Sanofi-AventisAventis Limited Fisons (Bangladesh) Limited

Hoechst Martion Roussel Limited

SITE HISTORY

Pakistan Pharmaceutical Industry (PPI):

In 1960 incorporated as a joint venture company- Pakistan Pharmaceutical Industry (PPI) with May & Baker owing 60% and Pakistan Industrial Development Corporation 40% shares. Started production and marketing of Largactil, Flagyl, Stemetil, Phenergan etc in 1962.

Bangladesh Pharmaceutical Industry (BPI):

After the Independence of Bangladesh (1971), the company was renamed as Bangladesh Pharmaceutical Industry (BPI) in 1972.

Rhone-Poulenc Bangladesh Limited:

In 1986 the company was renamed as Rhone-Poulenc Bangladesh Limited and in 1990 Profenid, Peflacine, Imovane etc were developed for sale. In 1995 renamed as Rhone-Poulenc Rorer Bangladesh Limited (RPR) and animal health & nutrition and agrochemical business were reformed as a new company Rhone-Poulenc Agrovet Bangladesh Limited. Acquisition of Fisons held at the end of 1995. In 1997 GMP was upgraded and implementation of GMPs on site and Qualification & Validation activities were started in 1998.

Aventis Pharma : 1999 was the most important year in the History as merger of Rhone-Poulenc Rorer and Hoechst Marion Roussel (HMR) was done to form a new company- AVENTIS PHARMA. In 2001 complete transfer of Fisons and HMR products on site and Complete technology transfer of Amryl and Tritace tablets from Scopitto, Italy.

Sanofi-aventis: In 2004 a new company was developed, named Sanofi-aventis.

Sanofi Aventis In Bangladesh

10 Multinational Pharmaceutical Company in Bangladesh.

964 Employees.

80+ Bands.

7 major therapeutic areas

Cardiology

ThrombosisOncology

Central Nervous System

Diabetes

Internal Medicine

Vaccine

Introduction:

Tablet manufacturing and design is the most important, challenging and also critical process. To maintain its correct amount of drug(s) in the dosage form, extra care and alertness is essential in the tablet manufacturing process. Tablet constitutes a major class of dosage form.

Sanofi-Aventis produces commercial batch by validating the processes. . They follow -CGMP - SOP and -BMR during tablet manufacturing.

Some Basic Requirements For Successful Tablet Manufacturing:Sanofi-Aventis follows some basic requirements for quality tablet production. Such as: 1. Design: During our training in tablet section we observed that solid manufacturing section is well designed. They have-Separate rooms for different operations.There are two separate entrances for personnel and material respectively.Air lock doors. The operators don’t open the two doors simultaneously. Rooms are partitioned by transparent glass, which facilitates visual inspection from adjacent and far rooms.

Floor and walls have no sharp edges which prevents dust deposition.Floor is painted by epoxy paint.Rooms include within the tablet section are:Hand washing, shoe cover & gown wearing room.Office room.

Solution preparation room.Coating room (2)Dispensing room.Store

Granulation room (2)Blending room (2)Equipment store (mainly die and punch are stored here)Compression room (5)Capsule filling room (1)

2. Facility:

For CGMP Sanofi-Aventis have some essential facilities in solid manufacturing area. They have-Adequate space for separate operationAdequate electricity supplyHVAC systemPW (Process Water) supplyHPS (High Pressure Steam) supplyICA (Instrumental Compressed Air) SupplyVacuum linePressure differential gauze. Positive air pressure.TelephoneGenerator

3. Equipment:

Some old and some advanced machine are available in tablet manufacturing unit. For using equipments following points are maintained:

Safety card: provides safety instructions to machine operators.

Labeling: describes state of operation. As for example: MACHINE LABEL: TO BE CLEANED, CLEANED, UNDER TEST, UNDER INSTILATION etc.Machine logbook.

Proper cleaning of the machine.List of authorized persons. List of Equipments:

Name of equipments Manufacturing country Extra information UseManesty Rotogram granulator

England Mesh size 12 Granulator machine

Saizoner mixer granulator

India Granulator machine

Drum blender Dry granulation Mixer machineJaguar mixer India Capacity 250 L Mixer machineClinocone blender India Capacity 700 L Mixer machineRoto cube mixer England Mixer machineCube mixer England Mixer machineApex blender Mixer machineRAMA COTA 50 coating

Thailand Coating machine

Se jong SFC 170 coating pan

For coating solution preparation

Coating machine

Manesty acclacota 150 Coating machine

coating panOscillator England Sieving machineFitz mill Sieving machineAlexander werk For wet mixer Sieving machineManesty Rotapress MK11

England Tablet Compression machine

Manesty BB3B(27) England Tablet Compression machine

Cadmach tablet compression machine

India Capacity 1200/min35 station

Tablet Compression machine

Se jong machine Capacity 1200/min Tablet Compression machine

Sapphire fluid bed dryer Dryer machineAlliance fluid bed dryer tube

India Dryer machine

Marken capsule inspection  machine

Capsule inspection machine

4. Personnel:

All the process is validated in Sanofi-Aventis. In solid manufacturing unit, highly trained, experienced and skilled personnel are involved in tablet manufacturing ie. Granulation, compression, and coating Sanofi-Aventis is rich in skilled persons in tablet section. They are serving for the company for 15- 25 years.For the health and safety of the operators Sanofi-Aventis provides:Gowning

Mask:

According to hazard of the product all the products are divided into 3 categories as follows:OEB (operational exposure band) –2: Cotton maskOEB (operational exposure band) –3: N 100 maskOEB (operational exposure band) –4: PAPR (Powered Air Purifying Respirator)For blending: HFNP (Half Phase Negative Pressure)Ear protectorShoe coverGloves

Different solid manufacturing unit:

The different solid manufacturing units are:Dispensing unitGranulation unit:Dry granulationWet granulation Compression unit Coating unit

The manufacturing unit sends a demand paper according to their need, to the warehouse. Central Dispensing Unit weighs the required amount of active ingredient & excipients and then sends it to the manufacturing unit. Manufacturing unit received and rechecked it. Raw materials must be approved from IQC department before dispensing.

There are two types of granulation:Dry granulationWet granulation Steps of granulation process:

FLOW CHART

After proper blending granules are stored in a container and then it is delivered to the compression unit. Before compression some parameters are checked: -Proper cleaning of machine. -Proper arrangement of die and punch. -Removal of all the material relevant to previous product - HVAC system. -Dust collecting system -Humidity -Temperature -Pressure differential -Granules are poured into hopper

Dispensing unit

Granulation unit

From dispensing unit

Active ingredient & Excipients

Granulation unit

Mixing of Active ingredient & Excipients

Milling (size reduction & sieving)Drying

Further milling Blending

Compression unit

Then tablets are compressed. Some problems are may arise during compression. Such as- -Capping

–Sticking etc.

Coating is one of the important step after compression. Reasons for coating-Stability Taste masking Elegance etc.

Types of coating:

Sugar coating Film coating: Aqueous coating Organic solvent coating Enteric coating.

Steps of film coating:

FLOW CHART

Capsule filling unit:

In this unit pellets are just filled into shell and then inspected by Markem Inspection machine.

Tablet test:

After compression and coating tablets are delivered to IQC for some test. The tests are: AppearanceWeight variation Friability Disintegration time testDissolution testThicknessHardness

Preparation Observed:

Name of the product Active ingredient Types of dosage formTab. Avomine Promethazine theolate 25mg

Coating unit

Compressed tablets in feeding pan

Spray of coating solution

Simultaneous drying

Coated tablets

Tab. Amizide Amiloride hydrochloride 5mgTab. Asinar Ranitidine 150mgTab. Betanol Atenolol 25mg, 50mg, 100mgTab. Flagyl Metronidazol 200mg, 400mgTab. Fisat Co- trimoxazole 480mgTab. Inflam Ibuprofen 200mg, 400mgTab. Profenide Ketoprofen 50mg, 100mgTab. Salbutal Salbutamol 4mgTab. Stemetil Prochlorperazine Maleate 5mgTab. Amaryl Glimepiride 1mg, 2mgMacrocine granules For Suspension

Water Treatment Plant:

The Water Treatment plant runs 24 hours in a day. The water is circulating all the time and it reduces the chance of microbial growth.

Temperature Maintained: 800C Purified water reservoir tank capacity: 2200 liter WFI reservoir tank capacity: 700 liter

Diagram of Water treatment plant:

If conductivity is > 0.9Regeneration with 32% HCl & 30% NaOH

Water for cleaning purpose

Supplied Water

Disinfectant unit ( Use UV as disinfectant

1µ Filter

Ion Exchanger(Anionic & cationic)

CarbonFilter

StorageTank

10µ filters

0.2µ Filters Treated WaterStorage

Conductivity meter

Water for Injection:

Different Areas of Sterile Department

Class A Area under laminar airflowClass B Aseptic filling roomClass C Aseptic manufacturing & terminal fillingClass D Terminal product manufacturing

Bottle washingDispensingOther area of class 10,000

Class E1 Material entry, inspection & sterilization

Class E2 Packaging

Condition required & maintained:Pressure maintained: Temperature: 17 250CHumidity maintained: 30-60% RH

Laminar air flow ( LAF ):

Air is flowing as parallel stream in unidirectional & vertically. The area under LAF is class A. Air velocity near the point of fill should be 0.4m/s (0.36 – 0.54)

Equipments:

Sartosius BalanceMfg. vessel 50L for Aseptic, 100L & 200l for terminal (Five pionees, Wedster’s heddersfield)

Greatide bottle washing Machine (100mL)H.Struck & Co. Ampule washing machine (20mL)Bausch & Strdel Ampule filling & sealing machineRota ampoule filling & sealing machineGetinge Autoclave; Sanauij 6.V Autoclave; Royal Dutch Ad linder Autoclave.Hoong-A Blister packing machine

Process Description:

Receiving of raw materials:

Purified Water

Distillation column(4 Column)

UV irradiation

WFI800C

Cleanliness of incoming drums, containers & bagsNo materials except relevant to the productsQuality assurance approval

Dispensing of raw materials:

All materials of previous product are removedShop is cleanedBalance are calibratedTemperature, humidity & pressure are checked every hour

Manufacturing:

Mixing in WFI/distilled waterN2 gas passed to dissolve O2

PH adjustment. (QA approval)Temperature, humidity & pressure are checked every hour

Filtration unit:

Filtration through 0.2μ sterilize cartridgeFilter integrity test (bubble point) before and after filtration

Sterilization (apparatus):

PrevacuumSteavingPulsingWarming upSterilizingDryingAir inlet

Filling:

Headspace oxygen content ≤1.5%Gas bulk solution with N2 gasSample checked by QC for volume & O2 contentSample to microbiological lab for pre sterilization

In process control

Volume N2 gas flowO2 content

Shop clearance Sterilization (Product):

Prevacuum- 3 timesHeatingSterilizationPost vacuumPressure equalizationEnd

Leak testingInspectionPackagingCleaning:

First week – Savlon 17.5% solutionSecond week – Dettol 2.5%Third week – Savlon 17.5%Fourth week – Dettol 2.5%Last 1% hypochlorite solution to clean floor & IPA to clean walls & ceiling on every Thursday

QC Test:

Before filling of the solution into the ampouleAfter filling of the ampoule that is before autoclave called pre-sterilization test.After autoclaved for pyrogen test & sterility test

Maintenance of the filter:

10-inch cartridge filter for terminal & 6-inch capsule filter for aseptic of pore size 0.2µ.Washing:

Before use washed with 20L WFI, N2 gas. After used washed with 25L WFI & N2 gasApplying gas pressure (N2/compressed air) to the upstream sides of wetted filter to determine the minimum pressure required to foce bubbles of gas through the wetted filter (WFI + 60% IPA respectively). Pressure range 4 to 8 barPreparation Observed:

Avil 1 ml injectionFiclon 3 ml injectionLargactil 2 ml injectionWFI 5 ml, 10 ml, 20 ml

INTRODUICTION

Liquid section of Sanofi-Aventis Ltd is within the T4 building, which is divided into two separate zones, one is for liquid & cream manufacturing & another for liquid filling & packing. Cream & suppository filling is done within the manufacturing zone. Sanofi-Aventis follows BMR (Batch Manufacturing Record) for each product, which is validated according to GMP or CGMP. We observed that the section is provided with a variety of supplied line like N2, Compressed air, Hot water, Purified water, Boiler steam, Processed water, Low pressure steam etc.There is a separate DM water system ( 100% pyrogen free) for this section also.

ORAL LIQUID MANUFACTURING

Equipments observed

Equipment PurposeS.S.S.J. Manufacturing Vessel (2250L, 675L, 225L)

Manufacturing liquid preparation

S.S. Storage Vessel (2250L, 500L, 700L)

Store liquid preparation

Vortex Mixer For syrup mixingAgitator Mixer For suspension mixingDoser for ethanol supply To adjust the volume of ethanolMeta filter For syrup filtrationNylon cloth bag filter For suspension filtrationAir operated diaphragm pump

Pump syrup from storage vessel to filling unit

Centrifugal pump Pump one phase to another during emulsion preparation

Graduated dip stick For volume adjustmentS.S. Bucket To dissolve solid materialsS.S. bowl scoopS.S. Spatula & Scoop

For weight adjustment & solution preparation

Measuring Cylinder For volume measurementElectronic balance For weight measurement

Flow chart for oral syrup manufacturing

Remaining portion

Dispensing Manufacturing Filtering with Meta filter

Buckner filter

Storage vessel

Flow chart for emulsion manufacturing

In case of manufacturing accurately weighted raw materials of one batch will enter at a time. It will reduce the chance of cross contamination. Before manufacturing Temperature, Humidity, Pressure of the room is checked. Then manufacturing is performed in manufacturing vessel. For each preparation In Process Control Test is done to observe Appearance, Color & Odor of the preparation.

Syrup filtration is performed with meta filter before which meta filter is prepared with Hyflo Supercel. The syrup left unfiltered in the meta filter is collected into a labeled container as reworks which is filtered with Buckner filter. Suspension & emulsion filtration is performed with a special type of Nylon cloth bag filter using centrifugal pump.

After filtration syrup is stored in storage vessel & labeled as ‘Under Test’. Then ‘Quality Control Request’ & ‘Request for Analysis’ forms are submitted to QAD for collection of sample & analysis. After approval a new label, ‘Approved For Filling’, is attached & filling is started. In liquid manufacturing unit we have observed an ‘Eye Wash Kit’ for emergency eyewash, which is helpful in accidental eye injury.Oral liquid filling

Equipments observed

NAME FUNCTIONMaster bottle washing machine (6000 bottle/hr)

Wash bottles first with hot water then portable water (cold PRW) & then dried with steam.

Master bottle dryer Dry bottles, which are used for water sensitive powder filling.

E. Chung bottle washing machine Wash bottles with hot water then portable water (cold PRW) & then dried with steam manually.

Automate liquid filling machine Fill 130 bottle/min automaticallyKing cap sealing machine Seal bottle with cap automatically, capacity

120cap/minMyth cap sealing machine Semi automatic cap sealing Turn table machine After inspection excess bottles are arranged

in turn tableKing bottle labeling machine Label 100bottle/min

Preparation of oil phase in one vessel

Preparation of water phase in another vessel

Addition of oil phase into water phase using centrifugal

pump

Filtration with nylon cloth bag filter

Storage vessel

Carton sealer machine Carton sealingGravil liquid filling machine Fill 100 bottle/min semi-automaticallyInspection light machine Visual inspection of bottle through lightJC-M/L/S Automatic Labeler machine Bottle labelingMaster cap sealing Semi automatic cap sealingSime Cap sealing machine Semi automatic cap sealing

Liquid filling machine-shrunk type Semi automatic piston dosing filler

Flow chart for oral liquid filling

CREAM & SUP POSITORY MANUFACTURING

Equipments observed

NAME FUNCTIONKalix Dupuy Cream filling machine Cream fillingCream stirrer Cream stirringSSSJ Manufacturing Vessel (125L) Suppository & cream manufacturingPremier Colloid mill Cream millingOsborn Stirrer Ointment & Suppository StirringSarong Suppository sealing

Flow chart of suppository manufacturing

Empty bottle supply Bottle washing Filling Cap

sealingInspection

TurnableLabelingCap wipingInk-jet print checkingOuter

labeling

Outer making

Inserting in to outer

Closing of outer

Checking & Stacking

PR card writing

Heating the vessel by

steam (700C)

Melting of suppository mass

with stirring

Cooling up to 40-450C & add the

active ingredient

Sieving through 100 mesh sieve

FillingCooling up to 5-

150C

Sealing & cutting

In process quality control test of melted suppository mass is done to check the presence of agglomerates, average weight & microscopic appearance. If the fatty mass is not processed immediately after melting it is stored under N2.After filling it is kept for 1 day in refrigerator to form a solid mass. During sealing pre welding temperature is adjusted at 1430C & sealing temperature at 1650C.Quality control test of final product is done to check the appearance, sealing & leak.

Flow chart for cream manufacturing

There are several Packaging sections in Sanofi Aventis. Each of the sections are specified for particular group of dosage forms and drugs. The sections are as follows:

1. Non-Antibiotic Solid Packing sectionHere the non-antibiotic solid preparations such as Tablets, Capsules are packed which located in T4 building premises.

2. Liquid Packing sectionLiquid preparations such as emulsion, suspension, syrup, suppositories are

packed here which is also located in T4 building.

3. Penicillin Packing sectionInside the CPR building, there is separate packing section for Penicillin group

of products.4. Cephalosporin Packing section

Inside the CPR building, there is separate packing section for Cephalosporin group of products. In this section of the report only the Non-Antibiotic Solid Packing section has been described.

Non-Antibiotic Solid Packing Department

The Non-Antibiotic solid drugs (Tablets, Capsules) are packed in this section. Two types of packing materials are used here.

1. Primary Packing Materials

These materials actually come into the contact of products; such as aluminium foil, PVC film, PVDC film etc.

Preparation of oil phase in one vessel

Preparation of H2O phase in another vessel

Addition of oil phase to H2O phase through 100 mesh S.S.Screen

Homogenization with continuous stirring (30-40 rpm)

Passing through colloid mill into storage vessel

Cooling & filling

2. Secondary Packing Materials

These materials do not come into the contact of the product rather they provide extra protection and facilities for transport and use. These materials include-Printed cartoonFiberboard outerFilament partitionLinerHoneycombCellulose tapePacking Machines

There are two types of machines for packing products. Blister packing machine and Strip packing machine. There are a few strip-packing machines among which one is used for striping. The Blister packing machines are kept inside separated rooms to maintain healthy environment as well as safety. Each of the rooms is facilitated with individual Air Conditioning System.

Machines used for Blistering purpose are as follows:

Room No. Machines1. Horn Noack Blister Packing Machine2. Horn Noack Blister Packing Machine3. E.Th Noack Blister Packing Machine4. Hoong-A Automatic Blister Packing Machine5. E.Th Noack Blister Packing Machine (DPN-760)6. KLOCKNER Hansel Blister Packing Machine (CP3)

Process of Blister Packing

Blister packing is the most common practice in Sanofi Aventis. Most of the products are packed in this method. Usually PVC film and Aluminium foil are used for this purpose. The steps involved in Blistering are:

Rolling of PVCPocket formation by heat and vacuum pressureTransfer of tablets or capsules in the pocketsSealing of the pocket by Aluminium foil using heatPrinting over the foil if requiredPerforation of the stripsCutting of the strips.

