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Wednesday, May 12, 2010

STANDARD OPERATING PROCEDURE Title: Washing of Utensils/Scoops

Purpose:

It is established for washing of equipments used in the store.

2. SCOPE:
It is applicable to Ware house.
3. RESPONSIBILITIES:
1. Manager Stores
2. Assistant Manager Stores
3. Supervisor
4. PROCEDURE:

1. Wash the scoop/bucket with warm water.
2. Put the soap / detergent on it and rub with a clean cloth.
3. Rinse thoroughly to remove the detergent completely.
4. Dry with a clean cloth.
5. Soak a clean cloth with IPA and rub it once on the scoop/bucket & let it dry.
6. Put the washed tools in polythene bags and keep in the specified place.

STANDARD OPERATING PROCEDURE Title: VIAL WASHING

1. Purpose
It is established to provide a standard procedure for “Vial Washing”.
1 Scope
It is applicable to injection section.
2 Responsibilities
1. Production Pharmacist
2. Supervisor
3. Worker
3 Procedure
Vial washing is done in two steps
1. Pre-washing
2. Final washing

1. Pre- Washing
a) Wear the mask and cover the hair properly with cap.
b) Stack the vial cartons received from store on the clean pallet in de-cartoning area.
c) Wash thoroughly the sinks of washing station and drain out any dirty water.
d) Fill the sinks of washing stations up to half with tap water.
e) In sink-1,add one bottle of liquid hands to make lather.
f) Pick up one carton of vial from de-cartoning area, remove its secondary packing, and dip the vials in the sink. Discard primary packing in the dust bin kept for this purpose in de-cartoning area.
g) Add to the 2-3 vials cartons similarly.
h) Brush each of the vial in sink with nylon material from in and outside.
i) Transfer each of the brushed vial in sink-2.
j) In sink-2 give the vial individually a rinse of tap water by filling the vials with water in the sink and emptying in the same sink.
k) Rinse each of the vial two times in this way and drop into the sink -3.
l) In sink-3, process of rinsing is repeated and the vials are arranged in the washed SS trays.
m) In the trays vials are placed with their neck downward These vials rare ready for final washing
n) Cycle of washing from Sink-1 to Sink-3 is repeated for whole of batch.
o) Water in each of the three sinks is changed with fresh one after it gets dirty.
2. Final washing
a) Give the pre-washed a final washing on the “ vial washing machine” following the Standard Operating Procedure for “Vial Washing Machine(GL/SOP/M/078)”

Standard Operating Procedure Title: VALIDATION OF STEAM STERILIZATION

Purpose:
• It is established for the proper validation of the sterilization process.
2. Scope:
• It is applicable to microbiological Lab.
3. Responsibilities:
• GM Production
• Quality Control Manager
• Microbiologist.
4. Procedure:
• Biological indicators to be used:
 Strain of bacillus stearothermophillus ATCC 7953
• Take 3-4 ampoules of above mentioned biological indicator in container in which the other filled ampoules are placed which are to be sterilized in autoclave.these ampoules of biological indicators are placed at different places of autoclave so that to check the proper sterilization process.Close the access door and continue to operate the apparatus.
• After completion of the sterilization procedure, and at a noted time with in 2 hours, aseptically add each contents of ampoule in 30 ml of Soybean Casein Digest Medium.Incubate each media at a temperature of 55-60oC. Observe each inoculated medium at 24 hours and 48 hours,and every 1 or 2 days thereafter for a total of 7 days. If after 7 days of incubation there is no growth in the medium the test for sterilization is met.
Quality Record(s)/Form(s)

The following quality records shall be generated in accordance with the procedure for Control of Company Quality Records (4.12).

Required Record Form No.
Destruction Note QF/115/01

Standard Operating Procedure Title: VALIDATION OF ANALYTICAL METHOD

1.0 Purpose
1.1 It is established to assure quality in all aspects, and to avoid any unintentional contravention of Drug Act, cGMP and company standards.
2.0 Scope
2.1 It is applicable to all types of incoming and out going materials and all type of activities / process, conditions, equipment, documents, material and any “thing” (i.e. conditions, process, activity, material, equipment and document) which can affect quality directly or indirectly.
3.0 Responsibilities
3.1 Manager Quality Assurances.
3.2 Assistant Manager Quality Assurance.
3.3 Quality Assurance Officer.
4.0 Procedure
4.1. During the routine in process checks if any thing found to be in contravention of any requirements, regulations, system (which are well defined in SOPs, SMPs, and Product Specification) matter will be discussed with relative incharge / Departmental Head to remove that short coming.
4.2. If the production department takes no action on verbal intimation that particular thing will be “HOLD” by affixing red specified label of “HOLD” which means to stop that “thing” (already defined).as and where it is.

7. Precision: Reference Standard deviation calculation by 5 injection / reading of the same dilution should not be greater than 1%.
8. Accuracy of the Method: Different concentrations of active ingredient are mixed with the auxiliaries. The results should not differ by + 2 %.
9. Results are recorded by the Analyst in ledger and data is reviewed by the QC Manager.

STANDARD OPERATING PROCEDURE Title: WEIGHING BALANCE

PURPOSE:

It is established to provide guidelines for use of weighing balance.

2. SCOPE:
It is applicable to Ware house.
3. RESPONSIBILITIES:
1. Manager Stores
2. Assistant Manager Stores
3. Supervisor
4. PROCEDURE:
1. Switch on the balance.
2. Check that the reading is zero.
3. Put the empty bag container on the pan of the balance.
4. Press “Tare”.
5. Put the material in bag/container.
6. Carefully take the reading.
7. Remove the material from balance and press “zero” to adjust the balance reading at zero.

5. CAUTION:

1. Use only specified adapter.
2. Never put the material on balance with jerk.

STANDARD OPERATING PROCEDURE Title: Temperature/Humidity Daily/Weekly Record

1. PURPOSE

• It is established Humidity & Temperature.

2. SCOPE
• It is applicable to Q.A Department.

3. RESPONSIBILITY
Procedure:
• Readout the dry bulb reading of hygrometer.
• Also readout the wet bulb reading of hygrometer.
• Subtract the wet bulb temperature from dry bulb temperature and note the humidity by taking the difference in humidity chart in contrast with dry bulb reading.

LIMITS:
Section HUMIDITY TEMPERATURE
Dry Injection NMT 40% 30 oC
Controlled Room NMT 50% 25 oC
Capsules NMT 45% 30 oC
Dry Suspension NMT 45% 30 oC
Tablet
(In case of Ranitidien) NMT 50 %
NMT 40% 30 oC
30 oC
Powder NMT 36% 35 oC


4. QUALITY RECORD(s)/FORM(s)
The following Quality Records shall be generated and managed in accordance with the procedure for Control of Company Quality Records (4.12).

Required Record Form Reference No.
Temperature /Humidity
Daily /Weekly Record QF/005/01

STANDARD OPERATING PROCEDURE Title: Procedure for Sterility Testing

1. Purpose
It is established to provide a standard procedure for “Sterility testing”.
2. Scope
It is applicable sterile products and raw materials.
3. Responsibilities
QC Manager
Microbiologist
4. Procedure
The following procedures are applicable for determining whether test sample complies with the pharmacopoeial test for sterility or not.
1. Membrane filtration method
2. Direct transfer method
Membrane filtration method:
• A suitable membrane filtration unit consists of an assembly, which makes easy, the aseptic handling of the test sample and allows the transfer of processed membrane to the sterile media, for incubation.
• A membrane suitable for sterility has a rating of 0.45µ and a diameter of 47mm approx.
• The membrane should wet prior to testing with D/water.
• The filtration unit and membrane must be sterilized and store to maintain the performance characteristic.
• Dissolve the material to be tested in the sterilized peptone buffer.
• Shake to dissolve.
• Pass through membrane filter unit.
• Divide the processed membrane into parts.
• One part is put into FTM and other into SDB media.
• Place the FTM in an incubator at temperature of 30o –35oC, while SDB media is incubated at 20o - 25oC for 14 days.

5. Interpretation of test results:
• When no microbial growth is observed the article passes the sterility test.
• When microbial growth is observed, and then repeats the process. If no growth is observed this time, the test sample passes the sterility test.
If the growth of the same physical appearance is observed, then repeat the test with double volume or weight of test sample.
• If the test sample is free from microbial growth this time, then material passes the test. But in case of growth of same physical appearance, the test sample is rejected.

