To lay down the procedure for Tablet granulation, compression and coating.
This SOP is for the all the process from granulation up to the coating including the change over for the next batch at Production department.
3.1 Execution : Operator
3.2 Checking : Production Pharmacist & Above
HOD-Production / Assigned Designee
5.1 WET GRANULATION
5.1.1 After getting the line clearance form QA person for the area and for the equipment, bring the dispensed material of the batch to the manufacturing area by Checking and assuring that the balance is calibrated. Then check all the ingredients for name, weight, and batch number against the bill of material and sign on the checked by column of Bill of material and dispensed slip.
5.1.2 Flush first few liters of the D.M.Water and collect and use fresh D.M.Water for the manufacturing process.
5.1.3 Give Product status label to all the equipments.
5.1.4 Check all the equipments for proper assembly and run it in empty condition to check for friction or abnormal sound or presence of foreign material, If any of the abnormalities observed, inform the maintenance, get it rectified and re-clean the equipment after maintenance.
5.1.5 Change the D.M.Water from the hygrometer on daily basis.
5.1.7 Check intactness of the screen & sieves of the Multi mill and sifter before & after completion of the work.
5.1.8 Refer the instructions given in the batch manufacturing record and make all the entries timely in good and clean handwriting.
5.1.9 Avoid the overwriting while making the entries in the batch manufacturing record. In case of the error it is to be cut with single line and to be re-entered with counter sign and date.
5.1.10 During material handling and carrying out the manufacturing process, the operator should wear mask and gloves.
5.1.11 Any deviation during manufacturing process should be immediately informed to shift in-charge and QA person.
5.1.12 No material should be kept on the ground or unlabeled during the manufacturing process.
5.1.13 The required cleaned empty utensils should be kept in area for carrying out the manufacturing operation.
5.1.14 After completion of sifting of the material should be added in the mixer as per the sequence given in the batch manufacturing record.
5.1.15 Operate sifter as per SOP; sift the Raw material / granules as per instructions given in BMR.
5.1.16 Operate the Multi mill / cad mill as per SOP, during milling operation check the appearance of discharge material as per requirement of individual products.
5.1.17 Operate the
PLM or RMG as per respective
SOP. Dry mix & granulation the material as per instruction given in BMR.
5.1.18 After achieving the end point of the granulation the time and other details should be recorded for wet mixing in the batch manufacturing record.
5.1.19 Operate the FBD as per SOP. Dedicated finger bags of the fluidized bed dryer should be used for individual products. During fitting and before starting the fluidized bed dryer check the finger bag for intactness. Any damage if observed, the respective fluidized bed dryer finger bag should be rejected and should be reported to shift in-charge.
5.1.20 If the drying is continued for more than three days, the bag should be removed, cleaned and then to be used.
5.1.21 During drying procedure check and record the inlet air temperature and outlet air temperature as per the batch manufacturing record.
5.1.22 Before lubrication, check the weight of dried granules and record it in the batch manufacturing record. Lubricate the batch as per instruction given in BMR.
5.1.23 After completion of the manufacturing process, unloaded material should be checked for proper labeling, closing of the bags and the lids of the container before sending it to storage area.
5.1.24 After completion of manufacturing activity, the equipment use logbook is to be entered with all the details including stoppage of activity and equipment breakdown if any in “Equipment Log Book” (Annexure I).
5.1.25 The equipment stoppage during the manufacturing activity should be immediately informed to shift in charge and maintenance department by filling equipment breakdown form.
5.1.26 After repairing of the instrument/ equipment the line clearance is to be taken from quality assurance person to restart the activities and recalibration of the same should be carried out if applicable.
5.1.27 If the manufacturing of the new product is to be carried out in the same area follow the standard operating procedure for change over as per the SOP.
5.1.28 Remove all the documents, left over material and status label of the previous product from the area.
5.1.29 Put “To be cleaned” label on all equipments and area.
5.1.30 Remove all the deposited material from the electrical parts like motor, panel and switches and cover with poly bags.
5.1.31 Clean all the equipments as per standard cleaning procedure.
5.1.32 Remove riser filter of the air handling unit and clean after every Product changeover and after completion of three consecutive batches of same product or if required.
5.1.33 Before fitting check the filter for cleanliness, intactness and absence of leakage, if any, record the same in respective records.
5.1.34 Clean door frame, walls, tables, chair, tube light covers and floors and filters of return air supply ducts as per standard cleaning procedure.
5.1.35 After completion of cleaning check all the equipments and the area for cleanliness and give technical information sheet for swab test to quality control department.
5.1.36 The filled containers should be stored in storage area in segregation.
5.1.37 The racks and the drums in the storage area should be in clean condition.
5.1.38 The recoverable residue if any should be entered in recovery register & containers should be stored under lock and key.
5.2.1 After cleaning the compression machine as per respective
clean the compression area, dust extractor and its pipe, racks, door frames,
diffusers and return filters of Air Handling Unit.
5.2.2 While fitting the return filters, check it visually for intactness and absence of leakage.
5.2.3 Intimate quality control department to collect swab samples/rinse water as per requirement.
5.2.4 After receiving the approval from quality control department put ‘cleaned label’ to all the equipments.
5.2.5 If machine is to be kept ideal then the turret of the machine is to be covered with a thin layer of food grade oil with status label ‘to be cleaned’.
5.2.6 It is to be cleaned with 70 % isopropyl alcohol before taking clearance from quality control department.
5.2.7 If the compression of product is to be started, remove the ‘cleaned’ status label and affix the status label to the machine along with product name & Batch details, which is to be compressed.
5.2.8 Issue the punch set suitable for the product to be compressed as per the description of the punch set in the compression record of the batch manufacturing and as per SOP.
5.2.9 Fill up the punch tool record with all the details of the punch set issued.
5.2.10 Set the compression machine as per SOP and check the setting of the machine by rotating hand wheel.
5.2.11 Bring all the containers of lubricated granules of respective batch along with the batch manufacturing record to the area. Counter check the labels of all the containers for correct batch details as per the batch manufacturing record.
5.2.12 Set the machine as per the tablet parameters given in batch manufacturing record.
5.2.13 Destroy the tablets of first few rotations before starting the machine for the compression of the batch as per the SOP.
5.2.14 Collect the tablets generated during machine setting in a container as Utilisable residue and keep it duly labeled and packed. It should be used in same batch or next batch.
5.2.15 At the end of the compression, when the material in the hopper reaches to the lowest level stop the compression and destroy the left over from the feed frame or use it as an Utilisable residue.
5.2.16 After completion of the compression of the batch weigh the containers of the compressed tablets and record the same in the batch manufacturing record and do reconciliation of the same.
5.2.17 Clean all the containers from outside and transfer it to in process store with the label having all batch details.
5.2.18 If next batch of same product is to be taken follows the above steps from 1 to 220.127.116.11 If the batch of the new product is to be taken for compression remove all the left leftover materials and record of the previous batch from the area and put “to be cleaned” label to all equipments and area.
5.2.20 Remove the punch sets and record the same in punch tool record. Clean the punch set as per respective SOP and store the punch set in punch tool cabinet as said in SOP.
5.2.21 At the time of setting and checking the in process parameters of the tablet assure the I.P.Q.C.
5.2.22 Ensure that equipments like hardness tester, friability test apparatus, disintegration test apparatus and Vernier caliper are calibrated.
5.2.23 For disintegration test uses fresh water every time and discards the previously used water.
5.3.1 Clean the coating pan as per the SOP and intimate quality control department to collect swab samples/rinse water as per requirement.
5.3.2 After receiving the approval from the quality control department put’ cleaned’ label to all the equipments.
5.3.3 Assemble the hot air blower assembly. Start the exhaust and coating pan and check it for proper working.
5.3.4 Set the rpm of the coating pan and the temperature of the inlet air as per instruction given in the batch manufacturing record.
5.3.5 Assemble the spray gun assembly with peristaltic pump or dosing pump and check it for proper working.
5.3.6 Write the Status on coating pan, other equipments and the area.
5.3.7 Bring all the containers of the batch to be coated and batch manufacturing record. Check all the containers detailed label as per the batch manufacturing record.
5.3.8 Load the tablets from the containers serially and check the labels accordingly.
5.3.9 Weigh 100 tablets before coating and record the same in the batch manufacturing record.
5.3.10 Coat the tablets as per the parameters given in batch manufacturing record.
5.3.11 During coating, frequently check the spray gun nozzles for correct spraying, inlet air temperature and exhaust.
5.3.12 Clean the compressed air filters before starting the coating.
5.3.13 Check the appearance of the tablets for smoothness and intactness of edges.
5.3.14 Abnormality if any, observed stop the coating procedure and inform it to shift in charge. If coating is to be stopped in between, dry the tablets in the pan inching at 35°C to 40°C for 30 minutes.
5.3.15 After completion of coating procedure check the tablets for desired appearance and weight gain as per the BMR.
5.3.16 After completion of coating process, dry the tablets as per instruction given in BMR and allow it to come to room temperature and then unload it in the containers lined with double poly bags.
5.3.17 Clean the spray gun assembly as per respective
5.3.18 If the next batch of the same product is to be taken, check the inner surface of the coating pan for cleanliness. If required clean the pan and spray guns.
5.3.19 If the batch of the new product is to be taken for coating remove all the left over materials and record of the previous batch from the area and put “To be cleaned” label to all equipments and area.
5.3.20 Clean the air inlet and exhaust assembly and check the air inlet filters for absence of leakages if any and intactness.
5.3.21 After completion of cleaning of the area and the equipment give intimation to quality assurance department for collection of swab /rinse water sample as per requirement.
6.1 SOP: Standard Operating Procedure
6.2 BMR: Batch Manufacturing Record
6.3 Q.A.: Quality Assurance
6.4 HOD: Head of The Department
Ankur Choudhary is India's first professional pharmaceutical blogger, author and founder of Pharmaceutical Guidelines, a widely-read pharmaceutical blog since 2008. Sign-up for the free email updates for your daily dose of pharmaceutical tips.
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