IN-PLANT TRAINING
Introduction Square symbolizes a name-a state of mind. From the inception in 1958, it has today burgeoned into one of the top line conglomerates in Bangladesh. Square pharmaceuticals Limited, the flagship company, is holding the strong leadership position in the pharmaceutical industry of Bangladesh since 1985 and is now on its way to becoming a high performance global player. Square pharmaceuticals Limited is an organization with equal emphasis on Leadership, Technology, Quality & Passion. Square pharmaceuticals Ltd. is the leading generic pharmaceutical manufacturer in Bangladesh producing quality essential and other ethical drugs & medicines. Square pharmaceuticals has three GMP compliant formulation plants. The Dhaka unit plant started its operation at the end of 2002 with a view to meet challenges of globalization & to expand export horizon. Dhaka unit plant is situated at Kaliakoir, 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. All facilities like HVAC (Heating Ventilating And Air Conditioning), Purified water system, Environment, Equipment and staff training are validated in accordance with Code of federal regulation 21. It enjoys its brilliant reputation due to high quality standards maintained at all sectors. According to the training schedule we have visited all the departments of square pharmaceuticals Dhaka unit. 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. Square Pharmaceuticals Limited has extended her range of services towards the highway of global market. She pioneered exports of medicines from Bangladesh in 1981 and has been exporting antibiotics and other pharmaceutical products. This extension in business and services has manifested the credibility of square pharmaceuticals limited. As a result of completing in-plant training in a well organized & well reputed company such as Square pharmaceuticals Ltd (SPL), our theoretical concept has become developed on the basis of practical view. This plant is UK MHRA approved.
Layout The plant is designed as linear order. RM-GPB-FG
Res. Building
Parking Area
RMW Future Biotech Unit
Lab Building
GPB
FGW Laundry Eng. Office SVP &O
CSB
Amenity Building ETP Eng. Warehouse
Cephalosporin Building
Fig. Layout of Square Pharmaceuticals Ltd. Dhaka unit. SPLU2)
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Factory Administration Job: -Maintaining of leave information. -Necessary support & Development. -Employee • Office administration • Training for employee • Uniform • ID • Residence (During Emergency) • Transport • Security • Canteen • Laundry • Compensation sheet • Maintaining personal file & Information • Landscaping -Official function: • Liaison with Corporate head quarter. • Guest entertainment • Factory visit for outsiders. PPIC (Product Planning and inventory Control) PPIC (Production Planning & Inventory Control) is one of the most important departments in SPLU2. This department is brought into the SPL at 1986 before which there was no separate dept. for combining the production, commercial and the sales dept. PPIC has been established a synchronized function between these three depts. to achieve the commercial target in a smoother way. The main features of PPIC can be summarized as follow:
• • • • •
It is a communication based job. Prepare annual production plan on the basis of the production facilities and sales target. Prepare monthly production plan on the basis of the production facilities, sales target and stock in the Factory, DPG and Depot. Maintain a production schedule on the basis of the production facilities and raw materials supply. Targets subsequent two months product stock.
Communication chart of PPIC.
Production Dept. Sales Dept.
PPIC
QA
Ware-House
Ware house
DPG Depot
Ware-house is the appointed place where the raw materials are stored after arriving and the finished goods are stored after production. So generally two ware-houses: ♦ Raw material ware-house and ♦ Finished goods ware-house. There is also a ware house under the engineering dept. named Engineering Ware-house. Cephalosporin unit & SVP&O unit have individually different ware houses. Ware House
FG
RM
Considerations of Receiving Raw materials: 1. Checking of the vehicle & ensuring that it has not carried any goods or persons in cargo other than pharmaceutical goods only. 2. Documents should be checked as whether it is local or abroad. If it is local than it includes VAT challan or if , abroad than in voice or custom bill of entry. 3. Check that Invoice, Label & Certificate of Analysis have been given with the respective materials. 4. Label is attached as cascade order. 5. Check the following seven information during label check entry • Name of the materials • Batch • Mfg date • Exp date • Quantity • Manufacturer name • Country of origin. Facilities of the Ware House: 1. During unloading Air curtain is used to prevent insect entrance. 2. For more safety Photo insecticide is used. 3. The vehicle & ware House height is equal to facilitate unloading. 4. Marshall Area has two gates which is air lock so if the first gate is opened than the others will not be open. 5. For low temperature storage raw materials cool ware House is available 6. By the HVAC system the ware house temperature is maintained at below 25◦C and humidity at 65% RH 7. To carry the container fork leaf is available
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Procedure: Incoming raw material vehicle checking Unloading Document recieving Separation according to Batch wise or Product wise Keep it in the marshaling area Label Check entry & registration Checking the integrity of the container Cleaning of the container with the IPA(Isopropyl Alcohol) 70% Wight Checking (gross wt. is taken) Preparation of Quarantine label Prepare GRN (Goods Received Note) Keeps the RM into Quarantine area attaching Quarantined Label (Orange Color) Sampling by QC Passed area if materials are passed by QC& Passed label (Green Color) is attached When requisition is obtained from Dispensing Area, the RM is dispensed Here FIFO is followed. The materials kept in the warehouse are identified by the “alpha-numerical system�. Important terms in ware-house: #First in first out (FIFO): The raw material which comes first in the quarantine area will go for production first and thus a finished product which comes first will also go for marketing first. FIFO is only applicable to the passed materials. #Quarantine area:
The quarantine area is the area where the status of raw materials or packaging materials , intermediates or bulk products isolated physically or by other effective means while a decision is awaited on their release, rejection or reprocessing for QC department before going to store room. #GRN: GRN means the Goods Received Note. The ware house manager issues a note after receiving the goods in ware house. Labels used: Generally four types of labels are used in ware-house. 1. Quarantined 2. Sampled 3. Under test 4. passed These labels are labeled in a “cascading manner�. Documents used (for finished goods): The following documents are used in case of finished goods. 1. Delivery challan 2. VAT challan Gate pass
Production Unit At present Square Pharmaceuticals Limited Dhaka unit (SPLU2) basically a solid dosage manufacturing plant (eg, Tablet, Capsule). Lay out of the general production (GP) area: Raw material ware house Dispensing Dispensed material store Sieving (If applicable) Granulation Blending
Compression
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Encapsulation
Coating (Where necessary) Primary packaging (Blistering/Stripping) Secondary packaging Finished goods ware-house
DISPENSING AREA
Dispensing processes are generally maintained in this area. This area is just by the side of the warehouse (raw material), so that the approved raw materials can easily be carried in the dispensing area. This area is separated from the warehouse by the double door air lock system. This area is maintained with the negative air pressure. The air pressure of the room is lower than the corridor, in order to prevent the microbial contamination and the cross contamination among the ingredients. There are four similar dispensing booths in this area. These booths have been provided by Extract Technology from U.K. In dispensing area Down flow air system is applied to prevent cross contamination or entering the dust to the dispensing people. Each booth has a protective air filtration system which is guided by the following filters: Supply air flow Pre filter Fine dust filter Mid stage HEPA filter (0.2 micron) There are specific four gauges for the specific filtration unit. Each meter possesses two distinct zones:
•
Orange zone &
•
Green zone
Before operation it should be ensured that the gauges are all in the green zone. There is a downward air flow in the booth which passes right angle through the filtration system. All the operation should be carried out inside the “Red zone” of the booths. During dispensing production executive & Quality compliance executive should be present as it is initial stage for production & error chance may be aroused. They sign against operator signature called cross check. Change over: Back to Back cleaning if the product is same of another batch Complete cleaning is done if product is changed. Cleaning procedure is done by vacuum cleaner& 70% IPA. In dispensing area Class D environment is maintained There are another two rooms adjacent to the dispensing room.
