B.Pharm (Hons) Part –IV Examination 2004

In Plant Training Report 2006 Faculty Of Pharmacy University Of Dhaka

Submitted By-

Tasnuva Haque Exam Roll: Curzon No: 45 Reg. No: HA-3647

Md. Mesbah Uddin Talukder Exam Roll: Curzon No: 28 Reg. No: HA-4653

Md. Ashraful Islam Exam Roll: Curzon No: 22 Reg. No: HA-4168

Md. Mynol Islam Vhuiyan Exam Roll: Curzon No: 01 Reg. No: HA-4658

Tania Sultana Exam Roll: Curzon No: 40 Reg. No: HA-3934

Shahanaj Begum Exam Roll: Curzon No: 46 Reg. No: HA-3645

In the name of ALLAH, the merciful, the compassionate

We, the student of Faculty of Pharmacy, University of Dhaka have the honor and privilege to express our heartiest thanks and gratitude to the following authority of Sanofi Aventis.

A.B.M. Anwar HossainDilruba Sharmin KhanShahanaz ParvinAbdur RazzakMd. Muin Uddin MazumderS.Y.R, QuadriA.K.M. Akhlaqul HossainAbdus SelimJabair HossainM Manjurul Islam

……..and all the employees of Sanofi Aventis for their co-operation.

We would like to express our gratitude to Prof. Dr. Abdur Rashid Dean, Faculty of Pharmacy, University of Dhaka for his kind effort to make this training possible.

We specially would like to recall Prof. Dr. Nurun Nahar Rahman for her kind co-operation.

Lastly we wish the cumulative progress of Sanofi Aventis in the forth-coming future.

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.

In Bangladesh

10 Multinational Pharmaceutical Company in Bangladesh.

964 Employees.

80+ Bands.

7 major therapeutic areas

Cardiology

Thrombosis

Oncology

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 operation Adequate electricity supply HVAC system PW (Process Water) supply HPS (High Pressure Steam) supply ICA (Instrumental Compressed Air) Supply Vacuum line Pressure differential gauze. Positive air pressure. Telephone Generator

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 informationUse

Manesty Rotogram granulator

England Mesh size 12 Granulator machine

Saizoner mixer granulator

India Granulator machine

Drum blender Dry granulationMixer machine

Jaguar mixer India Capacity 250 LMixer machine

Clinocone blender India Capacity 700 LMixer machine

Roto cube mixer EnglandMixer machine

Cube mixer EnglandMixer machine

Apex blenderMixer machine

RAMA COTA 50 coating

ThailandCoating machine

Se jong SFC 170 coating pan

For coating solution preparation Coating machine

Manesty acclacota 150 coating pan Coating machine

Oscillator EnglandSieving machine

Fitz millSieving machine

Alexander werk For wet mixerSieving machine

Manesty Rotapress MK11

EnglandTablet Compression

machine

Manesty BB3B(27) EnglandTablet Compression

machine

Cadmach tablet compression machine

India Capacity 1200/min

35 stationTablet Compression

machine

Se jong machine Capacity 1200/minTablet Compression

machine

Sapphire fluid bed dryerDryer machine

Alliance fluid bed dryer tube

IndiaDryer 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:1. OEB (operational exposure band) –2: Cotton mask2. OEB (operational exposure band) –3: N 100 mask3. OEB (operational exposure band) –4: PAPR (Powered Air Purifying

Respirator)4. For blending: HFNP (Half Phase Negative Pressure)

Ear protector Shoe cover Gloves

Different solid manufacturing unit: The different solid manufacturing units are:

Dispensing unit Granulation unit:

1. Dry granulation2. Wet granulation

Compression unit

Coating unit

Dispensing 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:1. Dry granulation2. Wet 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

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

-Temperature -Pressure differential -Granules are poured into hopperThen 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:

1. Aqueous coating 2. 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:

Appearance Weight variation Friability Disintegration time test Dissolution test

Coating unit

Compressed tablets in feeding pan

Spray of coating solution

Simultaneous drying

Coated tablets

Thickness Hardness

Preparation Observed:

Name of the product Active ingredient Types of dosage form

Tab. Avomine Promethazine theolate 25mg

Tab. Amizide Amiloride hydrochloride 5mg

Tab. Asinar Ranitidine 150mg

Tab. Betanol Atenolol 25mg, 50mg, 100mg

Tab. Flagyl Metronidazol 200mg, 400mg

Tab. Fisat Co- trimoxazole 480mg

Tab. Inflam Ibuprofen 200mg, 400mg

Tab. Profenide Ketoprofen 50mg, 100mg

Tab. Salbutal Salbutamol 4mg

Tab. Stemetil Prochlorperazine Maleate 5mg

Tab. Amaryl Glimepiride 1mg, 2mg

Macrocine 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 airflow

Class B Aseptic filling room

Class C Aseptic manufacturing & terminal filling

Class D Terminal product manufacturing

1. Bottle washing

2. Dispensing

3. Other area of class 10,000

Class E1 Material entry, inspection & sterilization

Class E2 Packaging

Condition required & maintained:

Pressure maintained:

Temperature: 17 250C

Humidity maintained: 30-60% RH

Purified

Water

Distillation column(4 Column)

UV irradiation

WFI800C

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 Balance Mfg. 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 machine Rota ampoule filling & sealing machine Getinge Autoclave; Sanauij 6.V Autoclave; Royal Dutch Ad linder

Autoclave. Hoong-A Blister packing machine

Process Description:

1. Receiving of raw materials: Cleanliness of incoming drums, containers & bags No materials except relevant to the products Quality assurance approval

2. Dispensing of raw materials: All materials of previous product are removed Shop is cleaned Balance are calibrated Temperature, humidity & pressure are checked every hour

3. Manufacturing: Mixing in WFI/distilled water N2 gas passed to dissolve O2

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

4. Filtration unit: Filtration through 0.2μ sterilize cartridge Filter integrity test (bubble point) before and after filtration

5. Sterilization (apparatus): Prevacuum Steaving Pulsing Warming up Sterilizing Drying Air inlet

6. Filling: Headspace oxygen content ≤1.5% Gas bulk solution with N2 gas Sample checked by QC for volume & O2 content Sample to microbiological lab for pre sterilization

7. In process control Volume N2 gas flow O2 content

8. Shop clearance 9. Sterilization (Product):

Prevacuum- 3 times Heating Sterilization Post vacuum Pressure equalization End

10. Leak testing11. Inspection12. Packaging

Cleaning: First week – Savlon 17.5% solution Second 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 ampoule After 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 gas Applying 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 bar

Preparation Observed:

Avil 1 ml injection

Ficlon 3 ml injection

Largactil 2 ml injection

WFI 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 Purpose

S.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 mixing

Agitator Mixer For suspension mixing

Doser for ethanol supply To adjust the volume of ethanol

Meta filter For syrup filtration

Nylon cloth bag filter For suspension filtration

Air 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 adjustment

S.S. Bucket To dissolve solid materials

S.S. bowl scoopS.S. Spatula & Scoop

For weight adjustment & solution preparation

Measuring Cylinder For volume measurement

Electronic balance For weight measurement

Flow chart for oral syrup manufacturing

Remaining portion

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.

Dispensing Manufacturing Filtering with Meta filter

Buckner filter

Storage vessel

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

Oral liquid filling Equipments observed

NAME FUNCTION

Master 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 automatically

King cap sealing machine Seal bottle with cap automatically, capacity 120cap/min

Myth cap sealing machine Semi automatic cap sealing Turn table machine After inspection excess bottles are arranged

in turn table

King bottle labeling machine Label 100bottle/min

Carton sealer machine Carton sealingGravil liquid filling machine Fill 100 bottle/min semi-automatically

Inspection 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

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

NAME FUNCTION

Kalix Dupuy Cream filling machine Cream filling

Cream stirrer Cream stirring

SSSJ Manufacturing Vessel (125L) Suppository & cream manufacturing

Premier Colloid mill Cream milling

Osborn Stirrer Ointment & Suppository Stirring

Sarong Suppository sealing

Flow chart of suppository manufacturing

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

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

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

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 section

Inside 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.

2. Secondary Packing MaterialsThese 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 cartoon Fiberboard outer Filament partition Liner Honeycomb Cellulose tape

Packing 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. Machines

1. Horn Noack Blister Packing Machine

2. Horn Noack Blister Packing Machine

3. E.Th Noack Blister Packing Machine

4. Hoong-A Automatic Blister Packing Machine

5. 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 PVC Pocket formation by heat and vacuum pressure Transfer of tablets or capsules in the pockets Sealing of the pocket by Aluminium foil using heat Printing over the foil if required Perforation of the strips Cutting of the strips.

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

Lippke Blister-Tester VC 1380This 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-

Feeding Laying Visual checking Cartoon making Inserting Flap closing and Tapping Outer making and filling Outer 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 system Three different water treatment plant for supplying purified

water and WFI Gowning Manufacturing area Packaging Warehouse QC lab Waste management tank Non-pharmaceutical activity Official 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 products:

Capsule Tablet Dry powder for syrup Pediatric drop Dry powder for injection

Production Equipments observed:

Name of the machine Made in FunctionDrum blender England Blending

Clincone blender India Blending

Cube mixer England Mixing

J.G. Jackson & croikatt Glasgow

England Granulation

Appex granulator England Granulation

Manesty oscillating granulator England Granulation

Manesty Petrie Dryer England Drying

Manestry 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 filling

Capsule filler Zanasi AZ40 Italy Capsule filling

Capsule filler Zanasi MG2 Italy Capsule filling

Arenco auger filler Syrup filling

Hauser filling machine Korea Injection filling

Getinge autoclave Sterilization

Hot air depyrogenation oven Depyrogenation

Bottle Dryer Drying

Hoong-A Blister packing

Gansons strip packer India Strip packing

E.TH. NOACK Germany Strip packing

Imperial Electric and Gas Apppliances Co. Dehumidifier

Dehumidification

Penicillin Laboratory Equipment:

Name of the Equipment FunctionPolarimeter Optical rotation detection

Moisture Analyzer Percent of moisture detection

Chromato-VUE cabinet TLC plate observation

Hot water bath To make a solution warm

Ultrasonic vibrator Rapid dissolution

Kurl Fisher Titrator Percent of moisture detection

Disintegration Tester Determination of disintegration time

Dissolution Tester Dissolution with respect to time

Friability Test Apparatus Friability determination

Vacuum Oven Drying

Unicom UV/Vis Spectrophotometer Quantitative analysis

Genesis Series IR Qualitative analysis

HPLC Impurities determination

Electronic Balance Weighing

Refrigerator Cooling

Cephalosporin Section

Types of products:

Capsule Tablet Dry powder for syrup Pediatric drop Dry powder for injection

Production Equipment observed:

Name of the machine Made in FunctionDrum blender England Blending

Rotogran Granulaton

Rotary bottle washer Washing

Botttle Dryer Drying

Rotary vial washer Taiwan Washing

Getinge Autoclave Sweden Sterilization

Hot air oven Drying

Imperial Electronic and Gas oven

Dehumidification

Hauser Machinary Dry Syrup filling, sealing

Zanasi AZ20 Germany Capsule filling

Gansons Strip Packer Strip packing

OTTO-Hansel vial blister packer

Blister packing

Jagenberg-Wene AG Germany Labeling

Automatic Bottle Labeler Labeling

Cephalosporin Laboratory Equipment:

Name of the equipment Function

Electric Balance Weighing

Disintegration Tester Determination of disintegration time

PH meter Determination of PH

Dissolution Tester (6 chamber) Dissolution with respect to time

Dissolution Tester (8 chamber) Dissolution with respect to time

Refrigerator Cooling

Ultrasonic Bath Rapid dissolution

UV/Vis spectrometer Quantitative analysis

Decon Ultrasonic Equipment Rapid dissolution

Bulk Density Apparatus Density determination

Gallenkamp oven Drying

Cleaning:

MOP solution:

1st week: Savlon17.5% Solution 2nd week: Dettol 2.5% Solution 3rd week: Savlon 17.5% Solution 4th 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:

Capsule Tablet

Production Equipment observed:

Name of the equipment Made in FunctionDrum blender England Blending

Grams mill India Milling

Jaguar machine Granulation

Rotorgran (Manesty) England Granulation

Sophire fluid bed dryer Drying

Manesty RD3 (16) Rotary Tablet Machine

England Tablet compression

Deduster Removal of dust

Manesty 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 Dryer

-

R-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/CKarl Kolb CoatingPan Capacity:50 kg3.Hot Air Blower

India

Germany

R-19 Blister Packing Section

Uhlman Pac System

Germany

R-20 Blister packing Section

HMR Product List

Following solid products are manufactured here.

Avil 2.7 mgAvil retard

Daonil 5 mg Frisium 10 mg Roxit 75 mg

Roxit 150 mg Lasix 40 mg Trental 400 mg

Operational scheme

The 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

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-

Quality Assurance

Industrial quality & compliance

Quality Control

Microbiology AS/AD QARL

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

Documentation

Approval

Auditing

Self inspection

Corporate audit

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 requisition

Packing material requisition

Cleaning mapping records (aseptic area)

Cleaving label of mfg. machine

Weighing label of raw materials.

Environmental study report (out put area)

Purified water analysis report

BMR.

Temperature & humidity chart

Request for analysis

In process inspection sheet

Results of sterility/ pyrogen test

Microbiological test report of bulk/ finished product.

Analytical report (in-house control)

Line-store –up inspection sheet

Packing 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.CIn Sanofi Aventis following instruments are used for analysis

1. HPLC

2. Electric oven

3. Monsanto hardness fester

4. Pharma test disintegrator

5. Friabilator

6. Shaking machine

7. PH meter

8. Centrifuge machine

9. UV and Visible spectrophotometer

10. IR spectrophotometer

11. Melting point apparatus

12. Moisture analyzer

13. Dissolution test apparatus

14. Muffle furnace

15. Pinometer

16. Liq particle counter

17. Conductivity meter kit.

18. Total dissolved solid meter

19. LAP cabinet

20. Automatic refractometer

21. Magnetic stirrer

22. Electrical stirrer

23. MS and heater

24. Viscometer

25. Analytical balance

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

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:

1. 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.

