In plant training programme in advanced chemical industries (aci) limited

IN-PLANT TRAINING PROGRAMME IN ADVANCED CHEMICAL INDUSTRIES (ACI) LIMITED

Company Profile ACI was established as the subsidiary of Imperial Chemical Industries (ICI) in the then East Pakistan in 1968. After independence the company has been incorporated in Bangladesh on the 24th of January 1973 as ICI Bangladesh Manufacturers Limited and also as Public Limited Company. This Company also obtained listing with Dhaka Stock Exchange on 28 December, 1976 and its first trading of shares took place on 9 March, 1994. Later on 5 May, 1992, ICI plc divested 70% of its shareholding to local management. Subsequently the company was registered in the name of Advanced Chemical Industries Limited. Listing with Chittagong Stock Exchange was made on 22 October 1995.

Advanced Chemical Industries (ACI) Limited is one of the leading conglomerates in Bangladesh, with a multinational heritage. The company has diversified into three major businesses.

Strategic Business Units 1.

2.

3.

4.

5.

6.

7.

8.

9.

Pharmaceuticals Consumer Brands & Commodity Products Agribusinesses: Crop Care Public Health Livestock & Fisheries Fertilizer Cropex Seeds Mission; Vision & Values:

Mission ACI’s mission is to enrich the quality of life of people through responsible application of knowledge, skills and technology. ACI is committed to the pursuit of excellence through world-class products, innovative processes and empowered employees to provide the highest level of satisfaction to its customers.

Vision

• • • • • •

To realize the mission ACI will: Endeavor to attain a position of leadership in each category of its businesses.

Attain a high level of productivity in all its operations through effective and efficient use of resources, adoption of appropriate technology and alignment with our core competencies.

Develop its employees by encouraging empowerment and rewarding innovation.

Promote an environment for learning and personal growth of its employees.

Provide products and services of high and consistent quality, ensuring value for money to its customers.

• •

Encourage and assist in the qualitative improvement of the services of its suppliers and distributors.

Establish harmonious relationship with the community and promote greater environmental responsibility within its sphere of influence.

Values: 1.

2.

3.

4.

5.

6.

Quality Customer Focus Fairness Transparency Continuous Improvement Innovation

Quality Policy: •

ACI's mission is to achieve business excellence through quality by understanding, accepting, meeting and exceeding customer expectations.

•

ACI follows International Standards on Quality Management System to ensure consistent quality of products and services to achieve customer satisfaction. ACI also meets all national regulatory requirements relating to its current businesses and ensures that current Good Manufacturing Practices (cGMP) as recommended by World Health Organization is followed for its pharmaceutical operations.

•

The management of ACI commits itself to quality as the prime consideration in all its business decisions. All employees of ACI must follow documented procedures to ensure compliance with quality standards.

•

The pool of human resources of the company will be developed to their full potential and harnessed through regular training and their participation in seeking continuous improvement of work methods.

Environmental Policy: ACI is committed to maintain the harmonious balance of our eco-system and therefore constantly seeks ways to manufacture and produce products in an eco-friendly manner so that the balance of nature remains undisturbed and the environment remains sustainable.

In pursuit of this goal, ACI will • • • • • •

Comply fully with all local and national environmental regulations.

Conserve natural resources like water and energy for sustainable development, and adopt environmentally safe processes.

Ensure appropriate treatment of all effluents prior to discharge, to prevent pollution or degradation of environment.

Ensure appropriate communication and cooperate with internal and external interested parties on environmental issues.

Create awareness on environmental issues among our employees and suppliers.

Adopt modern waste management technology.

ORGANIZATION CHART

Chairman ↓

Managing director

Chief operating officer Director,QA

General Manager(operation)

Production manager(unitI&unit-II)

Asst.Manage r,warehouse -I&II

Chief engineer

HR & Admin Manager

Manager, QC

QA Manager

Manager ,Microbiology.

Manager ,PD.

Manager ,NDDS

Manager ,Compliance.

INTRODUCTION Warehouse (RM&PM) is the place where raw materials are preserved,dispensed and 1. Local raw materials.

2. Imported raw materials.

Labelling of packed raw materials: Local raw materials are labeled as RML 001 Imported raw materials.are labeled as RMI 001 Local packedmaterials are labeled as PML 001 Imported packed materials.are labeled as PMI 001 Areas of warehouse (RM&PM) Quarantine area After receiving of raw materials they are stored first in the quarantine area. Then Q.C. sampling and checking is approved and then shifted to the main storage area.

Main storage areaHere raw materials are stored. There is another isolated storage area for sophisticated materials maintaining temperature and humidity in side the main storage area named cooling room. The storage department performs some important functions such as

A) Specific raw materials are stored in specific mentioned area with proper documentation. Cool area: 15-24°C &Cold storage: 2-8°C. B) According to monthly program, this department has the responsibilities to get final Q.C. approval for raw materials.

C) According to plan and recovery maintenance, the raw materials are supplied to the production area for required batch size.

Released area Here raw materials are stored those only passed the tests performed by QA and QA provides green tag.

Not released area: Here raw materials are stored those the tests not yet performed by QA and QA provides yellow tag.

Rejected area Rejected materials are stored here those failed the tests performed by QA and QA provides red tag and the local raw materials are returned to the suppliers.imported raw materials are destroyed.

Storage Area for Packaging Material Packaging material including master pack, carton, foil, inner pack, catch cover etc are stored here.

Operation of warehouse-I

Material receive by primary ‘Quarantine’ Keep the record and send GRN with pass label to QC. QC department takes sample All types of tests are performed by QC. ‘Rejected’ tag is given if materials fail to pass the tests QC fixes ‘Approved’ tag if tests are passed Approved material goes to Production Department in first in first out process Keep the record.

GRN (GOODS RECEIVE NOTES): Local raw materials a) Purchase oder. b) Challan no. c) VAT receipt. d) certificate of analysis. e) Track receipt.

a) b) c) d) e) f)

Imported raw materials.

Purchase oder.

Challan no.

Invoice no.

VAT receipt. certificate of analysis.

Track receipt.

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

Total Units in Solid Department

Manufacturing area

Granulation unit

Compression unit

Packaging area

Coating unit

Capsule filling

TABLET

A tablet is a mixture of active substances and excipients, usually in powder form, pressed or compacted into a solid. The excipients include binders, glidants (flow aids) and lubricants to ensure efficient tabletting; disintegrants to ensure that the tablet breaks up in the digestive tract; sweeteners or flavours to mask the taste of bad-tasting active ingredients; and pigments to make uncoated tablets visually attractive. A polymer coating is usually applied to hide the taste of the tablet's components, to make the tablet smoother and easier to swallow, and to make it more resistant to the environment, extending its shelf life.

A TYPICAL TABLET CONTAINS

TABLET EXCIPIENTS: Antiadherents Antiadherents are used to reduce the adhesion between the powder (granules) and the punch faces and thus prevent sticking to tablet punches. Most commonly used is magnesium stearate.

Binders Binders hold the ingredients in a tablet together.

Binders ensure that tablets and granules can be formed with required mechanical strength, and give volume to low active dosis tablets. Binders are usually starches, sugars, cellulose or modified cellulose such as microcrystalline cellulose, hydroxypropyl cellulose, lactose, or sugar alcohols like xylitol, sorbitol or maltitol.

Disintegrants Disintegrants expand and dissolve when wet causing the tablet to break apart in the digestive tract, releasing the active ingredients for absorption. Disintegrant types include: 1. Water uptake facilitators 2. Tablet rupture promoters They ensure that when the tablet is in contact with water, it rapidly breaks down into smaller fragments, thereby facilitating dissolution. Examples of disintegrants include: crosslinked polyvinyl pyrrolidone, sodium starch glycolate, crosslinked sodium carboxymethyl cellulose (crosscarmellose).

Fillers and diluents Fillers fill out the size of a tablet or capsule, making it practical to produce and convenient for the consumer to use. By increasing the bulk volume, the fillers make it possible for the final product to have the proper volume for patient handling. Plant cellulose (pure plant filler) is a popular filler in tablets or hard gelatin capsules. Dibasic calcium phosphate is popular tablet filler. A range of vegetable fats and oils can be used in soft gelatin capsules. Other examples of fillers include: lactose, sucrose, glucose, mannitol, sorbitol, calcium carbonate, and magnesium stearate.

Flavours

Flavours can be used to mask unpleasant tasting active ingredients and improve the likelihood that the patient will complete a course of medication. Flavourings may be natural (e.g. fruit extract) or artificial.

Colours Colours are added to improve the appearance of a formulation. Colour consistency is important as it allows easy identification of a medication.

Glidants Glidants are used to promote powder flow by reducing interparticle friction and cohesion. These are used in combination with lubricants as they have no ability to reduce die wall friction. Examples include colloidal silicon dioxide, talc, and magnesium carbonate.

Lubricants Lubricants prevent ingredients from clumping together and from sticking to the tablet punches or capsule filling machine. Lubricants also ensure that tablet formation and ejection can occur with low friction between the solid and die wall.

Common minerals like talc or silica, and fats, e.g. vegetable stearin, magnesium stearate or stearic acid are the most frequently used lubricants in tablets or hard gelatin capsules.

Sweeteners Sweeteners are added to make the ingredients more palatable, especially in chewable tablets such as antacid or liquids like cough syrup. Therefore, tooth decay is sometimes associated with cough syrup abuse. Sugar can be used to disguise unpleasant tastes or smells.

In tablet production there are several steps involved which are following: 1.

2.

3.

4.

5.

6.

Dispensing and Granulation.

Blending Powder compression Coating Blistering.

Secondary Packaging.

GRANULATION UNIT Granulation may be defined as a size enlargement process which converts small particles into physically stronger and larger agglomerates in order to facilitate compression for the production of tablet. All the materials are received from the dispensing unit and granulation is performed. For suitable granulation, it is required to have 30-40% powder and 60-70% granules and also 1-5% moisture in compressing particles.

PURPOSES OF GRANULATION 1. -To produce tablets of appropriate size.

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

3. -To improve the flow properties of the powder mix.

4. -To improve compression nature of powder.

Types of granules

Two types of granules are produced in the four-granulation units of the industry, which include; Granules with active ingredient/s Placebo granules without any active ingredient/s for moisture sensitive active/s or drug/s Granulation Processes which are performed in the ACI plant are following: 1. Wet Granulation.

2. Dry Granulation.

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

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

Dry granulation This process is used when the product needed to be granulated may be sensitive to moisture and heat.

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

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

Weighing of drugs and excipients ↓ Mixing of all ingredients ↓ Sieving Discharge for compression MACHINERIES USED DURING GRANULATION NEW PLANT NO. NAME OF MACHINARY 1.

3.

RAPID MIXER GRANULATOR LIFTING AND TILTING MACHINE. FLUID BED DRIER

4.

WET GRANULATOR

5.

SIFTER

6.

V-CONE BLENDER

2.

COMPANY NAME YENCHEN CO.LTD,TAIWAN. YENCHEN CO.LTD,TAIWAN YENCHEN CO.LTD,TAIWAN YENCHEN CO.LTD,TAIWAN YENCHEN CO.LTD,TAIWAN YENCHEN CO.LTD,TAIWAN

CAPACITY MACHINERY 300KG MACHINERY 300KG MACHINERY 400KG MACHINERY 80-200KG MACHINERY ---------MACHINERY 400KG

OLD PLANT NO. NAME OF MACHINARY 1.

RAPID MIXER GRANULATOR 2.

LIFTING AND TILTING MACHINE. 3.

FLUID BED DRIER 4.

CALMIC CISA FLUID BED DRIER. 5.

SIFTER 6.

BIN BLENDER 7.

PLANETARY MIXER 8.

9.

JACKET SCREENING MILL

COMPANY NAME

CAPACITY

GANSON LIMITED MUMBAI,INDIA

200KG

GANSON LIMITED MUMBAI,INDIA

200KG

GANSON LIMITED MUMBAI,INDIA ROME,ITALY.

200KG 60KG

GANSON LIMITED MUMBAI,INDIA GANSON LIMITED MUMBAI,INDIA PEERLESS&ERICSSON LTD.BIRMINGHAM,ENGLAND.

---------200KG 50KG

BANGLADESH.

-----------

Compression of powder means reduction in bulk volume of a material as a result of displacement of the gaseous phase. Compression is used for the manufacturing of tablet.

In the compression of active pharmaceutical ingredients, overall control is essential to ensure high quality. Haphazard operations cannot be permitted in the compaction of substances that may be used to save life or to restore or promote health.

Adherence to the practices, complementing the various control tests carried out from the beginning at dispensing to the end of the production cycle with compaction, will contribute substantially to the production of consistently uniform batches of high-quality active pharmaceutical ingredient.

FLOW CHART OF TABLET COMPRESSION

Granules (previously made) ↓ Transfer of granules in the Hooper of tablet press machine by hand or auto powder/granules loader ↓ Rising of upper punch & dropping of lower punch ↓ Filling of die cavity through feed frame ↓ Removal of extra granules by scrape off plate ↓ Coming down of upper punch for ↓ Compression to produce tablet ↓ Raising of both upper & lower punches to certain extent ↓ Ejection of tablet with the help of take out plate ↓ Conventional Uncoated Tablets of desired shape and size MACHINERIES USED DURING COMPRESSION: SL. NAME NO. MACHINARY 1.

2.

3.

4.

5.

6.

7.

8.

9.

OF COMPANY NAME

CADPRESS IV CADMACH CMB4.

CADMACH CMD420 CADMACH CTX-32 MANESTY D3B MANESTY BB3B MANESTY MANESTY BB4 SEJONG MRC-37D.

CADMACH,INDIA. CADMACH,INDIA CADMACH,INDIA CADMACH,INDIA MANESTY,ENGLAND MANESTY,ENGLAND MANESTY,ENGLAND MANESTY,ENGLAND KOREA.

Common Problems that generally arise during compression are1.

2.

3.

4.

5.

6.

7.

Capping Chipping Sticking Weight variation Mottling Hardness problem Lamination

NUMBER OF PUNCHE PUNCHES TYPE 45 35 20 32 16 27 1 35 37

D B B B D D D D B

Coated tablets are tablets covered with one or more layers of mixtures of various substances such as natural or synthetic resins, gums, gelatin, inactive and insoluble fillers, sugars, plasticizers, polyols, waxes, coloring matter authorized by the competent authority and sometimes flavoring substances and active substances. The substances used as coatings are usually applied as a solution or suspension in conditions in which evaporation of the vehicle occurs. When the coating is a very thin polymeric coating, the tablets are known as film-coated tablets.

Coated tablets have a smooth surface which is often colored and may be polished;a broken section, when examined under a lens, shows a core surrounded by one or more continuous layers with a different texture.

Objectives of tablet coating 1. To protect against deterioration by environmental factors like sunlight, temperature variations, moisture, environmental gases etc 2. To facilitate swallowing.

3. To mask taste and odour 4. To increase shelf-life.

5. To enhance aesthetic appeal and brand image.

6. To facilitate product identification during manufacture and prevent wastage during packing and handling 7. To provide immediate release, specific release, sustained release, controlled release and targeted drug delivery properties.

8. To provide enteric release properties for release in the intestinal tract.

9. To facilitate identification of oncological drugs Classification of Coating: Mainly three types of coating are performed in the solid section. They are as follows: Coating Sugar coating

Film coating

Aqueous coating

Enteric coating

Organic coating

IN ACI,THE FOLLOWING THREE PROCESSES ARE EMPLOYED FOR TABBLET COATING‌ Film coating: a)Aqueous coating b)Organic coating Enteric coating A)Lquid enteric coating.

B)Powder enteric coating FILM COATING: Application of thin barrier films, protective layers and coloured or functional coatings.

Process principles

A very even application of the coating material is an important feature of the coating process.

Coatings must be dense and without mechanical damage and cracks. Film coating is an effective process for the application of protective films for manipulating the product characteristics. Glatt offers various technical solutions for coating different particles and tablets: 1. Fluid Bed Coating (Top Spray Coating, Bottom Spray Coating, Rotor Coating) 2. Drum Coating 3. Spouted Bed Technology 4. In each case, the coating fluid is sprayed onto the solid material, which is presented to it. The introduction of the process air evaporates the fluid and dries the film coating. Small droplets and a low viscosity ensure a uniform distribution.

Enteric coating: An oral dosage form in which a tablet is coated with a material to prevent or minimise dissolution in the stomach but allow dissolution in the small intestine. This type of formulation either protects the stomach from a potentially irritating drug (e.g., aspirin) or protects the drug (e.g., erythromycin) from partial degradation in the acidic environment of the stomach erythromycin) from partial degradation in the acidic environment of the stomach.

Instruments / Apparatus Used In Tablet Coating

There are various types of sophisticated instruments are used for the purpose of tablet coating. The instruments are SI No. 01 02 03

Name of the Machine GANSON RAMA COTA SEJONG SFC130

Company

Source

GANSON LTD,INDIA. RAMA COTA CO.LTD SEJONG PHARMATECH CO.LTD.

INDIA THAILAND KOREA

We observed the film coating of ACICAL core tablets Materials used in film coating: 1. OPADRY II 85G52478 YELLOW Ph.GRADE 2. OPADRYII85G58921 WHITE Ph.GRADE 3. OPADRY OY-S-29038 Ph.GRADE 4. PURIFIED WATER Coating Procedure 1.Preparation of coating suspension: Take purified water in a s.s vessel. ↓ Add the ready coating materials carefully to the region of vortex ↓.

Stir the dispersion for 45 minutes. ↓ Filter through 60 mesh size(if necessary) ↓ Add extra purified water for good dispersion(if necessary) 2.Coating process Coating suspesion(Aqueous ) ↓ Tablets into coating pan ↓ Warm up the core tablets for 10 minutes at 35-40°C ↓ Set the required inlet (60-70°C)and outlet(45-55°C) temperature. ↓ Start the coating pan ↓ Set the RPM of coating pan within 2-3 ↓ Set the RPM of peristaltic pump within 8-12 ↓ Set the atomizing air pressure within 3.5-4 kg/cm² ↓ Continue to spray by spray gun until all dispersion has been used ↓ Stop spraying after coating is completed ↓ Rotate the pan for 10 minutes to remove any solvent. ↓

capacity (Kg) 300 150-200 60-90

No.of sprays 6 2 2

Stop the blower,exhaust and heater and allow cooling.

