DIFFERENT EXAMPLES OF SOPs

Which activities require SOPs?

1. Equipment and analytical apparatus: Assembly, validation Calibration Internal labelling, quarantine and storage of materials Operation Maintenance and cleaning2. Personnel matters: Qualification Training Clothing Hygiene

Which activities require SOPs?

3. Environmental monitoring4. Pest control5. Complaints6. Recalls7. Returned goods 8. SOP and records for receiving materials

Name of material as on delivery noteName and in-house codeDate of receiptSupplier's and manufacturer's nameBatch numberQuantity and number of containers receivedState of container and other information

Which activities require SOPs?

9. Other SOPs : Internal labelling, quarantine and storage of

materialsOperation, maintenance, calibration and

cleaning of all instruments and equipment – production and QC

Sampling of materialsBatch numbering systemsMaterial testing at all stages of productionComplaints, recallsBatch release or rejectionMaintenance of distribution recordsEquipment assembly and validationMaintenance, cleaning and sanitationPersonnel recruitment, training, clothing and

hygieneEnvironmental monitoring

DOCUMENT CONTROL SOP

1.0 PURPOSE :To provide a procedure for document control.2.0 SCOPE :To ensure a complete control over all the authorised documents.3.0 RESPONSIBILITY :QA Personnel4.0 PROCEDURE :4.1 All documents should be identified by a unique title and document number.4.2. Document should be designed, prepared, received, approved, signed and dated by authorised persons and distributed to concerned departments.4.3. Approved documents should not be corrected manually with a pen / pencil for any reason.

Preparation of Documents4.4 Master Formula Record -Master formula record to be prepared by QA in consultation with Formulation development, Production and Quality Control.Master formula record includes :4.4.1 Batch Manufacturing record (BMR).4.4.2 Batch Packing record (BPR).4.4.3 Intermediate/ Packing Material / Finished product specification.4.4.4 Specimen of Printed packaging material.

4.5 All documents of “ Master Formula Record” should be stamped as “Master Copy” in Green at the non- text side (back side).4.6 Batch Manufacturing Records consists of following.4.6.1 Manufacturing Work Order.4.6.2 Coating Work Order4.6.3 Stage wise processing details4.6.4 In-process checks4.6.4.1 Compression and coating (Tablets)4.6.5 Deviation (if any)

4.7 Batch Packing Records consists of following.4.7.1 Packing work order.4.7.2 Over printing details4.7.3 Packing details4.7.4 In-process checks4.7.4.1 Over printing4.7.4.2 Bottle washing and filling (liquid orals)4.7.4.3 Bottle cleaning and filling (Dry Syrup)4.7.4.4 Packing4.7.4.5 Shipper weight profile4.7.5 Deviation record (if any)

Document Issuing

4.8 During the issue of a document the necessary entries have to be made in the respective document control register with details of Document name, Document number, Issued by, received by, Retrieved document No., (if any) Number of copies retrieved, destroyed by, Date, Checked by details.

4.9 BMR / BPR - photo copies of master copy are issued for regular production. All sheets of photo copies should be signed and dated by QA Personnel.

4.10 Completed batch record should come back to QA for review.

4.11 After review of the records and QC analytical results, QA will release the batch (Product) for sale.

4.12 All the completed batch records should be controlled by QA.4.13 All batch record should be retained atleast for five year after the shelf life of the product.4.14 Validation protocol / Report / Summary: All validation protocols to be prepared by QA and issued to respective department.4.15 After completion of validation, the Protocols, Reports along with the QC results and Summary report to be prepared and filed by Q.A. department in respective validation records.4.16 Protocols and reports of cleaning validation with the QC analytical reports to be prepared and filed in a Cleaning validation file.4.17 Equipment Qualification: Equipment Qualification protocols / Reports to be issued by QA to the respective department.

4.18 All completed Equipment Qualification Protocol / Reports should be compiled by QA in respective qualification files.

4.18.1 Design Qualification4.18.2 Installation qualification4.18.3 Operational qualification4.18.4 Performance qualification4.18.5 Visit reports (if any)

4.19 Specifications :All specifications of Raw material / Packing material / Intermediate / Finished product specification to be prepared by QC and authorised by QA. Original documents should be filed in respective master files of QA Department with a “MASTER COPY” seal in green colour on the text side (backside) of the page.4.20 A controlled copy of specification should be issued to the QC department with “CONTROLLED COPY” seal in red colour on top of each page on the printed side.

4.21 Standard Operating Procedure :SOP to be prepared as per the SOP preparation of SOP.4.22 Master copies of SOP should be filed in QA department in respective files with “MASTER COPY” seal in green colour on the non text side (backside) of the page.4.23 Different stamps should be used for circulating SOP to the concerned departments either with a “CONTROLLED COPY” seal in red colour or “DISPLAY COPY" in blue colour on top of each page on the printed side as per the need.

4.24 Third party document :Separate files to be maintained for each third party. 4.25 Batch records for Third parties to be prepared by QA Department according to their requirement.4.26 Master copy of the records to be filed in respective files and controlled copies should be issued to concerned parties.4.27 Batch summary sheet and other related documents to be collected by them, reviewed and filed by QA.4.28 Art worksAll documents related to artwork approval including the specimen samples to be filed and controlled by QC and QA department.

4.29 Stability samples Details of stability samples to be maintained.4.30 Log Books : Following Log books should be maintained (Annexure – List of log books with numbers)4.30.1 Production Department4.30.1.1Equipment Operation4.30.1.2 Equipment Cleaning4.30.1.3 Planned Preventive Maintenance of Equipment4.30.1.4 Temperature and Humidity4.30.1.5 Pressure Differential4.30.1.6 Balance Calibra

4.30.1.7 General House Keeping4.30.1.8 PestoFlash4.30.1.9 Issue and control of stereos4.30.1.10 Issue and control of Punches and dies4.30.1.11 Intermediate log4.30.1.12 Overprinting of Packaging Materials4.30.1.13 pH meter log4.30.1.14 Transfer pump and Transfer line log4.30.2 Utility Department4.30.2.1 DM Plant Operation4.30.2.2 DM Plant Regeneration4.30.2.3 Planned Preventive Maintenance of AHUs4.30.2.4 Compressed Air4.30.3 Quality Control Department4.30.3.1 Instrument Operation and cleaning4.30.3.2 Volumetric Solutions4.30.3.3 Reference Standard4.30.3.4 Working Standards4.30.3.5 Reserve Sample

4.30.3.6 Control Sample4.30.3.7 Glass ware calibration4.30.3.8 Calculation sheet4.30.3.9 pH meter4.30.3.10 Distilled water log4.30.3.11 Autoclave Calibration4.30.3.12 Sub culturing and destruction of sub culture4.30.3.13 Media Stock Register4.30.3.14 De-fumigation checks log 4.30.3.15 Media Preparation4.30.3.16 Media destruction4.30.3.17 Growth Promotion test

4.30.3.18 Plate exposure4.30.3.19 UV lamp log4.30.3.20 Raw materials analysis4.31 Training record : The training records of individual personnel, should be retained till the last record which has to be signed by him expires.Training Records consists of4.31.1 Annual training Schedule4.31.2 Training modules4.31.3 Individual Training records4.31.4 General Training record4.31.5 Material/Visual aids/Literature used for Training4.32 Apart from the above documents, QA Department should also maintain the following records.4.32.1 Technical Change Procedure4.32.2 Audit report4.32.3 Fumigation record4.32.4 Packing specification 4.32.5 Monthly report

4.32.6 Annual report4.32.7 Training record- Schedule and individual training files4.32.8 Medical checkup record4.32.9 Pest control record4.32.10 Market complaint4.32.11 Instrument calibration(External agency)4.32.12 Batch Record Register4.32.13 Validation Register (Cleaning, Process and Method)4.32.14 Change control4.32.15 Deviation4.32.16 Out of specification records4.33 Document RetrievalA revised document will be issued only after retrieval of the superceded Control copy and Display copy from concerned department. The superceded Master Copy will be retained with the "OBSOLETE COPY" stamp in black colour for future reference and other copies (Controlled and Display copy) will be destroyed.A record of issue of documents and retrieval and destruction of the superceded documents will be maintained.

Retention of Documents 4.34 All documents should be retained for at least one year after the expiry of finished products.

1.0 OBJECTIVE1.0 OBJECTIVETo lay down a procedure for maintenance of dies and punches.To lay down a procedure for maintenance of dies and punches.2.0 SCOPE2.0 SCOPEModule –2,3,4Module –2,3,43.0 RESPONSIBILITY3.0 RESPONSIBILITYConcerned operator.Concerned operator.4.0 ACCOUNTABILITY4.0 ACCOUNTABILITYProduction officer.Production officer.5.0 PROCEDURE5.0 PROCEDURE5.1 Get required number of punches and dies from Quarantine and make 5.1 Get required number of punches and dies from Quarantine and make necessary entries in punches and dies stock card and get it checked by necessary entries in punches and dies stock card and get it checked by production officer.production officer.5.2 Transfer the required punches and dies to the compression area.5.2 Transfer the required punches and dies to the compression area.5.3 Remove punches from plastic cover and wipe out the oil adhering to the 5.3 Remove punches from plastic cover and wipe out the oil adhering to the punches and dies.punches and dies.5.4 Set up and fix punches and dies as per the SOP of compression machine 5.4 Set up and fix punches and dies as per the SOP of compression machine change over operation.change over operation.5.5 If any abnormal sound is observed during compression, immediately 5.5 If any abnormal sound is observed during compression, immediately stop the compression machine to avoid punches and dies damage and stop the compression machine to avoid punches and dies damage and inform production officer.inform production officer.5.6 Examine critically the punches and dies, remove the damaged punches 5.6 Examine critically the punches and dies, remove the damaged punches and dies if any from the machine and replace them.and dies if any from the machine and replace them.5.7 Remove the punches and dies after the compression.5.7 Remove the punches and dies after the compression.5.8 Clean thoroughly the punches and dies with lint free duster.5.8 Clean thoroughly the punches and dies with lint free duster.5.9 Smear the punches with oil and put inside the plastic covers.5.9 Smear the punches with oil and put inside the plastic covers.5.10 Count and keep separately the upper and lower punches and dies in 5.10 Count and keep separately the upper and lower punches and dies in separate boxes.separate boxes.5.11 Make necessary entries in stock card and transfer to the punches and 5.11 Make necessary entries in stock card and transfer to the punches and dies storage area.dies storage area.5.12 Get the signature in the stock card by production officer.5.12 Get the signature in the stock card by production officer.

1.0 OBJECTIVE : 1.0 OBJECTIVE : To specify norms for clothing to be used at To specify norms for clothing to be used at workplace.workplace.2.0 SCOPE: 2.0 SCOPE: Appropriate clothing at workplace, footwear and Appropriate clothing at workplace, footwear and headgear are extremely important from safety point of view.headgear are extremely important from safety point of view.3.0 RESPONSIBILITY3.0 RESPONSIBILITYAll Employees of XYZ Ltd.All Employees of XYZ Ltd.4.0 ACCOUNTABILITY4.0 ACCOUNTABILITYCheif Executing OfficerCheif Executing Officer5.0 PROCEDURE5.0 PROCEDURE5.1 Get dressed for work wearing clothing, headwear and shoes 5.1 Get dressed for work wearing clothing, headwear and shoes prescribed for the type of your work.prescribed for the type of your work.5.2 Wearing of neckties, scarves, ornaments like bangles or loose 5.2 Wearing of neckties, scarves, ornaments like bangles or loose necklaces, earring etc. may prove hazardous while working on or necklaces, earring etc. may prove hazardous while working on or near moving or unguarded parts of machines and hence should near moving or unguarded parts of machines and hence should not be worn while at work.not be worn while at work.5.3 Never wear loose fitting sleeves when working on moving 5.3 Never wear loose fitting sleeves when working on moving machinery.machinery.5.4 Laboratory overalls should be worn while working in laboratory 5.4 Laboratory overalls should be worn while working in laboratory to avoid chemical contamination and for the purpose of personal to avoid chemical contamination and for the purpose of personal safety.safety.5.5 Work clothing should be regularly laundered and kept in good 5.5 Work clothing should be regularly laundered and kept in good repair.repair.5.6 Appropriate sterile uniforms should be worn while working in 5.6 Appropriate sterile uniforms should be worn while working in sterile area. A suitable laundering and sterilization schedule sterile area. A suitable laundering and sterilization schedule should be followed.should be followed.5.7 Protective wear such as caps, helmets, safety footwear, 5.7 Protective wear such as caps, helmets, safety footwear, gloves, masks and goggles must be used as per job requirement. gloves, masks and goggles must be used as per job requirement. Other appropriate personal safety equipment should be used Other appropriate personal safety equipment should be used while carrying out hazardous jobs.while carrying out hazardous jobs.

1.0 OBJECTIVE

To provide standard operating procedure for calibration, operation and cleaning of weighing balance.

2.0 SCOPE

Production Department.

3.0 AREA OF OPERATION

Store Department.

4.0 RESPONSIBILITY

Operator concerned

5.0 ACCOUNTABILITY

Stores Incharge.

6.0 CALIBRATION

6.1 Check the cleanliness of the balance & weighing area.

6.2 For calibration of the balance standard weights which are calibrated are used.

6.3 Level the balance properly.

6.4 Select the standard weights according to the capacity of balance i.e. lower weight, middle weight, & upper weight of a balance capacity.

6.5 Switch ON the balance adjust to "0".

6.6 Place standard weight one by one on the weighing pan & record the reading in the balance calibration record.

6.7 Check that the observed weights are with in the limits. Acceptable limit is _ñ_ 0.1%.

7.0 REVIEW DATE

After 2 years or when procedure is changed.

1.0 PURPOSE

Purpose of this procedure to maintain & establish a documented system for Issue of Drugs from Stores.

2.0 SCOPE

This procedure is applicable to the issue of Drugs at XYZ Healthcare. This includes supplied by contact Giver Parties.

3.0 RESPONSIBILITY

Store incharge is responsible for implementation of this procedure.

4.0 PROCEDURE

4.1 Preparation And Preliminary Steps

4.1 a) Ensure the accountability of drug approved slip only.

4.1 b) Follow the procedure only after receiving the approved drug slip only.

4.2 Preparation And Safety Consideration Used only specified drugs.

5.0 Chronological Activity And Sequence

5.1 Store Officer will Issue the drug material in presence of Q.A. Officer only.

5.2 Take only approved amount.

5.3 Check the following before Issuing

5.3 a) Name of the product on label.

5.3 b) A.R.No. of the drug material.

6.0 POST OPERATIONAL ACTIVITY6.1 After completion of issuing of drug material , store officer & production officer will sign on the Test

Substance Accountability Form.6.2 Enter the details in Drug material stock register.

7.0 REPORTINGMake the relevant entries in drug material sheet & batch document.

8.0 REFERENCE DOCUMENTSDrug Substances stock register.

9.0 REVIEWAfter two years or when procedure is changed.

1.0 OBJECTIVETo lay down the Standard Operating Procedure for cleaning and maintenance of the Millipore Filtration Unit.

2.0 SCOPE The procedure is applicable to cleaning and maintenance of the Millipore Filtration Unit.

3.0 RESPONSIBILITYLaboratory Technician, Scientific Assistant, Assistant Scientific Officer and Officer In charge of the Section.

4.0 PROCEDURE 1. The assembly should be checked every day for the leakage and the filters of the Swinny Filter holder ( 13 mm Millipore Filtration Unit ) before giving for sterilization.2 The cups and the funnels also the stainless steel manifold must be washed and rinsed with the distilled water .3 In case of leakage the O rings are to be changed 4 Once in two months clean the sintered funnels with chromic acid keeping them for over night. All the O rings are to be changed.5 The sintered Funnels are to be cleaned thoroughly in distilled water after chromic acid treatment before assembling.The rubber parts if they are deformed change them with new one.6 After washing the Millipore Filtration Unit plug the unit with nonabsorbent cotton and keep ready for sterilization.

1.OBJECTIVE:To lay down a standard procedure for Bubble Point Test.2.SCOPE:This procedure provides a standard guidelines to validate the membrane by performing the Bubble Point test.3.RESPONSIBILITY:Senior Chemist. Head - Production.4.PROCEDURE:4.1.Check and make sure that the area is clean & free from the previous product and any other materials related to previous products.4.2.Fill the distilled water in the bubble point apparatus which has been autoclaved.4.3.Connect the Nitrogen tube with the Bubble point apparatus and outlet of the Bubble point apparatus to the membrane holder.4.4.Pass the Nitrogen in the Bubble point apparatus to pump the water to membrane holder. The filtered water gets collected in the collection tank.4.5.After completion of filtration, dip the Nitrogen tube in collection tank and observe for the bubbles.4.6.If any air bubble was found at less than the pressure level mentioned below. It is concluded that the membrane fails in bubble point test and cannot be used for the filtration of solution. 0.22µ membrane¬ - 40 psi.0.45µ membrane - 25 psi.

1.OBJECTIVE:To lay down a standard procedure for Optical Checking of filled vials and ampoules.

2.SCOPE:This procedure provides a standard method of optical checking of filled Vials and Ampoules for the presence of any foreign particles.

3.RESPONSIBILITY:Supervisor - Visual checking.Senior Chemist. Head - Production.

4.PROCEDURE:4.1.Check and make sure that Line clearance is duly checked and signed by QA Personal as per SOP No:P/P/0494.2.Transfer the filled ampoules/vials into the plastic crates with proper labelling and given for individual checking.4.3.Keep the ampoules/vials in an inverted position to check for sealing, black particles under white board and Glass pieces, white pieces & fiber particles under black board by shaking the Ampoules/Vials for two to three times.4.4.If necessary clean the ampoules/vials with a wet cloth.4.5.Segregate and put the good and rejected Ampoules/Vials in the respective crates with lids.4.6.Put green label for good Ampoules/Vials.4.7.Put pink label for rejected Ampoules/vials.4.8.Collect and send 10 to 20 Nos of good Ampoules/Vials for In-process checking.

1. OBJECTIVE:To lay down a standard operating procedure for Automatic Ampoule Filling & Sealing Machine

2.SCOPE:This procedure provides a standard method to operate and handle the Automatic Ampoule Filling & Sealing Machine.

3. RESPONSIBILITY:Machine Operator. Senior Chemist. Head - Production.

4.PROCEDURE:4.1.Check and make sure that Automatic Ampoule Filling and Sealing machine has been cleaned as per SOP No: P/P/0104.2.Make sure that Line clearance is duly checked and signed by QA Personal as per SOP No: P/P/0444.3.Make sure that the filling area has been cleaned properly.4.4.Switch on the Laminar flow and make sure that, it has been wiped with 70% IPA.4.5.Feed the Ampoules to an inclined charging hopper from Sterilized S.S boxes.4.6.The Ampoules are passed continuously through rotating feeding wheel, which in turn transfers the Ampoules positively to Ampoule conveyor with the help of charging hopper.4.7.The Ampoule conveyor carries the Ampoules vertically at an angle of 300.4.8.Pass the nitrogen (Inert Gas) into the empty Ampoules.4.9.The volume to be filled passes through the pumps, by positive displacement through the non-return valve, filling tubes and filling needles, finally into the Ampoules.4.10.Again pass the nitrogen (Inert Gas) into the filled Ampoules.4.11.The filled Ampoules are moved to sealing station.4.12.In sealing station the Ampoule necks are pre-heated and the pre-heated necks are gripped by the draw-off tongs and sealed.4.13.Make sure that the sealing has been done before the Inert gas can diffuse to the outside.4.14.Collect the sealed Ampoules through the collection hopper and finally to the crates with proper labeling.

Ampoule filling and sealing Ampoule filling and sealing machinemachine

Vial filling machine

1. OBJECTIVE:To lay down a standard operating procedure for Automatic injectable powder vial filling & rubber stoppering Machine.

2. SCOPE:This procedure provides a standard method of operation and handling of the Automatic injectable powder vial filling & Rubber stoppering Machine.

3. RESPONSIBILITY:§ Machine operator.§ Senior Chemist. § Head - Production.

4. PROCEDURE:4.1. Check and make sure that Automatic Injectable Powder Vial and Rubber stoppering machine has been cleaned as per SOP No:P/P/0114.2. Make sure that Line clearance is duly checked and signed by QA Personal as per SOP No:P/P/0504.3. Make sure that the filling area has been cleaned properly.4.4. Switch on the Laminar flow and make sure that it has been wiped with 70% IPA.4.5. Receive the incoming sterilized, siliconised and dried containers on the unscrambler and suitably guided on to the moving woven conveyor belt at the required speed for the correct placement below the powder wheel. 4.6. Put the sterile powder in powder hopper, which will agitate powder by a pair of mechanical agitators for maintaining consistency and uniform bulk density.

4.7. The precise fill volume of powder is sucked into the port of the powder wheel by means of vacuum.

4.8. The excess powder is doctored off by a blade when powder wheel indexes further and remains in the port due to the vacuum till it reaches just vertically above the container. 

4.9. The time dose of Nitrogen sequentially flushes out powder from the port of powder wheel into container one by one.

4.10. The filled containers are immediately separated on the conveyor by container separator and moves further for the stoppering operation.

4.11. Put sterilized, siliconised Rubber stoppers in the Rubber stopper hopper.

4.12. Rubber stoppers are made to pass through mechanical orientation system and stacked vertically in the rubber stopper chute from Rubber stopper hopper.

4.13. The moving container is held firmly between two cogged neoprene belts for correct pick up of rubber stopper from the outlet of Chute.

4.14. Further the container is passed beneath two pressing rollers for tight sealing of rubber stopper.

Automatic injectable powder vial filling & rubber stoppering Machine.

1.OBJECTIVE:To lay down a Standard operating procedure for Rubber Bung Washing Machine.

2.SCOPE:This procedure provides a standard method to operate the Rubber Bung Washing Machine.

3.RESPONSIBILITY:Machine Operator.•Senior Chemist. •Head - Production.

4.PROCEDURE:4.1.Check and ensure that the Rubber Bung washing

machine is free from dust & it is cleaned as per SOP No:P/P/015.

4.2.Make sure that Line clearance is duly checked and signed by QA Personal as per SOP No:P/P/053

4.3.Fill the vessel with solution of 0.1% Tween 80 and DM water.

4.4.Transfer the Rubber Bungs to be washed into the vessel. Supply the steam into it at 116°C/10 lbs for 35 mins.

4.5.After 35 mins cut the steam supply & give compressed air to remove the foam which is formed because of the Tween 80 solution. Drain the washed water.

4.6.Add sufficient quantities of DM water which is filtered through 5µ filter. Apply the filtered steam and compressed air at a pressure of 4 Kgs/cm2 for half an hour.

4.PROCEDURE (Contd.)4.7. Drain the water through the suitable valve and check for the clarity.4.8. Repeat the step 4.5 & 4.6 until to get the clarity.4.9. For liquid Injectable, add specified preservatives solution of specified concentration in the rubber bungs to avoid the chemical reaction with products to be sealed.4.10. For powder injectable, add silicone oil emulsion at a concentration of 0.1% in the rubber bungs instead of preservatives.4.11. Distribute the rubber bungs into SS Rubber Bung box. Drain the water by lifting down the SS hole Rubber Bung box. 4.12. Sterilize it at 116°/10 lbs for 35 mins in steam heat sterilizer. 4.13. Finally put all washed Rubber Bungs in the Dry heat sterilizer for drying.

RUBBER BUNG WASHING RUBBER BUNG WASHING M/CM/C

1. OBJECTIVE:

To lay down a standard procedure for Sterile Filtration of Solution

2. SCOPE:

This procedure provides a standard method of Filtration of Solution.

3. RESPONSIBILITY:

Senior Chemist. Head - Production.

4. PROCEDURE:

4.1. Check and make sure that the area is clean & free from the previous product and any other materials related to previous products. Refer SOP No. P/P/076

4.2. Wash and Autoclave the Membrane holder.4.3. Place the membrane followed by 2-20 prefilter in the 293mm

membrane holder.

4.4. Connect the Nitrogen tube to the pressure vessel.4.5. Connect the inlet and outlet tube of the membrane holder with

pressure vessel and collection vessel respectively which has been already autoclaved.

4.6. Fill the solution to be filtered in the pressure vessel and pass the Nitrogen at the pressure of 3 to 4 kgs/cm2 in the pressure vessel which will pump the solution to the membrane holder.

4.7. The solution will come out and enters into the membrane assembly and then get filtered through membrane.

4.8. The filtered solution gets collected in the collection vessel.

1.0 PURPOSE : To provide a procedure for periodic calibration of pH meter.

2.0 SCOPE : Covers procedure for the calibration of pH meter (daily and monthly) and also for the activation of electrode and maintenance of electrode.

3.0 DEFINITION :

3.0.1 pH: pH value conventionally represents the acidity or alkalinity of an aqueous solution.3.0.2 Calibration : The set of operations which establish, under specified conditions, the relationship between values indicated by a measuring instrument or measuring system or values represented by a material measure and the corresponding known values of a reference standard.

4.0 PROCEDURE :

4.1 PREPARATION OF BUFFER SOLUTION:Buffer solution D: (pH 4.01) Dissolve 10.21 g of potassium hydrogen phthalate, previously dried at 110 degree to 130 degree for 2 hours in sufficient carbon dioxide free water to produce 1000mL.Buffer solution E: (pH 6.87) Dissolve 3.40 g of potassium dihydrogen phosphate and 3.55 gram of anhydrous disodium hydrogen phosphate previously dried at 110 degree to 130 degree for 2 hours both in sufficient carbondioxide free water to produce 1000mL.Buffer solution G: (pH 9.18) Dissolve 3.814 gram of borax in sufficient carbondioxide free water to produce 1000.0 ml.Store all the above solutions in alkali free glass. Label the bottle as follows:Frequency of preparation : MonthlyEvery week transfer 250ml of this buffer to the secondary bottle after checking for clarity and label the bottle with details as under : Solution showing precipitation, haziness or growth of fungus shall be discarded.

4.2 CALIBRATION OF pH METER :4.2.1 Use the service beaker provided for each buffer and do not transfer the buffer from service beaker back to the bottle. Discard after every use. 4.2.2 Calibrate the apparatus using 25ml from the stock solution of buffer solution D as the primary standard adjusting the meter to read appropriate pH 4.01 Plus or minus 0.05 corresponding to the temperature of solution (25degreeCPlus or minus 2 degree C). To set the scale use a second reference buffer solution either E (6.87) or G (9.18).

If the difference between this reading and the original value is greater than 0.05, the set of measurements must be repeated. When measuring pH values above 10.0 ensure that the glass electrode is suitable for use under alkaline conditions and apply any correction that is necessary.

IMPORTANT CONDITIONS :a) All solutions of substances being examined must be prepared using

carbon dioxide free water.b) pH determination is carried out at a temperature of 25degreeC Plus

or minus 2 degree C. c) Buffer solutions should be stored in bottles made of alkali free glass.

5.0 ACTIVATION OF ELECTRODE :

FREQUENCE : EVERY 15 DAYS5.1 COMBINED GLASS ELECTRODE.Soak the electrode overnight in 6 M Hydrochloric acid, next day wash repeatedly with distilledwater and immerse the electrode in distilled water.5.2 GEL FILLED ELECTRODE

5.2.1 Between measurements (upto 1 hour)leave the electrode in an open air lab environment not in distilled

water.5.2.2 Short term storage (upto one week)Soak electrode in 200ml pH 7 buffer added with 1 g potassium chloride.5.2.3 Long term storage (over one week).Cover the electrode tip with a protective cap used for shipment.

6.0 MAINTENANCE OF ELECTRODE :CLEANING PROCEDURE6.1 GLASS ELECTRODE6.1.1 General : Soak electrode in 0.1 M HCl or 0.1 N HNO3 for 15 minutes.6.2 GEL FILLED ELECTRODE :6.2.1 Removal of Deposits6.2.2 Protein : Digest with 1% pepsin in 0.1 M HCl.6.2.3 Inorganic : Rinse with 0.1 M tetra sodium EDTA solution.6.2.4 Grease and oil : Rinse with mild detergent or methanol solution.

7.0 RECORDS :7.1 Record the pH calibration & activation of electrode in form F:Sxxxx/DPHR/A.7.2 Record the monthly calibration in form F:Sxxxx/PHR/A7.3 Record the pH of all solutions checked in daily pH log book.

8.0 DOCUMENTATION :8.1 F:Sxxxx/PHR/A pH Meter calibration record8.2 F:Sxxxx/DPHR/A Daily pH checking record.

pH METERpH METER

1.0 PURPOSE : To provide a procedure for operation of Blender Granulator.

2.0 SCOPE : It Covers procedure for the operation of Blender Granulator used in the Tablet Manufacturing Section of XYZ Pharmaceuticals Ltd.

3. 0 RESPONSIBILITY:Senior Chemist.

4.0 ACCOUNTABILITYHead - Production.

5.0 PROCEDURE :5.1 Check the blender status. It shall be clean and ready for use. Refer SOP No. P/P/078. If not clean, get the same cleaned and ready for use.5.2 If the materials required for a batch are dispensed from a central dispensary, all the weighed materials should be collected as one batch per pallet (wherever possible.) The pallet should be clean and no material should be received in dirty containers or in the original containers of the suppliers.5.3 Each raw material from the central dispensary should be weighed to verify the gross weight indicated by the dispensing department. 5.4 Any discrepancies in the weight should be suitably rectified. 5.5 The weights should be recorded on the manufacturing sheets and countersigned by the supervisor. 5.6 If the materials are dispensed from the stores, they should be weighed on appropriate scales with adequate capacity and sensitivity (see document entitled Weighing of Materials ).

5.7 It must be ensured that materials in their original or other containers are not contaminated by the measuring and dispensing devices such as scoops, spoons, etc. Each material should be handled by means of its own dispensing device; all such equipment used for handling the materials should be cleaned immediately after each use and kept aside covered in plastic.

5.8 All materials should be weighed into clean, tared and labeled containers, The balance of material not dispensed should be returned to the bulk stock.

5.9 Weighed materials should be transferred to the blending area which should be separate from the weighing area.

5.10 The ingredients for the batch should be added to the mixer through suitable sieve, if needed. After the addition is over, the blender shall be covered.

5.12 Operate the blender for the required time at required rpm.

5.13 Check the speed of the rotor .5.14 After the required blending has been achieved, stop the

blender.5.15 Remove the contents manually or by tilting into clean

polythene bags.5.16 Clean the blender to remove all residues. Cover it with

Polythene Cover for next operation.

1.0 PURPOSE : To provide a procedure for Use of Fluid Bed Drier.2.0 SCOPE : It Covers procedure for the operation of Fluid Bed

Drier used in the Tablet Manufacturing Section of XYZ Pharmaceuticals Ltd.

3. 0 RESPONSIBILITY:Senior Chemist.

4.0 ACCOUNTABILITYHead - Production.

5.0 PROCEDURE :5.1 It should be ensured that the drier is clean and ,fit for use (see SOP entitled "Cleaning of Fluid Bed Drier” SOP No. P/P/ 088).

5.2. The cleaned bags should be examined to ensure that they are free from holes and other defects.

5.3. The finger sleeves of the bag should be fixed to the respective hooks on the holding ring. The bag support frame should be inserted and the filter bag unit should be clipped to the retaining strap.

5.4. The cleaned bowl of the drier should be examined to ensure that the inner surface is clean and that there is no damage to the wire mesh sieve at the bottom. The bowl should be labeled with the name and batch number of the product being processed.

5.5 The wet material (to be dried) should be loaded into the bowl and the mass spread uniformly. The trolley carrying the bowl should then be wheeled in and positioned beneath the sealing ring in such a way that the sight glass is in the front and the bowl raising lever on the base is accessible.

5.6. The earthling should be clamped on to one of the legs of the bowl trolley or alternately, it should be ensured that the bowl comes in contact with the earthling strap when pushed into position.

5.7. The bowl should be raised with the help of the lever. Where a pneumatic device is provided on the machine, it should be ensured that the bowl gets locked in position and the bags are also held in place.

5.8. The heater should be switched on and the temperature setting on the thermostat adjusted to the required inlet air temperature. Where a time switch is provided the drying time should be set by turning the knob clockwise to the extent required.

5.9. The dampers should be adjusted to the required level and the locking nuts tightened to keep the dampers in place.

Operation of Fluid Bed Drier:1.0 Preferred room temperature should be around 25°C. 2.0 Fix all the fingers of the dryer bag securely to the apex

which must be earthed. Do not patch up the tom bag by a synthetic cloth. It is dangerous from electrostatic hazard point of view.

3.0 Check that the bowl is free of a metal piece. The frictional spark could be externally dangerous. Lift the bowl pneumatically.

4.0 Check that all the detachable parts of the dryer are properly earthed.

5.0 Start the dryer, if there exists any discontinuity electrically the interlocking would not actuate starting of the dryer. Do not make short cuts by isolating the safety device.

6.0 Run the dryer for 15 minutes with cold air only. Start heating of air by hot water / steam only.

7.0 Monitor fluidization of the batch and maintain specified temperature of air inlet and outlet.

8.0 Beware of the hazard due to sharp pointed spikes hanging in the expansion chamber while cleaning dryer from inside. Use helmets while cleaning. Use only flame proof torch whenever necessary. Keep the area clean and free of chemical dust.

9.0 Use hand gloves, dust mask and goggle while shoveling the batch, charging and discharging of the dryer.

Cleaning of Fluid Bed Drier:1 Before dismantling the equipment the electric supply must be turned off. 2. The strap retaining the filter bag unit is unclipped and the finger sleeves of the bag are detached from the holding hooks. 3. The bag is removed and taken to the washing area where the external surface of the bag is washed with hot water. The bag is turned inside-out and then washed with hot 1 water. Where material is adhering to the bags it will be necessary to scrub the surface with a detergent solution (such as Teepol) using a nylon brush. 4. After washing, the bag is placed on a hanger and allowed to dry in air. 5. The bag support frame as well as the sleeve supports are washed with hot water and the washed surfaces are then wiped with a clean, dry cloth. 6. The drier bowl should preferably be washed after every drying cycle although if the same product is being dried in lots it will be sufficient to wash at the end of the working shift. The bowl is wheeled to the washing area where it is freed from the wheel base. It is first flushed with hot water and then scrubbed, if necessary, with a nylon blush to dislodge all adhering solid material. Care should be taken while cleaning the sieve so that it is not damaged. A cleaning agent (such as Teepol) and/or a scouring powder may also be employed to facilitate cleaning. The bowl is finally rinsed with hot water in the form of a jet and then dried by wiping with a clean, dry cloth. The bow 1 is then covered with a nylon cloth or any other suitable cover and stored in a dust-free area.

7. Powder from the interior surfaces of the drier cabinet is removed by suction using vacuum. A nylon brush may be used to remove adhering powder. The surfaces are cleaned with a clean, damp cloth and then allowed to dry. 8. The air intake filter is removed and replace with a freshly cleaned filter. 9. The external surfaces of the fluid bed drier are wiped with a clean, damp cloth and then allowed to dry. 10. The drier should be switched on and the airflow adjusted according to the drying 'conditions specified for the process. It should be ensured that the material is adequately agitated and that channels are not formed in the mass of the wet material. Channel formation is normally recognized when the air outlet temperature is close to that of the air inlet temperature soon after the drying process staI1s. 11. At the end of the time cycle when the drier stops automatically, the air bags should be shaken by pulling the lever attached to the drier, in order to dislodge the fines which collect in the bags. 12. The main switch should be turned off, the bowl should be lowered and the trolley holding the bowl wheeled out. The contents of the bowl should be examined to know if any further drying is required. 13. If redrying is necessary, the material in the bowl should be stirred with a scoop and the bowl should be put back into the drier. Steps 7 to 12 should be repeated until the material complies with the relevant specifications at the stage of processing. 14. The details of drying, including the inlet and outlet air temperatures, the drying times of the cycle, the date of drying and batch details should be entered on the fluid bed drier log sheets. CAUTION : If a flammable liquid, such as, alcohol, has been used in preparing the granules, such granules should be exposed in trays in an explosion proof area, before being taken up for drying in fluid bed drier.

 

1) DEVELOPMENT,PREPARATION, AND FLOW OF FORMULATIONS FOR PRE CLINICAL SAFETY EVALUATION:4.1 Receive ‘request form’ for formulation in the FORMULATION REQUEST SHEET from PCSED along with active bulk drug and analytical report / COA for the same.

4.2 Make a record of quantity of test substance received and utilised in TEST SUBSTANCE ACCOUNTIBILITY FORM.

4.3 Develop formulation at least three. Send the formulation to ADL for analysis with TEST REQUEST SHEET and respective placebo.

4.4 If the assay value is +5% of label claim, manufacture a stability batch of the formulation with prior intimation to the ADL. Send the samples to ADL for initial analysis.

4.5 Formulation for ACUTE ORAL TOXICITY STUDIES, stability for 4 hrs. shall be conducted. For ACUTE I.V. TOXICITY STUDIES, stability for 24 hrs. shall be conducted.

Stability studies should be conducted at 25+ 2ºC and 2-8ºC as per STABILTY STUDY PROTOCOL

4.6 For any other Toxicity Studies, limit is

SUB ACUTE TOXICITY STUDIES: 8 days

CHRONIC TOXICITY STUDIES: 30 days

4.7 Any other toxicity studies of longer duration: 3 months.

4.8 Once the formulation vehicle safety is established, document the composition in MASTER FORMULA CARD.

4.9 Send the samples to PCSED along with FORMULATION DETAIL SHEET.

 

 

 

 

 

FORMULATION AND DEVELOPMENT OF ORAL & IV FORMULATION FOR PCSED TRIALS:

 

ORAL:Information required: Solubilty, pKa, Solution Stability, PS Note: The information should be collected in case of Development molecules from

Literature & from MCD for Discovery molecules. Based on the concentration required & drug solubility decide whether solution or suspension is to be formulated.Make a batch sheet.Screen through 100 # if suspension is to be formulated.For Suspension, formulate different batches with different viscosities and check for suspendibility & syringibility. The formulation should be viscous enough to allow withdrawal of uniform dose repeatedly, at the same time, it should lend itself for easy administration by syringe.

 IV:Based on the concentration required and solubility of the drug make a prelimnary formulation.If solubility of the drug is not sufficient , try following:Try solubility at different pH.Try co solvents like PEG 400, PG, Ethanol, Glycerine.Try surfactants like T-80, T-20, Cr RH 40, Cr El, etc.Try complexing agents like PVP K 30, Cyclodextrins , caffeine, etc.Formulate microemulsion.

  If by this also, formulation is not attained then try another formulation with another concentration.

    

 

 

3) ARCHIVING AND RETRIVAL OF RECORDS AT CENTRAL ARCHIEVE:

 Following items should be archieved:

Equipment log books including use log books, calibration log books and maintenance log books.(Frequency of archiving: once in a month)

Training records.(Frequency of archiving: once in 6 months)

C.V. job description.(Frequency of archiving: within one month of person joining the GLP)

4) REPAIR & MAINTENANCE OF EQUIPMENTS

With the help of the eng. dept. all the equipments of the GLP area should be maintained & if problem is out of control then vendor is to be informed.

5) RETAINING SAMPLES OF TEST SUBSTANCE WHICH HAVE BEEN USED FOR THE CONDUCTANCE OF REGULATORY TOXICITY STUDIES & SAFETY STUDIES:

  Quantity: 500mg-1.0 gms

  Properly label the container containing the test Substance:

Name of the Product:

B.No.

Mfg.Date:

Expiry /Reanalysis Date:

Storage Condition:

GLP TRAINING:

  Develop the formulation under the guidance of the GLP in charge.Carry out the stability study of the formulation as per SOP.Compiles the stability Data of all formulation & get it checked & approved and selects the best suitable formulation.Prepare the master formula card for the selected formulation.Manufacture the final formulation for PCSED as per the MFC.Prepare the Batch records for all batches & get it checked by the GLP in charge before manufacturing any batches.Perform instrument calibration as per individual SOP’s and maintains the use log books for all the instruments.Follow the cGLP principal of the lab.Follow the safety rules & regulations.

SR.NO. PARTICULARS DATAILSStudy number:Fnd Reference number:Active Material Used:Purpose of the study:Description of the sample:Dose required:Total duration of study:Final Date of summation:Safety information:

Annexure I 

FORMULATION REQUEST SHEET

FROM: PCSED TO: ADL 

Kindy provide the formulation as per following details:

SOP For Perforated Basket Centrifuge: Filterable products are separated in a perforated basket. The

liquid/solid slurry is introduced into the rotating body of the centrifuge via a feed pipe. The centrifugal force pushes the slurry to the side, forcing the liquid through the perforations in the basket while the solids are retained within by means of a fine screen or cloth.

The remaining solids (cake) can then be washed and spun at higher Cs to achieve a relatively dry cake. The resultant cake is then discharged through the bottom of the basket by means of a single motion plow mechanism.

Install a clean filter bag Securing the lid Connect the three process lines on the cover, Start the centrifuge. Adjust the machine speed via the speed controller. When the tachometer indicates that the machine is at feed

speed, the process slurry is introduced into the rotating bowl. Solid particulate accumulates in a uniform ring on the bowl’s

inside diameter while liquid filters through the porous solid cake and exits the centrifuge discharge outlet.

When the solids holding space is completely full, the feed is stopped, the washing cycle is started and adjusted to a higher speed to obtain the dryest cake possible.

At the end of the cycle, the centrifuge is stopped and the filter bag with the solids is removed.

1.OBJECTIVE:To lay down a Standard Operating Procedure for laminar flow.2.SCOPE:This procedure helps to provide standard guidelines to operate and handle the laminar flow. 3. RESPONSIBILITY:Operator.Senior Chemist.Head - Production.

4.PROCEDURE:4.1 Check and make sure that the area is clean & free from the previous product and any other materials related to previous products.a.Ensure that the instrument is clean, free from dust and placed in such a position, that any air dust while opening the air-lock door do not affect the positive pressure of the instrument.b.Switch on the mains.c.There are three switches and a pressure barometer side panel of the instrumentSwitch (1) AIR-FLOWSwitch (2) LIGHTPress ’switch (1)’ to start the AIR-FLOW through the HEPA Filtersd.The AIR-FLOW should be kept ‘ON’ for about 5 minutes before carrying out any work under laminar flow.e.Check the level of red-oil indicator should be at 10 to15 mm mark of water column, when AIR-FLOW is ‘ON’.f.Switch ‘OFF’ the instrument when not in use.

B. CALIBRATION PROCEDURE:The performance of the HEPA filters could be checked by the following two methods.(i)DOP (Di Octyl Pthlate) test: (Done on contract basis)(ii) Anemometer Test: This is one of the suitable tests for validation of the HEPA Filter. During the time of validation, place the anemometric sensor on the Laminar Air Flow at different location in front of the HEPA Filter. Efficient -- 90 to 110 feet/minute(iii) Plate method: Prepare nutrient agar plates (or) soyabean casein digests agar plates and exposes it in different corners of the instrument base. Then incubate these plates at 350C for 48 hours. No growth is observed, the HEPA Filter is working in good condition.C. GENERAL CARE & PRECAUTIONSProper handling of the instrument.Clean the instrument with 70% Iso propyl alcohol, before and after use.A routine cleaning of filters should be done by blowing air.D. MAINTENANCE / REPAIRS:If the instrument does not procedure required calibration results or its response is poor then it should be labeled “FAULTY” and should be repaired or serviced.

LAMINAR AIR FLOW

1. OBJECTIVE:To lay down a Standard Operating Procedure for Moist Heat Sterilizer with

circular chart2. SCOPE:This procedure provides a Standard method to operate the Moist Heat Sterilizer

with circular chart.3. RESPONSIBILITY:v Operator.v Senior Chemist. v Head - Production.4. PROCEDURE:4.1. Make sure that Line clearance is duly checked and signed by QA Personal

as per SOP No:P/P/0514.2. Open the pressure lock door by turning the handle anti-clockwise, till the

quick throw handle easily pushed down.4.3. Load the materials to be sterilized into the chamber by keeping the

materials in trolley with proper labeling.4.4. Close the pressure lock door by pulling up the quick throw handle, after

which the handle is to be turned clockwise till it is reasonably tight.4.5. Open the bypass valve of the moisture separator for 5 minutes to remove

all the condensed water which is already present, from the line and then close it.

4.6. Open the main line steam inlet valve.4.7. Switch on the solenoid jacket steam valve, it will allow the steam inside of

the jacket and due to this, pressure will gradually build up in the jacket. 4.8. Safety valve will open, if the inside pressure exceeds 15 lbs. So it will

maintain the constant pressure in it.

4.9. Switch on the Inner solenoid steam valve, it will allow the steam inside of the chamber and due to this, pressure will gradually build up in it.

4.10. Open the outlet valve of the chamber and switch on the vacuum pump to suck out the air from the chamber to atmosphere to avoid the formation of air pocket.

4.11. After few minutes, close the outlet valve and switch off the Vacuum pump.

4.12. Drain the condensed steam for few minutes from the chamber by opening the bypass valve of the chamber.

4.13. Check thermograph for recording chart, ink and then put it on.4.14. ‘Exposure Period & Temperature’ should be as per the

validated time for various loads.For Example: § 1210C/15 lbs for machinery parts, Latex gloves, tanks, sterile area

dresses.§ 1160C/10 lbs for Autoclaving (Non-aseptic) pharmaceutical

products.4.15. Switch off the solenoid jacket steam valve, Inner solenoid

steam valve and close the Main steam valve.4.16. Allow the steam to exhaust until both the pressure gauge

indicates zero psi by opening the outlet steam valve of the chamber.

4.17. Prior to unloading the sterilized load on the sterile side, make sure that the sterilized load has been cooled to room temperature and the door of Non-sterile area side has been closed.

VERTICAL AUTOCLAVE