The strips are checked for any kind of leakage every half hourly. The instrument used is-

Lippke Blister-Tester VC 1380

This machine is operated at 380-400 mm Hg pressure for two and half minutes.

After completion of blistering, the finished strips are then sent to the packing lines. There the following steps are done-FeedingLayingVisual checkingCartoon makingInsertingFlap closing and TappingOuter making and fillingOuter closing.Finally the finished packets are sent to warehouse after Quality Assurance approval.

Introduction:

Sanofi-Aventis, a multinational pharmaceutical company in Bangladesh is renowned for manufacturing quality antibiotic products. Very few companies in Bangladesh follow the guidelines of CGMP in case of manufacturing antibiotics. Sanofi-Aventis is one of them. According to CGMP antibiotics (C = Cephalosporin, P = Penicillin, R = Rifampicin) has to be manufactured in isolated area from that of non-antibiotics. The reason behind this guideline is that it prevents cross contamination and resistance development. Sanofi-Aventis has a separated building namely CPR for lactam antibiotic and Rifampicin.

CPR building has divided into three different premises for Penicillin, Cephalosporin and Rifampicin respectively. These three different premises are completely isolated from each other regarding the following features:

Different HVAC systemThree different water treatment plant for supplying purified water and WFIGowning Manufacturing areaPackaging WarehouseQC labWaste management tankNon-pharmaceutical activityOfficial activity

Due to these above reasons Sanofi-Aventis is the only company that can claim that they are supplying quality antibiotics and that’s why they got the offer of toll manufacturing from another renowned multinational company NOVARTIS and the second largest local company BEXIMCO PHARMACEUTICALS. This type of toll manufacturing can be a profitable business for Sanofi-Aventis as we realized that they have a huge production facility but don’t have that sort of production load.

Penicillin SectionTypes of produ

Capsule TabletDry powder for syrupPediatric dropDry powder for injectionProduction Equipments observed:

Name of the machine Made in FunctionDrum blender England BlendingClincone blender India BlendingCube mixer England MixingJ.G. Jackson & croikatt Glasgow

England Granulation

Appex granulator England GranulationManesty oscillating granulator England GranulationManesty Petrie Dryer England DryingManestry B3B (16) Rotary tablet machine

England Tablet compression

Manestry B3B (23) Rotary tablet machine

England Tablet compression

Manestry D3A Rotary tablet machine

England Tablet compression

Automatic Film coating machine

Thailand Tablet coating

Capsule filler Zanasi AZ20 Italy Capsule fillingCapsule filler Zanasi AZ40 Italy Capsule fillingCapsule filler Zanasi MG2 Italy Capsule fillingArenco auger filler Syrup fillingHauser filling machine Korea Injection fillingGetinge autoclave SterilizationHot air depyrogenation oven DepyrogenationBottle Dryer DryingHoong-A Blister packingGansons strip packer India Strip packingE.TH. NOACK Germany Strip packingImperial Electric and Gas Apppliances Co. Dehumidifier

Dehumidification

Penicillin Laboratory Equipment:

Name of the Equipment FunctionPolarimeter Optical rotation detectionMoisture Analyzer Percent of moisture detectionChromato-VUE cabinet TLC plate observationHot water bath To make a solution warmUltrasonic vibrator Rapid dissolutionKurl Fisher Titrator Percent of moisture detectionDisintegration Tester Determination of disintegration timeDissolution Tester Dissolution with respect to time

Friability Test Apparatus Friability determinationVacuum Oven DryingUnicom UV/Vis Spectrophotometer Quantitative analysisGenesis Series IR Qualitative analysisHPLC Impurities determinationElectronic Balance WeighingRefrigerator Cooling

Cephalosporin Section

Types of products:

Capsule TabletDry powder for syrupPediatric dropDry powder for injection

Production Equipment observed:

Name of the machine Made in FunctionDrum blender England BlendingRotogran GranulatonRotary bottle washer WashingBotttle Dryer DryingRotary vial washer Taiwan WashingGetinge Autoclave Sweden SterilizationHot air oven DryingImperial Electronic and Gas oven

Dehumidification

Hauser Machinary Dry Syrup filling, sealingZanasi AZ20 Germany Capsule fillingGansons Strip Packer Strip packingOTTO-Hansel vial blister packer

Blister packing

Jagenberg-Wene AG Germany LabelingAutomatic Bottle Labeler Labeling

Cephalosporin Laboratory Equipment:

Name of the equipment FunctionElectric Balance WeighingDisintegration Tester Determination of disintegration timePH meter Determination of PH

Dissolution Tester (6 chamber) Dissolution with respect to timeDissolution Tester (8 chamber) Dissolution with respect to timeRefrigerator Cooling

Ultrasonic Bath Rapid dissolutionUV/Vis spectrometer Quantitative analysisDecon Ultrasonic Equipment Rapid dissolutionBulk Density Apparatus Density determinationGallenkamp oven Drying

Cleaning:

MOP solution:

1st week: Savlon17.5% Solution2nd week: Dettol 2.5% Solution3rd week: Savlon 17.5% Solution4th week: Savlon 2.5% Solution

Weekly Cleaning:

1% Hypochlorite solution to clean the floor.70% IPA (700ml IPA +300ml WFI) to clean walls and ceiling on every Thursday.70% IPA (700ml IPA +300ml WFI) to clean floor everyday.

Container:

Disposable drum, bucket, polyethene bag etc are cleaned by 10% Na2CO3 or 3% NH3

Gowning:

100ml of 10% Na2CO3 or 3% NH3 in washing tank

MOP solution and IPA (flammable solvent) is sterilized by 0.2 cartidge filter.

Some Special Feature:

Fumigation:

To revalidate the aseptic area fumigation is done by 37% formaldehyde with water in 1:1 ratio. As formaldehyde is highly carcinogenic fumigation is done at best twice in a year according to corporate guideline. Sanofi- Aventis is able to maintain the aseptic area by taking precaution other than fumigation such as proper HVAC, LAF, personnel etc.

Decontamination: Antibiotic molecules present in the waste are not drained as such. First it is decontaminated ie. The lactam ring is broken down by adding 1.5 liter of 25% NH3 solution twice daily on working days.