Important critical parameters to check prior to spray coating solution • Pump speed • Pan Rotation • Bed Distance • Negative Pressure • Inlet Air Temperature • Outlet Air Temperature • Atomizing Air Pressure • Fluid Return Volume • Nozzle Distance from the Tablet Bed. COMMON PROBLEMS ASSOCIATED WITH TABLET COATING: Logo bridging

Cause: 1. Surface characteristics of the product being coated 2. Inadequate adhesion of film coating 3. Inadequate design of logo (e.g. too detail/fine logo) Remedy: 1. Modify core formulation to include more hydrophilic ingredients 2. Increase core porosity 3. 0Using formulation with increased adhesion property.

4. Increase area within the debossing and modified angles.

Core erosion

Cause: 1.

2.

3.

4.

Inherent softness or high friability of core.

Excessive pan speed in coating process.

Spray rate too low.

High sensitivity of core to moisture as coating is applied.

Remedy:

1. Increase mechanical strength of core.

2. Decrease pan speed.

3. Increase spray rate.

Edge chipping/erosion

Cause: 1.

2.

3.

4.

5.

6.

Low mechanical strength of coating Excessive pan speed Low solid content in coating liquid Low spray rate Sharp edges on tablets Worn tablet punches

Remedy: 1. Using formulation with increased mechanical strength 2. Decreased pan speed 3. Increase solid content in coating liquid 4. Decrease spray rate 5. Use modified punch design Picking/sticking:

Cause: 1.

2.

3.

4.

5.

Spray rate too high Inadequate drying condition Pan speed too low Inadequate atomization of coating liquid Poor distribution of coating liquid

Remedy: 1. Decrease spray rate 2. Increase drying condition 3. Increase pan speed 4. Increase atomizing air pressure/volume 5. Increase number of spray gun Cracking:

Cause: 1. Low mechanical strength of coating, exacerbated by inadequate plasticization, excessive pigmentation.

2. Core has significantly different thermal expansion characteristics than coating.

3. Extended strain relaxation of core after compaction.

Remedy: 1. Selecting formulation with increased mechanical strength and elasticity properties.

2. Avoid use of mineral type fillers (e.g. CaCO3, CaSO4, MgCO3 etc.)

3. Extend holding period of tablets prior to submitting them to coating process.

Peeling Cause: 1. Low mechanical strength of coating 2. Poor adhesion of coating to tablet surface Remedy: 1. Using ingredients of improved mechanical strength.

2. Using ingredients with improved adhesion properties.

Orange peel/roughness Cause: 1.

2.

3.

4.

Viscosity of coating liquid is too high Poor atomization of coating liquid Excessive drying condition Over wetting (causing coating too rub)

Remedy: 1. Decrease solid content of coating liquid 2. Increase atomizing air pressure/volume 3. Decrease inlet air temperature/flow rate 4. Decrease spray rate Twinning Cause: 1. Spray rate too high 2. Pan speed too low 3. Inappropriate tablet shape Remedy: 1. Decrease spray rate 2. Increase atomizing efficiency 3. Increase pan speed 4. Select new tablet shape that decrease chances of flat surfaces coming into contact during application of coating liquid. (e.g. avoid capsule shape tablet with thick side wall)

Tablet-to-tablet color variation Cause: 1. Too little coating applied 2. Inadequate mixing of tablet during coating 3. Poor opacity (or hiding power) 4. Solid content of coating liquid too high 5. Insufficient number of spray gun Remedy: 1. Increase quantity of coating applied 2. Increase pan speed/increase improve baffle system 3. Reformulate coating with respect to colored ingredients or use an opacified white pre-coat.

4. Decrease solid contents of coating liquid.

5. Increase number of spray gun.

Capsules are solid preparations with hard or soft shells of various shapes and capacities, usually containing a single dose of active substance(s). They are intended for oral administration.

The capsule shells are made of gelatin or other substances, the consistency of which may be adjusted by the addition of substances such as glycerol or sorbitol. Excipients such as surface-active agents, opaque fillers, antimicrobial preservatives, sweeteners, colouring matter authorised by the competent authority and flavouring substances may be added. The capsules may bear surface markings.

The contents of capsules may be solid, liquid or of a paste-like consistency. They consist of one or more active substances with or without excipients such as solvents, diluents, lubricants and disintegrating agents. The contents do not cause deterioration of the shell. The shell, however, is attacked by the digestive fluids and the contents are released.

Several categories of capsules may be distinguished:

1. hard capsules; 2. soft capsules; 3. gastro-resistant capsules;

4. modified-release capsules; 5. cachets.

In this pharmaceutical industry filling (encapsulation), sealing and polishing (if required) of capsules of hard gelatin shell are done during manufacturing, as the industry does not manufacture any capsule shell.

The active is filled in the empty the hard gelatin capsule shell in the form ofa. a.Powder b. b.Pellets Size of capsule shells There are 8 different sizes of empty hard gelatin capsule shells used for general production, which include 1.

2.

3.

4.

5.

Capsule shell size 000 Capsule shell size 00 Capsule shell size 0 Capsule shell size 1 Capsule shell size 2

6. Capsule shell size 3 7. Capsule shell size 4 8. Capsule shell size 5 In ACI LTD.,the following gelatin capsule shells are used----1. Capsule shell size 0 2. Capsule shell size 1 3. Capsule shell size 2 4. Capsule shell size 4 Encapsulation Process by Automatic Capsule Filling Machine: We observed the encapsulation of XELDRIN 20mg &PANTEX 20mg in hard gelatin capsule shell….

Process of capsule filling: 1. Manual 2. Auto 1. Procedure of Manual Capsule Filling Loading of capsule in the loading plate

↓ Removal of caps of the shells ↓ Filling of powder ↓ Rejoining of caps of the shells ↓ Encapsulation ↓ Sorting of Capsules and Polishing of Capsule 2. Procedure of automatic Capsule Filling Capsule shells are given into the hopper ↓ capsule shells come in a secondary section ↓ shells are automatically fitted in capsule dies ↓ caps and bodies are separated by vacuum pressure through rubber stopper which cause the upper and lower dies to be separated↓ ↓→ powders/pellets are given in hopper pellets/powders are automatically filled in the body of shells ↓ Close the body and cap by closing pin ↓ displaced shells are automatically sealed ↓ filled capsules are automatically ejected .

Machineries used for encapsulation Machine name

Machine specification

Automatic Capsule Capacity: filling machine Capsule fill

Manufacturer

90000/hr P+am AF90 T pharmaceuticals

Origin

India

Automatic Capsule Capacity:30000/hr filling machine Capsule fill

Se jong

Korea

Capsule machine

P+am pharmaceuticals

India

Pharmachem

India

polishing --------------------

Hand fill machine

Capacity:8000/hr

Packing can be defined as an economical means of providing, presentation, protection, identification/information, containment, convenience, and compliance for a product during storage, carriage, display and use until such time as the product is used or administered.

After compression of tablets and coating [if required], the tablets are packed either in blister pack or in the strip.

Purpose of packaging: 1.

2.

3.

4.

5.

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

At ACI Limited, two types of combination is used depending on the upper & lower layers as well as product requirement. They are; 1. PVC-Aluminium Blister 2. Aluminium -Aluminium Blister Besides blister packaging, at ACI Pharmaceuticals Limited, other packaging includes; 1. Striping 2. Filling of tablets &capsules in bottles 3. Labeling of bottles 4. Secondary Packaging (Both on-line & off-line) 5. Packaging of Ampoules 6. Packaging of Vial

Blister packing machine: Machine Name Automatic Blister Pack machine Automatic Blister Pack machine Automatic Blister Pack machine Automatic Blister Pack machine

No. of Manufactured by Machine 1 Buchon 1 Buchon 1 Horn noack 1 Hoong-A

Origin Korea Korea Germany Korea

Primary Packaging Materials Materials Polyvinyl Chloride [PVC], (PVC/PVC) Aluminium Foil

Sources korea India, Korea, Bangladesh

\ Blister packaging: We observed the blister packaging of BRODIL 2

PVC sheet

Heating plate

Foil soften by hot plate Temp. 125-145°C

Passed through desired dies plate which is kept cold & air pressure is applied to make pocket for small time & desired shape is resulted (air pressure 6-8 bar)

with ALU PressedAlu-alu by twofoil plates properly labeled simultaneously (upper plate temp.

160-180°C for PVC & lower plate is cold).Embossed the batch no.& shelf life.

Passed through cutter

Tablets or capsules are filled into the pockets

Desired blister pack

Trouble shooting: Preheating problem – malleability Forming problem Sealing problem Slitting problem – perforation

Feeding problem – Chute channel Gate transfer Spiral

Loading problem Air pressure Scanner problem Emboss problem Heat exchanger

Brush

Strip packaging: We observed the strip packaging of XELDRIN 20mg……….………..

ALU sheet

Hydrolic pressure

Air pressure is applied to make pocket for small time & desired shape is resulted (air pressure 9-12 bar)

with ALU PressedAlu-alu by twofoil plates properly labeled simultaneously (upper plate temp.

160-180°C for PVC & lower plate is cold).Embossed the batch no.& shelf life.

