What is Line Clearance :
Line clearance is a process which provides a high degree of confidence or assurance that the said line or area is free from any unwanted residue or left over of previous processing’s before proceeding for next process. Quality assurance has to provide Line clearance before the start of any activity whether it is batch to batch change over and Product to product change over
Criteria of Batch to batch change over :
Change over from one batch to another batch of same product and same Strength or increasing in strength provided the excipients is same.
Cleaning between batches of same product but in ascending or increasing strength.
Criteria of Product to Product change over :
- Change over from one product to another product.
- Change over form one product to same product with descending or decreasing strength.
- Change over between batches / product with different colour/ Flavour / Excipients.
- Change over after post maintenance or when the next product is not known (as applicable).
- Continuously running of one batch for a longer period of time.
- Area or Equipment is kept ideal for more period of time.
Line clearance should be carried out at change over by Manufacturing, Packaging, Raw Material Store, Packing Material Store etc independently for the stages where final dosage form & intermediates are formed, handled and processed.
Line clearance for all area should be given as per following points (but not limited to) :
- On request from concerned area for line clearance, QA will Check all the points/line & shall ensure the type of cleaning (Product to Product or Batch to Batch). If the machine/Area having Product to Product cleaning, then ensure the machine is in dismantling condition and check for absence of previous product/material in each dismantled parts of the machine.
- After complete verification of equipment at dismantled condition from IPQA checklist as well as respective documents like batch records to be signed, then production person shall go for assembling of equipment as per the plan.
- Once the equipment line clearance is done, the equipment can be used up to its cleaning validity only, if it crosses the validity date, then re-line clearance of equipment shall be done
- Check and ensure that the previous product/ batch materials and status labels are removed from the area.
- Ensure that dustbins in the area are emptied out and do not carry debris of previous product / batch.
- Check the ceiling, floor, walls, windows and door frames and electrical panels in the area are clean and free from visible traces of previous product/ batch. (Where ever applicable).
- Ensure cleanliness of Drain point provided in the area
- Ensure cleanliness of pendants, dust extraction hose are cleaned
- Ensure cleanliness of Weighing balance platform and Display of balance
- Ensure that the cleaning record for the area is updated.
- Ensure calibration status of all pressure gauges, balances and timers are updated
- Check that the documents pertaining to the previous product are removed from the area.
- Check that the equipment log sheets of all machines in the area are complete as on date with cleaning details.
- Ensure that environment conditions (Temperature & RH) record is updated.
- Ensure that the Batch Manufacturing Record is complete in all respects up to the stage.
- Line clearance for all equipments should be given as per check points mentioned in checklists and for specific areas / Parts of machine shall be verified accordingly the photographs available in checklist as well as in respective Operation and cleaning SOP’s of manufacturing equipments.
- Ensure that, the rejects of previous product are destroyed.
- Ensure that the area and equipments are appropriately labelled for status
- Ensure Batch manufacturing record & Batch Packing record are completed up to the executed activity and verified.
- Check that the machines have been cleaned as per respective SOP of respective department for the removal of previous batch/ product.
- The checking during line clearance should include all machine places where the product/ packaging material may get trapped. Use Additional flash light or compressed air if required to ensure adequacy of cleanliness at critical parts/areas.
- All excess / rejected packing materials of previous product shall be removed from the line.
- All used hand gloves, dusters of previous product shall be removed from the line
- All stereos of the previous product shall be removed/ destroyed by cutting into pieces (as applicable).
- During line clearance of primary packing line and secondary packing line Quality Assurance personnel shall checks the complete deletion of Pharmacode / Barcode of previous product on PLC/HMI of Machine.
- Check conveyor belt and area below the belt for absence of previous product.
- Tools box checked for absence of previous product and Sorting tray checked for absence of previous product.
- Verify and ensure correctness of next product/ batch for label, Integrity, storage & other appropriate parameters.
- Individual line clearance checklist shall be done and checked by production for respective equipments which shall be verified by Quality Assurance.
- Production and Quality Assurance shall check & verify the specimen of Aluminium foil,PVC, Carton, label etc before start of packing activity.
- In case of dispensing of Raw & Packing material Quality assurance shall verify the release of the same from Quality Control.
- Potency Calculation of Raw material shall be checked by production & verify by Quality Assurance.
- Individual line clearance checklist shall be done and checked by production for respective equipment which shall be verified by Quality Assurance.
Note : Any non-compliance observed during line clearance should be investigated and documented as per the respective SOP if required deviation shall be raised.
- Types of Line clearance terminology may vary from Organization to Organization like Type A, Type B & Type C . In most case Type A shall be considered for Batch to Batch cleaning & Type B & C for Product to product cleaning.
- Type A Cleaning shall be done with the help of Vacuum Cleaner & Lint free cloth. Water is not used
- Type B & Type C cleaning with the help of Potable and Purified water. 70 % IPA can be used in case of Beta Lactam Facility.
- Every organization should follow line clearance procedure & the observation made by Quality Assurance shall be compiled before starting of activity.
- It is a control over the entire system.
- Doers can make mistake so somebody has to check or verify the same
19 thoughts on “Line Clearance Procedure in Pharmaceuticals”
Thank you Sir
In the pharmaceutical industry dustbin word is not acceptable replace with waste bin
Ok noted thanks
If Line clearances failure, then what is next process
Deviation shall be raised and investigation shall be carried out to find out the root cause and necessary CAPA shall be raised accordingly
if line clearence is fail initiated the deviation
Yes you can initiate the deviation if your quality system allows
Thank you for sharing the information, but I would like to ask where I can get the requirements or guidelines on line clearance from an authorized regulatory organization (hopefully FDA).
Yes you are correct and you can get it from EU GMP and from FDA Guidance
Having read this I thought it was extremely enlightening. I appreciate you spending some time and energy to put this content together. I once again find myself personally spending way too much time both reading and posting comments. But so what, it was still worthwhile!
There is definately a great deal to learn about this subject. I like all the points you have made.
What actual the line clearance failure
Line clearance failure could be from the following things but not limited to
1. During QA line clearance if some previous product material are observed which might have some quality impact
2. Pending in previous documents which might have impact on Good documentation practices or can lead to data integrity.
3. Failure in maintaining the area Temperature and RH as per product requirement.
4. Not complying the line clearance checklist checkpoints etc..
Does batch to batch clearance cover a small facility GMP buffer preparations? These are non product designated operations a batch to batch criteria apply in this case?
Yes it can be apply in this case and the question here is not related to batch to batch however it is a additional verification or control to avoid any type of error so it is required
Thankks for the post