Validation of proposed packing-line configuration and organization
Qualifications of key process components were carried out. The vial-labeling machine was qualified according to the protocol
designed for that purpose (8). The technical balance used to checking MUB completion by weighing was calibrated and verified
according to in-house metrological procedures. In addition, the balance's ability to detect missing components was also qualified,
taking into account MUB weight variations caused by the weights of individual components. The technical balance's sensitivity
for reproducibly detecting single leaflets missing from MUBs leaving the packaging line was tested. The results of the testing
are shown in Table I. Six MUBs were taken from the end-of-line at different moments (i.e., the start, middle, and end times)
during the packing process. Weight differences were determined by removing a single leaflet from each MUB. When the weight
differences were compared statistically with the corresponding leaflet weights, they did not vary significantly (9).
Table I: Technical balance qualification for checking multiple-unit boxes (MUB) completion by weighing.
The packing line was then validated to determine the buffer and packing operators' ability to detect and correct the failures
described previously. Three consecutive runs were performed for this purpose by simulating automatic labeling and manual packaging
operations in each run on 1440 placebo vials with printed packing material (i.e., vial labels, cartons, and leaflets for testing).
Labels for MUB and shipping boxes were not used. To challenge the operators, vials were introduced during each run that had
been deliberately prepared with defects. Among them were 40 unlabeled vials, 40 vials with badly pasted or wrinkled labels,
and 45 vials with primary information missing from their labels, making a total of 125 faulty vials to detect.
To establish an acceptance criterion in each run, a single sampling plan for normal inspection was employed based on a general
inspection level II and 0.10 acceptance-quality limit index (10). It was established that if any of the deliberately defective
vials were not detected during a run, the packing-line performance would be considered unsatisfactory. The test also required
the detection of all other faulty vials that resulted from errors in labeling-machine operation.
The packing operators' ability to ensure MUB completion was simultaneously verified by weighing MUBs at the end-of-line workstation.
Based on the above qualification, an operational procedure determined weight limits at the beginning of each packing operation
by averaging the weight of the first three complete MUBs leaving the line. A tolerance of ±1.8 g (i.e., the weight of the
lightest leaflet) was established.
Results and analysis
All runs demonstrated that operator performance was good and that the barriers implemented against failure were effective.
All 125 of the faulty vials deliberately prepared and introduced into the packing line as failures were detected (see Table
II). The buffer operator rejected 73.6–94.4% of the faulty vials. The packing operators rejected the rest. In the worst case,
33 faulty vials reached them.
Table II: Results from packing-line simulation runs: Visual checking of defects by operators.