OBJECTIVE:

• This SOP describes the procedure for performing and documenting line clearance in manufacturing and packing areas to prevent product mix-up, cross-contamination, documentation errors, and environmental non-compliance prior to commencement of any batch.

 SCOPE:

• This procedure shall apply to:
  • • Granulation Area
    • Compression Area
    • Tablet Inspection Area
    • Coating Area
    • Blister Packing Area
    • Secondary Packing Area
    • Dispensing Area
    • Overprinting Area

RESPONSIBILITIES:

• Cleaning of equipment and area shall be performed by Production personnel as per approved Cleaning SOP.
• Line clearance shall be performed by Production personnel prior to commencement of any batch activity.
• Line clearance shall be independently verified and reviewed by Quality Assurance personnel.
• Approval for commencement of manufacturing or packing activity shall be granted by Quality Assurance after satisfactory verification of line clearance.
• Engineering Department shall ensure that preventive maintenance and calibration status of equipment are within validity prior to use.

DEFINATIONS:

• Line Clearance: A systematic and documented verification to confirm that the manufacturing or packing line is clean, cleared of previous batch materials, and ready for the next batch operation.

 PROCEDURE:

General line clearance requirements

• Line clearance shall be performed:
  • • • Before starting a new batch of same product
      • After product changeover
      • After major maintenance activity
      • After prolonged shutdown
• No batch processing shall commence without documented line clearance approval by Production and QA.
• The area shall be free from any materials, residues, labels, documents, packaging components, or remnants of the previous product.
• All equipment shall be cleaned as per the respective Cleaning SOP and shall bear a valid “CLEANED” status label.
• All materials and printed packaging components of the previous batch shall be removed from the area.
• Rejection bins shall be emptied, cleaned, and properly identified before initiation of the new batch.
• Preventive maintenance status and Calibration status of the equipment / sensor / Timer shall be verified and shall be within validity period.
• Supply and Return air risers shall be free from previous product traces.

Area Line Clearance:

• Area status boards shall be updated with the current product name and batch number.
• The manufacturing or packing area shall be physically inspected to confirm that it is clean and orderly.
• Floors, walls, doors, and working surfaces shall be free from visible dust, powder, granules, tablets, or packaging debris.
• No unidentified materials, containers, tools, or documents shall remain in the area.
• The area surrounding the machine shall be free from unused or unidentified materials.
• Environmental conditions (Temperature, RH, Pressure Differential) shall be verified and recorded prior to Line Clearance in the Batch Manufacturing Record / Batch Packing Record (BMR/BPR).
• Area Line Clearance shall be recorded in the Area Line Clearance Record and shall be approved by QA before start of operations in case of product changeover and Line clearance of same product shall be approved by Designee production.
• Equipment and area logbooks shall be completed prior to release of the area.
•  QA shall independently verify and sign the line clearance section in BMR/BPR prior to commencement of the respective activity.
• No activity shall be initiated without QA authorization in case of product-to-product changeover.

Dispensing Area Line Clearance:

• Area status boards shall be updated with the current product name and batch number.
• The dispensing area shall be free from raw materials, labels, containers, and documents of the previous batch.
• Dispensing booths, balance tables, and working surfaces shall be free from powder residues and foreign matter.
• The Reverse Laminar Air Flow (RLAF) unit shall be cleaned as per approved Cleaning SOP prior to line clearance.
• The RLAF working surface, side panels, and stainless-steel surfaces shall be free from powder deposits and foreign matter.
• The pre-filter and visible HEPA grill surface shall be clean and intact.
• RLAF shall be operated for the specified pre-run time prior to dispensing activity.
• Dispensing balances shall be clean and shall have valid calibration status prior to use.
• Scoops, utensils, and dispensing containers shall be clean and shall correspond only to the current material being dispensed.
• The area surrounding the machine shall be free from unused or unidentified materials.
• Environmental conditions (Temperature, RH, Pressure Differential) shall be verified and recorded prior to Line Clearance in the Batch Manufacturing Record / Batch Packing Record (BMR/BPR).
• Area and Equipment Line Clearance shall be recorded in the Area / Equipment log and shall be approved by QA before start of operations in case of product changeover and Line clearance of same product shall be approved by Designee production.
• Equipment and area logbooks shall be completed prior to release of the area.

Granulation Area Line Clearance:

• Area status boards shall be updated with the current product name and batch number.
• The Rapid Mixer Granulator (RMG), Fluid Bed Dryer (FBD), Steam Kettle, Multimill, Sifter, and Blender shall be cleaned and visually inspected to confirm absence of residual material.
• All previous raw material containers, empty bags, and labels shall be removed.
• Product contact parts shall be free from powder deposits and foreign matter.
• Filter bags of FBD shall be clean and intact.
• Screens and meshes shall be verified for correct size and integrity.
• The area surrounding the machine shall be free from unused or unidentified materials.
• Environmental conditions (Temperature, RH, Pressure Differential) shall be verified and recorded prior to Line Clearance in the Batch Manufacturing Record / Batch Packing Record (BMR/BPR).
• Area and Equipment Line Clearance shall be recorded in the Area / Equipment log and shall be approved by QA before start of operations in case of product changeover and Line clearance of same product shall be approved by Designee production.
• Equipment and area logbooks shall be completed prior to release of the area.

Compression Area Line Clearance:

• Area status boards shall be updated with the current product name and batch number.
• The Compression Machine shall be cleaned and shall be free from powder, dust, and tablets.
• Hopper, feed frame, turret, punches, dies, and discharge chute shall be inspected to ensure removal of previous product.
• Dedusters and Metal Detectors shall be cleaned and dust collection containers shall be emptied.
• Metal Detector challenge test shall be performed using standard test pieces and results shall be recorded in the BMR.
• Analytical balances used for in-process checks shall have valid calibration status and shall be verified prior to use.
• The area surrounding the machine shall be free from unused or unidentified materials.
• Environmental conditions (Temperature, RH, Pressure Differential) shall be verified and recorded prior to Line Clearance in the Batch Manufacturing Record / Batch Packing Record (BMR/BPR).
• Area and Equipment Line Clearance shall be recorded in the Area / Equipment log and shall be approved by QA before start of operations in case of product changeover and Line clearance of same product shall be approved by Designee production.
• Equipment and area logbooks shall be completed prior to release of the area.

 Inspection Area Line Clearance:

• Area status boards shall be updated with the current product name and batch number.
• The Tablet Inspection Machine shall be cleaned and visually inspected to confirm absence of previous tablets.
• Feeding hopper, inspection belt, reject channel, and collection bins shall be empty and clean.
• Good and Reject collection bins shall be properly identified.
• Reject bin shall be empty before commencement of inspection activity.
• The area surrounding the machine shall be free from unused or unidentified materials.
• Environmental conditions (Temperature, RH, Pressure Differential) shall be verified and recorded prior to Line Clearance in the Batch Manufacturing Record / Batch Packing Record (BMR/BPR).
• Area and Equipment Line Clearance shall be recorded in the Area / Equipment log and shall be approved by QA before start of operations in case of product changeover and Line clearance of same product shall be approved by Designee production.
• Equipment and area logbooks shall be completed prior to release of the area.

 Automated Coating Area Line Clearance:

• Area status boards shall be updated with the current product name and batch number.
• The Automated Coating Machine shall be cleaned and free from residual tablets and coating material.
• Spray guns, solution preparation vessel, and silicon tubes shall be cleaned, dried, and visually inspected.
• No leftover coating solution from previous batch shall remain in the area.
• The area surrounding the machine shall be free from unused or unidentified materials.
• Environmental conditions (Temperature, RH, Pressure Differential) shall be verified and recorded prior to Line Clearance in the Batch Manufacturing Record / Batch Packing Record (BMR/BPR).
• Area and Equipment Line Clearance shall be recorded in the Area / Equipment log and shall be approved by QA before start of operations in case of product changeover and Line clearance of same product shall be approved by Designee production.
• Equipment and area logbooks shall be completed prior to release of the area.

Blister Packing Area Line Clearance:

• Area status boards shall be updated with the current product name and batch number.
• The Blister Packing Machine shall be cleaned and free from previous tablets, foil remnants, and packaging components.
• The feeding hopper, feeder box, feeding channel and guide tracks shall be free from tablets of the previous product.
• The forming station and sealing station shall be free from foil scraps and product remnants.
• The discharge chute shall be free from blisters of the previous batch.
• The rejection box attached to the machine shall be empty and free from rejected blisters of the previous product.
• Batch coding unit shall be verified to ensure correct batch details as per approved BPR.
• All printed packaging materials including foils, cartons, and leaflets present in the area shall correspond only to the current batch.
• The area surrounding the machine shall be free from unused or unidentified materials.
• Environmental conditions (Temperature, RH, Pressure Differential) shall be verified and recorded prior to Line Clearance in the Batch Manufacturing Record / Batch Packing Record (BMR/BPR).
• Area and Equipment Line Clearance shall be recorded in the Area / Equipment log and shall be approved by QA before start of operations in case of product changeover and Line clearance of same product shall be approved by Designee production.
• Equipment and area logbooks shall be completed prior to release of the area.

 Secondary Packing Area Line Clearance:

• Area status boards shall be updated with the current product name and batch number.
• Conveyor belt shall be cleaned and free from previous cartons and shippers.
• Coding and printing machines shall be verified for correct batch details.
• Only approved packaging material for the current batch shall be present in the area.
• Environmental conditions (Temperature, RH, Pressure Differential) shall be verified and recorded prior to Line Clearance in the Batch Manufacturing Record / Batch Packing Record (BMR/BPR).
• Area and Equipment Line Clearance shall be recorded in the Area / Equipment log and shall be approved by QA before start of operations in case of product changeover and Line clearance of same product shall be approved by Designee production.
• Equipment and area logbooks shall be completed prior to release of the area.

Overprinting Area Line Clearance:

• The overprinting machine shall be clean and free from cartons, foils, leaflets, or shippers of the previous batch.
•  Printing rollers, ink trays, and coding units shall be free from previous batch details.
• All previous printed packaging materials shall be reconciled and removed from the area.
• Only packaging materials approved for the current batch shall be present in the area.
•  The rejection box shall be empty and free from previously rejected printed materials.
• Overprinting details (Batch No., Mfg. Date, and Exp Date) shall be verified against the approved BPR before start of operation.
• Environmental conditions (Temperature, RH, Pressure Differential) shall be verified and recorded prior to Line Clearance in the Batch Manufacturing Record / Batch Packing Record (BMR/BPR).
• Area and Equipment Line Clearance shall be recorded in the Area / Equipment log and shall be approved by QA before start of operations in case of product changeover and Line clearance of same product shall be approved by Designee production.
• Equipment and area logbooks shall be completed prior to release of the area.

REFERENCE:

• WHO Technical Report Series (TRS) 961, Annex 6 – WHO Good Manufacturing Practices for Pharmaceutical Products: Main Principles.
•  WHO Technical Report Series (TRS) 986, Annex 2 – Good Manufacturing Practices for Pharmaceutical Products.

 RECORDS:

 REVISION HISTORY: