An Industrial Training Report at Biogenetic Drugs Pvt.ltd. Baddi (h.p.)
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AN INDUSTRIAL TRAINING REPORT AT BIOGENETIC DRUGS PVT.LTD. BADDI (H.P.)
Duration: - 2 months From 15 July, 2009 to 15 September, 2009
RAJASTHAN UNIVERSITY OF HEALTH SCIENCES, JAIPUR.
Mr. N.MARKUNDE GENERAL MANAGER
PANKAJ KUMAR B.PHARMA (FINAL YR.) REGIONAL COLLEGE OF PHARMACY, JAIPUR
Every mature individual in professional life is keenly aware of his sense of ineptness to many people who have stimulated and influenced his intellectual development. Ordinarily, this feeling is expressed in customary gesture of acknowledgement. Therefore, it seen as a right to acknowledge my gratitude with sense of veneration to the Almighty GOD and various people who helped me during the course of Industrial training. Their valuable guidance and wise direction have enabled me to complete my practical training. Their valuable guidance and wise direction have enabled me to complete my practical training in systematic and smooth manner. I am also quite thankful to Sh. Tarachand Kumawat. Principal Regional College of Pharmacy who guided me during my training at BOIGENETIC DRUGS PVT.LTD. I am also thankful to Mr. M.B.GOYAL, BOIGENETIC DRUGS PVT.LTD who allowed me to be a part of traning and completing it successfully. A part of thanks is attributed to Mr.N.MARKUNDE, Director, Mr.M.L.SHARMA, Production Manager for giving assistance during tranining. I am also thankful all towards all other technical staff for giving their advice during training.
CONTENTS 1. Introduction 2. Company Organization 3. Working of a Pharmaceutical Industry 4. Raw Material Storage Area 5. Production Department • • • •
Tablets Capsules Oral Liquid Powder
6. Recent Products 7. Quality Control 8. Software Study-Criscon and OasisLIMS
CHAIR PERSON:MANAGING DIRECTOR
- Mr. Vinod Kalani
- Mr. P.C. Tapariya
ORGANIZATION OF QUALITY CONTROL:DIRECTOR
- Mr. Subhash Gupta
- Mr. Rajesh Sain
- Mr. Radhe Shyam Gupta
- Mr. Ashok Maheshwari
ORGANIZATION OF PRODUCTION:PRODUCTION MANAGER
- Mr. Sandeep Nikam
- Mr. Mukesh Sharma
Working of a Pharmaceutical Industry Pharmaceutical Industry: - A Pharmaceutical Industry is an industry where life saving drugs is prepared with excessive care and standards. So it is very different from other industries.
Cycle of Formulation Unit:1. Plant Development:• Plant and Premises (a) Location and Surrounding (b) Water Supply (c) Sewage and Drainage System • Building and Premises (a) Walls and floors (b) Adequate Working Space (c) Logical Placement of Equipments and Material (d) Air Handling Unit • Method and Machine Validation (a) Process Validation (b) Performance Qualification (c) Installation Qualification (d) Design Qualification (e) Operational Qualification •
Standard Operating Procedure and Standard Testing Procedure (SOP & STP) (a) Purpose (b) Scope in Industry (c) Area of Operation (d) Responsibility (e) Procedure • Manpower Training and Development (a) To update with new technology (b) To minimize the possibility of errors (c) To minimize the risk of cross contamination (d) Awareness of Personnel Hygiene (e) Awareness of cleanliness and sanitation
2. Material Management:• Vendor Selection and Development • Purchase System • Status of the received material • Assuring Water System 8
3. Storage and Issue:• Control over Approval and Release of Materials • Dispensing of Material 4. Production:• Manufacturing Process control and record (a) MFR:- Master Formula Record (b) BMR:- Batch Manufacturing Record (c) BPR:- Batch Process Record • Release by QC/IPQC • Environment Monitoring • Quality Audit of all record before release • Complete and Satisfactory QC check before release • Monitoring of finished goods storage condition 5. Sales and Distribution:• Commercial invoice for Distributors 6. QA Activity:• Conducting Accelerated and Periodical Stability Studies • Handling of Complaints, Rejection, Reprocessing and Recall • Process and System Revival
RAW MATERIAL STORAGE AREA The store department of JPW is divided in two compartments, one for excisable and other for non excisable goods. The product is sent to the receiver along with one copy of bill which has information related to Name, Amount, Tax and final cost of the product. The transporters consignment and a copy of bill are stored in commercial store. Entries of in coming and outgoing goods are made in the same ledger. There are following auditors assigned for inspections of records are:-
1. Internal auditors- Check the ledger daily. 2. Excise auditors- Time to time check, especially for excisable goods. 3. Statutory auditors- Representatives of state govt., check through year. The store of JPW is divided into following rooms:1. Cold room – In which aluminum foil, empty capsules, loose drugs and vitamins are stored. Temperature of this room is 15`c to 20`c. 2. Dispensing Room 3. Drug store Room 4. Excepient Room 5. Under test material store Room 6. Packaging material store Room. ITEMS IN RAW MATERIAL STORE:a. Acetic Acid I.P. b. Chloroquine Phosphate I.P. c. Colloidal Silicon Dioxide I.P. d. Essence Spearmint e. Gum Xanthin I.P. f. Propylene Glycol I.P. g. Sodium Benzoate I.P. h. Sodium Saccharine I.P.
TABLET MACHINES / EQUIPMENTS:GRANULATION:1. 2. 3. 4. 5. 6. 7.
Mass Mixer 110 kg. Capacity Oscillating granulator Multi-Mill Fluid Bed Drier Tray Drier Sifter Weighing balance 10kg capacity
COMPRESSION:1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11.
16 Station rotary tablet compression machine Air Conditioner Punch and Die storage cabinets Dehumidifier, Portable Disintegration time test apparatus Hardness tester, Monsanto, Pfizer type Hygrometer + Thermometer Vernier caliper (Japan) Tablets Counters (different sizes) Strip packing machine Blister packing machine
COATING:1. 2. 3. 4. 5. 6. 7. 8.
Coating pan 36” Coating pan 18” Polishing pan Hot plate Hygrometer Spray gun (750ml) Fire extinguisher Air Conditioner
PACKAGING:1. Blister Pack Machine 2. Stripping Machine
CAPSULE MACHINES / EQUIPMENTS:-
BETA LACTAM GROUP DRUGS: 1. 2. 3. 4. 5. 6. 7. 8.
Mass Mixer, 65 lit. Capacity Cone blender 25 lit. Capacity 300 holes capsule filling machine (size 0) 300 holes capsule filling machine (size 2) Air conditioner Dry powder/granules filling machine Balance Dehumidifier 14
9. Hygrometer + Thermometer 10. Capsule counters (different sizes) 11. Disintegration time test apparatus 12. Capsule Inspection table
OTHER THEN BETA LACTAM GROUP DRUGS: 1. Mass Mixer, 45 kg. Capacity 2. 200 holes capsule filling machine (size 0) 3. 200 holes capsule filling machine (size 00) 4. Air conditioner 5. Balance 6. Capsule counters (different sizes) 7. Dehumidifier 8. Dry and wet bulb 9. Semi automatic capsule filling machine
ORAL LIQUID MACHINES / EQUIPMENTS:1. Jacketed manufacturing Tank (Steam) 2000 ltrs. 2. Manufacturing Tanks 1000 ltrs. 3. Storage tanks 650 ltrs. 4. Storage tanks 500 ltrs 5. Storage tanks 450 ltrs. 6. Storage tanks 250 ltrs. 7. Homogeniser 8. Stirrer 9. Colloidal mill 10. Rotary bottle washing machine 200 head 11. Horizontal filter press 12. Volumetric filling machine (double head) 13. Volumetric filling machine (four head) 14. Bottle visual inspection unit 16
15. ROPP cap sealing machine (four head) 16. ROPP cap sealing machine 17. D.M. Water plant CA-60 18. D.M. Water plant CA-33/1 19. H.D.P.E tank 300 ltrs. 20. Air Curtain 21. Fire extinguisher 22. Isectocutor 23. Bottle Labeling machine DIVISIONS OF ORAL LIQUID: A. The liquid section of JPW is sub divided into following sections:1. Bottle Washing Chamber 2. Formulation Chamber 3. Filling, Sealing and labeling Chamber 4. Packing B. Demineralised water plant: - Demineralised water is used in all pharmaceutical preparations and it can be prepared by ion exchange method. There are following columns in this section: • Sand filter • Regeneration tank for acid (HCL) • Cation tank / Acidic resin tank • Anion tank / alkaline resin tank • Regeneration tank for alkali (NaOH)
POWDER MACHINES / EQUIPMENTS:1.Octagonal Blander 2.Pouch filling and sealing machine 3.Sifter 4.Weighing balance 5.S.S. Vessels 6.Scoops 7.Air conditioner
ORS prepared in JPW has following basic requirements 1. Dehumidifier 18
2. Dust Extractor 3. Air Conditioner (Temp.- 15`-20`c) 4. Weighing Machine
The contents of ORS are as follows:1. Dextrose I.P. 2. Sodium Chloride I.P. 3. Potassium Chloride I.P. 4. Sodium Citrate I.P. 5. Aerosil 6. Sodium Saccharine 7. Flavor Orange D.C.
1. TABLETS: b. ALERCOLD TABLETS Each uncoated tablet contains Cetrazine Hydrochloride BP 5 mg, Phenylpropanolamine Hydrochloride BP 10 mg, Paracetamol IP 500 mg c. ARTECRIS TABLETS Each uncoated tablet contains Artesunate 50 mg c. AZICRIS TABLETS Azithromycin 500 mg d. AZICRIS TABLETS Azithromycin 250 mg e. OCRIS TABLETS Each film coated tablet contains Ofloxacin USP 200mg f. ROBINAC TABLETS Each enteric coated Tablet contains Diclofenac Potassium BP 50mg Serratidopeptidase (as enteric coated granules) 10 mg g. SPASCRIS TABLETS
Each uncoated tablet contains Mefenamic Acid IP 250 mg, Dicyclomine Hydrochloride IP 10mg h. SURLOX TABLETS Each film coated tablet contains Ciprofloxacin Hydrochloride IP Eq. to Ciprofloxacin 250 mg i. ELCET TABLETS Each film coated tablet contains Levocetrazine Dihydrochloride 5 mg j. NEUROCRIS TABLETS Each uncoated tablet contains Mecobalamine 500 mg
2. SYRUP a. ALERKOF SYRUP Each 5 ml contains Chlorpheniramine Maleate IP 2 mg, Dextromethorphan Hydrobromide IP 10 mg, Phenylpropanolamine Hydrochloride IP 12.5 mg b. CRIMOX-DRY SYRUP Each 5 ml contains Amoxicillin Trihydrate IP c. APICRIS SYRUP Each 15 ml contains Cyproheptadine Hydrochloride IP (anhydrous) 2 mg, Vitamin B1 IP 2.5 mg, Vitamin B2 IP 2.5 mg, Vitamin B6 IP 0.75mg, Niacinamide IP 22.5 mg, D-Panthenol IP 2.5mg d.
ASVIT SYRUP Each 5ml contains Vitamin B1 IP 2.5mg, Vitamin B2 IP 1mg, Niacinamide IP 25 mg, Vitamin B12 IP 2.5mg. 3. CAPSULE
EZEE 20 CAPSULE Each capsule contains Omeprazole IP 20 mg (as enteric coated granules)
b. CRIMOX-250 CAPSULE Each capsule contain Amoxicillin Trihydrate IP Eq. to Amoxicillin 250 mg d. CRIMOX-500 CAPSULE Each capsule contain Amoxicillin Trihydrate IP Eq. to Amoxicillin 500 mg e. LANCRIS-30 CAPSULE Each capsule contains Lansoprazole 30 mg (enteric coated pellets)
f. EZEE 20 PLUS CAPSULE Each capsule contains Domperidone BP 10mg (coated pellets), Omeprazole IP 20 mg (as enteric coated granules)
3. SUSPENSION a. NIMWIN-P SUSPENSION Each 5 ml contains Nimesulide BP 50 mg, Paracetamol IP 125 mg b. NIMWIN SUSPENSION Each 5 ml contains Nimesulide BP 50 mg c. OCRIS SUSPENSION Each 5 ml contains Ofloxacin USP 50 mg d. OCRIS PLUS SUSPENSION Each 5 ml contains Ofloxacin USP 50 mg, Ornidazole 125 mg
QUALITY CONTROL The concept of quality control refers to the process starving to produce a perfect product by a series of measures requiring an organized effort at every stage in production. Quality Control ensures product stability keeping the compliance to GMP going and assures that product will retain all there claim till they are consumed. The sample should be inspected for defects which could affect the performance or stability of the product. Functions of quality control are:-
1. To prepare the detailed instructions for each test and analysis. 2. To release or reject • Each batch of raw material • Semi finished/finished products • Packing & labeling material 3. To evaluate the conditions under goods are store. 4. To evaluate the quality & stability of product. 5. To establish and revise control procedure and specifications.
Procedure for Quality Control: - Step involved are:1. Raw Material Analysis: - After recording raw material in store division in store division quality control dept is called for sampling for testing its quality and purity as per pharmacopoeias. Where the raw material stand in its quality. The quality control passes the raw material for production. For inspection two sample from each of tablet, capsule and liquid section are selected. One is meant for testing and another one is for storage. As the sample reaches the quality control lab, it is recorded in the SAS register and a sampling slip is put in the sample. 2. In Process Control: - There is a real and significant difference between a finished product compounding standard and the manufacturing process. For quality assurance the sample size usually taken as:A. B. C. D. E.
40 Tablet (min.) 2 Liquid preparation (sealed) 2 Sterilized preparation (sealed) 40 Capsules 2 Powder preparations (packed)
Under in process control the sample is collected from immediately processed bulk. The process of sending sample to quality control is very burdensome. So in order to case this process, convenient equipment is available in the mfg. dept. near to the site or activity. 1. 2. 3. 4.
Electronic balance – for testing weight variation. Hardness tester (Tablets) Measuring Cylinder – To measure volume of liquid preparation. Inspection chamber – To inspect antiforeigner particle or turbidity in solution. 5. D.T. Machine 6. Friabilator The immediate recording of result is made in register is made in register with other information e.g. name of the product, Batch No., Date, time etc. Method used to check the quality 1. 2. 3. 4.
Electronic method Solvent Extraction Method Spectrophotometer Method Chromatographic Method
Program adopted for observing GMP and to build quality of the product
There are many tests that are used for quality assurance of various formulations as:(A) For Tablets From manufacturing batch of tablets 30-40 tablets are sent Q.C. to test them for:1. Weight Variation: - A tablet must contain the proper amount of drugs. For testing weight variation a sample of 10 tablets are taken hourly and weighted on electronic or physical balance. The tablets must have acceptable average weight. 2. Friability Testing: - This is an internal standard test. This test is essentials for consumer acceptance. Tablets require certain amount of strength to withstand mechanism shocks on handling packing, and shipping. 3. Hardness testing: - Hardness testing determines the cursing strength of tablets. To check the hardness the tablet is placed between two finger of tester both horizontally and vertically and force is applied. The hardness of tablet must not be less than 4 kg, and not more than 6 kg. 4. Disintegration time: - This is the time on which breakdown of tablet in GIT occurs. To test D.T. a disintegration test apparatus is used that is set as per pharmacopeias. Starch paste is employed as disintegrating agent who may draw water in to the tablet, causing tablet to swell and burst apart. There are internal standards for D.T. i.e. 15minutes. If tablet disintegrates within 10 minutes then the batch of tablet is contained otherwise batch is cancelled. 5. Dissolution time: - As the tablet break down in small particles it should offer a grater surface area to the dissolved media. Dissolution apparatus is a 8 paddled machine and temperature, speed and time can be adjusted. 6. Strip leakage test: - To test whether the strips are leak-proof or not. (B) For Capsules 1. Weight Variation: - A sample of 10 tablets is hourly taken and average weight is taken. Then each capsule is weighted individually and compared with average weight. • •
Not content less then 300mg ---- 7.5 Not content more then 300mg ---- 10%
2. Dissolution time :- Same as for tablet 3. Disintegration time :- Same as for tablets (C) Sterile Preparation 1. Clarity test
2. Sterility test RECORD MAINTENANCE IN Q.C.:For record maintenance in Q.C. there are separate recording registers, having columns for the name, batch No, date & result for the product being analyzed e.g.:• One register for in process control analysis • One register for raw material analysis • One register for finished and packed product analysis Daily entry is made to avoid any error. A part form this, for incoming of reagent in Q.C. another record is maintained. MICROBIOLOGICAL ANALYSIS: - It include following instruments – • Hot air oven • Autoclave • Incubator • Aseptic room