•
Secured stock (To stock the excess of active
•
Excess stock (To stock several common excipients)
ingredient) The common 12 excipients stocked in the “Excess stock” are • Mg-stearate • Avicel Ph 101 • Na-starch glycolate (primogel) • Lactose • Colloidal SiO2 • Povidone • Purified talc • Dibasic Ca-phosphate • Maize starch 1500 • Maize starch • Polyethylene glycol • HPMC (Hydroxy propyl methyl cellulose) A “Bin Card” recordes total amount of excipients consumed. Required amount of raw materials are ordered from the ware house by a form named “raw material requisition form”. The exact amount of raw materials are measured, sealed, labeled and supplied for the next steps. Tools used in the dispensing area: Name Avery balance Sartorious balance Temperature and detector
Model L115 BL6 humidity 5566
Capacity 150kg-200gm 6kg-100gm
Some important SOPs in dispensing area:
1. 2. 3. 4. 5. 6. 7.
Operations and cleaning of room vacuum cleaners. Operations of balances. Production equipment log book. Batch reconciliation of raw materials retained in stock store in dispensing area. Receiving of dispensed raw materials. Cleaning of dispensing area. Dispensing of raw materials.
SIEVING: The technique of shaking a sample through a mesh with holes of a uniform size is termed as the sieving. It is a widely used method for measuring particle size distribution. The equipment used in sieving is- RUSSEL SIEVE (London). SLUGGING:
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This process is used in tablet manufacturing in which the powder mixture is compacted in specially designed equipment, followed by milling and screening prior to final compression into a tablet. The compacted masses are called slugs and the process is called the slugging. The equipment used in slugging is- Fitz Mill (USA) Fitz Mill Fitz mill is the combination of two partsChilsonator Comminutor Purpose Chilsonator Reprocess after compression ie, tablet crushing Comminutor
If granules are not appropriate (too fine) for the compression, then granules are comminute/biscuit form to go through the process.
GRANULATION Granulation is the process in which powder particles are adhere to form larger particles called granules. This process is very much applicable to the materials that cannot go through the direct compression. Causes of granulation:
♦ ♦ ♦ ♦
To prevent segregation of the constituents in the powder mix. To improve the compression characteristics of the mixture. To improve the flow property of the mixture. Essential to the powders materials that cant be compressed directly.
Instruments used in granulation: Instrument CMG Vacuum Unit Wet Miller Dry Miller FBD Vacuum Unloading IBC Moisture Analyzer
Name Eurovent-600 Eurovent-600 Eurovent-600 Quadrocomill-1945 Eurovent-600 Eurovent-600 Matcon Sartorius
Capacity 600 Liter. 600 Liter. 600 Liter. 600 Liter. 300-1500kg 4gm-0.1gm
•
There is another granulation suite with same instruments having capacity with 300 liter of Eurovent. All the materials dispensed in the dispensed area are brought in to this area for granulation according to the production demand. The total process of granulation is carried out through the following process:
Pressure Vessel(solvent)
Vacuum Unit
Vacuum Unloading
FBD CMG Wet Mill
Dry Mill
Discharge in IBC
Loading Vessel Fig: Schematic Diagram of the process of granulation CMG (calmic mixer granulator) contains a agitator and a chopper or side cutter. Agitator causes the mixing of the materials and the chopper mills the granules initially in the CMG. Two types of chopper is used: ♦ Cutter type ♦ Hammer type But the hammer type chopper is used in SPLU2. The FBD (fluidized bed drier) is generally contains these parts: ♦ Filter back housing ♦ Expansion chamber ♦ Container ♦ Diffuser Critical parameters in granulation: ♦ Loading ( materials adding sequence must be followed, if needed vacuum loader should be used) ♦ Dry mixing -Mixing time -Agitator speed -Mixer capacity ♦ Wet granulation -Agitator speed -Chopper speed -Solution addition pressure -Mixing time ♦ Wet milling -Screen size -Wet granule feed rate -Mill speed -Milling duration ♦ Drying -Inlet air temperature -Bag shaking frequency -Drying duration -Air flow rate -Final exhaust air temperature -Loss on drying (LOD) ♦ Dry milling -Screen size
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-Dry granule feed rate -Mill speed -Milling duration IPC During Granulation:
•
Mixing uniformity
•
Moisture Content (2 – 3 % is acceptable)Determination of Moisture content in IPC Check:
The moisture in the granules is an important parameter in granulation. So the moisture is checked in the IPC at a time interval to get the required moisture. There is a moisture analyzer (Sartorius) to determine the moisture content. The moisture is determined by the following formula:
(Empty beaker wt.+ Sample wt.)-Final wt. Sample wt. X100
The specialty of the granulation process in SPLU2 is that the total granulation process is occurred in a closed system machine and there is no chance of hand contact to the granules. This is the most modern process of granulation in the pharma-world.
Blending After granulation the IBC is then brought to the blending area which is just beside the granulation room. The IBC then fitted with the blender (Matcon) and rotate the blender at a specific RPM for required time to get a uniform granulation. Blending is necessary to mix-up granules & powders with lubricant for easy compression & to render the tablet surface polished. Some parameters: RPM and Time.
Compression Unit Compression is a process in which we can get the original size of a tablet containing drug or drugs with excipients on stamping machines called presses. There are two types of compression: ♦ Direct compression ♦ Compression after granulation There are some tablets that are compressed directly after dispensing. Eg. Neotack (Ranitidine HCl). This is an easy and less time consuming process. On the other hand, there are some tablets that cannot be gone through the direct compression due to their hardness problem. These are first passed through the wet granulation and then the compression is done. Eg. Alatrol (Cetirizine HCl). In Square pharmaceuticals Limited (SPL) we saw three types of compression machines: Name BWI Manasty unipress diamond BWI Manasty Rotapress diamond Korsch pharmapress 3300 Korsch XL 800
Manufacturer UK
Station 27
Capacity 3300tpm
UK
55
900tpm
Germany Germany
36 71
3000tpm 703280rpm
Korsch is one of the latest model machines in the world. It has some extra advantages over others:-
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• • • •
Pre and main compression force in a single cam. Sealing off upper and lower punch. Less noise generation. Two sites for tablet passing
Additional Machines used in Compression: • Metal detector • De duster.
In to the Hopper Granules discharge Dose adjustment Controlling pre and main compression presser Feeder rotator Granules within dies Compressed tablets by upper & lower punch Tablet into the Deduster & metal detector Tablet collection Flow diagram of compression:-
Parameters for controlling compression:
• • • •
Weight adjustment within the specific range Adjust pre & main compression force Rotation per minute(RPM) Tablets per minute (TPM)
All the required parameters are programmed in the CFC (Compaction Force Controller) for each product and the total compression process is run through an automatic way maintained by the PLC (Programmable Logic Control) system. In process check during compression • Desired hardness & thickness • Diameter • Friability • Weight variation • Gross weight • Disintegration time (DT)
ENCAPSULATION UNIT Capsules are the solid dosage forms in which the medicaments are enclosed within a small shell of gelatin.
Capsules having advantage of elegance, ease of use & portability, have become a popular dosage from because of the fact that they provide smooth, slippery, easy to swallow and tasteless shell for drugs, which is especially advantageous for drugs having unpleasant taste and odor. Depending on the nature of the gelatin shell there are two types of capsules: ♦ Soft gelatin capsules & ♦ Hard gelatin capsules. The SPLU2 produces hard gelatin capsules only. For filling of hard gelatin empty capsule shell pellets, granules and powders are used by the following steps:o Developing and preparing the formulation o Selecting the size of capsule. o Filling the capsule shells. o Capsule sealing. o Cleaning and polishing the filled capsules. There are two machines for capsule filling. Name: BOSH GKF 2000 Capsule filler. Country of Origin: Germany Capacity: 120 rpm, 2160 cpm. (1.20 lac capsule) Auxiliary part: Empty capsule shell container. P & AM capsule polisher. Another:
• • •
Name: MG 2 & G140 Origin: Italy Capacity: 1.45 lac capsule per hour.
Process flow diagram for automated capsule filling:-
Empty capsule shell Powder blend or pellets. Shells in Magazine
Held by Segment
Separation of cap and body Filling Enclosing of cap and body Ejection In encapsulation unit the humidity is strongly controlled which must be less than 40%. The control procedures must ensure that the finished, filled capsules must meet the appropriate current regulatory test:♦ Weight variation. ♦ Content uniformity. ♦ Solubility. ♦ Disintegration.
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Generally the major part of the capsule shell is imported from CAPSUGEL (Thailand). Some shells are also imported from India.
COATING Tablet coating is the application of a coating material to the exterior of a tablet with the intention of conferring benefits and properties to the dosage form over the uncoated variety. The application of tablet coating is usually based on one or more of the following objectives: To provide chemical and physical stability. To mask the bitter and unpleasant taste, odor and color. To control the release of the drug from the tablet. To protect the drug from gastric environment of the environment. To improve the pharmaceutical elegance and rapid identification of product by manufacturer, the dispensing pharmacist and the patient. CLASSIFICATION OF COATING Coating
Film
Sugar
Enteric
Film coating is the Aqueous more modern Organic and generally used technology in the tablet coating. Nearly all newly launched coated products are film coated rather than the sugar coating. The Dhaka unit of SPL only performs the film coating. Nine of the 22 tablets are film coated here. Equipments used in tablet coating: Seria l no. 1 2 3 4
Machine
Enteric film Capacity coating
Ganscoater 1500 Ganscoater 3500 Gansons 50L preparation vessel Gansons 100L preparation vessel
150 kg 350 kg 50L 50L
Products that are coated in the Dhaka Unit Serial no. 1 2 3 4 5 6 7
Product Name
Generic Name
Angilock Alatrol Ciprocin Eromycin Clofenac Famotack Neotack
Losartan Cetirizine Ciprofloxacin HCl Erythromycin Diclofenac Famotidine Ranitidine
Enteric sugar coating
8 9
Motigut Zimax
Domperidon Azithromycin
Coating materials used in film coating: 1. HPMC 2. PEG (Polyethylene Glycol) 3. PG (Propylene glycol) 4. Eudragil 5. Tween-80 6. TiO2 7. Methanol 8. Methylene Chloride 9. Opa-dry (Ready-made coating material) 10. Purified water etc. Critical parameters in coating
1. 2. 3. 4. 5. 6. 7. 8. 9.
Inlet air temperature Exhaust air temperature Pan speed Atomizing pressure Spray rate Gun to bed distance program parameter Height of core sample after pre jag drying cycle Peristaltic pump speed.
Steps of coating Suspension making (for about 45-60 minutes) Compressed tablets (core) in feeding pan Pre-jag (Warm up for about 30 minutes at 40o c temperature Drying + spraying Drying Cooling Unloading of coated tablet
IPC check during coating:
1. 2. 3. 4. 5. 16
Weight of tablet Inlet air temperature check Exhaust air temperature check Pan speed Pump speed
} Post jag
6. Spray gun atomizing air pressure check Problems of film coating:
1. Tablet to tablet color variation/mottling Causes: ♦ Too little coating applied ♦ Inadequate mixing of tablet during coating ♦ Poor opacity of coating ♦ Inadequate number of spray gun ♦ Poor spray pattern bed distribution ♦ Slow pan speed 2. Cracking Causes: ♦ Low mechanical strength of coating ♦ Inadequate plasticization 3. Orange peel roughness Causes: ♦ Too high viscosity of coating liquid ♦ Poor atomization of coating liquid
4. Peeling Causes: ♦ poor adhesion between core and coating material 5. Edge chipping/ erosion 6. Logo bridging 7. Twinning 8. Logo infilling 9. Core erosion 10. Picking/ sticking * The relative humidity (RH) of the coating area should not be more than 50%.
Packaging Packaging is the process that protect product from environment, help to transportation, storage &handling the product. In the pharmaceutical industry the packaging material is selected adequately to preserve the integrity of the product. The selection of a package therefore begins with a determination of the product’s physical and chemical characteristics, its protective needs, and its marketing requirement that is it enhance appearance &elegancy of the product. The packaging of SQUARE includes only the solid dosage form. There are two packaging areas--------a) Primary packaging area b) Secondary packaging area a) Primary packaging area In the primary packaging area, 5 machines are involved for packing. Among them, 3 for blister pack &2 for strip pack.
Types of packaging: Packaging of Solid dosage form is of two types1) Strip Packaging 2) Blister Packaging 1) Strip packaging: Striping materials is: a) ALU-ALU type b) PVC-ALU-PVC type 2) Blister Packaging: Blistering materials are of three typesa) ALU-ALU type b) ALU-PVC type c) ALU-PVDC type A thin PVC coating is present on the aluminum foils that help to seal the aluminum foil to PVC foil. The whole forming on PVC foil is accomplished by firstly by heating that softens the foil & secondly by pressure which enhance to forming hole. SOLID PACKAGING SECTION LIST OF EQUIPMENT: Work center Tablet/Capsule
Room No Blister
Equipment supplier Horn + Germany
Blister Packaging
Packer-1
NOACK
Model 920
with
HAPA printer NOACK blister packaging machine Blister
Horn +
Packer-2
NOACK blister
Germany
920
packaging Blister
machine Hong-A
Packer-3
blister
Korea
packaging Strip Packaging
Strip
machine Gansons Strip India
Packer-1
Packaging
Strip
machine-1 Gansons Strip India
Packer-2
Packaging
G8V D G8V D
machine-2 Defoiling
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India
India
Capacity
Parts of Blister and Strip Machines: • Hopper. • Feeding channel. • Feeding roller. • Feeding disk. Lidding foil Deviation roller
Perforation station
Deviation Feeding roller device
Guide rail
Left draw Forming off rollerstation
Forming film
Heating station
Splicing table
Filling inspection
Right draw off roller
Coding station
Indexing roller Blister take off
Die cutting device
Sealing station
Unwind
Fig: Flow diagram of blistering machine. Parameters for Blister/Strip Packs: 1) Product name 2) Cutting 3) Perforation 4) Embossing of batch no. & expire Date is legible &correct printing 5) Empty/torn/Dented pocket 6) No broken, chipped, spotted Tablet/Capsule 7) Proper sealing by leak test 8) No. of Tab/Cap in a Strip/Blister 9) No. of sample checked In-Process check of primary packaging: For strip pack checkingLeak test Coding Appearance Stoppages/Adjustments
Compression roller
For blister pack checkingLeak test Coding Appearance Stoppages/Adjustments Camera challenge test Coding of primary Packaging: Strip pack
Blister pack
3 lines coding ●Batch No. ●Mfg Date ●Exp Date 1 line coding with two parameters together, Batch no& Exp Date (Because of sophisticated PVC)
b) Secondary packaging area There are sixes Belts-
Belt Belt Belt Belt Belt Belt
1 2 3 4 5 6
There are two line packaging systems: 1) On line packaging system 2) Off line packaging system Steps of Secondary Packaging: Completed Primary packaging Visual Inspection into the conveyer Include insertion Gathered same packs Put in inner carton with inspection slip Coding of inner carton Transferred to shipper carton Shipper carton label check Weight of shipper carton Go to the Good own
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When one batch is completed, it goes to the ware-house Parameters for inner carton: 1) Product name with strength 2) Printing on proper slap 3) Batch No. / Mfg Date /Exp Date /MRP 4) DAR No. / Mfg License No. /Pack size 5) Presence of leaflet 6) No. pf Strips/Blisters Parameters for Shipper’s carton: 1) Label 2) Batch No. / Mfg Date/Exp Date 3) No. of Carton In-Process check of secondary packaging: IPC of secondary packaging is manually1) Strip & blister pocket check 2) Coding check 3) Label check 4) Inspection slip check Coding of secondary Packaging: 1) For carton coding 4 lines coding in inner carton ●Batch No. ●Mfg Date ●Exp Date ●MRP 2) For shipper’s carton label coding 4 lines coding ●Batch No ●Quantity ●Mfg Date ●Exp Date 3) For physician Batch
The inner carton is called catch cover. 3 lines coding in catch cover ●Batch No ●Mfg Date ●Exp Date
Types of printer: In SQUARE, there are two types of printer for coding1) Image printer 2) Video zet printer-MRP is added by lab top Sheet /Record/list for secondary packaging: 1. SAF (Sampling Advice Form) 2. BPR (Batch packaging Record) 3. Secondary Packing In-Process Control Record 4. In-Process check list (QA) 5. Carton/leaflet/label/inspection slip approval 6. Bill of Materials 7. Line clearance certificate
Cephalosporin: Cephalosporin is one of the most significant & prescribed beta-lactam antibiotic This world class facility is housed in a 95,000 sq. feet of covered area and will manufacture Cephalosporin antibiotics in tablets, Capsules, Dry Syrup and Injectable preparations. The annual capacity per shift of the plant is 64 million tablets, 47 million capsules, 3.32 million bottle of dry syrups and 10.58 million of injectables. The facility was built by Telstar S.A. of Spain, a world renowned pharmaceutical manufacturing facility, on a turn key basis.
The facility will add new era in Pharmaceutical export from Bangladesh. Patients in the country will also now get developed country standard Cephalosporins from the facility Powder for suspension Bottle decartoning
Bottle washing
Dispensing Filling
Sieving
Bottle drying
Sugar crushing
Carton printing Dry mixing
Cap sealing Injection
Vial decartoning Packaging
Vial washing & sterilization
Vial labeling
Vial inspection
Packaging Environment monitoring: E.M is depends on the -Temperature -Humidity Generally: Humidity Temperature
22±2 °C 45±5 %
Several conditions for several portion is given bellow ---
•
22
For vial: Humidity: Bellow 40% Temperature: Bellow 25°C
Vial filling Label printing
Vial sealing
•
For dry syrup: Humidity: Bellow 45% Temperature: Bellow 25°C
•
For tablet/ capsule: Humidity: Bellow 50% Temperature: Bellow 25°C
Equipments Used In Cephalosporin Plant:
• • • •
Dispensing ( Telstar spain) Granulation ( yen chen Taiwan) Sieving ( Yen Chen Taiwan) Compression ( Sejong Korea 15 punch) Entrance and exist from the production area: • Air shower machined provided by telstar. Wash Room for equipment cleaning: • Yen chan Taiwan ( Washing machine) Auto Calve Machine: 121 deg c 25 minutes. Machine Used in Micro dosing (Injecition): • Macofar (Italy) Machine Used in Macro dosing (Powder for suspension): • Macofar ( Italy)
• • •
Production area is maintained in class C Operation Area is Class B Filling Area is class A
SVP & O SVP & O unit stands for small volume parenteral and opthalmics. Here world recognized BFS (blow fill and seal) technology is applied where highly sophisticated ASEP- TECH machine origin from USA is used. This machine can produce 4,500 – 5,500 containers per hour.