6. Safety precautions:
1. For cleaning of sterile area before Sterility testing, follow SOP “Cleaning procedure for sterility room” GL/SOP/QC/030
2. For personnel safety measure, follow the instruction for entering in Sterility room, GL/SOP/QC/029

STANDARD OPERATING PROCEDURE Stability Testing Of Products

. Purpose:
It is established for Stability Testing of Products.

2. Scope:
It is applicable to Product Testing.

3. Responsibility:
1. Manager F&D
2. F&D Analyst /F&D Pharmacist
1. Procedure
1. Testing is done Physically and Chemically on Pharmaceutical Products to assure the stability of Product.
2. Original containers to be used for stability testing.
3. Stability testing can be on going, first three consecutive batches of production and if formulation or packaging Material or the source changes.
4. All the products will be tested with the available testing procedures of the Products.
5. Stability studies are conducted at ambient storage condition/special storage conditions
The product is evaluated under following storage condition:
• Room temperature 15 oC to 30 oC
• Refrigeration 2oC to 8oC
• Accelerated condition 38oC + 2oC, 65% + 5% RH
6. Stability testing is performed at certain intervals confirming shelf life of the product.
7. Stability testing schedule is initially 6 months, 1 year, 2 years, expiry date and one year after expiry.
8. A stability study at accelerated conditions is one month equivalent to one year (38OC, 65% RH).
9. Results are documented in the folders and Manager F&D reviews the data.
Official Storage Conditions are defined as follows:
• Freezer = -10OC to -20OC
• Cold = NMT 8OC (Refrigerator= 2OC to 8 OC)
• Cool = 8OC- 15OC
• Room Temperature = 15OC- 30OC
• Warm = 30OC- 40OC
• Excessive heat = above 40OC

STANDARD OPERATING PROCEDURE Stability Testing Of Products

. Purpose:

It is established for Stability Testing of Products.

2. Scope:

It is applicable to Product Testing.

3. Responsibility:
1. Manager R&D
2. Assist. Manager R&D
3. Analyst R&D
1. Procedure
1. Testing is done physically and chemically on Pharmaceutical Products to assure the stability of Product.
2. Original containers to be used for stability testing.
3. Stability testing can be on going, first three consecutive batches of production and if formulation or packaging Material or the source changes.
4. All the products will be tested with the available testing procedures of the Products.
5. Stability studies are conducted at ambient storage condition/special storage conditions
The product is evaluated under following storage condition:
• Room temperature
• Long term condition 30oC + 2oC, 60% + 5% RH
• Accelerated condition 38oC + 2oC, 65% + 5% RH


6. Stability testing is performed at certain intervals confirming shelf life of the product.
7. Stability testing schedule is initially 6 months, 1 year, 2 years, expiry date and one year after expiry.
8. Stability study at accelerated conditions is of three months.
9. Results are documented in the ledger and the Manager R&D reviews the data.


Official Storage Condition are defined as follows:

• Freezer = -10OC to -20OC
• Cold = NMT 8OC (Refrigerator)
• Cool = 8OC- 15OC
• Room Temperature = 15OC- 30OC
• Warm = 30OC- 40OC
• Excessive heat = above 40OC

STANDARD OPERATING PROCEDURE Title: Spectrophotometer Calibration

1. PURPOSE

• It is established to assure the accuracy of results.
2. SCOPE
• It is applicable to Quality Control Department.

3. RESPONSIBILITY
• Quality Control Manager
• Assistant Manager Quality Control
4. PROCEDURE

WAVELENGTH CALIBRATION:

1. Go to Calibration mode by pressing “8” on the keyboard and “Enter”. Press “1” “Enter”, for wavelength calibration then the “Start”.
2. SAMPLE ZERO: Insert Shutter (solid Black Cuvette) in Sample Holder (closest to the front of the instrument) and close sample door. Press “9” “Enter”, then “Start” key.
3. REFERENCE ZERO: Insert Shutter (solid Black Cuvette) in Reference Holder (towards back of the instrument) and close the sample door. Press “10” “Enter”, then “Start” key. Remove Shutter.
4. Set CLOCK Press “3” “Enter” (Cursor will be on right menu). Press “1” “Enter”, to turn CLOCK ON (Cursor will move to HOUR). Enter “Hour” on numeric keypad, then “Enter Key” (this is a 24 hour clock,.i.e.2 P.M. should be keyed as “14”) Enter Minute,Month,Day,Year,and date format.
5. System Baseline Press “2” “Enter”, then the Green” Start” key.]
6. SET UP IS NOW COMPLETE.Press blue “Main Menu” key.
CONTROL OF ABSORBANCES:
Check the absorbance using a solution of potassium Dichromate at the wavelength indicated in the following table, which gives for each wavelength the exact value of the specific absorbance (A 1%,1 cm) and the permitted limits. The tolerance for the absorbance is ± 0.01.
Wavelength A (1%, 1cm) Maximum tolerence
nm
235 124.5 122.9 to 126.2
257 144.0 142.4 to 145.7
313 48.6 47.0 to 50.3
350 106.6 104.9 to 109.2
Use a solution of potassium dichromate prepared in the following manner. Dissolve 57.0 to 63.0 mg of potassium dichromate, previously dried to constant weight at 130oC, in sufficient 0.005M sulphuric acid to produce 1000 ml.
The absorbance of a potassium dichromate solution containing exactly 60.06 mg of k2Cr207 1000 ml of 0.005M of sulphuric acid were used as the basis for the table above. Measured at a path length of 1 cm, the absorbances are as shown in the table below.
_______________________________________________________________________
Wave length_(nm)_____________________Absorbance_____________________________
235 0.748
257 0.865
313 0.292
350 0.640
Limit of stray light Stray light may be detected at a given wavelength with suitable filters or solutions. For example, the absorbance of a 1.2% w/v solution of potassium chloride with a path length of 1 cm should be more than 2 at 200nm when compared with water as reference liquid.
Resolution When prescribed in a monograph record the spectrum of a 0.02 % v/v solution of toluene in hexane. The ratio of the absorbance at the maximum 269 nm to that at the minimum at 266 nm is stated in the monograph.
Spectral slit width When measuring the absorbance at an absorption maximum and when using an instrument the slit-width should be small compared with the half width of the absorption band.However,it should be as large as possible to obtain a high values of I and should be such that further reduction does not result in an increased absorbance reading.

Standard Operating Procedure Title: SOP for Batch Travel

1. Purpose
• SOP is established to provide a standard procedure for the step wise completion of a product batch record starting from the issuance of materials up to its final packaging.
• SOP provides the procedure for record of personnel performing different tasks of manufacturing at various stages.
• SOP also helps trace the checks & controls subjected to the manufacturing processes.
• SOP outlines the procedure for reconciliation & batch yield calculation.
2. Scope
• Procedure is applicable to all manufacturing & packaging sections of production including the processes of issuance, manufacturing & packaging.
3. Responsibilities
• GM Production
• QC Manager
• Production Manager
• QA Manager
• Production Pharmacist
4. Reference:
• SOP for the issuance of Material (GL/SOP/P/001)
• SOP for Line Clearance (GL/SOP/008)
• SOP for Packaging Operation (GL/SOP/P/008)
• SOP for Destruction of Material (GL/SOP/P/002)
• SOP for the return of material to warehouse (GL/SOP/P/003)
• SOPs for Machinery & Equipment (All relevant SOPs)
5. Procedure

Standard Operating Procedure Title: Procedure for Line clearance

1.0 PURPOSE:

1.1 It is established to assure quality of Product and to minimize the chances of error.

2.0 SCOPE:

2.1 It is applicable to Quality Assurance Department.


3.0 RESPONSIBILITIES AND AUTHORITIES:

3.1 Manager Quality Assurances.
3.2 Assistant Manager Quality Assurance.
3.3 Quality Assurance Officer.

4.0 PROCEDURE:

4.1 GENERAL POINTS:


a. After receiving intimation for line clearance from Production, Q.A Officer
visit the concerned department.
b. Check that work station is clean of previous product and spillage on the line
area is suitably mopped and cleaned and in case of injectable it is mopped
with Dettol phenol solution and properly fumigated with formalin and
KMnO4.
c. See name of product ,batch no, batch size, manufacturing and expiry date.
d. Check that all relevant documents are complete in file.
e. Check status of product i.e. commercial, sample or supply.
f. Issue line clearance after confirmation that all the requirements of check list
of the relative process have been fulfilled.
.