Rifampicin Section

Types of products:

CapsuleTablet

Production Equipment observed:

Name of the equipment Made in FunctionDrum blender England BlendingGrams mill India MillingJaguar machine GranulationRotorgran (Manesty) England GranulationSophire fluid bed dryer DryingManesty RD3 (16) Rotary Tablet Machine

England Tablet compression

Deduster Removal of dustManesty accelacota England Coating

Introduction

As we know, Hoechst Marion Roussel(HMR) merged with Aventis (Rhone Poulenc Rorer) in 1999. But for some legal purposes, a separate building for HMR still exists. Manufacturing and packaging of the eight HMR products take place here. We visited the HMR building as a part of our training program.

Description and Observations

This particular building is arranged in twenty separate rooms or areas where different operation are performed.

Room no Operations Equipment used OriginR-1 Storage of raw

materials- -

R-2 Dispensing of raw materials

1.Metter PM 6000 balance2.Sauter wt balance 3.120 kg August sauter balance

-

GermanyGermany

R-3 Preparation of solutions for coating

1.Stirrer2.Oven3.Heater

---

R-4 Drying Heraccus Hot Air -

DryerR-5 Wet granulation Diaosna Mixer

R-6 Dry granulation 1.Cadmack Slugging Machine2.Ferwitt Granulator3. Sieving Machine

India

Germany

R-7 Preparation of solution for coating

R-8 Compression of granules

ROTA Press Manesty compressor.

England

R-9 Compression of granules 2

Cadmack Rotary Press.Capacity: 1800Tablet/min(35punch)

India

R-10 Wash-BayR-11 Storage of punches.

Different punches Are used for every Individual products

R-12 Wire House of In –Process Products(WIP)

R-13 What?R-14 Strip Packing Jaguar Strip

Packer With Batch PrinterCapacity:35Stroke/min (1 stroke=3 strip)

India

R-15 Personnel changing Room

R-16 Strip Packing zone 2 - -R-17 Strip Sealing 3 1.Uhlman Strip

packer2.Ganson Batch printer

Germany

India

R-18 Sugar Coating 1.Coating M/CCadmack Coating panCapacity:100 kg2.Polishing M/C

India

Germany

Karl Kolb CoatingPan Capacity:50 kg3.Hot Air Blower

R-19 Blister Packing Section

Uhlman Pac System

Germany

R-20 Blister packing Section

HMR Product ListFollowing solid products are manufactured here.

Operational schemeThe operational sequence in the HMR Building is similar to that observed in the solid section.

Quality control and quality assurance services are involved in every necessary step

Avil 2.7 mgAvil retard

Daonil 5 mg Frisium 10 mg Roxit 75 mg

Roxit 150 mg Lasix 40 mg Trental 400 mg

Raw Materials Dispensing Granulation(wet or dry)

Drying

Compression

Packaging Coating (if necessary)

Wear House

Rclcase

The origination of the concept of quality & Compliance: -

Now a days the manufacturing of Pharmaceuticals is quite complex & there also arise some responsibilities; for example ethical, legal and economic responsibilities. These responsibilities are immensely important for the production, control & marketing of quality products. A systematic checking form the raw materials in process, Packaging materials, labeling & finished products can ensure quality products. This is the Prime concern of the industrial Quality & Compliance Department. The Concept of total Quality 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 the production. During our training part in IQC, we observed that sanofi Aventis Performs almost everything that ensures quality of medicine.

WINGS OF IQC:

Industrial quality compliance department has 5 wings-

A. QUALITY ASSURANCE DEPARTMENT:

Quality Assurance department is responsible for assuring that the quality policies adopted by a company are followed and in most organizations it serves as the contact with regulatory agencies and are the final authority for product acceptance or rejection. It also helps to prepare the standard operating procedures (SOP) related to the control of quality. The in process duty of QA department are-

Monitoring DocumentationApprovalAuditing Self inspectionCorporate audit

Quality Assurance

Industrial quality & compliance

Quality Control

Microbiology AS/AD QARL

The role in documentation:

All production & control records should be reviewed, approved & maintained by the QA department to determine the manufacturing compliance with the established procedures before a batch of finished product is released for distribution.

The batch compilation process encompasses the following documents-Raw material requisitionPacking material requisitionCleaning mapping records (aseptic area)Cleaving label of mfg. machineWeighing label of raw materials.Environmental study report (out put area)Purified water analysis reportBMR.Temperature & humidity chartRequest for analysis In process inspection sheetResults of sterility/ pyrogen test Microbiological test report of bulk/ finished product.Analytical report (in-house control) Line-store –up inspection sheetPacking material record with specimen sample/ reconciliation Transfer note.Release for sale certificate.

B.QUALITY ASSURANCE DEPARTMENT:

Quality control (QC) department is responsible for the day-to-day control of quality within a company. The responsibilities of this department are-Testing of raw materials.Inspection test of Packaging materials.In Process control.Monitoring and inspection of operation fore compliance. Testing of finished products.

INSTRUMENTS USED IN ANALYTICAL UNIT OF Q.C

In Sanofi Aventis following instruments are used for analysis 1. HPLC2. Electric oven3. Monsanto hardness fester4. Pharma test disintegrator5. Friabilator6. Shaking machine7. PH meter8. Centrifuge machine9. UV and Visible spectrophotometer10. IR spectrophotometer11. Melting point apparatus

26. Micro melting point apparatus

27. Oven humidity, drying

28. Decon ultrasonic bathhot spot furnace

30. Sieve shaker

31. Karl-Fischer apparatus.

32. Dissolved oxygen meter

33. COD reactor

34. Refrigerator

35. TOC analyzer

36. Compactometer

37. Potentiometer

38. Compound microscope binocular

39. Polarimeter

40. UV/VIS double beam

spectrophotometer

41. Ammonia distillation machine

42. Nitrogen estimation tester

12. Moisture analyzer13. Dissolution test apparatus14. Muffle furnace15. Pinometer16. Liq particle counter17. Conductivity meter kit.18. Total dissolved solid meter19. LAP cabinet20. Automatic refractometer21. Magnetic stirrer22. Electrical stirrer23. MS and heater24. Viscometer25. Analytical balance

Raw material control:Good raw material specifications must be written in precise terminology, must be

complete, must be provide specific details of test methods, type of instruments & manner of sampling & must be properly identified.

Role of Q.C in purchasing raw materials:

The samples of raw materials from suppliers (demanded by procurement department) are tested by the Q.C department & if the sample meets the specification, them the sample is ready for approval. The approval comes from Q.A department after submission of the Q.C test reports.

After approval of the sample, the supplier asked for raw material, raw materials are tested, if the quality complies, the procurement department buys the raw material.Raw materials are kept in the quarantine are a during the testing of the supplied sample& after testing if everything complies to the standard demands then it is shifted to the store & labeled as approved.

THE TEST PERFORMED FOR RAW MATERIALS:

According to GMP each raw materials should be tested for conformity with specification for identity, strength, purity and quality parameters.

The quality control department .of AVENTIS performs the following tests on raw materials -------• Appearance • Odor• Identification- (melting point, UV/ VIS method, IR absorption spectrum method.)• Solubility• Refractive index• Wt.per ml/specific gravity• Chloride/bulk density• Loss of drying• Residue of ignition/sulfated ash• Specific rotation/acid value

• Viscosity/iodine value• Saponification value• Acidity/alkalinity• Oxidising/reducing agent• Microbial count• Assay

IN CASE OF PACKAGING MATERIALS:

For ensuring better safety and attractiveness of packaging materials QC department conduct the following tests of packaging materials –

LABEL:

1. Grain direction: The label is kept on water in a pot and observed that it is properly rolled or not. After a while it will be opened to indicate that it is passed.2. The printing, the expire date, batch no and other items are checked and compared to a standard one.

2. The color and size are also checked against a standard.

CARTOON:

1. The color and text are compared with an approved standard.2. Proper gumming or gluing check3. Strength of the cartoon is checked in gram/sq. meter4. Proper locking check5. Flap cut checking

VIALS: 1. Alkalinity2. Thickness3. Cap diameter4. Proper aluminum seal

FOILS:

The color, the plastic layer and the thickness are compared with a reference standard.

COLLAPSIBLE TUBES:

a. Textureb. Specification measurementc. Inside lacquering testd. Latex seal checke. Presence of Aluminum seal

RUBBER CLOSURE

a. PHb. Stickiness

c. Toxicityd. Ash contente. Densityf. Alkalinity

AMPULES:

a. Surface and sometimes-total alkalinityb. Thicknessc. Heightd. Breaking pointe. Volume

CAP:

Printing, color, diameter, height etc are checked.After packaging of the product, packed materials such as strips, ampules, blisters, bottles etc are checked for accuracy. It is not possible to check all the products of a batch. Random sampling on the basis of the following rule checks them√N+1Where N=no of containerAfter sampling every sample is checked. Usually three types of mistakes are checked———

1. Critical: this is the problem, which cannot be overlooked. E.g.-DAR No. (Drug administration registration number).If DAR is wrong the whole batch will be discarded.2 Major: For this type of problem reprocessing is possible. E.g.-spelling mistake.

3. Minor: Simple mistakes which can be overlooked.

FINISHED PRODUCT

GMP specification

a. For each batch of drug product, there should be appropriate laboratory determination of satisfactory conformance to its finished product specification prior to release.

b. Drug products failing to meet the established specifications and other relevant quality criteria should be rejected. Reprocessing may be performed if possible but the reprocessed product should meet all the specification and other quality criteria prior to its acceptance and release.

Finished product should be checked in the laboratory by suitable procedures. These tests are designed to determine compliance with specification and hence arc critical factor for the QC department.

Each lot of products is tested to ensure identity, quality, purity and potency. Q.A Authorizes the releases for further processing based on actual physical, chemical & biological laboratory testing

The following tests are performed here for the finished product-

For Emulsion (e.g.- Ascabiol 100 ml Emulsion)

Parameters checked——Appearance—Odor —Miscibility with water—Benzyl benzoate content—Percent stated dose

For Elixir (eg-Phenergan 125ml Elixir)

Parameters checked—— Appearance—Odor—Identity—Weight/ml at 20° C—Volume—Pi I at 25° C—Alcohol content—Drug content— Percent stated dose—Microbiological test

For solid dosage form:

Parameter checked—— Description— Identity— Diameter— Thickness— Uniformity of weighta) Average weightb) Maximum individual variation— Hardness— Friability— Disintegration time— Assay---- Percent stated dose

In Process quality control (IPC) To assure batch-to-batch uniformity and integrity of the products, written procedures describing sample taking, the controls and tests or examinations is conducted on in process products of each batch should be established and followed. Such control is intended to monitor the product yield and validate the performance of the production process that may be responsible for causing variability in the characteristics of in process products.

The following in process quality control procedures are adopted

IPC for Manufacturing Section: -Product Tests performed

Tablet Wt. Variation Friability Disintegration Dissolution Hardness Thickness

Capsule Wt. variationMoisture contentSealing

Liquids Bottle volumeSterile products Over all supervision for all steps performed

by the operators whether they complies or not with the SOPs.

IPC for Packaging Section:

The quality control/ quality assurance officer checks the packetsThe labels are checked by the officer to the standard labelsThe cartoons are checked randomly whether they contain specific no. Of packs or not.The blister and the sealing of the finished product are checked.After all these inspections, the finished product is ready for storage. The relevant papers of the packaged products and storage are verified and maintained by the quality assurance officer.

B. ANALYTICAL SUPPORT AND ANALYTICAL DEVELOPMENIYASNAD)

This department is responsible for stability testing as well as changing anything in SPEC; here three types of products are tested

1) Marketed product:

For marketed product at least one product from each batch isStored in ambient condition. Drugs are stored in such a condition that is naturally provided by chemist shops in rural areas. The stability of the product is tested after a certain frequency which may be 0,3,6,9...months and so on.

2) New product:

For new product three batches are produced. If the drug is INN five times analysis is performed from each batch.For new products stability is tested in 3 types of conditions, these are— a.

Accelerated condition:

• In 45° c temperature & 75% RHIf the new drug is stable in this condition for 6 months then it is forwarded to drug administration.For vaccine accelerated condition is 2° c

b. Ambient condition

Drugs are tested after every 3 months.

C.25°c+60% humidity control,Stability under this condition is tested after every 3 months.

3) Change control:

The ultimate goal of change control is to reduce the cost Change control may include the change of• Coating materials• Packaging materials• ExcipientsChange control products are also stored in ambient condition. Samples are tested after every 6 months up to 36 months.

D) MICROBIOLOGY DEPARTMENT

The department of Microbiology performs the role of immense importance to follow the cGMP and to formulate as well as to implement the SOPs. The overall activity profile of the microbiological section of QC department of Aventis can be presented briefly in the following way------

INSTRUMENTS USED IN MICROBIOLOGICAL ASSAY

Microbial count

Pyrogen test (LAL test) sterility test

Environmental study

Preservative efficacy test

Validation

Pyrogen hygiene test

Bioassay

Penicillin cross contamination study

Water,Raw materials. Bulk samples, finished products (sterile) packaging containers

Water, injectables.raw materials, other sterile products

All manufacturing & filling areas including aseptic filling room.

Finished pack samples, preservatives

Steam & dry heat sterilization, oven cleaned equipment

All production area operation

Antibiotic, raw materials, comperative study of other antibiotics

Penicillin in environment & non-penicillin production area

Particle counterAir samplerIncubatorAnaerobic jarCentrifuge machineWater bathFreeze to preserve bacteriaPPH meterColony counterMicroscopeLaminar flow machineHot ovenDust collectorAutoclaveBalanceLAL testing kit

E) QUALITY ASSSURANCE REGULATORY LIASION

This department submits the paper, which is necessary for product registration. The necessary steps that is required for drug registrations are----

For registration of new product

If

If approved

FOR INN DRUGS

Recipe summationStability data + enexir + foil design carton,Should be submitted

Product is registered

Sample + test report +procedure +analyzing data submission

If approvedRecipes submission

Then again submit the sample +annexure

Product is registered

If approved

If approved

INTRODUCTION

Store is the transit point of any Pharmaceutical Industry because it is the place where raw materials first gets entry, goes to manufacturing and the finished products after manufacturing are also temporarily stored here before releasing to the market.During our visit in Sanofi-Aventis Ltd. we went through the warehouse i.e. the storage, dispensing facilities.

OBSERVATION AND DESCRIPTION

There are several areas for the storage of different materials. They are stated here-

In T4 building for non-antibiotic products-

Warehouse 1- it is the storage place for finished productsWarehouse 2- it is the storage place for finished products. There are two separate zones for the storage of rejected products& promotional sample in this site also.Warehouse 3- it is the storage place for packaging material (both for antibiotic & non-antibiotic).Warehouse 4- it is the storage place for raw material of Aventis Ltd. & HMR.Warehouse 5- it is the storage place for raw material of FBL.Cool store- there is two cool stores, one for raw materials & another for finished goods, which are heat sensitive & the temperature is maintained below 200c.Foster store- here temperature is maintained between 2-80c.Antibiotic active ingredients, vaccines (imported), Insoman (an insulin preparation) are stored here.For glass bottle & shipping carton storage there is a separate storehouse in Aventis.

In CPR building for antibiotic products-

Warehouse 6-Active ingredient and finished products of Penicillin section are stored. Temperatures maintained below 300c.Despensing of raw material are also done.There is a specialized raw material store of antibiotic section where temperature is maintained between 15-180c.

Warehouse 7-Active ingredient and finished products of Cephalosporine section are stored. Temperatures maintained below 300c.

Type of material in raw material stores-Quarantine- the material that is just entered in to the warehouse& Quality control tests do not perform yet.

Sampled- the material from which samples are taken for quality control test.

Approved- the materials, which passes QC tests & can be used for manufacturing. In this type of product QC fixes an expiry date after which the product must be retested for further use.

Rejected- the materials which fails QC tests & must be discarded.

Type of products in finished product stores-Awaiting Approval-after manufacturing finished product is labeled as ‘awaiting approval’ before quality inspection by QA department.

Approved-QA approved product, which is ready for distribution.Within the warehouse each type of products are stored in separate & identified zone for easy & proper identification.

Some important factors we were informed during our visit are:

FEFO (first expiry first out) strategy is followed for the release of raw materials to manufacturing.

Although materials are always taken from approved source; batch no of the vendors, manufacturing date, expiry date & quantity are checked before entryComplete security and prevention of pilference of every material including the promotional are said to be confirmed.

Central dispensing unit

According to cGMP guideline recently Sanofi-Aventis has started Central Dispensing Unit. It is a specially designed area from which accurately weighted raw materials according to process order are dispensed to production floor. When required raw material from warehouse enters in to central dispensing unit & then weighted under Laminar Air Flow Cabinet to prevent any type of contamination. Before weighing the area is inspected & certified as clean & weighing is performed on calibrated weighing devices that are sufficiently sensitive to the quantity of materials being weighed. After weighing rest of the materials (broken materials) also stored in this unit for further use. In this case the broken material container contains a label on which dates of the material used are noted.

Sampling room

There is a sampling room for the quality control group to take sample from the quarantine materials for quality control test. In this room also sample is taken under Laminar Air Flow cabinet to prevent any type of contamination.

OPERTIONAL SCHEME

Material receive by primary checking

‘Quarantine’ tag is fixed

The engineering department of Sanofi Aventis proceeds with a group of engineers, technicians and workers. Their activities can be divided into two classes.

Maintenance of the existing systems

The function of this section is to operate the utilities and services in the plant. They also perform the maintenance functions. The utilities and services handled by this section include-ElectricityPotable or Drinking waterSteam BoilerAir compressor

QC department takes sample & ‘Sampled’ tag is fixed

QC fixes ‘Approved’ tag if tests are passed‘Rejected’ tag is given if materials fail to pass the tests

Approved material goes to Production Department

Manufacturing

Packing

Finished product come to store again

‘Awaiting Approval’ tag is given

Quality Inspection on finished products are done by QA department

Goes to depot for distribution

Destruction

HVAC SystemCentral Vacuum System &Calibration Department.

Project

The personals involved in this section have design new facilities as per requirement, generation, setup of the facilities. The section also prepares the initial documents such as design outlet, capital expenditure for machines, building or any other facilities. After completion of the project, it is handover to the Maintenance Department for further services.Calibration Department

This department is responsible to calibrate all the instruments and machines for performance to assure their effectiveness. The general process is to calibrate the instrument or machines against a Standard which is also standardized against International Standards.

According to product quality management the instruments used in Sanofi Aventis have been divided into 4 authentic classes.

Class Description CalibrationClass- 1 These instruments are directly related to product quality

and any deviation will harm the products.Calibrated 3 or 6 monthly

Class- 2 These are standard instrument which are used to calibrate other instruments.

Calibrated one yearly

Class- 3 These instruments are indirectly related to product and quality or any deviation will not harm the products.

Calibrated one yearly

Class- 4 Tools instruments used for various purposes --

Electricity

There are three substations to provide continuous electricity in the plant 500 KVA1250 KVA2000 KVA.

There are also several generators to provide emergency power supply to the plant.

Generators Capacity No.

Gas 2000 KW 1 no

Diesel 500 KW 2 no.

800 KW 1 no.125 KW 1 no.

HSE

Implementation Of HSE Concept in SANOFI AVENTIS Bangladesh

The concept of HSE (Human Safety and Environment) is a modern and dynamic one and most recently has been implemented in a few industries in Bangladesh. In case of a Third world country like Bangladesh, HSE concept in industrial areas is hard to find. Among the Pharmaceutical Industry leaders of Bangladesh, Sanofi Aventis adopted this Policy successfully with continuous modifications and authenticity.Mission

The mission is to integrate HSE in all function to build a safety and healthy workplace and to ensure a sustainable environment.

HSE Policy

The HSE policy is based on 8 guiding principles which define a framework of actions with respect to their Group employees and external partners. It has been applied to all of their activities.

The HSE policy is an integral part of the general policy of the Group.

The management and the employees of the Group apply the policy at all levels. Each person is aware of their roles and their personal responsibilities with regard to the prevention of accidents, risk top health or damage to the environment.

In all places in which the Group operates it respects the applicable laws and regulations, applies expert recommendations and uses the best industrial practices.

Sanofi Aventis operates management systems relating to safety, health at work and protection of the environment adapted to each of its activities. These systems are assessed periodically, by measurement of the results obtained, by defining objects for progress and by implementing action plans called PASS with associated control system. This process depends on basis understanding, learning from experience, working together and training.

Every development project and every product launch will be subjected to a safety, health and environmental risk assessment integrating all the scientific and technical knowledge of the Group. Such project will be developed using the best available technology throughout a products half life.

Sanofi Aventis take care to economies on natural resources to minimize the residual impact of atmospheric emissions of effluents or of waste in all its industrial activities in order to preserve the natural environment.

With regard to its suppliers, contractors an subcontractors, Sanofi Aventis aims to promote the applications of the rules of safety and protection of environment and considers the adoption of these rules as criterion to be applied to suppliers, contractors or subcontractors.

Sanofi Aventis has a constructive attitude of transparency and dialogue with regard to third parties with respect to its safety, health and environmental protection policy, its achievements and its commitment.

Good Practices

HSE Concept has been implemented in Sanofi Aventis through some good practices which are as follows:

The site has set up a health center to provide regular medical checkup and emergencies.The site has Automatic External Defibrillator (AED) to attend Emergency Cardiac Arrest Problem.

Installation of public address system.Formation of team for crisis management, emergency response, fire aid and fire fighting.

Emergency preparedness.Implementation of risk assessment review program.Process monitoring and controls. Efficient Waste management system to ensure maximum environmental protection.Review of HSE management system.

Protection of Environment

The major approach to protect environment includes waste management; whether solid, liquid or gaseous. The basic waste management procedure includes-IdentificationInventoryCharacterizationClassification / LabelingSeparationCollectionAccumulation storageInternal treatment if necessary (neutralization, compaction, shredding)TransportationDisposal / recoveryRegister maintaining

The plastic, metallic, paper wastes are directly sent to salvage to dispose. The glass wastes are crushed before sent to salvage. But the chemical wastes are treated in the following way-

Effluent Treatment Plant

Chemical waste

Liquid waste Solid waste

Incineration

Treatment

Alkali / Ammonia treatment in case of Antibiotic

Disposed Outside

Figure: Flow chart of Chemical waste management.

Health and Safety management

By keeping environment clean and pollution free Sanofi Aventis Bangladesh is maintaining a very healthy environment. Also the natural scenario adds boost to the working environment.They provide in house medical facilities through Medical Center and in house Doctors. The medical center is well equipped with systems to manage emergency situations.

In an industrial area Safety is the most important issue and Sanofi Aventis is providing safety to each sector of the organization. It has a good security system which is enforced with Group-4 flack.

As the employees work in close rooms and sometimes with flammable liquids, every room has fire alarms and fire extinguishers. There are emergency exit doors in every areas. Fire alarms and the extinguishers are regularly checked for their effectiveness.Every machine and procedure have safety instructions in written form. The employees are trained according to the safety instructions. There are first aid medical boxes inside each department. There is also protective gowning system which includes dress, mask, cap, arm cover, gloves, safety glasses, ear muff etc.

Training Programs

The site provides regular training to the workforces on HSE matters, carry out Risk assessment studies, Emergency fire drills and Emergency evacuation drills.

In details the training program includes –ErgonomicsFire protectionFirst aidHazard protectionElectrical safetyAccident preventionLife style modificationPersonal hygieneHSE leadership training for Supervisors & Line Managers.

HR

Implementation Of HR Mission

Positive ThinkingGroup ApproachTransparent CommunicationShared and cared GrievancesPractices of Creativity

Open door policy

HR Activities::Human Resource Department consists of two divisions-A. Human Resource and B. Administration.HR performs the following activities-Policy FormulationStaffing:RecruitmentResignation

DismissalRetirementTraining and DevelopmentEmployee RecognitionCompensation and BenefitIndustrial RelationsPerformance EvaluationAdministration performs the following activities-CanteenSecurityTransportSite cleanlinessExternal Relations

HEAD COUNT AND DISTRIBUTION

Conclusion:

During our visit in Sanofi-Aventis from 10th Aug to 7th Sep.2006 we enjoyed every moment and have learn many things .The experience was delightful and it will encourage our performance in the future days. This experience will support us to follow cGMP accordingly and will be very helpful in producing innovative products.

1. During our visit we found huge number of female employees working in Sanofi-Aventis in different positions. Sanofi-Aventis believes in empowerment of female.

2. All the employees are very helpful and co-operative.

3. Facilities provide by the Sanofi-Aventis are excellent for the workers and the working environment is friendly. All the workers are efficient enough to carry out their respective duties as they are trained up regularly. All these make workers to work with smiling face.

Function Registered (ITC)Production 271IQC 36Engineering 36HR & Admin 9Plant Logistics 39Project 2HSE 2IA Controlling 3Total 398

Unique features of Sanofi–Aventis Limited in Tongi Plant:

4. They provide us food and transport facilities.

5. All machineries and the written procedures (BMR, MI, PR etc) are validated and calibrated regularly to ensure the best quality of the products.

6. Internal audit is done all the year round. This helps to improve the performance, fixing the errors.

7. Cephalosporin Penicillin and Rifampicin (CPR) are produced in separate building with require facilities.

In warehouse the dispensing section should be maintained by a pharmacist to look after all the necessary ins and outs of dispensing drug and raw materials.Automatic double door system must be installed in production area.HVAC system should be installed in the solid packaging section.In IQC, the analysts must have to wear protective gloves on their hands.Solid packaging machines should be totally automated.

Jet printer should be used in strip packaging in Penicillin section of CPR.An AC is essential in the patient cabin of the medical center.Manpower shortage in officer’s level might harm the process of production and Quality Assurance.

Supply chain department should be situated in the industrial area.In suppository department full-automated filling and sealing machine with cooler attached, which is latest, might be introduced.

We would like to draw your kind attention on the following matters that we believe will be helpful to improve the system: