Follow
1.0 OBJECTIVE
To provide a procedure to regulate the production, installation and servicing processes, which directly affect the quality of a product.
2.0 SCOPE
This SOP shall be applicable for all personnel of Infusions Unit.
3.0 ASSOCIATED DOCUMENTS
3.1 SOP No. INFPS002 Dress Requirement and Gowning Procedure for Clean Areas
3.2 SOP No. INFPS003 Cleaning of Clean Areas
3.3 SOP No. INFPS007 Cleaning of Tanks, Filters and Pipelines to Bottelpack
3.4 SOP No. INFPS008 Sterilization of Tanks, Filters and Pipelines to Bottelpack
3.5 SOP No. INFPS009 Solution Preparation
3.6 SOP No. INFPS010 Filter Integrity Test for Product Filters
3.7 SOP No. IONEU011 Requirements for Water for Injections
3.8 SOP No. INFPI001 Operating Procedure of Injection Moulding Machine and Cap Assembling Process
3.9 SOP No. INFPB002 Filter Integrity Test for Product Filters of Bottelpack Machines
3.10 SOP No. INFPB007 Operating Procedure of Bottelpack Machine Line # 01
3.11 SOP No. INFPB009 Operating Procedure of Cap Welding Machine Line # 01
3.12 SOP No. INFPB012 Operating Procedure of Bottelpack Machine Line # 02
3.13 SOP No. INFPB014 Operating Procedure of Cap Welding Machine Line # 02
3.14 SOP No. INFPB018 In-process Control of Bottelpack Machine
3.15 SOP No. INFPA001 Operating Procedure of Autoclave Machine Line # 01
3.16 SOP No. INFPA002 Operating Procedure of Autoclave Machine Line # 02
3.17 SOP No. INFPA003 Area Clear Inspection of Autoclave Area
3.18 SOP No. INFPA004 Loading of Bulk Products in Trolleys
3.19 SOP No. INFPA007 Leak Test of Welded Caps of Finished Product
3.20 SOP No. INFPP001 General Packaging Guidelines for Infusions Products
3.21 SOP No. INFPP003 Dress Requirement and Gowning Procedure for General Production Areas
3.22 SOP No. INFPP004 Area Clearance Inspection and Work Distribution in Packaging Area
3.23 SOP No. INFPP006 Feeding of Sterilized Bottles and Adjustment of Pressing Belt
3.24 SOP No. INFPP008 Loading and Adjustment of Label Roll in Labeling Machine
3.25 SOP No. INFPP009 Jet Printer Setup for Printing of Overbag / Inner Carton
3.26 SOP No. INFPP010 Inspection of Bottles under Pressing Belt and Visual Checking Station
3.27 SOP No. INFPP012 Use of Overbag, Leaflet and Carton
3.28 SOP No. IONWH010 Delivery of Raw Material to Clean Area
3.29 SOP No. IONGE006 Classification of Different Areas in ION and Infusions Unit
3.30 SOP No. IONQC011 Environmental Control – Monitoring of Airborne Particulate Count
3.31 SOP No. IONQC012 Environmental Control – Monitoring of Air-borne Microorganisms
3.32 SOP No. IONQA011 In-process Control of Bulk Solution
3.33 SOP No. IONQA025 Bottel Pack In-process Control
3.34 SOP No. IONQA032 In-process Control of Packaging of Infusions Unit
3.35 SOP No. IONES005 Monitoring of Differential Air Pressure in Clean Areas of Infusions Unit
3.36 SOP No. IONES009 Air-Lock Light Controls in Clean Areas
3.37 SOP No. INFPS011 Dispensing and Handling of Excess Materials for Infusions Products
3.38 Form No. PS011-01 Manufacturing Work Order
3.39 Form No. PS011-02 Primary Packaging Work Order
3.40 Form No. QA025-01 Bottel Pack – In-Process Control
3.41 Form No. PB014-02 PE Cap Work Order
3.42 SOP No. INFPM101 Operating and Cleaning Procedure of Dispensing Booth
3.43 SOP No. INFPM102 Operation and Function Checking of Digital Platform Balance
3.44 SOP No. INFPM103 Dispensing and Handling of Excess Materials after Batch Accomplishment
3.45 SOP No. INFPM104 General Production Principles and Operating Guidelines for Infusions Products (Line # 03)
3.46 SOP No. INFPM105 Operating of Manufacturing and Storage Vessel
3.47 SOP No. INFPM106 Cleaning and Sterilization of Manufacturing and Storage Vessel, Filter Filling Buffer Tank, Filling Nozzles, Connecting Tubes and Pipelines