4.2 AT GRANULATION.

 Check the granulation area with respect to its cleanliness and other required equipments including mixer, oscillator, granulator,fludized bed dryer, etc.
 Check that humidity/temperature of area(if necessary) is suitable for process.
 Check that all the ingredients are present and identified properly with reference to product specification.
 Assure that the approved SOPs and the Work instructions are being followed.
 Issue line clearance certificate and check list after confirmation that all the requirements of check list for granulation have been fulfilled.



4.3 AT MANUFACTURING ( LIQUIDS)

 Check that clean protective clothing ,gloves and masks are being used.
 Check the cleanliness and identification of manufacturing tools including manufacturing storage/filling tanks, mixer and other containers.
 Check that manufacturing is being carried out against approved raw material requisition and approved manufacturing instructions are being followed.

 Check that all the ingredients are properly identified with product name, batch no, material name and quantity.
 Assure that Water for injection is approved from Q.C before starting manufacturing process (in case of injection).
 Assure the addition of active ingredients and other excipient under controlled humidity and temperature.
 Issue line clearance certificate and check list after confirmation that all requirements of check list have been fulfilled.


4.4 AT COMPRESSION

 Make sure that dissolution/disintegration time what ever the specification is and friability have been checked and result are within range.
 Check physical appearance of granules/ powder and tablets.
 Check that humidity is under control if necessary.
 Check the weight adjustments of machine by weighing the tablets as given by Q.C.
 Check sticking, capping and all other in process physical problems.
 Check hardness / thickness of tablets, limits of hardness/thickness should be within range of product specification.
 Check weight variation sheet and enter weight and hardness in it.
 Products which are not compatible can not be compressed in same compression area.
 Issue line clearance certificate and line clearance check list after confirmation that all the requirements have been fulfilled.
 Check the compliance of line clearance at regular intervals of time.

4.5 AT COATING

 Check cleanliness of coating pan,containers,siliverson mixer exhaust duct, hot air supply and compressed air filter etc.
 Assure that approved SOP and Work instructions are being followed.
 Check the ingredients of coating solution.
 Issue line clearance certificate and check list after assuring that all requirements of coating check list have been fulfilled.

4.6 A T FILLING

 Check cleanliness and washing of filling machine and filling containers(bottles,vials,ampoules etc ).
 Check volume/weight what ever is the case filled by machine as given by Q.C,Weight 6 sachets in case of powder, Make pool volume of 5 ampoules in case of injectable , weigh 20 capsules in case of encapsulation.
 Check bubble test before ampoule filling the injectable in area for integrity of filter.
 Assure sterilization of vials and ampoules at 240 degree centigrade for 2 hours and rubber stoppers at 100 degree centigrade.
 Issue line clearance certificate and check list after confirmation that all the requirements of the check list have been fulfilled.
 Check the compliance of line clearance at regular intervals of time.


4.7 AT BLISTER
 Check that machine is set according to product batch no,mfg.and exp.date.
 Check that product expiry should comply with product specification.
 Check coding on blisters and sign the blisters.
 Check physical appearance of tablets/capsules,PVC,PVDC,and Al:foil.
 Issue line clearance certificate and line clearance checklist after confirmation that all the requirements of checklist have been fulfilled.
 Check compliance of line clearance at regular intervals of time.



4.6 AT PACKAGING

 Check all the packaging material identities of the product according to product specification.
 Check that all the relevant record is complete.
 Check that all the materials are released for packaging from Q.C.
 Check the batch no, manufacturing and expiry date of product to be packaged and that printed on packaging material.
 Confirm the price in case of commercial packaging.
 Issue line clearance certificate and check list for packaging after confirmation that all the requirements of packaging check list have been fulfilled.
 Check the compliance of line clearance at regular intervals of time.









5.0 RECORD REQUIRED:
The following record shall be generated in accordance PROCEDURE FOR LINE CLEARANCE.:

Required record Form reference number
Line clearance slip QF/037/01
Check list for granulation QF/108/01
Check list for compression QF/185/01
Check list for coating QF/186/01
Check list for blistering QF/O74/01
Check list for liquid manufacturing QA/204/01
Check list for encapsulation QF/075/01
Check list for packaging QF/O33/01
Check list for filling QF/109/O1
Check list for injectable QF/049/01

STANDARD OPERATING PROCEDURE Title: LIFTER

. PURPOSE:
It is established to provide guidelines for the use of “Lifter”
2. SCOPE:
It is applicable to Ware house
3. RESPONSIBILITIES:
1. Manager Stores
2. Asst.Manager Stores
3. Supervisor
4. PROCEDURE:

1. First check the working of the lifter by pushing the knob.
2. Bring the arms of the lifter at appropriate height.
3. Keep the material on it.
4. Move the lifter carefully to the required area.
5. Unload the material & keep it in required place.

5. PRECAUTION:
1. Don’t move lifter too fast.
2. Don’t hit walls or racks with lifter.

STANDARD OPERATING PROCEDURE Title: “Sealing/Leakage Test”

1. PURPOSE
It is established for sealing / leakage Test.
2. SCOPE
It is applicable to QA Department.
3. RESPONSIBILITIES
3.1 Manager Quality Assurance.
3.2 Assistant Manager Quality Assurance.
3.2 Quality Assurance Officer.
3.3 Quality assurance assistants.
4 PROCEDURE
“SEALING/LEAKAGE TEST”
1. Collect 3 strips in case of Tablet & 6 Sachets in case of powder for sealing test with regular intervals as & when required.
2. Fill glass desiccators with water properly.
3. Add 2-3 drops of Methylene Blue in Vacuum desiccator’s water.
4. Immerse the strips/Sachets properly in desiccator’s water. In such a way that vacuum desiccators containing enough water to cover the sample with at least one inch of water from top surface.
5. Cover the strips/sachets with grid.
6. Apply the vacuum for 3 minutes/ or -600 mm of Hg for sachet & -400 mm of Hg for Tablet or Capsule strips.
7. Release the pressure slowly.
8. Wipe off droplets over sachets, strips whatever the case with tissue or soft cloth till complete dryness.
9. If any strip/ sachet whatever the case is shows evidence of leakage (sign of blue coloring of sample) reject the sample, inform Incharge Pharmacist so that corrective action may be taken.
10. Enter this in In-process register of sealing record register.
“CLEANING PROCEDURE FOR VACCUM DESICCATOR”
1. Switch off main electric supply of the apparatus.
2. Clean Instruments inside & outside with clean cloth.
3. Wipe off surrounding water.
4. Change water regularly.

5. RECORD REQUIRED:
The following record shall be generated and managed in accordance with the procedure for control of company quality records:

Required Record Form Reference No.
Sealing/Leakage test Log book

STANDARD OPERATING PROCEDURE Title: HPLC (SYKAM)

1. Purpose
a) To define the activities which need to be followed for working on the HPLC system in the Quality Control department.
2. Scope
a) It is applicable for chemical testing.
3. Responsibilities
a) QC Manager
b) Asst. QC Manager
c) Senior Analyst
4. Procedure
Operation of HPLC is based on its four parts.
1. Solvent Delivery System(PUMP)
2. Detector
3. Rheodyne Injector
4. Computing System( Signal Channel & computer)

