Eskayef Bangladesh Ltd

View with images and charts In-Plant Training Program At SK+F Eskayef Bangladesh Ltd.

Introduction SK+F symbolizes a name-a state of mind. From the inception in 1990, it has today burgeoned into one of the top line conglomerates in Bangladesh. Eskayef Bangladesh Limited, the flagship company, is holding the strong leadership position in the pharmaceutical industry of Bangladesh since 1990 and is now on its way to becoming a high performance global player.

Eskayef Bangladesh Limited is an organization with equal emphasis on Leadership, Technology, Quality & Passion.

Eskayef Bangladesh Limited is the leading generic pharmaceutical manufacturer in Bangladesh producing quality essential and other ethical drugs & medicines. Eskayef Bangladesh Limited has three GMP compliant formulation plants. The Tongi unit plant started its operation to meet challenges of globalization & to expand export horizon.

Tongi plant is situated at Tongi, Gazipur. It is constructed as per the requirement of the UK MHRA. All the facilities and equipment have been designed and built to ensure cGMP compliance.

All facility is an excellent blend of modern architecture, advanced technology, quality assurance and professionalism. It enjoys its brilliant is the prominent Drag manufacturing company in Bangladesh. It has started its production & Drag delivery from 1990. Eskayef Bangladesh Limited Tongi Plant is especially established for achieving the MHRA approval.

For this reason, this unit provides the products with high quality.

According to the training schedule we have visited all the departments of Eskayef Bangladesh Limited. The process of manufacturing & of maintaining qualities according to the cGMP guidelines were observed & in this light standard operating procedure (SOP) has been developed. All performances in the factory are highly documented.

Besides, Eskayef Bangladesh Limited providing local pharmaceutical needs & has been exporting its products to the many countries. It has been also receiving the order from the many Pharmaceutical Industry ( Tole Manufacturing ).

Eskayef Bangladesh Limited not only provide the high quality Drugs but also prevent the nature from its wastage affect. For this reason, it has established ETP plant which destroys the harmful effect of various toxic chemicals.

As a result of completing in-plant training in a well organized & well reputed company such as Eskayef Bangladesh Limited, our theoretical concept has become developed on the basis of practical view.

About Tongi Plant : Area (Infrastructure): Total area of Tongi Plant is 39,000 square feet (approximate) and the capacity of Warehouse 7,34,000 square feet.

Manufacturing Dosage Facilities: 1.

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Tablet (Uncoated, Film Coated, Enteric Coated Tablet) Capsule Liquid Sachet Topical Preparation

HVAC System: Total manufacturing area is under HVAC System.

Power Back up System: Normally Electricity supplied from Dhaka Electric Supply Company (DESCO) & 24 hours back up power supply available through 03 Generators having capacity of 1250 KVA. Purified Water System: Water treatment plant have the capacity of 1000 Ltr./hr following Reverse Osmosis & UV Radiation Technology.

Current Plant Capacity: Present production capacity in value is 120 Crore Taka & in unit packs 1.61 Crore Packs per year.

Waste Management System: Have separate area for waste disposal under the supervision of the authorized person according to the standard operating procedure (SOP) following the direction of WHO guideline.

Manufacturing Dosage Facilities: 1. Tablet 2. Capsule 3. Eye drop 4. Vial 5. Dry Syrup HVAC System: Total manufacturing area is under HVAC System.

Power Back up System: Captive own power supply from gas generator of 2.2 MW capacity which is back up by 800 KW diesel generator.

Purified Water System: Water treatment plant has the capacity of 1000 Ltr./hr following Reverse Osmosis Technology and the capacity of WFI 800 kg / hr.

Distribution channel : Transcom Distribution Co. Ltd. (TDLC) is the sole distributor of Eskayef products throughout Bangladesh.

Eskayef at a glance Company name Company logo Company slogan Company type Acquisition from Company started Ownership Factories Marketing office Commercial Dept.

International Business Finance & Accounts AHND office Annual turnover Web address E-mail Managing Director Employees IMS ranking Prime brand Business Distribution Depots Regions Vision & mission :

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Eskayef Bangladesh Limited

Excellence through quality Private limited company SmithKline & French 1990 Transcom group Mirpur (generic), Tongi (generic & cepha) Taneem Square, Banani, Dhaka Taneem Square, Banani, Dhaka Taneem Square, Banani, Dhaka Gulshan Tower, Gulshan 2, Dhaka Motijheel C/A, Dhaka BDT 3000 million , US$ 44 million www.skfbd.com info@skf.transcombd.com Mr. A M Faruque 1500 5th largest in Bangladesh Pharma Industry Losectil (omeprazole) Formulation, Consumer, Bulk Pellets, AHND Transcom Distribution Company Limited, : TDCL : 20 Depots : 20 Regions

Eskayef envisions a leading role for itself as a catalyst for improvement of the healthcare environment.

The company's mission is to maintain people's health and combat disease to enhance the quality of human life so that people may live longer, healthier and more meaningful lives.

Business : Eskayef Bangladesh Ltd. started its operation with pharmaceutical finished products for the home market. Over time we have diversified our operations into bulk products as well as animal health and nutrition products.

Finished Products : Backed by our strong technical and marketing teams we offer 149 products in 55 therapeutic segments.

Bulk Products : We produce Timed Release Blended Pellets. Eskayef is the first and only pellet manufacturer in Bangladesh.

Animal Health and Nutrition Products : We manufacture 28 animal health and nutrition products in 57 dosage forms and market them throughout Bangladesh.

Export : Eskayef Bangladesh Ltd. has been showing a significant outcome in exporting medicines to many countries. Eskayef Bangladesh Ltd. has started supplying medicines in 16 countries like Germany, UAE, Nepal, Bhutan, Sri Lanka, Myanmar, Vietnam, Ghana, Iraq, Indonesia, Kenya, Guatemala, Belize, Yemen, Macau and Somalia.

Marketing of International Brands : We are the sole agent in Bangladesh for marketing the ophthalmic products of Allergan Pharmaceuticals Ltd., Ireland in Bangladesh.

People : The workforce of Eskayef consists of more than 1200 to 1500 appropriately qualified, trained and skilled personnel who are drawn from different disciplines that have a bearing on the pharmaceutical industry. Our team of dedicated professionals includes a panoply of pharmacists, medical graduates, microbiologists, chemists, engineers and business management experts. Their competencies, experience and strict adherence to the work ethic go into the manufacturing and marketing of each of the company's products.

Quality Approach

Our Total Quality System is our key strength. We have inherited the Standard Operating Procedures and Quality-Approach of SmithKline & French. Our WHO audited plants produce the products conforming to the highest international standards. And to maintain the excellence that we strive to achieve we use the most advanced technology for quality control and at each and every stage of the manufacturing process.

History: The chairman of Transcom group planted a seed of dream in 1885. As the years went by the seed began to grow and soon turned into a full-grown tree with its leaves branching out in innumerable ventures. The company which started its business in the jute and tea sectors gradually diversified its operations into: 1.

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Health care sector Household electronic products Beverage Print media Restaurant franchise Software, and Distribution Channel

Today, TRANSCOM is one of the leading conglomerate companies of the country. The dream has turned into reality by the pragmatic vision of Mr. Latifur Rahman, the Chairman of TRANSCOM GROUP and Eskayef Bangladesh Limited and the company proudly stands symbolizing the epic tree of the seed that was planted 120 years ago.

Continuing its journey towards diversification, TRANSCOM entered the health care sector and acquired ownership of the world-renowned multinational pharmaceutical company SmithKline & French in the wake of the merger between SmithKline & French, USA and Beecham, UK in 1990. After the acquisition, the new company was styled - Eskayef Bangladesh Ltd and that has subsequently culminated under the bold and dynamic leadership of Mr. A M Faruque, the driving force and the Managing Director of Eskayef Bangladesh Limited.

Profile of MD

Mr. A M Faruque is the Managing Director of Eskayef Bangladesh Ltd., one of the top five pharmaceutical companies in Bangladesh. He started his pharmaceuticals career with Fisons Bangladesh Ltd. in 1974. In his long and illustrious career, he has also served in different positions in ICI, Hoechst, Smith Kline & French and Gulf Pharmaceuticals Industries, UAE. Mr. Faruque rejoined SK&F as Marketing Manager in the United Kingdom Overseas Group (UKOG), based at Welwyn Garden city, Hertfordshire, UK. After that he was relocated to the Bangladesh Smith Kline & French operation as their Marketing Manager till 1990, prior acquisition of the company by Transcom group, one of the leading conglomerate companies of Bangladesh.

Mr. Faruque started working at Eskayef Bangladesh Limited as a Plant Manager. Later on he served as the General Manager and then the Executive Director of the company from till July 2004. Since July 15, 2004 he has been assigned with the responsibility of Managing Director of Eskayef Bangladesh Ltd. It is to be mentioned here that in the history of Bangladesh pharma market this is the first instance, where a private limited company, Eskayef, has appointed a Managing Director from the professional stratum.

Having started with a modest business of 1.20 crore taka in 1990, Eskayef Bangladesh Ltd. has now an annual turnover of 350 crore taka. This phenomenal growth was achieved under the bold and dynamic leadership of Mr. A M Faruque, the driving force and the navigator of Eskayef Bangladesh Limited. Keen to explore newer horizon, Mr. Faruque also has turned its focus on exporting the products. With its pioneering venture in international market with Nepal, Eskayef has expanded its business to Germany, UAE, Sri Lanka, Belize, Vietnam, Yemen and some other Central American countries.

True to his vision of offering world-class healthcare products, Mr. Faruque has undertaken a new project to expand its state-of-the-art pharmaceutical operations under the exclusive technical supervision of an UK pharmaceutical consultant. The new facility is being designed to conform to international cGMP with particular emphasis on meeting MHRA standards of the UK in order to facilitate exports to overseas markets.

Mr Faruque has obtained BSc (Hons) and MSc in Chemistry from Dhaka University. He has undergone an extensive training on marketing and sales force management in Ashridge Management College, UK. Backed by our strong technical and marketing teams we offer 160 products in 59 therapeutic segments.

