through the best quality pharmaceutical products. Bearing this in mind, our

technical experts (pharmacist, Chemists, Biochemists, Microbiologists Analysts and other

professionals ) skilled and trained staffs always try to leave no stone unturned in their

professional works by following the US cGMP, British & WHO GMP guidelines and the

guidelines & instructions of the Drug Administration & Licensing Authority of Bangladesh to

ensure the production of quality medicine. Ever since we at GLP ( Good Laboratory practices

) have always been performing with a strict discipline to follow our professional ethics. By

virtue of the highest quality of drugs, the company has already obtained the confidence and

trust of doctors and patients all over Bangladesh and earned excellent reputations in the

market through introducing very exciting new molecules and dosage forms in many

therapeutic areas. We are now producing a wide range of Biological and Biological

pharmaceutical products in different dosage forms and presentations including tablets,

capsules, syrups, suspensions, powder for suspensions, paediatric drops, sterile creams &

ointments and injectable preparations.

BIOPHARMA defines progress and innovation as a Challenge to achieve continuous

improvement in the increasingly competitive markets and for the better health services to the

people; hence our Research & Development scientists are always devoted to do their efforts

to ensure maximum safety, therapeutic efficacy and reasonable prices in the development of

new products (new therapeutic molecules ) .

BIOPHARMA values to all of its employees and makes effort through Quality of Work Life

to help their growth. Our training programs include training at work

( e .g. cGMP training ) as well as professional seminars. Thus, we have a good management

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system to encourage initiatives talent, teamwork spirit and mutual to develop the full

potential of each employee and the company. The people working in the company share its

value and mission to dedicate themselves for enhancing human healthcare by making

available the best quality pharmaceutical products at affordable prices.

They are committed to excellence in their product quality. Their innovation is driven by:

• RESPONSIBILITIES TO THEIR CUSTOMERS• COMMITMENT TO BRING THE LATEST FORMULATIONS TO THE MARKET• UNCOMPROMISING COMMITMENT TO QUALITY

THEIR PRODUCT CATEGORIES INCLUDE:

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Products:

Antibiotics 

Anti-Fungal-Drugs  Anti-Protozoal-Drugs

Anti-Histamines  Anti-Emetic

Anthelmintics  Antacid & Anti Ulcerants

Laxative Drug  Anti-Oxidant

Vitamins & Minerals NSAIDs

Bronchodilators  Expectorants

Anti-Diabetic Drugs  Anti Depressants & Anxiolytics

Cardiovascular DrugsDermatological Products

ANTIBIOTICS

AMOTIDAmoxicillin BP 250 capsuleAmoxicillin BP 500 capsuleAmoxicillin BP dry powder for suspension 100ml (125mg/5ml)Amoxicillin BP dry powder for suspension 100ml (250mg/5ml) Amoxicillin BP paediatric drops 15ml (100mg/5ml)

BIOPEN VK

Phenoxymethyl penicillin BP 250mg tablet Phenoxymethyl penicillin BP dry powder for suspension 50ml (125mg /5ml) Phenoxymethyl penicillin BP dry powder for suspension 100ml (125mg /5ml)

REVISTAR

Flucloxacillin BP 250 mg capsuleFlucloxacillin BP 500 mg capsuleFlucloxacillin BP dry powder for suspension 60ml (125mg /5ml )

 

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Flucloxacillin BP dry powder for suspension 100ml (125mg /5ml)

CIPCIN

Ciprofloxacin USP 250mg film coated tabletCiprofloxacin USP 500mg film coated tabletCiprofloxacin USP 750mg film coated tabletCiprofloxacin USP powder for suspension 60ml (250mg /5ml)Ciprofloxacin USP powder for suspension 100ml (250mg /5ml)

LIFCIN

Levofloxacin INN 250 mg film coated tablet Levofloxacin INN 500 mg film coated tablet

 

SUPRACEF

Cephradine BP 250mg capsule Cephradine BP 500 mg capsule Cephradine BP dry powder for suspension 100ml (125mg /5mlCephradine BP dry powder for suspension 100ml (250mg /5ml)Cephradine BP paediatric drops 15ml (100mg /ml )

 

SUPRALEXCefuroxime BP 250mg capsule Cefuroxime BP 500mg capsule Cefuroxime BP powder for suspension 100ml(125mg /5ml)

BESTCEF

Cefixime USP 200mg capsuleCefixime USP dry powder for suspension 37.5ml (100mg /5ml)Cefixime USP dry powder for suspension 50ml (100mg /5ml)

MEXTIL  

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Cefuroxime BP 125 mg tablet Cefuroxime BP 250 mg tablet Cefuroxime BP powder for suspension 70ml (125mg /5ml )

BIOTRIMCotrimoxazole (Sulphamethoxazole BP 400mg & Trimethoprim BP 80 mg ) tabletCotrimoxazole BP dry powder for suspension 60ml(SMZ 200 mg/ 5ml & TMP 40 mg /5ml)

BIOTRIM DS

Cotrimoxazole double strength(Sulphamethoxazole BP 800mg & Trimethoprim BP 160 mg ) tablet

EROSAErythromycin USP 250 mg film coated tabletErythromycin USP 500 mg film coated tabletErythromycin USP powder for suspension 100ml (125mg /5ml)Erythromycin USP paediatric drops 15ml (100mg /ml )Erythromycin USP paediatric drops 30ml (100mg /ml )

MACZITH

Azithromycin USP 250 mg capsule Azithromycin USP 500mg film coated tablet Azithromycin USP dry powder for suspension 15ml (200mg /5ml)

ANTI-FUNGAL DRUGS

FUNGATAFluconazole BP 50 mg capsuleFluconazole BP 150 mg capsule Fluconazole BP dry powder for suspension 35ml (50mg /5ml)Fluconazole BP dry powder for suspension 60 ml ( 50mg /5ml)

ANTI - PROTOZOAL DRUGS

BIOZYLMetronidazole BP 400mg film coated tebletMetronidazole BP suspension 60ml (200mg/5ml)

 

ANTI - HISTAMINES

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BIOCINChlorpheniramine maleate BP 4mg tabletChlorpheniramine maleate BP syrup 100ml(5mg/5ml)

LORFAST

Loratadine INN 10mg tablet Loratadine INN suspension 60ml (5mg/5ml)

ANTI - EMETIC

ESOGUTDomperidone BP 10 mg film coated tablatDomperidone BP suspension 30 ml ( 5mg /5ml)Domperidone BP suspension 60 ml ( 5mg /5ml)Domperidone BP paediatric drops 15ml (5mg /ml )Domperidone BP paediatric drops 30ml (5mg /ml )

 

AVERT

Meclizine HCI USP 50mg tablet

 

ANTHELMINTICS

AZOLEAlbendazole USP 400mg chewable tabletAlbendazole USP suspension 10ml (200mg/5ml)

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BIOTREX

levamisole BP syrup 30ml (40mg/5ml)

ANTACID & ANTI-ULCERANTS

BIOCIDAntacid (Aluminum Hydroxide BP250mg + Magnesium Hydroxide BP 500mg chewable tablet)

BIOCID MH

(Aluminum Hydroxide BP +Magnesium Hydroxide BP ) suspension 200 ml 

BIOCID PLUS

(Aluminum Hydroxide BP +Magnesium Hydroxide BP + Simethicone BP) suspension 200 ml 