1. Solvent Delivery System:
1.1 Insure that the instrument is clean and free from dust.
1.2 Put the power plug in the socket and switch it ON.
1.3 Switch on the pump by pressing “On/Of” button, located on back side of the instrument.
1.4 Press program button to set parameter e.g. flow rate, minimum pressure, maximum pressure, constant and analysis time.
1.5 Using up and down button adjust the required parameters and press stop button to exit the program.
1.6 Dip the inlet filter into the solvent (Pre-filtered and degassed HPLC grade water or Mobile phase or washing solvent etc)
1.7 Connect the syringe to the adapter in the waste port; twist the syringe slightly to make a leak free connection. Open the bypass valve by turning it anticlockwise.
1.8 Slowly pull the syringe plunger back, solvent steadily appears in the syringe collect two or three syringe volumes and ensures that no air bubbles are present in the solvent line, close the bypass valve.
2. Detector:
2.1 Switch on the detector by pressing “On/Of” button, located on back side of the instrument, after completion of self test the main window will display.
2.2 Press menu button twice to set wavelength, using “up () & down ()” button set your required wavelength and press “Start Status” button once to start the detector.
2.3 Press “Auto zero” button before going to run a sample.
3. Column & Injection System:
3.1 Join a required column (ensure the direction of flow of column) to the outgoing line of solvent delivery system to the upper part of the column and down ward of it is join with the line going to the detector.
3.2 Injection system is used to inject the sample into system.
3.3 Turn the injector (anti-clock wise) to load position, enter the needle to injector & inject the sample & rotate the valve (Clock wise) to inject position.
Note: Rotation of the injector valve & pressing of space bar of the computer key board will be done at the same time.
4. Computing System:
4.1 Switch on computer system.
4.2 Double click “Peak Simple” icon from the desktop of the computer, after completion of self test the main window will display.
4.3 Open file in which we want to work.
4.4 Run sample by pressing “Space Bar” of keyboard or by clicking Run from acquisition menu at top of the page.
4.5 Stop sample by pressing the end key of the key board or by clicking Stop from acquisition menu at top of the page.
4.6 Print Out result from file option.
Flow Diagram:

Switch off the whole system at the end of the working.
5. Precautions:
5.1 Clean the system before and after use.
5.2 Handle with care.
5.3 Give washing to the system with water first for at least 30 minutes when mobile phase containing buffer is used & then with methanol: water(70:30) for another 30 minutes , at the end give washing to the system with pure methanol for 20-30 minutes.
5.4 If mobile phase is free from water & buffer then give washing directly with methanol for 40-45 minutes.

STANDARD OPERATING PROCEDURE Title: Shoes Washing

1. Purpose
1.1 It is established to provide a standard procedure for “Shoes Washing” used in general areas of sterile sections (i.e.; ampoule, sterile powder filling & ophthalmic).
1.2 Procedure is established to avoid dust/soil/dirt in sterile mfg areas carried by the personnel shoes.
2 Scope
2.1 It is applicable in Sterile Manufacturing Sections.
2.2 Procedure is applicable for collective shoes; for individual shoes appropriate washing procedure may be adopted dust/soil free shoe being the criteria.
3 Responsibilities
3.1 Production Pharmacist
3.2 Supervisor
3.3 Worker
4 Procedure
4.1 Schedule of Washing
4.1.1 Daily after working.
4.1.2 At any time when the shoes are dirty.
4.2 Washing Steps
4.2.1 Take 50 Liters of water in the clean tub/bucket etc.
4.2.2 Add to it sufficient of liquid detergent to give rich foam.
4.2.3 Dip in the above solution shoes one by one after cleaning & scrubbing with the nylon brush in order to remove any soil or sticky dirt.
4.2.4 Keep the shoes soaked in solution for 20 minutes.
4.2.5 Scrub each of shoes with nylon brush while dipped in solution.
4.2.6 Drain the solution & rinse the washed shoes with plenty of clean water.
4.2.7 Let the shoes dry.
4.2.8 Place the shoes in shoe rack kept in entrance buffer of sterile section after cleaning shoe rack.
4.2.9 Record the washing in Shoes Washing Log Book.
5 Required Quality Record
5.1 Shoe Washing Log Book. (QF/ 183/01)

STANDARD OPERATING PROCEDURE Title: Sanitation

1. PURPOSE
• It is established to provide the proper sanitation schedule for the areas of the plant...
2. SCOPE
• It is applicable to all departments under ISO 9002 Scope.
3. PROCEDUR
o Factory areas are divided in to the following
1. Surroundings
2. corridors
3. Manufacturing Area
4. Washroom & Change Room
5. Stores
6. Quality Control Department
7. Manufacturing Personnel
8. Canteen(Dining area & Kitchen)
9. Toilets
10. Parenteral
11. R & D
12. Water Tank Sanitation
Q.A will maintained monthly sanitation record on General cleaning procedure checklist.
4. QUALITY RECORD(s)/FORM(s)
The following Quality Records shall be generated and managed in accordance with the procedure for Control of Company Quality Records (4.12).
Required Record Form Reference No.
Cleaning Procedure checklist.
QF/176/01

STANDARD OPERATING PROCEDURE Title: Sampling of Raw Material

1. PURPOSE

• It is established to provide the guidelines for the sampling of raw material.
2. SCOPE
• It is applicable to all types of incoming material.
3. RESPONSIBILITY
• Quality Control Manager
• Quality assurance Officer
4. PROCEDUR
ITEMS REQUIRED FOR SAMPLING:
1. Spatulas
2. Pipettes
3. Tissue Paper
4. Glass vials
5. Glass bottles with screw caps
6. Dusters
7. Labels
8. Glass bottles
9. Raw material receiving receipt
10. Polythene bags (sample size)
1. Upon receipt of raw material the warehouse Incharge will issue a respective
Goods receiving report, by which the Quality assurance Department will be requested to collect samples for analysis and retaining samples.
The Warehouse Incharge will also affix raw material Quarantine slips with all necessary information on each container together with a label, date of sampling, name of person and signature.
2. Before sampling the following points should be checked:
 Condition of the container. It should not be damaged, torn, contaminated with dust, water etc.
 Incase of any abnormalities, all details should be noted on Raw material receiving receipt.
 In any damaged / Deteriorated case of insured imported material, the supervisor should be informed immediately to note down the location & condition of damaged material container(s). In such case the container should be opened on the presence of supervisor.
3. Sampling should be carried out according to the formula


4. Availability of certificate of analysis of imported materials should be confirmed.
5. In case of consignment does not bear any batch number/lot number, the whole consignment would be considered as one batch.
6. Put serial number on all containers.
7. Solid Materials
With the aid of a spatula take three samples from the same container from top to bottom, collect in a suitable air tight container.
8. Semi Solids:
Stir the content of the container to mix thoroughly. Insert a Stainless steel rod from top to bottom in the material. Collect the material sticking to rod, in a suitable jar.
9. Liquids:
Stir the content of the container to mix and take sample with the pipette or a suction pump. Collect in a suitable bottle.
10. After sampling all containers should be properly closed or sealed and labeled.
11. Identification on each container and mixed assay to be carried out.
12. Mix the samples taken from one batch. This sample also serves as retaining sample.
13. After analysis, released label or rejected label, whichever applicable, should be affixed the Quarantine Label.
14. Released label must bear the due date for re-analysis.
Standard sample quantity for each sampling container is as follow:
I. Solids = 10 g regarding batch / lot size.
II. Semi solids = 10-5- g.
III. Liquids = 100 ml.
IV. Active = 5 g


5. QUALITY RECORD(s)/FORM(s)
The following Quality Records shall be generated and managed in accordance with the procedure for Control of Company Quality Records (4.12).

Required Record Form Reference No.
Request for analysis (Raw material) QF/064/01
Raw Material Receiving Receipt QF/013/01
Sampled QF/059/01
Under Test QF/057/01
Quarantined QF/083/01

The sampling of packaging material

It is established to provide the guidelines for the sampling of packaging material.
2. SCOPE
It is applicable to all types of incoming material.
3. RESPONSIBILITY
1. Quality Assurance Manager
2. Quality Assurance Officer
4. PROCEDUR
1. Upon receipt of packaging material the warehouse Incharge will issue a respective goods receiving report, by which the quality assurance department will be requested to collect samples for analysis and retaining samples. The ware house Incharge will also affix packaging material identification slip with all necessary information on each container of the same lot together with a quarantine label, data of sampling, name of person and signature.
2. Before sampling the following points should be checked:
3. During sampling the quality assurance personnel will give all details of the quarantine label regarding date of sampling name of person and signature.
a) Packing materials are placed in the Quarantine Area, properly labeled.
b) Condition of the container – it should not be damaged, torn, contaminated with dust, water etc.
c) In case of any abnormalities, all details should be noted on packing material receiving receipt.
d) Each uniform looking delivery of packaging materials is considered as one batch.
e) Primary packaging materials are to be considered equivalent to raw materials as far as Quality is concerned.
4. In case of an already marketed drug product a new primary packing material which is not stated in the respective GLOBEL packing requisition is supposed to be used, a sufficient amount of samples have to be sent to QC for compatibility testing before use. Only after QC have given their consent, this new primary packaging material may be used.
5. Sampling plan should be carried out according to MIL-STD-105D (Table 1 and 2).
6. Knowing the lot size and inspection level, obtain a code letter from table 1.
7. General Inspection Level l = Relaxed
General Inspection Level ll = Normal
General Inspection Level lll = Tightened
8. The delivery is checked according to the GLOBAL Testing standard and has to comply with the quality requirements stated therein (full analysis).
9. After analysis, released label or rejected label, whichever is applicable, should be placed on the quarantine label and the material should be placed in the respective area.
SAMPLING PLAN FOR PACKAGING MATERIALS