2. 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.

3. 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.

3. 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 check

3. Strength of the cartoon is checked in gram/sq. meter

4. Proper locking check

5. Flap cut checking

VIALS:

1. Alkalinity

2. Thickness

3. Cap diameter

4. Proper aluminum seal

FOILS:

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

COLLAPSIBLE TUBES:

a. Texture

b. Specification measurement

c. Inside lacquering test

d. Latex seal check

e. Presence of Aluminum seal

RUBBER CLOSURE

a. PH

b. Stickiness

c. Toxicity

d. Ash content

e. Density

f. Alkalinity

AMPULES:

a. Surface and sometimes-total alkalinity

b. Thickness

c. Height

d. Breaking point

e. 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+1

Where N=no of container

After 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 weight

a) Average weight

b) 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. variation

Moisture content

Sealing

Liquids Bottle volume

Sterile 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 packets

The labels are checked by the officer to the standard labels

The 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.

C. 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 is

Stored 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% RH

If 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

• Excipients

Change 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------

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

INSTRUMENTS USED IN MICROBIOLOGICAL ASSAY

Particle counter Air sampler Incubator Anaerobic jar Centrifuge machine Water bath Freeze to preserve bacteria PPH meter Colony counter Microscope Laminar flow machine Hot oven Dust collector Autoclave Balance LAL 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

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

Product is registered

If approved

FOR INN DRUGS

Sample + test report +procedure +analyzing data submission

If approved

Recipes submission

Then again submit the sample +annexure

Product is registered

If approved

INTRODUCTIONStore 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 entry

Complete security and prevention of pilference of every material including the

promotional are said to be confirmed.

Central dispensing unitAccording 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 roomThere 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

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

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

1. 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-

Electricity Potable or Drinking water Steam Boiler Air compressor HVAC System Central Vacuum System & Calibration Department.

2. 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 Calibration

Class- 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 1. 500 KVA2. 1250 KVA3. 2000 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.

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.

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

2. 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.

3. In all places in which the Group operates it respects the applicable laws and

regulations, applies expert recommendations and uses the best industrial practices.

4. 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.

5. 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.

6. 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.

7. 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.

8. 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:

1. The site has set up a health center to provide regular medical checkup and

emergencies.

2. The site has Automatic External Defibrillator (AED) to attend Emergency Cardiac

Arrest Problem.

3. Installation of public address system.

4. Formation of team for crisis management, emergency response, fire aid and fire

fighting.

5. Emergency preparedness.

6. Implementation of risk assessment review program.

7. Process monitoring and controls.

8. Efficient Waste management system to ensure maximum environmental

protection.

9. 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-

Identification

Inventory

Characterization

Classification / Labeling

Separation

Collection

Accumulation storage

Internal treatment if necessary (neutralization, compaction,

shredding)

Transportation

Disposal / recovery

Register 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-

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.

Effluent Treatment Plant

Chemical waste

Liquid waste Solid waste

Incineration

Treatment

Alkali / Ammonia treatment in case of Antibiotic

Disposed Outside

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 –

Ergonomics

Fire protection

First aid

Hazard protection

Electrical safety

Accident prevention

Life style modification

Personal hygiene

HSE leadership training for Supervisors & Line Managers.

Implementation Of HR Mission

Positive Thinking

Group Approach

Transparent Communication

Shared and cared Grievances

Practices 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 Formulation

Staffing:

1. Recruitment

2. Resignation

3. Dismissal

4. Retirement

Training and Development

Employee Recognition

Compensation and Benefit

Industrial Relations

Performance Evaluation

Administration performs the following activities-

Canteen

Security

Transport

Site cleanliness

External Relations

HEAD COUNT AND DISTRIBUTION

Function Registered (ITC)

Production 271

IQC 36

Engineering 36

HR & Admin 9

Plant Logistics 39

Project 2

HSE 2

IA Controlling 3

Total 398

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.

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.

Unique features of Sanofi–Aventis Limited in Tongi Plant:

1. 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.

2. Automatic double door system must be installed in production area.3. HVAC system should be installed in the solid packaging section.4. In IQC, the analysts must have to wear protective gloves on their

hands.5. Solid packaging machines should be totally automated.6. Jet printer should be used in strip packaging in Penicillin section of

CPR.7. An AC is essential in the patient cabin of the medical center.

8. Manpower shortage in officer’s level might harm the process of

production and Quality Assurance.9. Supply chain department should be situated in the industrial area.

10. 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: