Download - In Plant Traning on Bio Pharma[1].Doc Final
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.