STORAGE CONDITIONS FOR IN-PROCESS

ST — 111
STORAGE CONDITIONS FOR IN-PROCESS


INTRODUCTION
All raw materials, packing material, semi-finished goods and finished products must be stored under suitable condition to ensure their stability and integrity.
Storage of semi finished (in-process goods) in W.I.P. area
All the in-process goods such as filled vial/ampoules waiting inspection, labelling or packing and the overprinted packing materials etc. will be stored at temperature between 2-35 ºC. Temperature record for this W.I.P area will be maintained in the following format and will be displayed conspicuously in the W.I.P. areas.

DAILY TEMPRATURE RECORD

Location: W.I.P. Area (Sterile Department)
Time of Recording Temperature: 12:30 p.m
Month


DATE
TEMPRATURE

STERILIZATION CYCLES – DRY HEAT STERILIZER

ST — 110
STERILIZATION CYCLES – DRY HEAT STERILIZER


Equipment: Double door dry heat sterilizer with mounted HEPA filter module.

Temp. required for sterilization : 220 ºC
& Depyrogenation

Time of cycle : 90 min. at 220 ºC

Set temperature : 260 ºC

Time : Validated time depending on load

PROCEDURE – (NON STERILE SIDE)

1. Remove the lock and open the pressure lock door by turning the handle anti-clockwise, till the quick throw handle could be easily pushed down.
2. Unload the carriage on the trolley provided.
3. Check working of the alarm system when the door is opened. If not, report to the supervisor or engineering department.
4. Wipe and clean the carriage and the chamber of the dry heat sterilizer with distilled water.
5. Place systematically the load to be sterilized as per the loading pattern on the carriage and put the carriage back into the chamber of the dry heat sterilizer.
6. Close the pressure lock door, by pulling up the quick throw handle and turn the handle clockwise till the door is tight and display ‘‘DO NOT OPEN’’ board on the door
7. Fill the sterilization card provided stating date, items sterilized, time, no. of units and operators.
8. Put ‘ON’ the mains and check working of the booster fan and the HEPA module.
9. Put ‘ON’ the panel switch on ‘AUTO’.
10. Affix a thermograph duly labeled on to the validated set time depending upon the load to be sterilized.
11. Set the temperature to 260 ºC on the temperature controller unit.
12. Set the timer on the temperature controller unit to the validated set time depending upon the load to be sterilized.
13. Start the ‘Heater’ switch and simultaneously start the ‘Timer’ switch. The heater timer display and the HEPA timer display should start with ‘ZERO’ readings.
14. Check the current in all the three phase of the heater with the aid of the built in ammeter switch (ammeter reading should be between 35-38 amperes for each phase).
15. Check the thermograph, the thermograph recorder and the ink flow through the thermograph recorder.
16. The temperature will gradually rise and will be indicated by the temperature indicator and the thermograph.
17. After the sterilization cycle is completed, the heater will stop and the HEPA module will start to cool the load, the starting of the HEPA module will be indicated on the Magnehelic Gauge provided and the time will be indicated on the HEPA timer.
18. Prior to unloading the charge on the sterile side check the following
a. Thermograph has recorded the desired time and temperature relationship.
b. HEPA module is operating
c. Plenum pressure on the Magnehelic gauges of the HEPA module and record the same.
d. Load is sufficiently cool to be unloaded on the sterile side.
19. Initial the sterilization card and release the load for unloading in the sterile area for filling of sterile products.
20. Indicate on the load, date of sterilization and the date before which it should be used.

CLEANING PROCEDURE FOR DISTILLED WATER STROAGE TANK

ST — 039
CLEANING PROCEDURE FOR DISTILLED WATER STROAGE TANK


INTRODUCTION

The distilled water storage tank is used to collect and store pyrogen free distilled water obtained from the distillation still. It has to a temperature of 80 ºC to keep it pyrogen free since the distilled water is used for critical operation in sterile product manufacturing like rinsing of process equipment, vessels and utensils, rinsing of rubber stoppers etc.

Apart from being pyrogen free the distilled water should also be free from any particulate matter, hence, to endure this, the distilled water storage tank is periodically cleaned thoroughly and recored maintained.