Passed through cutter

Tablets or capsules are filled into the pockets

Desired blister pack

Leak Test Vacuum pump leak tester is used to test the packing material……

Procedure: Strips Are Labelled With Specific Number ↓ Strips Are Then Taken In A Perforated Box ↓ Transfer The Box To The Tester ↓ Start The Machine To Suck Air For 5 Minutesto Produce Negative Pressure Inside The Tester ↓ Stop The Tester ↓ Check The Strips ↓ If Any Leak Presents,Water Enters Into The Tablet And The Strip Considered As Leak.

Total Units in LCO Department ↓ ↓ Manufacturing area 1. Cream/Oinment 2. Topical liquid 3. Oral liquid

↓ Filling and sealing area

A cream is a topical preparation usually for application to the skin. Creams for application to mucus membranes such as those of the rectum or vagina are also used. Creams may be considered pharmaceutical products as even cosmetic creams are based on techniques developed by pharmacy and unmedicated creams are highly used in a variety of skin conditions (dermatoses).Creams are semi-solid emulsions that is mixtures of oil and water. They are divided into two types: oil-in-water (O/W) creams which are composed of small droplets of oil dispersed in a continuous aqueous phase, and water-in-oil (W/O) creams which are composed of small droplets of water dispersed in a continuous oily phase.

Savlon A/C MATERIALS USED: 1. Strong cetrimide BP 2. Chlorohexidine HCL BP 3. Cetostearyl alcohol BP 4. Liquid paraffin BP 5. Antiseptic perfume compossed Ph.grade 6. Purified water Flow chart of savlon cream manufacturing

WATER PHASE Collect purified water in jacketed vessel

OIL PHASE Collect base in jacketed vessel & melt at 150oC

Addition of water phase and boiled at 95-98oC with stirring

Addition of other oil phase with continuous stirring

(Add slowly aqueous phase to the oil phase with stirring When the temp.of both phase becomes 80°C) Using negative preessure Main vessel Continuous stirring for 45minutes(milk like look)

Cool the system to 60oC and add perfume ↓ Add emulsifier at 50 oC for 1 hour with Continuous stirring ↓ Preserve the prepared bulk cream in containers with proper tagging Flow chart of filling and sealing of savlon A/C Loading the tube and air pressure is used toremove the dust.

Counter to sense the presence of tubes. photosun (to set the tubes for filling) Filling the tube by filling nozzle Heat is applied chill the tubes by a chiller seal the tubes with embosse(batch&shelf life) Cut the back side of the tube Pressure by pin to come out for ejection

MACHINARIES USED IN CREAM FILLING & SEALING: Machine Name Automatic tube filling machine and sealing machine Automatic tube filling machine

Specification and Origin ZHE JIANG HUALIAN machinery co.ltd,CHINA. MAHARSHI Liquid machine,INDIA.

Positive liquid filling machine

Bangladesh

Vacuum emulsification mixer

TIANFU MACHINE,CHINA.

Automatic labeling machine

HUNAN

CHINASUN co.ltd,CHINA.

Pharma filling

Pharmaceutical

Round over pilfer proof sealing machine(R.O.P.P Bangladesh cap sealing machine)

The oral use of liquid Pharmaceutical has generally been justified on the basis of ease of administration to those who have difficulty in swallowing solid dosage form. A drug administer in solution is immediately available for absorption and in most case is more rapidly and efficiently absorbed than the same amount of drug administered in tablet and capsules.

In liquid section oral suspension, syrup etc. are manufactured. During our visit, we have observed the manufacturing of 1. BRODIL SYRUP (100 ml)..

2. AVLOCID PLUS.

GENERAL MANUFACTURING PROCESS OF ORAL LIQUIDS: The general manufacturing of oral liquids in the liquid section of ACI Ltd is briefly described below with a flowchart; Weighing of active ingredient/s along with excipients ↓ Mixing of excipients with certain amount of demineralized (DM) water as specified in the Batch Production Record (BPR) by the aid of a mechanical stirrer ↓ Addition of active ingredient/s ↓ Passing through a pump to the storage vessel to the ↓ Transfer of the solution to the filling vessel through 0.2µ Cartridge filter.

BRODIL SYRUP: Materials used: 1.

2.

3.

4.

5.

6.

7.

8.

9.

Sulbutamol sulfate BP Saccharin Na BP Methyl hydroxybenzoate BP Propyl hydroxybenzoate BP Anhydrous citric acid BP Na citrate BP Lemon essence Ph.grade Quinoline yellow Ph.grade Purified water BP

MANUFACTURING PROCESS OF BRODIL SYRUP: Step-1: Water is taken at 3900 liters ganson manufacturing vessel and raise the temperature 80-85°C Then add 1. Saccharin Na BP 2. Methyl hydroxybenzoate BP 3. Propyl hydroxybenzoate BP And dissolved by stirring.

Step2: Add the following materials into step 1 with stirring.

1. Anhydrous citric acid BP 2. Na citrate BP 3. Quinoline yellow Ph.grade Step-3: Add the following materials with continuous stirring a mix for 20 minutes.

1. Sulbutamol sulfate BP 2. Lemon essence Step4: Passing through a pump to the storage vessel to the .Transfer of the solution to the filling vessel through 0.2µ Cartridge filter.

MACHINARIES USED IN ORAL LIQUID FILLING AND SEALING Machine Name Manufacturing vessel(4000 liters)

Specification and Origin

Storage vessel(1000Liters)

Ganson,INDIA. Ganson,INDIA.

Cartridge filter (.8,.45,.2µ) Automatic tube filling machine

Sertorius,Germany.

MAHARSHI Liquid filling machine,INDIA.

Positive liquid filling machine Automatic labeling machine

Bangladesh HUNAN CHINASUN co.ltd,CHINA.

Pharmaceutical

Penicillin (sometimes abbreviated PCN or pen) is a group of antibiotics derived from Penicillium fungi. Penicillin antibiotics are historically significant because they are the first drugs that were effective against many previously serious diseases such as syphilis and Staphylococcus infections.

Penicillins are still widely used today, though many types of bacteria are now resistant. All penicillins are Beta-lactam antibiotics and are used in the treatment of bacterial infections caused by susceptible, usually Gram-positive, organisms.

Mode of action All penicillin derivatives produce their bacteriocidal effects by inhibition of bacterial cell wall synthesis. Penicillins prevent bacteria from using a substance that is necessary for the maintenance of the bacteriaТs outer cell wall. Unable to use this substance for cell wall maintenance, the bacteria swell, rupture, assume unusual shapes, and finally die.The penicillins may be bactericidal (kill the bacteria) or bacteriostatic (stop the growth of bacteria).

Classification of Penicillins There are 4 classes of penicillins, based upon their ability to kill various types of bacteria. From narrow to broad range of effectiveness they include: 1.Natural Penicillins (Penicillin G, Procaine, Penicillin G, Penicillin V, Benzathine). The natural penicillins are based on the original penicillin-G structure. They are effective against gram-positive strains of streptococci, staphylococci, and some gram-negative bacteria such as meningococcus.

Penicillin V is the drug of choice for the treatment of streptococcal pharyngitis.

2.Penicillinase-Resistant Penicillins (Cloxacillin, Dicloxacillin, Methicillin, Nafcillin, Oxacillin).

Methicillin was the first member of this group, followed by oxacillin, nafcillin, cloxacillin and dicloxacillin. The penicillinase-resistant penicillins have a more narrow spectrum of activity than the natural penicillins.

3. Aminopenicillins (Ampicillin, Amoxicillin, Bacampicillin). The aminopenicillins were the first penicillins discovered to be active against gram-negative bacteria (such as E. coli and H. influenzae).

Aminopenicillins are acid-resistant so administered orally. Orally administered amoxicillin and ampicillin are used primarily to treat mild infections such as otitis media, sinusitis, bronchitis, urinary tract infections and bacterial diarrhea. Amoxicillin is the agent of choice for the treatment of otitis media.

4. Xtended Spectrum Penicillins (sometimes called anti-pseudomonal penicillins). Extended Spectrum Penicillins include both alpha-carboxypenicillins (carbenicillin and ticarcillin) and acylaminopenicillins (piperacillin, azlocillin, and mezlocillin.

In ACI Limited,the penicillin plant is completely separated from other plants because penillin can grow resistance by contaminating with other materials.

This unit deals with two types of preparations.These are 1.Parenteral preparations:Vial filling and sealing.

2.Oral preparations:Preparation of dry syrup,capsule.

In this plant,we observed the production of FLUCLOX 500mg Capsule.

Materials required: 1. Flucloxacillin Na BP(compacted) 2.Mg stearate 3.Empty hard gelatin shells.size 0 having dark blue cap and opaque light blue body.

Room condition: Room temperature:24°C Relative humidity 43% Process: Weighing and mixing in a drum mixer(Flucloxacillin Na BP compacted) ↓ Weighing Mg stearate and pass through mesh no.40 into the drum mixer ↓ Mix both for 30 minutes at a definite speed. ↓

Discharge the granules in a plastic drum and ready for encapsulation.

Procedure of flucloxacillin encapsulation: Capsule shells are given into the hopper ↓ capsule shells come in a secondary section ↓ shells are automatically fitted in capsule dies ↓ caps and bodies are separated by vacuum pressure through rubber stopper which cause the upper and lower dies to be separated ↓ flucloxacillin powders given in hopper powders are automatically filled in the body of shells ↓ Close the body and cap by closing pin ↓ displaced shells are automatically sealed ↓ filled capsules are automatically ejected In this plant,we also observed the production of AVLOMOX D/S 500mg Room condition: Room temperature:23°C Relative humidity 41% Materials required: 1.

2.

3.

4.

5.

6.

7.

8.

9.

Amoxicillin trihydrate BP(micronised) Na benzoate Na citrate anhydrous Methyl cellulose dried Citric acid BP Colloidal Silicon dioxide USNF Banana flavour powder Ph.grade Polysorbate 60 BP Sucrose BP

Flow chart of Dry syrup manufacturing:

Material Weighing

Blending active with ← excipients in a drum mixer.

Milling to reduce the particle sizeof Na citrate anhydrous(3.0 mm) & Citric acid BP(1.0mm).

Weighing and sieving other excipients through specific mesh..

Drying sucrose in FBD at 90°C for 45 minutes.

Drying Na citrate& Methyl cellulose in FBD at 80°C/90°C for 1.5/4.5 hours.

Sifting the dried materials separately by russel sifter using 24 mesh.

Final blending of all materials for 1 hour.

Instruments / Apparatus Used In PENICILLIN unit: Sl no.

1.

2.

Name of machine Drum mixer machine Auger dry syrup filling machine

Capacity 150 kg 1500-1800 (manually) -------------

Source Bangladesh Hayser machinery Ltd,Canada.

Bangladesh

3.

4.

Bottle cap Sealing machine (ROPP-Round over pilfer proof cap) Auto capsule filling machie

30000cps/hr

Sejong pharmatech SF-40,South korea.

E.chung industries Co, Taiwan.

Chas F.Thackery.Leeds London.

5.

Hot air sterilizer

-------------

6.

Autoclave

------------

Parenteral preparation: Parenteral preparations or injectables are the sterile solutions or suspensions of drugs in aqueous or oily vehicles meant for introduction into the body by means of an injection under or through one or more layers of the skin or mucous membrane.

Parenteral preparations must be introduced through the same route for which they are intended, for example, if an oily suspension meant for intramuscular injection is introduced by intravenous injection may prove fatal.

Types of parenteral preparation: Parenteral preparations may be classified as follows: 1. Solutions ready for injections.

Example: Insulin injection, USP 2. Suspensions ready for injection Example: Methylprednisolone acetate suspension 3. Emulsions suitable for parenteral administration .

Example: Propofol.

4. Dry, soluble products which are dissolved in a suitable solvent immediately before its administration.

Example: Cefamandole Na for injection.

5. Dry, soluble products which are combined with a suitable vehicle just before its administration.

Essential qualities of parenteral products: A parenteral product must possess the following characteristics: 1.

2.

3.

4.

5.

It should be free from living microorganisms & microbial products.

It should be free from pyrogens.

It should be free from foreign particles such as dust, etc.

It should be free from chemical contamination.

It should be isotonic with body fluids.

6.It should have matching specific gravity with respect to some body fluids 7.Multidose injections must contain preservatives.

8. Container must not affect the product.

Advantage of parenteral preparation: 1.

2.

3.

4.

5.

6.

It may produce immediate response in case of critical illness.

Rapid onset of action.

Escaping first pass metabolism.

Complete utilization of drug & loss of drug.

Best way to administer the potent drug.

For long acting & 100% bioavailability.

Routes of administration: The above mentioned preparations may be administered by any of the routes such as subcutaneous, intravenous, intradermal, intramuscular, intraspinal, intracisternal, intrathecal, intracardiac, or intraartecular. Out of these routes, the subcutaneous, intramuscular & intravenous are the most commonly used routes of SVP of ACI Ltd includes vial, ampoule & ophthalmic preparations.

Instruments used in SVP unit: A. For water for injection (WFI): STILMAS HIGH EFFICIENCY MASCARINI (Redistillator) Made in Italy Model: FA-100 HR Capacity: 40 liter/hr Working pressure: 4 bar Pyrogen free warm / cool WFI is produced B. For sterilization: 1. Linden (Moist heat autoclave) Steriltech, Holland Capacity: 500kg Sterilization: 1210c at 15 lb/ cm2 for 15 min.

Usually sterilization is performed for 30 min.

2. Hot air sterilizer E. Chung Industries Co, Taiwan Model: ECHS-90 Capacity: no. of vial’s trays- 40, no. of vial’s per tray-210 No. of ampoule’s tray = 80, no. of ampoules (10ml) per Sterilization: 1900c for 1 hr for ampoule 2500c for 1 hr for vial

tray=500

3. Reserve vessel Lio Chang Kung Hardware Enterprise Co Ltd. Capacity: 200L 4. Getings (Moist heat sterilizer) Sweden 5. Sartorious (pressure vessel) Sartorious AG, Germany Capacity: 40L Temperature: 950c Pressure: 5 bar C. For washing: 1. COZZOLI (Ampoule, vial & plastic container washing machine), 2 pcs Cozzoli Mchine Company, USA RPM: 2 Nozzle: 16/ machine Capacity: 32 ampoule/ min Each vial is washed 6 times in one cycle & out that water with air flow.

2. Rubber stopper washer Capacity: 10000 stopper/ batch 3. Chempharm Chempharm Industries Ltd, India Model: CP-PB D. For vial labeling: 1. Pharmalab Pharmalab MKTG Agency, India Capacity: 3000 vial/hr 2. Greatide Greatide Industrial Co Ltd, Taiwan Model: SHL-2570 E. For vial filling & sealing: Greatide Auto vial filling & sealing machine Greatide Industrial Co Ltd, Taiwan Filling nozzles: 2 Capacity: 25 Product capacity: 50 Volume capacity: 2-100 ml

F. Others: 1. CFM (Vacuum dust collector) Aspiratori Industriali, Italy Model: 3156-AX 2. Becker (Vacuum pump compressor) Germany Model: U4100 3A/K Mechanism of vial / ampoule washing: Ampoules are placed manually on tray Passed to ample washing room [ Ampoule’s trays are placed in washing machine where a flash of DM +WFI flows from upper and lower and upper part of the machine After certain period it is removed and the ampoules are replaced from that tray to another tray

Performed dry heat sterilization for depyrogenation at 190 0 C for ampoule and 2500 C for vial for 1one hour Allowed to cool and remove it for filling and sealing in aseptic area.

Vial filling & sealing process: Receive ingredients

Deboxing Passed trough change box under laminar air flow Filling & sealing in aseptic condition Ampoule filling & sealing machine: 1. COZZOLI Ampoule filling & sealing machine Origin: USA Filling nozzles: 3 Sealing nozzles: 2

Type of ampoule: Open mouthed Visual inspection for ampoule: • • • • • • • •

Fiber Particle Inadequate volume Printing Faulty filling & sealing Satisfactory appearance Clarity of solution Sealed integrity & leakage

Types of packaging materials: 1. Primary packaging materials: it includes • • • •

Glass vials (7.5 ml or 15 ml) Rubber stopper Flip off seal Ampoules (1ml, 2ml, 3ml, 5ml& 10ml)

2.Secondary packaging materials: it includes • Leaflet • Disposable syringe • Inner cartoon • Master cartoon Classification of aseptic room: 1. 100-Class room: Particle count of this area must be below 100 particles of 0.5 micron size per cubic ft or 3500 particles of 0.5 micron size per cubic meter. a. A-Grade room: this area is completely under laminar air flow. Non-viable particle must be below 100 particle & viable particle is less than 1. b. B-Grade room: in resting condition, this area contain particle less than 100 but in working condition its particles become more than 100 & viable particle is less than 5.

2. 10,000 class or C Grade room: Other portion of filling room except A-class. Particle count of this zone is usually bellowing 10,000 particles & viable particles is less than 50.

3. 100,000 or D-Grade room: It consists of cooling room, sealing room & third change room & is below 100,000 particles & viable particles are less than 100.

Criteria of A-Class zone: • • • •

Air pressure is maintained 90mmHg for positive air flow.

Moisture must below 45% Temperature must below 250c Particles count must below 100.

Particle limits condition: For ampoules: Places

Limit(less than)

1. LAF workstation

100

2. Ampoule Filling & sealing room

100

3. Filtration room

100

4. Liquid vial filling room

100

5. Ophthalmic products filling room

100

6. Compounding

10000

7. Dispensing

10000

8. Corridor

10000

9. Final Changing room

100

For vials: Places

Limit(less than)

1. LAF workstation

100

2. Ampoule Filling & sealing area

100

3. Aseptic corridor 4. Final Changing room

10000 100

Process of getting WFI: Portable water → Chlorine + water → Reverse osmosis process → Passed through carbon filter → Deionized water → DM water → Filter & pass UV light → Purified water → Filter → Distillation → Condensation → Distilled water → Sterilized in autoclave → WFI (Water for injection)

The cephalosporins are a class of β-lactam antibiotics originally derived from Acremonium, which was previously known as "Cephalosporium".Together with cephamycins they constitute a subgroup of β-lactam antibiotics called cephems.

Cephalosporin According to cGMP regulations separate facility for cephalosporin is required to prevent cross contamination with other penicillin products or non beta-lactum products. Unintended exposure with Cephalosporin products may cause health concern to patients sensitive to Cephalosporin.

• • • • • • • •

Fully separated, well established and isolated manufacturing area only for Cephalosporin.

Highly sophisticated HVAC system and AHU are used to condition, monitor and supply clean air to the working zone.

Production floors and wall are covered with epoxy resin.

A complete set up of machineries required for tablets and capsule productions is established only for Cephalosporins.

More precautions are maintained in each and every steps during production, filling, sealing and packaging to prevent cross contamination.

Officers and the workers are trained specially to work more carefully in order to minimize cross contaminations.

Well furnished change rooms are maintained each floor of the production areas.

Samples during various steps of manufacturing are collected by QC officers all the times for proper manufacturing.

Instruments used in Cephalosporin: 1. IMA (Vial filler) IMA (Industrial Machine Automatic, Italy)

Model: 150 RPM: 150 Capacity: 150 vial/ min 2. IMA (Vial sealing) IMA (Industrial Machine Automatic, Italy) Model: ZG 3. Auger dry syrup auto filling machine (China) Company: Sanghai 4. Oblicone blender Capacity: 400kg RPM: 30 5. Shifter Process: Avlosef dry powder for suspension (Cephradine) Raw materials → Weight → Blend in Oblicone blender → Charged it to hopper (Auger Filling Machine) → Filling → Stoppering → Sealing.

In animal health section,the following types of products are produced 1. Bolus tablet (2-10mg):DIGIMIX20mg,DIATRIM(Combination of sulfadiazine, sulfapyridine, sulfadimidine, streptomycin sulfate.

2. Tablet:Oral-Z(Zinc sulfate) 3. Dry pwder:Eryvet Dry Powder.

4. Parenteral preparations We observed the production of BACTITAB 500mg Tablet Materials used: 1.

2.

3.

4.

5.

6.

7.

8.

Oxytetracycline HCL BP Maize starch BP Sucrose BP Aerosil-200 Mg stearate BP Kollidon CL USP Pregelatinized starch Kollidon VA 64

FLOW CHART OF DRY GRANULATION

Weighing and sieving of drugs and excipients Dry mixing of drugs and diluents Slugging or pre-compression Milling and sieving Lubrication Discharge for compression MACHINERIES USED DURING GRANULATION NO.

NAME OF MACHINARY

COMPANY NAME

1.

3.

RAPID MIXER GRANULATOR LIFTING AND TILTING MACHINE. FLUID BED DRIER

4.

SIFTER

5.

V-CONE BLENDER

YENCHEN CO.LTD,TAIWAN. YENCHEN CO.LTD,TAIWAN YENCHEN CO.LTD,TAIWAN YENCHEN CO.LTD,TAIWAN YENCHEN CO.LTD,TAIWAN

2.

CAPACITY MACHINERY 300KG MACHINERY 300KG MACHINERY 400KG MACHINERY ---------MACHINERY 400KG

MACHINERIES USED DURING COMPRESSION: NAME MACHINARY 1.

2.

3.

CADMACH RIMEK RIMEK

OF COMPANY NAME CADMACH,INDIA. CORNOBOTI ,INDIA CORNOBOTI ,INDIA

NUMBER PUNCHES 14 10 16

MACHINERIES USED DURING PACKING: SL NO. 1.

2.

3.

Machine Name AUTOSACHET MACHINE AUTOMATIC BLISTER MACHINE AUTOMATIC BLISTER MACHINE.

No. of Manufactured Machine by 1 Pakona PACK 1 Ganson

Origin

PACK 1

Korea

Hoong-A

India India

OF

INTRODUCTION Warehouse (FINISHED PRODUCTS) is the place where finished packed products are preserved and distributed.

Areas of warehouse (RM&PM) Quarantine area After packaging of finished products, they are stored first in the quarantine area.

Then Q.C. sampling and checking is approved and then shifted to the main storage area, which is escorted by grille.

Main storage areaHere finished products are stored. There is another isolated storage area for sophisticated materials maintaining temperature and humidity in side the main storage area named cooling room. The storage department performs some important functions such as A)Specific products are stored in specific mentioned area with proper documentation.

Cool area:15-24째C &Cold storage:2-8째C. B)According to monthly program, this department has the responsibilities to get final Q.C. approval for raw materials.

C)According to demand in the market(Invoice memo),released products are distributed to the depos.

Released area Here products are stored those only passed the tests performed by QA and QA provides green tag.

Not released area: Here products are stored for those the tests yet not performed by QA and QA provides yellow tag.

Rejected area Rejected products are stored here those failed the tests performed by QA and QA provides red tag.

OPERTIONAL SCHEME (From sampling to finished product)

After packaging of finished products,QA provides not released yellow tag to the products and stored in the not released zone.

QC department takes sample All types of tests are performed by QC. QC fixes ‘Approved’ tag if tests are passed Approved products are distributed to depos throughout the country in first in first out process

‘Rejected’ tag is given if products fail to pass the tests

Keep the record.

Introduction In pharmaceutical market few companies ensure qualitative products. ACI Ltd is one of them. Now a days, manufacturing of quality product is quite difficult from the raw materials to the finished product in each and every step quality operation department plays a very important role. Quality Assurance Department is very important for a pharmaceutical industry to maintain G.M.P. The concept of total quality management and total quality control refers to the process of striving to produce a perfect

product by a series of measures requiring an organized effort by the entire company to prevent or eliminate errors at every stage in production. Although the responsibility for assuring product quality belongs principally to Quality Assurance Department, it involves many departments and disciplines within the company. To be effective it must be supported by a team effort. The Quality Assurance Department is vital for a pharmaceutical industry since it controls and assures the quality of the products starting from the raw materials.

Quality assurance department consists of three sections,these are: QUALITY ASSURANCE

QUALITY CONTROL

COMPLIANCE

MICROBIOLOGY

Functions of QA 1. Raw Material Analysis: a)Vendor selection b)Source approval c)Sampling d)Assay e)Potency f)Water content determination g)Identification etc 2. In Process Analysis 3. Finished Goods Analysis 4. Packaging Material Analysis: a)Visual inspection b)Size c)Dimention d)Weight e)Adaptability f)Adherence 5. Calibration and validation of Laboratory Instruments 6. Fixation of Expiration Date (Stability test) 7. Process Validation 8. Product Complained analyses 9. Investigation of Out of specification 10. Environmental Analysis 11Development of New test Procedures 12GMP Audit 13.New source approval 14.Raw material validation 15.Microbiological analysis QA activity performs in ACI Limited is given in the following chart:

Visual inspection & testing for the quality of supplied Taking sample of raw materials & packaging materials of Q.C analysis Release or rejection based upon the quality control results If the material passes the quality control test, the raw & the packaging materials are dispensed.

If the cleanliness of equipment & area of manufacturing are ok, giving approval.

Some parameters are checked during in plant process.

Product as taken as sample from in process product for Q.C In process checking of packaging operation.

Collection of the retention sample & transfer of finished product for distribution.

Quality control is under QA department,concerned with sampling ,specification & testing to ensure that the necessary & relevant tests are carried out & the materials are not released for use until the quality has been judged as per regulation. It is the part of good manufacturing practice, which is concerned with sampling, specification and testing as well as the organization and documentation and released procedures. It ensures the necessary and relevant tests that are necessary to determine whether the products will be released or not for use, the raw materials can be used or not until their quality has been judged to be satisfactory.

QUALITY CONTROL OPERATIONS The Q. C. department assures manufacturing of quality product. It is completely related with production operation, mainly done in the production area to check o o o o o o o

Dispensing of materials Checking in pharmacy weighing Compounding in ingredients Process validation In process checking Complains of G.M.P., mainly storage of raw materials, finished products.

Label control.

The objectives of quality assurance are achieved when processes have been defined which, when followed, will yield a product that complies with its specification & when the e finished product o o o o o o

Contains the correct ingredients in the correct proportion.

Has been correctly processed according to the defined procedures.

Is of purity required.

Is enclosed in its proper container, which bears the correct label or otherwise suitably marked or identified.

Is stored, distributed and subsequently handled in such a way that its quality is maintained throughout its designated or expected life.

Customer satisfaction.

o

Safety assurance.

Various Tests done in QC  Chemical Assay  Physical Assay  Bio-Assay • Solid raw material  Characters: a)Appearance b)Solubility

•

•

FOR FINISHED PRODUCTS •

•

•

•

 Identification  Optical Rotation  LOD\KFR Test  Sulfated ash  Additional test  Residual solvent by gas chromatography  Bulk density  Heavy metal testing  Impurities  Melting point Liquid raw material  Refractive index  ph  Weight per ml  Viscosity Solid preparation ♠ Description ♠ Potency ♠ Dissolution and Disintegration time ♠ Weight variation ♠ Assay ♠ Titration Liquid preparation ♠ Weight per ml ♠ Microbiological limit test ♠ pH Semisolid preparation ♦ Microscopic examination ♦ Assay

FOR PACKAGING MATERIAL ♦ ♦ ♦ ♦ ♦ ♦ ♦

Description Text Colour Dimension Weight (gm/m2)/GSM Visual inspection for defects Adaptability

In the Quality control department all the information is written in a specific S.O.P. SHEET is prepared according to ACI Pharmaceuticals Ltd, Test procedure, BP and USP procedure. Several information, included, in the SHEET is as follows.

• Trade name and official name of the material • Date • Manufacturer date • Lot No. • Expiration date • Quantity • Label Potency • Test Procedure (As described before) • S.O.P. no.

Instruments in QC Department In Quality control Department the following sophisticated instruments are used: •

High Performance Liquid Chromatography (HPLC) device

HPLC Prominence (PDA) ,Model:515& 2487,Company:Shimadzu HPLC Prominence(Normal)-4 pieces ,Model:QAD-02B, Company:Shimadzu •

Refractometer

Hilger& Watts Atago Model:3T •

Karl- Fischer Titrator

Mettler Teledo Model:DL31  Mettler Teledo Model:DL18 •

UV visible spectrophotometer

Shimadzu Model:UV-160IPC •

Dissolution Tester

Logan ModelUDT:804 •

Disintegration tester

Shin k wang Machinery CO.Ltd. Model:SK-32020 •

Micropocessor PH Meter

Model:HANNA PH 210

• •

Electronic PH Meter Melting point Testing Apparatus

Buchi Melting point Model:B-540 • •

Copley Friabilator Hardness tester & Diameter tester

Schleuniger Pharmatorn Ind. Model:6D •

Electric Balance

Model:BOECO •

Drying Oven

Sanyo Gallencamp • •

Slide calipers Humidity test chamber (for stability test)

Climacell Model:707 • • • • • • •

Thermometer Conductivity meter Magnetic Shaker Muffle furnace Desiccator Sonicator:Use ultrasonic sound to mix solutes with solvents Vibrator

 Edmund Bucler Model:KL-2 • •

Atomic absorption spectrophotometer Brookfield Viscometer

Model:DV-1 • •

Tap density tester(USP) Water purification system

Model:Alpha-Q • •

IR detector (Fourier Transform) Optical Polarimeter

High-performance liquid chromatography, (HPLC) High-performance liquid chromatography, HPLC is a popular method of analysis because it is easy to learn and use and is not limited by the volatility or stability of the sample compound. The information that can be obtained includes identification, quantification, and resolution of a compound.

Figure: HPLC machine Principle A liquid mobile phase is pumped under pressure through a stainless steel column containing particles of stationary phase with a diameter of 3-10 um. The analyte is loaded onto the head of the column via a loop valve and separation of a mixture occurs according to the relative lengths of time spent by its components in the stationary phase. It should be noted that all components in a mixture spend more or less the same time in the mobile phase in order to exit the column. Monitoring of the column effluent can be carried out with a variety of detectors.

Applications • • • •

The combination of HPLC with monitoring by UV/visible detection provides an accurate, precise and robust method for quantitative analysis of pharmaceutical products and is the industry standard method for this purpose.

Monitoring of the stability of pure drug substances and in drugs in formulations with quantization of any degradation products.

Measurement of drugs and their metabolites in biological fluids.

Determination of partition coefficients a p Ka values of drugs and of drug protein binding.

Advantages • •

Easily controlled and precise sample introduction ensures quantitative precision.

HPLC is the chromatographic technique, which has seen the most intensive development in recent years leading to improve columns, detectors and software

control.

The variety of columns and detectors means that the selectivity of the method can be readily adjusted.

Ultra violet Visible Spectroscopy, (UV) It is a type of absorption spectroscopy that useses the ultra violet &visible part of the electromagnetic spectrum.UV&Visible spectrum is obtained by passing UV& Visible light through a transparent layer of the substance being examined & then recording the transmitted light.

When a beam of electromagnetic radiation is passed through a sample ,the radiation can be either transmitted or absorbed ;depending upon the structure of the molecule.So the radiation not absorbed that is transmitted can be measured by UV&Visible spectrometry.

Figure: UV&Visible Spectrometry machine UV Range:(190-400nm);Visible Range:(400-800nm)

Monitoring cGMP to ensure that products and consistently produced and controlled to the quality standard appropriate to the product specification. 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.

Major duties and responsibilities: -

Inspection and reporting that manufacturing operations are running as per SOP. IPC of the bulk products. IPC of the finished products Checking general cleanliness Checking that manufacturing instructions and packing instructions of followed properly.

Analysis of product, raw materials and water Identification constraints of existing manufacturing and testing operations in compliance with cGMP and find out the possible solution Prepare the compliance related reports/inquires Generation or revision of SOP Coordinating and participating in cGMP, GLP and other training programs that focus on the elements of the compliance program thus striving to ensure that all appropriate

employees are knowledgeable of WHO, cGMP standard, local and other regulatory norms.

Documentation: - The site quality policy manual - Reports on general cleanliness - Training records - Stability study records - IPC records - Instrument requisition record - SOR/Protocol record - Training materials - Maintains the follows of reports - Minutes of meeting - Inter-departmental correspondence - ISO/cGMP audit circular files - The modification the record of MI, PI,CI. - The customer complain handling documents

Observation: We have observed various tests carried out by compliance personnel. The tests are as follows— - Hardness - Weight variation - Average weight - Friability test - Disintegration - Thickness - LOD - Leak test - Sanitation reports - Microbial count test We observed these tests during the production of the following products— - Acical Tablet - Anaflex Tablet - Sintel Tablet

Quality Compliance

Change Control

Deviation

NCR

Customer Complain

Product Quality Review

Central Archive

Training

Audit

External Audit

Internal Audit

Documentation Local Market

Global

Introduction Microbiology section is one of the vital section of any pharmaceutical to ensure quality product. The microbiology section of QC department in ACIpharmaceutical Ltd is a well-decorated and segregated area that evaluates microbial load and particulate matter of both raw materials and finished product particularly sterile products.

Tests in microbiology lab: 1. Sterility test.

2.Microbial limit test of liquid preparations for the pathogenic organisms like Pseudomonas aerogenosa, Escherichia Coli, Staphylococcus aureous. Salmonella species & for raw materials and finished products.

3. Pyrogen test 4.Growth promotion test 5.Media validation test 6.Solid media 7.Liquid media.

Environmental tests 1.SWAB test 3.Contact plate technique

2.Settle plate technique 4.Air bone particle count

5.Air sampling Availability of written procedures  SOP for sterility testing of ampoule, vial and ophthalmic products.  SOP for microbial limit test.  SOP for microbial examination of raw materials.  SOP for detection and measuring the penicillin contamination in drug and equipment.  SOP for microbiological monitoring in sterile production environment  SOP for identification of bacteria by gram staining method.  SOP for microbiological monitoring of water.  SOP for cleaning and sanitation of area and utensils.

 SOP for antimicrobial preservative effectiveness test.  SOP for safety test of different raw materials and formulated products.  SOP for determination of particle size and crystallinity.  SOP for calibration of the microscopic scale.  SOP for preparation of different buffer and stock solutions.  SOP for microbiological monitoring of empty bottle.  SOP for microbiological monitoring of clean room including LAF station of microbiology lab.  SOP for working in LAF station.  SOP for disposal of expired media and biochemical.  SOP for entry, exit and downing procedure for the clean area.  SOP for media preparation and its quality control.  SOP for bacterial endotoxin test (BET).  SOP for calibration of bioindicator.  SOP for preservation and maintenance of laboratory control organisms.  SOP for Laboratory control numbering system.

Extent of implementation of the WHO’s cGMP and Regulatory norms:  Procedures shall be prepared and documented in consistent with the requirements of ISO 9001: 2000 WHO- cGMP standard and the quality policy set by the top management.  Procedure shall identify the person (s) who are responsible to perform activities according to approved document.  Procedure shall be identified as’ master procedure’.  All personnel will be trained on procedures that affect their activities.  Controlled copies of master procedure shall be distributed according to the distribution list of each master procedure.

Figure: Laminar Air Flow Bench.

Equipment and Accessories Tungsten loop, Bunsen burner, Forcef, Volumetric flask, Test tube, Conical flask, Measuring cylinder. Glass petridish (9cm diameter), water bath, Microliter pipette, Electronic balance,Vortex mixer.

Specialized locations - This section is completely separated from other sections.

- There is a class 100 clean room in this section.

- Different equipments are placed in different rooms.

Category, Type and Number of products being analyzed o In microbiological section generally assays the liquid and semisolid preparations such as suspension. Syrup, cream, ointment and gel are analyzed for microbial load. o

The most important job of microbiological section is injectable product analysis. Because these products are intended to inject through one or more layer of the body which reaches the blood directly.

o Reagents and glass ware management  Caso agar. 

Macconkey agar.



Tryptic soya broth.

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Tryptic soya agar plate.

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Bismuth ,Sulfate agar .

Sterility test Fluid Thioglycollate broth, Alternative thioglycolate,Soyabean casine ,Digest medium etc. are used to perform sterility test.

Glass ware management Petridish, separating funnel, pipette, volumetric flask, test tube etc are to be used with extra care.