TOTAL PRODUCT LIST BRAND AMBOTEN ANAPRIL AROCEF AROTIDE BONFLEX BRIZY BROMID

GENERIC NAME Ambroxol HCl Enalapril maleate Cefadroxil monohydrate Salmeterol and fluticasone Glucosamine sulfate 250 mg & chondroitin sulfate 200 mg Levosalbbutamol Hyoscine butylbromide

CARBAZIN CARBAZIN CR CARBOLIN CARDON CARDOPLUS CEDNIR CEFLON CELIPRESS CLORON CORTIDER COSAT CRESTON DANAMET DAYPROX DELOXI DESODIN DEXPOTEN DEZIDE DIALON DIETIL DILATOR DORENTA EDENIL EFOPAM EMEZIN EMEZIN PLUS ESORAL ETORIX EXPOTEN EZY XINC FACID FACID-HC FENOBAC FEOFOL FEOFOL-CI FEOZIN FLUCLOXIN FLUCODER FOLVIT FOLVIT CI GASNIL

Carbamazepine Carbamazepine Carbocisteine Losartan potassium Losartan potassium + Hydrochlorothiazide Cefdinir Cefaclor Celiprolol hydrochloride Clonazepam Hydrocortisone acetate Co-trimoxazole Rosuvastatin Danazol Oxaprozin Duloxetine HCl Desloratadine Dextromethorphan HBr + Pseudoephedrine + Triprolidine HCl Hydrochlorothiazide + Triamterene Glimepiride Orlistat Bambuterol Diphenhydramine hydrochloride Furosemide + Spironolactone Nefopam hydrochloride Meclizine hydrochloride Meclizine HCl and Pyridoxine HCl Esomeprazole Etoricoxib Guaiphenesin+ Pseudoephedrine HCl+ Triprolidine HCl Zinc sulfate monohydrate USP Fusidic acid / Sodium fusidate 2% fusidic acid with 1% hydrocortisone acetate Baclofen Ferrous sulfate + Folic acid Carbonyl iron and folic acid Falic Acid USP and Zinc Sulfata Monohydarate USP Flucloxacillin Fluconazole Ferrous sulfate , folic acid, vitamin B-complex and vitamin C Carbonyl iron, folic acid, vitamin C, vitamin B complex Simethicone USP Paediatric Drops

GATINOX GELICON GLUNOR GLUNOR XR GTN 2.6 SR HANDIRUB HUNNY Hi-C IRBES KETONIC KILMAX KYNOL KYNOL D LAMIDIN LAXITOL LIPICON LODIBEN LOSECTIL LOSECTIL DR LOSECTIL PFS LOSITA LUMONA MEBIDAL MECOPEN METCO METOPA MILAM MIXAVIT MUPIRON MYCOFIN CREAM MYCOFIN TABLET NAPROX NEOREX NEORICE NEOSALINE NIMODI NOCLOG NOFICON NORIUM

Gatifloxacin Gemfibrozil Metformin hydrochloride Metformin hydrochloride Nitroglycerin Chlorhexidine Gluconate & Isopropyl Alcohol solution Glycerol & Liquid sucrose Ascorbic Acid USP Irbesartan Ketorolac tromethamine Cefuroxime Ketoprofen Dexketoprofen trometamol Lamivudine Lactitol monohydrate Atorvastatin calcium Amlodipine +Benazepril Omeprazole Omeprazole Omeprazole Escitalopram Montelukast Mebhydroline Mecobalamin Metronidazole Metformin hydrochloride and Pioglitazone hydrochloride Midazolam Cod liver oil with multivitamin Mupirocin Terbinafine hydrochloride Terbinafine Naproxen Cefalexin Rice Based ORs Sodium chloride, potassium chloride, trisodium citrate as dihydrate and anhydrous glucose Nimodipine Clopidogrel Fenofibrate BP Capsula Flunarizine

NRG ONTIN ORADIN ORADIN PLUS OSTOCAL OSTOCAL D OSTOCAL M OSTOCAL-C PANORAL PARLOX PEPTIL-H PEROSA PRIOCIN PRIOVIT PROACTIN Parisii@osoud.net Parisii@osoud.net QUINOX Quinox DS Quinox XR 1000 REOMEN RESTOL RIDON ROXIM SALOMAX SENSIT SENTIX SIDOPIN SIDOPLUS SK-CEF SK-FLU SK-MOX SOFTI SOLBION SOLVITONE SOMINEX STARIN STOMA SULIDAC

Glucose Cetirizine Loratadine Calcium carbonate Calcium carbonate + vitamin D3 Calcium carbonate + Magnesium + Manganese+ Boron + Zinc + Vitamin-D3 + Copper Calcium Lactate Gluconate INN, Calcium Carbonate USP and Ascorbic Acid (Vitamin-C) Pantoprazole Sparfloxacin Ranitidine Permethrin 5% (w/w) creame Erythromycin Vit.A + Vit.E + Vit.C Cyproheptadine parisii hacker Ciprofloxacin Ciprofloxacin Ciprofloxacin Clomiphene citrate Bromazepam Domperidone Cefixime Salbutamol 100 mcg Flupentixol dihydrochloride and melitracen hydrochloride Flupentixol dihydrochloride Amlodipine Amlodipine + Atenolol Cephradine Oseltamivir Phosphate Amoxicillin Zinc and castor oil Vitamin B1, B6 & B12 Vitamin B-complex Eszopiclone Cefpodoxime proxetil Aluminium hydrox. + Magnesium hydrox.

Sulindac

TAMEN TAMEN-X TELABID TELAZINE TIMOTHY TOPERIN TOPRESS TOTI TOZA TRIJECT TUFFOX TUFNIL TULAC TUMY URITOL UROKIT UROSIN VEDILOL VERON VINCET VIROXI VITRUM GOLD VITRUM SILVER VOLMAX XENOXIN XENTHOL 30 XINC XINC B ZATRAL ZEEFOL ZEEFOL-CI ZILVIT ZITHROX ZOFRA ODT

Paracetamol Paracetamol and Caffeine Trifluoperazine +Isopropamide Trifluoperazine Tiemonium methylsulfate film coated tablet / syrup / injection Tolperisone hydrochloride Metoprolol tartrate Ketotifen fumarate Nitazoxanide Ceftriaxone sodium injection Aceclofenac Tolfenamic acid Lactulose oral solution Calcium carbonate Tolterodine tartrate Potassium citrate Tamsulosin hydrochloride Carvedilol BP Coated Tablet Mebeverine HCl Vinpocetine Aciclovir Multivitamin and multimineral Supplement Multivitamins and Multimineralsl Diclofenac sodium Levofloxacin Methyl salicylate 30% & Menthol 8% cream Zinc sulfate Zinc and vitamin B complex Alfuzosine hydrochloride Iron+Folic acid+Zinc Carbonyl iron, folic acid and zinc Zinc,carbonyl iron, folic acid, vitamin B complex and vitamin C Azithromycin dihydrate Ondansetron

Warehouse : Generic Date :21.06.2010 Instructor : Shujib Biswas, Warehous Officer.

Key Service Benefits Of Warehouse :

Compliance Fit for purpose facilitiesWritten Standard Operating ProceduresWarehouse personnel are trained in GWP Matters (hygiene, Protective clothing,handling Of Goods, computersystems And Preventativemaintenance Interface and computer systems validation Increase productivity and efficiency With an outsourced warehouse, we let you focus on your core business activities and reduce or eliminate your capital investment in non-core areas such as equipment and facilities.

Certainty and reliability With a proven track record and an impressive customer portfolio, we will work to defined service levels to improve your entire supply chain.

Fast, accurate, detailed A professional and progressive company, with the added partner resources of POD, Couriers Please, Star Track, Toll, Australia Post, Jet Express and more.

A complete, integrated solution Supply chain management, leading edge technology and the most comprehensive distribution network available.

Responsive Dedicated support personnel and regular service reviews ensure that our services continue to provide the best solution for your business needs. We’ll adapt as you grow.

Materials that are stored : Raw materials ( RM ) Packaging materials ( PM ) Finished goods ( FG ) Functions : 1.Receiving Raw Materials : Receiving raw materials from approved source according to SOP. 2. Storing Materials : Storing raw materials, finished goods and packaging materials.

3. Dispensing : Dispensing raw materials, distributing packaging materials and loading finished products to the booth for marketing.

Central warehouse : warehouse-1 and warehouse-2 Source of RM : Remo – Big Source

Ganashasthya and Square Pharmaceuticals.

Dealing Documents : Receiving Record : Receiving Record No. Materials Name Batch No. Manufacturer Supplier Quantity Remarks BMR request form Manufacturing Order Finished Order Central Warehouse : Unit- 01 Temperature : CRT ( 15-25 degree celcius ) Observation : 1.Sampling Booth : In Which sampling of raw materials is done.The following raw materials are available that were observed…

Active :161 Excipients : 160 2.Narcotic Station : Stored according to govt. Regulations. The drugs that are stored in narcotic station are very much potent CNS stimulant and sometimes called controlled drugs.

Stored in a locking system.

Example : Dexpoten , Clonazepam, Pseudoephedrin ( Max. 3000 kg every year ) 3. Capsule shell storing ( RH – 25-65% ) Raw Materials Room Ext – 01: Active materials at CRT condition Raw Materials Room Ext – 02: Active materials at CRT condition Raw Materials Room Ext – 03: Active materials at CRT condition 4. Packing Materials Ext-01 : Bottle label Leaflet Zinc syrup Dexpoten 5. Packaging Material Ext-02 : Cap Storing -22, 25, 28 Color : White , Blue, Gold, Brown Pet bottle

Central Warehouse : Unit -02 Temperature : Ambient ( below 40 degree celcius ) Observation : Maximum-Minimum thermometer Log book Cold room Temperature range : 2-8 degree celcius.

Observed temperature : 5 degree celcius.

Stored materials : Na frusitate, Benzyl alcohol, Injectables.

Cool room Temperature range : 8-15 degree celcius.

Observed temperature : 12 degree celcius.

Stored Materials : Omeprazol E.C Pellates, Mg powder, Flavor’s, orange flavor powder, Essence, etc.

Shelf block Contains : Glass bottle, Plastic bottle, Raw materials that are not degraded in ambient conditions.

Solvent Room ( SR ) : Temperature : Ambient Stored Solvent : Methanol , Ethanol, Nitric Acid, HCl, isopropile alcohol, carbon tetrachloride, etc.

Miscellaneous bottle Stored -1 : Bottle ( Bengal bottle from Hindustan ) EGC shell Room.

Warehouse : Cepha Block 21.06.2010 Entering the Cepha block : Shoe Cover

Aprone

Head Mask

Instructor : Nazir , Warehouse Officer , Cepha block Cephalosporine Collection : Active materials : Various generations of cephalosporin Excipients : Methyl hydroxy benzoate Propylene glycol

Handirub spray

Arocef – 500 Etc Cold room Temperature range : 2-8 degree celcius.

Observed temperature : 5 degree celcius.

Stored materials : Benzyl alcohol, Injectables.

Cool room Temperature range : 8-15 degree celcius.

Observed temperature : 12 degree celcius.

Stored Materials : Cefradin with l-Arginine, Flavor’s, orange flavor powder, Essence, etc.

Room – 2003 : Flip off Seal. Eg- Triject 500 Cap Color : Golden, Pink, Sky. Cap Size : 22, 25, 26, 28 Bottle Size : 70, 75, 100 ml Room – 2005 : Engineering work shop : Change Part.

Room -2007 : Master Carton size : 48-130 Syringe disposable Master Carton specifications : Tablet, Capsule, PFS, Injections.

Room – 2008 : Vial : 7.5, 15, 30 ml Rubber Stopper – Blue color Flip off seal Carton Leaflet Room – 2013 : Simplification : Finished Goods ( FG ) Eg : SK-Cef ( Cefixim 500mg ) Master Carton : 24*100 Shelf-Life : PFS -2 years, Injectable-3 years.

Room- 2125 : Simplifications : Buffer Room Utilization : Mainly for finished goods delivery.

Room – 2126 : Simplifications : Waste disposal room Utilization : For storing waste products with waste packaging materials Production : Solid Dosage Form Unit : Manufacturing Unit – 02

Date : 02.02.2010 Entering Procedure : Officers Chage Room

Shoe cover

Aprone and Head masking

Handirub Spraying

Instructor : Ishtiaq Ahmed, Asst. Manager, MU – 2 Wet granulation : Wet granulation is a process of using a liquid binder to lightly agglomerate the powder mixture. The amount of liquid has to be properly controlled, as 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 solvent-based systems.

Procedure Step 1: The active ingredient and excipients are weighed and mixed.

Step 2: The wet granulate is prepared by adding the liquid binder–adhesive to the powder blend and mixing thoroughly. Examples of binders/adhesives include aqueous preparations of cornstarch, natural gums such as acacia, cellulose derivatives such as methyl cellulose, gelatin, and povidone.

Step 3: Screening the damp mass through a mesh to form pellets or granules.

Step 4: Drying the granulation. A conventional tray-dryer or fluid-bed dryer are most commonly used.

Step 5: After the granules are dried, they are passed through a screen of smaller size than the one used for the wet mass to create granules of uniform size.

Low shear wet granulation processes use very simple mixing equipment, and can take a considerable time to achieve a uniformly mixed state. High shear wet granulation processes use equipment that mixes the powder and liquid at a very fast rate, and thus speeds up the manufacturing process. Fluid bed granulation is a multiple-step wet granulation process performed in the same vessel to pre-heat, granulate, and dry the powders. It is used because it allows close control of the granulation process.

Dry granulation : Dry granulation processes create granules by light compaction of the powder blend under low pressures. The compacts so-formed are broken up gently to produce granules (agglomerates).

This process is often used when the product to be granulated is sensitive to moisture and heat.

Dry granulation can be conducted on a tablet press using slugging tooling or on a roll press called a roller compactor. Dry granulation equipment offers a wide range of pressures to attain proper densification and granule formation. Dry granulation is simpler than wet granulation, therefore the cost is reduced. However, dry granulation often produces a higher

percentage of fine granules, which can compromise the quality or create yield problems for the tablet. Dry granulation requires drugs or excipients with cohesive properties, and a 'dry binder' may need to be added to the formulation to facilitate the formation of granules.

Direct Compression : The term “direct compression” is defined as the process by which tablets are compressed directly from powder mixture of API and suitable excipients. No pretreatment of the powder blend by wet or dry granulation procedure is required.

The events that motivates the industry people to use direct compression technique I.Commercial availability of the directly compressible excipients possessing both good compressibility and good flowability.

SorbitolFor example, Spray dried lactose, Anhydrous lactose, Starch-1500, microcrystalline cellulose, Di-Pac II. Major advances in tablet compression machinery, i) Improved positive die feeding ii) Precompression of powder blend Merits i)Direct compression is more efficient and economical process as compared to other processes, because it involves only dry blending and compaction of API and necessary excipients. ii)The most important advantage of direct compression is economical process.Reduced processing time, reduced labor costs, fewer manufacturing steps, and less number of equipments are required, less process validation, reduced consumption of power. iii)Elimination of heat and moisture, thus increasing not only the stability but also the suitability of the process for thermolabile and moisture sensitive API’s. iv)Particle size uniformity. v)Prime particle dissolution.

In case of directly compressed tablets after disintegration, each primary drug particle is liberated. While in the case of tablets prepared by compression of granules, small drug particles with a larger surface area adhere together into larger agglomerates; thus decreasing the surface area available for dissolution. vi)The chances of batch-to-batch variation are negligible, because the unit operations required for manufacturing processes is fewer. vii)Chemical stability problems for API and excipient would be avoided. viii)Provides stability against the effect of aging which affects the dissolution rates.

Merits over wet granulation process

The variables faced in the processing of the granules can lead to significant tableting problems. Properties of granules formed can be affected by viscosity of granulating solution, the rate of addition of granulating solution, type of mixer used and duration of mixing, method and rate of dry and wet blending. The above variables can change the density and the particle size of the resulting granules and may have a major influence on fill weight and compaction qualities. Drying can lead to unblending as soluble API migrates to the surface of the drying granules.

Pharmaceutical Manufacturing

Dispensing Post Hoists Blending Granulation & Drying Tablet Compression Containment Interfaces (Hicoflex速) Tablet Coating Room : P- 23 Specifications : Wash Bay -2 Pressure Difference : 10-30 pas ( between corridor and room ) Instrument and materials : Document Saline IPA for Cleaning Clotech Vim ( detergent ) Detol Jet Glass cleaner Tablet coating

Many tablets today are coated after being pressed. Although sugar-coating was popular in the past, the process has many drawbacks. Modern tablet coatings are polymer and polysaccharide based, with plasticizers and pigments included. Tablet coatings must be stable and strong enough to survive the handling of the tablet, must not make tablets stick together during the coating process, and must follow the fine contours of embossed characters or logos on tablets. Coatings are necessary for tablets that have an unpleasant taste, and a smoother finish makes large tablets easier to swallow. Tablet coatings are also useful to extend the shelf-life of components that are sensitive to moisture or oxidation. Opaque materials like titanium dioxide can protect light-sensitive actives from photodegradation[citation needed]. Special coatings (for example with pearlescent effects) can enhance brand recognition.

If the active ingredient of a tablet is sensitive to acid, or is irritant to the stomach lining, an enteric coating can be used, which is resistant to stomach acid, and dissolves in the less acidic area of the intestines. Enteric coatings are also used for medicines that can be negatively affected by taking a long time to reach the small intestine, where they are absorbed. Coatings are often chosen to control the rate of dissolution of the drug in the gastrointestinal tract.

Some drugs will be absorbed better at different points in the digestive system. If the highest percentage of absorption of a drug takes place in the stomach, a coating that dissolves quickly and easily in acid will be selected. If the rate of absorption is best in the large intestine or colon, then a coating that is acid resistant and dissolves slowly would be used to ensure it reached that point before dispersing. The area of the gastrointestinal tract with the best absorption for any particular drug is usually determined by clinical trials.

Room : P- 22 Specifications : Coating -2 Pressure Difference : 10-30 pas ( between corridor and room ) Instrument and materials : GS Coater: Origin : Italy Id : T-04-013-001 Capacity : 350 kg max.( 450 Lt ) Inlet air flow : 50 pas Pan negative pressure : -1 psig Pan rpm : 13 Operation : Dried Fe. Sulfate TR pellets Types of coating : Sustained release, Enteric coating, Wax coating.

Spray nozzle : 04 Pressure Pump Eudragit L-30, B-55 Room P-21 Specifications : Seiving Room Pressure Difference : 10-30 pas ( between corridor and room ) Instrument and materials : Vibratory sifter-06 Id : T-04-072-006 Mesh : 40/60 ( shamsur rahman ) Operation : pellets powder sieving

Room P-18 Specifications : Oven-01 Pressure Difference : 10-30 pas ( between corridor and room ) Instrument and materials : 22/36 Pelletes Non perile seeds ( NPS ) Ingredients : Sucrose BP, Maize starch, Lactose BP, Povidon, etc.

Steam heated Oven Id : T-04-025-002 Origin : Indo German Temperature Range : 50-100 degree celcius Room P-17 Specifications : Centrifugal Fluidized Coater Pressure Difference : 10-30 pas ( between corridor and room ) Instrument and materials : CF Coater : Id : T-04-013-002 RPM : 100 Capacity : 35 kg Coating time : Product dependent, around 1 hr.

Volt : 400 Encapsulation Process : When selecting the appropriate encapsulation process to meet customer objectives, Southwest Research Institute (SwRI) scientists, with collaborative support from clients, evaluate and balance a variety of performance and formulation criteria.

Microcapsule size is highly dependent on the process. The above graph illustrates general guidelines.

Encapsulation Process Selection Criteria Core/shell material properties Gas/liquid/solid Solubility Viscosity/surface tension Density Reactivity Capsule size Capsule percent payload Capsule morphology Production capacity Release profile/mechanism Stability Encapsulation Process Applications Pharmaceuticals Food and nutraceuticals Consumer and diversified products Cosmetics Agricultural and Industrial Room P-12 Specifications : Encapsulation Pressure Difference : 10-30 pas ( between corridor and room ) Instrument and materials : Automatic Capsule filling Machine : Brand : Sejong Origin : Korea Id : T-04-027-001 Volume : 20 mg ( in operation ) Product : Losectil pellets ( omeprazole ) during operation.

Output : 1000 capsule / min.

Capacity : 800-1000 capsule Rpm : 70 Process : ………………………..

