A Industrial Training Report

Industrial Training Report Introduction

Plethico 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), (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 bottle-manu facturing unit using a latest state of art ‘Direct Heat Conditioning Stretch-Blow Stretch-Blow Molding’ Machine. In addition to India in the OTC segment, Plethico is also a leading player in the Commonwealth of Independent 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 – Natrol – aa 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.


Page 2

Industrial Training Report

2. MILESTONES 1963-70

The beginning of the group activity This decade saw the establishment of the company's first formulation plant, manufacturing tablets, Capsules and Liquid Orals, at Indore, Madhya Pradesh, India. 1971-80

Up-gradation and expansion of Manufacturing Facilities Establishment of a nationwide marketing and distribution network. Introduction of branded formulations in various categories. 1981-90

An ultra modern formulation plant was established at Manglia, near Indore, to manufacture a wide range of allopathic formulations. Innovative branded formulations were introduced and established in Anti-malarials, Anti-tubercular, Cardiovascular & Cough & Cold segments. The company pioneered the launch of Doxycycline and Cotrimoxazole in the Indian market. 1991-2000

Diversification into Herbal & Natural formulations wit h scientific and modern manufacturing plant for Herbals set up at Indore. Introduction of novel herbal products for Hepatocare, Diabetes and Syndrome X developed with in-house research and clinical evidence. Major thrust into International Marketing. Travisil, an indigenously developed herbal Cough & Cold product became a star performer in the entire CIS market. 2000-2005

Commissioning of the state of the art formulation manufacturing plant at Kalaria, Indore, as per the requirements of WHO GMP, UK MHRA and US FDA.Plethico brand topped the Anti-Malarial segment of quinines. (AC Neilson 2002). Plethico, ranked amongst the TOP 5 Anti-TB companies in India, with its revolutionary 3/4 drug fixed dose Anti-TB combinations. The company re-oriented its business strategy and launched its Consumer Healthcare Division in India. Ultra modern fully integrated plants set up for manufacture of PET bottle (AOKI, Japan) and hard boiled candies (Klockner Hansel GmBH, Germany).The company acquired a marketing and distribution chain in the CIS, with subsidiaries in Russia, Ukraine, Kazakhstan, Moldova, Azerbaijan and Kyrgyzstan. Marketing and Distribution Joint


Page 3

Industrial Training Report Ventures formed in South East Asia, Africa and Latin-America. Establishment of Plethico Africa Limited (Kenya), a manufacturing Joint Venture to cater to the East African market. 2006 - 2008

Plethico raises Rs 110 crore from IPO to part finance:  The 

up-gradation of its Kalaria plant to make it UK MHRA compliant.

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.  Setting

up a R&D and formulation and development centre.

 Acquiring  Setting

stake in domestic herbal/OTC/nutraceutical company or a brand.

up its corporate office in Mumbai.


Page 4


3. 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

Dosage Forms

Category

Paraquin

Tablets/ Suspension

Antimalaria

P-Quin

/ Injection

RezQ

Tablets/ Suspension

Name

Chloroquine Phosphate

Quinine sulphate

/ Injection Arteether

Rezart-E

Injection

Paracetamol

Pletin

Tablets/ Suspension

Antipyretic,

Nimesulide

Nimez

Tablets/ Suspension

Analgesic,Anti-

Diclofenac Sodium

Maxi

Tablets/ Injection

inflamatory

Ciprofloxacine HCl

Cebect

Tablets

Antibiotic/antibacterial

Ofloxacine

Gonocin

Tablet

Co-trimoxazole

timizol

Tablets/ Suspension

Gentamycine

Zentotic-

Injection

80 Amlodipine besylate

amloz

Tablets

Amlodipine besylate &atenolol

Amloz-at

Tablets

Amlodipine &lisinopril

Amloz-L

Tablets

Diltiazem HCl

Diitiaz

Tablets

Ranitidine HCl

Aciran

Tablets


Cardiovascular

Antiulcer / antacid Page 5

Industrial Training Report Omeprazole

Pleom

Capsules

Pantaprazole

Pantoz

Tablets

Coolz

Tablets/ Suspension

Dried

aluminium

hydroxide,Mg.

