The Problem
This well-known prescription tablet was stuck in the testing cycle after some small process changes were initiated.
NO ONE HAD AN ANSWER…AND TIME WAS RUNNING OUT.
THE ASSIGNMENT
An external consultant, working with the manufacturer, suggested the need for additional investigative work.
QUANTUM ANALYTICS GROUP WAS CALLED IN TO REVIEW THE SITUATION AND PERFORM ANY ADDITIONAL TESTING.
THE CHALLENGE
The tablets were inconsistent. Not in color or size, but in how they went into solution for the testing itself, causing variability in analytical results.
ONLY ABOUT 1 IN EVERY 100 TABLETS DISSOLVED DIFFERENTLY BUT IT WAS ENOUGH TO ALLOW THE BATCH TO FAIL THE RELEASE ASSAY.
THE ISSUES
This instance had never been seen before within the company… the client’s QA team began focusing on the coating and excipient as possible culprits. And even suggested the method might be flawed.
COMPLICATING THE ISSUE, THE EXTERNAL CONSULTANT HAD 2 ANALYSTS RE-TESTING THE TABLETS 3 TIMES AFTER A FAIL…AND THEN PASS THEM.
THE TIMING
With such random variation, the Quantum team was looking at an assay schedule of at least 100 tablets a day. Ultimately, within our 30-day time limit we assayed over 2500 tablets.
MULTIPLE SHIFTS WERE SET UP TO HANDLE THE LAB DUTIES AND RUNNING RESULTS VIA HPLC.
THE SOLUTION
The real culprit was hiding in plain sight. By careful review of the recent process changes, Quantum was able to discover that one of the actual tablet presses was malfunctioning.
A CALIBRATION ISSUE CAUSED THE PRODUCT TO BE PRESSED AT A PRESSURE EVER SO SLIGHTLY OUTSIDE THE NORMAL RANGE, LEADING TO THE VARIABILITY.
Our earlier observations proved that the problem was not in the coating…and our review of the method showed no error. Essentially, we had to look in front of the method.
TRAINED OBSERVATION ALONG WITH KNOWLEDGE OF THE CHEMISTRY AND MANUFACTURING PROCESS LED US TO THE PRODUCTION LINE…AND ULTIMATELY, THE FAULTY PRESS. BEING ANALYTICAL YET OPEN-MINDED WAS THE KEY TO THE SOLUTION.