Room P-13 Specifications : Compression Pressure Diference : 10-30 pas ( between corridor and room ) Instrument and materials : Rotary Tablet press Machine : Brand : Sejong Origin : Korea Id : T-04-016-001 Model : MRC- 37D Hopper : 02

Capacity : 5 lac /hr ( 105 rpm ) Outlet : 02 Room P-14 Specifications : Oven -02 Pressure Difference : 10-30 pas ( between corridor and room ) Instrument and materials : Steam heated Oven Id : T-04-025-002 Origin : Indo German Temperature Range : 50-100 degree celcius Room P-11 Specifications : Clean Store Pressure Difference : 10-30 pas ( between corridor and room ) Instrument and materials : Peppermint oil Sieve Container Drum Room P-09 Specifications : IBS ( Intermediate bulk store ) Pressure Difference : 10-30 pas ( between corridor and room ) Instrument and materials : Container NPS : Fe sulfate, diclofenac , ascorbic acid, folic acid Tablet : Tamen, Alben-DS, Solbion Room P-10 Specifications : Wash bay Pressure Difference : 10-30 pas ( between corridor and room ) Instrument and materials : Various types machine washing Room P-08 Specifications : IBS-1 ( Intermediate bulk store ) Pressure Difference : 10-30 pas ( between corridor and room ) Instrument and materials : Container NPS : Fe sulfate, diclofenac , ascorbic acid, folic acid Tablet : Tamen, Alben-DS, Solbion, etc.

Room P-01

Specifications : FBC Pressure Difference : 10-30 pas ( between corridor and room ) Instrument and materials : Fluidized Bed Coater Id : T-04-013-003 Coating : Pelletes ( in operation ) Operation : Coating and Drying concomitantly.

Peristaltic Pump Specificity : For solution coating Id : T-04-061-003 Room P-02 Specifications : Granulation Pressure Difference : 10-30 pas ( between corridor and room ) Instrument and materials : High Speed Mixer Id : T-04-036-001 Fluid Bed Dryer Id : T-04-031-001 Room P-03 Specifications : Coating -1 Pressure Difference : 10-30 pas ( between corridor and room ) Instrument and materials : Nicomac Coating System Brand : Nicomac Id : T-04-013-004 Operation : All types of coating.

Capacity : 450 kg.

Room P-05 Specifications : Blending -01 Pressure Difference : 10-30 pas ( between corridor and room ) Instrument and materials : Room P-06 Specifications : Blending -2 Pressure Difference : 10-30 pas ( between corridor and room ) Instrument and materials : Gansons Multimill ( 1000 L ) Double Cone Blender Nicomac Coating system ( 500 L ) Room : Pellets Section

Extruder-35 Spheronizer – 500 Room : Dispensing Bulk Store Log Book Electronic balance Department : Quality Control Site : Generic Portion Starting Date : 22 June, 2010 Ending Date : 24 June, 2010 Instructor : Kazi Mohammad Rafiqul Islam Sr. Officer , Analytical developmet.

Briefing ; Assurance: The act of giving confidence, the state of being certain or the act of making certain.

Quality assurance: The planned and systematic activities implemented in a quality system so that quality requirements for a product or service will be fulfilled.

Control: An evaluation to indicate needed corrective responses; the act of guiding a process in which variability is attributable to a constant system of chance causes.

Quality control: The observation techniques and activities used to fulfill requirements for quality.

GMP Quality Assurance and Compliance Procedures How to Write Standard Operating Procedure All Documents - Classification, Definition and Approval Matrix GMP Quality Documentation Management and Change Control Documentation Rule for GMP Documents GMP Quality Documentation - Control, Tracking and Distribution Preparation, Maintenance and Change Control of Master Documents Pharmaceutical Deviation Report System Shelf Life of Product Vendor Selection and Evaluation Procedure Vendor Certification Procedure Pharmaceutical Product Complaint Procedure Annual Product Review Manufacturing Rework Procedure Responsibility of Authorized Person Procedure for Product Identification and Traceability GMP Audit Procedures Example of Checklist for Batch Documentation Evaluation of Batch Documentation and Release for Sale GMP Training Procedure How to Write GMP Training Materials House Keeping Audit Procedure Management and Control of Contract Work

Criteria for Sourcing of Raw Materials, Critical Packaging Components and Finished Goods Quality Concern Investigation Process

Imported

Analysis that are done : Raw materials analysis Finished products analysis Stability analysis Equipments : Exclusive Non exclusive From warehouse to QC : Commercial requisition  Materials in warehousePreparing receiving record  Sending it to QC  Sampling completion  Analysis in QC lab  Passed  Bill Paying to Manufacturer.

Analysis of Sample : Physical Parameters Appearance Odor Identification FTIR HPLC UV spectrophotometer Gas Chromatography HPTLC AAS Potency test ( Assay ) Water content determination Dried basis ( LOD ) Anhydrous basis ( KFT ) Impurity test Potency Expression : As dried basis ( depending on LOD ) As anhydrous basis ( depending on KFT ) As it is Simple Calculation : AB/DB = ( As it is *100 ) / (100-LOD/AB ) Stability Study : Stability Chambers, Stability Rooms, and Environmental Chambers by Parameter Generation & Control.

Parameter Generation & Control (PGC) specializes in humidity control chambers and environmental chambers by providing precise relative humidity and temperature control with walk-in rooms, reach-in chambers, and relative humidity generators to serve existing structures. Precise humidity control systems are our specialty.

Our products include: Stability chambers and stability rooms for the pharmaceutical industry that exceed ICH guidelines in regards to temperature and relative humidity control.

Temperature humidity chambers and temperature/relative humidity generating units for minienvironments within the Semiconductor industry.

TAPPI rooms for the paper industry.

Environmental test chambers for temperature and relative humidity calibration utilizing chilled mirror technology.

Environmental chambers and environmental rooms for stress testing of products within various industries.

Relative humidity calibrations chambers to the Metrology industry for relative humidity and temperature sensor calibration.

WHO guideline : 25 degree celcius 60 % Relative Humidity ( Long Term-1 year, UK ) 30 degree celcius 70 % Relative Humidity ( Long Term-1 year, Asia ) 40 degree celcius 75 % Relative Humidity ( Stress Condition-6 months ) ICS ( International Conference of Harmonization ) guideline : Grade – A Grade – B Grade – C Grade – D Observation : Room : Central QC lab Instruments : Dissolution Tester-1 : Id : T-07-029-001 Brand : Logan Instrument Corp.

Origin :UK Criteria : 8 Container 8 Paddle Heater Motor

RPM : Adjusted ( Approx. 50 ) Dissolution Tester -2 : Id : T-07-029-002 Brand : Erweka Origin :Germany Criteria : 8 Container 8 Paddle Heater Motor Product : Feofol pellets ( in operation ) Media : USP buffer.

Volume : 500 ml RPM : 50 Temp. : 37 dc De Ionization Water Plant : Id : T-07-105-001 Brand : Barnstead Origin : USA Criteria : Water Container Filtering chamber Ball Valve : HPLC : Id : T-07-040-005 Brand : Shimadzu Origin : Kyoto, Japan Volt : 220-240 Freq. : 50-60 Hz Total quantity in lab : 05 Criteria : Reservoir Pump Automatic sample injection port Sophisticated column Detector Controller unit Supporting unit : Degasser Column oven Software UV- Specttrometry : Atomic Absorption Spectroscopy

Criteria : Oxiacetylene Flame : 3000 dc Pressure : 7 bar Operational wavelength : 589 nm Simple View of Sampling Procedure : Preparing RR Checking for quarantined Inspection For broken or torned If exposed in environment  No need for sampling  If not exposed in environment  Sampling done.  Materials in Sampling booth  Appropriate Apparatus and hand masking  Excipients sampling  If bellow or equal 3 then all should be sampled If 3-100 then root over n+1 If Greater than 100 then 11 should be sampled  Active ingredients Each bag should be Sampled.

Room : R-3 Instruments : Laminar Air Flow ( LAF ) / Fume hood operator Id : T-07-117-001 Desk of LAF : Base alkali Sauer : Basic Substances Acidos acid Sauer : Acidic Substances Muffle Furnance Id : T-07-058-001 Brand : Nabertherm Temperature Range : 30-3000 dc Atomic Absorption Spectrophotometer ( AAS ) Id : T-07-005-001 Brand : Shimadzu Origin : Japan Automated Melting Point System : Brand : Optimelt Capacity : max. 350 dc Refractometer : Brand : Bellinghum and Stanley TOC Analyzer : Id : T-17-086-001 Brand : Shimadzu Origin : Japan Volt : 220-240 VA : max.1200 Potentiometer : Id : T-07-085-002 Brand : Metrohm Origin : Switzerland

Contains : Titrant Sample Solution Stirrer Titrando ( 0.1 M EDTA, 0.1M KOH etc. ) Karl Fisher Titration : Id : T-07-109-001 Brand : Metrohm Origin : Switzerland Electric balance : Id : T-07-006-003 Brand : Sartorious Capacity : Upto 220 gm Vacuum Pump V-700 Brand : Buchi Origin : Switzerland Volt : 100-240 VAc Freq. : 50-60 Hz Power : 210 w Vacuum Controller V-850 Brand : Buchi Origin : Switzerland Volt : 30 VDc Freq. : 50-60 Hz Power : 10 w Heating bath B-491 Brand : Buchi Origin : Switzerland Volt : 220-240 VAc Freq. : 50-60 Hz Power : 1700 w Distillation Chiller B- 741 Brand : Buchi Origin : Switzerland Temperature range : +10 dc Refrigerant : 280 Volt : 220-240 VAc Freq. : 50-60 Hz Tecator Digester :

Brand : Foss Origin : Switzerland Tecator Scrubber Brand : Foss Origin : Switzerland Freq. : 50-60 Hz Volt : 100-240 Pressure : 50w Foss Water : Brand : Kjeltech-2100 Origin : Switzerland Room : R-02 Instruments and materials : Retention Sample of raw materials Small Chamber : 28 Large Chamber : 28 Very large Chamber : 32 P.P Cap Liflet Pellates Shipper label Bottle label Plastic Container Alu Alu tube Measuring Cup Physicians sample Dropper / Spoons Carton Test Sieve : Mesh Size : 20, 24, 12, 250, 28, 60, 25 100, 325, 300, 200, 35, 325 100 mesh size ………………….150 Micron 20 mesh size …………………..850 Micron 60 mesh size …………………..250 Micron 24 mesh size …………………..710 Micron 12 mesh size …………………..1.40 Micron 250 mesh size …………………63 Micron 28 mesh size …………………..600 Micron 35 mesh size …………………..425 Micron

200 mesh size …………………75 Micron RM Register Book Hardness Tester HDT – 300 Room : Wash Bay Glass wear Eye Washer Water bath ( Above 100 dc ) Glass Wear drying oven Id : T-07-025-003 Measuring cylinder Room : R-01 Instruments : Ultrasonic Bath : Id : T-07-075-002 Origin : Switzerland Inhalar Equipment : Brand : Erweka Origin : Germany Centrifuge 5702 : Id : T-07-043-002 Brand : Eppendorf Origin : Germany Refrigerator Tap- Ds : Tap density tester Brand : Logan Origin : UK LOD Oven : Id : T-07-025-004 Brand : Memmart Origin : Temperature : 105-110 dc Operation time : 14.49 hr Vacuum Oven : Id : T-07-025-005 Brand : Memmart

Origin : Temperature : 60-62 dc Operation time : 15.46 hr Department : QC Room : Packaging Materials Instructor : Sabina Checking of Packaging Materials : Design of Materials Printing of Materials Supplier Receiving Record Sending RR to QC Sampling Analysis in QC lab Observation of Packaging Materials : Paper : Art Card eg- Oradin Finish Board UV laminated glossy. eg- Bonflex UV laminated mat . eg- Amboton Chromolax. Eg- Alben Offset : Generally liflet Art Paper : usually for labeling.

Metal : Wat : Cork + Aluminium + Polythin Alu- Foil : Aluminium + Polythin Cap : Aluminium Tube : Aluminiu Blister : Blister. Eg- Tamen Test of Metal : Wat : 5M NaOH 8 hr Alu – foil : 5M NaOH 8 hr Cap : 12.5 % Cu-sulfate 8hr Tube : 12.5 % Cu-sulfate 8hr Scotch tep test Acetone cotton for thickness test Amber glass : Considerations : Height Diameter Color height

Extra neck diameter Appearance Ampoul : Clean Ampoule : Generally Printed Type-1 Glass for preventing any sort of leaching Test : Heating at 90ºC +Titration with 0.2 N sulfuric acid Amber Ampule : Printed Non printed Test : Heating at 90ºC +Titration with 0.2 N sulfuric acid Plastic : Handerub bottle Test : Normal Water pouring test.

Sampling Booth : Instructor : Tajul , QC Officer, Generic block Period of Sampling :

=

RR 





Log Book  

QC

RR send to warehouse

Department : Quality Control Sub- Department : Microbiology Date :27.06.2010 Instructor : Sanowar, Microbiologist, Generic block Instructs on : Types of water : Portable water

Data Entry

Sampling

Soft water Purified water WFI Sterile WFI Injectable Analysis : Endotoxin test : An endotoxin assay utilizing Limulus lysate (LAL) and a chromogenic peptide substrate is described. The assay of picograms of a compound, present in significant quantities almost everywhere, is obviously associated with a serious risk of contamination. Measures to avoid and detect contamination have been considered. When a quantitative assay like the present one is used, the inhibitory effects of samples analyzed are obvious and also possible to quantify. Methods to avoid such inhibitory effects have been studied and the simplest procedure seems to be dilution with endotoxin-free water, in some cases also combined with heat treatment (75 degrees C for 5 min).

Particulate matter test Sterility test : A sensitive sterility testing procedure for the detection of microbial contamination in petrolatum-based ointments is described. The method involves dissolving the ointment in filter-sterilized isopropyl myristate and filtering through a membrane filter. Improved sensitivity is obtained by blending the membrane in Trypticase Soy Broth before incubation.

Filter-sterilized isopropyl myristate is shown to be less toxic to microorganisms than heatsterilized isopropyl myristate. The isopropyl myristate method is more sensitive than the polyethylene glycol-ether method for the detection of microbial contamination.

Environmental Monitoring : Grade – A Grade – B Grade – C Grade – D Cleaning Validation : Microbial removal Residual removal Limit test : Bacterial count Fungal count LAL Test : The sensitivity of Limulus amebocyte lysate (LAL) to LAL-reactive glucans (LRGs) and lipid A was tested by using commercially available and experimentally formulated LAL reagents.

The glucans included two kinds of beta-(1,3)-D-glucans, laminarin and curdlan, and cellulosic

material, LAL-reactive material (LAL-RM), extracted from a hollow-fiber (Cuprophan) hemodialyzer. LAL-RM loses its LAL activity when it is digested with cellulase and thus appears to be a beta-(1,4)-D-glucan or a mixed glucan containing a substantial proportion of beta-(1,4) linkages. All LAL reagents tested were at least 1,000-fold more sensitive to endotoxin than to LRGs. The presence of the surfactant Zwittergent was shown to interfere with reactivity to LRGs; LAL reagents without added Zwittergent reacted more strongly to LRGs than did the same reagents containing Zwittergent. Chloroform extraction of LAL increased the reagents' sensitivity to both endotoxin and LRGs, but it was not responsible for LRG reactivity. The addition of Zwittergent significantly reduced the sensitivity of LAL reagents to lipid A. LAL without the surfactant was equally sensitive to endotoxin and lipid A. Both curdlan and LAL-RM amplified or enhanced the LAL response to endotoxin. Kinetic turbidimetric studies demonstrated that the enhancement was dependent on the glucan concentration.

Mode of Action of endotoxin : The pathogenetic sequence of reactions mediated by endotoxin (LPS) leading to the production of sepsis involves the oxygen radicals or reactive oxygen species, which has been evaluated in the present review. Among reactive oxygen species hydroxyl radical either singly or in combination with peroxynitrite, produces tissue damage often observed during septic injury. Inactivation of these damaging radicals by antioxidants or nitric oxide inhibitor(s) may be helpful for protecting sepsis mediated derangements but the application of these agents as drugs in humans has not been fully successful. Transcription factor NF- B is reported to be the oxygen sensor in LPS induced endotoxemia. Polyphenols, especially the catechin group of compounds, are important therapeutic agents, which may be used for the treatment of endotoxin mediated sepsis.

Observation of Microbiology Lab : Balance Specific Culture Media Fungal Culture Media Growth promotion test Growth inhibiting test Incubator ( Memmert ) 16-22 dc Conductometer ( Metrohm ) PH meter Lasir Particle measuring system ( Non viable ) Air sampling Machine ( Viable ) Systec V- 95 Autoclave ( Germany ) Bi -septic Cabinet : For endotoxin test Culture Preparation Subculture Preparation Bio assay HVAC system Sterilizing Oven 230 dc for 2 hr Sometimes up to 14 days

Analytical Development Department Starting Date : 29.06.2010 Instructor : Nili, QC, Generic Block Functions of Analytical development : Where the Analytical development : New product   launch Y/N

Decission Making

Approving  3  Source

ADL

ADL 

Analysis / Justifying.



Observation of ADL : UV- 1601 PC : Brand : Shimadzu Origin : Japan Instrument : UV- Visible Spectrophotometer.

Orbital Shaker : Id : T-09-071-001 Purpose : For shaking Hardness Tester : Id : T-09-037-001 Brand : Sotex Origin : Switzerland Frequency : 8700 Hz Volt : 50-60 Dissolution Tester : Id : T-09-023-001 Brand : Logan Origin : UK Purpose : Determination of release pattern Desiccators Electronic Balance Fume hood Disintegration Tester :

Commercial dept.

PD for EB

Improvement of product.

Brand : Erweka Origin : Germany Purpose : For determining disintegration time of tablet Centrifuge : Brand : Eppendorf Origin : Germany.

PH Meter 827 Water bath : 6 holes Power Sonic Ultrasonic bath.

For aiding in solubilization.

Vacuum Pressure Pump.

Production : Liquid Dosage Form Unit : Manufacturing Unit – 01 Observing Date : 30.06.2010 Instructor : Ripon Saha Roy, Deputy Production Manager, MU-01 Borun Kumar Roy, Sr. Production Pharmacist, MU-01 Jahad, Sr. Production Pharmacist, MU-01 Dispensing Booth : RR Check : RR No. Material name Batch No. Manufacturer Supplier Quantity, etc Passed Check : Material name RR No. QC Reference no.

Batch no.

Re-evaluation date Storage Condition Analyst Sampled Check : Initial Date Loose Tag Check ( Sometimes ): Manufacturer name RR no.

QC reference no..

Cleaning Check : Area/ Machine/ Others Types of Cleaning Previous Product Cleaned by Checked by Liquid Compounding -01 Unit : 01 Instruments : Compounding Vessel ( 1000 L ) Holding Vessel (1000 L ) Bin ( 50,100 L ) Homogenezer Log Book BMR ( Bach Manufacturing Record ) Stirrer Bottle Deboxing Room Bottle Automatic Bottle Washing and Filling Machine : Brand : Komatech Origin : Korea Washing : RW, PW, Air Drying RPM : Around 40 Washing holder : 28 Filling Nozle : 04 ( 15 ml released / nozzle ) Capping stick : 24 Checking unit Conveyer : 1 Wheel : 4 Piece Automatic bottle Labeling Machine : RPM : Around 40 Label with gum Labeling wheel : 01 Liquid Compounding -01 Unit : 02 Instruments : Steam Jacketed Mixing Vessel : Capacity : 1000 L Brand : Local Origin : Bangladesh Steam line Pressure : 0-14 kg / scm Types of Operation : Syrup, Oral Solution

Product in-line Point Holding Vessel - 02 : Capacity : 3600 L Brand : Local Origin : Bangladesh Homogeniger – 02 Tolley : Capacity : 1000 kg Filter Press : Brand : Indo Garman Origin : India Capacity : 8*6 Basic Operational View in Liquid Compounding – 1 :

Steam jacketed mixing tank

To filling machine nozzle

Bottle Washing & Filling Liquid Compounding -02

Storage Tank

Filter Press

Holding Vessel in unit -1

Compound ing vessel in unit-1

Labeling

Packaging

Instruments : Steam Jacketed Mixing Tank : Capacity : 3750 L Brand : Water Town Pharmaceutical Equipment Company Origin : China

Pressure : 0-0.6 Mpa Types of Operation : Syrup, Oral Solution Volume Indicator Point Product in-line Point Spray ball Ven filter Storage Tank : Capacity : 3200 L Brand : Local Origin : Bangladesh Pump : ( 4 Pieces ) Automatic Bottle Washing Machine : Brand : Yoo Sung Origin : Korea Rpm : Around 40 Automatic liquid filling Machine : Brand : Strunck Origin : Germany Holder : 24 Holder in Wheel : 06 Rpm : Around 40 Filling Nozle : 3 ( 5 ml / Operation ) Labelling and printing Machine : Brand : Ambica Origin : India RPM : Around 40 Label with gum Labeling wheel : 01

Basic Operational View in Liquid Compounding – 2 :

Steam jacketed mixing tank

Bottle Washing & Filling

Storage Tank

Filter Press

Output from Filling nozle

To filling Nozle by pump

Labeling

Liquid Compounding -03 Instruments : External cleaning Machine : Rpm : 60-180 Cleaning by : Normal Water Bottle specifications : 50-500 ml Automatic Ultrasonic Bottle washing Machine : Origin : China Sun Holding capacity : 1800 Rpm : 40 Washing Stage : Potable water Purified water Compressed Air Holding / class : 16 Filling and Cap sealing : Origin : China sun

Packaging

Nozle : 15 ( 100 ml / nozzle ) Cap filling holder : 10 Cap sealing : 83 Bottle / min Rpm : Around : 85 Bottle labeling and packaging unit : Origin : China Sun Rpm : 60-150 Steam Jacketed Mixing Tank : Capacity : 3750 L Brand : Water Town Pharmaceutical Equipment Company Origin : China Pressure : 0-0.6 Mpa Types of Operation : Syrup, Oral Solution Volume Indicator Point Product in-line Point Spray ball Ven filter Storage Tank : Capacity : 3200 L Brand : Local Origin : Bangladesh Pump : ( 4 Pieces ) Basic Operational View in Liquid Compounding – 3 :

Steam Jaketed mixing tank

External Cleaning

Conveyer

Storage Tank

Filter Press

Ultrasonic washing machine

Filling nozzle

Bottler tray

Filling

Deboxing Packaging

Production : Solid Dosage Form Unit : Manufacturing Unit – 01 Observing Date : 01.07.2010 Instructor : Jahad and A. Karim, Production officer, Generic block Observation : Sachet filling Machine – 01 : Brand : Enflex Origine : Spain Model : F-14 Rollaer Scalling Unit : 85/70 Eye mark sensor Lower sealing – 145 dc Vertical sealing – 155 dc Batch Printer Scizer Vacuum Pump – 04

Filling from Hopper Nitrogen gas incorporating unit Upper sealing – 165 dc Finger for turning Room Temperature : 19-25 dc RH : Up to 40% Rpm : 2400 sachet / hr Sachet filling Machine – 02 : Brand : Enflex Origine : Spain Model : F-14 DX Roller Scalling Unit : Cutting at 140 ( 70/70 ) Eye mark sensor Lower sealing – 145 dc Vertical sealing – 155 dc Batch Printer - 02 Scizer - 02 Vacuum Pump – 04 Filling from Hopper - 02 Nitrogen gas incorporating unit Upper sealing – 175 dc Finger for turning – 16 L + 36U Room Temperature : 19-25 dc RH : Up to 40% Rpm : 2400 sachet / hr Current volt : 370-390 Eleftronic Balance : Neosaline : 9.48-11.02 ( for keeping 10 gm ) Losectil : 5.5- 6.12 ( for keeping 6 gm exactly ) Encapsulation Machine : Brand : Sejong – SF – 100 Origin : Korea Shell in operation : 0,2,1 Station : 12 Holes in each station : 14 Rpm : 65 Operation : Zeefol – CI capsule Operational View :

Hopper ( 10- 15 kg )

Pressure Pin

Passing channel

Capsule station

Defective shell ejector

Dosing & Filling of

ingredients

Capping

Room : Granulation Observation : Planetary Mixer : Brand : Sams Origin : India Capacity : 100 L Rpm : Slow / high speed Fluid bed dryer : Brand : Solace Origin : India Capacity : 30-50 kg Drum Blender : Brand : Local Origin : Bangladesh Capacity : 70 kg Silversion Stirrer : Brand : Silversion Origin : England Rpm : Fixed.

Capsule ejection

Multimill : Brand : Gansong Origin : India Capacity : 100 L Operational Sequence : Planetary Bowl Dry mixing High speed

Multi mill At 2000-3000 rpm at sp. mesh

Solution Spraying

Slow mixing For 5 min

FBD drying At 100 dc then sieving@sp.mesh

Blending and Compression

Room : Sieving Observation : Double cone blender : Capacity : 50 L Origin : India Vibratory Sifter : Mesh : 12, 24, 30 Origin : India Kilburn Oven : Capacity : 30-50 kg Origin : India Temperature : 0-120 dc Room : Compression Clit Tablet Compression Machine- 01 : Brand : Clit Origin : India Station : 12 Type : D Rpm : 15-20 Feed frame Upper trait and Lower trait Antidevice lock Hopper : 02 ( 15-20 ) Quantity : 20000 / hr

Clit Tablet Compression Machine - 02: Brand : Clit Origin : India Station : 27 Type : D Rpm : 15-20 Feed frame Upper trait and Lower trait Antidevice lock Hopper : 02 ( 15-20 ) Quantity : 70000 / hr Tablet polishing Machine : Origin : Indian Blender : Brand : Gratig Double cone blender Origin : Taiwan Rpm : 25 Frequency : 50 Hz Stone : 8 bar- 120 psi Room : Packing Hall Date : 03.07.2010 Instructor : Badol, Asst. Product Manager Observation : Blister Machine – 01 : Brand : Hoong A Origine : Korea Bottom foil – 236 mm Pre heater : 120 dc Forming unit pressure : 6-8 bar Hopper capacity : 20kg Channel : 15 Chut : 15 Sealing unit : 200 dc Feed checks : 12 Sensor Cooling unit : 15 dc Slitter unit : 70-80 d c Rpm : 28 Blister Packing – 02 Brand : Horn Noack Origin : Germany Rpm ; 25-30 Heater Plate : 140 d c

Blister Machine – 03 : Brand : Hoong A 2 Origine : Korea Bottom foil – 236 mm Pre heater : 120 dc Forming unit pressure : 6-8 bar Hopper capacity : 20kg Channel : 15 Chut : 15 Sealing unit : 185 dc Feed checks : 12 Sensor Cooling unit : 15 dc Slitter unit : 70-80 d c Rpm : 28 Packaging cycle in Hoong A : Bottom foil In Bottom foil Station

Guide rell

Drop roller

Forming Unit

Hopper

Chut Vibrator

Channel

Shutter get unit

Feed Check

Top foil guide

Sealing unit

Batch Printing

Cutting unit

Conveyer

Packaging

Room : Packaging Hall Unit : Topical Application Temperature : 19-25dc RH : 55% Instruments : Glen – 160 Planetary Mixer Origin : Verginia, USA Beater Rpm : 13-30 Steam jacketed vessel : Capacity : 150L Working Capacity : 120 L Origin : Local Steam jacketed Vessel : Capacity : 50 L Working Capacity : 40 L Origin : Local Emulsifying Stirrer : Capacity : Fixed Working Capacity : Fixed Origin : Local Type : Silversion Filling And Sealing Room : Semisolid Filling and Sealing Machine : Brand : Kalix Dupy Origine : France Hopper Capacity : 60-70 kg Dosing nozzle : 10gm Dice : 16 piece Rpm : 15-20 Manual Liquid filling machine Department : Quality Assurance Sub-Department : In-Process Control ( IPC ) Unit : Manufacturing Unit – 01 Date : 05.07.2010 Instructor : Khaza Nazimuddin, QA Officer, MU - 01 Rajib, QA Officer, MU- 01 Observation : Viscometer :

Brand : Brokfield Origin : USA Rpm : 50 Running Viscosity : 242 cp pH- Meter : Brand : Metrohm Origin : Switzerland Purpose : Detrmining the pH of the liquid formulation Leak Tester : Brand : Erweka Origin : Germany Vacuum Pressure : 550 Mbar Room Condition: HVAC system Department : Quality Assurance Sub-Department : In-Process Control ( IPC ) Unit : Manufacturing Unit – 02 Date : 07.07.2010 Instructor : Liton, QA Officer, MU- 02 Observation : Electric Balance : Brand : Erweka Origin : Germany KF Titrator : Brand : Metrohm Origin : Switzerland Titer : 5.0045 mg/ml Hardness Tester : Brand : Sotex Origin : Switzerland Friability Tester : Brand : Logan Origin : USA Electric Balance : Brand : Sartorius Origin : Switzerland Disintegration Tester : Brand : Pharmatest Origin : Germany

LOD Oven : Brand : Memmart Origin : USA Temperature : Up to 250 dc Drying Oven : ( Fixed Temperature ) Product Development Department Dated : 08.07.2010 Instructors : Shushmita Laila, Development Maneger.

Nazma Begum, Sr. Development Pharmacist Juwel, Sr. Development Pharmacist Involved Issue : Formulation Development Packing Materials Development Scale Up Existing Product Development Trouble Shouting of Existing product Where The PD : Marketing Proposal

Preformulation Study

Sourcing

Sample from Sources

QC

PD

ADL

EB in PD

ADL Then Again PD

PB in PD

ADL Then Again PD

Commercial Batch Production

Instruments : Dissolution Tester-1 : Id : T-07-029-001 Brand : Logan Instrument Corp.

Origin :UK Criteria : 8 Container 8 Paddle Heater Motor RPM : Adjusted ( Approx. 50 ) Disintegration Tester.

HPLC Hardness Tester Friability Tester Others Instruments : All Instruments in the Manufacturing Unit-01 are used when needed.

Calibration, Maintenance, Validation And Engineering Department Dated : 09.07.2010 Calibration : Instructor : Sara Instruments : Sound Meter Thermo Hygrometer Calibrator Pressure Prob Stop Watch Anemometer Prob Temperature Prob Data Logger Universal Calibrator Tester ( Germany ) Infra- Red Thermometer Distance Meter ( By Laser ) Aerotest Alpha ( Compressed Air Check ) Pressure Checker Air Compressor Check in top floor.

Validation and Documentation : Instructor : Luna Responsibility of Technical Services Department ( TSD ) : Calibration

Validation Training New employee training SOP Basic training In- Plant training Operator training Officer training.

Project Engineering Documents Preserving : Soft entry Hard entry Log Book Validation : The ICH guidelines achieved a great deal in harmonising the definitions of the required validation characteristics and their basic requirements. However, they provide only a basis for a general discussion of the validation parameters, their calculation and interpretation. It is the responsibility of the analyst to identify parameters which are relevant to the performance of the given analytical procedure as well as to design proper validation protocols including acceptance criteria and to perform an appropriate evaluation.

In order to fulfil this resposibility properly, the background of the validation parameters and their consequences must be understood. In this part, the general concept of an integrated validation is discussed. The interdependencies to other ICH guidelines and topics during drug development (e.g. impurities and degradants, stability and specification design) must be taken into account to define the required acceptance criteria.

Evaluation of the results in order to prove the suitability of the analytical procedure must be based on the specification limits. Important parameters and aspects are discussed for the individual validation characteristics. In the following parts, these parameters will be discussed in detail. Examples will be given for their interpretation in order to facilitate the selection of parameters which are relevant to the performance and suitability of the given analytical procedure.