TABLE 1
SAMPLE SIZE CODE LETTERS
LOT OR BATCH SIZE GENERAL INSPECTION LEVELS
I II III
2 TO 8 A A B
9 TO 15 A B C
16 TO 25 B C D
26 TO 50 C D E
51 TO 90 C E F
91 TO 150 D F G
151 TO 280 E G H
281 TO 500 F H J
501 TO 1200 G J K
1201 TO 3200 H K L
3201 TO 10000 J L M
10001 TO 35000 K M N
35001 TO 150000 L N P
150001 TO 500000 M P Q
500001 AND OVER N Q R
Table ll
SAMPLING PLANS (Normal Inspection)
Sample size code letter Sample size
A
B
C 2
3
5
D
E
F 8
13
20
G
H
J 32
50
80

K
L
M 125
200
315
N
P
Q 500
800
1250

R
2000




. QUALITY RECORD(s)/FORM(s)

Required Record Form Reference No.
Request for analysis (Packing material) QF/112/01
Raw Material Receiving Receipt QF/012/01
Sampled QF/059/01
Under Test QF/057/02
Quarantined QF/083/01

Standard Operating Procedure Title: Sampling of In-process/Finished product

Purpose:
• It is established to provide the guidelines for the sampling of In-process/Finished Products.
2. Scope:
• It is applicable to QA Department.
3. Responsibilities:
• Quality Control Manager
• Quality assurance Officer
4. Procedure:
After receiving “ Intimation for in-process/Finished Sampling from production Department,QA Officer checks the product to be sampled according to the manual for Product specification. “ Sampled” & “ Under test” stickers are pasted over the container from where sample is to be taken
Sampling Quantity
 Liquids
100 ml in a clean dried beaker.
 Powder/Granules
10-20 Grams in poly bags.
 Tablet
30-50 Tablets in poly bags.

 Capsules
30-50 Capsules in poly bags.
 Gel/Ointment
50-100 Grams in clean dried beaker.
 Injectable
Inprocess: 100 ml (in case of bulk liquid)
30-50 units (In case of filled /sealed units)
Finished: 2 x 10 Units (For commercial)
20 x 1 Units (For Sample)
Quality Record(s)/Form(s)

The following quality records shall be generated in accordance with the procedure for Control of Company Quality Records (4.12).

Required Record Form No.
Sampled QF/059/01
Under Test QF/057/01

STANDARD OPERATING PROCEDURE Title: Test Method for Rubber Stoppers

1. Purpose
a) It is established to provide a standard procedure for Rubber stopper testing.
2. Scope
a) It is applicable for Rubber stoppers.
3. Responsibilities
a) QC Manager
b) Analyst
4. Procedure
Physical Test:
Description: Grey rubber stoppers.
Surface after Dry Autoclaving: Rubber stoppers are rapped in aluminum foil and autoclave at 180oC for ½ hour. No crack and no sticking are observed.
Chemical Tests:
Aspect of Autoclaved solution: weigh 17 g of Rubber stoppers and transfer it to a titration flask. Add 150ml of CO2 free purified water. Prepare a blank in the same manner, with 150 ml of purified water (CO2 free). Cover the flasks with aluminum foil and autoclave tape.
Autoclave it at 121oC, 15pb for 30minutes. (Solution S)
Note the color of solution after 24 hours standing after autoclaving. Compare the solution with blank; it should be colorless to slightly hazy.
Reducing Substances:
After 24 hours standing, take 50 ml of solution S and titrate it with N/100 iodine solution, using Starch solution as indicator.
Carry put a blank titration.
Limit: Not more 0.5ml of N/100 Iodine solution are required to produce blue color.

pH of solution: pH of Solution S should be in the range of 6.5 – 7.5.

%age Transmission: Take the transmission of solution S at 550nm, use blank preparation as blank.
Limit: transmission must be above 95%

STANDARD OPERATING PROCEDURE Title: RELEASE OF COATING MATERIAL WITH ADJUSTMENT REMARKS

1. Purpose

It is established to minimize the color variation problem in tablets.

2. Scope

Applicable to R&D , Q.A, Q.C and production department.

3. Responsibilities

1. Manager Quality Control
2. Manager R&D
3. Manager Quality Assurance
4. Manager Production

4. Procedure
1. Quality Control will intimate Quality Assurance before releasing any coating material when adjustment required.
2. Quality Assurance will inform Research & Development about this material.
3. Research & Development will decide the quantity of that material by conducting trial & will inform to R.M.S, Q.A & production department in written.
4. Solution of that product will be prepared in the presence of production, R&D and Quality Assurance
5. Coated tablet will then be matched with standard, if available, otherwise to previous last three batches.

STANDARD OPERATING PROCEDURE Reference Samples (Finished Packs)

Purpose:

It is established to keep reference sample of 1st three commercial batches for the period of shelf life plus one year.

2. Scope:

It is applicable to R&D Department.

3. Responsibility:

1. Manager R&D
2. Assist. Manager R&D
3. Analyst R&D
4. QA Manager
5. Production Manager/Production Pharmacist

4. Procedure

1. QA takes out finished packs as soon as one of the 1st three commercial batches starts.
2. If the samples are of more than one pack, these must be wrapped with rubber band and the packs must clearly indicate batch number.
3. QA deptt acknowledges the sample receiving on the control sample receipt.
4. Quantity of the samples (finished packs) for each item is mentioned below:









Tablets-----------------------------------150 Tablets
Capsules--------------------------------150 Capsules
Dry Suspension------------------------18 Bottles
Sterile Dry Powders Injections-----18 Vials
Sterile Liquid Injections---------------60 Ampoules/vials
Cream/ Ointments---------------------18 tubes
Ophthalmic----------------------------- 60 unit packs (Droppers)
Sachets (Dry Powders) -------------18 Packs

5. Retain the samples through out shelf life and one year Additional or as per local health authorities requirement.

5. Quality Record Form
The following Quality Records should be generated in accordance with the procedure for Control of Company quality Record.
Required Record Form Reference No.
Control sample receipt QF/114/01

STANDARD OPERATING PROCEDURE Title: RAW/PACKAGING MATERIAL RECEIVING & QUARANTINE

1. Purpose

This procedure is established for receiving and storage of incoming Raw/Packaging materials.

2. Scope

This Procedure is applicable to Raw/Packaging material stores.

3. Responsibilities

1. Manager Stores
2. Assistant Manager (stores)

4. Procedure
1. All the incoming materials are received in store and Goods Acknowledgement Note is issued.
2. Material is placed in respective quarantine area designated for packaging and raw materials and quarantine slips are pasted.
3. Basic Information (item name, B # lot size, origin/supplier name) are noted on daily entry logbook for raw material/daily entry logbook for packing material.
4. If outer packing is damaged then it should be transferred to proper and safe packing.
5. Request for analysis (Packaging material/Raw material is raised by Manager Stores and is forwarded to QA department and material is Quarantined)
6. Sample is drawn by QA department & handed over to QC department for testing.
7. After QC approval the material is entered in respective stock (inward and outward) position logbook and is transferred to their respective places in approved areas.
8. Slips of approval are pasted on each container /carton.
9. If material is not approved by QC department a slip of not approved is pasted and material is transferred to the designated rejected areas.
10. For rejected raw materials goods Return note is prepared by the store manager and material is returned to the supplier after getting the approval from Director Operations. For rejected packaging components, a destruction note is prepared and the material is fired as per procedure for destruction in the presence of supplier.
Note: Store Manager checks reanalysis date of all the active raw materials on monthly basis from the stock (inward and outward) position log and will raise the request of analysis for retesting following the above procedure.

5. Precautions
1. Materials must be handled very carefully and should be placed at its proper place.
2. Each material must be labeled and well identified.

6. Quality Record(s)/Form(s)
The following quality records shall be generated and managed in accordance with the procedure for Control of Company Quality Records (4.12)

Required Record Form Reference No.
Goods Acknowledgement Note QF/148/01
Request for analysis (Packaging Materials) QF/112/01
Request for Analysis (RAW Materials) QF/064/01
Stock (inward & outward) position log QF/106/01
Daily entry log book for Raw materials QF/071/01
Daily entry log book for Packing materials QF/040/01
Goods return note QF/051/01
Destruction note QF/115/01

Standard Operating Procedure Title: Pyrogen Testing

Purpose:
• It is established for the verification of absence of any pyrogen in the sterile Product or the Raw Material/Water thereof.
2. Scope:
• It is applicable to Microbiological Lab.
3. Responsibilities:
• Quality Control Manager
• Microbiologist
4. Procedure:
• Rabbits on which test has to be performed should be separated and kept without food for at least 18 hours prior to the test.
• Select the rabbits of weight not less than 105 Kg of either sex.
• Insert the thermometer or Electrical device showing a precision of 0.1oC to a depth of 5 cm in the rectum of each rabbit and put them in the retaining boxes,in which the animals are retained by loosely-fitting neck stock and rest of the body remains free so that rabbit can sit.
• Record the temperature of animals at least 90 min. before injection.
• Rabbits showing a temperature difference greater than 0.2oCbetween any two successive readings are with drawn from the test.
• All rabbits having an initial temperature greater than 39.8oC or lower than 38.0oC are excluded from the test.
• Take three 250 ml volumetric flasks which are previously sterilized by dry heating,at 200 o C in oven for one hour in oven for one hour in hot air oven.
• Put 1.8 g of NaCl of Anal grade in every flask.
• Take the sample of D/W 200 ml in each of three flasks.
• Sealed the flask with Al-sheet and with autoclave tape.
• Autoclave these flasks at a pressure of 15 pound for 15 minutes.
• After completion of autoclaving cool the flasks at room temperature to about 38-40oC.
• Take syringes and needles previously washed and sterilized at 200 oC for 1 hour.
• Inject the solution slowly into the marginal vein of the ear of each rabbit in accordance with the weight of rabbits i.e. 10 ml/Kg.
• Note the temperature of each rabbit for 3 hours after injection.
Interpretation Of Results.
• Note the average temperature of rabbits before injection.
• Note the maximum temperature of the rabbits after injection.
• Note the difference between the initial temperature in addition, the max temp. of each rabbit is taken to be its response.
• If the summed response is exceeded from 1.15oC button more than 2.65oC repeat the test.



Quality Record(s)/Form(s)

The following quality records shall be generated in accordance with the procedure for Control of Company Quality Records (4.12).

Required Record Form No.
Report of Pyrogen Test QF/059/01

PRODUCT FEASIBILITY PROFORMA

Purpose:

It is established for Product Feasibility Proforma.

2. Scope:

This procedure is applicable to R&D department.

3. Responsibilities:

1. Manager R&D
2. R&D Pharmacist

4. Procedure:
1. R&D deparment initiates this proforma in response to marketing requirement proforma through Chief Executive.
2. This proforma is raised for the new product or change /improvement in the existing formulation.
3. The trade name, generic name and dosage form of the product is mentioned.
4. In case of metto product, the name of product and company is also mentioned
5. Resourses like material, machine, equipment required etc., are documented by R&D deparment.
6. The statement whether required product manufacturing is feasible or not also mentioned.
7. The complete proforma must be approved by Chief Executive.

Standard Operating Procedure Title: Procedure for Hold

1.0 Purpose
1.1 It is established to assure quality in all aspects, and to avoid any unintentional contravention of Drug Act, cGMP and company standards.
2.0 Scope
2.1 It is applicable to all types of incoming and out going materials and all type of activities / process, conditions, equipment, documents, material and any “thing” (i.e. conditions, process, activity, material, equipment and document) which can affect quality directly or indirectly.
3.0 Responsibilities
3.1 Manager Quality Assurances.
3.2 Assistant Manager Quality Assurance.
3.3 Quality Assurance Officer.
4.0 Procedure
4.1. During the routine in process checks if any thing found to be in contravention of any requirements, regulations, system (which are well defined in SOPs, SMPs, and Product Specification) matter will be discussed with relative incharge / Departmental Head to remove that short coming.
4.2. If the production department takes no action on verbal intimation that particular thing will be “HOLD” by affixing red specified label of “HOLD” which means to stop that “thing” (already defined).as and where it is.
4.3. After “HOLD” the particular thing should be Segregated/Removed from that place into safe custody of either Production / Q.A Department.
4.4. In case of “HOLD” it is responsibility of QA department to intimate relative Incharge in Written and to give suggestion, advice or direction in that particular mater, and to direct relative department to submit the reasons in written about that particular matter.
4.5. In that particular “thing” which is under “HOLD” will be released after the submission of written acceptable justification by relative department.
4.6. If the matter will remain disputed, meeting of all departmental heads will be called to resolve the matter.
4.7. Finally the matter will be brought into the notice of Director Operation /Chief Executive and they are the the supreme authority to make any decision.
5.0 RECORD REQUIRED:
The following record shall be generated in accordance with “HOLD” procedure:
Required Record Form Reference No.
HOLD sticker QF/070/01
Interdepartmental memo QF/028/01

STANDARD OPERATING PROCEDURE Title: “Recall of Product”

1. PURPOSE
1.1 It is established for the establishment of procedure for recall of finished product from Market.
2. SCOPE
2.1 It is applicable to all products in market suspected or found to be defective.
2.2 Any packs returned from patient to the pharmacy will not be accepted.
3. RESPONSIBILITIES
3.1 General Manager Production
3.2 Manager Quality Assurance.
3.3 Assistant Manager Quality Assurance.
3.4 Manager Stores
3.5 Marketing Manager
4 PROCEDURE
4.1 Reasons for recall
1. Any complaint from market regarding quality & which after evaluation by QC is found to be justified.
2. Any observation from within the organization regarding quality & which after evaluation by QC is found to be justified.
3. Any product which is 6 months near to expiry date.

4.2 Initiation for recall
1. In case of 1st reason for recall, Marketing Manager receives the complaint from market, documents its detail (Date, Name of Complainer, address, nature of complaint, frequency of complaint, Product name, strength, batch no, Mfg date & Expiry date, any other necessary information) on Inter office memo & sends it to Quality Control Manager along with the sample of the product.
2. In case of 2nd reason for recall, Quality Control Manager informs Marketing manger about the nature of problem, Product name, strength, batch no, Mfg date & Expiry date, any other necessary information on Inter office memo.
3. In case of 3rd reason for recall, Marketing Manager will write to the distributors to submit information of their stock level for that particular product & after receiving the same intimate to the Quality Control Manager.
4.2 Execution of recall
1. If Quality Control Manger with consultation of Quality Assurance & Production comes to the conclusion that product is not of stated/intended quality and/or it may affect the patient or his compliance to the product he immediately writes to Marketing Manager to recall the product from all of distributed areas.
2. Marketing Manager writes to all of the distributor to dispatch the product stock to the Factory premises within the specified time period addressed to the Manager Stores (Finished Goods).
3. Manger Stores (Finished Goods) receives the stock & quarantine it in the specified quarantine area being product in its original packing.
4. Manager stores (Finished Goods) verifies the quantities & identity of the product.
5. If product is not near expiry date, Manager stores sends request for analysis to the Quality Control Department.
6. Quality assurance department samples the product & sends to QC.
7. In case product is not identified regarding its Batch No., Mfg. date, identity or strength (in case if more than one strength registered) it will never be sampled & will be rejected in straight.
8. Quality Control department subjects the product to analysis & may suggest
a. The product reprocessing
b. The partial destruction of the quantity
c. The complete destruction of the product.
4.3 Product reprocessing
1. In case reprocessing is recommended by QC, Quality report to store clearly indicates the same. One copy of quality report is sent to Production Manager.
2. Production Manager intimates the same to the relevant section head.
3. Section head raises the request for issuance of recalled product to the store & after verifying the quantity receives the stock.
4. If required, new batch number is allotted to the reprocessed product in such a way that the parent batch number is identified as being reworked.
5. After reprocessing is completed product is transferred to the store on Batch transfer note indicating clearly the new batch number & the previous one. One copy of this note is attached with the parent batch file.
4.5 Destruction of recalled product
1. If QC department after necessary testing activity comes to the conclusion that no reprocessing is possible or there can be no identification of the Batch number of the product & destruction is recommended by the QC department the Manager stores raises the “Destruction Note” clearly indicating the reason for destruction & quantity thereof; he sends this note to QA department.
2. QA department receives the stock & destroys it in the presence of deputed QA person.
3. Destruction of recalled Vaccines:
a. Vaccines are destroyed in manner that assures there remains no life in the product.
b. Secondary packing of the packs is removed off & packs are arranged in autoclave box and sealed completely.
c. Subject the product to autoclaving at 1210C for 1 hour.
d. After autoclaving packs are opened & buried the contents in soil.
e. Primary packing components (glass vial, ampoules etc) are not reused & broken away.
4. Destruction note is duly signed by the deputed QA officer, QA Manager & is filed in the parent batch file.
5. Quality Control manager intimates in writing to Marketing Manager about the action taken towards the reprocessing or destruction of the stock.

STANDARD OPERATING PROCEDURE Title: Preparation of Petri-dishes for Microbial Testing

Purpose:
To describe the method of preparing Petri-dishes for carrying out different microbiological tests

2. Scope:


3. Responsibilities:

1. Microbiologist
2. Lab Assistant

4. Procedure:

1. Transfer all the required materials to LFC bench taking all necessary microbiological precautions.
2. Remove plates from SS box on to the bench and let them cool.
3. After cooling of the plates obtain Media (TSA) from water bath and mop outer surface with duster wet with disinfectant.
4. Now carefully take one plate and half open it by one hand and pour approximately 20 ml of agar media and close the plate. Care should be taken that do not lean over the open plate or media nor take your hand or arm over opened plate.
5. Similarly pour all the plates as soon as possible as agar media starts solidifying. Plates are spreaded on the bench to ease the solidification.
6. Pour media in such a way to inhibit the bubble formation in the agar media.
7. Let plates as such for at least 20 minutes for solidification.
8. After solidification label each plate with abbreviation of media name, date of preparation.
9. Gather all the plates and transfer in a container into the appropriate incubator for pre-incubation in inverted position for at least 24-48 hours.
10. Before conducting any test observe the plates carefully for the evidence of any growth.

5. Precautions

1. Store the plate in refrigerator if testing is delayed.
2. Plates should be used as early as possible as de-moisturing starts.
3. See that media is not overheated.
4. Check that the sterilization cycles are satisfactory..
5. Check the expiry date of dehydrated media.
6. Check the washing process of the glassware.

Standard Operating Procedure Title: Preparation of Media For sterility Testing.

Purpose:
• It is established for the preparation of media for sterility test first assure that all the glassware properly washed and sterilized in oven at 200o C for 1 hour.Cool the glassware at room temperature by covering the mouth of glassware from environment.
2. Scope:
• It is applicable to Microbiological Lab.
3. Responsibilities:
• Quality Control Manager
• Microbiologist
4. Procedure:
• FOR FTM:
• Take a sterilized 500 ml screw capped conical flask and take 500 ml of distilled water in it
• .warm it about 70-80oC.
• Weigh 14.750 g of media on weighing boat /tulip funnel and pour it into flask containing distilled water.
• Swirl it to dissolve while heating until a clear solution is obtained.
• Take sterilized 250 ml media glass bottles and pour 100 ml of media in each bottle.
• Autoclave the media bottles at 121oC at apressure of 15 pound.
• After autoclaving cool the media bottles to room temperature.
• Preserve the media for 3-4 days and assure that media is free from contamination.
For SDB:
• Take a sterilized 500 ml screw capped conical flask and take 500 ml of distilled water in it
• .warm it about 40-45oC.
• Weigh 15.0 g of media on weighing boat /tulip funnel and pour it into flask containing distilled water.
• Swirl it to dissolve, until a clear solution is obtained.
• Take sterilized 250 ml media glass bottles and pour 100 ml of media in each bottle.
• Autoclave the media bottles at 121oC at and pressure of 15 pound for 30 minutes.
• After autoclaving cool the media bottles to room temperature.
• Preserve the media for 3-4 days and assure that media is free from contamination.
Peptone water buffer:
• Take a sterilized 500 ml screw capped conical flask and take 500 ml of distilled water in it
• Add 0.5 g of peptone water buffer and shake to dissolve.
• Autoclave the buffer bottles at 121oC at and pressure of 15 pound pressure for 30 minutes.
• After autoclaving cool the buffer to room temperature.
• Preserve the media for 3-4 days and assure that media is free from contamination.
Procedure:
In case of liquid, use 20 representative containers.
• Clean the exterior surface of ampoules with Isopropyl alcohol and gain access to contents in aseptic manner.
• Remove the liquid from test container with sterile pipette or sterile syringe and needle.
• Aseptically transfer 20 ml of the contents from 20 containers to a 200 ml sterile peptone buffer solution.
• Sterilize filter paper, filtration assembly, pipes dress, waste bottle.
• Fit the filtration assembly on waste bottle. Dip one end of the pipe from filtration assembly into peptone buffer solution.
• Filtration assembly is attached with the vacuum pump. Apply vacuum to affect filtration.
• After filtration, Open aseptically remove filter paper containing expected counts with the help of a sterile forcep and cut it into two pieces with the help of a sterile scissor.
• Place half paper aseptically in FTM media and second in SDB media. Incubate FTM media at 30-35oC and SBD media at 20-25oC for seven days.
Interpretation of results:
If FTM is hazy or turbid, bacterial count is positive.
If SDB is hazy or turbid, fungal count is positive.
If both are transparent, bacteria and fungus are absent.
Procedure:
In case of tablet take 20 units, corresponding to not less then 300 mg from each container being tested or to the entire contents of each vial contains less than 300 mg of solids. Clean the exterior of vial with Isopropyl alcohol and gain excess to the contents from container in an aseptic manner. Aseptically transfer about 6.0 g of contents to 400 ml sterile peptone buffer solvent. Sterilize filter, filter holder assembly, pipes, dress and bottle for waste.
Place one end of the pipe from filter holder into the peptone buffer solution.2nd end of the filtration assembly is attached with the vacuum pump apply vacuum to affect filtration, after filtration pass 400 ml of buffer, open aseptically and remove filter paper containing expected count with the help of a sterile forceps and cut it into two pieces with the help of a sterile scissors, place half paper aseptically in FTM media and 2nd in SDB media, Incubate FTM media at 30-35oC SDB 20-25oC for fourteen days.
Interpretation of results: If FTM is hazy or turbid bacterial conc. +ve
If SDB is hazy or turbid fungus +ve
If both are transparent bacterial fungus both assent.

Quality Record(s)/Form(s)

The following quality records shall be generated in accordance with the procedure for Control of Company Quality Records (4.12).

Required Record Form No.
Report of Pyrogen Test QF/059/01

STANDARD OPERATING PROCEDURE Title: Preparation of Disinfectant

Purpose:
To describe the procedure for the preparation & use of the disinfectants to be used in microbiology laboratory.

2. Scope:
This procedure is applied when the preparation of the disinfectants is required.

3. Responsibilities:

1. Microbiologist
2. Lab Assistant

4. Procedure:

A. DISINFECTANTS

1. PHENOL 5% V/V (Carbolic acid)
Phenol 5.5 ml
Distilled water 100 ml q.s. (Can be sterilized for sterile areas at 121°C for 30 min.)
This concentration is normally used for mopping walls, floors, table tops, gloves and outer surfaces of sample containers and Petri-dishes etc.
Adverse Effects
They are poisonous if swallowed.
Causes chemical burns if directly contacted with skin.
The odour is highly irritating.
They may stain wool, cotton and synthetic fabrics.
Storage
Sterilized Phenol can be stored for one month.

2. ALCOHOL 70% V/V
Isopropyl Alcohol 74 ml
Distilled water 26 ml to make 100 ml of 70% Alcohol. (It is filtered for sterile area use).
They are normally used where prolonged disinfection is not required. This concentration is used to disinfect the gloves, surfaces of Laminar Flows, outer surfaces of samples containers and Petri-dishes etc.
Adverse Effects
Alcohols are toxic and irritant to skins and generally unsuitable for application to mucous membranes.
Rubber swells and plastics may be hardened by frequent or prolonged contact with alcohols.
Storage
Filtered Alcohol can be stored up to one week.

3. DETTOL 2% V/V (Chloroxylenol)

Dettol concentrated 20 ml
Distilled water 980 ml
It can be used as disinfecting surfaces, gloves, outer surfaces of sample containers etc.
Adverse Effects
Same as of Phenols at high concentrations.

4. FORMALIN 5%

Formalin (37-40%) 70 ml
Make up the volume to 500 ml
It is basically used for fumigation purposes in sterile areas in Pharmaceutical industries. The spray after work to disinfect hazardous microbes is recommended.
Adverse Effects
Vapours are extremely irritant to the eyes and respiratory tract at 2-5 p.p.m conc.
Direct contact causes skin irritation and allergic dermatitis.

B. PERSONAL PROTECTION
Take all necessary safety measures during preparation of disinfectants because they all are toxic to human beings too.
Wear goggles.
Wear appropriate protective gloves.
Wear respiratory full face mask with appropriate filter where applicable.

C. EMERGENCY CASES
Immediately inform the supervisor.
In case of injury contact for medical help

STANDARD OPERATING PROCEDURE Title: PILOT PLANT SCALE-UP

1. Purpose

It is established for Pilot Plant Scale-Up
2. Scope

This Procedure is applicable to R&D Department

3. Responsibilities
1. Manager R&D
2. Assist. Manager R&D
3. Analyst R&D
4. Procedure
1. After conducting successful trial on any of the product, R&D Department keeping in view the production area facilities and provision will prepare a pilot formulation.
2. Pilot Plant Scale-Up will be planned for the 1st three commercial scale batches by the production department.
3. This will take the shape of standard formulation after the completion of these 3 consecutive batches.

STANDARD OPERATING PROCEDURE Title: pH Calibration

1. PURPOSE

It is established for the calibration of pH meter.
2. SCOPE
It is applicable to Quality Control Department.
3. RESPONSIBILITY:
1. Quality Control Manager
2. Assistant Manager Quality Control
4. PROCEDUR
pH CALIBRATION for H19318 PROCEDURE.
• Switch the instrument on after the electrode and temperature probe.
• Immerse the pH electrode and the ATC probe into pH 7.01 buffer solution.Shake briefly and wait 1-2 minutes for thermal equilibrium.
Note: The electrode should be submerged approximately 4 cm (11/2) into the solution.The temperature probe should be positioned as close to the pH electrode as possible.
Press the CAL key.

The Printer will then print step by step instructions for the
Calibration procedure.

At the same time the pH symbol will flash to indicate that calibration is in progress.The ph value at the measured (or manually) adjusted temperature will be displayed.
If “Err 4” appears on the display it means the electrode is in the wrong buffer.Check to make sure that the electrode is in ph 7.01 beaker and wait for the “Err4” to disappear.
• After approximately 30 seconds, press the CON key to confirm the calibration.


The printer will print further instructions for the calibration procedure.



The LCD will show “Err5” to indicate that the electrode is now ready for slope calibration.
• Immerse the probe into 4.01 or 10.01 solution.










The LCD will show the corresponding buffer vaue at the working temperature.








• Wait approximately 30 seconds,and then press the CON key to confirm the calibration.

STANDARD OPERATING PROCEDURE Title: Sterile Area Particle Counting

1. Scope

It is established to provide guideline for the use of particle counter.

2. Purpose

It is applicable for counting of particles in sterile area

3. Responsibilities

1. Manager Q.C
2. Microbiologist.

4. Procedure

Personal entering in sterile area should wear first sterilized uniform goggles, surgical gloves and wipe off equipment before caring in sterile area.

1. Press blue colour on/off button on right side of the instrument.
2. Main menu shows table having different particle size e “zero values”
3. Set main statistics sampling set up icons for specific location, as during the statistical certification process.
Process we will move the unit to different locations for sampling. The (LASAIR ll) particle counter allow us to choose one of the two following option for identifying different locations.
1. Auto incrementing names/numbers.
2. Manual user selection of the location name or number and our choice of numbering method will determine the setting. We must made in statistical set up page.
3. To edit the statistics set up main screen press the enter button to enable the edit mode.
4. Use the Tab forward / Tab backward keys to move to the desired location, select the particle size, type of flow (unidirectional or multidirectional), Purge time, area/volume (sample vol can not be changed while the statistics mode is enabled)
5. First when we have set up the (lasair ii) for sampling, operation is a simple matter.
6. Press the green button on the control panel after fixed the sampler in sample prob for purging and sampling in particular area.
7. After a purge the unit will begin sampling and the results of sampling can be observed on the main display. When the sampling is complete the pump will stop.
When all samples are complete the dialog box with following comments”statistics sampling is complete” will appear.
8. Take print out of results through statistics “print icon soft keys” and compare with following different class limits.


Classes 0.1 0.2 0.3 0.4 1.0 5.0
1 10
2
2 100
24 10 4
3 1000
237 102 35 8
4 10,000
2370 1020 352 83

5. Precaution:

1. Keep close sampler prob after use.
2. Never wipe the display screen with anything that is hard or sharp

6. Cleaning:

For cleaning purpose tested cleaning chemicals which can be use are.

1. 50—90% sol of IPA in deionized H2O
2. 30% Amonia sol can also be use
3. Ethyl alcohol in a sol of <50%

STANDARD OPERATING PROCEDURE Title: Particle Counter

1. Purpose

It is established to provide guideline for the use of Particle Counter.

2. Scope

It is applicable for counting of particles in sterile area.

3. Responsibilities

1. Manager Q.C

2. Microbiologist.

4. Procedure

1. Press blue color on/off button on right side of the instrument.

2. Main menu shows table having different particle size e zero values.

3. Go to main option “purge” and select area, sample size area code, purge time and enter it.

4. Then fix sampler in sampler prob and press “Start” green button for purging & sampling in particular area.

5. After the data obtain after few time will show different particle sizes.

6. Take print out through pressing printer button.

5. Precautions:

1. Keep close sampler prob after use.

STANDARD OPERATING PROCEDURE Title: Packing Material Analysis

1. Purpose

a) It is established to provide a standard procedure for “PM Analysis”.

2. Scope

a) It is applicable for PM analysis.

3. Responsibilities

a) QC Manager

b) PM Analyst

4. Procedure

a) PM sample is handed over by QA officer to PM Analyst, along with PM Analysis request.

b) Following parameters are needed to be checked.

1) Text

2) Card color

3) Printing color

4) Grammage

5) Thickness

6) Dimension

Text, card color and printing color are compared with reference standard checked and signed by QC Manager.

To check card grammage, cut a square piece (e.g. 4x4 cm or 5x5 cm) and find out its weight.

Weight of card or paper is divided by area (e.g. 16 or 25 respectively) and multiplies it with 10,000 to convert cm2 into m2. The unit for grammage is gm/m2.

In case of labels, vials, ampoules, seals, rubber stoppers, average weight is required.

Micrometer (Screw gauge) is used to measure the thickness of card. Note the reading on circular scale and multiply it with least count 0.01. It shows the thickness in mm; convert it to μm by multiplying it with 1000.

Dimensions are measured either by scale or vernier caliper.

Grammage, thickness and dimensions are compared with packing material specifications.

In case of Al. tubes, glass containers, and rubber stoppers testing, follow the procedure specified in relevant SOPs.

PM sample is physically checked for any color variation, pasting problem, misprinting or any sign of damage.

After complete analysis, QC # is allotted to the specified lot, in Daily Entry Log book for Packing Material. PM report is prepared accordingly, and “PM Approval” slips in case of approved material and “Not Approved” slip in case of rejected material, is issued.

5-10 samples of packing material are kept as “Retained Sample”, labeled with QC # and analysis date, whether it is approved or rejected.

5. References:

Chemical test for glass containers GL/SOP/QC/033

Chemical test for Al.Tubes GL/SOP/QC/032

Chemical test for Rubber Stoppers GL/SOP/QC/035

6. Quality Records:

Required Record

Form Reference No.

Daily Entry Log book for Packing Material

QF/040/01

Packing material analytical report

QF/066/01

Packing material approval slip

QF/060/01

Not approved slip

QF/019/01