Report on in plant training program in navana pharmaceuticals limited

Report on In Plant Training Program in Navana Pharmaceuticals Limited

Acknowledgements Navana Pharmaceuticals Limited was established in Rupshi, Narayangonj with the main aims and objectives of providing the best pharmaceutical prod ucts to the people of this country.

The industry being well-equipped with modern machineries and equipments is strengthened by the efficient management and expertise. The commercial production started in April 1992 with 8 (eight) antibiotic products. During end of 1996 the production range expanded up to 41 numbers. The company is subjected to further expansion while work is in progress to introduce other new products.

Navana Pharmaceuticals Limited is a business unit of Islam Group, which is one of the largest groups of industries in Bangladesh having diversifying activities.

Navana Pharmaceuticals Limited is one of the leading Pharmaceuticals companies in Bangladesh having modern manufacturing plants near by the capital city Dhaka. The total manufacturing area of Navana Pharmaceuticals Limited is 3500 square feet that have all facilities like electricity, water supply, sewerage & natural gas supply. The manufacturing plant of Navana Pharmaceuticals Limited is equipped with sophisticated & modem machineries. Navana Pharma offers a wide range of human Pharmaceuticals & animal health products in different experienced & well trained Pharmacists, Biochemists, Microbiologists, Chemists, Zoologists and Engineers engaged in various stage of production, Quality Assurance, product development and validation. In every phase of production Navana follows WHO cGMP. Navana has gained recognition for the value of it’s technology and quality of the work. Navana Pharmaceuticals Limited is an ISO 9001: 2000 certified company for it’s quality management system.

QUALITY POLICY OF NAVANA PHARMACEUTICAL LTD. Navana’s mission is to achieve business excellence through product quality and committed to ensure customer satisfaction by exceeding their level of expectations.

It is the policy of Navana to ensure all products manufactured in the factory pass through appropriate product development activities and to monitor product quality throughout its shelf life.

Navana is committed to comply with the WHO cGMP standards and will follow local drug regulatory norms in every phases of product development, manufacturing quality assurance and distribution of medicines.

Ensure all activities through documented quality management system (QMS) complying International standard requirements of ISO 9001:2000 through continuous developing of Human resources.

Navana will continually improve the effectiveness of quality Management System and will undertake appropriate review, evaluation and performance measurement of its operations to ensure complains Quality policy.

Purposes of in-plant training: Pharmacy is the art and science of preparing & dispensing medications and the provision of drug & related information to the public. A pharmacist is a specialist in medications, a custodian of medical information, a companion of physician, a counselor to the patient, and above all, a guardian of the public health. Thus pharmacists, have a very important role- in the national health care system. They are rendering valuable services to the people- by making quality medicines.

In order to build up more efficient pharmacist in all aspects of this noble profession the students studying in B.Pharm (Honors) course are designed by their respective authorities to acquire practical knowledge from the renowned pharmaceutical industries because they could not have opportunities of occupying themselves with applied phenomenon on the medicinal products beyond their theoretical lessons as well as industrial operations.

With this view i.e. to make the students efficient and professionally skilled pharmacists, the Department of Pharmacy, University of Science and Technology, Chittagong (USTC) sent us to the NAVANA Pharmaceuticals Ltd. for our training. It was our great pleasure to join this In-Plant Training iin NAVANA Pharmaceuticals Ltd. which is one of the most well organized Drug manufacturing companies in Bangladesh. There we completed the In-Plant Training from 6th November, 2010 to 7th December, 2010. During this training, we were exposed to different production sites, Quality Assurance and Quality control department, Product development. We also gathered knowledge about Administration, Inventory control and planning, Marketing and Warehouse. We would try our best to summarize our gathered achievement at In-Plant Training on this report. The certificate given by the company after completing the training is to be submitted to the pharmacy council or pharmacy registration examination. Without this certificate no student will be allowed to appear in this exam.

Purpose of this report: The report which is submitted after the training program is a reflection what the trainee have learnt. It also improves the writing and presenting skills. It also says the limitation and perfection of the company, so the report is important both for the trainee and the plant.

We, the three students of 15 th batch of Pharmacy Department of University of Science and Technology, Chittagong (USTC) have successfully completed the one month training in Navana Pharmaceuticals Ltd. We took the notes during our visit to different departments. So, this report will only represent what we have seen, what we have learnt and what we have been taught. .

We hope this report will help us to implement our experiences in our working field. We will feel worthy, if this report helps other pharmacy students to learn about Navana Pharmaceuticals Ltd.

Quality of drugs: Generally we take drug to prevent, moreover to treat a disease. If the drug is therapeutically active and has the capability to show its credit for the desired reason then we can call the drug as a quality drug.

We should remember that the elegancies as well as appearance can increase the drugs acceptability.

According to ISO 8402 quality is defined as” Total of features and characteristics of a product or service that bears on its ability to satisfy a given need’’.

Aspects of the quality of a drug: Drug is one of the prime tools for saving lives. A medicinal product must satisfy certain standards to claim it to be a quality drug. The main criteria for quality of any drug in dosage form are it’s• Safety • Efficacy • Acceptability

• Potency • Stability • Regulatory compliance

QUALITY ASSURANCE: Quality Assurance is the sum total of the organized arrangements made with the object of ensuring that the product will be of the quality require by their intended use. It is good manufacturing practice plus factors outside the scope of these guidelines. The chain of quality assurance activity stretches from the product development stage up to the end users. Quality Assurance is a wide ranging concept which covers all matters which individually or collectively influence the quality of a product. It is the sum total of the organized arrangements made with the object of ensuring that medicinal products are of the quality required for their intended use. Quality Assurance therefore incorporates Good

Manufacturing Practice plus other factors outside the scope of this Guide.

QA = Product design + GMP + QC + Quality goal activities Objectives of quality assurance: 1. Raw material specifications 2. Packaging material specifications 3. Intermediate product specifications 4. Bulk product specifications 5. Finished product specifications Quality control: Quality control is a part of quality assurance. Quality control refers to the process of striving to produce a perfect product by a series of measures requiring an organized effort by the entire company to prevent or eliminate errors at every stage in production. It concerns quality control of raw materials, finished products and packaging materials.

Quality control is a comprehensive course which will help all students quickly and easily identify and correct error in quality control procedure.