trisilicate,Mg. hydroxide,simethicone Paracetamol,triplodine&pseudoepedrine Recofast

Tablets

Cough&cold

plus Codiene

phosphate

&cholrpinramin

planokuf

Syrup

B-complex with vitamin-c&zinc

Delirek

Capsules

Folic acid

Plelic

Tablets

Mebendazole

Bendam

Tablets/ Suspension

Anti-diarrheal,anti

Metronidazole

Emigyl

Tablets/ Suspension

amoebic

mallaite Vitamins&minerals

&anti

helmintics Herbal hepato protective agent

octogen

Capsules/suspension Herbal

Herbal hepato protective agent

Previl

Capsules/suspension

Mometasome furoate

Metacort

Cream

Terbinafine 1%

Dermafine Cream


Dermatological

Page 6


4. DEPARTMENTS  Research

and development

 Formulation

& Development

 Quality

Assurance

 Quality

Control

 Stores

(RM/PM)

 Distribution  Production  Engineering  Personnel

& Adm.

 Security

4.1 FORMULATION & DEVELOPMENT

Plethico takes pride in a team of dedicated scientists with expertise in botany, pharmacognosy, phytochemistry, analytics and pharmacology, as well as consultants having a long association with the herbal drug industry. Procuring authentic plant material, pharmacological evaluation in laboratory models, formulation development and modern clinical trials are an integral part of the herbal product development activities. Herbal Research unit focuses on developing standardized, clinically proven and safe herbal products for therapeutic and cosmetic use. They are engaged in various activities that enable us to bring out the most efficacious herbal products to consume. Some of the activities are:  Research

on new herbs/ existing herb ingredients for better therapeutic usage, dosage form/

Novel Drug delivery system (NDDS).  Spearheading 

improvements in existing formulations to meet growing regulatory demands.

Stabilizing of existing dosage forms based on stability studies as per International

Guidelines.  Development

of marker based standardized dosage forms.

Methods of extraction


Page 7

Industrial Training Report Commercially herbal crude materials are extracted by water as the extraction medium, which is achieved at Plethico by following methods:  Cold maceration,  Hot percolation,  Hot

extraction,

 Distillation,

etc. based on the type of material to be extracted

 Supercritical

or Liquid CO2 extraction

4.2 QUALITY ASSURANCE

Quality assurance is a major challenge, particularly in light of growing regulatory stringency and the international dimensions of trade, rightly so, since manufacturing of substandard medicines result in prolonged treatment for patients, drug resistance and increased incidence of adverse effects. The self-implied stringent quality standards are followed to ensure that all the products being manufactured are consistently safe, effective and of good quality. While the general principles of GMP apply for all types of pharmaceutical products, herbal products differ from conventional pharmaceutical products in that they are prepared from herbal substances, which include materials derived from leaves, seeds, bark, essential oils and resins. Because of their unique origin, herbal products often require procedures for their processing; manufacturing and storage that differ from those used for conventional pharmaceuticals, and therefore present a degree of complexity. In Plethico, I took pride in stringent following of specially developed protocols for hygiene; sanitation and processing that are specific to herbal products. Some of these are: 

Storage facilities with quarantining of incoming herbal matter to prevent the spread of

microorganisms, 

Maintenance of segregated areas for different herbal materials and of appropriate

environmental conditions.  Production

areas controlled for dust, fumes and vapors generated by the processing of these

substances, 

Cleanliness of equipment to avoid microbiological contamination as per US FDA GMP

norms.

At Plethico, I learned that each major stage of the manufacturing process is validated to


Page 8

Industrial Training Report ascertain that the finished products comply with all quality and design protocols, and consistently meet their specifications.

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, i.e., to ensure total Quality, Safety and Efficacy of each and every herbal product. 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  Group

of extractive values

analysis

 Chromatographic profile  Marker

matching

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  Gas 

Absorption Spectroscopy for analysis of Heavy metals

Liquid Chromatography (GLC) for analysis of Pesticides

Thin Layer Chromatography (TLC) for detection and chemical analysis of certain

phytochemicals such as Alkaloids, Tannins, etc. The Quality Control and Assurance Laboratories have following facilities.  Chemical

Analytical Laboratory

 Microbiological Laboratory  Instrumental Analysis Laboratory  Sterility

Testing Section

 Control

sample and record room

 Other

supporting facilities.

 Well-equipped shop floor IPQC Laboratories.

4.4 BRIEF DESCRIPTION OF MICROBIOLOGICAL ACTIVITY : .

Bacterial endotoxin test Plethico Pharmaceuticals Private limited

Page 9

Industrial Training Report  Principle:

There are two types of techniques for this test: the gel-clot techniques, which is based on gel formation, and the photometric techniques. This MOA i s based on gel clot technique. In gel clot technique, equal volume of LAL & diluted test specimen are mixed in tubes and incubated at 37+1°C for 60 + 2 min. The tubes are then observed for gel clot formation. A positive response in the gel clot test indicates the Endotoxin in the sample, which equals or exceeds the reagent labelled sensitivity represented by the symbol lambda ( ). Reconstitution of LAL reagent:  Remove  Tap 

Aluminium seal of the Lysate vial without opening the rubber stopper.

on the rubber stopper to collect the LAL powder in the bottom of the vial.

Carefully remove the stopper. Keep the stopper in a clean surface without touching the

inner portion of the stopper.  Reconstitute  Stop

the lyophilized LAL reagent with LRW as per the COA.

the re-constituted vial. Do not shake, mix gently avoiding formation of air bubbles and

keep aside till clear solution is not visible. Storage:

Lyophilized LAL reagent should be stored at 2-8°C. Reconstituted LAL reagent ideally should be stored in a refrigerator at 2-8°C during intermittent use for up to 24 hours, otherwise, store LAL reagent in freezer upto 28 days. LAL reagent can be frozen and thawed only once. Testing Procedure:

Take 2 depyrogenated test tubes for each negative and positive control. Arrange TT of negative and positive controls in separate rows of the stand. Take depyrogenated tubes in duplicate for sample and mark them as 1, 2, 3… or with batch no. of the sample. Add the reagents as mentioned below in the table 04. In case of water sample (Water for Injection and Pure Steam Condensate) , transfer 100μl of water sample in 2 depyrogenated TT and add 100μl Lysate to them (when testing at EL = 0.125 EU/ml). When testing at EL = 0.25 EU/ml, take 50μl of water sample to be tested, 50μl of LRW and add 100μl Lysate. Record the results in the respective formats. Mix gently and incubate the tubes in heating block at 37 °C ±1 for 60 + 2 min.


Page 10

Industrial Training Report After incubation remove the tubes gently from the heating block and slowly invert through 180°C and note the observations. If a firm gel has formed that remains in place after inversion, record the results as positive. A result is negative, if an intact gel is not formed. Record the results and other details in respective format. 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.B.C T.F.C

1st p.d +20-25 ml of SCDA 2nd p.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. coli salmonellaS.aureus p. aurigenosa

Transfer 1ml in M.B media Directly streaked it on Directly streaked it on M.S.A media C.A media

Incubate it for 48 hours at 42-44c transfer 1.0 ml in R.V.S.E.B media

Then streaked it on M.A media Then streaked it on X.L.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 4.5. BRIEF DESCRIPTION OF MAJOR PRODUCTION EQUIPMENT  Major

production equipments are as follow:

 Mechanical vibrating

sifters


Page 11

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, etc.  Vial washers  Vial

filler & Sealer

 PET

bottle mfg. unit (Stretch blow moulding)

 Lozenges

Forming Line

 Ointment/Cream Line

4.6. BRIEF DESCRIPTION OF LABORATORY EQUIPMENTS : Major Analytical instruments in Quality Control Department are as follows:  H.

P.L. C. – With Auto Sampler

 U.V. -- Visible  F.

Spectrophotometer.

T. I. R. Spectrophotometer.


Page 12

Industrial Training Report  Gas Chromatograph.  Dissolution Apparatus.  K.

F. apparatus for Water determination.

 pH

Meter.

 Potentiometric Titrator  Incubators.  Humidity control ovens.  Autoclave  Refractometer  Atomic Absorption

Spectrophotometer

 H.

P. T. L. C – With Photo Documentation System

 T.

O. C. Analyzer

 Laser diffraction particle size

analyzer

 BOD Incubators  Incubator  LAL testing Equipments  Sterility Testing related  Zone

equipments

reader

4.7. BRIEF DESCRIPTION OF WATER SYSTEM As we consider water as the most important ingredient of our process, whether it remains in the product or not we use raw water, soft water, drinking water, purified water & water for injection in this plant.  Source 

of raw water is underground natural water.

Raw water is treated using water softening plants and converted into soft water, which is

used in the boiler, chillers, cooling towers, etc. 

Potable water is passed through either a two pass Reverse – Osmosis System (Capacity –

3000 Ltr. Per hour) with Electro Deionising Unit, or Demineralization plant followed by mix bed unit to prepare purified water.

4.8. Table: 2 PRODUCTION EQUIPMENT LIST Equipment Name

Equipment ID

MAKE

MODEL

Lifting & Tippling device

DTB – 03

Tapasya

-


Page 13

Industrial Training Report Sifter

DTB – 05

Pharmac

-

Planetary Mixer

DTB – 07

Tapasya

-

Blister packing m/c

DTB – 23

P.G.

240 CH

Conveyor Belt

DTB -25

Pharmac

-

Shrink Machine

DTB -27

Shrink packing

HS-115X

Carton coding M/c

DTB -31

Nimach

-

Stirrer

DTB – 41

Pharmac

-

Rapid Mixer Granulator

DTB-56

Anchor mark

RMG 600

Fluid Bed Dryer

DTB-57

Anchor mark

FBD 250

Blister packing m/c

DTB-62

P.G.

PG Ecostar

Sifter

DTB-64

Anchor mark

VFST

RMG

DTB-65

Anchor mark

RMG-250

Lifting Positioning Device

DTB-66

Anchor mark

LPU

FBD

DTB-67

Anchor mark

FBD100

Tippler

DTB-69

Anchor mark

LTU

Planetary Mixer

DTB-70

Anchor mark

PLM100

Conta blender

DTB-71

Anchor mark

CB250

Conta blender

DTB-72

Anchor mark

CB600+250L


DTB-73

Anchor mark

-


DTB-74

Anchor mark

-

Coating m/c

DTB-75

Gansons

-

Coating m/c

DTB-76

Gansons

-


DTB-77

Anchor mark

-

Compression m/c

DTB-78

Cadmach machinery Cadmach

-

Compression m/c

DTB-79

Compression m/c

DTB-80


DTB-81

Anchor mark

-

Static Pass Box

DTB-82

Fabtech

-

Static Pass Box

DTB-83

Fabtech

-


machinery Cadmach machinery

-

-

Page 14

Industrial Training Report Vacuum Tray Drier

DTB-84

Grovers

VTD-48

(Production equipment list continue)

