Line Clearance – A systematic assessment performed prior to the start of a GMP production that confirms all raw materials, containers/closures are released and within their retest/expiry, equipment is clean and within calibration expiry, and room cleaning, environmental monitoring, and other environmental conditions meets requirements.  

Why it Matters – Line clearance is intended to verify that all GMP requirements are met before initiation of a production.  This includes, among other things, that the correct batch record has been issued, preventing the use of incorrect, unreleased, or expired materials, contamination of the product from dirty equipment or a dirty room, use of incorrect product labels to product etc.  

Case Study – A sponsor requested a Contract Development and Manufacturing Organization (CDMO) to formulate and manufacture drug product capsules for clinical trials. The batch record was drafted and approved by the CDMO and the sponsor and on the day of the scheduled campaign a production line clearance was performed.

The first-shift production staff initiated the production and the second-shift completed it working overnight into the next day.  When the executed batch record was submitted to QA, the reviewer noticed that two different excipient lot numbers were hand-written into the batch record for the same excipient.  Since she verified the line clearance herself, she recalled that only the excipient with the first lot number was in the clean room at the time of line clearance.  She then pulled up the inventory record for the second excipient lot and discovered that it remained in quarantine status and had not been released for GMP use. 

CDMO’s QA manager discussed the matter with the warehouse staff who showed her that the top of the Quarantine cage fencing was crushed down.  Further digging into security camera footage revealed that a manufacturing technician had climbed over the Quarantine fencing in the middle of the night and removed the excipient (crazy, but true!).  The technician later confessed that they had run out of the first lot of excipient and took the material from quarantine because they were under pressure by management to complete the production.

Release testing for the second lot of excipient was submitted to QA few days after the production was completed.  The result failed to meet the specification for water content. 

Discover how Eastlake Quality Consulting can design and implement robust materials management and production controls to ensure that this does not happen to you.