QC = Test +Assessment Raw materials specification depends upon the following parameters: • Appearance • Odor • Solubility • Water Content • PH • Residue on ignition • Heavy metals • Absorptivity • Assay (HPLC/IR/UV) • Loss on drying • Viscosity • Melting point • Turbidity • Bulk density • Sterility/Pyrogen • Screen test • Specific gravity • Specific volume In process control: The In-process control is the checks made during the course of manufacturing process which aims to ensure that product will comply with specifications. Thus quality is built into the product. Although these checks are not a part of final product specifications but done as a part of control evidence that the correct operations did apply during manufacture.

Advantages of IPC: • Allows timely action • Improves productivity • Reduces rejection cost • Reduces the chance of batch failure

Some commonly performed IPC checks: Process

In-Process checks

1.Dispensing

Weighing and recording.

2.Mixing

Time and speed, Temperature.

3.Granulation

Time and speed, Homogeneity of the content.

4.Drying

Temperature (Inlet and outlet air ),Time, Pressure, LOD(Loss on drying).

Machine speed, Compression pressure, Thickness, Hardness, Appearance, Friability, Disintegration time, Dissolution test.

Temperature, speed, Uniformity, Spray rate, Degree of atomization and Weight.

Temperature curve of heating jacket.

5.Tableting 6.Coating 7.Oral liquid

In process quality control depends on the following parameters: A) • • • • • • B) • • • •

For Tablet: Blend uniformity Appearance Dosage uniformity Thickness Weight variation Dissolution For Liquids: Appearance Specific gravity Re-suspend ability Preservative

• Loss on drying • Average weight • Hardness • Friability • Disintegration

• • • •

pH Viscosity Flavor Average fill intent

Quality control after granulation: Only moisture content will be detected after granulation.

Quality control after mixing: • Moisture content.

• Blend assay (for those drug, which has very small quantity of drug content) Quality control after compression: • Length • Thickness • Friability Quality control for coating approval:

• Width • Hardness • Disintegration time

• • •

• Friability • Disintegration time • Drug content

Hardness Moisture content Average weight of tablet

In process quality control for Blistering: • • • • •

sealing temperature Air press in bar Humidity Visible defects Leak test.

• Pre heat temperature • Room temp.

• Batch coding • Foil Alignment

In process quality control for Packaging Materials: • Faulty container or closure • Mislabeled product • Printing errors Finished Product: Finished product testing should be performed by the quality unit & should conform to written specification.

Finished product specification depends on the following parameters: For Tablets: • -Dosage uniformity • Hardness of tablets • -Disintegration • -Average weight

• Loss on drying (LOD) • Thickness of tablets • Dissolution

For coating: • Temperature ‹Inlet and outlet air› • Speed and time • Uniformity and weight • Appearance • Disintegration time Dissolution test For Liquid: • Appearance • Specific Gravity • Assay • Fill variation

For Capsule:

• PH • Foreign matter • Viscosity • Volume in container

• • • • •

Moisture Content Disintegration Average weight Sealing Polishing

For Dry syrup: • PH • Moisture Content • Weight variation

●

Viscosity ●Potency

Documentation: Documentation is a prime necessity in quality assurance. Its purpose is to define the system control, to reduce the risk of error, so that personnel are instructed in details of and follow the procedures concerned and to permit investigation and tracing of defective products.

To facilitate proper and effective use of documents they should be designed and prepared with care.

1. The title, nature and purpose of the document is to be clearly stated.

2.

The way the document is to be used, and by whom, should be clearly apparent from the document itself.

3.

Where documents bear instruction they should be written in the imperative. They should be clear, precise and in language the user can understand.

4.

Documents, which require the entry of data, should provide sufficient space for the entry.

5.

Reproduced documents should be clear and legible.

Flow chart for Quality Assurance activity: Receiving of Raw & packaging Materials by visual inspection

Attachment of quarantine Tag of yellow color

Sampling of raw & packaging Materials for QC analysis Release / rejection

Dispensing of raw & packaging Material Checking of cleanliness,

Attachment of respective tag for raw & packaging materials.

Approval of equipment &area of manufacturing In process checking of Some parameters during Compression, filling etc.

Sampling of in process Product to Q.C.

In process checking of Packing operation

Transfer of finished product For distribution after Collecting the retention sample

Investigation of product complaints, product recall returned product from market Equipment in Quality Assurance: Name

Source

Scope

Digital Polarimeter

England

Determination of Specific Optical Rotation Bound moister 1 month determination Qualitative and 6 month Quantitative analysis Sample 3 month identification

Karl Fischer High Pressures Liquid Poland Chromatography (HPLC) Fourier Transform Infra- Japan Red Spectrophotometer (FTIR-8101A)

UV-Spectrophotometer (UV-1601pc)

Japan

Calibration Time Interval 6 month

Identification 3 month and Potency determination

Calibratio n Factor Quartz control cell Electrode sensitivity Retention time, Peak area.

Shape of power spectrum , Wavelengt h (accuracy, resolution, reproducibi lity) Control of absorbance (235, 257, 313 and 350 nm.),Cell (Holmium

Disintegration Tester

India

Dissolution Tester 8 stage India basket system‹TDT-08L› Tablet Friability Test India apparatus USP Digital Tablet Hardness England Tester‹TSF-1000›

Disintegration time Dissolution

6 month

Friability

6 month

3 month 1 year

6 month

Analytical balance

Switzerland

Determination of Tablet Hardness Weight

Melting point Apparatus

England

Identification

Slide Caliper

Poland

Size, Diameter, Thickness

Centrifuge Machine‹ S- UK 549› Magnetic stirrer Germany

Analytical Work in QA Mixing

Opti-melt ‹Automated England melting point system›

Determination of Melting Point.

Vacuum Oven

Drying

England

Laminar Air flow cabinet (HEPA)

and Didymium cells ) Temperatur e and cycle.

Temperatur e and rpm rpm

Wight (BSTI approval).

Vanillin, Phenacetin and Caffeine

rpm

1 year

Vanillin, Phenacetin and Caffeine Temperatre

To avoid cross contamination

Sartorius PH meter

Germany

PH

daily

PH (4,7,11)

Moister Analyser

USA

LOD

3 month

Wight

Digital Automatic Tap Germany density test Apparatus(350T) Micrometer(PAT Japan No.200959)

Determination of Density Thickness package

of

Figure: UV machine (Double beam spectrophotometer)

Figure;F510 FT-IR Spectrophotometry

Some of the reagents: ●Karl-Fischer reagent, ● Bromocresol green, ●Crystal violet, ●α-Naphthol benzene, ● Methanol, ●Methyl orange/ red, ●Phenolphthalein, ●Chloroform, ●Starch, ●Na-acetale buffer, ●Potassium iodide, ● Acetic acid. ●Iodine solution, ●Acetonitrile, ● 2- Butanol, ●Citric acid, ●Cyclohexane, ● Hexane, ●Ether, ●Dithiozone etc.

All reagents are of pharmaceutical standard sources.

Some of the glass wares: ●Conical flask, ● Burette, ●Pipette, ●Volumetric flask, ●Beaker, ●Graduated cylinder, ●Separating funnel. ●Glass bottles, ● Round bottom flask, ● Desicator etc.

All instruments are of pharmaceutical standard.

General Introduction: Solid dosage forms are some of the least expensive, most popular and convenient methods for drug delivery. They can be produced in a non-sterile environment and the technology is well-known after more than 100 years of development. Since most pharmaceuticals are produced in solid dosage forms, it is important that the unit operations for their production be thoroughly understood. This course focuses on the fundamentals of each discrete processing step (unit operation) required for the manufacture and packaging of tablets and capsules, the most common of solid dosage forms.

Total Units in Production Area

Manufacturing area І Liquid manufacturing

↓ Granulation unit

Compression unit

Packaging area

Solid manufacturing

Coating unit

Capsule filling unit

1. Introduction of Tablet DEFINITION: Tablets may be defined as a solid unit dosages form of medicament or medicaments with or without suitable diluents and prepared either by molding or by compression. They vary greatly in shape, size and weight which depend upon the amount of medicament and mode of administration.

Tablet contents: Compressed tablets usually consist of active medicaments mixed with a number of inert substances known as excipients. These additives are added to given the qualities of good tablet. Although these additives are termed as inert but they have a great influence on stability, bioavailability and the process by which the dosage forms are prepared. According to the functions, which these additives play in the preparation of tablets, they are follows: 1.Diluent

5.Lubricants

2.Binders

6.Colouring agent

3.Granulation agent

7.Flavouring agent

4.Disintegrating agent

8.Sweetening agent

Diluent When the quantity of the drug for an individual dose is very small and it is not practicable to compress such small amount in the form of a tablet then the inert substances which are to increase the bulk of powder to be easily compressed are known as diluent. For example-lactose, sucrose, mannitol, dextrose, calcium sulfate dehydrate, starch, microcrystalline cellulose (Avicel PH101,RC 591), sorbitol.

Binder: Agents that are used to convert granules from crystalline form before compression to impart cohesiveness to the powdered substance are known as binders. e.g: Polyvinyl pyrrolidone (povidone K-90),Crosspovidone,Starch-1500 partially pregalatinize maize starch.

Disintegrant They help the tablet to break down into small fragments, when it is ingested to dissolve and be taken up by the body so that it can act more quickly. For example-Sodium starch glycolate (Primojel),

veegum, bentonite, agar, CMC, MC, Na-alginate, citrus pulp, microcrystalline cellulose (Avicel), maize starch(dry).

Glidant: The glidant helps to make the powder free flowing stopping it from forming lumps.e.g: Talc, corn starch, aerosil, colloidal silica etc.

Lubricant Lubricants ensure that the tablet has a smooth surface and that the powder does not stick to the equipment used to make the tablet. eg : stearic acid, Mg-stearate.

Switeening agents These are used for tablets need to be dissolved in buccal cavity.eg: Sucrose, lactose, mannitol, saccharin, aspartame, Acesulfame potassium ,Sorbitol solution 70% etc.

Flavour: Flavouring agents help to make the tablet taste better. Example: Cherry cream, Lemon, Orange, Pineapple, Raspberry, vanillia etc.

Colourant: Colours are added to help you to recognize your tablet and to make it easier to take your medicine correctly.e.g: Color iron oxide (red,yellow), Color lake brilliant(blue), Color lake orange (yellow), Color lake quinoline (yellow), color raspberry (red), Color red 2G, Color lake erythrocine(red) etc.

Tablets are usually right, circular solid cylinders, the end surfaces of which are flat or convex and the edges of which may be beveled. They may have break-marks and may bear a symbol or other markings. Tablets may be coated.

2. PRODUCTION OF TABLET: In tablet production there are several steps involved which are following: • • • • • •

Dispensing and Granulation.

Blending Powder compression Coating Blistering / Striping /Filling.

Secondary Packaging.

GRANULATION UNIT DEFINITION: Granulation may be defined as a size enlargement process which converts small particles into physically stronger and larger agglomerates in order to facilitate the flow and compression for the production of tablet. All the materials are received from the dispensing unit and granulation is

performed. For suitable granulation, it is required to have 30-40% powder and 60-70% granules and also 1-5% moisture in compressing particles.

PURPOSES OF GRANULATION: -To produce tablets of appropriate size.

- To prevent segregation of the constituents in the powder mix.

-To improve the flow properties of the powder mix.

-To improve compression nature of powder.

Types of granules: Two types of granules are produced in the four-granulation units of the industry, which include; • •

Granules with active ingredient/s Placebo granules without any active ingredient/s for moisture sensitive active/s or drug/s

Granulation Processes which are performed in the NAVANA plant are following: • Wet Granulation.

• Dry Granulation.

• Direct compression Wet granulation: Wet granulation is a process of using a liquid binder or adhesive to the powder mixture to produce the granules. The amount of liquid can be properly managed, and over wetting will cause the granules to be too hard and under wetting will cause them to be too soft and friable. Aqueous solutions have the advantage of being safer to deal with than solvents.

Weighing of active ingredient as well as excipients ↓ Dry mixing ↓ Wet mixing (in case of wet granulation) by addition of de-mineralized (DM) water or Maize starch paste in Rapid Mixer Granulator (RMG) for a certain time period specified in the Batch Production Record (BPR) ↓ Initial Phase drying in Fluid Bed Dryer (FBD) ↓ Milling in the Multi mill ↓ Partial drying in FBD ↓ Milling in the Multi mill ↓ Terminal/Final drying in the FBD ↓ Sieving in the Vibratory Sifter according to the required particle/granule size ↓ Measurement of Loss on Drying (LOD) ↓ Granules of desired size ready for blending.

Dry granulation: This process is used when the materials needed to be granulated are sensitive to moisture and heat.

Dry granulation can be conducted on a press using slugging tooling or on a roller compactor commonly referred to as a chilsonator. Dry granulation equipment offers a wide range of pressure and roll types to attain proper densification. However, the process may require repeated compaction steps to attain the proper granule end point.

Dry granulation Weighing of drugs and excipients Dry mixing of drugs and diluents Slugging or pre-compression Milling and sieving Lubrication Discharge for compression Direct compression: This method is used when a group of ingredients can be blended and placed in a tablet press to make a tablet without any of the ingredients having to be changed. This is not very common because many tablets have active pharmaceutical ingredients which will not allow for direct compression due to their concentration or the excipients used in formulation are not conducive to direct compression.

Mixing & Blending: Mixing/blending may be defined as a process where two or more components or substances are treated so as to lie as nearly as possible in contact with particle of each of the other components or substances with uniform distribution of each component. A powder blend should be as uniform as possible to assure the proper amount of medication in each dosages unit. Small particles are difficult to blend because they exhibit poor fluidity. However, more important than actual particle size is particle size range.

EQUMPMENT IN PRODUCTION UNITS: Name

Source

Capacity

High speed mixer Granulator (MG -300) Mechanical Shifter-30�M Multi mill-SMT

Thailand India India

120Kg/300L

GFG High Efficiency Fluid Bed Dryer

China

120Kg

Oil Jacked Vessel for Paste preparation

Bangladesh

40L

Double Cone blender (DCB-120)

India

150Kg

Double Rotary Tab Compression Machine (Clit-27 station)

India

65000/hr

Double Rotary Tab Compression Machine (Adept-25 station)

India

52000/hr

Excella-2000(20 Station)

India

Thai-coater 32”

Thailand

NR-Cotar-39”‹FC-39›

Thailand

33000/hr 50Kg 80Kg

Features

Excella-2000(20 Station)

Double Rotary Tab Compression Machine (Adept-25 station

Double Rotary Tab Compression Machine (Clit-27 station)

Source

India

India

India

Based on pressure

Dtooling

Dtooling

Btooling

rpm

28

18

22

Capacity

33000∕hr

52000/hr

65000/hr

No. of station

20

25

27

Rapid mixing granulator(RMG)

Fluid bed dryer

Fig: Double cone blender TABLET COMPRESSION: Compression of powders or granules means a reduction or bulk volume of a material as a result of displacement of the gaseous phase. Compression may also be defined a s the process of applying external mechanical forces to the material or the process of pressing materials to make it more firm and rigid solid.

Compression is used for the manufacturing of tablet.

In the compression of active pharmaceutical ingredients, overall control is essential to ensure high quality.

Physics of tablet compression: ►Transitional packing ►Deformation ►Fragmentation ►Bonding

►Deformation of solid body ►Ejection

Fig: Tablet compression cycle.

Common Problems that arise during Compression: Common Problems that generally arise during compression are● Binding to the dies and punches

• • • • • • • • •

Capping and splitting Lamination and Chipping Picking and Sticking Weight variation Mottling Hardness variation Double impression Pitted surface Drug instability

TABLET COATING:

Fig: NR-Cotar-39”‹FC-39› DEFINITION: Coating is the process of compressing a granulating layer around the preformed or pre-compressed tablet that is the core tablet. It is an additional step for manufacturing of tablet. The substances used as coating substances are usually applied as a solution or suspension in conditions in which evaporation of the vehicle occurs leaving a polymeric layer.

Classification of Coating: Mainly three types of coating are performed in the solid section. They are as follows: Coating Sugar coating

Film coating 1 Aqueous coating 2 Non aqueous coating

Enteric coating

1. Film coating: Film coating is the process which involves the deposition of polymeric substances as continuous and non-porous membrane over the surface of the core tablet. In film coating the thickness of the coat is 30-100µ.

Film coating process is based on two distinct phenomena1. Formation of film over the surface of the core tablet known as cohesion, 2. Bonding between polymeric film and the surface of the core tablet known as adhesion.

Polymers used in film coating:

Hydroxy propyl methyl cellulose, methyl hydroxy ethyl cellulose, ethyl cellulose, hydroxy propyl cellulose,Na-CMC, Poly ethylene glycol, acrylate polymer.

Steam temperature: Coating Organic Aqueous Enteric

Inlet 62-650c 70-750c 5o0c

Outlet 42-450c 50-550c 320c

3. Enteric coating: It is a coating technique applied to tablets to protect the tablet core from disintegration in acid environment of the stomach to protect the acid labile drug and to avoid gastric discomfort or to delay disintegration until they reach the upper intestine.

There are two steps for enteric coating І.Sub-coating: By using HPMC as polymer with either organic or aqueous solution. This process performs for 5 hours. іі.Enteric coating: By using udragil L-100 or L-50 over the sub coating. This is done for 15 hours.

Polymers used in enteric coating: Hydroxy propyl methyl cellulose phthalate, poly vinyl acetate phthalate, cellulose acetate phthalate, methacrylic acid‹Udragil›-L-100, S-100,L-300.

Condition required during Coating: •

Relative Humidity: Not more than 50%.

•

Temperature: Below 250C.

COMMON PROBLEMS ASSOCIATED WITH TABLET COATING: 1. Logo bridging

2.

Core erosion

3. Edge chipping/erosion

4. Picking/sticking:

5. Cracking:

6. Peeling

7. Orange peel/roughness

8.

Twinning:

9. Tablet-to-tablet color variation

Trade name AZIROX REVAM GOLD OMETAC FEA CHEWCE

Generic name Azithromycin Multivitamin (A-Z) Omeprazol Paracetamol Ascorbic acid

Number of tablet being produced in Navana Pharmaceuticals ltd.

•

2. Capsule

DEFINITION The word “capsule” is derived from the Latin word “capsula” meaning small box. Dosages forms in which unit doses of powder, semisolid or liquid drugs are enclosed within either a hard or a soft envelope or a shell are called capsules. Usually the shells are composed of gelatin.

Several categories of capsules may be distinguished:

• hard capsules; •

soft capsules;

•

gastro-resistant capsules;

•

modified-release capsules;

Steps involves in capsule manufacturing: ●Developing and preparing the formulation and selecting the capsule size ●Filling capsule shells (encapsulation), ●Sealing and ●Polishing the filled capsule (if required) (The industry does not manufacture any capsule shell.

The active is filled in the empty the hard gelatin capsule shell in the form of• Powder • Pellets The different sizes of hard gelatin capsule shells used in pharmaceutical manufacturing are- SHELL SIZE

FILL VOLUME‹in ml›

000

1.36 00 0.95 0 0.67 1 0.50 2 0.37 3 0.30 4 0.21 5 0.12 The capsule sizes used in Navana Pharmaceuticals Ltd. for general productionSize-0, 1, 2, 4.

# Encapsulation Process by Automatic Capsule Filling Machine: For encapsulation of pellets the following procedure is done with the help of Automatic Capsule Filling Machine in the capsule filling units of Navana Pharmaceuticals Ltd. Blend Pellets with NPS ↓ Encapsulation ↓ For encapsulation of powder, ↓ Blending ↓ Slugging ↓ Granulation ↓ Sieving ↓ Encapsulation

Encapsulation Process by Manual Capsule Filling Machine by Hand: For encapsulation of powder the following procedure is done with the help of Manual Capsule Filling Machine by hand in the capsule filling units of the industry: Loading of capsule in the loading plate ↓ Removal of caps of the shells ↓ Filling of powder

↓ Rejoining of caps of the shells ↓ Encapsulation ↓ Sorting of Capsules ↓ Polishing of Capsule Machineries used in capsule manufacturing: Machine name

Machine No of station/hole specification Semi automatic Capsule Capacity: 18000/hr 600 filling machine Capsule fill (Scorpio)

Automatic Cap-filling machine Hand filling capsule machine Double cone Blender(DCB150) Capsule polishing machine

Capacity: 40000/hr 48 Capsule fill Capacity: 12000/hr 300

Model

Manufacturer

MEC-

P+am pharmaceuticals, India.

M X .1 1 51 AF-40T MF-30

Capacity: 150Kg(rpm:25)

Hoong-a corporation,korea.

Number of Capsule being produced in Navana Pharmaceuticals Ltd. Trade name OMETAC DINAC-TR NAVACEF NAVAMOX NORTIN 10

P+am pharmaceuticals, India.

P+am pharmaceuticals, India India

Generic Name Omepraxole Diclofac-Na Ciprofloxacin Amoxacillin Nortriptyline

DRY SYRUP Manufactured method in Navana Pharmaceuricals Ltd, • Direct Mixing, Flow chart for Direct Mixing for the manufacturing of Dry Syrup:

Crushing the sucrose in mill at 3000 rpm ↓ Transfer of half portion of sucrose from step-1 into a double cone blender by passing through a 20 mesh screen ↓ Transfer of all other excipients in the blender to blend for 30 minute ↓ Transfer the mix from the double cone blender by Passing through a 20 mash screen

•

Machines used in the Dry Syrup Manufacturing unit:

Name of the Machine

Function

Double cone Blender Bottle Filling Machine Bottle Sealing Machine

Blending/Mixing Filling of Dry Syrup Sealing of Dry Syrup Bottle

•

Condition for manufacturing Dry Syrup: •

Relative Humidity: Not more than 45%.

•

Temperature: Below 270

Purpose of packaging: • • • • •

To increase the acceptability of the drug To increase the stability of the drug To minimize the transport/shipping hazards To improve patients compliance To improve the pharmaceutical elegance by use of special color or contrasting printing

At Navana Pharmaceuricals Ltd. Three types of combination is use depending on the upper & lower layers as well as product requirement. They are;

•

PVC-Aluminium Blister

•

Aluminium -Aluminium Blister

•

PVDC- Aluminium Blister

Besides blister packaging, at other packaging includes;

•

Striping ‹Alu-Alu›

•

Filling of tablets &capsules in bottles

•

Labeling of bottles

•

Secondary Packaging (Both on-line & off-line)

Packaging machineries: Name

Model

source

Automatic blister

DPP-250DII

China

capacity 60000/hr

Packing Machine MINISTAR VAT Automatic M.S dal Hooga-A South Korea 12000-90000/hr blister Packing Machine (Scorpio) Automatic Strip

Leo-4

India

Packing Machine Material Used: ●Alu.Foil (Blister/Strip) ●Alu-Alu Foil(Bottom)

●PVC/PVDC Film ●PP Cap

●Label

●Unit Carton

●Inset

●Plastic Spoon

●Plastic Cap

●Stopper

●Shipping Carton

●Cotton.

30000/hr

Fig: Aluminium foil Fig: Blister machine

NAME OF THE PVC/PVDC FILM USED: Name of the item

Width (mm)

1. Coffee brown 2. Glass Clear 3. Glass clear PVDC 4. Alu-Alu Bottom Name of the Bottle size: • • • • • •

Thickness (mm)

146 160 202 221

0.250 0.250 0.350 0.250

35 ml bottle Round Amber 70 ml bottle Round Amber 100 ml bottle Round Amber 130 ml bottle Round Amber 200 ml bottle Oval Plastic Container with Cap & Washer

Primary Packaging Materials: Automatic Blister Packing Machine: Machine Parts: ●Bottle Foil (P.V.C) uncoiler ●Pre-heating & forming station ●Hopper ●Feeding System ●Cover Foil ●Embossing Station ●Conveyor ●Control Panel

●Drive Motor ●Pneumatic Circuit ●Sealing Station ●Cooling & Slitting System ●Punching Station ●Waste Foil coiler ●Refrigerator & Cooling Unit

Flow Chart of Blister packaging Machine: Pocket formation (By Compression air & temperature)

Filling Station (Channel, feeder, dosage channel) Sealing (temperature) Cooling Code embossing Slitting Punching Pneumatic Actuator Automatic Strip Packing Machine: Flow Chart of Strip packaging Machine: Pocket formation Filling Station Sealing (temperature station) Cooling Batch Printing Slitting Secondary Packaging (Both on-line & off-line): Secondary packaging includes-

•

Unit Cartooning with -Container -Leaflet -Spoon/dropper (in case of liquid) -Security seal/ Hologrammed Seal

•

Master Cartooning with -

In-process check:

Unit cartoons

1. Observation no.

2. Leak test 3. Room condition a) Temperature & humidity b) Segregation of bulk materials/finished packs c) Product identity d) line, display board 5. Aluminum foil leaving in machine and stock 6. Number of individual strips/blisters checked 7. Number of finished products checked 8. Quality and identity of components compliant slip/labels/cartons/leaflets/outer labels/outer box/ spoon 9. Identity and appearance of product in packs 10. Quantity: No./volume/weight 11. Overprinting/embossing: batch no./MFD/Exp date/MRP 12. Label/carton with product name, batch no., Mfg date, price and Exp date.

Liquid Oral liquid preparations include-

• •

Oral Syrup Suspension

GENERAL MANUFACTURING PROCESS OF ORAL LIQUIDS: The general manufacturing of oral liquids in the liquid section of Navana Pharmaceuticals Ltd is briefly described below with a flowchart; Weighing of active ingredient/s along with excipients ↓ Mixing of excipients with certain amount of dematerialized (DM) water as specified in the Batch Production Record (BPR) by the aid of a mechanical stirrer ↓ Addition of active ingredient/s ↓ Passing through a pump to the storage vessel to the ↓ Transfer of the solution to the filling vessel through 0.5µ Cartridge filter. ↓

Filling, Flushing of Nitrogen (N2) & Sealing of Bottles (glass or pet) containing oral liquids Machines used in the Oral Liquid & Suspension Manufacturing units: Name

Speed

Source

Variable speed stirrer

1400rpm

India

Emulsifying Stirrer

2800rpm

China

Horizontal Filter Press

1400rpm

India

Inline emulsifier mixer

800 rpm

India

Colloid mill

2810rpm

Stainless steel Vessel Semiautomatic liquid Filling Machine Cap sealing Machine.

Fig: Inline emulsifier mixer Condition for manufacturing of Oral Liquids: •

Relative Humidity: Not more than 55%.

•

Temperature: Below 300

Steps involved in Suspension Preparation:

England

Dispersion of suspending agent Transfer to compounding vessel containing sucrose solution Addition of drugs & other ingredient Mixing with continuous stirring Adjustment of final volume with purified water Filling & sealing

Packaging

Research and Development: To launch a new product, the Research and Development department develops a formulation and manufactures the product on a laboratory scale. The stability tests are performed on these new products. After passing the tests the product is manufactured commercially. Research & development department prepares the manufacturing instruction, coating instruction (if necessary), packaging instruction, product specification and testing procedure file of the new product.

Navana Pharmaceuticals Ltd has a well established R &D department. This Department Perform the following duties1. New Product Development 2. Lab Batch Preparation 3. Stability study Purpose of Research & development department:

• • • • • • • •

To be the most productive Research & Development Centre.

To develop safe & effective therapeutics options for undiscovered drugs.

Always develop a new formula for old items.

To comply with cGMP requirement.

To prevent cross contamination.

Compatible with product line and dosage form.

To facilitate maximum Productivity.

Decrease product cost.

Equipment in Research & Development: Name

Source

Humidity control Oven Tray dryer/NI.G.P.M 5kg Mass mixer/NL-5kg Double cone blender

Bangladesh Bangladesh Bangladesh Bangladesh

Working flow sheet of P&D department for new product development: Flow chart of new product Launching: In-put -Proposal from PMD -Feasibility study -Approval by director ↓ Product designing -Lab batch preparation -Stability study -Product master file preparation ↓ Drug administration approval -Recipe submission and approval -Inclusion -Price approval ↓ Packaging material designing -Design and development -PM approval by QA and DA ↓ Purchase/Procurement -Packaging material and raw material purchase ↓ Commercial production -Pilot batch manufacturing -Process validation ↓ Distribution -Finished product distribution/ depot ↓ Final launching -Product briefing to field force and launching.

# Estimated time for product development and launching is 6-12 months.

Validation: Validation is defined as establishing document evidence, which provide a high degree of assurance that a specific process or system will consistently produce a result meeting its predetermined specification Validation normally required for processing, equipment’s services, production process, test procedure & computer system. The parameters, considered for the validation, are - Linearity - Accuracy (Recovering) - Precision (Reproducibility), etc.

Formulation of New product, Lab batch preparation and stability study: In this purpose the followings are done: 1)

Marketing feasibility:

Product management department studies marketing feasibility.

2) Product brief: To determine the dosages form, color and pack size for commercial preparation, product management department studies this feasibility.

3)Technical feasibility: Research and Development department, Quality control department and Production department study this feasibility. Here specific needs in the manufacturing and quality control for the product and any special recipient needed for formulation and annual requirement of material according to sales forecast are discussed.

4)Product specification analysis: R&D department does this paper by comparing with market brand to prepare draft specification. If the drug has no any BP/USP specification (i.e. INN drug), they follow the In-house technique.

5)Investment feasibility: Commercial department does investment feasibility.

6) Product summary report: Summery report is done by product management department and marketing department which includes product summary, cost analysis and investment etc. Operative Director approves this.

Task of Research and Development: 1. To prepare technical data of a new product: To study the character of active ingredient, such as — moisture sensitivity, pH, interaction with excipients, color etc.

To test active ingredient To establish and validated the test method of active ingredient.

2. Lab batch preparation: It is the process for small scale production test for the large scale commercial purpose such as — small scale production of ingredient, specification, quantity for bottles unit, quantity for batch, unit, % overage, actual quantify, unit.

Then this formula submitted for manufacturing procedure and the sample is forwarding to product management department for its approval.

3. Accelerated stability test: The sample is then send for accelerated stability testing and the analytical report is made.

Annexure are made to submit to Drug Administration through product management department for approval.

For Solid dosage form: 400 c temperature and 75% RH for a minimum period of 3 months. Shelf-life determination: 2 years: If 90% label claims after 90 days 3 years: If 90% label claims after 150 days 4 years: If 90% label claims after 270 days 5 years: If 90% label claims after 360 days Physical and chemical parameter should meet the specification up to this schedule time.

Raw materials requisition to commercial: The time requirement for the raw material takes 15 to 20 days. In this period some task will be done, such as — a) Technical data: It includes---Active ingredient, excipients, specification,, quantity of average manufacturing and formulation process with finished product specification, control data, approved shelf-life. b) Raw material test c) Analytical method development

Moreover the following duties are performed by Research and Development department in Navana Pharmaceutical Ltd. 1. All types of revision of master file of old items.

2. Continuing the GMP training in factory. All document (Training letter, Schedule, Manual, Evaluation papers) are prepared and maintain by R& D. 3. All technical documents of new products (Factory portion) are prepared and submitted to Drug Administration (D.A) by R&D via Regulatory Affairs of Navana Pharmaceutical Ltd. 4. All packaging material specifications are checked by R&D. 4. The text of Carton, foil, Insert, Label of a upcoming product is checked by R&D (i.e. proof checking before printing).

Development of existing product (Reformulation): R&D department also deals with the development of existing product formulation.

Objectives: • Increased the quality of the product.

• Prevention of any type of problem existing of the product.

• To save time and cost.

• Increased the patient acceptance.

At last, we can say that R&D is a mini plant which is engaged in structural elucidation, development and validation of analytical methods, stability studies of bulk products, assuring compliance with GMP requirements, implementation of Quality Systems, inspections and checks during the design and development of pharmaceutical products. The regulatory operations of this department include compilation of New Drug Application, Drug Master File and submissions.

Involved departments: • • • o

Raw materials Packaging materials store Finished product store

Find out under safety stock.

Warehouse Operation (Raw materials) in Factory: Storage systems of raw & packaging materials Appropriate storage of materials is prerequisite for the manufacturing of quality pharmaceutical products. All the activities of warehouse must be performed in systemic and defined method to avoid confusion, material mix-up and to prevent deterioration or shortening of expiry period of the materials. Warehouse must have the following facilities — •

Adequate lighting designated area for receiving, quarantine and storage.

•

Appropriate and designated area with controlled temperature and humidity for storage of heat and moisture sensitive materials.

•

Sufficient racks, shelves and pallets.

•

Proper ventilation where required.

•

An appropriate and sufficient balance, scales, scoops, containers, poly bags and other equipment for weighing and handling of the items.

•

Separate dispensing booth/room.

•

Separate storage arrangement for inflammable, corrosive, rejected materials.

•

Separate sampling booth.

•

Adequate fire extinguisher.

•

Entry of storage will be restricted, store officer must be provided with authorized list of personnel who will have access to ware house.

•

Storage area must be kept clean and free from spider web ,bird ,rodent and insects entry.

Storage in-coming materials: • • • • •

•

Receive all incoming materials through invoice /challan.

Inspect all the containers for visible defects such as — damaged / torn container, broken security seal, missing label etc. In case of major abnormalities immediately inform Commercial and Accounts Department with intimation to general manager (factory).

After complete inspection, transfer the consignment to quarantine area and intimate quality assurance through material arrival report with copy to commercial and account department.

Affix. “Under test” label on all the containers.

QA will collect sample as per procedure and sampling must be done in sampling must be done in sampling booth. QA will affix “Sampled label” on the containers from where sample was collected.

QA will test the consignment and with inform the result through raw material analysis report.

QA will also fix “Passed” label on all the containers. In case of rejection and non-conformity “Reject” / “Nonconforming” label will be fixed accordingly. Store will issue MRR to concerned departments after obtaining QA report of the consignment.

Approved materials must be transferred to approved / released material storage area. Reject / Non-conforming materials must be separated from released material, reject material must be kept on reject area and nonconforming materials must be kept in non-confirming area.

Storage material maintenance: • • • • • • • • • • •

All material has identification label. Incase of any torn /damaged identification tag QA to be informed immediately for replacement of labels.

All material should be stored at temperature and humidity as mentioned.

Material should be stored on pallets / racks, must not kept ground.

Material stored in such a way, which will facilitate physical inspection and cleaning of the material.

Flavor and color should be stored at a distant from materials in poly bags / paper bags.

Storage material Should be done in a systematic way where materials delivered to follow FIFO (fast in fast out) All materials must have BIN cards and BIN cards must be updated immediately after withdrawal of materials.

After the expiration of expiry date as indicated in “Passed” label of any material or in the case of any damage of container/visible physical deterioration of material QA must be intimated through “Material Re-testing Request” form.

All instruction as started in master procedures and standard operating procedure must be followed in store operation.

Warehouse must be inspected daily by QA and findings to be record daily.

Conditions of storage must be assessed in every month by QA and findings to be recorded in “Storage condition Assessment”.

The store is divided in following area: • • •

Receiving Area Sampling Area Quarantine Area: a) Ambient condition b) Controlled room

•

Main store: a) b) c) d)

•

Flammable Item Area Bottle store room Empty shell room Packaging material store room Rejection Area

Storage Condition: (1) Ambient Condition: 300±50c (2) Controlled room: 250±30c and RH 65%±5% Some common terms of Ware house: Sampling: The process of taking a small portion from a lot for test and analysis to show the quality of the whole lot is sampling.

Sampling quantity: Sampling quantity should be the double of one complete test.

Batch/Lot: A quantity of the product or material which is processed in one run during manufacturing.

Campaign A campaign means number of batches manufactured without any interruption or product change.

Handling The term handling means checking according to invoice/challan and other documents during receiving of the materials.

Preservation The term preservation 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 Dispensing 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 material is not ready for use and it is under test after received. So a quarantine label is attached to the container.

FIFO The term FIFO stands for First In First Out. LIFO: The term LIFO stands for Last In First Out. Re-test The term re-test means the samples are needed to be repeated analysis for identify vs previous documentation and it has been done either 3/6/12 months.

Materials sampling plan The materials sampling plan is done on the basis of FIFO system i.e. first in first out. For active ingredients every container and for excipients √n+1 containers are sampled (where n = total number of containers).

Routine activities - The executive receives RM according to the invoice/challan.

- Takes complain, if any problem is found.

- Takes GRIR form to the Q.A. department.

- Store the entire RM according to the storage guide.

- Supplies RM on the FIFO basis to the production floor as per requirement.

- Adjust present stock after dispensing.

- Find out the raw materials.

Observation During our training period in the ware house and its related departments we observed the following processes - How to develop production plan.

- How to maintain safe stock of inventory - How to supervise RM, PM and FP store - How to receive and dispense RM, PM - How to receive, store and dispense FP.

ISO International organization for standardization is an organization which will give a certificate to the manufacturing organization after inspection of the manufacturing area. This section introduces the ISO 9000 standards, ISO 9000 concepts, and the ISO quality system certification process.

Diagram illustrates relationship of the ISO 9000 series standards.

ISO 9000 Guides ISO 9000 ISO 9000

Conformance Model ISO 9001 ISO 9002 ISO 9003

A conformance model is a standard to which our organization must conform in order to be certified.

Primary benefit of ISO: 1.

Customer satisfactions.

2.

Increased productivity.

3.

Reduced waste, ISO 9001 conformance model covers following these sections: 4.1 Management Responsibility 4.2 Quality system 4.3 Contract Review 4.4 Design Control

4.5 Document Control 4.6 Purchasing 4.7 Purchaser Supplied product 4.8 Product Identification and Traceability 4.9 Process Control 4.10 Inspection and Testing 4.11 Inspection, Measuring and Test Equipment 4.12 Inspection and Test Status 4.13 Control of non-conforming product 4.14 Corrective Product 4.15 Handling, Storage, Packaging, and Delivery 4.16 Quality Records 4.17 Internal Quality Audits 4.18 Training 4.19 Servicing 4.20 Statistical Techniques GMP Good Manufacturing Practice (GMP) is one of the parts of ISO. GMP rules are directed primarily to diminishing the risk, inherent in any pharmaceutical production that can not be prevented completely through the testing of final products. Such risks are essentially of two types: cross contamination and mix-ups caused by false labels being put on containers. a. All manufacturing processes are clearly defined, systematically reviewed in the light of experience and shown to be capable of consistently manufacturing pharmaceutical products of the required quality that comply with their specification. b. Critical steps of manufacturing processes and any significant changes made to the processes are validated. c. All necessary facilities are provided, including 1. Appropriately qualified and trained personnel.

2. Adequate premises and space.

3. Suitable equipment and services.

4. Correct materials, containers and labels 5. Approved procedures and instruction.

6. Suitable storage and transport.

7. Adequate personal, laboratories, and equipment for in-process controls under the responsibility of the production management. d. Instruction and procedures are written in clear and unambiguous language, specifically applicable of the facilities provided. e. Operators are trained to carry out procedures correctly. f. Records are made (manually and / or by recording instruments) during manufacture to show that all the steps required by the define procedures and instructions have infect been taken and that the quantity and quality of the product are an expected; any significant deviations are fully recorded and investigated.

g. Records covering manufacture and distribution, which enable the complete history of a batch to be traced, are retained in a comprehensible and accessible form. h. The proper storage and distribution of the products minimizes any risk to their quality. i. A system is available to recall any batch of product form sale or supply. j. Complaints about marketed products are examined the causes of quality defects investigated, and appropriate measures taken in respect of the defective products and to prevent recurrence.

Good manufacturing practices including the following section: > > > > > > > > > > > > > ~ > > ~ > ~ >

Process validation.

Products complain.

Self- inspection and quality audits.

Personal Hygienic.

Premises.

Storage areas.

Weighing areas.

Production areas.

Equipment.

Documentation.

Master formula.

Packaging Instruction.

Batch processing Records Batch packaging Records Good practices in production Prevention of contamination Processing operation Control of sampling Starting and packaging material Production record review

Audit Audits shall be scheduled on the basis of the status and importance of the activity to be audited and shall be carried out by personnel independent of those having direct responsibility for the activity being audited.

Purpose of audit: 1. To identify the problem.

2. To give a suggestion for a specific problem.

3. To see all the manufacturing step are correctly done or not. 

The result of the audit shall be brought to the notice of personnel responsible for the area audited and management representative.



The management personal responsible for the area shall take timely corrective action on deficiencies focused during audit.



The audit finds and the implementation status of corrective action are discussed in the management review meeting.



Follow up wherever the corrective action requires short time shall be carried out by the auditor himself before submitting his report to MR.



If required, internal audit could be conducted by external qualified auditors.

INVENTORY CONTROL AND PLANNING: Inventory: Inventory is a list of goods and materials that available in stock by a business needed to satisfy future demand.

Control: Control is a monitoring administration. Controlling ensure that actions are running according to the plans made.

Planning: Planning is deciding in advanced what is to be done. It is a design for tomorrow’s action.

Objective of inventory control: To provide superior management of over inventory by optimizing inventory stocking levels for excellent customer service and profit maximization, Inventory control: Inventory or stock represent a large portion of the business investment and must be well managed to maximize profits.

Inventory control is concerned with minimizing the total cost of inventory. The three main factors in inventory control decision making process are – 1. The cost of holding the stock 2. The cost of placing an order 3. The cost of shortage; that is, what is lost if the stock is insufficient to meet all demand.

Classification of inventory control: Inventory is classified as follows- Packaging material 1. Raw materials: Active ingredient and excipients.

2. For local and export market.

3. Work in process: These materials and components on which is being done.

4. Finished product: These are the salable items for customer orders made for special customers.

Functions of Inventory control: Functions include sales, manufacturing, warehousing, ordering and receiving. These functions must be performed in sequence in order to have a well run inventory control.

Benefit of inventory control: 1. Cost control/ financial benefit.

2. Material stock control 3. Better quality maintain

4. Properly record maintain 5. Proper utilization of storage area.

Inventory control management: Management is the art of getting things done through others. Inventory management is a vital element that can spell the difference between success and failure in today’s competitive business world.

Inventory control management maintains all information about activities within organization that ensure the delivery of products to customers.

Inventory management system: There are two sets of techniques that can be used in a manufacturing operation1. Statistical inventory control or order point 2. Material requirement planning.

Inventory control system in Navana Pharmaceutical Ltd: Navana Pharmaceutical management uses material requirement planning technique for inventory management. Management requirement planning is based on production planning and inventory control system. It is used to many manufacturing process.

MRP system is intended to simultaneously meet three objective— 1. Ensure materials and products available for production and delivery to customers.

2. Ensure the most possible level of inventory 3. Ensure manufacturing plan activity, delivery schedules and planning action.

In this process the management considers the following: 1. Material warehouse store.

2. Material Inventory transit 3. Stock equivalent production 4. Material lead time 5. Minimum order level 6. RM/PM requirement for next three months 7. Shipment made 8. Product moving category 9. Monthly FG and PM average consumption 10. Month concern with PM/PR and FG. To ensure smooth production and supply of materials IC&P department always maintain liaison with commercial, warehouse, production department.

Product Management Department lies in the center of all marketing activities. A dedicated team with solid professional background comprising of Pharmacists, MBAs, Biochemists and Medical Graduates work in this department. They formulate the strategies to uphold the market share of company’s products, select and introduce new products to keep the company growing and develop promotional materials for sales people to win in the market.

PMD plays a key role in Pharmaceuticals Marketing. It’s function is point out belowProduct Launching Action plan Packaging Material Specification Promotional Material Specification Field force and target Market analysis Export Work Order Monthly Meeting Doctors Visit Assign product monitoring Training of MPO EXPORT: Today, at the age of globalization, it is a world without boundaries. With the aim to cope up with the challenges of globalization, Navana started its export operation. Today Navana export to 9 countries of three continents namely Singapore, Sri Lanka, Myanmar, Vietnam, Bhutan.

Now Navana is moving aggressively to increase its market share in the operating countries as well as to invade new countries. Some other African countries & countries of Middle East are under active search.

Navana is moving aggressively to increase its market share in the operating countries as well as to invade new countries. Some other African countries & countries of Middle East are under active search.

• • • • • • • •

Singapore Sri Lanka Myanmar Afghanistan Kenya Vietnam Ghana Bhutan

Comments:

• • • • • • • •

Penicillin and nonpenicillin area should be separated.

Space of the R & D department should be expanded.

Production area of factory has not proper ventilation.

Sufficient equipment are not available for lab batch preparation.

Granulation room must be air- conditioned.

Have to set up automatic generator to prevent electricity hampering.

Ware house department should be expanded.

There was no adequate space for QA Lab & Packaging material testing lab.