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58054 Federal Register/Vol. 80, No. 186/Friday, September 25, 2015/Proposed Rules is, the study investigated whether the concentration of warfarin in the residues of warfarin pill bottles was greater than 0.3% and therefore met the listing criteria for P001 or whether the residues were at or below 0.3% and therefore met the listing criteria for U248. Although nicotine is not a concentration -based P -listing, packaging from nicotine -containing products were also investigated to determine total remaining residues. The researchers collected a total of 59 samples containers, including 44 sample containers that had held warfarin pills but had been fully dispensed and another 15 sample containers from nicotine -containing products. The samples included warfarin and nicotine from several manufacturers, in a range of dose strengths and in various container types. The residues were solvent -extracted and then dried by rotary evaporation to determine the total weight of residues. Subsequently, the residues were re- dissolved in methanol and analyzed using HPLC to determine the concentration of the active pharmaceutical within the residues. The majority of warfarin containers were plastic bottles, but some containers were blister packs and three samples were 30 -pill blister packs, sometimes referred to as a "bingo card." The results indicate that the concentration of the active pharmaceutical ingredient warfarin in the residues in plastic bottles was usually over the 0.3% concentration. However, the concentration of warfarin in the residues on blister packs, including the 30 -pack blister pack, was consistently below 0.3%. Overall, in the majority of cases, the warfarin within the residues was present at a high enough concentration to be considered P001 (33 of 44 samples, 75 percent of the samples). However, the results also confirm the results from the first two stakeholders. That is, the total weight of residues remaining in the containers after they were emptied of the warfarin pills is negligible. For the plastic bottles, the total weight of residue ranged from 4.3— 82.3 mg. For the single-dose blister packs, the total weight of residue ranged from 3.5-7.6 mg. And for the 30 -pack blister pack, the total weight ranged from 134.8-273 mg. Taking the smallest amount of residue of 3.5 mg, it would take close to 300,000 containers per month to exceed the 1 kg threshold to be an LQG. Even on the conservative side, taking the largest amount of residue of 273 mg, it would take close to 4000 containers per month to exceed the 1 kg threshold to be an LQG. The results for nicotine residues were Si For containers of gum and patches, the weight of total residues ranged from 9-111.2 mg, although the two containers of liquid nicotine SO contained more residues -1301 and 1616 mg. Although nicotine is not a concentration -based listing, it is worth noting that the active pharmaceutical in of nicotine in the residues was below the quantifiable limit of 1.5 µg/ml in 8 of the 15 samples and for the other 7 samples, the concentration of nicotine ranged from 0.01-0.09%. iv. EPA's Office of Research and Development. Finally, EPA's ORD conducted an analysis to evaluate whether simply removing a drug from the container is equivalent to triple rinsing the container. ORD's results are S in Table 11, but the Final Project Report containing the full results is in the docket for this proposed rulemaking (EPA–HQ–RCRA-2007— 0932). ORD analyzed three different P - listed pharmaceuticals: Warfarin, nicotine and physostigmine salicylate. Table 11 lists the 18 different combinations of active pharmaceutical ingredients, form, dosage strengths and packaging combinations that ORD analyzed. TABLE 11—PHARMACEUTICAL COMBINATIONS TESTED BY EPA's ORD Active pharmaceutical ingredient Manufacturer/Brand name Form Dosage Packaging type Warfarin ..................... Nicotine ...................... Physostigmine Salicy- Taro Pharmaceutical Industries, Ltd.............. Upsher-Smith/Jantoven.................................. GlaxoSmithKline/Nicorette ............................. Rugby Laboratories. GlaxoSmithKline/Nicorette ............................. Rugby Laboratories ........................................ Habitrol.......................................................... Rugby Laboratories ........................................ Pfizer/Nicotrol................................................. Akron Inc. Tablet 0000... Tablet 0000... Tablet 0000... Tablet 0000... Tablet 04.111. Tablet ....... Gum ......... Gum ......... Gum ......... Gum ......... Lozenge ... Lozenge ... Patch......., Patch ........ Patch ........ Spray"..... Inhaler 0000.. Liquid 0000... 1 mg ......... 5 mg ......... 10 mg ..04.11 2 mg ......... 1 mg ......... 10 mg ....... 2 mg ......... 4 mg ......... 2 mg ......... 4 mg ......... 2 mg ......... 4 mg ......... 7 mg ......... 14 mg 0000... 21 mg 0000... 10 mg/ml .. 10 mg Dole... 1 mg/ml .... Plastic bottle. Plastic bottle. Plastic bottle. Single-dose blister pack. Single-dose blister pack Single-dose blister pack. Single-dose blister pack. Single-dose blister pack. Single-dose blister pack. Single-dose blister pack. Plastic vial Plastic vial. Peel -off plastic. Peekoff plastic. Peel -off plastic. Glass vial. Plastic container. Glass ampoule. late. All combinations in Table 11 were analyzed in triplicate using the following three-step approach: (1) After removing the tablets, gum, lozenges, etc from the containers, the amount of total residuals remaining in the container was determined using a sensitive balance to weigh the container before and after triple rinsing, (2) The "maximum possible weight of residual drug/total residual/container" was calculated for each compound and packaging combination. This calculated result was used to infer a theoretical upper limit for the amount of active pharmaceutical compound in the total residue remaining in the container, and (TGA) was used to qualitatively evaluate the presence of active pharmaceutical ingredient in the residuals removed fr (3) Thermal gravimetric analysis om the containers before and after triple -rinsing. With respect to the weight of the remaining residuals in the containers, ORD's results are similar to the results