Classification of Validation : Equipment Validation Design Qualification ( DQ ) Factory Acceptance Test ( FAT ) Installation Qualification ( IQ ) Operation Qualification ( OP ) Performance Qualification ( PQ ) Method Validation Test According to Controlled Direction

Three times Check : If Reproducible result, validated.

Process Validation Same Process, Three times If reproducible result, validated Cleaning Validation Range maintaining Cleaning with purified water Involving ADL Involving Microbiology Four Ways of Validation : Retrospective Validation ( After Commercial data, existing data analysis ) Prospective Validation ( Before Commercialization, for new product ) Concurrent Validation ( Market and Validation Concurrently ) Re- Validation ( Again Validity Check ) Engineering Department : Instructor : Jahid, Mechanical Engineer.

Effluent Treatment plant : Types of Treatment : Chemical treatment Biological treatment

Effluent Treatment Pattern:

Waste water

Pipe

Equalization tank

Primary settling tank

Sediment water

Aerated tank

Condensed effluent

Filter

Pump

Clarified tank

Drain

Filter

Sun light heating

Upper part of water

Dried cake of sediment

Discharging

Transferring dried sediment to outer zone

Alum + Lime +DAP + Uria

Water Boiller : 400kg Steam / hr 450- 500 dc Air Compressor : Ambient Air

8 kg Load / cm

Cooling Unit

Compressed Air

Filtering

Water Treatment Plant ( WTP ) Instructor : Abul Khair, Engineering Officer.

Purified Water Plant : Raw Water ( Heated )

Multi grade Filter

Storage Tank ( 3000 L )

C- Grade Filter

Water Softener Unit ( Resin Column )

Cartridge Filter ( 5 Micron )

Cartridge Filter ( 3 Micron )

Soft Water Storage Tank

Reverse Osmosis ( RO ) Membrane

Heat Exchanger

EDI EDI

Purified Purified Water Water

Water For Injection ( WFI ) : Instruments of WTP : System : Steel Mass, Italy Vessel : China Pipe : China Purified Water Vartical 3 Column

Heating Chamber Heating ( 100 dc At ) 100 dc Again

Cooling Chamber WFI ( 25-30 dc ) ( 94 dc )

Water Loop System : Purified Water : PW Main Vessel ( 5000 L ) PW Generic Distribution Vessel ( 2500 L ) PW Cepha Block Distribution Vessel ( 2500 L ) PW always in circulatory moment with 18 - 25 dc temperature.

Water For Injection : WFI Main Vessel ( 5000 L ) WFI Generic Distribution Vessel ( 2500 L ) WFI Cepha Block Distribution Vessel ( 2500 L ) WFI always in circulatory moment with above 85 dc temperature HVAC System : Part of HVAC System : Chiller : 5.15 dc, 4.51 dc.

Heat Exchanger AHU Ducting System Filter HEPA ( H- 13 )……….Efficiency 99.9% Fine filter ( F- 9 ) …….Efficiency 95% Gross filter ( G- 4 )…...Efficiency 65% Common Sequence in AHU Unit : Return Air

Damper Smoke detector

Fire damper Smoke alarm

G-4 Fresh air

Exhaust Air

Cooling Point Heating Coil

F- 9 : 5 mic.m F- 9 : 3 mic.m

To HEPA filter In the terminal Of the room.

Department : Quality Control Site : Cepha Block Date : 10.07.2010 Instructor : Ismail Bablu, QC Manager, Cepha Block.

Tanvir, QC Officer.

Observations : High Performance TLC ( HPTLC ) : Improved resolution of complex brain ganglioside mixtures was achieved by highperformance thin-layer chromatography. The percentage distribution of individual gangliosides was then determined by direct densitometric seanning, employing a transmittance mode, of the resorcinol-positive spots on the plate. As little as 90 pmol (29 ng) of lipid-bound sialic acid could be detected with a good signal-to-noise ratio. A linear detector response was observed up to 3.0 μg of lipid-bound sialic acid. The brain white matter ganglioside patterns of eight animal species, including human, chimpanzee, monkey, chicken, bovine, sheep, and pig, were examined in detail.

In addition, human brain gray matter, rat cerebral, rat brain gray matter, and rat cerebellar ganglioside patterns were also studied. Ganglioside G M4 (G7) was found to be one of the major components in primate and chicken brain white matter, but it represented only a minor ganglioside in other species. Other major gangliosides in all brain samples studied were G M1, GD1a, GD1b, and GT1b. GM1 was more abundant in white matter than in gray matter. GT1a, a recently discovered ganglioside species, was found in all species examined, but was most abundant in the rat cerebellum. The latter source also contained high proportions of G T1b and GQ1b.

Fourier Transform IR ( FTIR ) : Biologically important apatite analogues have been examined by Fourier Transform Infrared Spectroscopy (FT-IR), and a method developed to quantitatively assess their crystalinity.

Changes in the phosphate v1 and v3 regions, 900–1,200 cm-1, for a series of synthetic (containing hydroxide, fluoride, or carbonate ion) and biological apatites with crystal sizes of 100–200 A were analyzed with curve-fitting and second derivative spectroscopy. The v1,v3 contour was composed of three main subbands. Correlations were noted between two spectral parameters and crystal size as determined by x-ray diffraction. The percentage area of a component near 1,060 cm-1 decreased as the length of the c-axis of the hydroxyapatite (HA) compounds increased, while the frequency of a band near 1,020 cm-1 increased with increasing length of the apatite c-axis.

These parameters are thus proposed as indices of crystallinity for biological (poorly crystalline) HA. The FT-IR spectra of highly crystalline apatitic compounds were also analyzed. For crystal sizes of 200–450 A, the percentage area of the phosphate v1 band (near 960 cm-1) decreased with increasing HA crystal size. IR indices of crystallinity have thus been developed for both well crystallized and poorly crystallized HA derivatives. The molecular origins of the various contributions to the v1,v3 contour are discussed, and a

preliminary application of the method to a microscopic biological sample (rat epiphyseal growth plate) is illustrated.

Mainly for Identity Peak against all functional group Brand : Shimadzu Origin : Japan Polarimeter : Brand : Perkineimer Origin : England High Performance Liquid Chromatography ( HPLC ) : Gas Chromatography ( GC ): Brand : Shimadzu Origin : Japan Gas Unit Head Space Column Glass Column 300m Pac Column Detector FID TCD Supporting Unit Column Oven ( 500 dc ) Inj. Port Department : Quality Control Sub-Department : Microbiology Date : 11.07.2010 Instructor : Abdullah, Microbiologist, QC- Cepha Block.

Tests That are Perfomed : Microbial Limit Test Endo toxin Test Area Qualification Test Sterility Test Water Analysis LAL Test Instruments : Bio septic Cabinet : 2 Dynamic Pass Box Autoclave Incubator ( Memmert )

Sterilizing Oven Kinetic LAL Analyzer ( BioTek ) Double Door Autoclave ( Systec ) Liquid Particle Counter ( Pamas, USA ) Shaking Water Bath ( Germany ) Production Unit : Solid Dosage Form Site : Dedicated Cephalosporin Plant Date : 12.07.2010

Sound health is vital to our meaningful and worthwhile existence. In finding sustainable solutions to healthcare challenges, Eskayef is committed to improve the healthcare environment in Bangladesh by providing access to safe, effective and affordable medicines and related healthcare services to the people who need them.

In order to prevent cross-contamination between products as well as to safeguard the workers' health and environmental safety, cephalosporin products must be manufactured in separate and dedicated self-contained areas with separate air handling facilities. True to its vision of offering world-class healthcare products, the new dedicated state-of-the-art cephalosporin plant has contructed under the exclusive technical supervision of one of the leading European pharmaceutical consultants.

This new facility is being designed to conform to international cGMP with particular emphasis

on meeting standards of the UK. Eskayef’s cephalosporin plant Infrastructure Building: » Basement : 10,500 sft (Store and Warehouse) » Ground floor : 11,400 sft (Change Room, Utility unit, Garment Washing Room, Material Receiving Unit, Training, Room, Library, Canteen etc) » First floor : 11,400 sft (Production floor) » Second floor : 11,400 sft (Utility Unit, Quality Control Unit and Microbiological Laboratory Unit) Manufacturing dosage forms » Oral solid: Tablet (Coated & uncoated) Capsule » Oral liquid: Powder for suspension » Parenteral: Vial Ampoule Salient features of manufacturing plant The dedicated cephalosporin plant has designed from Elomatic life science. All kinds of designs specially manufacturing specification, utility and production floor are designed by Elomatic life science, a renowned engineering and technical consultation services in Finland.

Completely isolated from other facilities, independent facility.

HVAC (Heating, Ventilation & Air-Conditioning) system: Most upgraded world-class HVAC system is designed. Terminal HEPA (High Efficency Particulate Air) filters exist in all processessing areas.

The plant is completely auto-controlled by Central Building Management System (BMS) from Siemens.

Purified water, Water For Injection and Purified Steam system of European origin (Italy) are installed for cephalosporin products. Cold loop temperature is maintained <12°c.

The entire production unit floor is composed of Self Leveling EPOXY coating with anitmicrobial component.

Captive power generator is available to guarantee uninterrupted power supply to the plant. Gas power generator- 2.4 MW is available in this plant.

Manufacturing equipments Sourcing of most of the equipments for the facility is made from Europe with provisions for proper validation and to guarantee consistent performance and reliability.

Vial lines including washing, sterilization, filling, labeling etc. complete operations are built up from European source (Italy). These systems also include auto weight control system.

Autoclave and machinaries of dry powder for suspensions are also from European source (Italy).

UPGRADED

WORLD-CLASS

STANDARD

HVAC

SYSTEM

HVAC stands for "heating, ventilation and air-conditioning". The three functions of heating, ventilation and air-conditioning are closely interrelated. All seek to provide thermal comfort, acceptable indoor air quality, reasonable installation, operation and maintenance costs. HVAC systems can provide ventilation, reduce air infiltration and maintain pressure relationships between spaces.

Heating, ventilating and air-conditioning (HVAC) systems can play several roles to reduce the environmental impact of buildings. The primary function of HVAC systems is to provide

healthy and comfortable interior conditions for occupants; well-designed, efficient systems do this with minimal non-renewable energy and air and water pollutant emissions.

Heating: Heating systems may be classified as central or local. Central heating is often used in cold climates to heat private houses and public buildings. Such a system contains a boiler, furnace, or heat pump to heat water, steam, or air, all in a central location such as a furnace room in a home or a mechanical room in a large building. The system also contains piping or ductwork to distribute the heated fluid, and radiators to transfer this heat to the air. The radiators may be mounted on walls or buried in the floor to give under-floor heat.

In boiler fed or radiant heating systems, all but the simplest systems have a pump to circulate the water and ensure an equal supply of heat to all the radiators.

The heated water can also be fed through another heat exchanger inside a storage cylinder to provide hot running water. Ventilation: Ventilation is the process of "changing" or replacing of air in any space to remove moisture, odors, smoke, heat, dust and airborne bacteria.

Ventilation includes both the exchange of air to the outside as well as circulation of air within the building. It is one of the most important factors for maintaining acceptable indoor air quality in buildings.

Air-conditioning: An air conditioning system provides cooling, ventilation and humidity control for all or part of a house or building. The Freon or other refrigerant provides cooling through a process called the refrigeration cycle. The refrigeration cycle consists of four essential elements to create a cooling effect. A compressor provides compression for the system. This compression causes the cooling vapor to heat up. The compressed vapor is then cooled by heat exchange with the outside air, so that the vapor condenses to a fluid, in the condenser. The fluid is then pumped to the inside of the building, where it enters an evaporator. In this evaporator, small spray nozzles spray the cooling fluid into a chamber, where the pressure drops and the fluid evaporates. Since the evaporation absorbs heat form the surroundings, the surroundings cool off, and thus the evaporator absorbs or adds heat to the system. The vapor is then returned to the compressor. A metering device acts as a restriction in the system at the evaporator to ensure that the heat being absorbed by the system is absorbed at the proper rate.

Terminal HEPA (high efficiency particulate air) filters: HEPA filter is a type of highefficiency air filter.

Function: HEPA filters can remove at least 99.97% of airborne particles 0.3 micrometres (Âľm) in diameter. Particles of this size are the most difficult to filter and are thus considered the most penetrating particle size (MPPS). Particles that are larger or smaller are filtered with even higher efficiency.

BUILDING MANAGEMENT SYSTEM (BMS) Building Management System (BMS) is a high technology system installed on buildings that controls and monitors the buildingâ&#x20AC;&#x2122;s mechanical and electrical equipment such us air handling and cooling plant systems, lighting, power systems, fire systems, and security systems building technologies are a leading supplier of products, systems and services for security, safety, comfort, eco-efficiency and economy in buildings.

PURIFIED WATER, WATER FOR INJECTION & PURIFIED STEAM SYSTEM

Purified water, water for injection and purified steam system are constructed by Stilmas, an Italian company specialized in the research, development and construction of the most advanced water treatment, distillation and purification plants, as well as ultra pure steam production systems in accordance with the latest guidelines and regulations set by FDA, cGMP and International Pharmacopoeias.

Water for Injection Water for injection Purified water generation unit Purified steam system Cold loop temperature is maintained below 12°c, which ensures no microbiol growth.

SELF LEVELING EPOXY SURFACING The production floor is made by self leveling EPOXY with anitmicrobial components in the entire process area. Self leveling epoxy (SLE) is a durable, cost-effective moderate duty floor surfacing that will provide a performance level in between a troweled surfacer and a protective coating.

Application: Suited for painting the floor require it is very clean, beautiful, no dust and no bacterium. Also especially suited for the area that requires abrasion resistance, pressure resistance, impact resistance and anticorrosion such as production area, laboratory, office etc.

Key features: Dust proof, wet proof, abrasion resistant and chemicals resistant.

The surface is smooth and beautiful, easy to construct and maintain, with a little elasticity.

Good adhesion, resistant to compress and impact.

Thickness: 3 mm.

CAPTIVE POWER GENERATION UNI Captive power generator is available to guarantee uninterrupted power supply to the plant. Gas power generator- 2.4 MW is available in this plant.

Simple Overview : Blending Machine Been 1000 L Vibratory Sifter ( Bangladesh ) Double Cone Blender : Origin : Bangladesh Capacity : 30 kg

High Speed Tablet Press : Origin : China Rpm : 1 lac / hr Encapsulation Machine : Brand : Sejong Origin : Korea Capsule Polishing Machine : Brand : Sejong Origin : Korea Inspection Machine Auto Tablet Coating Machine : Capacity -80 kg Bottle Washing Machine Filling and sealing Machine Macro Drying Machine ( Italy ) Blister â&#x20AC;&#x201C; 01 Brand : Buchon Origin : Korea For Tablet and Capsule Packaging Blister â&#x20AC;&#x201C; 02 Brand : Buchon Origin : Korea For Vial and Ampule packaging Dilema Autoclave : Brand : Dilema Origin : Italy Washing Machine : Brand : Romaco Origin : Italy Blister Packing Operation : PVC Wheel

Cooling Unit

Guide Wheel

Dropper

Forming Unit ( 108 dc )

Feed Tray Then Guide Rell

Sealing ( 145 dc )

Cutter

Conveyer

Secondary Packaging

Unit : Quality Assurance Sub- Unit : In-Process Control Site : Cepha- Block Date : 12.07.2010 Instructor : Responsibility : Documentation Preserving Each Step checking in manufacturing Line clearance checking Finding out any sort of problem Non- Viable Particles Count Sampling Inspection Analysis of each COFA for each batch Deviation Analysis Out of Specification ( OOS ) Analysis Re working Procedure Batch history Documentation Instruments : Leak Tester : Brand : Erweka Origin : Germany Electric Balance : Brand : Erweka Origin : Germany KF Titrator : Brand : Metrohm Origin : Switzerland Titer : 5.0045 mg/ml Hardness Tester : Brand : Sotex Origin : Switzerland Friability Tester : Brand : Logan Origin : USA Electric Balance : Brand : Sartorius Origin : Switzerland Disintegration Tester : Brand : Pharmatest

Origin : Germany LOD Oven : Brand : Memmart Origin : USA Temperature : Up to 250 dc Drying Oven : ( Fixed Temperature ) Department : Liquid Sterile Block Date : 12.07.2010 Instructor : Muhammad Maruful Hasan, Sr. QA Officer Mahmud Site Specification : Class – D : Washing, Labelling, Blistering Class – C : Compounding Area Class – B : Filling Area Class – A : Under Laminar Air flow / Instrument.

During Operation : Class- A becomes Class- B Class- B becomes Class- C Class- C becomes Class- D Class- D becomes Class- E Common Operation : Mixing

Pipe

Filling

Filter 0.2 micron

Packaging

Instruments : Lasair Perticle Counter : Brand : Climet Origin : USA Balance in Dispensing room Circulating Hot Air Tunnel Laminar Flow Bactericidal Dryer : Brand : SRM

Holding Tank

Origin : China Ultrasonic bottle washing Machine : Origin : China.

Common Cycle of Washing and drying :

Tunnel

Conveyer Motor

Holder

Rinsing Outer Surface

Bottle Inverssion

Compressed Air

Purified Water

Compressed Air

WFI

Compressed Air

Wheel

Preheating Unit Heating Unit ( 290 dc )

Depyrogenatio n

Cooling Unit

Tray Conveyer

Rpm change during filling : 1 ml : 280 rpm 2 ml : 270 rpm 3 ml : 250 rpm 5 ml : 240 rpm 10 ml : 180 rpm Rpm Change during washing : 10 ml : 10.5 rpm 5 ml : 5.3 rpm 2ml : 2.15 rpm 1 ml : 1.1 rpm Common cycle from dispensing to filling : Filling Operation:

Dispensing

Mixing

Compounding

Holding

Pump

Intermediate vassel Pump

Bottle

Conveyer

Tunnel

N2-gas filling 2

Product Filling

Heating

Gripping

Scaling

Ejection

Marketin g

WH

Slide Calipers Buchon Blister Packing Machine ( 18 rpm ) Ampule Labelling Machine ( China ) Tests : SIP ( Sterilization in- Process ) :

Pure Steam

Autoclaving At 121 dc for 20 minutes

FP-Test to QC

Filtration Integrity test :

Filter is Submarged in WFI

Pressure Driving

Filter is Effective

Passed Integrity test

Department : Documentation Date : 12.07.2010 Instructor : Md. Nezab Uddin Deputy Quality Compliance Manager Definition of Documentation ;

If Bubble Is formed over 3200 psi

From Birth to Marketing of A Product :

Supplier

Commercial Store

QC Sample

Approved

Manufacturing Plane

Dispensing

Compounding

Final Product To QC

Filling

Ware house

Documentation Pattern in Eskayef : Site Master file : Site for Cepha Block Site for Generic Block Site for MU-1 and MU-2 Validation Master Plan : Validation Policy ( for product and process ) Validated Products SOP : Procedure Set up Maintaining Procedure Validation Protocol : Written Way of validation Approving and Execution Specifications : Limit of Test

Packing

Distribution & Patient

Confirming The Parameters FP Specifications Batch Document : BMR BPR COFA Cleaned tag To be cleaned tag Line Clearance Check list Packing materials specifications QMS ( Quality Management System ) document : Participation of all person Deviation management Corrective and Preventive action ( CAPA ) Out of specification ( OOS ) Rejection Audit and Reporting OOs Reporting & Investigation Form : Date Sign of Dept. Head No. of OOS Investigation Investigation

Analysis

Recommendati on of Head

Head QA

Accept y/n

Preventive Measure

CAPA

Correlation

Date Selection & Follow up

Head of QA & Closing

Deviation Reporting & Investigation form : Date Sign of Dept. Head No. of Deviation Investigation Investigation

Analysis

Recommendati on of Head

Head QA

Accept y/n

Preventive Measure

CAPA

Correlation

Date Selection & Follow up

Head of QA & Closing

Eng. Dept.

Risk Analysis

Operation y/n

Impacted Thing

Drawing Impaction

Review

Recommendati on

Correlation

Date selection & Follow up

Closing

Change Head ofControl : Analysis of Change in Controlled way QA Retention Change Request form Sample

Analysis of Current Sample

Batch Document Observing

Market Compliance Handling : Rejection : Same Procedure is maintained Auditing : Internal Reporting : Vendor Auditing Record ( VAR ) Assessment External auditing : Should be Completed within 6 months Meeting in each month Follow Up Others Documentation : Validation Report Control Direction Analytical Note Book Log Book Calibration Record Maintenance Record Environmental Monitoring Record Viable : Settle Plate, Finger print, Active air sampling, Soft sample Non Viable : Particles count of 0.5 & 5 micron size.

CAPA