OPERATION AND MAINTENANCE OF INCUBATOR MAINTAINED AT 22 OC

1.0 OBJECTIVE
To ensure that the incubator performs satisfactorily and maintain accurate temperature for Microbial growth.
2.0 SCOPE
The SOP covers procedure for operation and calibration of incubator and is applicable to Quality Control Department formulation Units
3.0 RESPONSIBILITY
Microbiologist.
4.0 ACCOUNTABILITY
Department Head.
5.0 PROCEDURE
5.1 Ensure that the power supply to the incubator is switched ‘OFF’.
5.2 Dedust the incubator daily externally with a clean dry cloth.
5.3 Once a week remove adhered dust by wet mopping using detergent solution. Afterwards wipe the surface with a clean dry cloth to remove traces of detergent.
5.4 Once in a month clean the interior surfaces with 2.5 % savlon solution using a clean cloth.
6.0 OPERATING PROCEDURE
6.1 Ensure that the incubator is properly connected to the power supply.
6.2 Switch on the main .
6.3 Turn on the red colour power knob towards 0-1.
6.4 Turn on the cooling knob towards 0-1.
6.5 To set the incubator at 22°C , set the lower temperature 21 OC by pressing the ‘SET POINT -1’ and simultaneously adjust the temperature with the help of screw of SET and RST by screw driver.
6.6 .Set the higher temperature 23 OC by pressing the ‘SET POINT -2’ and simultaneously adjust the temperature with the help of screw of SET and RST by screw driver.
6.7 In the same manner the incubator can be set to 37°, 44° and 55°C whenever required by setting the lower temperature to 36°,43° and 54° C respectively and by setting the higher temperature to 38°,45° and 56° C respectively.
6.8 Record the temperature twice daily. i.e. in the morning and in the evening. The temperature should not differ ± 2° C from the set temperature.
7.0 Trouble shooting problems and remedial action :
7.1 The temperature display is not glowing. Check for power supply and proper electrical connections of instruments with power point.
7.2 Temperature is not even in the incubator. The air circulating fan may not be functioning. Check for it.
7.3 Report any discrepancy observed during operation or temperature monitoring to Q.C. Executive and notify the defect to Maintenance Department.
8.0 CALIBRATION
8.1 Set the incubator temperature to 22°C. Wait till the set temperature is reached.
8.2 Take a calibrated thermometer and dip it in a 500 ml beaker filled to 3/4 of the volume with Glycerol AR grade.
8.3 Keep the beaker inside, at the center of the incubator. close the incubator door. Allow the temperature to equilibrate for 30 minutes.
8.4 Observe the temperature shown by the thermometer. The temperature shown by the
display and by thermometer shall not differ by more than 0.5°C.
8.5 Record the temperature at two time intervals ( with a gap of 6 hours) in the temperature record.
8.6 By following the same procedure as above carry out calibration by setting the incubator temperature to 37°C, 44°C and 55°C.
8.7 Record any discrepancy observed during operation or during temperature monitoring to Quality Control Executive and notify the defect to technical assistant for rectification. Affix “BREAK DOWN” label on the instrument.
9.0 FREQUENCY OF CALIBRATION :
9.1 Once a month and after each maintenance job.
9.2 Record the calibration record in the format prescribed

OPERATING PROCEDURE FOR DIANA AIR SAMPLER (MICROMED)

1.0 OBJECTIVE:
To estimate Microbial Load in Production Area by Air sampling kit.
2.0 SCOPE
This SOP is applicable to Quality Control Department (Microbiology Lab).
3.0 RESPONSIBILITY:
Sr. Executive.
4.0 ACCOUNTABILITY :
Department Head
5.0 PROCEDURE:
5.1 Take sampling kit to area where sampling to be carried out.
5.2 Remove the sampler from kit and open the backside lid .
5.3 Put batteries in the sampler and ensure that it is in working condition.
5.4 Put the sterilized hand gloves.
5.5 Remove the strip holder and sanitize the complete assembly by isopropyl alcohol
(70% filtered through 0.2u membrane filter).
5.6 Remove agar strip from sealed sterile pouch and insert carefully into the strip holder.
5.7 Adjust the timer by a knob provided and set the time from 0 to 1 minute , 2 minute
upto maximum 4 minutes.
5.8 Press starts button .
5.9 After completion of sampling remove the agar strip and again put carefully in the sterile pouch.
5.10 Incubate the strip in an incubator at 37 °C for five days.
5.11 Finally sanitize the air sampler thoroughly and keep it sampler box .
6.0 PRECAUTION
6.1 Do not autoclave the air sampler kit , electronic circuit will get spoiled.
6.2 Handle carefully and check the batteries for spillage if any.

MICROBIAL LIMIT TESTS FOR RAW MATERIALS AND FINISHED PRODUCTS

1.0 OBJECTIVE:
To determine the bioload ofbacteria ,yeast and molds and specific pathogens in raw material and finished products.
2.0 SCOPE
This SOP is applicable to Quality Control Department (Microbiology Lab).
3.0 RESPONSIBILITY :
Sr. Executive.
4.0 ACCOUNTABILITY :
Department Head
5.0 PROCEDURE:
5.1 SAMPLE PREPARATION:
5.1.1 Total Aerobic Microbial Count :
Use the plate method for substance that are sufficiently soluble or translucent to permit the use of method; otherwise, use the multiple tube method.
5.1.2 For Water Soluble Products :
Dissolve 10 gms or 10 mL of substance in case of Raw material and 5gm or 5ml of finished product being examined in 100 mL, of soyabean casein digest medium and fluid lactose broth.
A suitable surface active agents such as 0.1% w/v of polysorbate, may be added to assist the suspension of poorly wettable substances.
5.1.3 For Fatty Products :
Homogenize 10gm or 10 mL of the preparation being examined with 5 gms of polysorbate 20, or polysorbate80. If necessary, heat to not more than 40°C. Mix carefully. Add 85mL of buffered sodium chloride – peptone solution pH7.0 or any other suitable medium shown to have no antimicrobial activity like fluid soyabean casein digest medium and make up the volume 100ml. Temperature should not exceed more than 40°C. If necessary maintain this temperature for the shortest time for necessary formation of an emulsion and is any case for not more than 30 minutes. If necessary, adjust the pH around 7.0
6.0 Determination of total microbial count in raw materials :
PROCEDURE :
6.1 a) General procedure for total microbial count : (Bacteria and Fungi)
1.0 Transfer 1 mL of dilution of substance being examined aseptically into two sterile pertiplates having 9 to 10 cm in diameter, labeled on plate as ‘Bacteria’ and on other plate as ‘Fungi’.
Add 15 ml of freshly prepared, sterilized soyabean casein digest agar into one pertiplate labeled as ‘Bacteria’ and add 15 mL of sterile sabouraud dextrose agar into second pertiplate labeled as ‘Fungi’ and allow the plates to solidify at room temperatures. Prepare at least two such plates for bacteria and two for fungi. Incubate the bacterial plates at 37°C for 3 days and incubate the fungi plates at 20° to 25° C for 5 days. Count the colonies and calculate the results.
6.2 b) Membrane filtration :
6.2.1 Use membrane filter 50 mm in diameter and having a nominal pore size not greater than 0.45 µm the effectiveness of which in retaining bacterial has been established for the type of preparation being examined. Sterilized and assemble the filtration the filtration apparatus.
6.2.2 Transfer 10 mL or quantity of each dilution containing 1 gms of the preparation being examined to each of two membrane filters and filter immediately. If necessary, dilute the pretreated preparation so that a colony count of 10 to 100 may be expected. Wash each of about 100 ml, of a sterile 1% peptone solution, pH 7.0. for fatty substances add to the liquid polysorbate 20 or polysorbate 80. Transfer one of the membrane filters, intend for the enumeration of bacterial , to the surface of the plate of casein soyabean digest agar and the other, intended for the enumeration of fungi, to the surface of the plate of sabouraud dextrose agar.
6.2.3 Incubate the plates for 5 days, unless a more reliable count is obtained in shorter time, at 37°C in the test for bacterial and 20° to 25°C in the test for fungi. Count the number of colonies that are formed, calculate the number of micro-organisms per gms or per ml, of the preparation being examined.
7.0 Determination of pathogenic organism for raw materials and finished products :
Dissolve 10 gms / 10mL ( Incase of viscous material 5 gm/5ml) , refer current Standard Testing Procedure for aerobic microbial count and for pathogens.
Pseudomonas aeruginosa

Escherichia

Salmonellae

Staphylococcus

ACCEPTANCE CRITERIA :

*-Total microbial count including bacteria and yeast and moulds.

ENTRANCE PROCEDURE FOR MICROBIOLOGY AREA.

1.0 OBJECTIVE
To lay down a procedure for entrance in microbiology working area.
2.0 SCOPE
This SOP is applicable to Quality Control Department Formulation Units
3.0 RESPONSIBILITY
Microbiologist.
4.0 ACCOUNTABILITY
Department Head.
5.0 PREPARATION OF DISINFECTANT SOLUTION.
5.1 Add 25 ml Dettol in 975 ml of purified water in S.S. Bowl to produce 2.5% solution.
5.2 Add 25 ml Savlon in 975 ml of purified water in S.S. Bowl to produce 2.5% solution.
5.3 Add 70ml isopropyl alcohol in 30 ml purified water in Bottle to produce 70% I.P.A. solution and filter through 0.45 micron membrane.
5.4 Daily prepare fresh Savlon and Dettol solution for cleaning and prepare 70% alcohol
once a week.
6.0 PROCEDURE
6.1 Remove street shoes and Apron in Ist change room and cross the bench by sitting on it.
6.2 Wash the hands with the Savlon or dettol prepared as above.
6.3 Enter into the II nd change room And wear the sterile Garments as follows, First wear the mask and put a head guard. Then wear the sterile gown followed by Booties.
6.4 Enter into IIIrd change room and put the sterile gloves, wash with 70% I.P.A and enter
into the testing area through cross over bench

EFFICACY TESTING OF DISINFECTANTS

1.0 OBJECTIVE
To lay down the procedure to determine the efficacy of the disinfectants being used for house keeping activities.
2.0 SCOPE
This SOP is applicable to the Quality Control Department (Microbiology Lab).
3.0 RESPONSIBILITY
Microbiologist.
4.0 ACCOUNTABILITY
Department Head.
5.0 PROCEDURE
5.1 Ensure that the availability of following material before start of analysis.
1) Pure cultures of Staphylococcus aureus ATCC 6538 &
Pseudomonas aeruginosa ATCC 9027
2) Sterilized Conical flasks ( 250 ml capacity)
3) Sterilized graduated pipettes ( 1 ml )
4) Sterilized Petriplates
5) Sterilized test tubes (18 x 150 mm)
6) Nutrient agar / Soya bean casein digest agar
7) Nutrient broth / Soya bean casein digest medium
8) Inactivating agent (Lecithin / Sodium thiosulfate/ Sodium thioglycollate)
5.2 Preparation of Inoculum:
5.2.1 Inoculate the organism in nutrient or soyabean casein digest medium and incubate at 37°C for 24 hours. Inoculate the same organism by transferring loop full of previous suspension in nutrient medium continuously two days.
5.2.2 Finally inoculate 100 ml of nutrient broth or Soyabean casein digest medium With one ml of the activated culture of both the organisms, individually and incubate At 37°C for 16-18 hrs. Keep the activated culture in refrigerator.
5.2.3 Estimate the viable count of bacteria per ml of the medium for both the organisms By pour plate method by diluting the culture appropriately to get 30 - 300 colonies Per plate.
5.3 Preparation of disinfectant :
5.3.1 Prepare the disinfectant solution in different concentration like 0.5%, 1.0%, 1.5% & 2.5% in 250 ml conical flask .
5.3.2 Add 1 ml of the cell suspension (concentration 10 5) of each culture, individually to the disinfectant solution, carefully and shake well.
5.3.3 After 10 minutes of contact time aseptically remove 1 ml of solution from the flask and transfer to tubes containing 9 ml of a sterile solution of inactivator . Shake well.
5.3.4 Determine the number of viable bacteria per ml present in the solution by using pour plate method and incubate at 37°C for 48 hrs. Record the result
5.3.5 Use any one inactivator of the following depending on the type of disinfectant. The inactivators are Sodium thiosulphate 5 % w/ v solution.
6.0 ACCEPTANCE CRITERIA
Use only those concentration where there is 90% reduction of microbial count .

IDENTIFICATION OF BACTERIAL ISOLATES

1.0 OBJECTIVE
To lay down the procedure for identification of the bacterial colonies obtained during the plate exposure in production area to know about the flora present in the production environment.
2.0 SCOPE
This SOP is applicable to the Quality Control Department (Microbiology Lab).
3.0 RESPONSIBILITY
Microbiologist/ Quality Control Executive
4.0 ACCOUNTABILITY
Department Head.
5.0 PROCEDURE
5.1 Pick the individual colonies from the plates exposed in change rooms, secondary packing rooms and finished goods stores.
5.2 Purify the colonies, if necessary by streaking on to Soyabean casein digest agar plate.
5.3 Observe and record the morphological characters of the colonies such as shape, elevation, colour and margins in . Record all the observation.
5.4 Using sterile inoculating technique, inoculate the organism on two soyabean casein digest agar slants. Use one slant culture to determine the cultural characteristics and the other to repeat any of the tests , if necessary as stock.
5.5 Make a smear of the colony by taking with a loop and subject it to Gram’s Staining procedure. Observe under microscope and note the reaction , morphology and arrangement of the cells.
5.6 Using aseptic technique ,inoculate the required media , to carry out the biochemical tests and incubate at 37°C for 24 to 72 hrs. Record the results.

OPERATION AND CALIBRATION OF PRECISION STANDARD ELECTRONIC BALANCE (OHAUS)

1.0 OBJECTIVE
To ensure that instrument performs satisfactorily and gives accurate and reproducible results.
2.0 SCOPE
This sop is applicable to the Quality Control Department.
3.0 RESPONSIBILITY
Quality Control Chemist/Executives
4.0 ACCOUNTABILITY
Department Head.
5.0 GENERAL CLEANING PROCEDURE
5.1 Daily clean the external surface of the balance with dry mop immediately after use.
5.2 Once in a month clean the external surface with a wet mop dipped in 2.5 % savlon solution and ensure that no water goes into the balance while cleaning.
6.0 PROCEDURE :
6.1 Place the balance in a place which is free from excessive air currents, vibration and temperature extremes.
6.2 Keep the balance on a leveled work surface.
6.3 Make sure the hole in the pan support faces the rear of the balance and place the pan on the support making sure that the guide pin is inserted in the hole in the pan support.
6.4 Plug the molded connector of the adopter into the receptacle at the rear of the balance and plug the adopter into power socket.
6.5 Turn the balance ‘ON’ when no load is on the pan ,by pressing the ON TARE button.
6.6 After the display check is over , the display will momentarily be blank and then indicate ‘* 0.00g’.
6.7 Weigh the sample as follows :
ON TARE
6. 7.1 Place a clean butter paper on the platter, and depress the "ON TARE" button twice.
6.7. 2 The weight window shows 0.00 kg.(If you remove the butter paper, the display reads the tare weight of the paper)
6.7.3 Transfer the substance to be weighed carefully on to the butter paper as required. Note the weight.
6.7. 4 Transfer the substance to the required container and place the butter paper on the pan. The balance displays any weight remained on the paper. Note the weight. Calculate the actual weight transferred.
7.0 Calibration against standard weights
7.1 Ensure that the power supply to the balance is switched ‘ OFF’ before cleaning
7.2 Clean the pan with a clean dry cloth.
7.3 Check that the air bubble is in the center of the level and of necessary adjust the level by turning the leveling screws and close the balance doors.
7.4 Switch on the balance and allow it to stabilize for 30 minutes.
7.5 Check the weight of the following standard weights 100 gm, 200 gm, 2000 gm.
7.6 Record all the results in the format as per annexure-I
7.7 ACCEPTANCE CRITRIA
For 100 gm ± 0.5 gm,
For 200 gm ± 0.5 gm,
For 2000 gm ± 2 gm.
7.8 Report for any discrepancy noted at the time of calibration or operating the instrument to Department Head and notify the defect to the technical officer for rectifying the instrument. Affix a “BREAKDOWN LABEL” to the balance and discontinue the use till the balance is rectified.

OPERATION AND MONITORING OF THE OIL FREE VACUUM PUMP(MILLIPORE).

1.0 OBJECTIVE
To lay down the procedure for Operation and maintenance of Oil free vacuum pump .
2.0 SCOPE
This sop is applicable to the Quality Control Department .
3.0 RESPONSIBILITY
Microbiologist
4.0 ACCOUNTABILITY
Department Head
5.0 GENERAL CLEANING PROCEDURE
5.1 Ensure that the power supply to the equipment is switched OFF before cleaning.
5.2 Dedust the equipment daily externally with a clean dry cloth.
5.3 Once in a week remove adhered dust by wet mopping using detergent solution. Afterwards wipe the surface with a clean dry cloth to remove traces of detergent.
5.4 Precaution has to be taken to clean the oven immediately with dry cloth to remove the moisture.
5.5 Once in a month clean the external surface with a wet mop dipped in 5 % Savlon solution and ensure that no water goes into the vacuum pump while cleaning.
6.0 PROCEDURE
6.1 Select the appropriately sized tube.
6.2 Prepare the necessary equipment or filter holder and connect the tubing to the equipment.
6.3 Use a vacuum flask - water trap, allowing a 0.22 µ vent filter between the vacuum pump and the filter holder.
6.4 Do not turn on the pump with all tubing and equipment fully connected. The pump may not function properly when turned on with initial load.
6.5 Plug the power cord into a grounded electrical socket.
6.6 Turn on the pump by flicking the switch, located on the right side of the pump.
6.7 Connect the tubing from the filter holder to the hose adapter meant for vacuum application of the pump and begin the filtration.
6.8 If filtration by pressure is required connect the tubing to the adapter meant for pressure application.
6.9 After completing the filtration , run the pump for about 30 sec. freely and turn off.
6.10 Disassemble the tubing first from the pump and then from the filter holder.
6.11 If the pump’s thermal over load switch automatically shuts off the motor, disconnect the tubing and allow the pump to cool for at least 10 min. before restarting.
6.12 Do not lubricate any of the parts of pump with grease, oil etc.,
6.13 Do not clean with acids , caustic or chlorinated solutions.
6.14 Do not tighten regulator knobs fully. This can cause jamming of the regulators.
7.0 PRECAUTION
7.1 Do not lubricate any of the parts of pump with grease, oil etc.
7.2 Do not clean with acids, caustic or chlorinated solutions.
7.3 Do not tighten regulator knobs fully. This can cause jamming of the regulator.
8.0 CALIBRATION OF VACUUM GAUGE
8.1 Calibration of vacuum gauge will be done by engineering department.
8.2 Report any discrepancy during operating the instrument to Department Head and notify the defect to service engineer to rectify the defect. Affix “BREAK DOWN” label on the instrument.
9.0 FREQUENCY OF CALIBRATION
Once a year and after each Maintenance Job.

OPERATION AND MONITORING OF THE CYCLOMIXER (REMI).

1.0 OBJECTIVE
To lay down the operating procedure for Cyclomixer.
2.0 SCOPE
This sop is applicable to the Quality Control Department.
3.0 RESPONSIBILITY
Quality Control Chemist/ Microbiologist
4.0 ACCOUNTABILITY
Department Head.
5.0 GENERAL CLEANING PROCEDURE
5.1 Daily clean the external surface of the cyclomixer with dry mop immediately after use.
5.2 Once in a month clean the external surface with a wet mop dipped in 2.5 %
Savlon solution and ensure that no water goes into the cyclomixer while cleaning.
6.0 Procedure
6.1 Place the cyclomixer on a rigid flat level or bench which is free from Vibration.
6.2 Sufficient clear area must be available around the cyclomixer to allow uninterrupted rotation of rubber top.
6.3 Connect the power plug to a suitable power socket having proper earthing.
6.4 When the unit is connected to power supply the lamp will glow.
6.5 Put ‘ON’ the switch and control the speed by rotating the regulator in clock wise & anticlock wise direction.
6.6 Switch off immediately after use.
7.0 Trouble shooting
7.1 If the speed control is moved clockwise and the pilot lamp is on, the instrument does not start, turn the speed control anticloclwise. Disconnect the unit from the power supply. Call the electrical person to check the wiring.

Procedure for Operation and Monitoring of Refrigerator

1.0 OBJECTIVE
To lay down the procedure for operation and monitoring of Refrigerator.
2.0 SCOPE
This sop covers the procedure for operation and monitoring of Refrigerator and is applicable for Quality Control Department
3.0 RESPONSIBILITY
QC Chemist/ Microbiologist
4.0 ACCOUNTABILITY
Department Head.
5.0 GENERAL CLEANING PROCEDURE
5.1 De dust the refrigerator daily externally with a clean dry cloth.
5.2 Once a week remove adhered dust by wet mopping using detergent solution . Afterwards wipe the surface with a clean dry cloth to remove traces of detergent.
5.3 Once in a month mop the interior surfaces with 2.5 % Savlon solution and then with a clean dry cloth.
6.0 OPERATING PROCEDURE
6.1 Ensure that the refrigerator is properly connected to the power supply, through a voltage stabilizer.
6.2 Switch ‘ON’ the main switch .
6.3 Keep the material in the fridge and close the door gently to avoid jerks.
6.4 Keep a calibrated thermometer at any one place in the fridge chamber and record the temperature, to know whether the fridge is functioning properly or not, once in the morning and once in the evening.
6.5 Report any discrepancy observed during operation or temperature monitoring to Quality Control executive and notify the defect to Engineering Department

FINGER DAB TEST

1.0 OBJECTIVE
To lay down a procedure for finger dab test to check the cleanliness of personnel.
2.0 SCOPE
This SOP is applicable to Quality Control Department.
3.0 RESPONSIBILITY
Microbiologist
4.0 ACCOUNTABILITY
Department Head
5.0 PROCEDURE
5.1 Prepare soyabean casein digest agar plates.
5.2 Take the plates to the test location.
5.3 Open the plate and ask the person to touch the agar surface with the fingers gently.
5.4 Close the plate quickly and bring to the lab.
5.5 Incubate soyabean casein digest agar plates at 30 - 35 OC for 3 days.
5.6 Count the number of colonies on each plate and record the observation.
6.0 FREQUENCY
6.1 Once a month 5 persons from each module.

SWAB TEST FOR LINEN

1.0 OBJECTIVE
To lay down a procedure for Swab Test of Linen.
2.0 SCOPE
This SOP covers the procedure for Swab Test of Linen and is applicable to Quality Control Department
3.0 RESPONSIBILITY
Microbiologist
4.0 ACCOUNTABILITY
Department Head.
5.0 PROCEDURE
5.1 Prepare absorbent cotton swab or ready made sterile swabs can be used.
5.2 Keep the prepared swab in test tube containing 1 to 2 ml normal saline. (Ensure that the swab gets moistened.) Ready made swabs can be used directly as such.
5.3 Sterilize the containers along with the swabs at 15 lb, 121 OC for 20 min.
5.4 Swab about 2 x 2 sq. inch area of the linen with two sterilized cotton swabs . And immerse the swab in test tube containing 10 ml of sterile normal saline.
5.5 Streak one of the swab from all the sides on the surface of the soyabean casein digest agar plate and the other on the surface of sabourauds dextrose agar plates.
5.6 Incubate soyabean casein digest agar and sabourauds dextrose agar plates at 37OC and 22 °C for 5 days respectively.
5.7 Count the number of colonies on each plate and record the observation in annexure-I.
6.0 FREQUENCY
6.1 Once a month .
7.0 ACCEPTANCE CRITERIA
Total microbial count = total bacterial count + total fungal count
Test: Finger dab
Alert Limit (Total microbial count):15
Action Limit (Total microbial count):25
6.1 If results are above alert limit, inform to concerned supervisor to improve the washing of the garment.
6.2 In case results reach the action limit, immediately instructions to be given to the concerned supervisor to change the lot of the garments and carry out investigation and take necessary action.

MICROBIAL COUNT MONITORING IN PRODUCTION AREA

1.0 Objective
To estimate Microbial Load in Production Area.
2.0 SCOPE
This SOP is applicable to Quality Control Department (Microbiology Lab).
3.0 Responsibility
Microbiologist
4.0 Accountability
Department Head
5.0 PROCEDURE
5.1 Plate Exposure method :
5.1.1 Prepare Soyabean Casein Digest agar (SCDA) and Sabouraud Dextrose agar (SDA)plates as per the current version of sop no. 32QC071 .
5.1.2 Incubate the plates for 24 hours at 37°C.
5.1.3 Carry the plates to production area for exposure.
5.1.4 Put the hand gloves and Clean the surface and outer side of plate by 70% isopropyl alcohol.
5.1.5 Open the plate carefully and keep it asper the time maintioned bellow .
5.1.6 Duration of Exposure :
30 minutes under working condition.
60 minutes under non-working condition.
5.1.6 After specified period of exposure, close the plates carefully and bring back to QC lab and incubate SCD agar plates at 37°C and SD agar plates at 22° C. plates after 5 days for colony forming units . Count colonies and record the result as per annexure-I .
5.1.8 Acceptable Microbial Levels

5.2 Air sampling with Dyna test air sampler :
Wrap the agar strip holder with aluminium foil and autoclave at 121°C (15 lbs) for 15 minutes. Carry the Dyna test unit to the test location. Carefully insert the pre sterilized agar strip into the holder and assemble the unit. Load the cells or connect the power point. Keep the timer switch at position one, sample the air for one minute. Focus the agar strip holder towards the area which is to be tested. Switch on the unit. After one minute the instrument will shut off automatically. Remove the agar strip from the holder and keep in the ‘case’ provided and incubate at desired temperature for 48-72 hours. Report the result as c.f.u/40 L of air samples. The instrument can draw 40 L of air on to the agar strip per minute.
5.2.2 Acceptable Microbial Levels :

5.3 Control :
5.3.1 If results are above alert limit, inform to concern supervisor to clean the area.
5.3.2 In case results reach the action levels, instructions will be given to concerned to stop the production. The process will be started only after rectification measures.
6.0 FREQUENCY
6.1 Twice a month and after each maintenance job.

AREA MONITORING OF MICROBIOLOGY LAB

1.0 OBJECTIVE
To lay down a procedure for microbial count in microbiology area.
2.0 SCOPE
This sop is applicable to Quality Control Department(microbiology lab).
3.0 RESPONSIBILITY
Microbiologist
4.0 ACCOUNTABILITY
Department Head
5.0 PROCEDURE
5.1 Prepare Soyabean Casein Digest Agar plates and Sabouraud’s Dextrose Agar Plates as per the current version of sop no. 32QC071.
5.2 Expose one soyabean casein digest agar plates and sabouraud’s dextrose agar plate as per the annexure-I for time specified as given below:
a. Critical area (i.e., on LAF bench) : 60 min
b. In other areas : 30 min.
5.3 Incubate the soyabean casein digest agar plates at 37OC and sabouraud dextrose agar plates at 22OC for 5 days.
5.4 Record the result as per annexure- I
5.5 Microbial Limits (CFU/Plate)

6.0 FREQUENCY
6.1 Once a Week and after every maintenance job.

FUMIGATION OF MICROBIOLOGY LAB

1.0 OBJECTIVE
To lay down a procedure for Fumigation of Microbiology Lab.
2.0 SCOPE
This SOP is applicable to Quality Control Department (Microbiology Lab).
3.0 RESPONSIBILITY
Microbiologist
4.0 ACCOUNTABILITY
Department Head.
5.0 PROCEDURE
5.1 Use safety goggles and hand gloves during fumigation.
5.2 Put ‘OFF’ the A/C unit .
5.3 Take Potassium Permanganate (about 15 gm.) in a petri dish and keep in the area where fumigation is to be carried out.
5.4 Place the petri plate on a polyethene bag.
5.5 Add about 25 ml of 35 % Formaldehyde solution to Potassium Permanganate .
5.6 Immediately close the area.
5.7 Label the area as “Area Under Fumigation” so that nobody enters the room.
5.8 Keep the room under fumigation for a minimum of 8 - 12 hrs.
5.9 Defumigate the room by putting on the A/C unit .
6.0 FREQUENCY :
6.1 once a week and after completion of any civil work.
Hazards of Formaldehyde :
1. It is toxic to inhalation and ingestion and causes irritation to eyes and respiratory tract.
2. Skin contact can cause dermatitis. Also cause skin burns.
3. Exposure to a concentration of 10 to 20 PPM can cause difficulty in breathing.
4. Slightly corrosive in nature, suspected carcinogen.
Fire Hazards :
1. Vapors of Formaldehyde are flammable and may form an explosive mixture with air.
2. It should be stored in a cool and well ventilated area.
3. Avoid storing below 16 Degree C because it forms a polymer ‘Paraformaldehyde’ which is a flammable solid which on heating may evolve a flammable gas and may explode.

SWAB SAMPLING FOR VALIDATION OF TEST SURFACES

1.0 OBJECTIVE
To lay down the procedure for swab sampling of test surfaces for validation
2.0 SCOPE
This SOP is applicable to Quality Control Department .
3.0 RESPONSIBILITY
Microbiologist.
4.0 ACCOUNTABILITY
Department Head.
5.0 PROCEDURE
5.1 MATERIAL & REAGENTS
SWAB : Sterilized Johnson’s bud/Hi-media’s sterile cotton swab
TRANSPORT CONTAINER : Capped test tubes made of glass/ cotton plugged test tubes
SAMPLING SOLVENT : Sterile Normal Saline.
5.2 SWAB SAMPLING PROCEDURE
5.2.1 Remove a swab from it’s protective bag using a clean latex hand glove.
5.2.2 Avoid touching the swab head to prevent it’s contamination.
5.2.3 Transfer the swab in transport container (test tube) containing 10 ml of sterile saline and allow the swab to soak completely.
5.2.4 Take out the swab from water and squeeze the tip against inner surface of test tube to remove excess water in such a manner that excess water drips inside the test tube.
5.2.5 Hold the stem of swab without touching the head of the swab.
5.2.6 Using one side of moistened swab wipe the test surface of 2” x 2” with 10 firm horizontal strokes.
5.2.7 At the end of each stroke, lift the swab carefully.
5.2.8 Turn the swab cover to its other side, wipe the test surface of 2 “ x 2” with 10 firm vertical strokes.
5.2.9 At the end of each stroke, lift the swab carefully.
5.2.10 Hold the stem of the swab without touching the head of the swab and let the swab deep into the transport container. Cap /plug the transport container and send for analysis after labeling the same.

PROCEDURE FOR PREPARATION OF CULTURE MEDIA

1.0 OBJECTIVE
To lay down a procedure for preparation of culture media.
2.0 SCOPE
This SOP covers the procedure for preperation of culture media and is applicable to Quality Control Department
3.0 RESPONSIBILITY
Microbiologist.
4.0 ACCOUNTABILITY
Department Head
5.0 PROCEDURE
5.1 Store dehydrated media in tightly closed bottles in the dark or as directed by manufacturer.
5.2 Follow the manufacturers direction for rehydration .
5.3 Check pH of the medium after rehydration and if necessary adjust the pH.
5.4 After rehydrating the medium dispense promptly into labeled flasks or tubes and cover with metal caps / plastic caps/ cotton plugs and wrap in butter paper and sterilize within two hours as per the manufacturers instructions.
5.5 Incubate the sterilized media for 24 hrs. before use at the appropriate temperature to check the contamination if any.
5.6 Store the media below 25 OC after pre-incubation and use within a week of preparation.
5.7 Check the nutritive properties of each new batch of medium using 100 cfu of the appropriate test organism and record the observation in format.
5.8 Use the dehydrated media as per the expiry given on container.
5.9 Records the preparation and sterilization of the culture media in a log book.
REASON FOR REVIEW
1. Routine review.
2. Scope modified.

Line clearance Procedure for dispensing area (Packing Materials)

1.0 OBJECTIVE
To lay down a procedure for line clearance of packing material dispensing area.
2.0 SCOPE
Primary and Secondary packing material dispensing area.
3.0 RESPONSIBILTY
Production officer.
4.0 ACCOUNTABILITY
Production Executive .
5.0 PROCEDURE
5.1 Check for the cleanliness of area and record the same in the checklist. (Annexure-I).
5.2 Inspect the dispensing area and thoroughly check for any left-overs of previous batch.
5.3 If all the points in check list is complied, then line clearance to be certified signing the check list.
5.4 The checklist should be preserved along with the Batch Packing Record.
ANNEXURE –I

Procedure for checking of dispensing operation (Packing materials)

1.0 OBJECTIVE
To lay down a procedure to check the points to be followed during dispensing operation of packing materials.
2.0 SCOPE
Primary and secondary packing material dispensing area.
3.0 RESPONSIBILTY
Production officer.
4.0 ACCOUNTABILITY
Production Executive.
5.0 PROCEDURE
5.1 Check the following points during dispensing operation.
5.2 Check the balance for cleanliness, its zero error and calibration as per SOP. No: xxxxxx
5.3 Ensure FIFO system is followed for dispensing.
5.4 Ensure that every container / package is having quality control approved label.
5.5 Ensure that the primary packing materials such as printed foil, plain foil, PVC film, PVDC film, are placed in poly bag after dispensing and before taking for packing.
5.6 Ensure each dispensed material is properly labelled and need to be preserved along with the batch packing record.
Ensure that cartons, catch covers, leaflets, shippers are dispensed exactly as per quantity in number wise and properly dispensed in HDPE crates with lid properly closed

Procedure for checking of dispensing operation (Raw material)

1.0 OBJECTIVE
To lay down a procedure to check the points to be followed during dispensing operation of raw material.
2.0 SCOPE
Raw Material Dispensing area I & II.
3.0 RESPONSIBILTY
Production officer.
4.0 ACCOUNTABILITY
Production Executive.
5.0 PROCEDURE
5.1 Check the following points during dispensing operation.
5.1.1 Check that materials dispensed are as per FIFO method.
5.1.2 Cross- check the values of moisture content and assay of each active ingredient against the A.R.No from SAP.
5.1.3 Check that the non – actives are dispensed first, followed by actives.
5.1.4 Ensure that double poly bags are used for dispensing.
5.1.5 Ensure dedicated marked and cleaned scoops are used for dispensing of active ingredients.
5.1.6 Ensure separate cleaned scoops are used for different non- actives.
5.1.7 Check for QC approved (Green) status label and the re-testing date on the container.
5.1.8 Check for the item description and item code on the approved label against the Manufacturing Work Order.
5.1.9 Check that the GRN No. on the approved label. Further check the under test label also matches correctly.
5.1.10 Check the gross weight of the container to be dispensed and the quantity matches with the labelled quantity.
5.1.11 Check that every container/ bag/ package is tightly closed before and after dispensing.
5.1.12 In case of loose containers, check for the weight as per the “ Loose container” label.
5.1.13 Check that the right capacity balance is used to weigh as per the required accuracy of net. Weight.
5.1.14 Check for the correctness of weight against the quantities in Manufacturing Work Order.
5.1.15 Ensure that every IPC/ Container/ Trolley is de-dusted externally before passing on to hold area / pass box respectively.
5.1.16 Ensure that the gloves used for dispensing of one active are not used for any other material.

Line clearance Procedure for dispensing area (Raw Materials)

1.0 OBJECTIVE
To lay down a procedure for line clearance of raw material dispensing area.
2.0 SCOPE
Raw material Dispensing area I & II.
3.0 RESPONSIBILTY
Production officer / QA officer.
4.0 ACCOUNTABILITY
Production Executive / QA Executive.
5.0 PROCEDURE
5.1 Check for the cleanliness of area and record the same in the checklist. (Annexure-I).
5.2 Inspect the dispensing area and thoroughly check for any visible contamination of previous product as per the checklist.
5.3 Recommend rewash, if visible contamination from the previous product is noticed.
5.4 If all the points in checklist is complied, then line clearance to be certified signing the check list.
5.5 The checklist should be preserved along with the Batch Manufacturing Record.

ANNEXURE –I

Procedure for Marking of Finished Product Shippers (Export)

1.0 OBJECTIVE
To lay down a procedure for marking of Finished product Shippers (Export.)
2.0 SCOPE
All Packing Halls
3.0 RESPONSIBILITY
Production officer.
4.0 ACCOUNTABILITY
Production Executive.
5.0 PROCEDURE
5.1 As per packing instructions given in the BPR the final shippers are over printed with Product, Batch No, Consignment details by klass marking and the same proof is marked in BPR.
Export labels are pasted as per the party requirement before dispatch from the factory

Procedure for Cleaning ,Calibration and Operation of the Analytical balance (METTLER AR 104)

1.0 OBJECTIVE
To lay down a procedure for cleaning, calibration & operation of the analytical balance (METTLER AR 104).
2.0 SCOPE
Module-4.
3.0 RESPONSIBILITY
Production officer.
QA chemist.
4.0 ACCOUNTABILITY
Production Executive.
5.0 PROCEDURE
5.1. Cleaning.
5.2. Calibration.
5.3. Operation.
5.4 Shut down.
5.1 Cleaning
5.1.1 Ensure that the power supply to the balance is switched ‘off’ before cleaning.
5.1.2 Clean the pan and inside of the balance with brush.
5.4.1 Clean the outside of the balance with clean and dry lint free duster every day.
5.2 Calibration
5.2.1 Frequency of calibration
5.2.2 Self Calibration Procedure
Frequency daily and after each maintenance job.
5.2.2.1 Clean the balance as per procedure given in 5.1
5.2.2.2 Check that air bubble is at the center of the level indicator and if required adjust the level by turning the leveling screws.
5.2.2.3 Switch on the balance and allow it to stabilize for 30 minutes.
5.2.2.4 Press the ‘cal’ button.The display should read ‘CAL’ followed by the blinking of 100.0000
5.2.2.5 Place 100.00g standard weight (METTLER).The display will blink 0.0000 g. Remove standard weight from balance.
5.2.2.6 After a few seconds the display should read ‘CAL DONE. This denotes end of self calibration.
5.2.3 Calibration against Standard weights
Frequency every month and after each maintenance job.
5.2.3.1 Clean the balance as per procedure given in 5.1
5.2.3.2 Check the weight of the standard weights 0.1000g, 0.2000g, 0.5000 g & 1.000 gms
5.2.3.3 Record the observations in calibration record.
5.2.3.4 If the variation is more than the least count label the balance ‘out of order’.
5.2.3.5 Error must be rectified and balance should be calibrated before use.
5.3. Operation
5.3.1 Ensure that balance is properly connected to the power supply.
5.3.2 Check that the air bubble of level indicator is at the center, and if required adjust the level by turning the leveling screws.
5.3.3 Switch on the main switch, this balance displays ‘88888888’ followed by 0.0000 g.
5.3.4 Place a clean petridish, close the balance door and press tare button on the bar to tare the petridish weight. The display should read 0.0000g.
5.4.1 Place the required No. of tablets/capsules on petridish and close the balance door.
5.3.6 Wait until the stability symbol “O” displayed, then read of weight.
5.3 Shout down
5.4.1 Clean the balance as per procedure given in 5.1
5.4.2 Switch ‘off’ the balance.
5.4.3 Switch ‘off’ the mains

Frequency for activities in Water system

1.0 OBJECTIVE
To lay down a procedure for defining Pre Determined Frequency for various operational activities in Water system.
2.0 SCOPE
This SOP is applicable to Formulations Units
2.1.0 AREAS
2.1.1 DM plant and UWF. System.
3.0 RESPONSIBILITY
Jr. Technical Officer / Executive –production/ Officer –Production.
4.0 ACCOUNTABILITY
Manager - Production
5.0 PROCEDURE
5.1.0 Frequency Chart
Backwash of sand filter - Daily 5minutes before starting the operation.
Backwash of activated carbon filter - Daily 5minutes before starting the operation.
Sanitization of purified water supply loop - Once in 7 days.
Sanitation of UWF by hydrogen peroxide - Once in 15 days.
Regeneration of Cation , Anion and Mixed bed - If the conductivity of Anion outlet water exceeds 20 µs / cm and conductivity of mixed bed outlet water exceeds 1 µs / cm.
Changing of 5mm filter in DM Plant - Once in 6 months.
Changing of 3mm filter in purified water plant - Once in 6 months or pressure exceeds 0.5 kg / cm².
Defouling treatment of cation and anion resines - Once in 6 months/ when choked.
Changing of air vent filters in UWF room - Once in a year
Cleaning of UWF membrane - Once in a year.
Changing of DM plant resines - 3 years or when the out put reduces than the design.
Changing of UWF membrane - When the Microbial counts are high even after chemical sanitization.
Chemical sanitization of purified water supply loop - When the Microbial counts are high even after hot water sanitization.

Operation of pH meter (Model pH scan-2)

1.0 OBJECTIVE
To lay down a procedure for operation of pH­ meter (Model pH scan-2).
2.0 SCOPE
This SOP is applicable to Formulations Units
2.1.0 AREAS
2.1.1 D.M. plant.
3.0 RESPONSIBILITY
Jr. Technical Officer / Executive (production)
4.0 ACCOUNTABILITY
Manager - Production
5.0 PROCEDURE
5.1.0 Precautions
5.2.0 Pre Startup
5.3.0 Calibration
5.4.0 Operation.
5.1.0 Precautions
5.1.1 Do not dip the pH meter more than the minimum immersion level.
5.1.2 E1 on display indicates, “Ensure that the battery is changed”.
5.2.0 Pre Startup
5.2.1 Ensure the cap of pH meter is removed.
5.2.2 Ensure the pH meter is calibrated before usage.
5.3.0 Calibration
5.3.1 Calibration to be done with the help of standard buffer solutions of pH 4, 7 and 10.
5.3.2 Calibrate initially with buffer solution of pH 7.
5.3.3 Select a standard buffer of pH 7.
5.3.4 Press the ON/OFF button on the key pad to turn on the pH meter.
5.3.5 Press the “CAL” button to enter calibration mode.
5.3.6 Dip the pH meter electrode up to the immersion level.
5.3.7 Stir the pH meter gently and wait for the displayed valve to stabilize.
5.3.8 Press “HOLD/ CON” button to confirm and complete the calibration.
5.3.9 Repeat the same procedure for buffer solution of pH 4 and pH 10.
5.4.0 Operation
5.4.1 Dip the pH meter electrode up to the immersion level.
5.4.2 Press the ON/OFF button on the key pad to turn on the pH meter.
5.4.3 Stir the pH meter and wait the display to stabilize.
5.4.4 Observe and record the pH.
5.4.5 Press the ON/OFF button to switch off.
5.4.6 Rinse the pH meter well with purified water.

Procedure for Setup, Operation & Cleaning of Jet cleaner

1.0 OBJECTIVE
To lay down a Procedure for Setup, Operation & Cleaning of Jet cleaner.
2.0 SCOPE
Module – 1,2,3,4&5.
3.0 RESPONSIBILITY
Operator Concerned.
4.0 ACCOUNTABILITY
Officer / Executive - Production
5.0 PROCEDURE
5.1 Precautions
5.2 Setup
5.3 Operation.
5.4 Cleaning
5.5 Shut down.
5.1 Precautions
5.1.1 Ensure the wheels of Jet cleaner are moving freely.
5.1.2 Never switch ‘ON’ the heater without water.
5.1.3 Remove the power plug from the socket before cleaning.
5.2 Setup
5.2.1 Switch on the mains.
5.2.2 Close the outlet valves of water tanks.
5.3 Operation
5.3.1 Fill both the tanks with potable water and cover with lids.
5.3.2 Ensure the level of water in tanks, is not up to the brim.
5.3.3 Switch on the heater , wait till required temperature is reached.
5.3.4 Switch OFF the heater.
5.3.5 Press the green button to start the blower.
5.3.6 Open the water outlet valve of hot water/ cold water as per the cleaning procedure.
5.3.7 Press the handle of Jet gun, facing towards the equipment surface.
5.3.8 Close the water outlet valve.
5.3.9 Press the red button to switch off the blower.
5.4 Cleaning
5.4.1 Drain out water from the tanks completely by opening the detachable SS connection clamps.
5.4.2 Wipe out the water with a dry lint free duster.
5.4.3 Clean the out surface with separate dry lint free duster.
5.4.4 Put cleaned status label and put the sign & date.
5.5 Shut down
5.5.1 Switch OFF the main power.
5.5.2 Take out the plug from the socket.

Changing of Air vent filters in Ultra Filtration room

1.0 OBJECTIVE
To lay down a procedure for changing of Air vent filters in Ultra Filtration room.
2.0 SCOPE
This SOP is applicable to Formulations Units
2.1.0 AREAS
2.1.1 Purified water plant.
3.0 RESPONSIBILITY
Technical officer / Executive (production)
4.0 ACCOUNTABILITY
Manager - Production
5.0 PROCEDURE
5.1.0 Precautions
5.2.0 Operation.
5.1.0 Precautions
5.1.1 Be careful while handling the filter cartridge.
5.2 Operation
5.3.1 For C.I.P tank vent filter remove the Tri Clover Clamp.
5.3.2 Remove the air vent filter from its base.
5.3.3 Reposition the new air vent filter. .
5.3.4 Tight the Tri Clover Clamp.
5.3.5 For storage tank remove the Tri Clover clamp.
5.3.6 Keep the entire filter housing down.
5.3.7 Remove the filter housing Tri Clover clamp.
5.3.8 To remove air vent cartridge rotate it on clock wise direction.
5.3.9 Put the new cartridge in position rotate it in anti clock wise direction for tightening.
5.3.10 Reposition the vent filter housing.
5.3.11 Tight the vent filter housing by Tri Clover clamp.
Fit the entire housing on storage tank and then tight the Tri Clover clamp

Changing of 3Micron filter in purified water plant

1.0 OBJECTIVE
To lay down a procedure for changing of 3mm filter in purified water plant.
2.0 SCOPE
This SOP is applicable to Formulations Units
2.1.0 AREAS
2.1.1 Purified water plant.
3.0 RESPONSIBILITY
Technical officer / Executive (production)
4.0 ACCOUNTABILITY
Manager - Production
5.0 PROCEDURE
5.1.0 Precautions
5.2.0 Pre-start up
5.3.0 Operation.
5.1.0 Precautions
5.1.1 Be careful while handling the filter cartridge.
5.2.0 Pre-start up
5.2.1 Stop the De-gasser pump.
5.2.2 Close the valves V-8.
5.3 Operation
5.3.1 Remove the Tri Clover clamps and kept the filter housing down.
5.3.2 Remove the filter housing Tri Clover clamp.
5.3.3 Remove the filter cartridge from its base .
5.3.4 Fit the new filter housing on its base.
5.3.5 Reposition the filter housing on its base.
5.3.6 Tight the filter housing Tri Clover clamp.
5.3.7 Put the filter in its original position then tighten the Tri Clover clamps.

Defouling treatment of cation and anion resins

1.0 OBJECTIVE
To lay down a procedure for Defouling treatment of cation and anion resines.
2.0 SCOPE
This SOP is applicable to Formulations Unit
2.1.0 AREAS
2.1.1 D.M. water plant.
3.0 RESPONSIBILITY
Technical officer / Executive (production).
4.0 ACCOUNTABILITY
Manager production.
5.0 PROCEDURE
5.1 Precautions
5.2 Pre – Start up
5.3 Operation
5.1 Precautions
5.1.1 Use correct size spanner while loosing bolts and nuts.
5.1.2 Be careful while removing top dish and top strainer plate.
5.1.3 Use acid & alkali proof hand gloves and nose mask before handling Hcl & NaoH.
5.2 Pre-Start up
5.2.1 Stop all the pumps (Raw water, De-gasser pumps).
5.2.2 Open the valve No:6 (C.B.V 6 and A.B.V 6 for cation and anion beds respectively ) to drain the water in side the vessel.
5.2.3 Ensure the availability of chemicals (Hcl, NaoH, Nacl).
5.2.4 Ensure the availability of Raw water.
5.3 Operation
5.3.1 Remove the top dish bolts and nuts using the spanner No: 26.
5.3.2 Keep the top dish on ground and then strainer plate.
5.3.3 Remove the resin from vessels by syphoning.
5.3.4 Soak the removed resin in chemicals for 8 hrs (For cation resin prepare 10% concentration of Hcl solution and soak the cation resin in this solution. For 100 lts of anion resin prepare a solution by using 100 lts of D.M water.Dissolve 10 lts of Nacl and 1 kg of NaoH in 100 lts D.M Water. Soak the anion resin in this solution.)
5.3.5 After 8 hrs clean the resins with fresh water twice.
5.3.6 Pour the resine in the vessels.
5.3.7 Put the removed strainer plate in its original position on the top of the vessel and then top dish.
5.3.8 Put the bolts and nuts and ten tighten using the spanner No: 26.
5.3.9 Close the valve No:6 (C.B.V 6 and A.B.V 6 for cation and anion beds respectively ).
5.3.10 Start the individual pumps (Raw water and degasser pumps).
5.3.11 Incase of leakage is observed tight all nuts.
5.3.12 After completion of leak test , regeneration of individual beds to be done according to the SOP. No:XXXXXX

Changing of 5Micron filter in D.M plant

1.0 OBJECTIVE
To lay down a procedure for changing of 5micron filter in D.M plant .
2.0 SCOPE
This SOP is applicable to Formulations Units
2.1.0 AREAS
2.1.1 D.M. water plant.
3.0 RESPONSIBILITY
Technical officer / Executive (production).
4.0 ACCOUNTABILITY
Manager – Production.
5.0 PROCEDURE
5.1.0 Precautions.
5.2.0 Pre-start up .
5.3.0 Operation.
5.1.0 Precautions
5.1.1 Be careful while handling the filter cartridge.
5.2.0 Pre-start up
5.2.1 Stop the De-gasser pump.
5.2.2 Close the valves M.B.V –1 and M.B.V –2.
5.2.3 Open the drain plug to drain the water in side the housing.
5.3 Operation
5.3.1 Remove the T.C clamp.
5.3.2 Remove the filter housing.
5.3.3 Remove the filter cartridge from its base by removing the top nut.
5.3.4 Kept the new filter cartridge on its base and then tighten the top nut.
5.3.5 Reposition the filter housing.
5.3.6 Tight the T.C clamp.
Tight the drain plug.

Changing the D.M water plant resins

1.0 OBJECTIVE
To lay down a procedure for Changing the D.M Water plant resins.
2.0 SCOPE
This SOP is applicable to Formulations Units.
2.1.0 AREAS
2.1.1 D.M. water plant.
3.0 RESPONSIBILITY
Technical officer / Executive (production)
4.0 ACCOUNTABILITY
Manager production.
5.0 PROCEDURE
5.1 Precautions
5.2 Pre – Start up
5.3 Operation
5.1 Precautions
5.1.1 Use correct size spanner while loosing bolts and nuts.
5.1.2 Be careful while removing top dish and top strainer plate.
5.1.3 Use suitable chain block to lift the vessle.
5.2 Pre-Start up
5.2.1 Stop all the pumps (Raw water, De-gasser pumps).
5.2.2 Open the valve No:6 or 10 (C.B.V 6 and A.B.V 6 for cation and anion beds respectively M.B.V 10 for mixed bed) to drain the water in side the vessel.
5.3 Operation
5.3.1 Remove the top dish bolts and nuts using the spanner No: 26.
5.3.2 Keep the top dish on ground and then strainer plate.
5.3.3 Remove the resin from vessels by syphoning.
5.3.4 Check the condition of the bottom strainer plate. Ensure that they are in good condition..
5.3.5 Clean the inside vessel with water.
5.3.6 Pour new resin in to the vessels (For cation vessel C-20, for anion vessel A 101 D for mixed bed cation resin is C-20 and anion resin is A 102 D).
5.3.7 Put the removed strainer plate in its original position on the top of the vessel and then top dish.
5.3.8 Put the bolts nuts on top dish plate and then tighten all the nuts by using the spanner No :26.
5.3.9 Close the valve No:6 or 10 (C.B.V 6 and A.B.V 6 for cation and anion beds respectively M.B.V 10 for mixed bed) .
5.3.10 Start the individual pumps (Raw water and degasser pumps)
5.3.11 Incase of leakage is observed tight all nuts.
After completion of leak test followed by regeneration of individual beds according to the SOP. No: xxxxx

Note: Users of this Document shell change the Valve and Pump names according to their DQ and IQ documents.

Cleaning of UF membrane

1.0 OBJECTIVE
To lay down a procedure for cleaning of UF membrane.
2.0 SCOPE
This SOP is applicable to Formulations Units
2.1.0 AREAS
2.1.1 Purified water plant.
3.0 RESPONSIBILITY
Technical officer / Executive (production)
4.0 ACCOUNTABILITY
Manager production.
5.0 PROCEDURE
5.1 Precautions
5.2 Pre – Start up
5.3 Operation
5.1 Precautions
5.1.1 Be careful while handling the chemicals.
5.1.2 Wear gloves and nose mask before handling the chemicals.
5.2 Pre-Start up
5.2.1 Ensure the availability of D.M water.
5.2.2 Ensure the availability of all chemicals and accessories.
5.2.3 Ensure the availability of compressed air.
5.3 Operation
5.3.1 Ensure the pump P1 is in off position during cleaning.
5.3.2 Collect 600 lts (1250. Mm WC) of DM water in CIP tank.
5.3.3 Collect the valve V14, V17, V20, V21, V23, V27, V28, V31,V V52 & V67.
5.3.4 Open valve V15, V16, V18, V19 & V 29,
5.3.5 Desolve the 500 gms of NaoH (100%) in a measuring beaker.
5.3.6 Pour this solution into CIP tank through air vent.
5.3.7 Recirculate the solution through U.F module by starting the pump P1 stop the pump P1 after 30 min.
5.3.8 Open the valve V14 to drain the solution from CIP tank. Close valve V14 after ensuring that complete solution is drained.
5.3.9 Collect DM water in to CIP tank. Circulate the water by stating the pump P1, drain the water opening the valves V17, V22, V27, V28 & V67.
5.3.10 Continue circulation till the rinse water conductivity and pH matches with DM water specification . Stop the pump P1, after 30 min. Then close the valves V17, V22, V27, V28 & V67.
5.3.11 Collect 100 lts (1250 mm WC) in to CIP tank through air vent.
5.3.12 Pour the 400 ml Naocl 5% (Sodium hypochlorite) concentration solution in to CIP tank through air vent.
5.3.13 Circulate the solution through U.F module by starting the pump P1. Stop the pump P1 after 30 min.
5.3.14 Open valve V14 to drain the solution from CIP tank. Close the valve V14 after ensuring that complete solution is drained.
5.3.15 Collect the D.M water into CIP tank. Circulate the water by starting the pump P1. Drain the water by opening the valves V17, V22, V27, V28 & V67 continue circulation till the rinse water conductivity and pH matches with D.M water specification. Stop the pump P1 after 30 min. Then close the valves V17, V22, V27, V28 & V67.
5.3.16 Chemical cleaning is followed by hot water sanitzation according.
5.4 The cleaning of U.F membrane by chemical shall be done at every 6 months.

Note: Users of this document shell change the abbrevations and code used, according to the DQ of their equipment

Changing of UF membrane

1.0 OBJECTIVE
To lay down a procedure for changing of UF membrane.
2.0 SCOPE
This SOP is applicable to Formulations Units.
2.1.0 AREAS
2.1.1 Purified water plant.
3.0 RESPONSIBILITY
Technical officer / Executive (production)
4.0 ACCOUNTABILITY
Manager – Production
5.0 PROCEDURE
5.1.0 Precautions
5.2.0 Pre-start up
5.3.0 Operation.
5.1.0 Precautions
5.1.1 Be careful while handling the membrane.
5.1.2 Wear gloves while handling the membrane.
5.2.0 Pre-start up
5.2.1 Ensure the availability of Hydrogen Peroxide
5.3.0 Operation
5.3.1 Frequency:
5.3.1.1 If the microbial counts are above the alarming limits even after chemical sanitization.
5.3.1.2 Changing of UF membrane shall be done when the output of purified water reduced to below 900 lts / hour even after cleaning the membrane.
5.3.2 Stop pump P1
5.3.3 Close valves V16 and open valve V17 to drain the water inside the U.F module. Close the valve V17 after U.F module was empty.
5.3.4
Disconnect the following T.C connections.
a) From feed water to U.F module.
b) From permeate water to U.V lamp
c) From reject water to drain.
5.3.5 Open the top and bottom T.C clamps and remove the top and bottom plates.
5.3.6 Connect the bottom plate to U.F module with help of T.C clamp.
5.3.7 Place the U.F membrane inside the U.F module.
5.3.8 Reconnect the following T.C connections.
a) From feed water to U.F module.
b) From permeate water to U.V lamp
d) From reject water to drain.
5.3.9 Open valve V16 and start the pump P1.
5.3.10 Tight the T.C clamps in case of leakage.
5.3.11 Carry out the chemical sanitization with hydrogen peroxide (H2O2) as per SOP No:xxxxx

Note: Users of this document should change the abbrevations suitably as per their Ultra filtration Unit's DQ

Chemical sanitization of purified water supply loop

1.0 OBJECTIVE
To lay down a procedure for Chemical sanitization of purified water system loop when the microbial limits are above alarming range.
2.0 SCOPE
This SOP is applicable to Formulations Units
2.1.0 AREAS
Purified water plant.
3.0 RESPONSIBILITY
Technical officer / Executive (production)
4.0 ACCOUNTABILITY
Manager production.
5.0 PROCEDURE
5.1 Precautions
5.2 Pre – Start up
5.3 Operation
5.1 Precautions
5.1.1 Be careful while handling the chemicals.
5.1.2 Wear gloves and nose mask before handling the chemicals.
5.2 Pre-Start up
5.2.1 Ensure the availability of D.M water & Purified water.
5.2.2 Ensure the availability of all chemicals and accessories.
5.2.3 Before starting the pumps P2 / P3 make sure that all user point valves should be closed.
5.3 Operation
5.3.1Collect 600 lts of purified water into 1500 lts storage tank. Keep the U.F system in re-circulation mode by opening the valve V24 and closing the valve V23.
5.3.2 Pour 15 kgs of NaoH (100%)in the tank through manhole. Mix the NaoH with water using S.S rod. Ensure that man hole is closed.
5.3.3 Start the pumps P2/ P3.
5.3.4 Re-circulate the solution through entire loop for 30 minutes.
5.3.5 After 30 minutes drain the solution through all user points and from the storage tank.
5.3.6 Collect the purified water in the storage tank by opening the valve V23 and closing the valve V24.
5.3.7 Start the pumps P2/ P3 when the water level was above 600 mm WC. Flush the entire pipe line for 30 minutes.
5.3.8 Inform the Quality control for collecting the sample from all user points. Go for next chemical after getting approval form Quality control.
5.3.9 Collect the 600 lts of purified water in the 1500 lts storage tank keep the U.F system in re-circulation mode by opening the valve V24 and closing the valve V23.
5.3.10 Pour 20 lts of Nitric Acid (69 %) in the tank through manhole. Ensure that manhole was closed.
5.3.11 Follow the points from 5.3.3 to 5.3.8.
5.3.12 Collect 600 lts of purified water into 1500 lts storage tank. Keep the U.F system in re-circulation mode by opening the valve V24 and closing the valve V23.
5.3.13 Pour 25 kgs of Citric Acid (100% ) in the tank through manhole. Ensure that manhole was closed.
5.3.14 Follow the points from 5.3.3 to 5.3.8.
5.3.15 Collect 600 lts of purified water into 1500 lts storage tank. Keep the U.F system in re-circulation mode by opening the valve V24 and closing the valve V23.
5.3.16 Pour 30 lts Hydrogen peroxide ( 100%) in the tank through manhole. Ensure that manhole was closed.
5.3.17 Follow the points 5.3.3 to 5.3.8.
5.3.18 After completion of the chemical sanitization continue the hot water sanitazation according to the SOP No.: XXXXX

Exit Procedure for Visitors

1.0 OBJECTIVE
To lay down a procedure for exit for visitors leaving from
a) Pharma production
b) Ware house (Raw and primary packing materials)
c) Primary packing / Secondary packing area.
2.0 SCOPE
Applicable to all the personnel who are leaving the areas mentioned in objective.
3.0 RESPONSIBILITY
Concerned person
4.0 ACCOUNTABILITY
PERSONS: Visitors
ACCOUNTABILITY: Concerned company official accompanying the visitor.
5.0 PROCEDURE
5.1.0 Precautions
5.2.0 Exit procedure.
5.1.0 Precautions
5.1.1 All visitors should leave the pharma manufacturing area through the specified visitors change room only.
5.2.0 Exit procedure
5.2.1 Enter visitor change room.
5.2.2 Remove disposal shoe covers while crossing the step over bench and put them in the waste bin.
5.2.3 Remove the apron and headgear and deposit them in the used linen container provided.
5.2.4 Open the door and leave the change room

Entry Procedure for Visitors

1.0 OBJECTIVE
To lay down a procedure for primary dress change for visitors entering into
a) Pharma production
b) Ware house (Raw and primary packing materials)
c) Primary packing / Secondary packing area.
2.0 SCOPE
Applicable to all the personnel who are entering into the areas mentioned in objective
3.0 RESPONSIBILITY
Concerned Person
4.0 ACCOUNTABILITY
S.N0
1.
PERSONS
Visitors
ACCOUNTABILITY
Concerned company official accompanying the visitors.
5.0 PROCEDURE
5.1.0 Precautions
5.2.0 Entry Procedure.
5.1.0 Precautions
5.1.1 All visitors entering in to the manufacturing areas should be accompanied by a company official always.
5.1.2 There is a separate entry available for Visitors.
5.1.3 Any visitor who wants to enter into pharma manufacturing areas, (external corridors of modules, dispensing rooms, raw materials stores, hold rooms, primary packing areas and secondary packing areas) should enter through the specified change room only.
5.1.4 Ensure the air curtains and insecticutors are working.
5.1.5 If not working inform maintenance for rectification.
5.2.0 Entry Procedure
5.2.1 Take a fresh apron from the locker provided and put it on.
5.2.2 Take a fresh headgear from the locker and put it on carefully to cover the hair properly.
5.2.3 Take disposable shoe covers from the tray provided and put them on while crossing the step over bench.
5.2.4 Enter the manufacturing areas accompanied by the company official.

Reprocessing Procedure

1.0 OBJECTIVE
To lay down a procedure for Reprocessing of batches.
2.0 SCOPE
Module -1,2,3&5
3.0 RESPONSIBILITY
Production Executive.
4.0 ACCOUNTABILITY
Production Manager / QA Manager
5.0 PROCEDURE
5.1.1 If the specified standards are not meeting at granulation stage / pelletisation stage / coating stage or not meeting analytical standards such as Dissolution, Physical appearance, Assay, Moisture content, the Batch will be taken up for reprocessing.
5.1.2 Reprocessing of batch shall be done as per procedure.
5.1.3 An investigation will be done by the concerned production Executive for the reasons and a report will be sent to Formulations Research & Development.
5.1.4 Formulations Research & Development after studying the report shall recommend a reprocessing procedure.
5.1.5 Based on Formulations Research & Development suggestion a process deviation form will be raised by production department for approval . The same deviation should be approved by QA Manager & R &D Manager.
5.1.6 Based on the approved process deviation production department will proceed for reprocessing as per the procedure given by Formulations Research & Development
5.1.7 Process deviation form and recovery procedure will be enclosed with B.M.R.
5.1.8 On the request of Formulations Research & Development, samples will be provided for stability studies as directed by R & D.

Procedure for cleaning, calibration & Operation of the Analytical moisture balance

1.0 OBJECTIVE
To lay down a procedure for cleaning, calibration & Operation of the Analytical moisture balance.
2.0 SCOPE
Module-x
3.0 RESPONSIBILITY
Production Officer / QA chemist.
4.0 ACCOUNTABILITY
Production Executive .
5.0 PROCEDURE
5.1 Cleaning
5.2 Calibration
5.3 Operation
5.4 Shut down.
5.1 Cleaning
5.1.1 Ensure that the power supply to be moisture balance is switched off before cleaning.
5.1.2 Lift the body & clean inside of the moisture balance with brush.
5.1.3 Clean the out side of the moisture balance with clean & dry lint free duster every day.
5.2 Calibration
5.2.1 Frequency of calibration.
5.2.1.1 Frequency daily & after each maintenance job.
5.2.2 Self calibration procedure.
5.2.2.1 Clean the balance as per procedure given in 5.1
5.2.2.2 Check that air bubble is at the center of the level indicator & if required adjust the level by turning the leveling screws.
5.2.2.3 Place a aluminum dish on
5.2.2.4 Switch on the moisture balance and allow it to stabilize for 30 minutes.
5.2.2.5 Press the ‘Ca ‘ button.
5.2.2.6 After a few seconds the display should read 100.000 gms, then place a std. 100.000 gms wt on aluminum dish, then it denotes 0.000 gms that denotes the end of self calibration.
5.2.2.7 Incase of display ‘error’ tare & press cal repeat the 5.2.2.6 procedure to ensure 0.000 gms.
5.2.3 Calibration against standards weights
5.2.3.1 Clean the balance as per procedure given in 5.1
5.2.3.2 Check the weight of the standard weights.
1.000 gms 0.500 gms 0.200 gms 0.100 gms.
5.2.3.3 Records the observations in calibration record.
5.2.3.4 If the variation is more than the least count label the balance ‘ out of order’.
5.2.3.5 Error must be rectified and balance should be calibrated before use.
5.3 Operation
5.3.1 Ensure that moisture balance is properly connected to the power supply.
5.3.2 Check that the air bubble of level indicator is at the center, and if required adjust the level by turning the leveling screws.
5.3.3 Switch on the main switches , then moisture balance displays 0.000 gms.
5.3.4 Place a clean aluminum dish and press tare button on the bar to tare the aluminum dish weight. This display should record 0.000 gms.
5.3.5 Place approx. 2.000 gms of powder on aluminum dish and close the main body.
5.3.6 Set the temperature by pressing temperature key.
5.3.7 Then press START button.
5.3.8 Wait till % of moisture display on the balance.
5.4 Shut down
5.4.1 Clean the moisture balance as per procedure given in 5.1
5.4.2 Switch off the balance.
5.4.3 Switch off the mains.

Labeling Procedure

1.0 OBJECTIVE
To lay down a procedure for labeling of containers, equipment’s accessories and areas at various stages.
2.0 SCOPE
Raw material stores, Module -1,2,3,4,5, hold areas, all packing areas and packing material stores.
3.0 RESPONSIBILITY
Concerned operator.
4.0 ACCOUNTABILITY:
Production officer, stores assistant.
5.0 PROCEDURE
5.1 Precautions
5.1.1 While sticking, ensure that labels contents are clearly visible.
5.1.2 Put the labels for SS-316 inprocess containers in specified place only.
5.2.0. Procedure
List of the labels used in production & ware house is given below.
5.2.1 Dispensing.
5.2.2 Quarantine label.
5.2.3 Do not use
To be cleaned.
5.2.4 Cleaned.
5.2.5 Recoverable residues
5.2.6 Status label.
5.2.7 Stock return.
5.2.8 On-line rejection.
5.2.1 Dispensing.
5.2.1.1 Stores Asst. shall prepare the dispensing label and sign for weighed by and production officer shall check and sign for checked by.
5.2.1.2 Take the cleaned container for dispensing load the material and paste the DISPENSING’ label.
5.2.1.3 Keep the ‘DISPENSING’ labels along with the B.M.R. After transferring the materials in to next stage.
5.2.2 Inprocess label.
5.2.2.1 The person /operator handling the ‘INPROCESS LABEL ‘has to fill the details and sign the same.
5.2.2.2 Keep the ‘INPROCESS LABEL’ along with B.M.R after transferring the material in to the next stage.
5.2.3 Do not use
To be cleaned.
5.2.3.1 The person /operator handling the ‘DO NOT USE TO BE CLEANED’ labels has to fill the details and sign the same.
5.2.3.2 Paste the label to the Containers, accessories and Equipment’s which are to be cleaned. Remove and tear the label after cleaning.
5.2.4 Cleaned.
5.2.4.1 The person /operator handling the ‘CLEANED’ has to fill the details and sign the same. Production officer /Jr technical officer/stores assistant has to cross check the same .
5.2.4.2 Put the ‘CLEANED’ label for the cleaned containers, equipments and accessories.
5.2.4.3 Keep the ‘CLEANED’ label along with the B.M.R. of next batch during product to product change over.
5.2.5 Recoverable residues(R.R’S).
5.2.5.1 The person /operator handling the RECOVERABLE RESIDUES(R.R’S)label has to fill the details and sign the same. Production officer has to cross check the same.
5.2.5.2 Remove and keep the label with BMR after transferring the material in to next stage.
5.2.6 Status label.
5.2.6.1 The person /operator handling the ‘STATUS LABEL’ has to fill the details and sign the same. Production officer /Jr. technical officer/stores assistant has to cross check the same.
5.2.6.2 Put the ‘STATUS LABEL’ to the respective Containers, accessories Equipment’s, areas. Keep the ‘STATUS LABEL’ along with B.M.R. When the status of the same is changed.
5.2.7 Stock return.
5.2.7.1 Write the ‘STOCK RETURN ‘label with all the details and get it signed by production officer (Returned by) and production Executive (checked by).
5.2.7.2 Put the above label to respective materials which are returning to stores.
5.2.8 On-line rejection.
5.2.8.1 Write the ‘ONLINE REJECTION’ label with all the details and get it signed by production officer(Returned by) and quality assurance Officer (checked by).
5.2.8.2 Put the above label to respective materials which are rejecting on line.

Handling of IPC and HDPE Containers

1.0 OBJECTIVE
To lay down a procedure for handling of inprocess containers (I.P.C’s) & H.D.P.E. containers.
2.0 SCOPE
Module -1,2,3,4,5, hold areas, primary packing areas and dispensing areas.
3.0 RESPONSIBILITY
Production officer.
4.0 ACCOUNTABILITY
Executive – Production.
5.0 PROCEDURE
5.1 Handling of S.S 316 containers.
5.2 Handling of HDPE containers.
5.1 Handling of S.S 316 containers.
5.1.1 Clean the SS -316 containers with potable water jet by scrubbing with lint free duster or plastic scrubber, use nylon brush to clean the butterfly valve.
5.1.2 Clean the lids with potable water jet.
5.1.3 Finally rinse the containers and lids with purified water jet.
5.1.4 Dry the containers and lids with lint free duster.
5.1.5 Keep cleaned SS 316 containers with “CLEANED” label in the dispensed material hold room for dispensing.
5.1.6 Ensure that wheels of the containers are moving freely.
5.1.7 Take the containers for dispensing.
5.1.8 Before dispensing ensure that bottom valve is closed.
5.1.9 Keep the dispensed containers in the hold room. Ensure that exterior of containers are cleaned with lint free duster.
5.1.10 Ensure that in process container airvent is closed.
5.1.11 Take the containers in to Module’s material hold area.
5.1.12 After usage of the containers put the’ TO BE CLEANED ’label and send it to washing area for cleaning.
5.2 Handling of HDPE Containers.
5.2.1 Receive the H.D.P.E. containers from primary packing (after completion of packing).
5.2.2 Clean the H.D.P.E containers with potable water jet by scrubbing with lint free duster.
5.2.3 Clean the lids with potable water.
5.2.4 Finally rinse the containers and lids with purified water jet.
5.2.5 Dry the containers and lids with lint free duster keep the dried containers in cleaned equipment hold area and put “CLEANED LABEL”.
5.2.6 Use only double poly bag layered HDPE containers for collection of granules /tablets, use black polythene bags wherever required.
5.2.7 After collection of granules/tablets tighten the poly bag with nylon thread.
5.2.8 Ensure that containers are properly labelled with product and batch details.
5.2.9 Transfer the containers to the respective hold/ process rooms as per the requirement with the help of trolley.
5.2.10 After usage of the containers put ’ TO BE CLEANED ’label and send it to washing area for cleaning.

Computerised System Validation Part-8

Prospective Validation - Design and Code Phase
During this phase of the life-cycle, the design is documented, verified by a design review, and the system coding/configuration performed against pre-determined standards. Design specifications may take a variety of forms. Diagrams should be used where appropriate to assist readability. Where large systems are being developed it is permissible to split the design specifications into a number of separate documents. Where this approach is adopted, effective change control must be implemented to ensure that the effect of changing one component on others is fully assessed.
Contents of the design specification should be cross-referenced to the system and functional requirements to demonstrate traceability.
System Overview
There should be a single document (clear, concise, accurate and complete) describing the purpose and function of the system. The system overview should be written in non-technical language so that personnel not trained in computing can understand it. It should include diagrams indicating the physical layout of the system hardware, any automated and manual interfaces to other systems, inputs, outputs and main data flows.
System overviews have a similar content compared to business requirements. The system overview is aimed however for use during inspections, providing a summary of the system scope, hardware and key functions. Business requirements may contain business case and business strategy information that is not appropriate to GxP regulatory inspection.
The system overview should be reviewed and approved prior to use of the system.
Functional and Design Specification Functional specification documents are commonly used as the highest-level design document from which more detailed design documents are developed.
The functional specification provides a response to the URS. Functional specifications will typically address:
• All inputs that the computerised system will receive.
• All functions that the computerised system will perform.
• All outputs that the computerised system will produce.
• All performance requirements that the computerised system will meet
(e.g. data throughput, reliability, timing).
• The definition of internal, external and user interfaces.
• What constitutes an error and how errors should be managed.
• The intended operating environment for the computerised system (e.g. hardware platform, operating system, etc. if this is a design constraint).
• All ranges, limits, defaults and specific values that the computerised system will accept.
• Safety considerations where inclusion of this information is deemed appropriate.
Detailed design specifications document the equipment hardware and/or software in sufficient detail and clarity to enable the hardware and software to be built and tested. The use of formal design techniques is encouraged.
Detailed design specifications should include but are not limited to:
• System architecture (software and hardware, modularity).
• System functionality (including reporting).
• Data processing and integrity.
• Security.
• Back-up, archiving and restoration.
• System interfaces (including human/operator interface).
• Disaster/failure recovery.
Detailed design specifications may be split into discrete elements for example, hardware design specification and software design specifications. Further subdivision is common for larger systems where for example unit/module design specifications may be produced. Other documentation includes:
• System architecture (including relevant design drawings).
• Software program specifications (All inputs, outputs, error/handling and alarm messages, ranges limits, defaults and calculations should be defined ready for programming and testing).
• Cabling/wiring schedules.
The design of a system should consider the partitioning of GxP and non-GxP elements such that they can be validated and supported separately.
Data Definition
Data dictionaries, architectures and flow should be defined. Actual data to be loaded into tables, files and databases should be specified by reference to its source. Data dictionaries should be used to describe different data types.
The data definition may standalone as a separate document or be incorporated within functional/design specification.
Specific functional aspects to be covered by the data definition include:
• ERES requirements
• Built in checks for valid data entry and data processing.
• Access controls to ensure data can only be entered or amended by persons authorised to do so.
Data Definitions may be incorporated into the Functional or Design Specification documents, or prepared as a separate document as appropriate.
Design Review
A design review is undertaken to ensure that all documentation from the requirements and design phases have been produced and are:
• Clear and concise: The specification should conform to documentation standards and should be readily understandable.
• Complete: To establish that the specifications unambiguously and adequately define the system and that the requirements traceability matrix (RTM) (or equivalent mechanism) has been maintained.
• Testable: Criteria within the specification to be used for user acceptance should be specific, measurable, achievable, realistic and traceable to the functional requirements and design specification.
• Fit for purpose: To generate confidence that the system will satisfy the user's requirements, have the necessary attributes of reliability, maintainability, usability, and minimise hazards. Methods such as a FMEA (failure mode effects analysis) or CHAZOP (computer hazard
and operability study) should be used to verify the design.
• Include ERES requirements (where applicable): The design review
should confirm whether or not electronic record and electronic signature functionality has been addressed.
• Current: Verify the documentation is current and necessary change
control has been applied.
After the review a report should be prepared and approved summarising the design review. The report should clearly state if the quality of the design is acceptable, list any deficiencies together with details of planned remedial action.
Design reviews may be known as design qualifications (DQ). Their scope of application may include use of the computerised system in its wider context including equipment, procedures, and operator interaction.
It should be understood that the requirement for this design review does not mean that other routine reviews are no longer appropriate. Activities and documents should be reviewed and approved as defined in the validation plan and management procedures. Coding, Configuration and System Build Prior to commencement of coding, configuration or system build the design
review should have been successfully completed. All software (including configuration) should be developed with good programming practices to appropriate standards.
Software/configuration developed internally should adopt programming standards. Such standards should reflect the type of programming language used, e.g. structured, object oriented, ladder logic, etc. Typically, programming standards will address:
• Content of header information in software listings (i.e. author, version, change details etc).
• Software/configuration structure and consistency (i.e. modular structure).
• Avoiding creation of non-executable code (i.e. dead code).
• In-code documentation.
• Naming and definition of variables.
• Data definition and scope (e.g. global versus local).
• Use of sub routines.
• Branching.
• Error/exception handling.
• Expandability considerations.
Hardware should be assembled and constructed in accordance with good practice taking into account aspects such as regulatory requirements and manufacturer.s recommendations.
Code/Configuration Review A source code or configuration review should be performed on all
bespoke/custom application software and configurations prior to formal testing. A two-tier approach is advocated: a high level overview of all software identifying areas of code and a low-level walk through of critical areas.
The source code review aims to provide confidence in the operability of the system and should:
• Verify expected use of good programming practices and adherence to programming standards referenced in development documentation.
• Determine a level of assurance that the code has been constructed against the approved requirements and design specifications.
• Provide assurance that the code is maintainable by a competent programmer.
• Detect possible coding errors.
• Identify evidence of dead code.
Configuration details should be reviewed to provide confidence in the operability of the system and should verify that:
• ’Unused’ options are deselected and cannot function.
• The configurable elements of the application fulfil design specifications. The outcome of the source code or configuration review will typically be a report providing an overview of the review conducted together with a list of all observations that have been noted. Care must be taken only to place actions on what is required from a regulatory or tangible business benefit perspective.
All actions should be completed before progressing to testing of the software unit/module.
Note: The correction of typographical errors is not needed if there is no impact on GxP functionality. Equally reports do not need to identify each individual typographical error where a general statement of observation can do just as well.
Complete hand-written annotated listings of software subject to detailed low-level walkthrough should be retained and attached to, or referenced by, the report. Where suppliers withhold software source codes then access agreements should be established. Other review evidence should also be retained and similarly managed.

Computerised System Validation Part-7

Prospective Validation - Requirements Phase
Business requirements are further developed to produce what is commonly called a user requirements specification (URS). The URS should focus on what the system should do and not to detail how to achieve this, i.e. design statements should not be incorporated. For large and complex systems, a number of URSs may be required. For small and simple systems the
business requirements and URS may be combined. The URS provides a statement of process/functional requirements of the proposed system. Each requirement should be categorised in order to define the level of importance, e.g. must, should, and could. All URS requirements should be successfully validated before system use unless otherwise justified
and approved.
Each URS requirement should be:
• Referenced to facilitate requirements tracking (Requirements Traceability Matrix [RTM]).
• Unambiguous, clear and concise.
• Testable/measurable.
• Be approved by the end-user.
The URS provides the basis for system acceptance testing and should be approved before a design review is conducted.
Requirements Traceability
An RTM or other equivalent mechanism should be established in order to provide a means of demonstrating how a particular function of a system/application has been validated through design (including any DQ), programming (including source code review), and testing (pre-qualification, IQ, OQ, PQ).

Computerised System Validation Part-6

Prospective Validation - Supplier Assessment Phase
Supplier assessments determine the level of assurance in the supplier that activities / deliverables equivalent to those outlined in this guideline have been followed/produced for development of computerised systems. The information is used to determine any corrective/additional activities to be undertaken by the supplier in order to address identified deficiencies. The need for follow-up supplier assessments should be commensurate with the number and severity of the identified deficiencies. The validation plan should document applicability and timing of supplier audits. The system category (Managing Hardware and Software) will assist in deciding when an audit is necessary. Supplier audits are most beneficial if they are conducted as part of the supplier selection and procurement process so that any actions arising can be planned and managed as part of the project implementation.
Key areas of assessment are:
• Existence and authority of quality assurance organisation.
• Availability and use of competent people.
• Availability and application of an effective quality management system (procedures and practices).
• Use of programming standards and good practices.
• Effectiveness of testing.
• Availability of a support service (as required)
• Ongoing viability of supplier's business (e.g. financial stability).

Computerised System Validation Part-5

Prospective Validation - Planning Phase
Business Requirements
This high level document describes the functions to be carried out, the operating environment and constraints, regulatory or otherwise. The emphasis is on the required functions and not the method of implementation and should therefore not be product specific. The business requirements will often document the business case and approval for work and capital
investment. The approved business requirements should provide sufficient information for the compliance assessment and system selection activities to be completed.
Compliance Assessment
All computerised systems should be assessed during the early planning phase to determine if there is a GxP impact and, therefore, whether the system should be validated or not. The compliance assessment should be approved by QA/Validation.
The Compliance Assessment should include a review of COTS product license requirements and release notes in order to determine any impact/restrictions on use within specific operating environments.
Electronic Records and Electronic Signatures Assessment (ERES)
Where the compliance assessment indicates a GxP impact an ERES assessment should be planned
Validation Planning
The validation plan is a document (or group of documents) stating the standards and the methods employed to maintain quality through the system life-cycle and to establish the adequacy of performance of the computerised system. Key roles and responsibilities, deliverables and authorities should be defined in the validation plans. The validation plan should be initiated at the earliest practicable stage and may be reviewed and updated through subsequent stages of the project. A rationale supporting any validation decisions made should be included within the validation plan. Validation plans should take account of the different
software categories comprising a computerised system and the mix of GxP and non GxP components. Guidance for the scope of validation required for different types of computerised system is defined in the forthcomming postwith the topic covered in as
Managing Hardware and Software. The need to conduct GxP Risk Assessments should be considered. Where a need is identified, the timing of/and approach to assessments should be
documented in the Validation Plan. For larger, more complex projects, GxP Risk Assessments may be conducted at several key phases of the system lifecycle. The IT Risk Management Framework can be used to help facilitate GxP Risk Assessments for larger projects.
Where there are validation plans for both the process/equipment/area and computerised system, then these should cross-reference each other. If the computerised system is relatively small and contained in its entirety within a stand-alone piece of equipment, then the validation plan for the computerised system may be embodied within the overall validation plan for the equipment.

Computerised System Validation Part-4

Prospective Validation
Validation of computerised systems requires careful planning to identify the set of validation activities required from initial design through to implementation use and final decommissioning. In practice it can be impossible to validate existing systems where initial design requirements are no longer available or appropriate activities were not performed or documented as the system was designed and implemented. The forthcomming posts in this topic describe the validation activities appropriate to a new system.
However, these life-cycle requirements should be considered when attempting retrospective validation of existing systems. The validation life-cycle activities and their order should be documented in a validation plan. A description of each phase of the life-cycle validation activities will be presented in the forthcomming posts as a sequential process, however certain activities may overlap or be combined. The validation plan should define such overlaps and amalgamations.
All validation activities should be carried out in a safe and secure manner, observing local safety procedures and requirements. A number of key issues should be addressed as soon as reasonably practical. Examples include procurement (supplier capability), regulatory expectations for electronic records/signatures, data integrity, user security, and hand-over issues such as advance knowledge of operation and support requirements.

Generic validation life-cycle will be presented in the forthcomming postes. The application of the life-cycle will vary as appropriate to the type of computerised system being validated. And also the forthcomming posts address how to approach the validation of laboratory systems, control systems, desktop (end-user) applications, IT systems, IT infrastructure and software tools.

Procedure for Product change over in Modules and Primary packing areas

1.0 OBJECTIVE
To lay down a procedure for product change over in modules and primary packing areas.
2.0 SCOPE
Module 1,2,3 and primary packing areas.
3.0 RESPONSIBILITY
Production Officer.
4.0 ACCOUNTABILITY
Executive / Sr. Executive - Production
5.0 PROCEDURE
5.1 The term “ product change over” denotes whenever an another product is to be taken for manufacturing, primary packing in an area / equipment which were used for the other product.
5.2 Remove the previous product and all accessories like punches and dies, FBD bags, FBD bowl covers from the module and transfer them to the quarantine area.
5.3 Arrange for cleaning of equipments for product to product changeover as per the respective SOP’s.
5.4 Send T.I sheet to QC through QA for swab sampling and analysis.
Note: (For the products where cleaning validation is not completed.)
5.5 Ensure that all the equipments are cleaned.
5.6 Arrange for cleaning of all the process areas by house keeping department as per SOP and ensure that cleaning is completed and recorded.
5.7 Send the communication note to engineering dept for AHU filter cleaned. Ensure the cleaning of module AHU’s by maintenance department.
5.8 Check thoroughly throughout the module for area cleanliness and ensure that no traces of the previous product is left over, status label and documents are removed from the areas.
5.9 Get the analytical results of the swab test (if applicable) and enclose with BMR of next product.
5.10 Ensure that clean secondary dresses and gloves are kept in gowning room for use, after the gowning room is cleaned.
5.11 Enclose the AHU cleaning confirmation note in the BMR of next product.
Primary Packing Areas.
1. Remove items and documents / labels of the previous product and accessories like change parts, and stereos.
2. Remove primary packing materials like foils and PVC film from the area and transfer them to the respective quarantine with required status labels.
3. Arrange for cleaning of the machinery for product to product change over as per respective SOP’s and ensure the cleaning is completed and recorded, get the tool box cleaned.
4. Send T.I. Sheet to QC through QA for swab sampling (if applicable) and analysis.
5. Arrange for cleaning of the area by House Keeping department and ensure that cleaning is completed.
6. Check thoroughly the areas and equipment for cleanliness and ensure that no material and documents / labels of the previous product is left over.
7. Get analytical result of the swab test and enclose the same with BPR of the next product.
8. Ensure that cleaned secondary dresses and gloves are kept in the gowning room for use, after the gowning room is cleaned. Put the clean status label on all equipment after cleaning.