Empty capsule sorter

DTB-88

PAM

ECS100

Sorter elevator

DTB-89

PAM

SE100

Minifilled capsule sorter

DTB-90

PAM

MCS100

Air displacement unit

DTB-91

PAM

ADU100

Metal detector

DTB-92

Technofour

MD2000

Punch polish M/c

DTB-93

ACG

-

Balance

DTB-94

Mettler Toledo

-

Balance

DTB-95

Mettler Toledo

Minicat-S2

Balance

DTB-96

Mettler Toledo

Minicat-S2

Balance

DTB-97

Mettler Toledo

Minicat-S2

Balance

DTB-98

Mettler Toledo

Minicat-S2

Balance

DTB-99

Mettler Toledo

Minicat-S2

Balance

DTB-100

Mettler Toledo

IND225

Capsule filling machine

DTB-85

PAM

AF40T

Compact air displacement unit

DTB-86

PAM

CADU100


Page 15

Industrial Training Report Fig.1:F.B.D


Page 16

Industrial Training Report Fig.2: Disintegration Test Apparatus

Fig.3: Tablet Punching Machine

Fig.4: Capsule Filling Machine


Page 17



Page 18

Industrial Training Report Fig.5: Blister Packing Machine


Page 19

Industrial Training Report PROCESS FLOW CHARTS

5. PROCESS FLOW CHART FOR TABLETS MANUFACTURING 1.Approved Raw Material Issue from R. M. Stores Weigh Approved Materials as per Batch 2.Wet Granulation Mixing Pulverization and Sifting Slugging 3.Fluidized Bed Drying Sieving 4.Tray Drying 5.Lubrication 6.Tablet Compression 7.De-dusting 8.For Uncoated For Coated QC Approval Tablets Tablets 1.Tablet Quarantine Visual Inspection Tablet Coating 2.Approved Tablets Approved P. M. Issue From P. M. Stores

3.BottlePacking Strip / Blister packing Labeling Strip checking 4.Induction Sealing Label / Carton Carton Packing 5.Coding 6.Shrink packing 7.Shipper Packing 8.QC Approval Finish Goods Store Dispatch 5.1. PROCESS FLOW CHART FOR CAPSULES MANUFACTURING 1.Approved Raw Material Issue From R. M. Stores Weigh Approved Materials As per Batch 2.Non-Aqueous Coating Mixing Shifting 3.Compactin 4.Tray Drying Sieving (At room temperature) 5.Blending 6.Capsule Filling 7.Polishing Plethico Pharmaceuticals Private limited

Page 20

Industrial Training Report 8.Visual Inspection 9.Capsule Quarantine 10.QC Approval 11.Approved P. M. Issue From P. M. Stores Approved Capsules Bottle Packing Strip / Blister packing 12.Labeling Strip checking

13.Induction sealing Label / Carton Carton Packing 14.Coding 15.Shipper packing 16.QC Approval 17.Finish goods Store 18.Dispatch 5.2. PROCESS FLOW CHART FOR INJECTION MANUFACTURING (AMPOULE) 1.Approved Raw Material issue Weigh Approved Materials As per Batch 2.From R. M. stores 3.Bulk preparation Approved W.F.I 4.QC Approval 5.Prefilteration 6.Approved P. M. from Aseptic Filtration 7.P. M. stores Ampoules 8.Approved In-process Checks 9.Purified WaterAmpoule Washing 10.Sterilization Filling & Sealing In Aseptic Area 11.Leak Test 12.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

Industrial Training Report 6. CONCLUSIONS Involving the class at all stages of industrial training motivates the students and helps to take full advantage of all learning opportunities presented. It also brings dimension to student’s education, which cannot be gained in the class room as well as helping to make connection between the different aspects of educational experience. During my training schedule, I have gone through various department of the company and find that company follow the latest CGMP and also meet the environment norms. During my industrial training in Plethico, I learned different things about the pharmaceutical industry. I came to know about functioning of different instruments used in the pharmaceutical company. Every task is performed in scientific manner. Target are presented and achieved within the time limit. The one thing that impresses every visitor is the discipline and the maintenance of the company. The understanding between the employee and the management is very precise and the cooperation between the departments is very good. 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.


Page 22

A Industrial Training Report

Recommend Documents