Methods and materials
Eisai Automated Inspection Machine (Model 587-2, Eisai Machinery of USA, Allendale, NJ) was used to conduct an automated inspection.
Mimic solutions were prepared by adding an estimated amount of PEG 1000 into desired buffer solution to reach a target viscosity
value. Upon proper mixing, a sample was tested for viscosity confirmation. The mimic solution was then filtered through a
0.22μm filter and aspectically filled into vials followed by manual inspection to ensure absence of foreign particles. These
clean vials were spiked with standard glass beads of three different sizes: 70μm, 100μm and 400μm (Duke Scientific Soda Lime
Glass, Palo Alto, CA). Each vial was seeded with a single glass bead. The seeded vials were manually inspected a second time
to ensure that each vial only had one particle and no other foreign contaminants. Two different buffer formulations (with
and without polysorbate) were used to prepare PEG solutions of different viscosities. Formulations comprised of a commonly
used stabilizing excipient (sucrose or sorbitol) and a buffering agent (acetate). The formulations are listed as follows and
are referred to accordingly in the remaining sections of this article:
Formulation A = PEG 1000 in acetate buffer + sucrose + Polysorbate 20
Formulation B = PEG 1000 in acetate buffer + sorbitol
Vials seeded with particles were inspected on the Eisai machine through a double-check system comprising two inspection stations.
A set of 24 vials (six clean and six each seeded with 70μm, 100μm and 400μm particles) were inspected at each inspection station.
Each vial was inspected 32 times in a single run. A total of three runs were conducted to estimate statistical error in the
performance. For selected experiments, a design of experiment (DOE) was performed using a space-filling design and spanning
a range of spin and brake settings for a fill configuration of 1.7 mL in 3 cc. All DOE experiments were conducted for solutions
with different viscosities using PEG solution in Formulation B.
Inspection data obtained from the Eisai AIM were analyzed by calculating the detection rate (%DR) as follows:
The detection rate can then be calcuated for each vial type (clean, 70μm, 100μm and 400μm) by averaging the %DR values for
all six vials in each group. For runs that were conducted in triplicates, the average and standard deviation were also computed
for the detection rate for each particle size. For the data generated through DOEs, contour plots were generated to depict
detection rates for 400 μm-particle size at various spin and brake settings.