COMPLIANCE INFO_2019 - Laserfiche WebLink

Home Browse Search

58054 Federal Register/Vol. 80, No. 186/Friday, September 25, 2015/Proposed Rules is,the study investigated whether the referred to as a"bingo card."The results to 4000 containers per month to exceed concentration of warfarin in the indicate that the concentration of the the 1 kg threshold to be an LQG, residues of warfarin pill bottles was active pharmaceutical ingredient The results for nicotine residues were greater than 0.3%and therefore met the warfarin in the residues in plastic similar.For containers of gum and listing criteria for P001,or whether the bottles was usually over the 0.3% patches,the weight of total residues residues were at or below 0.3%and concentration.However,the ranged from 9-111.2 mg,although the liquid nicotine li therefore met the listing criteria for concentration of warfarin in the two containers oq U248.Although nicotine is not a residues on blister packs, including the solution contained more residues-1301 concentration-based P-listing,packaging 30-pack blister pack,was consistently and 1616 mg.Although nicotine is not from nicotine-containing products were below 0.3%.Overall,in the majority of a concentration-based listing,it is worth noting that the active pharmaceutical also investigated to determine total cases,the warfarin within the residues remaining residues. was present at a high enough ingredient of nicotine m the residues The researchers collected a total of 59 concentration to be considered Pool (33 was below the quantifiable limit of 1.5 samples containers,including 44 of 44 samples,75 percent of the µg/ml in 8 of the 15 samples and for the sample containers that had held samples). other 7 samples,the concentration of warfarin pills but had been fully sam les . nicotine ranged from 0.01--0.09%. dispensed and another been sample However,the results also confirm the iv.EPA's Office of Research and containers from nicotine-containing then15sapl! results from the first two stakeholders. Development.Finally,EPA's ORD That is,the total weight of residues conducted an analysis to evaluate products.The samples included cotne from several remaining in the containers after they whether simply removing a drug from warfarin and nii manufacturers,co range of dose were emptied of the warfarin pills is the container is equivalent to triple strengths and in various container types. negligible.For the plastic bottles,the rinsing the container.ORD's results are The residues were solvent-extracted and total weight of residue ranged from 4.3– summarized in Table 11,but the Final then dried by rotary evaporation to 82.3 mg.For the single-dose blister Project Report containing the full results determine the total weight of residues. packs,the total weight of residue ranged is in the docket for this proposed Subsequently,the residues were re- from 3.5-7.6 mg.And for the 30-pack rulemaking(EPA I3Q–RCRA-2007– dissolved in methanol and analyzed blister pack,the total weight ranged 0932).ORD analyzed three different P- using HPLC to determine the from 134.8-273 mg.Taking the smallest listed pharmaceuticals:Warfarin, concentration of the active amount of residue of 3.5 mg,it would nicotine and physostigmine salicylate. pharmaceutical within the residues, take close to 300,000 containers per Table 11 lists the 1.8 different The majority of warfarin containers month to exceed the 1 kg threshold to combinations of active pharmaceutical were plastic bottles,but some containers be an LQG.Even on the conservative ingredients,form,dosage strengths and were blister packs and three samples side,taking the largest amount of packaging combinations that ORD were 30-pill blister packs,sometimes residue of 273 mg,it would take close analyzed. TABLE 11--PHARMACEUTICAL COMBINATIONS TESTED BY EPA's ORD Active pharmaceutical Manufacturer/Brand name Form Dosage Packaging type ingredient Warfarin ..................... Taro Pharmaceutical Industries, Ltd. ............. Tablet ....... 1 mg......... Plastic bottle. Tablet ....... 5 mg......... Plastic bottle. Tablet....... 10 mg....... Plastic bottle. Tablet ....... 2 mg ......... Single-dose blister pack. Upsher-Smith/Jantoven .................................. Tablet ....... 1 mg ......... Single-dose blister pack Tablet ....... 10 mg....... Single-dose blister pack. Nicotine ...................... GlaxoSmithKlinelNicorette ............................. Gum ......... 2 mg......... Single-dose blister pack. Gum ......... 4 mg......... Single-dose blister pack. Rugby Laboratories ........................................ Gum ......... 2 mg......... Single-dose blister pack. Gum ......... 4 mg ......... Single-dose blister pack. GlaxoSmithKline/Nicorette ............................. Lozenge ... 2 mg......... Plastic vial Lozenge ... 4 mg......... Plastic vial. Rugby Laboratories ........................................ Patch........ 7 mg......... Peel-off plastic. Habitrol ....................................................:...... Patch ........ 14 mg....... Peel-Off plastic. Rugby Laboratories ........................................ Patch........ 21 mg ....... Peel-off plastic. Pfizer/Nicotrol Spray 10 mg/ml .. Glass vial. Inhaler ...... 10 mg....... Plastic container. Physostigmine Salicy- Akron Inc. ..................... Liquid 1 mg/ml .... Glass ampoule. late. All combinations in Table 11 were (2)The"maximum possible weight of (3)Thermal gravimetric analysis analyzed in triplicate using the residual drug/total residual/container" (TGA)was used to qualitatively evaluate following three-step approach: was calculated for each compound and the presence of active pharmaceutical (1)After removing the tablets,gum, packaging combination.This calculated ingredient in the residuals removed lozenges,etc from the containers,the result was used to infer a theoretical from the containers before and after amount of total residuals remaining in upper limit for the amount of active triple-rinsing. the container was determined using a pharmaceutical compound in the total With respect to the weight of the sensitive balance to weigh the container residue remaining in the container,and remaining residuals in the containers, ORD's results are similar to the results before and after triple rinsing,