Novel drug delivery system

ACI is actively engaged in introducing newer molecules & Novel Drug Delivery Systems (NDDS) to meet the needs of the future. Novel Drug Delivery System is the choice of drug administration in future.ACI feels that to improve the drug action & selectivity. Pellets are the latest drug presentation in the modern world with better patient compliance. Pellets are the small particles having different size & color.ACI introduce different pellets such as • • • • • • •

Omeprazole(7.5,8.5,15)%, Esobeprazole7.5%E/C pellets, Pentoprazole, Lansoprazole8.5%E/C pellets, Diclofenach Sodium SR coating, Propanolol Hcl SR pellets, Ketoprofen SR pellets etc.

Apparatus used in NDDS: • • • • • • • •

Miller(Size:.3micron) Coating/Dusting Pan(Capacity:100kg,RPM:20-30) Tray Dryer Shifter Fluid Bed Granule Coater,From China,(Model:ACI FBC-300) Fluid Bed Granule Coater(Capacity:100kg) Fluid Bed Granule Coater,For PD,(Capacity:6kg) Seiving apparatus.

Materials used • • • • •

Suger Binding Solution(Ex:Povidone k-30) Hydroxy propyl methyl cellulose Sugary Active

Types of pellets • •

Neutral pellets Active pellets

Neutral pellet seed (NPS) production At first take suger & sieving through 35 to 45 meshes,collect 35-45 meshes suger & generate dust below 35& upper 45 range suger.Then (35-45) suger kept in pan coater.After that spray the binding solution by nozzle & add suger dust.Continue the process until (40-60)ranges suger round shape is obtained.Finally dry the round shape suger & sieve to form a desired size NPS. Pellets production There are two types of pellets formulation system.Such as: • Conventional Coating Pan Technique.

• Liquid System Pellets Technique.

Conventional Coating Pan Technique.

Neutral Pellet Seeds Spray Binding Solution & Active dusting Seiving Seal Coating Drying in tray dryer Enteric coating in Fluid Bed Coater Liquid System Pellets Technique.

Neutral Pellet Seeds Seal Coating Active drug Enteric Coating Seiving Parameters • Spray gun nozzle diameter:1.2mm.

• Silicon tube diameter:6mm/9mm.

• Maintain Atomizing air pressure.

• Maintain Product bed temperature.

• Controll Inlet air temperature.

• Controll Inlet air humidity.

• Spray rate.

ACI Limited has a strong engineering department, which rendering their services to act as a supportive hand for smooth production.

Engineering department: 1. Power House 2. Compressed gas system 3. Chiller system 4. DM water plant 5. Central heat, ventilation and air conditioning system(HVAC system) 6. Steam generation and supplied plant 7. Effluent treatment plant •

Power house of ACI:

ACI Ltd has an own complete power supply plant, which is considered as the heart of the factory. They do not use PDB electricity. The total factory demand is maximum about 2000kw which is completely fulfilled by this power house. They use PDB for lighting purpose after 10pm.

The power plant of ACI consist of1. Gas generator: They have three generators operate by using purified natural gas having capacity of 1600kw, 1145kw and 380kw.

Brand: Caterpiller 2. Diesel generator: One generator operated by diesel, output 55kw.

•

Compressed gas system of ACI:

Compressed gas used widely in various production such as blistering as well as cleansing purpose (Capacity is 10000L/min), in PLC (Programmable Logic Control) related operations and injectors.

•

Chiller system:

This system is involved for the production of chilled water which is supplied through the pipe to produce air conditioning system. ACI has both compression and absorption type chiller of which one is in new solid and another one is in old solid area. The chiller systems are1. Career, Singapur, supplied in new solid area (Compression type) Capacity: 160tone 2. Thermix, India, supplied to old solid and LCO area (Absorption type) Capacity: 172 tone 3. Trane, Singapur, supplied in SVP and Penicillin (Compression type) Capacity: 140 tone

•

DM water plant:

ACI has a well established DM water plant. At first the water is dematerialized by reverse osmosis which reduces the mineral contents about 90% and then passed through the ion exchange resin. The advantages of reverse osmosis are  

To decrease regeneration time To decrease chemical using To decrease conductance above 90%

Process: Water→ Bleaching dosing→ Sand filter→ water softener→pH adjustor (NaOH)→ Anti-scalant→ Micro filter→ Reverse osmosis→ EDI→ UV→ DM water.

HR & Administration consist of the performance or management of business and thus the making or implementing of major decisions. Administration can be defined as the universal process of organizing people and resources efficiently so as to direct activities toward common goals and objectives.

In ACI Ltd, administrative head is the factory’s General Manager Operations himself.

Administrative Functions: The main function of this department is to run the plant smoothly by performing the following functions: • • • • • • • • • • • • • • • •

Recruitment of personnel with appropriate qualifications & experience to fill all position that has an effect upon quality. Different standard are considered for different position.

Assist new employees to complete joining activities & ensure placement of new comers.

To arrange, induction-training program (orientation program) for new employees. After joining each employees is introduced with all of the departments & their functions to know about company operation.

Prepare & coordinate internship program for the students of different universities.

Maintain & update personal files of all employees monthly. Such as conformation of job increment, promotion, transfer & other letters is adjusted in the employee file.

Supervise & monitor employee monthly attendance. Job cards, prepare monthly attendance summary & daily absent report etc.

Monitor & update leaves of plant employees. Each employees has a leave file which integrated the all kinds of leaves.

Inform managers & employees regarding, personnel polices & procedure of the company.

Coordinate & monitor performance appraisal of plants employees annually.

Asses the training needs of personnel in light with cGMP &other work related issues.

Deals with industrial related issues like negotiation with employees union, ensure the labor rights etc.

Ensure proper implementation of labor laws applicable to factory employees.

Disciplinary action including suspension, punishment & termination.

Ensure healthy labor management relationship for smooth production.

Maintain liaison with Govt. regulatory Bodies.

Ensure safety of all employees & company assets.

ACI is one of the leading pharmaceutical companies in Bangladesh. It is first ISO certified company in Bangladesh and has achieved ISO 9001certification in 1995.So it is so difficult to find any anomalies in their operation. Albeit it is a super class plant, we may impart some suggestion to rectify some its observable problems to ensure the product safety as well as human safety in the plant.

From our point of view the following suggestions can be made: Quality Control Department:    

There ere many machines which are out of order should be repaired for better analysis.

It may be more specific to maintain its environment more strictly.

Space enlargement is desired.

Unhygienic sink should be avoided.

Production Department: 1. Solid Department:    

The dispensing area may be separated from solid and LCO Department Personal movement may be more controlled Here manufacture of antibiotics may be avoided.

During granulation procedure if workers wear long apron, it may be more appropriate.  Compliance activity may be improved here 2. LCO Department:     

Maximum machines are in slow output rate Filling and packaging in most cases are not automatic Some rooms are congested in space Room environment is not pleasant for working. It may be improved.

Humidity of dry syrup filling room may be more strictly controlled.

3. SVP and Cephalosporin unit:  Separation of Cephalosporin unit as soon as possible is desired.

4. Penicillin:  HVAC system installation and environment control may be done more strictly.  Space enlargement is desired.

5. Animal Health:  Cleanliness may be maintained more strictly.  Human pharmaceutical products should be separated from animal products.

6. NDDS Department:  Diclofenac solution may be prepared in a closed vessel more carefully to reduce the chance of contamination.  Touching the finished pellets with naked hands is not desirable.  No compliance activity observed

Ware House:  Proper place may be managed to separate storage of raw materials and finished products from warehouse-2  Space may be enlarged  Self-life storage room may be separated from warehouse.  More clean and healthy environment may be maintained inside the warehouse  Damaged products were stored in ware house-2 for more than enough time.These products may be removed to save some space.  Products of one region were located in another.So this should be taken under consideration  Animal health product and Human health product should be kept in totally different place.

Other:  There should be enough and clean apron, shoe cover. mask and hair cover for each trainer or visitor.

Although the four weeks time of our training in ACI Ltd. flew very quickly, with the co-operation of the authority and all the personnel, we have learnt a great and gathered a lot of experience which will be helpful for our future practical purposes. In every section, the respective authority cordially received us. They initiated our curiosity and interest regarding the relevant subjects. We are pleased with the behavior of every person involved in the factory. Thus, we have completed our training with great satisfaction and we hope that the feeling is mutual.

Some of the technical aspects of ACI Ltd, which we found very admirable, are as follows: The plant layout of the ACI Ltd. plant at Narayanganj is in a word, excellent. It was, no doubt, a very well planned layout that provides an optimum use of space and ease of operation and thus contributes highly towards optimum productivity. Furthermore, there is ample opportunity for expansion when the need will arise. The plant area is also very nice and, having its own Prayer room.

The plant is very well organized and the internal environment is very supportive to the employee, which is very nice since a congenial atmosphere increases the productivity of a company. The canteen is also very nice and the food menu was found to be very good, although there is always room for improvement in this regard.

One of the impressive things about ACI Ltd. is its wide range of products and its quality. We were also very impressed with the maintenance of GMP and the extensive documentation of all the works kept in the in the company, complying with the ISO 9001 requirements.

Another most impressive things about ACI Ltd is that they are trying to commence such kind of product which are valuable and they are marketing it in lower price.

We would like to end with a note of thanks, again, to Almighty Allah, and to everyone involved, for successful completion of this training and we hope that ACI Ltd will continue its co-operation to allow In-plant Training in future.