ACIN

(Ranitidine USP 150mg film coated tablet Ranitidine USP 300mg film coated tablet

INPRO

Omeprazole BP 20mg capsuleOmeprazole BP 40mg capsule

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PANPRO Pantoprazole INN 20mg enteric coated tabletPantoprazole INN 40mg enteric coated tablet

ESOM

Esomeprazole INN 20mg film coated tabletEsomeprazole INN 40mg film coated tablet

 

LAXATIVE DRUG

LACTULactulose BP solution 100ml (3.35g/5ml) Lactulose BP solution 200ml (3.35g/5ml)

ANTI-OXIDANT

VITAFORCE(Vitamin - E BP 50 mg + Vitamin - C BP 200 mg + Beta carotene USP 6 mg) film coated tablet

VITAMINS & MINERALS

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BIOVITVitamin B - Complex capsule Vitamin B - Complex syrup 100 ml Vitamin B - Complex syrup 200 mlMultivitamin pacdiatric drops ( vitamin B - complex BP +C BP +Vit- D USP + Vit - A USP + Calcium - D - panto thenate USP ) 15ml

BIOVIT -M

Multivitamins & minerals tablet

BIOVIT -E

Vitamin -E BP 200mg film coated chewable tablet

 

BIORON

Ferrous sulphate BP syrup (200ml/ 5ml )

BIRON PLUS

Ferrous sulphate BP +Zinc sulphate USP + Folic acid BP ) capsule

CEVALIN

Ascorbic acid BP 250mg chewable tablet  

FIVITA

(Ferrous sulphate BP+Folic acid BP + Vitamin - C USP + Vitamin B -Complex BP ) capsule  

ORTHOCAL

Elemental Calcium USP 500mg ( as Calcium carbonate USP ) film coated tablet

ORTHOCAL -D

Elemental Calcium USP 500mg as Calcium carbonate +Vitamin D USP 5mcg ) film coated tablet 

ZINGA DS

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Zinc sulphate BP syrup 100 ml (zinc BP 10mg / 5ml)

NSAIDs

ACETAParacetamol BP 500 mg tabletParacetamol BP suspension 60 ml ( 120mg /5ml)Paracetamol BP pediatric drop 15ml (80mg /ml )Paracetamol BP pediatric drop 30ml (80mg /ml )

TOPKetoprofen BP 50mg enteric coated tablet Ketoprofen BP 100mg enteric coated tablet

VOLCAN Diclofenac sodium BP 50mg enteric coated tablet

 

VOLCAN TR Diclofenac sodium BP100mg timed release capsule

 

CLOF

Aceclofenac BP 100mg enteric coated tablet

BRONCHODILATORS

SALBUSalbutamol BP 2mg tablet Salbutamol BP 4mg tablet Salbutamol BP 60ml syrup (2mg/5ml)Salbutamol BP 100ml syrup (2mg /5ml)

 

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EXPECTORANTS

KOFED Pesudoephedrine BP + Guaiphenesine BP + Triprolidine BP) syrup 100ml

 

MUCUTBromhexine HCI BP syrup 100ml ( 4mg /5ml )

 

ANTI - DIABETIC DRUGS

FORMETMetformin HCI BP 500mg film coated tablet Metformin HCI BP 850mg film coated tablet

GLUCOSTATGliclazide BP 80mg tablet

 

ANTI - DEPRESSANTS & ANXIOLYTICS

CALMClobazam BP 10 mg tablet

EUPHOR( Nortriptyline HCI( BP 10 mg + Fluphenazine HCI BP 0.5 ml ) film coated tablet

 BENZIT(Flupentixol INN 0.5 mg +Maletracin INN 10mg ) film coated tablet  

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CARDIOVASCULAR DRUGS

EMLONAmlodipine BP 5mg tabletAmlodipine BP 10mg tablet

ETNOLAntenolol BP 50mg tabletAntenolol BP 100mg tablet

LOPOLosartan Potassium INN 25mg film coated tabletLosartan Potassium INN 50mg film coated tablet

DERMATOLOGICAL PRODUCTS

Topical Corticosteroids:

XDERM Cream 10g (Clobetasol propionate USP 0.5% ) in Aluminum tube )XDERM Ointment 10 g (Clobetasol propionate USP 0.5% ) in Aluminum tube )MEXIDERM Cream 15 g (Betamethasone valerate BP 0.1%) in Aluminum tubeMEXIDERM Ointment 15 g (Betamethasone valerate BP 0.1% ) in Aluminum tube

Topical corticosteroids:

SCAPER cream 15 g (permethrin BP 5%) in Aluminium tubeSCAPER cream 30 g (permethrin BP 5%) in Aluminium tube

Topical Anti-infective:

NUBA Ointment 20g (Neomycin sulphate BP 0.5% & Bacitracin zinc BP 500 mg) in Aluminum tube

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Topical Anti-infectives with corticosteroids:

MEXIDERM-N cream 5g (Betamethasone valerate BP 0.1% & Neomycin sulphate BP 0.5%) in Aluminium tube MEXIDERM-N Ointment 5g (Betamethasone valerate BP 0.1% & Neomycin sulphate BP 0.5%)in Aluminium tubTopical:

anti-fungals ENAZOL PLUS cream 10g(Econazole nitrate BP 1% & Triamcinolone acetonide BP 0.1%)in Aluminium tube TERMIDER cream 15g (Terbinafine HCI INN 1%) in Aluminium Tube.

Administrations

This department is related to the management of affairs. It concerns with the following –

Working time recording, canteen, transport, liberty granted employment entrance & exit. In a single word this department controls almost all the sections in Biopharma laboratory Ltd.

Duties & Responsibilities of Executives: Planning of production of potent, safe, effective & stable medicines by maintaining

the WHO, cGMP procedure. Organizing & controlling of routine activity in the factory. Monitoring & reviewing of present production target. Distribution of work on the basis of machine availability and production priority and

check the attendance of the worker. Proper planning & implementation of routine production activity. Designing and the implementation of In-process checks at different steps of

manufacturing. Ensure production quality. Enforce house keeping & cleanliness. Supervise shift wise sectional activities. Shift wise man power distribution. Effective utilization of machine hours. Weekly & monthly production monitoring. Supervise export & institutional order processing

Duties of worker:

Manufacture of the product as per formulation & manufacturing instruction.

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Apply the In-process control measures as per required by the product according to the instruction procedure.

Perform packaging of product as per packaging instruction. Maintain house keeping and sanitation of the production floor.

Quality Control Department:

Quality control A new raw material / drug product before use or marketed must need to check the quality which is claimed. This department of Biopharma laboratory Ltd is stuffed with scientist and technicians who assess and assure that entire production process has been completed satisfactorily and satisfied all the aspects of GMP.

Physical test for raw material

Identification of appearanceColor of the materialAppearance of solutionIn solution ppt is present or notMelting pointSolubility

Loss on dryingOptical rotationBulk densitySulphated ashAssay

Physical test for finished product

Appearance

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Hard nessThick nessFinishing of coating materialClaimed weightFriability

Leak testDissolutionDisintegrationWeight variation

Chemical test for both Raw & Finished Products:

1. pH test2. Optical rotation3. Potency test a. Different titration method (Aqueous, non aqueous, complexometric, acid-base, potentiometric, iodometric & iodimetric titration) b. Extraction method c. Gravimetric method d. Absorbance test ( by- UV-spectrophotometer, HPLC, Atomic absorption photometer, Gas chromatography, FTIR etc) 4. Microbial test (colony counting, zone of inhibition, LAL test, sterility test, limit test)

Analysis of packing material:

Packing materials are examined carefully, because packing materials are directly touched by the finished products. Packing materials may degrade the finished products. This is why leaching capability, chemically active/inactive, stable/unstable, heat/chill stability, original size & shape, printing on insert/label, color, moisture content (for cotton), price, quality etc.All this checked for the- rubber, glass, plastic, collapsible tube, cap, ward, unit carton, master carton, insert, label etc.

Quality Control activities:

Q.C

Water & EffluentPackaging Documentation &

routine analysis

Microbiological testing

Analytical development & validation

Calibration

Finished products

Stability

Raw materials

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Protocol for quality control assignment:

Sampling

Supervising

Analysis

Checking

Final approval

Collection

Raw Material Collection from QUARENTAIN area:

Raw materials are collected by √n+1 formula.As example: there are 81 container of sample So we have to collect from √81+1=9+1=10 containerSample must be taken from the 3 portion (up, middle, below) of the container If any container opened in the customs area / before the quarantine area, they should not follow the √n+1 equation. Sample should be taken from all opened container and must be from the 3 portion of the container. After taking sample container should be close carefully because there may occurs microbial contamination.

Instrumentation of Q.C. Department:

1. HPLC (high performance liquid chromatography)2. IR spectrophotometer3. UV-Visible spectrophotometer4. Karl-Fischer titration

5. pH meter

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6. M.P.apparatus.7. USP dissolution test apparatus8. USP disintegration test apparatus9. Chemical Balance 10. Drying oven11. Microscope 12. Hot Plate13. Centrifuge14. Oven15. Vortex mixer16. Humidity Control Chamber17. Water Bath18. Leak Test Apparatus19. Tab Density Taster20. Tablet Tester including diameter, thickness, and hardness test of tablet21. Atomic Absorption Spectroscopy.

Apparatus for MICROBIAL Tests:

- Autoclave- Hot & cool Incubator. - Machine for laminar flow - Oven- Air & liquid particle counter- Colony counter & zone of inhibition reader

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Microbiology Section

Microbiology Section:

This section plays an important role in producing a quality product as it checks all the parameters related with manufacturing a quality product in a clean and healthy atmosphere. The tests that are regularly monitored by this section in the Biopharma laboratory Ltd are as follows-

1. Microbial limit test2. Sterility test3. Antibiotic bioassay4. Bacterial antitoxin test5. Environmental monitoring6. Water test

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Air Filtration for test:

Test for sterility of microorganism by using cellulose membrane filter in the filtration method. The pore size is 0.22 micron & diameter is 47 mm.

Procedure of sterility test by filtration method:

The procedure of filtration method by using test for microorganism is follows-(Filter paper and filtration apparatus to be sterile for filtration method)

Cellulose filter membrane + Apparatus is sterilized

To set a filter paper in the filtration apparatus

The liquid to be tested is added in the filter funnel

The liquid is passed trough the filter paper

Filter paper is removed from the filtration apparatus by forceps

Filter paper is cute by scissor

Added to the media

Filter papers with media keep the incubator(7 to 14 days)

Observation of microorganism growth

No turbidity

Sterility passed

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Tablet Department

Tablet Department

Tablets are solid dosage pharmaceutical forms containing drugs substance, with or without suitable diluents, disintegrates, binders, coloring or flavoring agents and prepared by compression.

Solid department is one of the most important sections in any pharmaceutical company. Solid section is the biggest unit in the Biopharma laboratory Ltd . About maximum of the total turn over per year is manufactured in this section. That is why this section plays the key role in the financial aspects of this company.

Solid Department

Manufacturing area Packaging area

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Granulation unit Compression unit Coating unit Capsule filling unit

Manufacturing area: Granulation Unit:

Fir:-Rapid Mixer Granulator

Granulation is the most preliminary process in the solid manufacturing area. Granulation is the process in which powder particles of raw materials are made to adhere to form larger particles called granules

1. To improve the flow of powdered materials by forming sphere like or regularly shaped aggregates and

2. To improve the compression characteristics of the mix (blend.)3. To prevent segregation of the constituents in the powder mix.

Two types of granulation processes are performed in this unit:

-Dry granulation -Wet granulation

Granulation units perform the following steps of tablet formulation to form larger particles in order to facilitate compression. General Procedure:

Mixing of active ingredient (wet or dry mixing)with necessary amount of excipients (except lubricant) in Rapid Mixer Granulator(RMG).

Wet milling / sieving by Multi-mill

Drying by fluid bed dryer

Dry milling / sieving by Multi-mill

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Final blending with rest amount of excipients/lubricant in Tote bin with the help of a tumbler

Flow Chart of Wet granulation:

Requisition for raw materials

Weighing

Mixing

Wet mixing

Sieving

Drying

Sieving

Mixing with lubricants

Compression

Filling & sealing

Packing

Flow Chart of Dry granulation:

Requisition for raw materials

Weighing

Sieving (if needed)

Mixing

Dry mixing

Drying

Sieving

Mixing with lubricants

Compression

Filling & sealing

Packing

Packaging within the shipping carton

Packaging within the shipping carton

Specification of Machineries:

Name of the machine Purpose1. Rapid Mixer Granulator To form wet granules2. Multimill Size reduction & sieving3. Fluid bed dryer Granules drying4. Cone Blender Granules blending with lubricants

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Fig:-Multimill Fig:- Fluid bed dryer fig:- Cone Blender

Compression Unit:

Fig: -Compression machine

After granulation, the granules are compressed to form tablets of specific weight, hardness and thickness. Tablets are compressed having 1/2 hopper and 16/28/36 multi punches where more then 10,000-50,000 tablets are compressed.

Tablet Manufacturing Problems:

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Capping and Lamination: Capping is the partial or complete separation of the top or bottom crown of a tablet from the main body of the tablet. Lamination is the separation of a tablet into two or more distinct layers.

Picking and sticking : In picking a small surface of the tablet materials is removed by the punches and adheres to the surface of punches, therefore the resulting tablet show a pitted surface instead of smooth surface. In sticking, granules adhere to the die wall and therefore the lower punch cannot move freely.

Mottling: It occurs in the colored tablet. The color does not distribute evenly throughout the tablet, zones of different shades appear on the surface of the tablet.

Weight Variation: Poor flow of the granules to the dies. It is due to Separation of granules, small and large granules, and poor mixing of lubricants.

Hardness Variation: Space between the upper and lower punches at the time of compression inappropriate pressure applied in the upper punches Excessive proportion of lubricant.

Coating Unit:

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Fig: - Coating machine

Some of the tablet dosage forms manufactured by Biopharma laboratory Ltd. are coated for the following reasons:

1. To improve the pharmaceutical elegance of the product by use of special colors.2. To mask the unpleasant taste, odor, or color of the drug.3. To control the release of the drug from the tablet.4. To protect physical and chemical protection for the drug

Classification of Coating:

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

Coating

Sugar coating Film coating Enteric coating

Aqueous coating Organic coating

Steps of FILM coating:Steps of FILM coating:

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Core Drying

Spray of coating solution

Polishing

Coating Solution Preparation:

Preparation of color Solution:

Complete procedure of tablet coating:

Pass through 80 mesh screen

Mix for 15 minutes in emulsifier

HPMC + Organic solvent(Methyle

nechloride, Methanol)

HPMC + water

Add talc

Mix for 15 minutes

Color solution

Mix and stir for 30 minutes

Coloring agent

Add opacifier (TiO2)

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Coating solution

Proper setting of inlet & outletTemperature, pan speed,

Air pressure distance of gunto the tablet bed

Place the compressed tabletin feeding pan

Dedusting

Spray of coating solutionby nozzle

Turning of the exhaust an & glower

Rolling the tablet

Simultaneous drying

Fig- Flow chart of tablet coating

Coating problem:

Logo bridging:

Possible causes1. Inadequate adhesion of the film coating surface characteristics of the products being coated (e.g. hydrophobic substrate).

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2. Inappropriate design of logo (e.g. too detailed or fine).3. Insufficient plasticizer in film/high internal stress.

Solutions1. Modify core formulation to include more hydrophilic ingredients (where possible/or increase

core porosity).2. Select a different logo design.3. Reduce spray rate/increase drying rate.

Logo in filling:

Possible causes1. Inappropriate design of logo.2. In filling of logo with spray dried coating material.3. Logo disappearance can be due to erosion of tablet surface around logo.

Solutions1. See solutions for logo bridging.2. Reduce erosion potential by either reformulating core. Changing logo design or modifying

curvature faces of tablet.’3. Reduce spray-drying potential by increasing spray rate.4. Reduce atomizing air pressure.5. Reducing inlet air temperature/air flow.6. Reducing distance between spray guns and surface of tablet bed.

Picking/Sticking:

Possible causes:1. Spray rate too high.2. Inadequate drying condition.3. Pan speed too low.4. Inadequate atomization of coating liquid.5. Poor distribution of coating liquid.

Solutions:1. Reduce spray rate.2. Improve drying conditions.3. Increase pan speed.4. Increase atomization air pressure/volume.5. Increase number of spray guns used.

Twinning:

Possible causes:1. Spray rate too high.2. Pan speed too low.3. Inappropriate tablet shape.4. Tacky coating formulation.5. Spray guns too close to tablet bed.

Solutions:1. Reduce spray rate and increase atomizing efficiency.

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2. Increase pan speed.3. Select new tablet shape that minimizes chances of flat surfaces coming into contact during

application of coating liquid (e.g. avoid capsule shaped tablet with straight edges or thick side walls).

4. Increase spray gun to tablet bed distance.

Core erosion:

Possible causes:1. Inherent softness or high friability of core. 2. Excessive pan speed in coating process.3. Spray rate too low.4. Low solids content of spray solution.

Solutions:1. Improve mechanical strength of core by increasing compaction force, modifying core

formulation process by which core is produced.2. Reduce pan speed.3. Increase spray rate.

Orange Peeling:

Possible causes1. Low mechanical strength of coating.2. Poor adhesion of coating to tablet surface.

Solutions1. Low spray rate.2. High drying rate.

Roughness:

Possible causes:1. Viscosity of coating liquid too high.2. Poor atomization of coating liquid.3. Drying condition excessive.4. Over wetting (causing coating to rub).

Solutions:1. Reduce solid contents of coating liquid.2. Increasing atomizing air pressure/volume.

Quality control and Quality assurance of Tablets:

The total QC refers to the process of striving to produce a perfect product by a

series of measures requiring an organized effort by there entire company to assure the

specified quality in each lot of drug products that are manufactured. Although QA

personnel are mainly responsible for assuring product quality, it involves many

departments and disciplines within a company. Quality must be built in all stages of drug products

including plant construction, product research development, purchasing of materials, production,

testing and inspection, labeling, storage and distribution. The essential qualities of good raw

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materials are BP/USP specifications, which include size, shape, thickness, weight, hardness,

friability, stability, dissolution time and potency.

Actually, eight quality parameters were taken for analysis in this research work namely- General appearance: There is no specification mentioned in the official pharmacopoeia for general appearance.

Weight variation test: There is ±5 specification mentioned in the British pharmacopoeia for weight variation.

Hardness: There is also no specification mentioned in the official pharmacopoeia for hardness. It is minimum 4 kg.

Potency determination: The specification for potency has been mentioned in the individual monograph. Riboflavin tablets should contain 95.0 to 115.0 percent of the prescribed or stated amount.

Disintegration test: For uncoated tablet disintegration time is 30 minutes or less.

Dissolution test: Specifications for riboflavin-dissolved not less than 75% with in 45 minutes.

Friability test: Conventional compressed tablets that loss the weight less than 0.5 to 1 % of their weight generally acceptable. The acceptable limit of weight loss could not be more than 1%.

Thickness test: Tablet thickness should be controlled within ±5% variation of a standard value.

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Capsule Department

Capsule Filling, Polishing & Checking Department:

This represents a multidiscipline having both antibiotic and non-antibiotic product has

distinctly been separated from each other for the convenience for production along with

corresponding manufacturing and packaging zones.

Subsection 1: Antibiotic Section.

Subsection 2: Non-Antibiotic Section.

Capsule Sizes (In Theory):

Empty gelatin capsules are manufactured in various sizes, varying in length, in diameter and

in capacity. The size selected for use is determined by the amount of material to be

encapsulated.

Sizes Volume(mL)

000 1.4

00 .95

0 .68

1 .50

2 .37

3 .30

4 .21

5 .13

Cleaning of capsule filling machine:

First fresh cloth is used to clean the machine

The jet powder is used to clean

Sufficient water is used to wash out the jet

Used DM water for final washing

Machine description:

1. Shell container

2. Channel which is movable

3. Turning table contain, 1. 24 upper bush, 2. 24 lower bush4. Holder 5. Dosing plate: Take granules from hopper.6. Rejection box7. Powder hopper8. Ejection pin plate9. Piston10. Funnel11. Closing and shell opening pin

Manufacturing procedure of capsule:

All Ingredient Blending

Empty Capsule Filling

Blister/Strip Sealing

Packing

In-process quality control of capsule:

The in- process control is made during the course of manufacture of capsule which aims to

ensure that product will comply with specification. Production does the IPC checks and

remains accountable for necessary corrective actions using procedures agreed with QA. The

performance of IPC checks are periodically monitored by QA or QC.

In Biopharma laboratory Ltd. the following parameters are performed for in-process

checks:

Processes In-process Checks

Dispensing Weighing and Recording

Mixing Time and Speed, uniformity of mixing and moisture content

Filing Uniformity of the Content, Time and Speed, avg. weight of

capsule, intactness of capsule shell.

Polishing & checking of filled Capsule:

After completing the filling process of capsules, it needs to polish and check for any types of filling errors such as cap or body defect, micro pores in capsule sealing etc. For this process, Biopharma laboratory Ltd. use both mechanical devices and also by manually. For checking purpose, it is very important for any types of capsule, because if a single defect capsule are goes to as finish product, it will became a issue for the quality of company, also the efficiency of works of any company.

Mechanical facilities are available in Biopharma laboratory Ltd. Capsule Department

Name Purpose

Double Cone mixer For blending and mixing filling materials for capsule.

Semi-Automatic Capsule Filling Machine For filling, sealing of capsules with filling materials

Polishing Apparatus For polishing of Tablet

Dry syrup Department:

Dry syrup:Introduction:

Dry syrup is the preparation that is formulated as dry powder but administered orally as liquid

dosage form. They are prone to hydrolysis during extended exposure of moisture. They are to

be reformulated by mixing with certain amount of boiled water and should be use up within

certain periods (5 days at normal temperature).

Physical plant design:

It is divided into two areas-

1. Manufacturing area

2. Filling and sealing area

Cleaning of dry syrup machine:

First fresh cloth is used to clean the machine

DM water used to clean

The jet powder is used to clean

Sufficient water is used to wash out the jet

Used DM water for final washing

Bottle washing:

1st Step: Tap water with high speed.

