sanofi aventis report 2006
DESCRIPTION
an overview on Sanofi Aventis Report 2006.TRANSCRIPT
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: