cGMP and Regulatory Updates

OBJECTIVE Test for Total Microbial Count is provided to determine compliance with the requirements given in individual monograph / specifications. PRINCIPLE Total microbial count is the estimation of the number of viable aerobic micro-organisms present in the pharmaceutical articles of all kinds, from raw materials to the finished forms. BUFFERS AND MEDIA 1. pH 7.2 Phosphate Buffer Stock Solution Dissolve 34 g of Monobasic Potassium Phosphate in about 500 mL of water contained in a 1000 mL volumetric flask. Adjust to pH 7.2 ± 0.1 by the addition of 4 % w/v aqueous solution of Sodium Hydroxide (about 175 mL), add water to volume, and mix. Dispense and sterilize. Store under refrigeration. For use, dilute the Stock Solution with water in the ration of 1 to 800 , and sterilize in an autoclave at 121 OC , 15 lb pressure for about 15 min. 2. Fluid Soyabean Casein Digest Medium Pancreatic Digest of Casein 17.0 g Papacy Digest of Soybean Meal 3.0 g Sodium Chloride 5.0 g Dibasic Potassium Phos...

OBJECTIVE The test for Abnormal / Undue Toxicity / Safety test is provided to determine compliance with the requirements given in individual monograph / specifications. PRINCIPLE This test is intended to detect any unexpected, unacceptable, biological reactivity in a substance. This is an invitro test designed for safety assessment of biologics and biotechnology derived products. ANIMAL QUARTERS 1. Keep the animals individually in a quiet area with an appropriate uniform temperature allowing a variation of ± 2 OC and uniform humidity and free from disturbance. 2. Carry out the test in a quiet room where there is no risk of disturbance which can excite the animals and in which the room temperature is within 3 OC of that of their living quarters or in which the animals have been kept for at least 18 h before the test. 3. Withhold food from the animals overnight and until the test is completed , with hold water only during the test. TEST FOR UNDUE TOXICITY ( As...

OBJECTIVE The test for Staphylococcus aureus is provided to determine compliance with the requirements given in individual monograph/specifications,. PRINCIPLE Identification of Staphylococcus aureus is the detection of a pathogenic bacteria which causes infection in human body. It can be identified by using specific, differential media which support growth of only Staphylococcus aureus. REAGENT AND MEDIA Fluid Soybean - Casein Digest Medium Pancreatic digest of Casein 17.0 g Papai digest of Soybean meal 3.0 g Sodium Chloride 5.0 g Dibasic Potassium Phosphate 2.5 g Dextrose (C6H12O6.H2O) 2.5 g Distilled Water 1000 mL Final pH after sterilization 7.3 ± 0.2 Dissolve the solids in the water, warming slightly to effect solution. Cool to room temperature and add, if necessary, sufficient 0.1 N Sodium Hydroxide to give a final pH after sterilization of between 7.1 and 7.5. Filter, if necessary, to clarify. Distribute into suitable containers and sterilize in an autoclave at 121 OC for about ...

1.0 OBJECTIVE The test for Anti-microbial preservative - Effectiveness is provided to determine compliance with the requirements given in individual monograph / specifications. 2.0 PRINCIPLE Preservative efficacy test is basically a challenge test in which the function of a preservative in pharmaceutical preparation use to be checked by challenging it with different microorganisms (bacteria, fungi and yeast.) Test Organisms Aspergillus niger IMI 147 007 (ATCC 16404, IP 1431.83) Candida albicans NCPE 3179 (ATCC 10231, IP 48.72) Pseudomonas aeruginosa NCIMB 8626 (ATCC 9027, CIP 82.118) Staphylococcus aureus NCTC 10788 (NCIMB 9518, ATCC 6538, CIP 4.13) . Single-strain challenges are used and the designated micro-organisms are supplemented by other strains or species that may represent likely contaminants to the preparation. For example, Escherichia coli [NCIMB 8545 (ATCC 8739, CIP 53.126)] is used for all oral preparations and Zygosaccharomyces Rouxii[NCYC 381 (IP 2021.92)] for oral prepa...

The test for Pyrogens is provided to determine compliance with the requirements given in individual monograph / specifications. PRINCIPLE Pyrogen test is the measurement of the rise in body temperature of rabbits following the intravenous injection of a sterile solution of a substance being examined. It is designed for products that can be tolerated by the test rabbits in a dose not to exceed 10.0 mL per kg. Weight injected intravenously within a period of to more than 10 min. SELECTION OF ANIMALS 1. Use healthy, adult rabbits of either sex, weighing not less than 1.5 kg, fed a complete and balanced diet not containing antibiotics and showing no loss of body weight during the week preceding the test. 2. The rabbits must not have been used in a similar test : a. during the preceding 3 days (as per BP) or 2 days (as per USP and IP) b. during the preceding 3 weeks (as per BP) or 2 weeks (as per USP and IP) unless the material being examined passed the test Rabbits used in a test for Pyrog...

1.0 OBJECTIVE To lay down a procedure for washing and sterilization of glass apparatus. 2.0 SCOPE This SOP covers the procedure for washing and sterilization of glass apparatus is applicable to Quality Control Department Formulation Units 3.0 RESPONSIBILITY Microbiologist. 4.0 ACCOUNTABILITY Department Head. 5.0 PROCEDURE 5.1 Wash the glassware thoroughly using soap solution (Extran 1.0%) followed by potable water rinses to remove all the traces of the residues. Finally rinse with purified water. 5.2 Dry the washed glassware at 105°C in oven. 5.3 Cover the open ends of glass apparatus with a caps / cotton plugs and wrap with aluminum foil. 5.4 Sterilize in the autoclave at 15 psi, 121 OC for 20 min. 5.5 Keep the sterilized material in separate and labeled area to avoid mix up with unsterilized material. 5.6 Record the details. 5.7 For new glassware follow the following procedure 5.7.1 Treat the glasswa...

1.0 OBJECTIVE To lay down a procedure for Consumption and accounting of Excess/Shortage material received from the vendor. 2.0 SCOPE This SOP is applicable to Raw and Packing Material Warehouse. 3.0 RESPONSIBILITY Officer - Warehouse. 4.0 ACCOUNTABILITY Asst.Manager – Warehouse 5.0 PROCEDURE 5.1 Weigh and label (Loose container label) for all materials after each issue. 5.2 Check the remaining available physical quantity with the recorded SAP R/3 stock. 5.3 At the completion of a particular consignment, check the physical stock with SAP R/3 stock. 5.4 Prepare an Excess/Shortage certificate(as per Annexure enclosed ) for the quantity in excess/shortage. 5.6 Update the stocks in the SAP R/3 system as & when the Excess/Shortage certificate is Approved and Authorized. 5.6 The posting of issues in SAP R/3 system related toExcess quantity than the specified norms as below, is done onl...

1.0 OBJECTIVE To lay down a procedure for Handling of loose containers, of raw materials. 2.0 SCOPE 2.1.0 This SOP is applicable to dispensing area 3.0 RESPONSIBILITY Officer Warehouse 4.0 ACCOUNTABILITY Assistant Manager-Warehouse 5.0 PROCEDURE: 5.1.0 After dispensing of material,container & inner polybag of the loose material to be closed properly. 5.1.1 Weigh the loose container and record the Gross weight on the label. 5.1.2 Based on the original tare weight calculate the net weight of the loose material and record the net weight on the label as per annexure attached. 5.1.3 Sign the label and affix the loose container label on the container over the earlier loose container label after verifying the details. 5.1.4 Before affixing the loose container label strike off the earlier loose container label. 5.1.5 Send back the loose container to warehouse through the material exit box after dedusting and cleaning 5.1.6 The same loose container to be taken first for next dispensing.

1.0 OBJECTIVE To laydown a procedure for Operation of Hi-Reach Truck. 2.0 SCOPE This SOP is applicable to Raw Material ,Secondary packing Material and Finished Goods Warehouse Hi-Reach Trucks, Capacity: 1500 Kg 3.0 RESPONSIBILITY Operator 4.0 ACCOUNTABILITY Executive Warehouse / Executive Services 5.0 PROCEDURE 5.1 Precautions 5.1.1 Check for Hydraulic Oil leakage and arrest. 5.1.2 Ensure that charger plug is removed from batteries. 5.2 Pre Start Up 5.2.1 Check for distilled water level in the cells of the battery unit and top up if necessary. 5.2.2 Check for specific gravity of the pilot cells that to be 1240 mm of Hydrometer. 5.2.3 Connect truck plug to the battery plugs. 5.2.4 Select mode of truck direction with direction lever. 5.3 Set Up 5.3.1 Set the rear wheel steering in straight. 5.3.2 Set forks clear from the ground 5.4 Operation 5.4.1 Sit firmly in the driving seat. 5.4.2 Insert the key in the key switch and ...

1.0 OBJECTIVE To lay down a procedure for material sent for job works and its stock accounting. 2.0 SCOPE 2.1.0 Raw Materials & Primary packaging materials. 3.0 RESPONSIBILITY Officer - Warehouse and Executive-Supply Chain Management Department. 4.0 ACCOUNTABILITY Asst.Manager – Stores & Excise and Executive -Supply Chain Management Department. 5.0 PROCEDURE 5.1 Supply Chain Management Department will coordinate with warehouse department on job works. 5.2 Material to be sent out for job work only on the advice of Supply Chain Management Department. 5.3 The details of the material to be sent for job work such as Item description,quantity received,date of receipt,invoice number against which received & its date,quantity being sent,nature of job work,place or unit where job work is to be done,expected date of return of finished good are to be given to Excise Department (at Factory) one day in advance. 5.4 Assemble the require...

1.0 OBJECTIVE To laydown a procedure for Operation of Battery Operated Pallet Truck. 2.0 SCOPE This SOP is applicable to Finished Goods Packing Material Warehouse Battery Operated Pallet Truck, Model: Commuter /1115, Capacity: 1500Kg 3.0 RESPONSIBILITY Technical Assistant. 4.0 ACCOUNTABILITY Executive-Warehouse and Executive-Services 5.0 PROCEDURE 5.1 Precautions 5.1.1. Check and arrest any oil leakages . 5.1.2. Ensure that the plug is removed from the battery after charger is switched off. 5.2 Pre Start Up 5.2.1. Check for distilled water level in the cells of the battery unit and top up if necessary. 5.2.2. Check for specific gravity of the pilot cells to be 1240mm of Hydrometer. 5.2.3. Ensure that battery cable connections are tight and that cell caps are dry and clean. 5.2.4. Check for load carriage and forks are free from visible defects i.e deformation, cracks or excessive wear 5.2.5. Ensure that brakes are functioning correctly. 5.3 Set Up 5.3.1...

1.0 OBJECTIVE To lay down a procedure for Operation of Electric Pedestrian Operated Pallet Truck. 2.0 SCOPE This SOP is applicable to Raw Material Stores Electric Pedestrian Operated Pallet Truck Type: EJE20, Capacity: 1500 Kg 3.0 RESPONSIBILITY Technical Assistant 4.0 ACCOUNTABILITY Electrical Executive 5.0 PROCEDURE 5.1 Precautions 5.1.1 Check for any Hydraulic Oil leakages and arrest. 5.1.2 Ensure that plug is removed from the battery after charger is switched off. 5.2 Pre Start Up 5.2.1 Check for distilled water level in the cells of the battery unit and top up if necessary. 5.2.2 Check for specific gravity of the pilot cells and to be at 1240 mm of Hydrometer. 5.2.3 Ensure that battery cable connections are tight and that cell caps are dry and clean. 5.2.4 Ensure that battery plug is securely connected. 5.2.5 Check for play in the steering system. 5.2.6 Check for load carriage and fork tins are free f...

1.0 OBJECTIVE To lay down a procedure for Receipt of excess Raw/ Packing Material from Production. 2.0 SCOPE Raw Material, Packing Material Warehouse and Production hold area. 3.0 RESPONSIBILITY Assistant / Officer - Warehouse Assistant / Officer - Production. 4.0 ACCOUNTABILITY Assistant Manager - Production and Assistant Manager - warehouse. 5.0 PROCEDURE 5.1 Excess packing material to be received with proper document through Stock Return Note (SRN) only. 5.2 Stock Return Note (SRN) contains the following details. A) S.No B) Date, Product and Batch No. C) S.No of materials. D) Code E) Item F) Quantity returned G) Analytical Report No H) Quantity Verified by signature and date. I) Reasons for return / remarks. 5.3 Stock Return Note (SRN) to contain the signatures of Officer – Production,Quality Assurance Personnel and Assistant Manager - Production. 5.4 Material being returned has to be labeled w...

1.0 OBJECTIVE To lay down a procedure for Receipt of “On-line Rejected Materials”. 2.0 SCOPE Production, Packing hold area and dispensing area. 3.0 RESPONSIBILITY Officer- Production / Officer - Warehouse 4.0 ACCOUNTABILITY Assistant Manager - Production and Asst.Manager -Warehouse. 5.0 PROCEDURE 5.1 On-line rejected materials to be received with On-line rejection note duly signed by the Assistant Manager - Production./Quality Assurance. 5.2 On-line rejected material to be labelled as “On-line rejects”. 5.3 On-line rejected labels are to be signed by the Officer Production /Officer - Quality Assurance Department. 5.4 Stock return note to be raised by the Officer - Production for returning the On-line rejects and counter signed by Quality Assurance. 5.5 The stock return note to contain the S.No. and Date of On line Rejection with reasons. 5.6 The On-line rejected material to be sent to Dispensing room properly labelled along with a Online rejection note. 5.7 The On-line rejected materia...

1.0 OBJECTIVE To lay down a Procedure for receipt of labels. 2.0 SCOPE Packing Material Warehouse. 3.0 RESPONSIBILITY Officer - Warehouse. 4.0 ACCOUNTABILITY Asst.Manager -- Warehouse 5.0 PROCEDURE 5.1 Labels received from the suppliers are cross-checked with Delivery Challan for quantity by Warehouse Assistant/officer. 5.2 Quantity is checked by counting 50/100 Nos. and taking the weight of the same, the remaining total consignment is weighed. 5.3 Goods Received Note (GRN) has to be prepared in SAP

1.0 OBJECTIVE To lay down a procedure for Opening & closing of Raw/Packing /Finished Goods/and Engineering material Warehouses. 2.0 SCOPE 2.1. Raw Material / Packing Material / Finished Goods Engineering material Warehouses. 3.0 RESPONSIBILITY Assistant / Officer - Warehouse. 4.0 ACCOUNTABILITY Asst.Manager - Warehouse 5.0 PROCEDURE : 5.1.1 At the beginning of every working day the Warehouse Key to be taken by Assistant / Officer - Warehouse from the security by making necessary entries in Key’s Register (Maintained by -Security). 5.1.2 Security to hand over the Key to the person Authorised to draw the Raw Material / Packing Material Finished goods/ & Engineering material Warehouse keys. 5.1.3 Security to ensure the drawee signature and counter sign in the Key register. 5.1.4 In the absence of authorised person Security Officer to handover the keys to the person named by Assistant Manager - Warehouse on written request. 5.1.5 Immediately on op...

1.0 OBJECTIVE To lay down a procedure for Handling and Storage of Flammable and Hazardous Materials. 2.0 SCOPE Raw Material Warehouse and Solvent Yard. 3.0 RESPONSIBILITY Assistant / Officer / Executive - Warehouse. 4.0 ACCOUNTABILITY Asst.Manager - Warehouse. 5.0 PROCEDURE 5.1 All the flammable items to be identified and a specific area to be allotted. 5.2 The following instructions to be strictly followed in monitoring the area. 5.2.1 The place of storage to be safe guarded by fencing to restrict the movement of people. 5.2.2 Materials to be unloaded in tankers with pipe line connections. 5.2.3 While unloading the material, they are to be handled properly . for example pressurized drums to be unloaded with the help of tyres to avoid blasting due to sudden impact. 5.2.4 No live wires to be passed through the area where inflammable materials can be exposed to the sparks. 5.2.5 No smoking in the area is allowed. 5.2.6 The material is to be complete...

1.0 OBJECTIVE To lay down a procedure for “Stock Verification and Reconciliation” of raw material and packing material. 2.0 SCOPE Raw Material, Packing Material Warehouses, and Solvent Yard. 3.0 RESPONSIBILITY Officer - Warehouse. 4.0 ACCOUNTABILITY Assistant Manager - Warehouse. 5.0 PROCEDURE 5.1 Stock verification and reconciliation of all the material in the warehouse is done as below. 5.1.1 Create a Physical Inventory document in SAP with reference to inhouse batch number in all working days & take printout of the same. 5.1.2 Note the physical stock against the SAP stock in the Physical Inventory document. 5.1.3 Post the physical stocks in SAP. 5.1.4 Assess the variance & prepare Excess/Shortage certificate after completion of the stock against that particular in-house batch number as per SOP No:XXXXX. 5.2 The above verification and reconciliation should be done in addition to the perpetual stock verification done during d...

1.0 OBJECTIVE To lay down a Procedure for Disposal of Obsolete Materials. 2.0 SCOPE This SOP is applicable to Raw and packing material Warehouses of Formulations Units 3.0 RESPONSIBILITY Officer - Warehouse. 4.0 ACCOUNTABILITY Assistant.Manager - Warehouse 5.0 PROCEDURE 5.1 Materials which are no more in use and lying in the Warehouse idle for more than six months has to be informed to the Supply Chain Management Department in writing. 5.2 Supply Chain Management Department to explore any alternative exits with Formulations Research and Development. 5.3 Obsolete material to be stacked on top slot of the rack duly labelled. 5.4 Write-off note to be generated by Supply Chain Management Department based on the decision taken on the disposal. 5.5 Destroy write-off materials within 10 days from the date of receipt of duly approved “Write-off “ authorization form. 5.6 Provide proof of destruction copy to the concerned person at Central Excis...

1.0 OBJECTIVE To lay down a Procedure for Disposal of on line rejections 2.0 SCOPE 2.1.0 Area 2.1.1 Raw & Packing Material Warehouse. 3.0 RESPONSIBILITY Officer - Warehouse 4.0 ACCOUNTABILITY Asst.Manager - Warehouse 5.0 PROCEDURE 5.1 Online rejections should be received from Production on authorized documents “ON-LINE REJECTION NOTE” only as per the Annexure-1 5.2 “ON LINE REJECTION NOTE” to be signed by Executive -Production and Executive - Quality Assurance Departments. 5.3 Online rejected materials to be received with clear Online Rejected labels signed by the Officer - Production and Officer - Quality Assurance Departments. 5.4 The action plan regarding the remaining qty. of the particular consignment which is Online rejected ,should be clearly mentioned in the On-Line Rejection Note. 5.5 Warehouse to forward the On-Line Rejection Note to Purchase Department for suitable action within 3 days. 5.6 Less than 0.5 Kg. ...

1.0 OBJECTIVE To lay down a procedure for intimation of shortages and damages of Incoming Goods. 2.0 SCOPE This SOP is applicable to all Warehouses of Formulations Units. 3.0 RESPONSIBILITY Assistant /Officer - Warehouse. 4.0 ACCOUNTABILITY Asst.Manager - Warehouse 5.0 PROCEDURE 5.1 If any shortage or damage in incoming Goods found, the same has to be mentioned on the Delivery Challan before acknowledging the receipt. 5.2 The damages should be checked in presence of Quality Assurance personnel / the supplier / transporter. 5.3 If the damage is on the outer container / packing the same should be changed in presence of Quality Assurance 5.4 Shortages has to be indicated in Goods Received Note and inward actual quantity received and inform the same with in 24 hrs to the Purchase Department. 5.5 If the consignment is extensively damaged and Quality Assurance confirms not fit for receiving, do not accept and act as per Purchase...

1.0 OBJECTIVE To laydown a procedure for Cleaning of Dispensing Tools 2.0 SCOPE This SOP is applicable for Raw Material Warehouse at Formulations Units. 2.1 Area 2.1.1 All the dispensing areas - Raw Material Warehouse 2.1.2 Scoops, Spoons and servers. 3.0 RESPONSIBILITY Assistant / Officer -Warehouse and Dispensing Chemist -Production. 4.0 ACCOUNTABILITY Assistsnt Manager - Warehouse and Assistant Manager - Production. 5.0 PROCEDURE 5.1 Keep the once used (i.e., one material) dispensing tools such as scoops, spoons and big size server spoons in the box containing polybag as specified “accessories to be cleaned” 5.2 On completion of each batch dispensing, arrange for cleaning of used dispensing tools in the wash room. 5.3 Ensure cleaning person to wash the tools with purified water and final rinsing with purified water. 5.4 After wash, tools to be wiped with a fresh lint-free cloth. 5.5 Ensure the drying and cover the same ...

