Beruflich Dokumente
Kultur Dokumente
Submitted to:
Md. Saiful Amin Director plant, Biopharma Laboratories Limited.
Submitted by:
1. Fahad Hussain
.
ID # ASH 0603014
DEPARTMENT OF PHARMACY NOAKHALI SCIENCE & TECHNOLOGY UNIVERSITY SONAPUR ,NOAKHALI -3802. BANGLADESH website: www.nstu.edu.bd
Contents
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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
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.
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.
Introduction
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.
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 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
THEIR PRODUCT CATEGORIES INCLUDE:
Products:
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
ANTIBIOTICS
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)
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 capsule Flucloxacillin BP 500 mg capsule Flucloxacillin BP dry powder for suspension 60ml (125mg /5ml ) Flucloxacillin BP dry powder for suspension 100ml (125mg /5ml)
CIPCIN
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)
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 /5ml Cephradine BP dry powder for suspension 100ml (250mg /5ml) Cephradine BP paediatric drops 15ml (100mg /ml )
SUPRALEX
Cefuroxime BP 250mg capsule Cefuroxime BP 500mg capsule Cefuroxime BP powder for suspension 100ml (125mg /5ml)
BESTCEF
Cefixime USP 200mg capsule Cefixime USP dry powder for suspension 37.5ml (100mg /5ml) Cefixime USP dry powder for suspension 50ml (100mg /5ml)
MEXTIL
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)
BIOTRIM DS
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)
ANTI-FUNGAL DRUGS
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)
ANTI - HISTAMINES
BIOCIN Chlorpheniramine maleate BP 4mg tablet Chlorpheniramine maleate BP syrup 100ml(5mg/5ml)
LORFAST
ANTI - EMETIC
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 )
AVERT
ANTHELMINTICS
AZOLE Albendazole USP 400mg chewable tablet Albendazole USP suspension 10ml (200mg/5ml)
BIOTREX
BIOCID MH
BIOCID PLUS
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ACIN
(Ranitidine USP 150mg film coated tablet Ranitidine USP 300mg film coated tablet
INPRO
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
LAXATIVE DRUG
LACTU Lactulose 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
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BIOVIT -E
BIRON PLUS
FIVITA
Elemental Calcium USP 500mg ( as Calcium carbonate USP ) film coated tablet
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ORTHOCAL -D
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)
NSAIDs
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
BRONCHODILATORS
SALBU Salbutamol Salbutamol Salbutamol Salbutamol
BP BP BP BP
2mg 4mg
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EXPECTORANTS
film
coated
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
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
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 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
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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.
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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
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Friability Leak test Dissolution Chemical test for both Raw & Finished Products:
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.
materials
Finished
products
Q.C
Packaging
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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 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
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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
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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 follows1. Microbial limit test 2. Sterility test 3. Antibiotic bioassay 4. Bacterial antitoxin test 5. Environmental monitoring 6. Water test
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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.
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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
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.
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
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
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Fig:-Multimill
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.
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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. 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
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Coating solution
Proper setting of inlet & outlet Temperature, pan speed, Air pressure distance of gun to the tablet bed
Dedusting
Coating problem:
Logo bridging:
Possible causes 1. Inadequate adhesion of the film coating surface characteristics of the (e.g. hydrophobic substrate). products being coated
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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.
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 causes 1. Low mechanical strength of coating. 2. Poor adhesion of coating to tablet surface. Solutions 1. 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.
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 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 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.
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Capsule Department
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
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
Processes
In-process Checks
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.
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:
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).
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
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.
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 The Biopharma laboratory Ltd. The following parameters are performed for in-process checks:
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%)
2. Colloidal silicon dioxide: Increase flow property 3. Na-citrate/citric acid: Buffering agent 4. Methyl paraben: preservative
5.
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
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.
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
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
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
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
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.
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
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
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],
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:
Purpose To print Batch No., Expire Date, and Mfg. Date.
Quality Assurance:
Quality Assurance at a Glance:
Quality assurance Department
Quality Control
Documentation
Microbiology
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 consumer Quality is =
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
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
R&D
- 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.
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
Solution
Suspension
Rate of sedimentation, Rate of re-dispersion, Rate of absorption, Potency, pH, Micro-contamination, Color, Flavor, Sweetening Phase separation, pH, Color, Flavor, Potency
Emulsion
Injectable Ointment
Sterility, Clarity, pH, Potency, Physical appearance, Optical rotation Phase inversion, Physical appearance, Smoothness, Potency, Color
ACCELARATED STABILITY TESTING PRODUCTS ARE GIVEN BELOWTEMPERATURE 60C 37C 45C Ambient RELATIVE HUMIDITY (%) 95 75 TIME 21days 6 months 3 months 6 months
FOR
PHARMACEUTICAL
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.
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.
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
Diagrammatic representation (Related to finished goods delivery to I & I service & export activities)
Solid Packing Liquid Packing Antibiotic formulation
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
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.
(fact)
Work of PMD:
1. 2. 3. 4.
5.
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
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
Procedures are written in instructional form, in clear and unambiguous language, and
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.
f)
g)
h)
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
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.
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.