3.48 SOP No. INFPM107 Solution Preparation and Transfer of Solution from Manufacturing Vessel to Storage Vessel and to the Filling
3.49 SOP No. INFPM108 Filter Integrity Test for Product Filters
3.50 SOP No. INFPM110 Operation, Cleaning and Maintenance Procedure of Pass Boxes
3.51 SOP No. INFPM112 Operation and Cleaning Procedure of Vertical Ultrasonic Bottle Washing Machine
3.52 SOP No. INFPM113 Operation and Cleaning Procedure of KSZ920/100(A) Sterilizing And Drying Tunnel
3.53 SOP No. INFPM114 Operating and Cleaning Procedure of SGS6 CR Bottle Filling Stoppering Machine
3.54 SOP No. INFPM115 Operation And Cleaning Procedure Of BIG Infusion Capping Machine
3.55 SOP No. INFPM116 Operating, Cleaning And Maintenance Procedure Of Moist Heat Sterilizer Model SAP-450DTVX-J-B700
3.56 SOP No. INFPP101 General Packaging Guidelines for Infusions Product (Line#03)
3.57 SOP No. INFPP102 Operating & Cleaning Procedure of Computer Control Vertical Round Bottle Labeling Machine
3.58 SOP No. INFPP103 Jet Printer Setup for Printing Inner Carton
3.59 SOP No. INFPP104 Receiving of Packaging Materials from Warehouse
3.60 Form No. PM103-01 Manufacturing Work Order (Line # 3)
3.61 Form No. PM103-02 Primary Packaging Work Order (Line # 3)
3.62 Form No. PP104-01 Secondary Packaging Work Order (Line # 3)
3.63 Form No. QA044-01 Filling In-Process Control (Line # 3)
3.64 Form No. QA032-02 Packaging In-Process Control (Line # 3)
4.0 RESPONSIBILITY/ACCOUNTABILITY
4.1 All personnel shall be responsible for implementation of the procedure.
4.2 All Departmental Head shall be accountable for ensuring implementation of the procedure.
5.0 ABBREVIATIONS AND DEFINITIONS
5.1 HRD – Human Resources Department
5.2 DP – Documented Procedure
5.3 SOP – Standard Operating Procedure
5.4 HEPA – High Efficiency Particulate Air
5.5 WFI – Water For Injections
5.6 QA – Quality Assurance
5.7 BMR – Batch Manufacturing Record
5.8 SPO – Senior Production Officer
5.9 SEO – Senior Engineering Officer
5.10 EO – Engineering Officer
5.11 AEO – Assistant Engineering Officer
5.12 PO – Production Officer
5.13 QAO – Quality Assurance Officer
5.14 HC – Hygiene Class
5.15 IPC – In – Process Control
5.16 PE – Polyethylene
5.17 BPR – Batch Packaging Record
5.18 APO – Assistant Production Officer
6.0 PRECAUTIONS /SPECIAL INSTRUCTIONS
Not applicable.
7.0 PROCEDURE
7.1 The process of Infusions Unit (Line # 01 & 02) consists of four sub-sections namely –
7.1.1 Solution Preparation.
7.1.2 Producing polyethylene bottles (PE) and filling them with solution and sealing them in Bottelpack Machine. Then PE caps are welded on the sealed bottles by Cap Welding Machine.
7.1.3 Sterilization of filled bottles.
7.1.4 Inspection and Packaging of PE bottles.
7.2 The process of Infusions Unit (Line # 03) consists of following sub-sections namely –
7.2.1 Glass bottle washing, depyrogenation and drying through drying tunnel.
7.2.2 Solution preparation and transfer of solution from manufacturing vessel to Storage vessel and to the filling.
7.2.3 Moist heat sterilization of filled bottles after attachment of flip-off seal.
7.2.4 Inspection and packaging of glass bottles.
7.3 Product quality is achieved by controlling various activities pertaining to the Process, System, Materials and Operations which are listed as:
Code Name
C01 Control of Entrance into Production Areas
C02(a) Control of Environment (Line # 01 & 02)
C02(b) Control of Environment (Line # 03)
C03(a) Control of Materials (Line # 01 & 02)
C03(b) Control of Materials (Line # 03)
C04(a) Control of Solution Preparation (Line # 01 & line# 02)
C04(b) Control of Solution Preparation (Line # 03)
C05 Control of Bottelpack
C06 Control of filling (Line # 03)
C07 Control of Autoclave
C08(a) Control of Packaging (Line # 01 & 02)
C08(b) Control of packaging (Line # 03)
These controls have been schematically presented in Enclosures 01, 02, and 03.
The descriptions of individual controls are given below :
7.4 C01 Control of Entrance into Production Areas
7.4.1 Every person who works in the production areas shall wear special dress. This gowning procedure is described in SOP No. INFPS002.
7.4.2 People who work in the areas of PE Cap Processing, Dispensing, Processing and BFFS & Glass bottle filling area shall change their cloths for the second time before they enter into those areas. This procedure is described in SOP No. INFPS002.
7.5 C02(a) Control of Environment (Line # 01 & 02)
7.5.1 Processing area of Infusions Plant (Line # 01 & 02) falls into the following grades according to SOP No. IONGE006.
Area Grade
Filling Nozzles (Bottel Pack Machine 01 & 02) A
Bottel Pack Conveyor (Line 01)
Bottel Pack Conveyor (Line 02) B
PE Cap Processing Area
Dispensing Area
Processing Area
Clean Corridor
BFFS (Blow, Form, Fill & Seal) Area C
Airlock – Personnel
Airlock – Material
Material Entry I
Technical Area
Material Entry II D
7.6 C02(b) Control of Environment (Line # 03)
7.6.1 Processing area of Infusions Plant (Line # 03) falls into the following grades according to SOP No. IONGE006.
Area Grade
LAF Unit of Filling Machine
Dispensing Booth A
Material Stage
Dispensing Area
Manufacturing Area
Bulk Stage
Filling Area -01
Corridor
Airlock
Filling Area-02
Autoclave
C
Material Airlock
Stage Area
PPM Airlock
D
7.6.2 Clean Areas shall be maintained
By supplying conditioned air through HEPA filters.
By maintaining positive air pressure inside the area and material and personnel airlock and
By restricting personnel entry.
7.6.3 The cleaning procedure for Clean Areas shall be according to SOP No. INFPS003.
7.6.4 The control of environment shall be monitored
By checking microbiological count (SOP No. IONQC012) and particle count (SOP No. IONQC011).
By monitoring differential air pressure (SOP No. IONES005).
By checking airlock light control (SOP No. IONES009).
7.7 C03(a) Control of Materials (Line # 01 & 02)
For processes of Infusions Plant the following materials are needed:
– Water for Injection (for Solution Preparation)
– Raw Materials (for Solution Preparation)
– Polyethylene Granules (for Bottelpack Machine and Injection Moulding Machine) and Rubber Disc (for Injection Moulding Machine)
7.7.1 Control of WFI
WFI is produced in Water Treatment Plant by multi-column distillation unit and stored in WFI Tank by constant circulation at a temperature above 800C.
For solution preparation it is pumped into the preparation tanks of Processing Area through a heat exchanger where it is cooled to 30 ± 5C.
The WFI shall be monitored according to SOP No. IONEU011.
7.7.2 Control of Materials
According to production plan, requisition (Form PS011-01) for raw materials shall be sent to warehouse by SPO/PO. The raw materials for solution preparation shall be sent from Warehouse to Material Entry I according to SOP No. IONWH010.
PO shall then check the status label on container/bags to check the R-No. and retest date given by QA Department. Material shall be weighed and double checked by PO and taken to Processing Area.
Requisition for Polyethylene Granules and Rubber Discs shall be raised by EO/AEO through Form No. PB014-01 for PE Cap Processing Area. Polyethylene Granules needed for BFFS Area shall be requisitioned by SEO/EO through Form no. PS011-02. Warehouse Officer shall issue and dispense the requisitioned amount to EO/AEO. EO/AEO shall check the status labels of materials for correct P Nos. and dates of approval given by QA Department and pour PE into the hopper of granule feeder of Bottelpack Machine and the hopper of Injection Moulding Machine. He shall also take delivered Rubber Discs to PE Cap Processing Area for assembling with caps.
7.8 C03(b) Control of Materials (Line # 03)
For processes of Infusions Plant (Line # 03) the following materials are needed-
– Water for Injection (for Solution Preparation)
– Raw Materials (for Solution Preparation)
– Type I & Type II (product specific) Clear Glass Bottles (for bottle washing & Depyrogenation tunnel and Glass Bottle Filling Machine)
– Rubber Stopper & Flip-off Seal (for Infusion Bottle Stoppering Machine & Big Infusion Bottle Capping Machine)
7.8.1 Control of WFI
WFI is produced in Water Treatment Plant by multi-column distillation unit and stored in WFI Tank by constant circulation at a temperature above 800C.
For solution preparation it is pumped into the preparation tanks of Processing Area. If required the WFI is passed through a heat exchanger where it is cooled to 30 ± 5C.
The WFI shall be monitored according to SOP No. IONEU011.
7.8.2 Control of Materials
According to production plan, requisition (Form PM103-01) for raw materials shall be sent to warehouse by SPO/PO. The raw materials for solution preparation shall be sent from Warehouse to RM Entry IA-01 according to SOP No. IONWH010.
PO shall then check the status label on container/bags to check the R-No. and retest date given by QA Department. Material shall be weighed and double checked by PO and taken to Manufacturing Area.
Requisition for Rubber Stopper & Flip-off Seal shall be raised by SPO/PO through Form No. PM103-02. Warehouse Officer shall issue and dispense the requisitioned amount to PO/APO. Then PO/APO shall check the status labels of materials for correct P Nos. and dates of approval given by QA. These materials shall be sent from Warehouse to Infusions unit through PPM Airlock IA-16(a). The Glass Bottles are transferred from Warehouse to Bottle washing area through Bottle Stage IA-07
7.9 C04(a) Control of Solution Preparation (Line # 01 & 02)
7.9.1 Solution Preparation shall be carried out in following sequences:
Cleaning of used tanks, filter lines and pipe lines according to SOP No. INFPS007.
Sterilization of Preparation Tank, filter lines and pipelines according to SOP No. INFPS008.
Rinsing the tank with 300 liters WFI at 30 ± 5C.
Integrity Test of filters according to SOP No. INFPS010.
Solution Preparation according to SOP No. INFPS009
7.9.2 During Solution Preparation following checks shall be performed:
Whether “Tank Flushed & Sterilized” label is attached to the tank before solution preparation. This label is later attached to BMR. The sterilization graph collected from control panel is also attached to BMR.
Before adding materials, whether the display on the control unit of flow meter is zero, which means that the required quantity of WFI has been pumped into the tank. Quantity of WFI is entered in BMR.
Whether the temperature of WFI shown on the Temperature Indicator (placed on the tank wall) is within the range (30 ± 5C). The actual temperature is stated in BMR.
Whether the bulk solution meets the specified requirements. When mixing is completed, a sample of prepared solution of 250 ml volume is taken from the tank by QAO according to SOP No. IONQA005 and analyzed according to SOP No. IONQC003. If results comply, bulk solution is released for filling. This release document is attached to BMR.
7.10 C04(b) Control of Solution Preparation (Line # 03)
7.10.1 Solution Preparation shall be carried out in following sequences:
Cleaning of used manufacturing & storage vessel, filter lines, pipe lines, buffer tank, filling nozzles and connecting tubes were done according to SOP No. INFPM106.
Sterilization of Preparation Tank, Storage Vessel, filter lines and pipelines according to SOP No. INFPM106.
Rinsing the vessels with 300 liters WFI at 30 ± 5C.
7.10.2 During Solution Preparation following checks shall be performed:
Whether “Tank Flushed & Sterilized” label is attached to the tank before solution preparation. This label is later attached to BMR. The sterilization graph collected from control panel is also attached to BMR.
Before adding materials, whether the display on the control unit of Load Cell is accurate, which means that the required quantity of WFI has been pumped into the vessel. Quantity of WFI is entered in BMR.
Whether the temperature of WFI shown on the Temperature Indicator is within the required range. The actual temperature in different steps are stated in BMR.
Whether the bulk solution meets the specified requirements. When mixing is completed, a sample of prepared solution of 250ml volume is taken from the vessel by QAO according to SOP IONQA005 and analyzed according to SOP No. IONQC003. If results comply, bulk solution is released for filling. This release document is attached to BMR.
7.11 C05 Control of Bottelpack
7.11.1 In BFFS Area following processes shall be carried out:
Blowing of bottles from PE granules, filling with the solution and sealing bottle in one operation according to SOP Nos. INFPB007 and INFPB012.
Production of PE Caps by Injection Moulding Machine according to SOP No. INFPI001.
Welding of PE Caps with the bottles in Cap Welding Machine according to SOP Nos. INFPB009 and INFPB014.
Stacking of filled and welded bottles from BFFS Area on autoclave trolleys according to SOP No. INFPA004.
7.11.2 Following check shall be performed in PE Cap Processing Area:
Weight of PE Caps from 8 mould cavities once every hour by Injection Moulding Machine Operator/EO/AEO. Actual weights are recorded in “In Process Control (Injection Moulding Machine)” which is later attached to BMR.
7.11.3 Following checks shall be performed in BFFS Area:
Wall thickness, weight, and cutting control of empty bottles by EO/AEO as per SOP No. INFPB015. Counter check done by QAO according to SOP No.
IONQA025. Values are recorded in the BMR and Bottelpack IPC Sheet QA025-01
Weight of filled bottles without cap by SEO/EO/AEO – one from each mould cavity once in an hour and recorded in the BMR. The counter checking done by QAO on the basis of weights of empty bottles and filled and cap welded bottles once in every two hours.
Vacuum test for checking leakage of welding, once every half an hour 8 bottles from eight heaters of Cap Welding Machine according to SOP No. INFPA007. Result of the test is recorded in the BMR.
7.12 C06 Control of Filling (Line# 03)
7.12.1 In Filling Area of Infusion plant (Line # 03) following processes shall be carried out:
Bringing the filtered solution into Buffer Tank. Connecting the Buffer Tank with the filling unit.
Placing the sterilized bottle on machine channel and operating the filling machine.
Starting the machine after adjusting the setting parameters of bottle filling, stoppering and capping.
Adjusting the fill volume according to filling specification stated on the BMR. Making necessary adjustment to the machine if the volume is outside the limit.
Recording of fill weight check and other check parameters to the primary packaging IPC sheet. Checking of fill weight at every 30 minutes interval for ensuring that fill volume is within the limits.
The counter checking done by QAO on the basis of weights of empty bottles and filled & sealed bottles within one hour maximum and data is recorded in BMR as well as Filling IPC sheet QA044-01
7.13 C07 Control of Autoclave
7.13.1 Following procedures shall be followed in Autoclave Section:
Clearing the loading area according to SOP No. INFPA003.
Loading of welded bottles on trolleys according to SOP No. INFPA004.
Loading of five trolleys, filled with bottles into Autoclave and then sterilized according to SOP No. INFPA001 and SOP No. INFPA002.
7.13.2 Following checks shall be performed in Autoclave Section:
Autoclave Tape shall be attached to each trolley before sterilization. Product name, code, pack size, batch no., part no., date and trolley no. shall be written on it. Before sterilization the autoclave tape must be signed by SEO/EO/AEO. During sterilization, the white stripes of tapes develop black colour. QAO checks it and Informs any non-conformity. Thus after autoclave it is possible to identify sterilized trolleys from the non sterilized ones. Tapes are later collected and retained by Packaging Department and attached to BMR.
Each sterilization cycle is recorded on a time-temperature graph installed on control panel of autoclave. Graph is plotted automatically and later collected and attached to BMR.
7.14 C08(a) Control of Packaging (Line # 01 & 02)
7.14.1 Packaging operation is carried out according to SOP No. INFPP001.
7.14.2 Packaging operation shall involve the following:
Attaching labels on bottles by labeling machine according to SOP No. INFPP008.
Putting labeled bottles along with leaflets into PE overbags according to SOP No. INFPP012.
Sealing the overbags in sealing machines according to SOP No. INFPP012.
Printing on overbags by Ink Jet Printer according to SOP No. INFPP009.
Cartoning according to SOP No. INFPP012.
Delivery to Warehouse.
7.14.3 Following checks shall be maintained in Packaging
Prior to start of operation the whole area shall be checked according to SOP No. INFPP004.
Pressure Belt check as mentioned in SOP No. INFPP006.
Visual inspection of bottles according to SOP No. INFPP009.
In-process control of packaging according to SOP No. IONQA032.
7.15 C08(b) Control of Packaging (Line # 03)
7.15.1 Packaging operation is carried out according to SOP No. INFPP101.
7.15.2 Operation & cleaning procedure of computer control vertical round bottle labeling machine is done according to SOP No. INFPP102.
7.15.3 Jet Printer setup for Printing Inner Carton is done according to SOP No. INFPP103.
7.15.4 Receiving of packaging materials from warehouse is done according to SOP No. INFPP104 and issued on Secondary Packaging Work Order (Form No. PP104-01).
7.15.5 The In-Process check of different packaging steps- feeding of sterilized bottle before labeling, labeling, insertion of different pack accessories, inner cartoning, carton overprinting, shipping cartoning in done by production department in production department in every thirty minutes. In-Process Control of packaging is also done by QA department according to SOP No. IONQA032 and recorded in the form no. QA032-02.