• • • •
Dosage From: Ampule ( Twist off) Eye drops ( Spike) Nasal drops Prefill injection Equipments Used: • Resin blender (USA) • Reactor ( celestar from Spain) • ASEP- TECH (USA) • DE-Flasher • Blister packing machine (Noack)
Resin: ( 3 types) • High density Polyethylene (HDP) • Low density Polyethylene (LDP) • Medium density Polyethylene (MDP) Among them LDP is widely used. Environment maintenance: Dispensing (air curtain, two filters Pre and hepa are used, outside is D class and inside is B Class) Filling zone is class A Reactor: (Solution Preparation Vessels) o Machine Name : Celestar spain o Capacity: max 500 litre o Tank type: Jacketed double layer Here inner and outer wall is cooled by chilled water, for cleaning automatic sterilization system is used, for transferring the solution compressed air pressure is used, if it is oxygen sensitive than Nitrogen gas is used. Cleaning: • Soft water. • Pure steam • Water for Injection WFI Two steps of cleaning: • Firstly clean in place (CIP ) 45 mins, • Secondly sterilization in place (SIP) 25 mins , Procedure
• • • • •
First rinse soft water, Second rinse caustic soda, Third rinse soft water, Fourth rinse water for injection (WFI) Finally WFI is used.
In every batch SIP and CIP must be performed.
FLOW DIAGRAM
Vacuum Resin 24
Compressed Air Dispensing Reactor Filling Container formation Sealing De flashing Packaging BFS
Quality Operations Quality Operations Department Consists Of:
1. 2. 3. 4.
Quality Assurance Quality Control Quality Compliance Product Development
Quality Assurance Quality Assurance is a widely ranging concept covering all matters that individually or collectively influence the quality of a product. It involves all the functions required to maintain the quality during manufacturing and also the factors that influence the stability during shelf-life. Quality Assurance =Product design (Formulation to shelf-life) +Good manufacturing Practice (GMP)+ Quality control (testing+ assessment)+Quality Goal Activities. QA Department must establish control or checkpoints to monitor the quality of the product that begins with #Raw materials and component testing and include In-Process.. #Packaging #Labeling #Finished product testing #Batch auditing & #Stability monitoring Activities of QA Department Example of some major responsibilities---------------a) Sampling of incoming raw and packaging materials using (√n +1) rule Where, n=Drum/container/Box no. b) Release or rejection of starting materials c) Dispensing of starting materials d) In-process checking of all production and packaging area
e) Final release of all finished goods for distribution in the market. f) Product compliant handling, investigation &making of corrective action g) Documentation h) Collection &preservation of retention sample of the final products in an easy retrievable way. Quality Assurance
Quality control
Quality compliance
Process validation Raw & packaging material Water analysis Microbiology
Documentation internal Auditvendor
Analytical method validation
In process check
Finish product
Product stability
Vendor Approval
Training
۞Quality Control: ☻Quality control is a part of quality assurance. ☻It 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. ☻It concerns quality control of raw materials, finished products & packaging materials. ☻QC is the day to day control of quality with a company, responsible for the acceptance or rejection of incoming raw materials and packaging components, inprocess tests, labeling, and inspection, assurance that systems are being controlled and monitored, and for the approval or rejection of finished dosage forms. ♣ Raw material analysis: 1) Appearance 2) odor 3) Identification 4) Solubility 5) pH 6) Melting point 7) Refractive index 8) weight/ml 9) Specific gravity
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10) LOD/Moisture content 11) Residue on Ignition /suphated ash 12) Viscosity STEPS of QC: Raw material sampling Testing Release of raw material Production Sampling from granulation Sampling after blending Passed for compression Testing after compression Passed for coating Packaging Stability tests Passed for commercial release Sampling:
Sampling may be defined as the process of removing an appropriate numbers of items from a population in order to make inferences to the entire population. The object of sampling and subsequent testing, is to provide an effective check on the quality of the product or substances being processed. In Square Pharmaceuticals Ltd, sampling is performed by the quality control department. ☻For the active ingredients, the sample is withdrawn from each container. ie, for active----100% sampling is done. ☻For the excipients, sampling is performed by the following formula√n+1 If any of active ingredients or excipients is damaged, the sample is collected from each container. Raw Material Analysis:
♣Appearance ♣Odor ♣Identification ♣Solubility ♣pH ♣Melting point
♣Refractive index ♣Weight/ml ♣Specific Gravity ♣LOD/Moisture Content ♣Residue on Ignition ♣ Viscosity (cps/mps) ♣ Sulphate ♣Chloride ♣Heavy Metals ♣Organic Volatile Matter ♣Related substances ♣Sp. Tapped Volume (ml/g) ♣Assay
Tablet Granules Analysis during Process Development:
• • • •
♣Appearance ♣Identification ♣Loss on drying ♣Assay
Finished product Analysis for Tablet/Capsule:
• • • • • • • • • • • •
♣Appearance ♣Identification ♣Average weight of tablet ♣Hardness ♣Thickness ♣Disintegration time ♣Friability test ♣Dissolution ♣Content Uniformity ♣Chemical Assay ♣Life of Expiry ♣Related substances
• • • • • •
♣Pack Analysis ♣Appearance (pack) ♣Appearance (Product) ♣Leakage Test ♣Unit pack Description ♣Life of Expiry
♣Appearance ♣Solubility
Packed Analysis:
Opa-Dry Analysis:
28
♣Color Difference ♣Loss on Drying ♣Ash ♣Dispersion
Quality compliance: • Process validation • Documentation • Audit • In-process check • Product stability test • Training
Validation Validation is the integral part of Quality Assurance. Validation may be defined as a systematic study which help to prove that the systems, facilities and process perform the job adequately and consistently as specified. To the more precise a validated operation is one which has been proved to have the potentials for the uniform outcome meeting the required specifications. Validation process:
URS DQ FAT
SAT
COMMISSIONING
IQ
PQ
OQ
PV
URS- User Requirement Specification DQ- Design Qualification FAT- Factory Acceptance Test SAT- Site Acceptance Test IQ- Installation Qualification OQ- Operation Qualification PQ- Performance Qualification PV- Process Validation. Method Validation: ☻Accuracy ☻Precision ☻Linearity ☻Specificity (Identification& Impurities) ☻Limit of detection ☻Limit of Quantification ☻Robustness ☻Range Process validation: Establishing documented evidence that provides a high degree of assurance that a specific process will consistently produce a product meeting its predefined specification & quality attributes. Good validation practice requires the close collaboration of departments such as those concerned with development, production, engineering quality assurance & control. An adequate validation may be beneficial for the manufacturing in many ways• It deepens the understanding of process, decrease the risk of processing problem & thus assure the smooth running of the process. • It decreases the risk of defect cost. • It decreases the risk of regulatory non-compliance. • A fully validated process may require less in process control & end product testing. Documentation: Specification for starting material, primary packaging materials, intermediate bulk product, finished products, master formula, batch manufacturing records, batch packaging records are documented in proper manner. Art work development
Carton Art Work Length Width
30
length width height Storage condition
Mfg lic.no DAR no Leaflet/insert Square logo
Height MRP + VAT Drug approval Art work & Drawing Text for carton Text for foil
Text for insert AuditVendor audit Internal audit In-process check: In-process checks are• Hardness • Thickness/Diameter • Weight variation • Gross weight • Leak test • Disintegration Training: Introduction training On the job training
pd purpose • •
to development of new product launch eg.letanopost(eye droop) to increase market demand of existing product development required of existing product eg.albendazole • when transfer the existing product of pabna plantto kaliakoyr plant development is required Procedure:
Stability Product Stability Test: The Quality Compliance Department should establish expire date & shelflife specification, on the basis of stability test to storage condition. According to ICH GuidelineCondition 1) Long Term 2)Intermediate Term 3) Accelerated
Storage condition Temperature Relative Humidity 25˚C ± 2˚C 60% ± 5% Or,30˚C±2˚C 65% ± 5%
Testing frequency
30˚C±2˚C
65% ± 5%
Initial-0,3,6,9,12 months 2nd-18,24 month 3rd-Annually 0,3,6 months
40˚C±2˚C
75% ± 5%
0,3,6 months
In SQUARE Pharmaceuticals (Dhaka Unit), Long term & Accelerated condition is maintained.
Stability test of the product in Stability Chamber is performed by Quality compliance. Following observations are performed during Stability testing---
♣Appearance ♣Color ♣Shape ♣Visual spot ♣Capping ♣Chipping ♣Dissolution ♣Disintegration time ♣Water content
♣ Microbial contamination etc.
Good Manufacturing Practice (GMP) GMP: Organization and authorities concerned with production and control of drugs have developed rules for pharmaceutical industry. These rules are commonly called GMP (Good Manufacturing Practice). GMP provides basic standards for the manufacturers of drugs and from the basis on which each company build its own systems procedures to assure the product quality. The objective of GMP is to assure quality of medicine for the safety, well-being, and protection of the patient. The main criteria of quality of any drug, in dosage form are its safety, efficacy, potency, stability, acceptability and regulatory compliance. Quality is everybody's responsibility. It is built into the product and it is a total commitment from the Machine Operator to the Managing Director. GMP ensures that products consistently produced and controlled to the quality standards appropriate to their intended use. GMP diminishes risk that cannot be controlled by testing the product:
•
Cross-contamination
•
Mix-up
There are number of national & international GMP regulatory boards:
32
•
WHO
•
PIC
•
FDA
•
MHRA
•
TGA
Goals of GMP
Company Productivity
Product Quality
GMP
Regulatory Compliance
Employee Health & Safety Quality requirements:
•
The product shall not harm for the consumer, have no unexpected side effects.
•
Have the expected effect during the shelf life.
Some implemented basic rules of GMP:
•
Every body who enter into Production area shall wear full head cover/cap, covering
all hairs.
•
Company provided shoe shall be put on before entering into production area.
•
Uniform shall be changed in the change room.
•
Company issued uniforms shall be worn only in the designated area not outside.
•
Face masks & gloves shall be worn by employee working over open products. Safety glasses shall be put on where needed.
•
All doors shall be kept closed to control the entrance of dust & insect.
•
Eating, drinking, smoking strictly prohibited in production area.
•
Spills of products /materials whether powder or liquid shall be cleaned immediately to avoid tracking the material into other areas.
•
At the end each shift, work areas/machines shall be cleaned by the operating personnel.
•
Hand shall be washed before starting the day work & after every break.
•
Hands must be washed with soap after using toilet.
•
All product/material containers shall be tightly closed when not in use
•
Carton holding packaging material shall be sealed with tape when not in use.
•
All cartons and drums holding intermediate, raw materials or packaging materials shall be clearly identified with product name, batch no/lot no, and quantity.
•
No master carton of finished/intermediate product to be closed without outer level.
•
Waste container shall be provided in specified locations and clearly identified.
GMP: Current Good Manufacturing Practice GMP remains “CURRENT” by
•
Publications of guidelines and other reference materials.
•
Oral and written comments and opinions referred by Regulatory authorities.
•
Regulatory actions
GMP is that part of quality assurance which ensures that products are consistently produced and controlled to the quality standards appropriate to their intended use and as required by the marketing authorization. GMP rules are directed primarily to diminishing the risks, inherent in any pharmaceutical production that cannot be prevented completely through the testing of final products. Under GMP: (1) All manufacturing process are clearly defined, systematically reviewed in the light of experience, and shown to be capable of cc .is instantly manufacturing pharmaceutical products of the required quality that comply with their specification. (2) Critical steps of manufacturing process and any significant change made to the process are validated; (3) All necessary facilities are provided, including: i) Appropriately qualified and trained personnel ii) Adequate premises and space iii) Suitable equipment and services iv) Correct materials, containers and labels v) Approved procedures and instructions vi) Suitable storage and transport, and vii)
Adequate personnel, laboratories, and equipment for in-process
controls under the responsibility of the production management. (4) Instructions and procedures are written in clear and unambiguous language, specifically applicable to the facilities provided (5) Operators are trained to carry out procedures correctly
34
(6) Records are made (manually or instrumentally) during manufacture to show that all the steps required by the defined procedures and instructions have in fact been taken and that the quantity and quality of the product are as expected; significant deviations are fully recorded and investigated (7) Records covering manufacture and distribution, which enable the complete history of a batch to be traced, are retained in a comprehensible and accessible form (8) The proper storage and distribution of the products minimizes any risk to their quality (9) A system is available to recall any batch of product from sale or supply; (10) Complaints about marketed products are examined, the causes of quality defects investigated, and appropriate measures taken in respect of the defective products and to prevent recurrence. MICROBIOLOGY LABORATORY According to the ICH guidelines the microbiological test of raw materials and finished product is an important parameter of the quality drug. Accordingly the SPLU2 has a special separate microbiology laboratory in order to carry out the microbiological tests of several sensitive products. The microbial test program includes the following: 1. Test of raw material and packaging material. 2. Test of finished product 3. Environmental monitoring 4. Purified water test 5. ETP water test 6. Personnel hygiene The microbiology laboratory of SPLU2 contains the following separate rooms:
♌ Testing room:
-Laminar air flow -Microscope -Water bath -Colony counter -PH meter -Anaerobic jar -Desiccators -Vortex mixer ♌ Incubation room: -Bacterial incubation chamber -Fungal incubation chamber -Air particle counter -Air bacteria counter This room is for incubating the microbial cultures-for bacteria and fungus. There are two incubation chamber here-one for bacteria and one for fungus. The bacterial
incubation chamber is maintained at 30 o-35o c and the fungal incubation chamber is maintained at 20o-25o c. The air particle count of the total production area is strictly maintained at <100000/room. â&#x2122;Ś Media preparation room: -Autoclave machine -Reverse osmosis water system -Laminar air flow There is also a store room to store the reagents, cultures, standard microbes, chemicals and other testing instruments in a required condition. The total testing procedure can be summarized as follows: Sample collection Media preparation Culture preparation Incubation Colony count Identification Final result For the Environmental inspections following tests are performed-------1) Air particle count- The air particles of the room of the total production area is maintained not more than 100,000. 2) Microbial Count (SWAP test)- The microbial count in the wall, floor &ceiling is measured by this method. For the bacteria, the incubation time is not less than 5 days and for fungi, it is 5 days. The incubation temperature for bacteria The incubation temperature for fungi
32-35oC 20-25oC
3) Settle plate testIn settle Plate test the plate is exposed to the environment for 4hrs. TSA (Tripton Soya Agar) media is mainly used. 4) Test for Heat resistant organism----Membrane filtration method is used. 5) Specific organism identification by using API strip. The total lab. is separated from the main building by the double door air lock system to prevent the hazard of microbial contamination. In Cephalosporins Microbilogy Test----c) Endotoxin test/LAL test:
36
It is an in-vitro test method for pyrogen, has been developed utilizing the gelling property of the lysate of amoebocytes of limulus polyphemus. Single test 025 ml in LAL and dissolve Incubation at 370 C for 1hr Gel formation Indicate presence of endotoxins from gram-negative bacteria. Fig : Flow diagram of LAL test.
Engineering department Engineering department of SPLU2 plays a vital role in maintaining all other departments & supplies energy to these departments. The engineering dept. of SPLU2 functions either indirectly or directly. The indirect functions of the engineering dept. of SPLU2 are to maintain the official documents and records. The direct functions of engineering dept. of SPLU2 are may be of two types:
♦ Preventive maintenance ♦ Breakdown maintenance. Preventive maintenance: The preventive maintenance of engineering dept. of SPLU2 includes the maintenance of the followings systems including:
♦ HVAC system (Heat ventilating and Air conditioning) ♦ Water systems 1. Iron removal plant 2. Pre-treatment plant 3. Soften water treatment plant 4. Purified water plant ♦ Power generation system
♦ ETP (Effluent treatment plant) ♦ Incineration
HVAC system The HVAC system means Heat ventilating and Air conditioning system. The main objectives of HVAC system is to maintain a constant temperature (24 o c) and a constant RH (<40%) in the general production building (GPB), laboratory and the office rooms. It is the most modern concept of air conditioning which is the most special features in the SPLU2. Why HVAC needed in Pharmaceuticals
1. To maintain specified temperature. ( Here 24 deg C) 2. To maintain specific relative humidity. (Less than 40% for some hygroscopic
material like ranitidine). 3. To remove dust particle from production area. 4. To maintain proper airflow to the rooms ensuring that cross contamination does not occur. 5. To prevent microbial contamination in some area by maintaining particle size within the tolerance range. (Using the HEPA Filters etc). The total system is an automatic process and is maintained by a software system named “Metasis”. The process is maintained in the different area by controlling the air pressure (positive and negative) and is performed by the following two:
♦ SD-Supply Diffuser and ♦ EG-exhaust Grill The conditioned air is supplied through the SD and the air inside the room is exhausted through the EG. The system is controlled from the BEMS (Building engineering and management system). There is also a central Dust Collector to collect the chemical dust produced in the production processes (granulation, compression and encapsulation). The chilling units are always remained at 8o c to cool the air. On the basis of the condition required, the HVAC system is subdivided into several units:
♦ Unit-3 & 4: For the production area ♦ Unit-5: For change rooms ♦ Unit-6: For secondary packaging area ♦ Unit-7: For general office rooms 38
♦ Unit-11, 12 & 13: For laboratory rooms. The air that is supplied in the rooms are filtered through a air filtration system which include the involvement of the filters-
o Panel filters o Back filters and o HEPA filters (13-0.3µ)
Air from
Rotary Screw Type Air Compressor
Prefilter (To remove particles to 1µ)
After-filter (to remove particles to.01µ)
Atmosphere
Odor removal filter
Reversed flow After-filter (To remove particles to 1µ
Regenerative Dryer Desiccant Type
Solid/liquid
Air Tank Capacity 200Gallons
Header
Solid/liquid Sterile Sterile
Warehouse Warehouse Cephalosporin Cephalosporin Block Diagram of Screw Type Air Compressor Iron Removal Plant Iron is an important feature in the industrial production as it hampers the normal flow of water and harmful for the supply pipes and ducts. So there is an iron removal plant in SPLU2. This plat contains layers of rocks of various size and sand. Water passes through the layers and the iron is absorbed finally in the sand layer. Water Treatment
Deep tube - well Sodium Hypochlorite â&#x2020;&#x2019; raw water tank (25 m3/hr) Pump
Alum First sand filter
Alum Second sand filter Activated Carbon Filter
Sodium
Hypo
RCC (20,000 gallon)
(17 m3/hr) Raw water plant (8000 liter) Pump Special/extra sand filter Duplex softener Semice Regeneration by NaCl Softened water Filter (Resinous) Softened water tank (2500 liter) Purified water
NaO 2
pumps
UV sterilizer Purified water plant
Purified Water Plant
40
Soft
water
plant
5 micron filter Duplex softener Activated carbon filter Buffer tank PUMP (Reverse osmosis) Pure water CDI Anode Cathode Feeding water system (<0.2 Âľ filter) UV sterilizer Purified water tank (10,000 liter) 1st & 2nd Heating and cooling exchanger Final UV sterilizer (254 nm intensity) User points Recycle to purified water tank Flow 11.4 m3/hr Various Agents used: Agents Na2S2O3 NaOH Anti-scalent NaCl
Purpose Chlorine neutralization pH, CO2 remove SiO2 remove Regeneration of ion-exchange resin
Iridium coated Titanium
Cathode, anode
Waste management:
Purpose: To ensure waste segregation, recycling, handling & final disposal to maintain a pollution free environment as per regulatory requirement. Responsibility: Engineering department is responsible for all technical assistance and handle liquid. waste management. Plant administration department is responsible for solid waste management. Waste classification: Based on the physical properties of plant wastes are of two types: -Solid waste -Liquid waste And based on the chemical property the regulatory authority define the waste as -Hazardous waste -Non hazardous waste Solid wastes are commonly: - Papers from office - Paper and leaflet, box & carton - Alu-PVC and Alu-Alu empty blister - Unused or rejected glass bottles, vial, ampoule, plastic & HDPE containers - Cloths and Rags from cleaning site - Canteen wastes - Metal scrapes from packaging - Wooden scrape from packaging - Air and lube oil filter - Scrape of rubber, plastic, nylon, Teflon, acrylic, GP sheet, SS sheet, GI & MS piping from maintenance. Liquid wastes are commonly: - Cleaning and washing liquid from production floor - Container rinsing liquid - Lubricants from generator, air compressor, gearbox of different machinery - Diesel from generator - Lab reagents
42
- Printing ink Disposal methods: Disposal methods of solid & liquid wastes for the plant are as follows: Solid waste: After collection firstly segregate the solid wastes as recyclable, incinerable, hazardous & saleable categories. - Incineration of hazardous waste to be carried out by 3rd party contractor. - Sale of non-hazardous waste to be disposed off to the enlisted buyer. - Land filling of non hazardous waste to be done by PPL stuff. Liquid waste: - Process waste and cleaning liquid by ETP at plant site. - Normal container rinsing, sewerage water and surface water directly discharge to municipal drain.
Incinerator: There is an incinerator in SPLU2 to burn out the chemical dusts. The mechanism of the burning operation is given by the following flow chart:
Neutral gas line (Flow 20 m3/hr Press. 100 m bar) ↓ LPS ↓ SFV ↓ STB ↓ TSV
↓ Low gas pressure switch (LPS) ↓ Safety valve (SFV) ↓ Gas stabilizer (STB) ↓ Two stage valve (TSV) ↓ Burner
↓ Cyclonic scrubber -225 mm WC 200ºC ↓ ID fan +75 mm WC 160ºC ↓ STACK Burner -5 mm WC 700ºC ↓ View port Feed door Ash-tray →FD fan Manometer (secondary) -25 mm WC 1000-1200ºC ↓ View port DFV (double flap valve) Neutral Gas Line → Ball valve → Needle valve → Filter
44
ETP (Effluent Treatment Plant)
ETP (Effluent Treatment Plant) is another
urea
special
TSP
feature of SPLU2 which is rare in Bangladesh,
except
2
several multinational pharmaceutical companies. The chemical and
2
3 2
first
neutralized
4 industrial
5
before
to
released
waste materials
6
the
environment
in
1 order to prevent the environmental pollution. Thus SPLU2 has a lot of contribution in environmental protection program. Inlet & Treated Effluent Characteristics:
7
Characteristics
Inlet Concentration
Chemical Oxygen Demand (COD) Biological Oxygen Demand (BOD) TSS pH
NMT 400 ppm
CSB (Central Service Building)
NMT 250 ppm
val
NMT 250 ppm 6.0-9.0
Treated Concentration (with optional item) < 100 <10
val 9
<1 6.5-8.0
2
1 ContainsElectrical generator- G 3516 USA 3 nos 16 cylinders Capacity 1020 kW. 1. Screen chamber tank 2. Equalization tank 3. Lime sodium tank & Chemical solution tank 4. Clarifloceulated tank 5. Aeration tank 6. Clarifier tank 7. Holding tank 8. Sand filter 9. Activated carbon filter 10. Final discharge 11. Filter press
Figure: ETP (Effluent Treatment Plant)
46
8
1
Exhaust gas boiler (EGB – FST - CS) Gas fried boiler (SM – 40A) – 500 kW gas generator Air compressor COM 1,2 (cyclone 455) COM 3 (cyclone 345 SR) Technical Specification Cooling medium Air end Total oil capacity Delivery air connection Ambient air temp. op. range Delivery air pressure Typical delivery temp. above ambient Typical cooling air outlet temp. above ambient Main drive motor nominal rating Main drive motor nominal speed Fan motor rating Length Dimensions Width Height Average sound level
COM 1,2 Air 4 40 lt DN-50-PN-16 (1-43)ºC (5-13) bar 12ºC 18ºC 55 kW 2975 rpm 2.2 kW 1800 mm 1200 mm 1650 mm 74 dB(A)
COM 3 Air 4 18.5 lt R½ (0-43) ºC (5-13) bar 10ºC 25ºC 50kW 5000 rpm 2.2 kW 1420 mm 990 mm 1650 mm 77 dB (A)
CALIBRATION Calibration means standardize the measuring instruments by a standard device applying a suitable and specific method. It is also one of the important functions of the Engineering Dept. of SPLU2. All the measuring equipments such as gauges, balances and weights are calibrated routinely by this dept. in order to restore the accuracy of these equipments.
♦ Small balances are calibrated at a 3 months interval internally. ♦ Large balances are calibrated at a 4 months interval internally. ♦ Gauges (temperature, humidity and all the gauges of different machines) are calibrated at a 12 months interval internally.
♦ All the equipments for calibration are calibrated from abroad. ♦ All the weights are calibrated annually by the B.S.T.I. (Bangladesh Standard Testing Institute).
The Engineering Dept. of SPLU2 is a model to the other pharmaceutical industries in Bangladesh.
OBSERVATION During the period of 28 days in-plant training we visited each department of SPLU2. According to not only the GMP guidelines but also the ICH guidelines maintains all the procedures and proper documentation, which is most appreciable. The tablet & the capsule section are well established and all the personnel perform their duties according to the SOP (Standard Operating Procedure). The operators are skilled enough which is necessary for a quality product. We were very lucky to be in touch with the wonder of the modern environmental protection technique the ETP & also the modern application of the air conditioning system, the HVAC system. During this period we also observed the good interaction between the officers and the staffs & workers. We think this helps them to work as a team. By the overall performance of all the departments we really feel lucky to be introduced with the worldâ&#x20AC;&#x2122;s most modern pharmaceutical technology. Thus SPLU-2 is serving the nation and continue her fight against the diseases.
LIMITATIONS There are some minor points yet to be achieved in this regard according to our observation. Change room: The change room of production & Q. A. is small enough. This problem may be arisen whenever more visitors visit the factory. Washing room: Another short coming of SQUARE is small sized washing room in production unit.
CONCLUSION This 28 days in-plant training program was the only opportunity to coincide our theoretical knowledge of pharmaceutical manufacturing, operation and the quality control with practical observations. We are hopeful that this in-plant training has certainly broadened our theoretical knowledge, which will help us a lot in our professional future.
48
In SPLU-2 during our training period we found a very friendly and cordial atmosphere. This was possible due to the co-operation of all officers here. Their helps and guidance made our training fruitful in SPLU-2. Although there are some negotiable limitations SPLU-2 is the only best company that never compromises with quality. So, we feel most lucky to complete our in-plant training in SPLU-2. All of our thinking is completely from our own point of view. Besides, we want to say that the purpose of our training was to gather some practical knowledge of our professional subject and not to inspect a company or to search faults to them. If any persons becomes annoyed with us for any of our activities please pardon us as learners. At the end, we are hearty thanks to Square Pharmaceuticals Ltd. from ourselves and from our department. We hope such co-operation between the authority of Square Pharmaceuticals Ltd. and Dept. of Pharmacy, will be far more strengthened in future than present. We wish SPLU-2 always prove worthy to attain its ultimate goal in promoting the worldwide pharmaceutical arena. BEST WISHES TO SQUARE PHARMACEUTICALS LTD.