A Industrial Training Report

Industrial Training Report

IntroductionPlethico Pharmaceuticals Limited, kalaria, IndoreCompany 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.

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 Private limited


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.



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 with 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

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

Setting up its corporate office in Mumbai.

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

Name

Dosage Forms Category

Chloroquine Phosphate Paraquin

P-Quin

Tablets/

Suspension /

Injection

Antimalaria

Quinine sulphate RezQ Tablets/

Suspension /

Injection

Arteether Rezart-E Injection

Paracetamol Pletin Tablets/

Suspension

Antipyretic,

Analgesic,Anti-

inflamatoryNimesulide Nimez Tablets/

Suspension

Diclofenac Sodium Maxi Tablets/ Injection

Ciprofloxacine HCl Cebect Tablets Antibiotic/

antibacterialOfloxacine Gonocin Tablet

Co-trimoxazole timizol Tablets/

Suspension

Gentamycine Zentotic-

80

Injection

Amlodipine besylate amloz Tablets Cardiovascular

Amlodipine besylate &atenolol Amloz-at Tablets

Amlodipine &lisinopril Amloz-L Tablets

Diltiazem HCl Diitiaz Tablets



Ranitidine HCl Aciran Tablets Antiulcer / antacid

Omeprazole Pleom Capsules

Pantaprazole Pantoz Tablets

Dried aluminium hydroxide,Mg.

trisilicate,Mg.

hydroxide,simethicone

Coolz Tablets/

Suspension

Paracetamol,triplodine&pseudoepedr

ine

Recofast

plus

Tablets Cough&cold

Codiene phosphate &cholrpinramin

mallaite

planokuf Syrup

B-complex with vitamin-c&zinc Delirek Capsules Vitamins&minerals

Folic acid Plelic Tablets

Mebendazole Bendam Tablets/

Suspension

Anti-diarrheal,anti

amoebic &anti

helminticsMetronidazole Emigyl Tablets/

Suspension

Herbal hepato protective agent octogen Capsules/

suspension

Herbal

Herbal hepato protective agent Previl Capsules/

suspension

Mometasome furoate Metacort Cream Dermatological

Terbinafine 1% Dermafin

e

Cream



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

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

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 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, 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

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

Tap 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 the lyophilized LAL reagent with LRW as per the COA.

Stop 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.

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 salmonella S.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

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 Spectrophotometer.

F. T. I. R. Spectrophotometer.

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 equipments

Zone 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 -



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

Lifting Positioning Device DTB-73 Anchor mark -


Coating m/c DTB-75 Gansons -

Coating m/c DTB-76 Gansons -


Compression m/c DTB-78Cadmach

machinery-


machinery-


machinery-


Static Pass Box DTB-82 Fabtech -

Static Pass Box DTB-83 Fabtech -

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-100 Mettler Toledo IND225

Capsule filling machine DTB-85 PAM AF40T

Compact air displacement unit DTB-86 PAM CADU100



Fig.1:F.B.D



Fig.2: Disintegration Test Apparatus

Fig.3: Tablet Punching Machine

Fig.4: Capsule Filling Machine



Fig.5: Blister Packing Machine



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



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



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.


A Industrial Training Report

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