Batch Processing – SOP & General Check Points

.perating Procedure (SOP) for General Check Point during Drug Product Batch Processing in the pharmaceuticals drug manufacturing plant.

General Checks and Precautions During Processing of Batch

1.0   PURPOSE:

    • The purpose of this SOP is to lay down the procedure for General Checks & Precautions during Processing of Batch.

2.0   SCOPE:

    • This SOP is applicable for all stages of Manufacturing and Packing during the Processing of Batch at the pharmaceuticals drug manufacturing plant.

3.0   REFERENCES – SOP FOR BATCH PROCESSING:

    • Handling and Destruction of Non-Recoverable Recovery (SOP)
    • General Cleaning Procedure for Production Area (SOP)
    • Handling of Containers, Hose pipes, and Accessories (SOP)
    • SOP for Environmental Monitoring
    • Stoppage and restarting of operations during utility Failure (SOP)
    • Material Movement in Manufacturing Premises (SOP)
    • SOP for Reprocessing
    • SOP  for Department Closing Procedure Draft
    • Procedure for Disposal of Waste (SOP)

4.0   RESPONSIBILITY – SOP FOR BATCH PROCESSING:

    • The operator having training or awareness about all safety requirements and special precautions for individual products mentioned in MBMR, shall follow all the general checks & precautions during the processing of individual drug products.
    • Production Supervisor shall ensure or cross-check about the general checks required & precautions during the processing of batch/ product as per respective MBMR.
    • The supervisor will also be responsible for awareness of involved operators regarding safety concerns and precautions to be followed.
    • Production Head or Designee shall be responsible for the proper compliance of the SOP.
    • Quality Assurance shall be responsible for the proper Compliance of the SOP.

5.0   ABBREVIATIONS:

    • FBD: Fluid Bed Dryer
    • HVAC: Heating, Ventilation and Air Conditioning
    • MBMR: Master Batch Manufacturing Record
    • MBPR: Master Batch Processing Record.
    • MRO: Material Requisition Order
    • NRR: Non-Recoverable Recovery
    • RR: Recoverable Recovery

6.0   PROCEDURE – SOP FOR BATCH PROCESSING:

  • Batch Processing – General Check Points – Part A

    • Transfer the dispensed material from post dispensing staging area to dispensed material quarantine/ staging area.
    • Keep the dispensed material containers on the pallet with lid.
    • Tied all containers kept on the pallet with nylon rope while transferring from one location to another.
    • Handle the solvents carefully during transfer to the required cubicle to avoid the chances of spillage of materials.
    • Transfer all materials required at the ground floor through an elevator or lift.
    • Do not transfer different batches of dispensed materials together in one pallet.
    • Before transferring the dispensed material to the dispensed material staging area storage condition of the area shall be ensured.
    • If not complies maintenance department shall be intimated.
    • After resolving the discrepancy dispensed materials shall be transferred.
    • Transfer the dispensed material to the cubicle where processing or compounding of the lot.

Note:       Place all containers on the cleaned pallet. Avoid placing directly on the floor.

    • Dispensed material staging area and all quarantine area shall be under lock and key.
    • Production supervisor shall collect the key from the shift in charge and after completion of activity should return to shift in charge.
    • Ensure the cleanliness of the cubical area before transferring the dispensed materials.
    • Concerns involved in cleaning shall wear safety shoes and safety proof suit.
    • Check and ensure daily cleaning of ceiling, walls, door, and view panel, pendent (if available) was performed properly.
    • Check and ensure daily cleaning of SS bins, SS Scoops, containers, Pallets, Hose pipes, sieve/screen, SS spatula, SS jugs, and Accessories properly.
    • Ensure proper cleaning of the equipment.
    • Perform type ‘A’ cleaning in case of batch change over and type ‘B’ cleaning in case of product change over.
    • Check and ensure the calibration status of Thermo hygrometer and monitor the temperature and RH of the area.
    • Check and ensure the calibration status of the Magnehelic gauge and monitor the pressure differential record.
    • Ensure calibration of balance on a daily basis and recalibrate the balance in case change in location of balance, before weighing of any material.
    • Before entering into the cubicle wear a secondary gown (headgear, overcoat), nose mask (wear 3M nose mask only in case of potent drugs otherwise wear disposable ordinary mask only), and hand gloves.
    • The production supervisor shall perform area clearance, equipment clearance, start-up clearance, and verified by the QA supervisor.
  • Batch Processing – General Check Points – Part B

