SOP FOR OPERATION AND CLEANING OF AMPOULE FILLING AND SEALING MACHINE

• CHECKS AND PRECAUTIONS:
• Ensure that proper electric supply & earthing are provided to the Machine.
• Ensure Oxygen, LPG and Nitrogen Supply is ON.
• Ensure that each & every ampoule rotating Bearing is working properly.
• Ensure that LAF is ‘ON’ and Pressure differential in Magnehelic Gauge is within Range.
• Ensure that Temperature of filling area is NMT 25ºC.
• Before starting the filling operation, ensure the machine setting by using empty ampoules for following:
• Filling nozzle shouldn’t touch the tip of ampoules to avoid any friction which may lead to generation of glass particles.
• Filling nozzle should be in the center of tip to avoid any spiking / deposition of solution over the neck of ampoules (Which may lead to charring of solution and results in generation of black particles).
• Ensure cleaning & sanitization of aseptic area done before activity.
• MACHINE SET UP:
• Transfer the sterilized machine parts from cooling zone to filling room through Mobile LAF.
• Take the machine parts from mobile LAF & assembled machine parts step by step as per requirement aseptically under LAF.
• Machine parts shall be assembled step by step in the below mentioned sequence.
• Transfer the piston from mobile LAF trolley to filling machine under LAF.
• Open the filling machine safety guard, and assemble the Pistons manifolds as below.
• Connect the inlet of piston with manifolds outlet by sterilized silicon tubing as below.
• Connect the outlet of piston with filter needles.
• Assemble Pre & Post Nitrogen needles manifold & connect the Nitrogen manifold outlet with needles by sterilized silicon tubing as below.
• Connect the nitrogen supply to Manifold inlet by using sterilized hydrophobic vent filter as shown below.
• After that Manifold inlet connected with outlet of buffer tank using product dedicated silicon tube.
• Set the ampoule height & proper sealing by adjusting the flame with empty ampoule and measuring the ampoule height by using vernier caliper / calibrated SS Scale.
• Cutting of ampoules to be done as per following parameters.

• Check nitrogen supply from pre & post nitrogen needle and adjust Nitrogen flow rate as per BMR by using Rota meter.
• Start the filling machine, and initially flush out the solution from filling needles and then adjust fill volume as per BMR.
• Initially check the fill volume by using Calibrated Measuring Cylinder or pre sterilized disposal syringe.
• FILLING OPERATION:
• Perform Challenge test of sensors before start of operation and after any break-down of machine.
• Record the details of sensors challenge test in Annexure-I
• Ensure that depyrogenated empty ampoules are ready for filling operation.
• Ensure that Post BPT of first filtration complies. For filter used between compounding to holding vessel (Cartridge)
• Switch On Machine. Following screen will get display, login the machine by user ID and password.
• After Login, HMI screen will show following MENU display.
• After selecting Auto –operation display will appear.
• Parameters settings and maintenance mode are allowed to run by authorized persons only.
• Get detail of inputs and outputs.
• Press Maintenance to check & run the machine equipments manually.
• Press Parameters setting to set machine parameters.
• After getting the required volume, check & adjust the pre and post Nitrogen flushing of the Ampoule.
• Check the volume of ampoules from each needle respectively.
• Ensure volume of individual ampoule is within permissible volume limit during initial setting as per BMR.
• Adjust the oxygen and LPG using gas ON/OFF buttons for ampoule sealing.
• Check the Sealed Ampoules for proper sealing.
• Filled and Sealed Ampoules are collected in pre sterilized perforated SS trays.
• Check the volume of each needle as per Batch Manufacturing Record.
• Check the height of the Ampoule as per specification.
• Record the operation details.
• CLEANING:
• Switch off the electric supply of the machine.
• Turn off the supply of nitrogen gas, oxygen gas and LPG.
• Take filtered WFI in holding vessel and connected to final filter housing, and operate the filling machine and Flush out the WFI through filling needle.
• Dismantle the filling parts: – Syringes, Needles, Silicone Tubes etc. and transfer it to pre wash area through the Dynamic pass box for its cleaning and sterilization.
• Remove the left over empty ampoules and transfer to pre wash area for destruction.
• Remove all the spread solution from the outer and inner side of the machine.
• Take all unused filling machine parts and other accessories and transfer in to pre wash area.
• Wipe all the guards, machine body & conveyor belt with WFI using lint free Moping pad.
• Clean all the guards, machinery & conveyor belt using 70% IPA solution spraying all over the Machine and by lint free Moping pad.
• Clean the surrounding area of the machine using disinfectant solution or and then sanitized the area as per SOP.
• CLEANING OF FILLING AND  SEALING MACHINE CHANGE PARTS
• (SYRINGES. NEEDLES, SILICONE TUBES ETC.)
• Disconnect all machine parts, silicon tubes & needles.
• Connect each set of silicon tubing to manifold system installed in pre wash area and flush out purified water for 2 min. with pressure of WFI for 2 min with pressure.
• Clean the Manifolds & Needles individually with Purified water followed by WFI for 1 min each.
• Connect the inner side of manifold’ to silicon tube and flush out with purified water for 2 min. and  followed by WFI for 2 min.
• Dismantle all pistons and collect in a tray and dip in purified water and thoroughly cleaned by using lint free MOP.
• After cleaning with purified water, clean the pistons with WFI.
• Cleaning of Final filter and Filter housing shall be performed as per respective SOP.
• Cleaning process shall be verified by production & IPQA personnel and after proper cleaning, inspect the Machine Parts visually.
• IPQA person shall collect rinse water sample (if product change) for analysis.
• After QA clearance, all machine parts and tubing to be sterilized in Autoclave as per validated load pattern.
• If cleaned machine parts not used within 12 Hrs., then cleaning of machine parts shall be performed again before using as per above procedure.
• Perform the cleaning of machine parts as per relevant SOP.
• FREQUENCY: Before use or every batch/product change over.
• REFERENCES:   Not Applicable
• ANNEXURES:
  

• ABBREVIATIONS:
• °C               : Degree Centigrade
• BPT            : Bubble Point Test
• ID No.        : Identification Number
• IPA              : Isopropyl Alcohol
• LAF            : Laminar Air Flow
• LPG            : Liquid Petroleum Gas
• Mm             : Millimeter
• MMI          : Man Machine Interface
• No.              : Number
• QA               : Quality Assurance
• SOP            : Standard Operating Procedure

Annexure I
Sensor Challenge Test Record