A Industrial Training Report

Industrial Training Report IntroductionPlethico Pharmaceuticals Limited, kalaria, Indore Company Owner : Mr. Shashikant Patel (Chairman & M.D.) Mr. Chirag S. Patel (Director & CEO) Ms. Gauravi Parikh (Executive Director) Mr. Hemant Modi (GM & COO) Mr. Rajiv Bedi (GM Export) Mr. Sharad Kumar (GM Production) Location: Site Address: Plethico Pharmaceuticals limited. Place: Kalaria village dharawara Indore (M.P.) 1. HISTORY PLETHICO PHARMACEUTICALS LIMITED is a group of companies engaged in the manufacturing of ethical Pharmaceuticals for more than 40 years. On implementation of the new Industrial Policy in 1963, for Indian entrepreneurs, by the Government of India, a small pharmaceutical company M/s. Plazma Laboratories Pvt. Ltd. was founded in 1963, in partnership by our Chairman, Shri Bhaskar A. Patel, a Pharmacy graduate and young entrepreneur. The company was initially engaged in the manufacturing and marketing of products required by Government Stores, Hospitals and Nursing Homes. In 1967-68 under their expansion programme, another new partnership concern under the name of M/s. Ethico Drugs & Chemicals Mfg. Co. was started under the guidance & supervision of a young technocrat, Shri Shashikant A. Patel for manufacturing and marketing of patent & proprietary medicines. Among the few products produced & marketed First Time in India by this company were Minicycline Capsules (Doxycycline), Timizol range of products, namely tablets, capsules & suspension, etc. (Timizol is Co-trimoxazole) & Anti T. B. range of products containing Rifampicin, Isoniazid, Ethambutol & Pyraziramide under the trade name of Montonex Forte & Montorip etc. Plethico Pharmaceuticals Private limited Page 1 Industrial Training Report In 1983-84 a new and modern manufacturing unit was established in Manglia a place about 16 Km away from Indore city on Mumbai Agra road. This company was named as M/s. PLETHICO PHARMACEUTICALS (A Partnership concern) for manufacturing of tablets, capsules & dry syrup etc. as per the Good Manufacturing Practices. In 1996-97, this partnership concern was converted into a Public Limited Company under the name M/s PLETHICO PHARMACEUTICALS LIMITED. Looking into the progress of the company, a new world-class manufacturing facility is created on Indore-Ahmedabad road, about 16 Km from Indore city at a place called Dharavara. The plant is designed to meet Indian, WHO, MHRA, MCC, TGA, MCA & US FDA requirements. The new Pharmaceutical plant at Dharavara has manufacturing facilities for tablets, capsules, injections, liquid oral preparations, ointments and neutraceuticals. It also has full - fledged Quality Control laboratory. This new plant also has a dedicated herbal product division along with a completely automatic Lozenges manufacturing plant using latest German technology & a PET bottle-manufacturing unit using a latest state of art ‘Direct Heat Conditioning Stretch-Blow Molding’ Machine. In addition to India in the OTC segment, Plethico is also a leading player in the Commonwealth of Independent States (CIS), Africa, South East Asia, and Latin America and in the GCC for its Travisil range of products. With the recent acquisition of Natrol – a leading manufacturer and marketer of branded nutritional products in the United States, Plethico has now expanded its global footprint to the regulated markets of the United States and Europe. Plethico Pharmaceuticals Private limited Page 2 Moldova. 1971-80 Up-gradation and expansion of Manufacturing Facilities Establishment of a nationwide marketing and distribution network. Azerbaijan and Kyrgyzstan. ranked amongst the TOP 5 Anti-TB companies in India. 1991-2000 Diversification into Herbal & Natural formulations with scientific and modern manufacturing plant for Herbals set up at Indore. Marketing and Distribution Joint Plethico Pharmaceuticals Private limited Page 3 . The company pioneered the launch of Doxycycline and Cotrimoxazole in the Indian market. Indore. Ultra modern fully integrated plants set up for manufacture of PET bottle (AOKI. MILESTONES 1963-70 The beginning of the group activity This decade saw the establishment of the company's first formulation plant. as per the requirements of WHO GMP. Travisil. Introduction of branded formulations in various categories.Plethico brand topped the Anti-Malarial segment of quinines. at Indore. Germany). to manufacture a wide range of allopathic formulations. Diabetes and Syndrome X developed with in-house research and clinical evidence. 1981-90 An ultra modern formulation plant was established at Manglia. (AC Neilson 2002). Cardiovascular & Cough & Cold segments. Japan) and hard boiled candies (Klockner Hansel GmBH. an indigenously developed herbal Cough & Cold product became a star performer in the entire CIS market. with subsidiaries in Russia. with its revolutionary 3/4 drug fixed dose Anti-TB combinations. manufacturing tablets.The company acquired a marketing and distribution chain in the CIS. Innovative branded formulations were introduced and established in Anti-malarials. The company re-oriented its business strategy and launched its Consumer Healthcare Division in India. India.Industrial Training Report 2. near Indore. 2000-2005 Commissioning of the state of the art formulation manufacturing plant at Kalaria. Kazakhstan. Capsules and Liquid Orals. Introduction of novel herbal products for Hepatocare. Anti-tubercular. Ukraine. Major thrust into International Marketing. Plethico. UK MHRA and US FDA. Madhya Pradesh.  Setting up a R&D and formulation and development centre.  Setting up its corporate office in Mumbai.  Acquiring stake in domestic herbal/OTC/nutraceutical company or a brand. 2006 . Establishment of Plethico Africa Limited (Kenya).  Setting up a WHO GMP (World Health Organisation Good Manufacturing Practices)compliant plant in Jammu & Kashmir and land to be used for organic farming of importan herbs.2008 Plethico raises Rs 110 crore from IPO to part finance:  The up-gradation of its Kalaria plant to make it UK MHRA compliant. Africa and Latin-America. a manufacturing Joint Venture to cater to the East African market. Plethico Pharmaceuticals Private limited Page 4 .Industrial Training Report Ventures formed in South East Asia. Antiinflamatory Antibiotic/antibacterial amloz Amloz-at Amloz-L Diitiaz Aciran Tablets Tablets Tablets Tablets Tablets Cardiovascular Antiulcer / antacid Page 5 . PRODUCT PROFILE This site manufactures Pharmaceutical Products like:  Tablets  Capsules  Oral Liquids  Injectables  Ointments and Creams  Herbal Products  Neutraceuticals Table: 1 Category of drugs are manufactured in the location Name of the Drug Product Name Chloroquine Phosphate Paraquin P-Quin Quinine sulphate RezQ Tablets/ Suspension Antimalaria / Injection Tablets/ Suspension / Injection Arteether Paracetamol Nimesulide Diclofenac Sodium Ciprofloxacine HCl Ofloxacine Co-trimoxazole Gentamycine Rezart-E Pletin Nimez Maxi Cebect Gonocin timizol Zentotic80 Amlodipine besylate Amlodipine besylate &atenolol Amlodipine &lisinopril Diltiazem HCl Ranitidine HCl Plethico Pharmaceuticals Private limited Dosage Forms Category Injection Tablets/ Suspension Tablets/ Suspension Tablets/ Injection Tablets Tablet Tablets/ Suspension Injection Antipyretic.Industrial Training Report 3. Analgesic. Mg.triplodine&pseudoepedrine Recofast plus Codiene mallaite B-complex with vitamin-c&zinc Folic acid Mebendazole Metronidazole Delirek Plelic Bendam Emigyl Capsules Tablets Tablets/ Suspension Tablets/ Suspension Anti-diarrheal.simethicone Paracetamol.anti amoebic helmintics Herbal hepato protective agent Herbal hepato protective agent Mometasome furoate Terbinafine 1% octogen Previl Metacort Capsules/suspension Herbal Capsules/suspension Cream Dermatological &anti Vitamins&minerals phosphate &cholrpinramin planokuf Syrup Tablets Cough&cold Dermafine Cream Plethico Pharmaceuticals Private limited Page 6 .Mg. Coolz Capsules Tablets Tablets/ Suspension trisilicate.Industrial Training Report Omeprazole Pantaprazole Dried aluminium Pleom Pantoz hydroxide. hydroxide. Herbal Research unit focuses on developing standardized.  Security 4. phytochemistry. They are engaged in various activities that enable us to bring out the most efficacious herbal products to consume. dosage form/ Novel Drug delivery system (NDDS). DEPARTMENTS  Research and development  Formulation & Development  Quality Assurance  Quality Control  Stores (RM/PM)  Distribution  Production  Engineering  Personnel & Adm.  Stabilizing of existing dosage forms based on stability studies as per International Guidelines. pharmacognosy.  Development of marker based standardized dosage forms. Procuring authentic plant material. analytics and pharmacology. clinically proven and safe herbal products for therapeutic and cosmetic use.  Spearheading improvements in existing formulations to meet growing regulatory demands. Methods of extraction Plethico Pharmaceuticals Private limited Page 7 .Industrial Training Report 4. pharmacological evaluation in laboratory models. as well as consultants having a long association with the herbal drug industry. formulation development and modern clinical trials are an integral part of the herbal product development activities.1 FORMULATION & DEVELOPMENT Plethico takes pride in a team of dedicated scientists with expertise in botany. Some of the activities are:  Research on new herbs/ existing herb ingredients for better therapeutic usage.  Maintenance of segregated areas for different herbal materials and of appropriate environmental conditions.Industrial Training Report Commercially herbal crude materials are extracted by water as the extraction medium. based on the type of material to be extracted  Supercritical or Liquid CO2 extraction 4.  Production areas controlled for dust. essential oils and resins. manufacturing and storage that differ from those used for conventional pharmaceuticals. particularly in light of growing regulatory stringency and the international dimensions of trade.  Hot extraction. which include materials derived from leaves.  Distillation. herbal products often require procedures for their processing. I learned that each major stage of the manufacturing process is validated to Plethico Pharmaceuticals Private limited Page 8 . At Plethico. herbal products differ from conventional pharmaceutical products in that they are prepared from herbal substances. Some of these are:  Storage facilities with quarantining of incoming herbal matter to prevent the spread of microorganisms.2 QUALITY ASSURANCE Quality assurance is a major challenge. In Plethico. since manufacturing of substandard medicines result in prolonged treatment for patients. bark. While the general principles of GMP apply for all types of pharmaceutical products. effective and of good quality. and therefore present a degree of complexity. The self-implied stringent quality standards are followed to ensure that all the products being manufactured are consistently safe. fumes and vapors generated by the processing of these substances. Because of their unique origin. seeds. drug resistance and increased incidence of adverse effects.  Cleanliness of equipment to avoid microbiological contamination as per US FDA GMP norms. which is achieved at Plethico by following methods:  Cold maceration. I took pride in stringent following of specially developed protocols for hygiene.  Hot percolation. sanitation and processing that are specific to herbal products. etc. rightly so. Standardization of herbal products at Plethico includes the following steps:  Authentication of the plant material  Determination of Foreign matter  Organoleptic evaluation  Macroscopy and Microscopy  Determination of extractive values  Group analysis  Chromatographic profile matching  Marker compound analysis  Contaminant analysis Few of advanced instruments used for the herbal products apart from pilot scale batch size machines are:  High Pressure Liquid Chromatography (HPLC) from Waters  Atomic Absorption Spectroscopy for analysis of Heavy metals  Gas Liquid Chromatography (GLC) for analysis of Pesticides  Thin Layer Chromatography (TLC) for detection and chemical analysis of certain phytochemicals such as Alkaloids.e. 4.  Chemical Analytical Laboratory  Microbiological Laboratory  Instrumental Analysis Laboratory  Sterility Testing Section  Control sample and record room  Other supporting facilities. i.4.3 QUALITY CONTROL Standardization is done to ensure that every batch of a product is consistent with respect to quality and results in beneficial therapeutic effect. to ensure total Quality. etc. Safety and Efficacy of each and every herbal product.Industrial Training Report ascertain that the finished products comply with all quality and design protocols. The Quality Control and Assurance Laboratories have following facilities. Tannins. and consistently meet their specifications. BRIEF DESCRIPTION OF MICROBIOLOGICAL ACTIVITY: Bacterial endotoxin test Plethico Pharmaceuticals Private limited Page 9 .. 4.  Well-equipped shop floor IPQC Laboratories. 125 EU/ml). and the photometric techniques.  Reconstitute the lyophilized LAL reagent with LRW as per the COA. In gel clot technique. which equals or exceeds the reagent labelled sensitivity represented by the symbol lambda (). A positive response in the gel clot test indicates the Endotoxin in the sample. Reconstituted LAL reagent ideally should be stored in a refrigerator at 2-8°C during intermittent use for up to 24 hours. take 50μl of water sample to be tested. This MOA is based on gel clot technique. Keep the stopper in a clean surface without touching the inner portion of the stopper. Take depyrogenated tubes in duplicate for sample and mark them as 1. LAL reagent can be frozen and thawed only once. which is based on gel formation. Arrange TT of negative and positive controls in separate rows of the stand. Testing Procedure: Take 2 depyrogenated test tubes for each negative and positive control. The tubes are then observed for gel clot formation. 3… or with batch no.Industrial Training Report  Principle: There are two types of techniques for this test: the gel-clot techniques. In case of water sample (Water for Injection and Pure Steam Condensate).  Tap on the rubber stopper to collect the LAL powder in the bottom of the vial. transfer 100μl of water sample in 2 depyrogenated TT and add 100μl Lysate to them (when testing at EL = 0. of the sample.25 EU/ml. store LAL reagent in freezer upto 28 days. mix gently avoiding formation of air bubbles and keep aside till clear solution is not visible. Plethico Pharmaceuticals Private limited Page 10 .  Carefully remove the stopper. When testing at EL = 0. Add the reagents as mentioned below in the table 04. otherwise. equal volume of LAL & diluted test specimen are mixed in tubes and incubated at 37+1°C for 60 + 2 min. Mix gently and incubate the tubes in heating block at 37 °C ±1 for 60 + 2 min. Do not shake.  Stop the re-constituted vial. 50μl of LRW and add 100μl Lysate. Record the results in the respective formats. 2. Storage: Lyophilized LAL reagent should be stored at 2-8°C. Reconstitution of LAL reagent:  Remove Aluminium seal of the Lysate vial without opening the rubber stopper. BRIEF DESCRIPTION OF MAJOR PRODUCTION EQUIPMENT  Major production equipments are as follow:  Mechanical vibrating sifters Plethico Pharmaceuticals Private limited Page 11 .D.A media Incubate it for 72 hrs at 30-37c Incubate it for 48 hrs incubate it for 72 hrs at 30-37c at 30-37c Incubate it for 48 hrs At 30-37c Flow Diagram of Microbial Limit Test 4.S. Record the results and other details in respective format.A media Incubate it for 48 hours at 42-44c transfer 1. A result is negative.F.d +20-25ml of SCA Mix & incubate it for 5 days at 30-35c Mix & incubate it for 7 days at 20-25c Incubate it for 24 hour at 37c E.A media C. if an intact gel is not formed.C 1st p. coli salmonella S. aurigenosa Transfer 1ml in M.V.B media Directly streaked it on Directly streaked it on M.B media Then streaked it on M.Industrial Training Report After incubation remove the tubes gently from the heating block and slowly invert through 180°C and note the observations.aureus p.0 ml in R.C T.L.S.E.A media Then streaked it on X. Microbial Limit Test Pour plate method Add 10gm of sample/10ml of sample in 90ml of SCDM media Place it on the shaker at 35-37c for ½-1 hour transfer 1ml into the petridish in duplicate T. If a firm gel has formed that remains in place after inversion. record the results as positive.B.5.d +20-25 ml of SCDA 2nd p. 6. -. P. I. Spectrophotometer. BRIEF DESCRIPTION OF LABORATORY EQUIPMENTS: Major Analytical instruments in Quality Control Department are as follows:  H. Plethico Pharmaceuticals Private limited Page 12 . unit (Stretch blow moulding)  Lozenges Forming Line  Ointment/Cream Line 4. T.L. etc.  Vial washers  Vial filler & Sealer  PET bottle mfg.  F.Visible Spectrophotometer. R. C. – With Auto Sampler  U.V.Industrial Training Report  Rapid Mixer Granulator  Fluidized Bed drier  Tray driers  Size reduction mills  Tablet compression machines  Tablet coaters  Tablet polishers  Liquid manufacturing tanks  Bottle washers  Bottle fillers & sealers  Bottle labelers  Ampoule washer  Sterilizing tunnels  Dry heat sterilizer  Autoclaves  Ampoule filler & sealer  Ampoule inspection machine  Ampoule labelers  Strip sealing m/c  Blister packing m/c  Shrink wrappers.  Potentiometric Titrator  Incubators. O. cooling towers. P. purified water & water for injection in this plant.  K. whether it remains in the product or not we use raw water. F. 4.  Autoclave  Refractometer  Atomic Absorption Spectrophotometer  H. chillers. which is used in the boiler. L.  Potable water is passed through either a two pass Reverse–Osmosis System (Capacity – 3000 Ltr.  pH Meter. C. C – With Photo Documentation System  T. drinking water. apparatus for Water determination. or Demineralization plant followed by mix bed unit to prepare purified water. Per hour) with Electro Deionising Unit. etc.  Dissolution Apparatus.Industrial Training Report  Gas Chromatograph. Analyzer  Laser diffraction particle size analyzer  BOD Incubators  Incubator  LAL testing Equipments  Sterility Testing related equipments  Zone reader 4. T. Table: 2 PRODUCTION EQUIPMENT LIST Equipment Name Lifting & Tippling device Equipment ID MAKE DTB –03 Tapasya MODEL - Plethico Pharmaceuticals Private limited Page 13 .  Humidity control ovens.  Source of raw water is underground natural water.7.8. BRIEF DESCRIPTION OF WATER SYSTEM As we consider water as the most important ingredient of our process.  Raw water is treated using water softening plants and converted into soft water. soft water. G. Pharmac Shrink packing Nimach Pharmac Anchor mark Anchor mark P.Industrial Training Report Sifter Planetary Mixer Blister packing m/c Conveyor Belt Shrink Machine Carton coding M/c Stirrer Rapid Mixer Granulator Fluid Bed Dryer Blister packing m/c Sifter RMG Lifting Positioning Device FBD Tippler Planetary Mixer Conta blender Conta blender Lifting Positioning Device Lifting Positioning Device Coating m/c Coating m/c Lifting Positioning Device Compression m/c DTB –05 DTB –07 DTB – 23 DTB -25 DTB -27 DTB -31 DTB –41 DTB-56 DTB-57 DTB-62 DTB-64 DTB-65 DTB-66 DTB-67 DTB-69 DTB-70 DTB-71 DTB-72 DTB-73 DTB-74 DTB-75 DTB-76 DTB-77 DTB-78 Pharmac Tapasya P.G. Anchor mark Anchor mark Anchor mark Anchor mark Anchor mark Anchor mark Anchor mark Anchor mark Anchor mark Anchor mark Gansons Gansons Anchor mark Cadmach machinery Cadmach machinery Cadmach machinery Anchor mark Fabtech Fabtech 240 CH HS-115X RMG 600 FBD 250 PG Ecostar VFST RMG-250 LPU FBD100 LTU PLM100 CB250 CB600+250L - Compression m/c DTB-79 - Compression m/c Lifting Positioning Device Static Pass Box Static Pass Box DTB-80 DTB-81 DTB-82 DTB-83 - Plethico Pharmaceuticals Private limited Page 14 . Industrial Training Report Vacuum Tray Drier DTB-84 Grovers VTD-48 (Production equipment list continue) Empty capsule sorter Sorter elevator Minifilled capsule sorter Air displacement unit Metal detector Punch polish M/c Balance Balance Balance Balance Balance Balance Balance Capsule filling machine Compact air displacement unit DTB-88 DTB-89 DTB-90 DTB-91 DTB-92 DTB-93 DTB-94 DTB-95 DTB-96 DTB-97 DTB-98 DTB-99 DTB-100 DTB-85 DTB-86 PAM PAM PAM PAM Technofour ACG Mettler Toledo Mettler Toledo Mettler Toledo Mettler Toledo Mettler Toledo Mettler Toledo Mettler Toledo PAM PAM ECS100 SE100 MCS100 ADU100 MD2000 Minicat-S2 Minicat-S2 Minicat-S2 Minicat-S2 Minicat-S2 IND225 AF40T CADU100 Plethico Pharmaceuticals Private limited Page 15 . B.Industrial Training Report Fig.D Plethico Pharmaceuticals Private limited Page 16 .1:F. Industrial Training Report Fig.3: Tablet Punching Machine Fig.2: Disintegration Test Apparatus Fig.4: Capsule Filling Machine Plethico Pharmaceuticals Private limited Page 17 . Industrial Training Report Plethico Pharmaceuticals Private limited Page 18 . 5: Blister Packing Machine Plethico Pharmaceuticals Private limited Page 19 .Industrial Training Report Fig. Non-Aqueous Coating Mixing Shifting 3. M.Blending 6. PROCESS FLOW CHART FOR TABLETS MANUFACTURING 1. Stores Weigh Approved Materials as per Batch 2.Compactin 4.Tablet Quarantine Visual Inspection Tablet Coating 2. Issue From P. M.Tablet Compression 7.For Uncoated For Coated QC Approval Tablets Tablets 1.De-dusting 8. Stores 3.1.BottlePacking Strip / Blister packing Labeling Strip checking 4.Approved Raw Material Issue From R.Capsule Filling 7.Lubrication 6.Fluidized Bed Drying Sieving 4. PROCESS FLOW CHART FOR CAPSULES MANUFACTURING 1. M.Shrink packing 7.Shipper Packing 8.QC Approval Finish Goods Store Dispatch 5.Approved Raw Material Issue from R.Tray Drying 5.Polishing Plethico Pharmaceuticals Private limited Page 20 .Wet Granulation Mixing Pulverization and Sifting Slugging 3.Induction Sealing Label / Carton Carton Packing 5.Tray Drying Sieving (At room temperature) 5. M. Stores Weigh Approved Materials As per Batch 2.Industrial Training Report PROCESS FLOW CHARTS 5.Approved Tablets Approved P.Coding 6. Industrial Training Report 8. M. M.Approved Raw Material issue Weigh Approved Materials As per Batch 2.QC Approval 11.Approved In-process Checks 9. M. PROCESS FLOW CHART FOR INJECTION MANUFACTURING (AMPOULE) 1. stores 3.Finish goods Store 18. M.Capsule Quarantine 10.Approved P. M.Visual Inspection 9.Induction sealing Label / Carton Carton Packing 14.2. Stores Approved Capsules Bottle Packing Strip / Blister packing 12.F.From R.QC Approval 17.Prefilteration 6.Labeling Strip checking 13. from Aseptic Filtration 7.Sterilization Filling & Sealing In Aseptic Area 11.Coding 15.Dispatch 5.Shipper packing 16. Issue From P. stores Ampoules 8.I 4.Approved P.Purified WaterAmpoule Washing 10.Leak Test 12.QC Approval 5.P.Bulk preparation Approved W.Visual Checking 13.Ampoule Ampoule Label Ampoule Labeling Label Coding Roundo Tray Roundo Tray / PVC Tray / PVC Tray Packing Carton Carton Carton & Insert Coding Insert Packing Shipper Shipper Packing BOPP Tape BOPP Taping QC Approval Finish Goods Store Dispatch Plethico Pharmaceuticals Private limited Page 21 . In very concise words I would say that this kind of training help us to know about the actual situation inside the pharmaceutical industries so that we get familiarize with that and work in a proper and systematic way. Plethico Pharmaceuticals Private limited Page 22 . CONCLUSIONS Involving the class at all stages of industrial training motivates the students and helps to take full advantage of all learning opportunities presented. I learned different things about the pharmaceutical industry. Every task is performed in scientific manner. It also brings dimension to student’s education.Industrial Training Report 6. During my training schedule. The one thing that impresses every visitor is the discipline and the maintenance of the company. During my industrial training in Plethico. I have gone through various department of the company and find that company follow the latest CGMP and also meet the environment norms. which cannot be gained in the class room as well as helping to make connection between the different aspects of educational experience. Target are presented and achieved within the time limit. I came to know about functioning of different instruments used in the pharmaceutical company. The understanding between the employee and the management is very precise and the cooperation between the departments is very good.