2nd Step: DM water with high speed

Bottle drying:

Inlet temperature: 60-80°C

Outlet temperature: 45-55°C

Try dryer:

Temperature: 130-140°C Drying

during: 90-120min

Bottle cooling condition:

Temperature: 28 CRelative humidity:60%

Manufacturing Flow Chart:

All excipient except color and flavor

Sieving properly

Blending 30min

Drying up to achieving required MC 0.3%, 4-5hrs within 95-100°C

Cooled above 50 C

Transferred to the proper room condition

Cooling and then crushing by Multi mill

Premix: add color, flavor, active ingredient

All premix are blended by V-blender

Blending on out Sugar + Premix

Filling of dry Syrup In bottle

Scaling of bottle

Checking

Ready for Packing

Normal Precaution:

1.During cooling the cooling temperature do not below 50°C.

2.Humidity must be strictly maintained.

Precautions Taken During Manufacturing of Dry Syrup:

♦ Manufacturing area and machineries are made clean as per respective SOP's before

starting of each production.

♦ Relative humidity and temperature of the production area are kept within 50% and

28°C respectively.

♦ The operators are skilled, healthy, physically fit and are properly dressed with clean

cloths, head cover and face cover. Hands and the starting materials intermediates or

finished products.

♦ Before and during manufacturing of a product the whole environment of the production

area are monitored by Q.C. personnel for maintaining proper condition of

production.

In-Process Quality Control of Dry Syrup:

The in- process control is made during the course of manufacture which aims to ensure that

product will comply with specification. The performance of IPC checks are periodically

monitored by QA or QC.

In The Biopharma laboratory Ltd. The following parameters are performed for in-process

checks:

Process In process checks

Dispensing Weighing and Recording

Mixing Time and Speed, uniformity of mixing and moisture content

Filling Uniformity of the Content, Time and Speed, average weight, pH

and leakage test (RoomTemperature:26°C.Humidity: 45%)

Machines used in Dry syrup section:

1. Double cone mixture

2. Automatic powder filling machine

3. Automatic sealing machine

Excipients used in dry-syrup:

1. Sugar: Sweetening agent

2. Colloidal silicon dioxide: Increase flow property

3. Na-citrate/citric acid: Buffering agent

4. Methyl paraben: preservative

5. Color: FDC grade (Lemon, orange)

6. Flavor: Raspberry, orange

7. Na-CMC: Only for Cefidoxim as a suspending agen

Liquid Department

Liquid Department:

The oral liquid pharmaceutical doses form is prepared for pediatric and geriatric patients. The oral liquid pharmaceutical doses form is very easy to swallowing than solid doses form. A drug administrated in solution is immediately available for absorption and in most cases, is more rapidly and efficiently absorbed than the same amount of drug administered in a tablet or capsules.The oral liquid section of Biopharma laboratory Ltd. consist of compounding area, filling & sealing area and packaging & packing area. The area is further subdivided as per antacid and non-antacid preparations. For the convenience and maintenance the oral liquid section is divided into six separate units, which are:

A. Oral liquid Unit:

Oral liquid compounding area Oral liquid filling and sealing area.

B. Antacid Unit

Antacid compounding area. Antacid filling and sealing area.

C. Central oral liquid packing Unit:D. Water heating and sucrose syrup preparation Unit: E. Bottle washing UnitF. Bottle drying room

During in plant training programme in Biopharma laboratory Ltd. we were observed two types of dosages form of oral liquid-

I. Suspension dosage form II.Syrup dosage form

I. Suspension Dosage Form:

Suspension is a oral liquid dosage form in which the active drug will be stay as suspended condition in the liquid media. All of those drugs which are not possible to formulate as syrup dosage form they are formulated as suspension dosage form. Biopharma laboratory Ltd. formulate the suspension dosage form to achieved the following desired advantages-

The water insoluble drugs can be formulated as suspension dosage form.

To reduce toxicity

To increase effectiveness

For economic benefit

For safety

PROBLEMS ASSOCIATED WITH THE SUSPENSION PREPARATION:

If colloidal mill is not properly setup

If avicel or CMC is stirring for long time due to decrease retain of principle size

If increase temperature, decrease viscosity than RM formed slugging

Due to increase particles separation, the potency of the product different in different parts of the suspension.

II. Syrup Dosage Form:

Syrup is an oral liquid dosage form in which the active drug will be completely dissolved in liquid media. Biopharma laboratory Ltd. formulate the syrup dosage form to achieved the following desired advantages-

To reduce toxicity

To increase effectiveness

For economic benefit

For safety

Total procedure before liquid filling in Biopharma laboratory Ltd.

DM water taken in steam jacket vat which contain coil. Temperature maintain 100C to140°C. This process used because less time consuming Pressure used 31b.

Sugar added

Mixing by heavy heat applying

Steam is applied

Boiling the mixture

Preservative added

Boiled for l hr

When preservative dissolve, then transferred into cold jacked tank by reducing Temperature

Cool at 35°C

Transfer into charge bed

Other excepients is mixed

Active ingredients is added

Finally mixed

Liquid filling and packaging procedure of oral liquid dosages form in Biopharma laboratory Ltd.

Bottle comes into washing chamber

First wash by tap water

2nd wash by DM water

Then dry at 130°C temperature

Bottle checking for defect visually

Bottle comes into filling machine

Bottle filled by filling machine

Bottle is capped

Filling bottle is checked visually

Bottle comes into labeling area

Bottle is labeled by labeling machine automatically

Labeled bottle packing

Then final packed into carton

Area for Bottle Washing:

There is a purified water plant in this area. Here bottle are washed by manually as well as semi automatic process.

Area for Packaging:

The overall environment was very nice, a rough figure of the environment was: Safety kits Central compression followed by negative pressure.

Sufficient lighting.

All equipments are stainless steel made & utensils like boxes, carriers are plastic made. Fly or mosquito destroyer. Central AC. Fire detector

All type of supply.

PROCEDURE OF FILLING & PACKAGING FOR ORAL LIQUID :

Biopharma laboratory Ltd.. oral liquid dosage form packaged throughout the following procedure-

Bottle washing

Drying

Filling

Cap placing

Cap sealing

Inspection

Bottle placing

Inserting into cartoon with leaflet

Inserting into outlet

Sealing and closing of outlet

Stacking in store

EQUIPMENT USED IN THE LIQUID SECTION:

1. Stainless steel jacket vat with stirrer2. Compounding vat with stirrer3. Stainless steel storage vat4. Stainless steel vats, buckets & hand stirrer5. Transfer pump6. Filter press machine7. Colloid mill8. Water purifier with UV monitor9. Bottle washing machine10. Rotary Bottle washing machine11. Automatic filling & sealing machine

PROBLEMS ASSOCIATED WITH ORAL LIQUID DOSAGE FORM : Microbial contamination Sedimentation Phase separation Cake formation Vortex formation during stirring Contamination with metal container or caps Color may be changed

OBSERVATION :

Cleanliness & environment are strictly maintained. Temperature, humidity aqurately maintained. Water purity aqurately maintained More purified water are used. Microbial contamination are maintained. Separate bottle washing and drying room. All machines are operated according to standard operating procedure (SOP). Machines are calibrated timely.

Semisolid Department

Cream and ointments are semisolid preparation for topical use. The whole

manufacturing process of cream or ointment is performed in a single room. But,

cream and ointment are manufactured in separate room.

Equipments Used In This Section:

Planetary mixer

Colloid mill (homogenizer)

Semi automatic tube filling and sealing machine

Vat, bowl, utensils

Balance

Cream:

It's a semisolid emulsion system with opaque appearance it may be water in oil or oil

in water type.

Steps of Cream Manufacturing in The Biopharma laboratory Ltd.

Weighing of ingredients

Preparation of water phase

Preparation, of oil phase

Mixing of oil and water phase

Addition of active ingredients

Mixing for 30 minutes

Homogenizing

Filling and sealing

Ointment:

This is a topical dosage form generally consisting of a hydrocarbon semisolid base containing dissolved or suspended drug. The IBN SINA Pharmaceutical Industry Ltd. manufactured only eye ointments. Ointments' are manufactured in aseptic zone because eye is very much sensitive to micro organism.

Steps Involving Ointment Preparation:

Melting of Ointment Base

Dispersion of Excipients

Mixing of Ointment Base and Excipients

Homogenizing

Filling and Sealing

Precautions Taken During Manufacturing of Cream and Ointment in the

Biopharma laboratory Ltd

Manufacturing area and machineries are made clean as per respective SOP's

before starting of each production.

Relative humidity and temperature of the production area are kept within 0%

and 28°C respectively.

The operators are skilled, healthy, physically fit and are properly dressed with

clean cloths, head cover and face cover.

Hand gloves are used to avoid direct contact between the operator's hands and

the starting materials intermediates or finished products.

Before and during manufacturing of a product the whole environment of the

production area are monitored by Q.C. personnel for maintaining proper

condition of production.

For ointment aseptic technique is followed during entry and working inside the

manufacturing room and transferring goods.

For ointment the room is fumigated by formalin & Na Nitrite on the preceding

(at least 12 hrs before production).

The filling & sealing of ointment is performed under laminar air flow.

Semisolid Products of Biopharma laboratory Ltd are:

Topical Corticosteroids :

XDERM Cream 10g (Clobetasol propionate USP 0.5% ) in Aluminum tube )XDERM Ointment 10 g (Clobetasol propionate USP 0.5% ) in Aluminum tube )

MEXIDERM Cream 15 g (Betamethasone valerate BP 0.1%) in Aluminum tubeMEXIDERM Ointment 15 g (Betamethasone valerate BP 0.1% ) in Aluminum tube

Topical corticosteroids :

SCAPER cream 15 g (permethrin BP 5%) in Aluminium tubeSCAPER cream 30 g (permethrin BP 5%) in Aluminium tube

Topical Anti-infective: NUBA Ointment 20g (Neomycin sulphate BP 0.5% & Bacitracin zinc BP 500 mg) in Aluminum tube

Topical Anti-infectives with corticosteroids: MEXIDERM-N cream 5g (Betamethasone valerate BP 0.1% & Neomycin sulphate BP 0.5%) in Aluminium tube MEXIDERM-N Ointment 5g (Betamethasone valerate BP 0.1% & Neomycin sulphate BP 0.5%)in Aluminium tube

Topical anti-fungal:ENAZOL PLUS cream 10g(Econazole nitrate BP 1% & Triamcinolone acetonide BP 0.1%)in Aluminium tube TERMIDER cream 15g (Terbinafine HCI INN 1%) in Aluminium Tube

Packaging Department

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 stripMaterials used for blister packing :

1. Polyvinyl Chloride [PVC],2. Polyvinyl dine chloride [PVDC]

3. Aluminum Foil,4. Alu-Alu Foil etc.

Steps of Blister packing: ---

Forming of pocket(By Hydraulic pressure or Temperature)

Filling Station(Channel / Feeder / Dosage-Channel)

Sealing (temperature station)

Cooling

Code embossing

Slitting

Punching Pneumatic actuator

Rejection of empty blister pack

Collection of blister pack

Trouble shooting :

Preheating problem – malleability

Forming problem

Sealing problem

Slitting problem – perforation

Loading problem

Air pressure

Scanner problem

Emboss problem

Heat exchanger Feeding problem

Chute channel

Gate transfer

Spiral

Brush

Printing Room:

PurposeTo print Batch No., Expire Date, and Mfg. Date.

Waste material destroying room :

Waste material such as finished products (tablets, capsules, injections, liquids etc), raw materials, and packing materials are destroyed in this room.

Quality Assurance Department

Quality Assurance:

Quality Assurance at a Glance:

Quality assurance Department

In process Quality ControlQuality Control Documentation Microbiology

Raw materials Q.C

Finished Product Q.C

Packaging materials Q.C

Stability Test

Quality:

The totality of features and characteristics of a product or service that bear on its ability to satisfy stated or implied needs.

Expectation of consumerQuality is = Performance QM (Quality Management)

Quality Assurance:

Quality Assurance is a wide-ranging concept, which covers all matters that individually and or collectively influence the quality of a product.

The impact of total quality maintenance is ~ Improved operating procedure Greater customer satisfaction Increased financial performance

The function of Q.A. in different section are given below:

1. Ware House:

Receiving raw material & packaging material only by visual inspection

Attachment of Quarantine & sampled tag by proper sampling rule

Sampling rule : If the no. of pack is within 24 than no. of sampled = N +1

Sampling for : - Assay Microbial test Retention sample

Released or rejection of raw materials & packaging materials

2. Production Area:

In liquid Only the physical inspection of Cleanliness Maintenance of BPR in production Packaging

In solid: Cleanliness of the area instrument by

Physical inspection In process QA checked -

a) Hardnessb) Thicknessc) Weight variation

3. Packaging Area:

During packaging QA checked:

Humidity of the packaging area Leak test (in case of bottle tilling) Appearance of tablet & cap Labeling of stripper & inner & outer cartoon

Research & Development

R & D

Research & development department deals with the following functions:

1. New product formulation.2. Reformulation.3. Reprocess.4. Trouble shooting. 5. Preparation of B.P.R. for a new product. 6. Development of existing product.

Development of a new product:

Step-1: Product information from marketing department along with necessary attributes such as

- Source - Sample - Q.C test (potency. LOD etc)

Step-2: Pre-formulation study of the active drug and excipient.- Chemical activity. - Function. - Interaction. - Boiling point. - Contraindication. - Moisture content etc.

Step-3: Collection of raw materials of active drug and excipients.

Step-4: Different trials for development of a stable, effective and active formulation.

Step-5: Drug administration formalities include:a) Submission of recipe to drugs administration which contains -

- Strength- Dosage form - Contraindication- Dosage form- Dissolution- Description- Precaution- Side effect- M.R.P.- Indication

b) Sample admission (if INN product)c) Approval of sample from drug administration and inclusion of D.A.R. and license no.d) Submission of Inclusion Dossier.e) Final approval for commercial production.

Step-6: Pilot trial and accelerated stability testing.

Step-7: Readjustment If necessary.

Step-8: BPR preparation if every aspect is satisfied which contains - Product name

- Code- Size- batch no- Theoretical yield- Batch size - Annexure etc.

Step-9: Transfer to commercial production. Development of existing products

Research & development department also deals with the development of existing product formulation.

Flow Chart of New Product Development Process:

Selection of new product

Development Annex

Trial the product formulation

Analysis method development

Review of formula and analytical method

Stability study

Review of formula and analytical method

Stability study

Again review

Pilot scale up

Process validation

Review of process

Preparation of master file

1st commercial batch

Fig- Flow chart of the new product development

Stability study for:-

Tablet

Potency study, Disintegration, Dissolution, Hardness, Bio-availability. Microbiological study, Pharmaceutical elegance, Flavoring agent, Weight variation

Solution Solubility, pH, Clarity, Physical appearance, Microbial contamination, Potency,

Color and flavorSuspension

Rate of sedimentation, Rate of re-dispersion, Rate of absorption, Potency, pH, Micro-contamination, Color, Flavor, Sweetening

Emulsion Phase separation, pH, Color, Flavor, Potency

Injectable Sterility, Clarity, pH, Potency, Physical appearance, Optical rotation

Ointment

Phase inversion, Physical appearance, Smoothness, Potency, Color

ACCELARATED STABILITY TESTING FOR PHARMACEUTICAL PRODUCTS ARE GIVEN BELOW-TEMPERATURE RELATIVE

HUMIDITY (%)TIME EQUIVALENT

DURATION60˚C 21days 2 years37˚C 95 6 months 2 years45˚C 75 3 months 2 yearsAmbient 6 months 2 years

Objective: a) Increasing the quality of the product.

b) Prevention of any type of problem existing in the product. c) To save time and cost. d) Increasing the patient acceptance.

The project file:

It contains project related every papers such as

Recipe Product attributes Lab tried process records Stability study protocol and report Approved product data sheet Sales forecast Standard packaging material sample Process validation protocol record Related correspondence.

Warehouse Department

Warehouse:

Involved areas:

- Raw material store - Packaging material store - Finished product store

Terminology:Sampling :

The process of taking a small portion from a lot for test and analysis to show the quality of the whole lot. The purpose of sampling and subsequent testing is to provide an effective check on the quality of the product or substances being processed.

Sampling quantity :

Sampling quantity should be the double of one complete test.

Lot: A batch or number of batches in a consignment. Batch:A quantity of the product or material which is processed in one run following manufacturing USP.

Campaign:A campaign means no. of batches manufactured without any interruption or product change.

Handling:The term handling means checking according to invoice and other documents during receiving of the materials.

Preservation: It means the materials are stored in different conditions according to its nature of stability i.e. to maintain a specific temperature and relative humidity.

Dispensing:It means the materials are supplied to the production areas by weighing according to the proper document and release it from the RM store.

Quarantine:The term quarantine means the materials is not ready for use and it is under test after receiving. So a quarantine label is attached to the container.

FIFO:The term FIFO stands for First In First Out.

Re-Test:The term re-test means the samples are needed to be repeated analysis for identification according to previous documentation and it has to be done either 3/6/12 months.

Materials sampling plan:

The material sampling plan is done on the basis of FIFO system i.e. First In First Out. For active ingredients, every container and for excipient, (n+1) containers are sampled (where n = total no. of the containers.)

Ware House Activities:

Diagrammatic representation (Related to raw & packaging materials)

ARRIVAL OF MATERIALS

IN VOICE CHECKING

PHYSICAL INSPECTION & RECEIPT

DISCREPANCY REPORT

QUARANTINE STORAGE

LOG BOOK ENTRY

MRR FOR IMPORTED ITEMS

Q.A. SAMPLING

Q.C.

Q.C release for production or Q.C rejects the raw/packing materials

Ware House Activities:

Diagrammatic representation (Related to finished goods delivery to I & I service & export activities)

Solid PackingLiquid PackingAntibiotic formulation

Finished Products

Physical Checking and verification complying the quantity mentioned in the transfer note

Ware House

With Tow copies of transfer noteAfter receiving one copy returns to Respective Dept.Ware House File

QA release

VerificationVerify the previously received quantity with QA released Quantity

Transfer the finished goods to I & I services

With 4 copies of dispatch Note &

With 3 copies of customs VAT Chelan (MUSAK-11)

Vehicle provided by I & I Services

I & I Services --MIS Dept.-A/C Dept.-Ware House

I & I ServicesCustoms OfficeWare House

Ware House Activities (Export activities):

Export Order

Apply to Customs

Delivery to C & F Agent

Receipt of Airway bill Submission to custom

DepositTreasury deposit

from A/C Up to date of current account register (MUSAK-18)

Purchase Register Entry (MUSAK-16)

Rebate from bill of entry, cashReceipt, local purchase VAT Chelan etc.

VAT payment 15%

Monthly return report with supporting paper submitted to customs office copy to - A/C dept.

Monthly reconciliation statement of Finished goods to-MIS dept Copy to - A/C dept.

- Prod. plan dept.(fact)

Product Management Department (PMD)

Work of PMD :

1. Suggestion of new product2. Provide technical information on different product of international & local market3. Prepare product strategies to explore business opportunity4. Prepare product profile of suggested new product5. Development of promotional materials (e.g.- literature, pad, product monograph)6. Preparing packaging insert7. Development of foil & other developing matter of packaging materials8. Preparing the theme of literature, pad, etc with suggested handling9. Ensure promotional campaign10. Development of advertising campaign for souvenir, journal etc11. Preparing display materials for stall in different conferences12. Contribution in training program13. Checking the quality of printing materials related to PMD14. Contribution in product development committee meeting15. Any other work as desired by the management

Feasibility Study:

1. Generic name2. Therapeutic group3. Total market size of therapeutic group (unit)4. Total market size of the molecule (unit)5. Growth of molecule6. Growth of therapeutic group7. Take wise market size of the group8. Take wise market size of (top 10) molecule9. Total number of companies in our country10. Name of the brand leader11. Seals value of the brand leader12. Product profile

Product brief:1. Product name, Generic name 2. Market strength3. Dosage form4. Unit pack size5. Sample size6. Diagram, W/V, Coating, Color7. Level, Insert8. MRP9. PVC/ closer10. license number11. Exp date12. Seals budget13. Package specification

14. Brand leader

Product developing plan (PDP)

1. Market feasibility studies2. Recipe3. Pack4. Manufacturing License5. Raw materials

6. Packing materials7. Price approval8. Product promotion9. Clinical trials 10. Launching program

Current Good Manufacturing Practice (cGMP)

BASIC REQUIREMENTS OF CURRENT GOOD MANUFACTURING

PRACTICE

The basic requirements of cGMP are :

a) the manufacturing process is defined before the commencement of any activity

b) the necessary facilities are provided including :

i) Appropriately trained personnelii) Adequate premises and spaceiii) Suitable equipmentiv) Correct materialsv) Approved procedures

vi) Suitable storage and transport

c) Procedures are written in instructional form, in clear and unambiguous language, and are applicable to the facilities provided.

c) operators are trained to carry out the procedures correctly.

d) records are made during manufacture (including packaging) to demonstrate that all the steps required by the defined procedures were in fact taken and that the quantity and quality produced were those expected.

e) records of manufacture and distribution which enable the complete history of a batch to be traced are retained in legible and accessible form.

g) a system is available to recall from sale or supply any batch of product ,should that become necessary.

h) Complaints about marketed products arc examined and measures taken to prevent recurrences, if appropriate.

QUALITY ASSURANCE OF Pharmacy UTICALS:

Table 1. Air classification system for manufacture of sterile products:

Maximum numberof particles

permitted per m3 Maximum number of-------------------------- viable microorganisms

Grade 0.5-5um >5um permitted per m3

A 3500 none less than 1(Laminar-airflow

workstation)B 3500none 5C 3500002000 100D 350000020000 500

The various operations of component preparation (such as containers and closures), product preparation, filling, and sterilization should be carried out in separate areas within the clean area.