PROCEDURE

Put the heater off and drain all the distilled water in the tank from bottom drain outlet.

Now disconnect the tank from multicolumn distillation still. Title the tank on the floor and dismantle the heating element, washers and temperature-sensing element.

Clean the tank from inside using clean sponge and filtered flowing DM water. Only if required, especially if any sticky particles are observed, use a nylon scrubber and 0.05% Benzalkonium Chloride solution (50%) for cleaning and then thoroughly rinse with flowing DM water.

Finally rinse three times with freshly collected pyrogen free distilled water, with completely draining the tank during each time of rinsing. Similarly, rinse he heating element, washer and the temperature sensor with only fresh pyrogen free distilled water thrice.

Fix the heating elements with washers and the temperature sensor to the tank and put the tank upright. Close the tank with the lid and connect it to the multicolumn distillation plant. Start the multicolumn distillation plant and collect about 50 liters of distilled water in the tank and then bottom drain the tank completely.

Now freshly collect the required amount of distilled water in the tank, and keeping the heater set at 80 ºC store the water for use, keeping the set heaters ‘ON’.

Record the date of cleaning and the name of the cleaning operator.

FREQUIENCY - MONTHLY

STERILIZATION CYCLES - AUTOCLAVE

ST — 109
STERILIZATION CYCLES - AUTOCLAVE


Temperature Used: 121 ºC Time to get F0 minimum 15
Time of Cycle: Validation minutes at coolest point for
(Theoretical Cycle Temperature) all loads


Various Loads of the Autoclave

1. MEMBRANE HOLDER AND VIAL FILLING ASSEMBLY LOAD

1. Membrane Filter Holder: 142/293 mm with 0.2µ membrane filter and 2 micron fiberglass prefilter
2. 10 Liters bubble test flasks 2 N0.
3. Vial filling machine unit: 10 ml/5ml glass syringes, stainless steel syringe casing, non-returned valves, filling needles, nitrogen manifold, SS ‘T’ joints, nitrogen gas reservoir.

Tubing
a. 2 Silicon tubing connecting outlets of solution holding vessel to the inlet of non-return valves
b. 2 Silicon tubing connecting outlets of non-return valve to the filling nozzles
c. 6 Silicon tubing to connect manifold to nitrogen gas nozzles
d. 1 Silicon tubing to connect nitrogen source to 25 mm filter
e. One PVC tubing for connecting two nitrogen filters
f. One Silicon tubing to connect manifold to nozzle of tank for gas overlaying
4. Sponges in bags.
5. SS bucket
6. 1 PVC tubing for drainage
7. Nitrogen filter holders: 25 mm with 0.2 micron hydrophobic membrane filter 4 Nos.
8. A bin containing tubing for filtration:
a) 1 silicon tubing for solution filtration
b) 2silicon tubing for nitrogen gas overlaying during filtration
c) 1silicon tubing to connect outlet of membrane holder to inlet of solution holding vessel.
9. 15 Liters distilled water in SS bucket.
10. Empty beakers 2 Nos.
11. 1 Liter round flat bottom B.T. flask
12. Tubing for integrity testing of nitrogen filters
a. 1 PVC tubing as an inlet to nitrogen filter
b. 1 silicon tubing at outlet of nitrogen filter
13. Air sampling drum and fan
14. Parchment papers 8 Nos.
15. Aluminum foil for covering distilled water flasks
16. Millipore breather filters 1 No.
As per validation cycle, the above load is run for 30 minutes from the time the digital temperature indicator reaches 123 ºC and in this time all the items including the item in coolest location satisfy F0 = 15 minutes.

2. Holding Vessel Load
Items sterilized in this load
1. 120 Liters holding vessel
2. 4 Nos. Pegs wrapped in a parchment paper
As per validation cycle, the above load is run for 30 minutes from the time the digital temperature indicator reaches 123 ºC and in this time all the locations including the coolest location satisfy F0 = 15 minutes.

3. GARMENT AND RUBBER STOPPER LOAD

Items sterilized in this load

1. 10 Sets of garments placed in perforated baskets
2. Cotton buds for swab testing
3. Rubber stoppers (approx. 30,000) in maximum 9 large and 6 small SS pots.

As per validation cycle, the above load is run for 60 minutes from the time the digital temperature indicator reaches 123 ºC and in this time all the items including the item in the coolest location satisfy F0 = 15 minutes.


4. MEMBRANE, HOLDER, HOLDING VESSEL AND AMPOULE FILLING ASSEMBLY LOAD

Items sterilized in this Load.

1. 40 liters holding vessel
2. Membrane filter holder: 142/293 mm with 0.2µ membrane filter and 2 micron fiberglass prefilter.
3. 10 liters bubble test flask 2 Nos.
4. Ampoule filling machine unit: Ss syringes along with SS spring, filling needles, nitrogen needles, nitrogen manifold, SS‘T’ joints.

Tubing:

a. 7 silicon tubing for nitrogen line
b. 6 silicon tubing for nitrogen line
c. 8 silicon tubing for pre and post nitrogen flushing
d. 4 silicon tubing for filling of solution

5. Sponges in bag.
6. SS bucket 2 Nos.
7. 1 PVC tubing for drainage
8. Nitrogen filter holders: 25 mm with 0.2µ hydrophobic membrane filters 4 Nos.
9. A bin containing tubing for filtration:
a. 1 silicon/PVC tubing for solution filtration
b. 2 silicon tubing for nitrogen gas overlaying during filtration
c. 1 silicon tubing to connect outlet of membrane holder to inlet of solution holding vessel
10. Empty beakers 2 Nos.
11. 1 Liter round flat bottom B.T. flask
12. Tubing for integrity testing of nitrogen filters.
a. 1 PVC tubing as an inlet to nitrogen
b. 1 silicon tubing at outlet of nitrogen filter
13. Air sampling drum and fan
14. Parchment papers 8 Nos.
15. Aluminum foil for covering distilled water flask

As per validation cycle, the above load in run for 15 minutes from the time the digital temperature indicator reaches 123 ºC and in this time all the items including the items in coolest location satisfy F0 = 15 minutes.


5. EMPTY ALUMINUM CONTAINER LOAD

Items Sterilized in this Load

1. 4Nos. of empty aluminum containers for collection of filled ampoules.

As per validation cycle, the above load id run for 15 minutes from the time the time the digital temperature indicator reaches 123 ºC and in this time all the location including the coolest location satisfy F0 = 15 minutes.


6. GARMENT LOAD

Items sterilized in this load
1. 10 sets of garments placed in perforated baskets
2. Cotton buds for swab testing

As per validation cycle, the above load is run for 60 minutes from the time the digital temperature indicator reaches 123 ºC and in this time all the location including the coolest location satisfy F0 = 15 minutes.

SERVICING POLICY – CLEAN AIR SYSTEMS AND DEVICES MONITORING

ST — 106
SERVICING POLICY – CLEAN AIR SYSTEMS AND DEVICES MONITORING


The system includes:

1. HEPA Filters
2. Prefilters
3. Grils
4. Manometer/Manometer Oil
5. Light and electricals
6. Blower/Impeller
7. Motors
8. Plenum
9. Airflow velocity

Monitoring Include

1. Cleaning and checking of equipment in the systems routinely
2. Leak test/integrity test of HEPA filters
3. Maintaining records of observation and readings
4. Repairing/replacing/rectifying whenever necessary

Equipment in the System includes
1. 4 terminal HEPA filters in filling room (i.e. class 10,000 area)
2. 3 terminal HEPA filter in the three change rooms ( one terminal filter in each room)
3. 12 ft. horizontal LAF unit with 4 HEPA filters in sterile filling room
4. Gradvel down-flow laminar unit with two HEPA filters for ampoule filling in sterile filling room
5. Gradvel down-flow laminar unit for aseptic filtration in sterile filling room
6. Down-flow laminar above small right angle conveyor in filling room
7. Down-flow laminar above large turntable in filling room
8. Down-flow laminar above vial sealing machine
9. One LAF down-flow unit for rubber stopper washing in component preparation room
10. One LAF down-flow unit for component wrapping before sterilization in component preparation room
11. Gradvel down-flow laminar unit with two HEPA filters for vial/ampoule washing
12. HEPA filter module on the dry heat sterilizer
13. All prefilters of the LAF units
14. Booster fan connected to the air handling system
15. Prefilters in the booster system
16. All grill in the air handling system

Frequency of Monitoring

Clearing & checking – once in 3 months
HEPA Filter – DOP Test – once a year
Integrity Test of HEPA filter by DOP Aerosol challenge using ATI Model TDA 2E particulate detection apparatus or any other suitable instrument. Velocity: Velocity reading using Alnor Velometer 6000P series suitable or any suitable instrument.

FEQUENCY: QUARTERLY

REMEDIES FOR HIGH MICROBIAL COUNTS

ST — 102
REMEDIES FOR HIGH MICROBIAL COUNTS


INTRODUCTION

It is an alarming situation to observe any microbial counts on the laminar because it is the critical area of product exposure. Hence immediate action is required when any counts are observed.

Also counts in other areas of the sterile room should be as possible to prevent any chance contamination of product. In case high microbial counts are observed, the following remedial action may be taken.

ON LAF

1. Confirm plates are taken into filling room only after they are kept under UV in the pass-through for 30 minutes.
2. Inspect each plate before exposure.
3. Plate exposure operator dose not cover plate during exposure.
4. Periodically spray benches with 70% IPA (Sterile). Sanitize LAF benches preferably before and after breaks.
5. Check for any leakages between bench and HEPA grill by smoke test.
6. Thoroughly sanitize the bench with 0.5% Aarshol after the day’s work.
7. If very high counts are observed, check the integrity of HEPA filters.

ROOM

1. Confirm the points 1 to 3 listed above.
2. Minimize the operators’ movements.
3. Thoroughly sanitize the required around the plate exposure location.
4. Clean the area periodically with sterile 70% IPA throughout the day.
5. Daily high counts will need area fumigation and change of disinfection agent.

PROCEDURE FOR ENTRY OF MAJOR EQUIPMENT INTO STREILE AREA

ST — 088
PROCEDURE FOR ENTRY OF MAJOR EQUIPMENT INTO STREILE AREA


By and large the major pieces of equipment into the sterile area such as large trolleys, ampoule filling sealing machine etc. by the very nature of the size will be moved into the sterile area either through the equipment entry door or through the change room.

Prior to moving such equipment into the sterile area, the production supervisor concerned and engineering department will ensure that it is in proper working condition. Additionally, it will be necessary to confirm that it is clean.

Just prior to the entry, the external portion of the machine will be sanitized with Sterile70% Isopropyl Alcohol and Sterile 2% Bacillocid solution (disinfectant). Initially, such a sanitized machine will be moved to the second cubical change room and retained there overnight under the UV lamp. On the following day, the machines external portion will once again be sanitized with Sterile 70% IPA and Sterile 2% Bacilloicd and then moved into the sterile area.

Should it be necessary, after the entry of the equipment, Fumigation may be carried out in the sterile room to ensure there has been no abnormal increase in Microbial Count due to the major piece of equipment.

Swab test should be taken of the equipment to confirm the proper disinfection.

MONITORING OF POSITIVE PRSSURE, AIR TEMERATURE AND RELATIVE HUMIDITY

ST — 069
MONITORING OF POSITIVE PRSSURE, AIR TEMERATURE AND RELATIVE HUMIDITY


Area under consideration: Class 100 to Class 10,000 under the same air handling units and air-conditioning plant and component preparation area (Class 10,000). Temperature Monitoring: Limit: Not to exceed 23ºC.

1. One calibrated thermometer permanently fixed on the body of 12’ LAF unit, which can be seen from the view panel in corridor.
2. The supervisor of sterile area must read and record the temperature of sterile room at any time between 11.30 hours – 14.00 hours on all filling days.
3. The chart is can annual record for the temperature in the one room.

The instrument is not calibrated semi-annually

Positive Pressure Monitoring: Daily Record

1. Filing room and change room pressure indicating manometers are mounted on a board outside the filling room in the adjoining passage.
2. the supervisor must read and record the pressure of the rooms in the ‘Daily Pressure Record’ chart at the time of recording temperature during the working hours.
3. Simultaneously, the pressure reading of each manometer mound on the LAF mentioned below should be similarly recoreded.

A. Filling Room

2 manometers mounted on one ft LAF (horizontal)

1 manometer mounted on one down-flow Gradvel laminar used for ampoule filling

1 manometer mounted on one4 ft. Gradvel down-flow laminar used for aseptic filtration

1 manometer mounted on the down-flow laminar above small right angle conveyor

1 manometer mounted on the down-flow laminar large turntable

Pressure Differential Across Terminal HEPA Filter Monitoring






The manometers indicating pressure differential across the terminal HEPA filter in the filling room and change rooms are mounted on a board outside the filling room in the adjoining passage. The pressure differential reading are recorded monthly

B. Component Preparation Area

One monometer on the vertical down-flow Gradvel laminar on the vial/ampoule washing machine.

One monometer on the vertical down-flow laminar on the final rubber stopper washing machine.

One monometer on vertical down-flow laminar above the table used for component wraping.

One manometer on vertical down-flow laminar flow hood above the vial sealing machine.

4. The filling room pressure must be grater than the adjacent 3rd change room pressure by 1.25 mm of water gauge (i.e.0.05 inches of water gauge).Similarly the 3rd change room pressure must be greater than the 2nd change room pressure by 1.25 mm water gauge. The 2nd change room pressure must be grater than 1st change room pressure by 1.25 mm water gauge and the 1st change room pressure must be grater than the outside passage by 1.25 mm water gauge.

Relative Humidity Monitoring

Sterile filling room is daily monitored for relative humidity. Dial type ‘Barigo’ brand instrument for measuring humidity is kept near the temperature indicator in the filling room. Humidity is recorded on all filling days in the prepared format. Limit not more than 55%. The instrument is calibrated semi-annually.

MONITORING OF HEPA FILTERS

ST — 068
MONITORING OF HEPA FILTERS


Air supply to the sterile area must be appropriately filtered to minimize the potential contamination by both viable and nonviable particulate matter. HEPA filters are used to filter the air, both at terminal points of blowers and in laminar flows where product will be expressed. The HEPA Filter fixtures are to be monitored periodically by the following tests to check that they maintain their rated efficiency.

1. Air velocity
2. Pressure drop across HEPA filters
3. Checking integrity of HEPA filter using cold DOP
4. Air direction

In addition to monitoring the filter surface, the seal of each filter element to its frame and the seal between the filter frame and the filter housing must be verify that particles are not escaping around the filter.

1. Air Velocity Measurement of HEPA Filters

Air velocity of laminar flow hoods is measured to assure an acceptable level airflow in the sterile area, component preparation area, and all terminal HEPA filters are to be monitored.

Equipment Used: Alnor Velometer no. 600 P

PROCEDURE

In case of laminar flow hoods, measure the air velocity by positioning the velometer probe at a distance of one foot above the work surface. Read velocity directly from the meter and record. Six reading should be taken and the average calculated.

In case of terminal HEPA filters, the velocity should be taken six inches away from the grill and six readings should be taken and averaged and these reading should be taken for calculating air changes in the room.

ACEPTANCE CRITERA
A minimum air velocity at work surface of 0.3 meters/second (i.e. 60.0 ft/minute) for vertical laminar flow hoods and a minimum velocity of 0.45 meters/second (i.e. ft/minute) for horizontal laminar flow hoods.

*If velocity drops below the acceptable criteria, replace the filters

Frequency of test: Quarterly

2. Procedure For Measuring Pressure Drop Across HEPA Filter

The amount of pressure drop across terminally mounted or laminar flow hood HEPA filter is related to the particulate loading of the filter or the amount of blocking of the filter output. The life of HEPA filter can be improved by cleaning the pre-filters in air handling units frequently. When the pressure drop across the HEPA filter reaches above the limit, the filter must be changed. Limit: 2’’ of water gauge (i.e. 50.8 mm of water gauge)

PROCEDURE

EQUIPMENT

1. Two sampling tubes, one upstream of the filter and one downstream.
2. Calibrated Magnehelic gauges or inclined manometer (zero adjusted)

Place one end of the sampling tube in the upstream of the filter under test, and connect the other end to the inlet of the calibrated Megnehelic or inclined manometer. Place one end of the other sampling tube downstream of the HEPA filter and the other end to the outlet of the Megnehelic gauge or inclined manometer, and record the reading directly from the Megnehelic gauge manometer.

Frequency of Testing: Quarterly

Limit = pressure drop not more than 2 inches of water gauge (i.e. 50.8 mm of water gauge). If the pressure drop is more than the limit, the filter has to be replaced.

3. 3. Procedure For Checking Integrity Of HEPA Filter Using DOP

Air supply to the sterile area must be appropriately filtered to minimize the potential contamination by both viable and nonviable particulate matter. HEPA filters are used to filter the air, both at terminal points of blows and in laminar flow where product will be exposed. To check the efficiency of particulate retention, the HEPA filter fixtures are to be monitored. The porosity of HWPA filter is 0.3 micron. Therefore, aerosol of DOP can be used to check the efficiency of retention since it has an average particle size of 0.45.

PROCEDURE
Start the system and introduce DOP in the upstream of the HEPA filter. Scan the down stream flow with suitable light scattering photometer which detects the DOP particles. Whole of filter surface and filter frame/housing to be scanned. Any leakages if observed, to be mentioned in a diagram and can be rectified, if leaks are within limit.

Frequency of integrity testing DOP of HEPA filters using DOP is at least once a year or when there is any replacement of filter, gasket housing etc.

Acceptance Limit is = 99.997% retention of particles.

Direction of Air-flow

Direction of air-flow of all terminal HEPA filters and HEPA filters of all laminar flow hoods are also monitored using smoke stick Titanium Tetrachloride (TiCl4). The smoke sticks are moved in front of the HEPA filters to note the direction of the airflow to confirm that the movement is in straight line and that there is not turbulence at critical areas of operation.

CONTROL AND PLACEMENT PLANS OF BIOLOGICL MONITORS

ST — 043
CONTROL AND PLACEMENT PLANS OF BIOLOGICL MONITORS


INTRODUCTION

Monitoring and controlling of vial micro-organism is as important as the controlling of non-viable particulate matter which often transport viable micro-organism, because there are chances that these viable micro-organism may find their way into the product and contaminate the product.

The most common method of monitoring the air in the sterile area is by the use of settling plates containing soybean casein digest agar.

1. Soybean casein digest agar medium is used to identify the presence of microbial organisms in containing soybean digest agar.
2. Petridishes containing soybean casein digest agar medium suitably prepared and provided by QC are marked with numbers that correspond to the locations where plates are to be exposed.
3. Plates should be exposed at work height, on tabletops or carts positioned to collect representative sample.
4. Sterile room must be monitored whether or not there is activity on every working day.
5. Plates should be exposed during each shift working.
6. One plate should be exposed upto 100 sq. ft of floor area and one additional plate for each additional 100 sq. ft of floor area.
7. Expose one plate at the location of highest particle count determined by long count.
8. All LAF hoods must be monitored in unmanned state.
9. One plate is kept as negative control; on this plate the time at which plates are to be exposed is marked.
10. All the plates are kept in pass box under UV lamp in lid sown position half an before the exposure commences.
11. Plates are exposed for minimum 60 minutes during working hours and then kept back in the pass box to be taken for incubation.
12. Plates are incubated at 30 ºC to 35 ºC for 48 hours and then 20 ºC to 25 ºC for further 72 hours.
13. At the end of 48 hours, total number of colonies of bacteria and fungus are down in plate count of sterile area from by equality control microbiologist and second reading taken after 72 hours for fungus.
14. Area disinfection procedure is reviewed and attention is paid to the area where high counts are observed consistently.
15. 5% Copper Sulphate treatment or 2% Bacillocid treatment is carried out when fungus presence is observed in the area consistently for two-three days.

FREQUENCY - DAILY

CHECK LIST OF JOBS START UP AND AFTER SHUTDOWN

ST — 016
CHECK LIST OF JOBS START UP AND AFTER SHUTDOWN


A. WASHING AREA

1. Cleaning of compresses air filters. (Shavo-Norgren)
2. Cleaning of DM water storage tank.
3. Setting of vials washing machine.
4. Fixing of filter of down-flow unit and to check working. Adjust manometer oil to zero. If HEPA is removed, check DOS test and air velocity.
5. Keep SS boxes washed with DM water.
6. Fix cleaned DM water filters in respective housings.
7. Check all tubing, if required, changed them.
8. Cleaning of split AC filters.

B. RUBBER STOPPERS TREATMENT

1. Get the washing machine cleaned thoroughly.
2. Check connections of steam and DM water line.
3. Clean SS Pall filters, GS filter and in-line.
4. Clean SS pots and lids.
5. Clean distilled water storage tanks and 20 Lt. capacity pressure unit.
6. Keep in the area, plastic containers required to soak the stoppers.
7. Clean membrane holder assembly and refill it.
8. Fix filter of air down-flow unit and check working. If HEPA is removed check DOS test and air velocity.
9. Set manometer oil level upto zero.
10. Check availability of Benzalkonium Chloride & Hydrochloric Acid in washing area.

C. STERILZATION

1. Clean, dry and connect distilled water storage tank.
2. Check working of thermostatic control.
3. Run distilled water plant for 2-3 hours and discard the collection.
4. Check leakages if any during run of distilled water plant. Check water conductivity.
5. Get chemical analysis of distilled water done.
6. Check rate of distilled water collection per hour.
7. Check cleaned SS Pall filter is fixed to the DM water inlet before running the plant.
8. Check working of autoclave thermograph. Check inkbottle for sufficient quantity of link. If possible, calibrate thermograph.
9. Normal servicing of autoclave is done by vendor.
10. Run autoclave for 30 minutes and observe any leakages through steam valves, door gasket and joint. Check working of dial thermometer.
11. Check fixing and conditions of air in-let filter.
12. Check working of pressure gagues.
13. Clean the autoclave with distilled water and Benzalkonium Chloride solution before operating.
14. Clean carriage of sterilizer chamber with vacuum cleaner and then with distilled water and sponge.
15. Cleaning carriage of sterilizer with diluted Hydrochloric Acid and then with water.
16. DOP test of HEPA filter module and air velocity.
17. Run dry sterilizer empty at 300 ºC for 1 hour to check its heating and cooling functions.
18. Check working of thermograph for temperature and time and working of HEPA filter after heating cycle.
19. Checks working of inter locking system of autoclave and dry sterilizer.
20. Check hot air leakages through door gasket.

D. COMPOUDING ROOM

1. Check working of homogenizer.
2. Replace N2 25 mm filter.
3. Connect N2 line for sparging and filtration.
4. Remove unwanted material from tables in compounding room.
5. Keep back material removed from sterile area.
6. Replace all UV tubes after noting intensity.
7. Provide new sippers for operators.
8. Check working of conveyer & filling machine.
9. Check grease in filing machine.
10. Check all nitrogen, oxygen and LPG gas lines for working and leakages. Check all gas liners are correctly identified.
11. Check the pressure of room and change rooms.
12. Check temperature of filling room.
13. Replace old sponge used for wiping foot soles change room.
14. Calculate air change per hour from velocity of air through each terminal HEPA filters.
15. Open all return air riser dampers.
16. Check working of fumigation switch and plate.
17. Get area cleaned with 0.5 % Aarshol again before starting fumigation.
18. Check working of down-flow unit, portable laminar including DOP test and air velocity.
19. Check working of ampoules filling machine if required.

E. SEALING ROOM

1. Run machine without vials for few minutes. Observe any abnormal sound.
2. Take trial of 2 ml vials sealing.
3. Lubricate the machine and keep ready for use.
4. Thoroughly wipe and clean vibrator with 70 % IPA.

F. INSPECTION ROOM

1. Keep batch ready in inspection room.
2. Remove labels of the product other than those that are under inspection.
3. Take trial of machine without vials.

G. LABELLING ROOM

1. Keep batch and labels ready for labeling on the first day of the start up.
2. Keep about 3.0 kg. Gum Acacia in container.
3. Remove previously labelled products from area.
4. Check al accessories required for labeling.

H. PACKING ROOM

1. Keep packing materials, batch ready for packing.
2. Check all accessories required for packing.
3. Confirm line clearance before packing start up.

I. DM WATER PLANT

1. Formaldehyde treatment and double regeneration of DM water plant. Formaldehyde treatment should be given only if viable counts are high.
2. Check DM water free from acid, alkali, formaldehyde traces for pH.
3. Clean SS storage tank used for multicolumn distillation still.