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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



No 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20

Subject Preface Acknowledgement Introduction Product list Administration Quality Control Department Microbiology Section Tablet Department Capsule Department Dry Syrup Department Liquid Department Semi-solid Department Packaging Department Quality Assurance Department Research & Development Warehouse Product Management Department (PMD) Current Good Manufacturing Practice (cGMP) About NSTU Pharmacy Department Conclusion

Page 3 4 5 6-15 16 17-20 21-22 23-33 34-37 38-41 42-47 47-50 51-53 54-56 57-60 61-65 65-66 67-70 71 72


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.

ACKNOWLEDGEMENT All praise to Al-mighty Allah who has given us the opportunity to undertake and complete this inplant 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.


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. Its 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.

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 to help products their growth. (new Our therapeutic training programs molecules include ) training at . work BIOPHARMA values to all of its employees and makes effort through Quality of Work Life ( e .g. cGMP training ) as well as professional seminars. Thus, we have a good management

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

Antibiotics Anti-Protozoal-Drugs Anti-Fungal-Drugs Anti-Emetic Anti-Histamines Antacid & Anti Ulcerants Anthelmintics Anti-Oxidant Laxative Drug NSAIDs Vitamins & Minerals Expectorants Bronchodilators Anti Depressants & Anxiolytics Anti-Diabetic Drugs Dermatological Products Cardiovascular Drugs


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

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)


Flucloxacillin BP 250 mg capsule Flucloxacillin BP 500 mg capsule Flucloxacillin BP dry powder for suspension 60ml (125mg /5ml ) Flucloxacillin BP dry powder for suspension 100ml (125mg /5ml)

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


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


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


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


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


Cefuroxime BP 125 mg tablet Cefuroxime BP 250 mg tablet Cefuroxime BP powder for suspension 70ml (125mg /5ml ) BIOTRIM Cotrimoxazole (Sulphamethoxazole BP 400mg & Trimethoprim BP 80 mg ) tablet Cotrimoxazole BP dry powder for suspension 60ml (SMZ 200 mg/ 5ml & TMP 40 mg /5ml)


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

EROSA Erythromycin USP 250 mg film coated tablet Erythromycin USP 500 mg film coated tablet Erythromycin 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)

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


BIOZYL Metronidazole BP 400mg film coated teblet Metronidazole BP suspension 60ml (200mg/5ml)

BIOCIN Chlorpheniramine maleate BP 4mg tablet Chlorpheniramine maleate BP syrup 100ml(5mg/5ml)


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

ESOGUT Domperidone BP 10 mg film coated tablat Domperidone 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 )


Meclizine HCI USP 50mg tablet

AZOLE Albendazole USP 400mg chewable tablet Albendazole USP suspension 10ml (200mg/5ml)


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


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


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


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



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


Omeprazole BP 20mg capsule Omeprazole BP 40mg capsule

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

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

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

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



BIOVIT Vitamin B - Complex capsule Vitamin B - Complex syrup 100 ml Vitamin B - Complex syrup 200 ml Multivitamin 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


Vitamin -E BP 200mg film coated chewable tablet

BIORON Ferrous sulphate BP syrup (200ml/ 5ml )


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

Ascorbic acid BP 250mg chewable tablet


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


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



Elemental Calcium USP 500mg as Calcium carbonate +Vitamin D USP 5mcg ) film coated tablet
ZINGA DS Zinc sulphate BP syrup 100 ml (zinc BP 10mg / 5ml)

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

TOP Ketoprofen 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

SALBU Salbutamol Salbutamol Salbutamol Salbutamol


2mg 4mg

tablet tablet 60ml syrup (2mg/5ml) 100ml syrup (2mg /5ml)



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

MUCUT Bromhexine HCI BP syrup 100ml ( 4mg /5ml )


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




GLUCOSTAT Gliclazide BP 80mg tablet


CALM Clobazam 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



EMLON Amlodipine BP 5mg tablet Amlodipine BP 10mg tablet ETNOL Antenolol BP 50mg tablet Antenolol BP 100mg tablet

LOPO Losartan Potassium INN 25mg film coated tablet Losartan Potassium INN 50mg film coated tablet


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

Topical corticosteroids:
SCAPER cream 15 g (permethrin BP 5%) in Aluminium tube SCAPER 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 tub

Topical: 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. 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. Bulk density Sulphated ash Assay Physical test for raw material Identification of appearance Color of the material Appearance of solution In solution ppt is present or not Melting point Solubility Loss on drying Optical rotation Physical test for finished product Appearance Hard ness Thick ness Finishing of coating material Claimed weight


Friability Leak test Dissolution Chemical test for both Raw & Finished Products:

Disintegration Weight variation

1. pH test 2. Optical rotation 3. 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: Raw Stabilit y Calibration Microbiological testing




Analytical development & validation


Water & Effluent

Documentation & routine analysis


Protocol for quality control assignment:





Final approval


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 container Sample 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 spectrophotometer 3. UV-Visible spectrophotometer 4. Karl-Fischer titration 5. pH meter 6. M.P.apparatus. 7. USP dissolution test apparatus


8. USP disintegration test apparatus 9. Chemical Balance 10. Drying oven 11. Microscope 12. Hot Plate 13. Centrifuge 14. Oven 15. Vortex mixer 16. Humidity Control Chamber 17. Water Bath 18. Leak Test Apparatus 19. Tab Density Taster 20. Tablet Tester including diameter, thickness, and hardness test of tablet 21. 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


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 follows1. Microbial limit test 2. Sterility test 3. Antibiotic bioassay 4. Bacterial antitoxin test 5. Environmental monitoring 6. Water test

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


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


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


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

Flow Chart of Dry granulation:

Requisition for raw materials Weighing Sieving (if needed) Mixing Dry mixing Drying

Sieving Sieving Mixing with lubricants Compression Filling & sealing Packing Packaging within the shipping carton Mixing with lubricants Compression Filling & sealing Packing Packaging within the shipping carton

Specification of Machineries:
Name of the machine 1. Rapid Mixer Granulator 2. Multimill 3. Fluid bed dryer 4. Cone Blender Purpose To form wet granules Size reduction & sieving Granules drying Granules blending with lubricants



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:


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:


Fig: - Coating machine Some of the tablet dosage forms manufactured by Biopharma laboratory Ltd. are coated for the following reasons: 1. 2. 3. 4. 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

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:


Core Drying Spray of coating solution Polishing

Coating Solution Preparation:

HPMC + Organic solvent(Methyle ne chloride, Methanol)

HPMC + water Mix for 15 minutes in emulsifier Add talc

Mix for 15 minutes

Add opacifier (TiO2)

Pass through 80 mesh screen

Preparation of color Solution:

Coloring agent Mix and stir for 30 minutes Color solution

Complete procedure of tablet coating:


Coating solution

Proper setting of inlet & outlet Temperature, pan speed, Air pressure distance of gun to the tablet bed

Place the compressed tablet in feeding pan


Spray of coating solution by nozzle

Turning of the exhaust an & glower

Rolling the tablet

Simultaneous drying Fig- Flow chart of tablet coating

Coating problem:
Logo bridging:
Possible causes 1. Inadequate adhesion of the film coating surface characteristics of the (e.g. hydrophobic substrate). products being coated


2. Inappropriate design of logo (e.g. too detailed or fine). 3. Insufficient plasticizer in film/high internal stress. Solutions 1. 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 causes 1. 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. Solutions 1. 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.

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.

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.


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 causes 1. Low mechanical strength of coating. 2. Poor adhesion of coating to tablet surface. Solutions 1. Low spray rate. 2. High drying rate.

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


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 Hardness:

for weight variation.

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 Friability test:

minutes. 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.


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: Subsection 2: Antibiotic Section. 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 000 00 0 1 2 3 4 5

Volume(mL) 1.4 .95 .68 .50 .37 .30 .21 .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 bush 4. Holder 5. Dosing plate: Take granules from hopper. 6. Rejection box 7. Powder hopper 8. Ejection pin plate 9. Piston 10.Funnel 11.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:


In-process Checks

Dispensing Mixing Filing

Weighing and Recording Time and Speed, uniformity of mixing and moisture content 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 Double Cone mixer Semi-Automatic Capsule Filling Machine Polishing Apparatus Purpose For blending and mixing filling materials for capsule. For filling, sealing of capsules with filling materials For polishing of Tablet

Dry syrup Department:

Dry syrup:
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 areas1. 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: 60-80C Outlet temperature: 45-55C

Try dryer:
Temperature: 130-140C Drying during: 90-120min

Bottle cooling condition:

Temperature: 28 C Relative 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 95-100C 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 50C. 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 28C 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 production. by Q.C. personnel for maintaining proper condition of

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 Dispensing Mixing Filling

In process checks Weighing and Recording Time and Speed, uniformity of mixing and moisture content Uniformity of the Content, Time and Speed, average weight, pH and leakage test (RoomTemperature:26C.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:


Sugar: Sweetening agent

2. Colloidal silicon dioxide: Increase flow property 3. Na-citrate/citric acid: Buffering agent 4. Methyl paraben: preservative

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 Unit F. Bottle drying room

During in plant training programme in Biopharma laboratory Ltd. we were observed two types of dosages form of oral liquidI. 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 to140C. 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 35C 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 130C 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 stirrer 2. Compounding vat with stirrer 3. Stainless steel storage vat 4. Stainless steel vats, buckets & hand stirrer 5. Transfer pump 6. Filter press machine 7. Colloid mill 8. Water purifier with UV monitor 9. Bottle washing machine 10. Rotary Bottle washing machine 11. 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


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


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 28C 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 For ointment the room is fumigated by formalin & Na Nitrite on the preceding

manufacturing room and transferring goods. (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 tube

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

Topical corticosteroids :
SCAPER cream 15 g
(permethrin BP 5%) in Aluminium tube

SCAPER 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 strip Materials 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)

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:
Purpose To 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

Quality Control


In process Quality Control


Raw materials Q.C

Finished Product Q.C

Packaging materials Q.C

Stability Test

The totality of features and characteristics of a product or service that bear on its ability to satisfy stated or implied needs. Expectation of consumer Quality 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)Hardness b) Thickness c)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


Research & development department deals with the following functions:

1. 2. 3. 4. 5. 6. New product formulation. Reformulation. Reprocess. Trouble shooting. Preparation of B.P.R. for a new product. 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 Solubility, pH, Clarity, Physical appearance, Microbial contamination, Potency, Color and flavor



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


Injectable Ointment

Sterility, Clarity, pH, Potency, Physical appearance, Optical rotation Phase inversion, Physical appearance, Smoothness, Potency, Color




EQUIVALENT DURATION 2 years 2 years 2 years 2 years

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

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.

A batch or number of batches in a consignment.

A quantity of the product or material which is processed in one run following manufacturing USP.

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

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

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.

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

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.

The term FIFO stands for First In First Out.

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


Ware House Activities:

Diagrammatic representation (Related to finished goods delivery to I & I service & export activities)
Solid Packing Liquid Packing Antibiotic formulation

Finished Products Ware House

Physical Checking and verification complying the quantity I & I Services - mentioned in Dept. -MISthe transfer note I & I Services Vehicle -A/C Dept.provided by I & I Customs Office Services -WareHouse Ware House

Transfer the finished goods With Tow copies of transfer note to I one copy returns After receiving& I services to With 4 copies of Respective Dept. dispatch Note & Ware House Verification File Verify the previously received With 3 copies of customs VAT quantity with QA released Chelan (MUSAK-11) QA release

Deposit Treasury deposit from A/C

Up to date of current account register (MUSAK-18) 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.

Purchase Register Entry (MUSAK-16) Rebate from bill of entry, cash Receipt, local purchase VAT Chelan etc.

Ware House Activities (Export activities):

Export Order Apply to Customs Delivery to C & F Agent Receipt of Airway bill Submission to custom


Product Management Department (PMD)

Work of PMD:
1. 2. 3. 4.

6. 7. 8. 9. 10. 11. 12. 13. 14. 15.

Suggestion of new product Provide technical information on different product of international & local market Prepare product strategies to explore business opportunity Prepare product profile of suggested new product Development of promotional materials (e.g.- literature, pad, product monograph) Preparing packaging insert Development of foil & other developing matter of packaging materials Preparing the theme of literature, pad, etc with suggested handling Ensure promotional campaign Development of advertising campaign for souvenir, journal etc Preparing display materials for stall in different conferences Contribution in training program Checking the quality of printing materials related to PMD Contribution in product development committee meeting Any other work as desired by the management

Feasibility Study:
1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. Generic name Therapeutic group Total market size of therapeutic group (unit) Total market size of the molecule (unit) Growth of molecule Growth of therapeutic group Take wise market size of the group Take wise market size of (top 10) molecule Total number of companies in our country Name of the brand leader Seals value of the brand leader Product profile

Product brief:
1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. Product name, Generic name Market strength Dosage form Unit pack size Sample size Diagram, W/V, Coating, Color Level, Insert MRP PVC/ closer license number Exp date Seals budget Package specification Brand leader

Product developing plan (PDP)

1. 2. 3. 4. 5. 6. 7. 8. 9. 10.

Market feasibility studies Recipe Pack Manufacturing License Raw materials Packing materials Price approval Product promotion Clinical trials Launching program

Current Good Manufacturing Practice (cGMP)

a) b) the manufacturing process is defined before the commencement of any activity the necessary facilities are provided including : i) ii) iii) iv) v) vi) c) Appropriately trained personnel Adequate premises and space Suitable equipment Correct materials Approved procedures Suitable storage and transport

Procedures are written in instructional form, in clear and unambiguous language, and

are applicable to the facilities provided. d)


operators are trained to carry out the procedures correctly. 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. records of manufacture and distribution which enable the complete history of a batch to be traced are retained in legible and accessible form. a system is available to recall from sale or supply any batch of product ,should that become necessary. Complaints about marketed products arc examined and measures taken to prevent recurrences, if appropriate.





Table 1. Air classification system for manufacture of sterile products: Maximum number of particles permitted per m3 -------------------------0.5-5um >5um 3500 3500none 3500002000 350000020000 none

Grade A (Laminar-airflow workstation) B C D

Maximum number of viable microorganisms permitted per m3 less than 1 5 100 500

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 (highefficiency 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 particles corresponds approximately to the United States Federal Standard 209E (1992) as follows. Class 100 (grades A and B), Class 10000 (grade C), and Class 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 level in order to minimize the risks of particulate or microbial contamination of the product or materials being handled. Section 17.5 gives the minimum air grades required for different manufacturing operations. The particulate and microbiological 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 order

to give low microbial and particulate counts, suitable for immediate filtration and sterilization. Solution preparation could be allowed in a grade D environment if additional measures were taken to minimize contamination, such as the use of closed vessels. For parenterals, filling should be done in a laminar-airflow workstation (grade A) in a grade C environment. The preparation of other sterile products, e.g., ointments, creams, suspensions, and emulsions, and filling of containers should generally be done in a grade G environment before terminal sterilization. Sterile filtered products The handling of starting materials and the preparation of solutions should be done in a grade C environment. These activities could be allowed in a grade D environment itl additional measures were taken to minimize contamination, such as the use of closed vessels prior to filtration. After sterile filtration, the product must be handled and dispensed into, containers under aseptic conditions in a grade 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.


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.