Clean areas for the production of sterile products arc classified according to the required characteristics of the air, in grades A, H, C, and D (see Table 1).

To obtain air of the required characteristics, methods specified by the national authorities should be used. It should be noted that:

Laminar-airflow systems should provide a homogeneous air speed of about 0.30m/s for vertical flow and about 0.45 m/s for horizontal flow but precise air speeds will depend on the type of equipment.

In order to reach the B, C, and D air grades, the number of air changes should generally be higher than 20 per hour in a room with a good airflow pattern and appropriate HE PA (high-efficiency particulate air) filters.

Low values for contaminants are reliable only when a large number of air samples are taken.

• The guidance given for the maximum permitted number of particlescorresponds approximately to the United States Federal Standard 209E(1992) as follows. Class 100 (grades A and B), Class 10000 (grade C), andClass 100000 (grade D).

It may not always be possible to demonstrate conformity with particular air standards at the point of fill when filling is in progress, owing to 'the generation of particles or droplets from the product itself.

Each manufacturing operation requires an appropriate air cleanliness levelin order to minimize the risks of particulate or microbial contamination ofthe product or materials being handled. Section 17.5 gives the minimum airgrades required for different manufacturing operations. The particulate andmicrobiological conditions given in Table 1 should be maintained in the zone immediately surrounding the product whenever the product is exposed to the environment. These conditions should also be achieved throughout the background environment if no personnel are present in the processing area, and if the standards all for any reason it should be possible to recover the conditions after a short "clean-up" period. The utilization of absolute-barrier technology and automated systems to minimize human interventions in processing areas can produce significant advantages in ensuring the sterility of manufactured products. When such techniques are used, the recommendations in these supplementary guidelines, particularly those relating to air quality and monitoring, still apply, with appropriate interpretations of the terms "workstation" and "environment".

Manufacture of sterile preparations

Manufacturing operations are here divided into three categories: first, those in which the preparation is sealed in its final container and terminally sterilized; second, those in which the preparation is sterilized by filtration; and third, those in which the preparation can be sterilized neither by filtration nor terminally and consequently must be produced from sterile starting materials in an aseptic way. Area grades as specified in sections 17.5.1-17.5.3, must be selected by the manufacturer on the basis of validation runs (e.g., sterile media fills).

Terminally sterilized products

Solutions should generally be prepared in a grade C environment in orderto give low microbial and particulate counts, suitable for immediate filtration andsterilization. Solution preparation could be allowed in a grade D environment ifadditional measures were taken to minimize contamination, such as the use ofclosed vessels. For parenterals, filling should be done in a laminar-airflowworkstation (grade A) in a grade C environment. The preparation of other sterileproducts, e.g., ointments, creams, suspensions, and emulsions, and filling ofcontainers should generally be done in a grade G environment before terminalsterilization.

Sterile filtered products

The handling of starting materials and the preparation of solutions shouldbe done in a grade C environment. These activities could be allowed in a grade Denvironment itl additional measures were taken to minimize contamination, suchas the use of closed vessels prior to filtration. After sterile filtration, the productmust be handled and dispensed into, containers under aseptic conditions in agrade A or B area with a grade B or C background respectively Other sterile products prepared from sterile starting materials in an aseptic way

The handling of starting materials and all further processing should be done in a grade A or B area with a grade B or C background respectively.

Personally the minimum number of personnel required should be present in clean areas; this is particularly important during aseptic processes. Inspections and controls should be conducted from outside the areas as far as possible.

All personnel (including those concerned with cleaning and maintenance) employed in such areas should receive regular training in disciplines relevant to the correct manufacture of sterile products, including reference to hygiene and to the basic elements of microbiology. When outside stall who have not received such training (e.g., building or maintenance contractors) need to be brought in, particular care should be taken over their supervision.

Staff who have been engaged in the processing of animal-tissue materials or of cultures of microorganisms other than those used in the current manufacturing process should not enter sterile-product areas unless rigorous and clearly defined decontamination procedures have been followed.

High standards of personal hygiene and cleanliness are essential, and personnel involved in the manufacture of sterile preparations should be instructed to report any condition that may cause the shedding ol abnormal numbers or types of contaminants; periodic health checks for such conditions are desirable, Actions to be taken about personnel who could be introducing undue microbiological hazard should be decided by a designated competent person.

Outdoor clothing should not be brought into the clean areas, and personnel entering the changing rooms should already be clad in standard factory protective garments. Changing and washing should follow a written procedure.

The clothing and as quality has to be adapted to the process and the workplace, and worn in such a way as to protect the product from contamination.

Wrist-watches and jewellery should not be worn in clean areas, and cosmetics that can shed particles should not be used.

Clothing should be appropriate to the air grade of the area where the personnel will be working. The description of clothing required for each grade is given below.

Grade D: The hair and, where appropriate, beard should be covered. Protective clothing and appropriate shoes or overshoes should be worn.

About Department of Pharmacy, Noakhali Science and Technology University !

Universities of a country are the place where the leaders of a nation are created. A university is the highest place of education where the students find the world class education and a door to enter the world of immense success. And the world is heading towards a new destination of science and technology. As why science and technology universities play vital role to create the quality graduates. These graduates will be the key of nation. To build a high quality society the Engineers and Technologist have to give their best. 

Noakhali Science and Technology University was established with immense hope for maintaining the high quality education. Since its establishment year 2006, it is

running without any session jam and student politics. This University family is fully determined to gain its ultimate goal of success. 

In our In-plant training report, we would like to add some information about our department. This is due to we are the students of 1st batch of our department. So it is our responsibilities to inform about our department.

Noakhali Science and Technology University (NSTU) is one of the 6 public universities in Bangladesh which provides Bachelor of Pharmacy Course for 50 students per year. We can proudly say that we are the quality output of our department. Because we found all types of facilities from our department, which are needs to make us quality. Our department made available all high status full-time faculty members for us. All instruments and lab equipments are available and of high quality. Some lab facilities are dissolution tester, tablet friability tester, single punch tablet compressor, manual capsule filling, plenty of reagents facilities, UV spectrophotometer, electronic balance, incubator, Laminar air flow, centrifuge machine etc.

Conclusion

We, the three students of Noakhali Science & Technology University feel very proud of us because of our presence in this Pharmaceutical industry, Biopharma Laboratories Limited. Our academic curriculum would be insufficient if we were not here. But why we feel proud, the cause is, first of all this is the fast growing pharmaceutical industry in Bangladesh that maintains QUALITY first. And this is the watchword of Biopharma Laboratories Limited. We would like to say that we have achieved our best knowledge here by having the opportunity to have our training here. So we are very much THANKFULL to the Authority of Biopharma Laboratories Limited. We think we have known the term QUALITY very efficiently and wherever we will go for the job we will try to maintain quality in each and every sector for the product.

Appraisal for all the officers and employees of this industry who give their intellectual thinking and labor for this industry and make this industry going upwards.

We have learned many others thing from here, one of them was discipline. Biopharma Laboratories strictly follows the discipline, which is the key to their success. The officers here try heart and soul to lead the company forward.

Last of all we are specially thanking to the Plant Director for his active help in our four weeks in-plant training in the factory. We hope that it is the starting of everlasting relationship between Biopharma Laboratories Limited and Noakhali Science and Technology University. We hope that it will continue in future.

We as well as Noakhali Science & Technology University are thanking the Authority of Biopharma Laboratories Limited.

We wish Biopharma Laboratories Limited long live.