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Line Clearance of Process during Drug Manufacturing

Standard Operating Procedure (SOP) for Line Clearance (LC) during the manufacturing process of pharmaceutical drug products. The term line clearance is used for the documented act of conducting any necessary removal of products and materials from a manufacturing/ packaging line to prepare the line for the next production.

Line Clearance (LC) Procedure

1.0   Objective :

    • To lay down the procedure for Line Clearance.

2.0   Scope :

    • This SOP is applicable in Production/Packing and Stores (Dispensing of raw materials) before starting a new process at the pharmaceutical manufacturing plant.

3.0   Responsibility :

Production Chemist / Designee : To verify the compliance regarding area/line clearance before calling the QA person for the same
Stores Officer / Designee : To verify the compliance regarding area for Dispensing of Raw Materials
QA chemist/ Designee : To verify the compliance regarding area/ Equipment before giving the clearance for that area/line for the process.

4.0   Accountability :

    • Head of Respective Department: For system compliance.

5.0   Procedure for Line Clearance :

    • Line clearance:

    • The term line clearance is used for the documented act of conducting any necessary removal of products and materials from a manufacturing/ packaging line to prepare the line for the next production.
    • Mix-Up:

    • Accidental mixing of raw material/ intermediate/ finished product/ packing material of one product/batch to another product/batch
    • Cross Contamination :

    • Contamination of a starting material, intermediate product, or finished product with another starting material or product during production
    • Contamination :

    • The undesired introduction of impurities of a chemical or microbiological nature, or of foreign matter, into or onto a starting material, or intermediate or finished product during production, sampling, packing or repacking, storage or transport.

Related: Cross Contamination, Mix-Ups & Microbial Contamination

    • Line clearance of each area/equipment shall be done to control:

      • Contamination & cross-contamination.
      • Mixing of products or batches.
    • Before starting each operation Production Chemist or Stores Officer should check the area/equipment used.
    • Check the area as per the checklist attached in BPR / BMR and put their initial.
    • If any point is not applicable then write NA.
    • After checking inform to QA chemist to release the area/equipment for the next process.
    • QA chemist should verify the area/equipment and record the observation in the checklist.
    • Visually check the cleanness of the area/equipment by using the battery torch during the line clearance where ever required.
    • If all the points comply, the QA chemist shall release the area/equipment for the next processing and put the initials with the date.
    • If the area/equipment does not comply with the checklist, inform to Production Chemist or Stores Officer to take necessary corrective action.
    • After the corrective action, the QA chemist shall verify the same and release the area/equipment for the next processing if the things comply.
    • Re-line clearance:

    • Manufacturing areas:

    • Re-Line clearance during manufacturing operation shall be done in the given below condition.
      • After machine/equipment breakdown followed by breakdown maintenance work.
      • If any non-conformance reported during line clearance and during operation.
    • The batch shall be continued after doing the line clearance as per the Annexure-IV which shall be conducted either by the next production chemist/Officer or by IPQA.
    • Packing area:

    • Reline clearance during packing operation shall be done in the given below condition:
      • Change over from sale to P.S. or institution or vice versa.
      • If the packing process continues to the next day.
      • After machine breakdown followed by breakdown maintenance work.
      • Re-line clearance shall be done using Annexure-I or Annexure-II as per the above procedure.
    • Controlled copies of these annexures shall be issued by QA as and when required.
    • In case some deficiencies are noticed during checks and verifications,
    • Then quick corrective action is taken to address the deficiency, and
    • only after rectifying the deficiency, line clearance shall be given
    • Dispensing Area:

    • Re-Line clearance during dispensing operation shall be done in the given below condition:
      • After machine breakdown followed by breakdown maintenance work.
      • If the dispensing process continues to the next day.
      • Re-line clearance of the dispensing area shall be done using Annexure-III.
    • During batch changeover of campaign manufacturing in the product:
    • Each equipment shall be cleaned as per the respective SOP and there shall be no loose/stuck bulk powder.
    • If any shall be removed.
    • General cleaning of area and riser filter/grill shall be cleaned and
    • No loose powder shall be there.
    • If cleaning of the filter is defined in the checklist, it shall be marked NA “Not Applicable”

6.0   Reference – Line Clearance :

    • Revised Schedule M
    • Volume 4:   EU Guidelines to Good Manufacturing Practice Medicinal Products for
      Human and Veterinary Use, Chapter 5 Production.

7.0   Glossary

    • QA: Quality Assurance
    • SOP: Standard Operating Procedure
    • BPR: Batch Packaging Record or Batch Processing Record
    • P.S.: Physician Sample

8.0   Annexures of SOP for Line Clearance (LC) :

Annexure I: Format for Re-line Clearance for Oral Liquids.

Product:………………………………………..                      Date:……………        

B. No……………….               Mfg. :…………………                        Exp.: ……………

Reason: ………………………………………………………………….

Checked By
Prod. QA
1. Bottle Washing:
1.1 Is the area clear off bottles of the product? Clear/Not Clear
1.2 Is the area clean? Clean/Not Clean
1.3 Is the machine is clean (Visual Inspection)? Clean/Not Clean
1.4 Is there a status label on the machine? Yes/No
1.5 The machine is released for washing bottles. Released/Not Released
2. Filling, Sealing & Inspection:
2.1 Is the area clear-off bottles, PP caps & other materials of the product? Clear/Not Clear
2.2 Is the area clean? Clean/Not Clean
2.3 Is the filling machine clean? Clean/Not Clean
2.4 Is the sealing machine clean & clear off the PP cap of the product? Clean/Not Clean
2.5 Is the inspection Machine & conveyer clean? Clean/Not Clean
2.6 Is there a status label on the machine? Yes/No
2.7 The machine is released/not released for filling, sealing & inspection Released/Not Released
3. Labeling Area, Coding & Packing:
3.1 Is the area clear of labels/cartons of the product? Clear/Not Clear
3.2 Is the area, machine packing belt clean? Clean/Not Clean
3.3 Are the stereos of the batch destroyed (SOP/PD-050)? Destroyed/Not Destroyed
3.4 Is there a status label on the packing line? Yes/No
3.5 The line is released/not released for labeling & packing Released/Not Released
Remarks:

Annexure-II: Format for Re-line Clearance for Tablets & Capsules.

Product:………………………………………..                      Date:……………        

B. No……………….               Mfg. :…………………                        Exp.: ……………

Reason: ……………………

Checked By
Prod. QA
1. Blister / Strip Area
1.1 The area along with doors, glasses & walls clean. Clean / Not Clean
1.2 Blister foil / PVC / aluminum foils and other materials relative to the previous products are removed. Removed / Not Removed
1.3 Stereos of previous products (foil) are destroyed, check records. Destroyed / Not Destroyed
1.4 Check the blister machine for cleanliness especially hopper, bowl, etc. Clean / Not Clean
1.5 Check the waste bin for cleanliness Clean / Not Clean
1.6 Check the gowning as per SOP Complies / Doesn’t Comply
1.7 Check temperature & Relative humidity record of the area Complies / Doesn’t Comply
1.8 The machine is released / not released for stripping.
2. Packing area
2.1 Ensure that the area is cleaned and free from previous product Clean / Not Cleaned
2.2 Check the proper status label on the machine. Affixed / Not affixed
2.3 Check that characters use for storage of carton is free from previous product materials. Ok / Not Ok
2.4 Check that stereo of the previous batch/product should be destroyed and entered on the logbook. Ok / Not Ok
2.5 Ensure the Waste bin shall be clean and free from previous products. Clean / Not Cleaned
2.6 The machine is released / not released for Packing.
Remarks:

Annexure III: Format for Re-line Clearance for Dispensing.

Product:………………………………………..              Date:……………       

B. No……………….               Mfg. :…………………                        Exp.: ……………

Reason: ……………………

*Checked By
Stores QA
Dispensing Area
1. The dispensing area &RLAF is clean. Clean / Not Clean
2. Materials of the previous Batch are removed.

Previous Product dispensed:…………………

Batch No.: ………………….

Removed / Not Removed
3. Balances are clean and calibrated (check the calibration record) Complies / Doesn’t Comply
4. Dispensing tools are clean. Clean / Not Clean
5. Fresh polythene bags are there. Complies / Doesn’t Comply
6. Containers used for dispensing are clean & bears a status label. Complies / Doesn’t Comply
7. Personnel involved in dispensing are properly dressed up i.e. wearing the gown, hand gloves & snood. Complies / Doesn’t Comply
8. AHU is ON. On/Off
9. The temperature and relative humidity of the dispensing area. Complies / Doesn’t Comply
10. A pressure differential of RLAF across HEPA & across pre-filter is checked. Complies / Doesn’t Comply
11. The weighment sheet duly signed by Production & Q.A. along with identity slip & BMR is there. Complies / Doesn’t Comply
Remarks:

Annexure-IV: Format for Re-line Clearance of production area during shift break.

Product:………………………………………..                       Date:……………       

B. No……………….               Mfg. :…………………         Exp.: ……………

Reason: ……………………

Checked By
Prod. QA
   
1. Check and ensure identification of the area and the equipment with the status label Yes/No
2. Ensure the cleanness of the waste bins Clean / Not Clean
3. Ensure that the gowning system is followed properly. Followed/Not Followed
4. Ensure that the Differential Pressure of areas is within the limit. Yes/No
5. Check temperature and RH maintain in the area? Yes/No
6. Is the area clean? Clean / Not Clean
7. Is the machine is clean (Visual Inspection)? Clean / Not Clean
8. Check and ensure the availability of cleaned utensils/scoops Available/Not Available
9. Check the cleanliness of the Inspection Belt and other accessories. Clean / Not Clean
10. Ensure the materials related to batch/products are available? Available / Not Available
11. Check the availability of the related documents. Available / Not Available
12. Check the availability of the data entered in the logbooks. Available / Not Available
Remarks:

 

 

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