A series of four previously studied compounds with established VRLs, listed in Table II, were diluted with methanol to sequentially
lower concentrations. The coupons were prepared using 100 µL of each solution resulting in four residue levels. The target
concentrations were the four lowest concentrations shown in Table I: 20 µg, 10 µg, 5 µg, and 1 µg. One residue level was spotted
per coupon. The spotted samples dried as elliptical residues. The resulting residue concentrations were calculated using the
two elliptical radii in Table III based on the amount of residue spotted and the area of the resulting residue.
Table IV: Random coupon identification grid.
The coupons were arranged in a random order as shown in Table IV and Figure 1. Sixteen sample coupons and four solventblank
coupons were prepared. In addition, five blank coupons brought the total matrix to 25 coupons in a five-by-five array.
Figure 1: Random coupon presentation.
The viewing parameters had been established previously: viewing distance was 18 in., viewing angle was 30°, and ambient light
intensity was > 200 lux (1). Eight observers participated in the study. The observers viewed the coupon array separately from
one another to avoid influencing their individual choices. The results for the random determinations are presented in Table
Table V: Observer results.
After the observations were completed for the random coupon presentation, the residues were ordered sequentially, two observers
were brought back to view the coupons, and their observations were recorded (see Table V). The sequential presentation was
a confirmation for the previously established VRLs because the residue preparations were, in some cases, much lower than the
reference VRL and because every residue preparation is slightly different based on the amount of compound weighed and the
area of the resulting residue.
Richard J. Forsyth is principal consultant with Forsyth Pharmaceutical Consulting, 907 Shamrock Ct, Royersford, PA 19468, tel. 484.535.1688, email@example.com.
Articles by Richard J. Forsyth
What do you think the role of continuous (rather than batch) processes in pharmaceutical manufacturing will be over the next five years?
Many companies in the industry will be using continuous processes for some products.
Companies in both pharmaceutical and biopharmaceutical production will be evaluating continuous processes but few will implement.
Only a few companies will be evaluating or implementing; most will stay with batch processing.