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Determinations of VRLs consistently followed the same manner of presentation for the observers. The arrangement of the soiled
coupons began with the ARL, which was the lower of either the health-based limit or the adulteration-based limit (4 µg/cm2 ). Residue levels decreased sequentially with a solvent blank as the last sample. The observers viewed all of the sample
soils as a single group. For the majority of samples (133 of 200 = 67%), the lowest spotted residue was visible for the observers.
The VRL was reported as less than the lowest residue concentration. This report resulted in a refinement of the sample preparation.
The updated residue preparation, as shown in Table I, targeted lower concentrations to determine the actual VRL and provide
more accurate program data. With this refinement, the observers continued to visually detect the lowest residue limit in the
majority of tested compounds.
Table II: Compound visible-residue limits (VRLs)
An alternative arrangement of the residue soils was considered to determine whether presenting the soiled coupons to the observers
affected VRL determinations. This alternative arrangement consisted of a randomized presentation of several compounds at or
near the determined VRL, including a number of blank coupons. The observers did not know beforehand the number of compounds
tested or their concentrations, the number of soiled coupons, or the number of blanks in a 25 coupon array. A randomized coupon
presentation is more scientifically justified and easier to defend.
Richard J. Forsyth is an associate director of worldwide GMP quality with Merck & Co., Inc, WP53C-307, West Point, PA. 19486, tel. 215.652.7462, fax 215.652.7106.
Articles by Richard J. Forsyth
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