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.