1.0 OBJECTIVE To lay down a procedure for Storage of Raw and Primary Packing Materials. 2.0 SCOPE This SOP is applicable to Raw Material Warehouse. 3.0 RESPONSIBILITY Assistant / Officer - Warehouse. 4.0 ACCOUNTABILITY Asst.Manager – Warehouse. 5.0 PROCEDURE 5.1 All material to be stored at temperature and relative humidity as specified in Annexure-1. 5.2 Record the temperature & R.H of Warehouse 5.3 Status label has to be affixed neatly to all material container possibly adjacent to the original Manufacturers label. 5.4 Materials should be neatly stacked on HDPE pallets and should be convenient for issue. 5.5 Clear PVDC films are to be stored in cool rooms. 5.6 Load on each pallet should be moderate and not exceed 500 kgs. Stack the material properly and uniformly on pallets. 5.7 Materials should not be protruding outside the pallets. 5.8 Arrangement of materials on pallets should be convenient for physical chec...

1.0 OBJECTIVE To lay down a procedure for Preparation of Goods Received Note for Raw and Packing materials. 2.0 SCOPE 2.1 Raw Material and Packing Material Warehouse. 3.0 RESPONSIBILITY Officer - Warehouse. 4.0 ACCOUNTABILITY Executive - Warehouse / Asst. Manager – Stores & excise. 5.0 PROCEDURE 5.1 For all the material received, prepare a Goods Received Note (GRN). 5.2 Prepare GRN immediately upon receipt and send the Certificate ofAnalysis (COA ),mentioning the GRN No.,to Quality control Dept.. 5.3 Note the GRN No. and Date on the Delivery challan/Invoice and file the same. 5.4 Raise fresh GRN for materials in case of subsequent reapproval after receiving the duly approved Non Conformance Report. 6.0 REVISION 6.1. Due to SOP review date expiry.

1.0 OBJECTIVE To lay down a procedure for operation of de-contamination booth. 2.0 SCOPE Raw material and Primary Packing material Warehouse. 3.0 RESPONSIBILITY Executive - Warehouse. 4.0 ACCOUNTABILITY Asst. Manager - Warehouse. 5.0 PROCEDURE 5.1 PRECAUTIONS 5.1.1 Ensure that the chain guards must be closed. 5.1.2 Containers should be placed on the conveyor, ensure that it should not touch the frame. 5.2 PRE START UP 5.2.1 Ensure for cleanliness of conveyor rollers. 5.2.2 Check the cleaning of suction filter, in case of any dust, get it cleaned. 5.3 SET UP 5.3.1 Set the selector switch in required mode i.e., Forward or Reverse. 5.4 OPERATION 5.4.1 Inform the warehouse personnel inside warehouse to organize pallets for unloading the material and to open the inside shutter. 5.4.2 Switch on the mains. 5.4.3 Start the side air blower by operating push button. 5.4.4 Start the top suction blower by operating push button. 5.4....

1.0 OBJECTIVE To lay down a procedure for receiving HPLC columns registering and its usage. 2.0 SCOPE This SOP is applicable to Quality Control Department. 3.0 RESPONSIBILITY Quality Control Executive / Officer. 4.0 ACCOUNTABILITY Department Head. 5.0 PROCEDURE 5.1 On receipt of a new column, enter the following details in the HPLC column register. A. Name of the column. B. Make C. Dimension and its particle size D. Date of receipt E. Mfr. Certificate : Received / Not received F. Application G. Manufacturers column number H. Column number allotted I. Usage with effective from (w.e.f.) [date] 5.3 All new columns in the lab should be numbered at the time of receipt. 5.4 Q.C Executive/Officer will be responsible to allot the number on receipt of the column. 5.5 All new columns / spare columns should be kept p...