    • Check and weigh each and every dispensed material’s physical appearance and quantity against confirmed MRO and MBMR of the particular Batch No. before compounding or processing of the batch.
    • Check and ensure ‘0.00’ display of the balance before weighing each and individual dispensed raw materials.
    • Record the observed weight in the weight verification record in MBMR.
    • If incase any discrepancies observed. Intimate QA and shift in charge.
    • In case of materials dispensed in the intact container; mother container label, affixed quarantine, dispensed material label, and verify its physical appearance along with quantity against confirmed MRO and MBMR.
    • If any discrepancies observed in dispensed materials. Intimate QA and shift in charge.
    • After rectification of the discrepancy. Execute the further process.
    • Before compounding the product, MBMR for characteristic type or nature of the product shall be referred.
      • Carry out the manufacturing of the light-sensitive product under a sodium vapor lamp.
      • Store the light-sensitive materials in duly labeled polyethylene lined containers where the outer polyethylene bag shall be transparent and the inner polyethylene bag shall be black colored.
      • Carry out the compounding of hygroscopic materials under controlled environmental conditions (Temperature and RH) as per MBMR.
      • Store the hygroscopic materials in duly labeled polyethylene lined containers along with 2 silica bags (NLT 250 gm. each) sandwiched between two polyethylene bags.
  • Batch Processing – General Check Points – Part C

    • Before handling any equipment, refer to the safety checklist mentioned in MBMR and MBPR at each stage of manufacturing.
    • Check and ensure the appropriate status label with required details as per the present status on products, containers, accessories, types of equipment, and areas.
    • After loading any material to the next step of under process, remove and discard the used poly bags from the drums and ensure that no residue is left inside the drum.
    • Ensure the absence of residues in containers before putting new polybags.
    • Affix new labels before making it ready for the next stage if the same containers used.
    • This procedure is not applicable for packing where the drums will be emptied and washed after use.
    • Different lots of a single batch can be taken for processing in a single cubicle with proper labeling and segregation.
    • Carry out in-process checks at regular intervals at the relevant stage specified in BMR.
    • On line, Carry out the weighing on calibrated balance and proper labeling of all the processed containers after each relevant stage of processing.
    • Use the processed containers in sequence as 1,2,3,4…..for the next stage of processing e.g. in granulation, compression, coating, capsule filling, and parking area.
    • The unique container numbering in the granulation dept. Alphanumeric in nature and numbering as Dept. code i.e. G followed by 3 digit serial no.
    • The first container of Granulation numbered as G001 and so on.
    • These containers with unique container no. shall be used after Dry milling stage and lubrication stage.
    • The unique container no. and cable tie details shall be recorded in Attachment-1 after each relevant stage of processing by concerned Production Officer.
  • Batch Processing – General Check Points – Part D

    • Record the details of NRR generated during granulation in MBMR.
    • Reconcile the lubricated granules along with NRR and in-process samples if any.
    • Review the BMR and handover to QA for the closure of the record and approval for further processing of the batch.
    • Transfer lubricated granules to the desired cubicle where batch’s compression activity or capsule filling activity to be carried out in case of the batch to be planned immediately.
    • In case of delay in further processing processed. Transfer lubricated granules to the desired quarantine area.
    • Transfer the lubricated materials to the cubicle where processing or compounding of the product to be carried out.
    • Ensure the cleaning and storage condition of granules before transferring the granules to the compression area.
    • Before commencing for compression or capsule filling all required LC related documentation and follow the instructions and executed as per SOP of line clearance. (SOP for Line Clearance)
    • Check the weight of the lubricated granules, as well as its appearance, for each container before starting the compression and capsule filling activity.
    • Check and ensure the ‘0.00’ display of the balance before putting on a balance platform for weighing each and individual lubricated containers for weight verification purposes.
    • If any discrepancies reported related to lubricated raw materials, Intimate the shift in charge and QA.
    • Evaluate the safety issue before handling any equipment.
    • Intimate to the maintenance department if any discrepancies observed.
    • Carryout compression or capsule filling activity as per MBMR’s Instructions and method described.
    • Carry out in-process checks at regular intervals at the relevant stage specified in BMR.
    • After completion of compression or capsule filling activity, Intimate to QA for bulk approval and sample collection.
  • Batch Processing – General Check Points – Part E

    • Collect the processing waste material or NRR (Powder, Capsules, and tablet) in a container & crushed the same to powder form & where not possible to be crushed then add some water just to make a slurry.
    • Reconcile the compressed tablets or filled capsules along with NRR and in-process samples if any.
    • Review the BMR and handover to QA for the closure of the record and approval for further processing of the batch.
    • Transfer uncoated tablets and capsules to the quarantine area after bulk approval from QA and reconciliation.
    • In the case of finished uncoated tablets, compressed tablets can be transferred to packing in case of the batch to be packed immediately.
    • In the case of finished coated products, compressed tablets can be transferred to the desired coating cubicle for the coating of the product.
    • Before transferring the core tablets to the coating cubicle area cleaning shall be ensured and the required environmental condition shall be ensured by the production supervisor.
    • Check and ensure the appropriate status label with required details as per the present status on products, containers, accessories, equipment, and areas.
    • Production supervisor shall perform area clearance, equipment clearance, start-up clearance, and verified by the QA supervisor.
    • The weight of the containers received from compression shall be verified before subjecting for the coating process.
    • Intimate to QA and shift in charge for any discrepancies reported.
    • Execute the further processing of the batch after rectification of the problem.
    • Divide the total batch in ‘n’ no. of lot equally (in kg) in which coating to be performed.
  • Batch Processing – General Check Points – Part F

    • After loading any material to the next step of under process, remove and discard the used poly bags from the drums and ensure that no residue is left inside the drum.
    • Ensure the absence of core tablets and dust in containers before putting new polybags.
    • Affix new labels before making it ready for the next stage.
    • Carryout coating of the product as per MBMR instructions and procedure outlined.
    • After completion of the coating of the product, Intimate QA for finish product sampling and bulk approval.
    • Perform reconciliation of the coated tablet as per MBMR.
    • Review the BMR and handover to QA for the closure of the BMR and approval for further processing of the batch.
    • Do not transfer the different baches of the same product dispensed materials on the same pallet together in order to avoid the chances of the batch mix up.
    • Transfer the primary packing material to the primary packing cubicle.
    • Keep the secondary packing materials on the left-hand side and finished shippers on the right-hand side of the packing line.
    • Before transferring the packing material to the desired cubicle area clearance of both primary and secondary packing areas shall be ensured.
    • Transfer coated tablets to the desired primary packing cubicle along with Closed MBMR from QA.
    • After line clearance carryout packing activity as per MBPR’s instruction and method described.
    • Transfer the packed shipper to BSR through ERP after QA approval.
  • Batch Processing – General Check Points – Part G

    • Reconcile all the packing materials and return leftover unprinted packing materials to the PMS after making a necessary entry in the BPR and ERP system.
    • While manufacturing or packing activity if a sudden utility failure occurs then discontinue all running process immediately except process which will result in damage to the product on discontinuation and note down the stoppage time in BMR/ BPR/ Log Book with the reason of stoppage.
    • Unload the leftover tablets or capsules on packing equipment in double polyethylene bag lined container, properly tied with a cable tie and status label before the closing of the manufacturing area in case of holiday or weakly off.
    • At the intermediate stage of processing if hold time was more than 48 hours.
    • Remove all the product containers from the area and Perform the clearance after the complete changeover.
    • After the end of the activity of individuals of a particular department, the concern department representative shall close the department after verifying all the checkpoints.
    • During and after processing (manufacturing and packing) of the product if any discrepancies observed related to the quality of the product. Intimate to shift in charge and QA.
    • Stack the batch under investigation in a separate or defined area with the proper status labels.
    • Reprocessing and reworking of all or part of a batch of the product of an unacceptable quality from a defined stage of production,
    • After a detailed investigation done by production and quality assurance to determine the reason for reprocessing.
    • Transfer the batch to the market after a satisfactory report of reprocessed batch COA and closure of product-related all documents (BMR, BPR, Change Control, Event, OOS, etc…) from QA.

7.0   ANNEXURES:

  • Annexure 1: Unique container no. /Cable ties no. details of processed containers in different stages of the process.

 Product Name  
 Batch No.    Lot/ Oper.  
Stage of Processing    Date  
Sr. no. Unique Container No. Cable Tie No. Gross Wt. Tare Wt. Net Wt.
1         
2         
3         
  • Annexure 2: Lubricated granule verification record Accountability of Container wise packed shippers.

 Product Name  
 Batch No.  
Stage of Processing  
Sr. No. Unique Container No. Cable Tie No. Appearance Gross Wt. Tare Wt. Net Wt.
  • Annexure 3: Accountability of Container wise packed shippers.

Product Name:  
Batch No. :  
Stage of Processing:  
Date Container No. Net Wt.

Shipper No.

Time Physically Shipper

Checked By Packing

Checked By QA

Start

End

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pharmabeginers

Janki Singh is experienced in Pharmaceuticals, author and founder of Pharma Beginners, an ultimate pharmaceutical blogging platform. Email: [email protected]

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