Metal Impurity Data on Various Excipients. For Priscilla s Presentation

Transcription

1 Metal Impurity Data on Various Excipients For Priscilla s Presentation

2 Common Excipients Existing Elemental Impurity Data Item Description TITANIUM DIOXIDE, USP/FCC/EP/JP HPMC 3 cp - USP/EP/JP HPMC 6 cp - USP/EP/JP PEG 400 NF/EP/JP SODIUM CITRATE - DIHYD. USP/EP/JP/FCC/JSFA POLYSORBATE 80 (VEG.) NF/EP/JP POLYVINYL ALCOHOL, USP/FCC/EP/JPE PEG 3350 NF/EP/JP Lead Limit Listed on COA Max 10 ppm NMT 20 ppm (Heavy NMT 20 ppm (Heavy < 5 ppm (Heavy Typical Lead Limit Test Method Frequency of Testing 1 to 9 ppm based on 2 year history, 2 to 5 ppm typically ICP Every Batch 0.2 to 2 ppm ICP-MS Once per year 0.2 to 2 ppm ICP-MS Once per year NMT 1 mg/kg * * < 2 mg/kg < 1 mg/kg ICP Weekly < 10 ppm (Heavy Max 1 ppm Atomic Absorption Electro-thermal Atomization (Furnace Atomization) according to Combined Compendium of Food Additives Specifications, FAO JECFA Monographs, vol 4 (2005). Statistic Basis NMT 2 ppm * AA Analysis Once per year < 5 ppm (Heavy * * *

3 Common Excipients Existing Elemental Impurity Data Item Description Lead Limit Listed on COA TALC USP/FCC/EP/JP < 10 ppm < 1 ppm GLYCERIN, 99.7%, USP/EP/JP/FCC/JSFA USL 1 ppm (Heavy Typical Lead Limit Test Method Frequency of Testing EP Talc ICP-oes acc EN ISO Once a year * * * FD&C RED NO. 40 DYE, POWDER < 10 ppm < 1 ppm AA Analysis FD&C BLUE NO.1 DYE, POWDER < 10 ppm < 1 ppm AA Analysis TITANIUM DIOXIDE USP/EP/JP POLYDEXTROSE FCC 10 ppm Max. < 0.5 mg/kg 4-7 ppm based on 2 year history, Average 5 ppm. All values from 2010 through 2011 have been < 0.06 ppm with most frequently found values ranging from < 0.01 ppm to < 0.02 ppm. THGA-AAS-Method AOAC , , Several Samples a year are tested Several Samples a year are tested Once per week Every 20 lots (across each of the 2 dozen product forms and packaging codes.) MALTODEXTRIN NF/FCC/EP/JP < % * * * MEDIUM CHAIN TRIGLYCERIDES NMT 10 ppm (Heavy ICP (reference EPA SW 846 < 0.3 ppm max (lead) (NF, EP, JPE) Content in Oil Substance) Once per year * = Still Awaiting Suppliers Response

4 Elemental Impurities from Supplier COAs Mineral Based Excipients Item Number Item Description Supplier/Manufacturer Arsenic Cadmium Lead Inorganic Mercury Chromium Copper Nickel IC07445 IC07484 IRON OXIDE YELLOW (NF,JPE) IRON OXIDE RED (NF,JPE) Supplier A 2 ppm 1 ppm 10 ppm 1 ppm 100 ppm 50 ppm 200 ppm Supplier A 2 ppm 1 ppm 10 ppm 1 ppm 100 ppm 50 ppm 200 ppm IC07453 IRON OXIDE BLACK JPE Supplier A 3 ppm max 1 ppm max 10 ppm max 1 ppm max 100 ppm max 50 ppm max 200 ppm max The following Elemental Impurities did not have Specifications or Results on the Suppliers COA & Specification: Manganese, Molybdenum, Palladium, Platinum, Vanadium, Osmium, Rhodium, Ruthenium, and Iridium.

5 Iron Oxide Red (NF, JPE) Lot Number Arsenic Cadmium Lead Inorganic Mercury Chromium Copper Nickel 1 < 1 ppm < 1 ppm < 2 ppm < 0.2 ppm 19 ppm 14 ppm 104 ppm 2 < 1 ppm < 1 ppm < 3 ppm < 0.2 ppm 38 ppm 25 ppm 100 ppm 3 < 1 ppm < 1 ppm < 3 ppm < 0.2 ppm 38 ppm 25 ppm 100 ppm 4 < 1 ppm < 1 ppm < 3 ppm < 0.2 ppm 38 ppm 25 ppm 100 ppm 5 < 1 ppm < 1 ppm < 2 ppm < 0.2 ppm 15 ppm 9 ppm 111 ppm 6 < 1 ppm < 1 ppm < 2 ppm < 0.2 ppm 41 ppm 9 ppm 108 ppm 7 < 1 ppm < 1 ppm < 2 ppm < 0.2 ppm 41 ppm 9 ppm 108 ppm 8 < 1 ppm < 1 ppm < 2 ppm < 0.2 ppm 41 ppm 9 ppm 108 ppm 9 < 1 ppm < 1 ppm < 2 ppm < 0.2 ppm 15 ppm 9 ppm 111 ppm 10 < 1 ppm < 1 ppm < 2 ppm < 0.2 ppm 15 ppm 9 ppm 111 ppm 11 < 1 ppm < 1 ppm 1 ppm < 0.2 ppm 16 ppm 16 ppm 111 ppm 12 < 1 ppm < 1 ppm 1 ppm < 0.2 ppm 16 ppm 16 ppm 111 ppm 13 < 1 ppm < 1 ppm 1 ppm < 0.2 ppm 16 ppm 16 ppm 111 ppm 14 < 1 ppm < 1 ppm 1 ppm < 0.2 ppm 16 ppm 16 ppm 111 ppm

6 CALCIUM CARBONATE PhEur Lot Number Arsenic Cadmium Lead Inorganic Mercury Chromium Copper Nickel ppm 0.73 ppm 2 ppm N/A N/A N/A N/A ppm 0.73 ppm 2 ppm N/A N/A N/A N/A 3 < 3 ppm 0.19 ppm 2.2 ppm N/A N/A N/A N/A 4 < 3 ppm 0.17 ppm 2.4 ppm N/A N/A N/A N/A ppm 0.21 ppm 2.3 ppm N/A N/A N/A N/A ppm 0.5 ppm 2 ppm N/A N/A N/A N/A ppm 0.3 ppm 1.1 ppm N/A N/A N/A N/A ppm 0.5 ppm 4.7 ppm N/A N/A N/A N/A ppm 0.6 ppm 2.5 ppm N/A N/A N/A N/A ppm 0.63 ppm 4.5 ppm N/A N/A N/A N/A ppm 0.44 ppm 2.6 ppm N/A N/A N/A N/A ppm 0.38 ppm 7.1 ppm N/A N/A N/A N/A ppm 0.6 ppm 3 ppm N/A N/A N/A N/A ppm < 0.1 ppm 1.4 ppm N/A N/A N/A N/A Excursion

7 Talc USP, PhEur Lot Number Arsenic Cadmium Lead Inorganic Mercury Chromium Copper Nickel ppm N/A 2.21 ppm N/A N/A N/A N/A ppm N/A 2.21 ppm N/A N/A N/A N/A ppm N/A 2.21 ppm N/A N/A N/A N/A ppm N/A 2.21 ppm N/A N/A N/A N/A ppm N/A 2.21 ppm N/A N/A N/A N/A ppm N/A 0.30 ppm N/A N/A N/A N/A ppm N/A 0.30 ppm N/A N/A N/A N/A ppm N/A 0.30 ppm N/A N/A N/A N/A ppm N/A 0.30 ppm N/A N/A N/A N/A ppm N/A 0.30 ppm N/A N/A N/A N/A

8 Testing of Aluminum Lakes Test Results Target Maximum Limits (ppm) Product Batch No Aluminum Arsenic Barium Cadmium Iron Lead Zinc Mercury Expected Target Maximums > Method Reference EPA 6010B EPA 7471B Method Detection Limit Reporting / Quantitation Limit FD&C YELLOW #5/TARTRAZINE ALUMINUM LAKES <0.191 <0.132 < low dye% <0.191 <0.132 < < <0.191 <0.132 < <0.191 < medium dye% < <0.191 <0.132 < <0.191 <0.132 < < <0.191 <0.132 < high dye% < <0.191 <0.132 < < <0.191 <0.132 <0.0309

9 Testing of Aluminum Lakes Test Results Target Maximum Limits (ppm) Product Batch No Aluminum Arsenic Barium Cadmium Iron Lead Zinc Mercury Expected Target Maximums > Method Reference EPA 6010B EPA 7471B Method Detection Limit Reporting / Quantitation Limit FD&C YELLOW #6/SUNSET YELLOW FCF ALUMINUM LAKES < <0.191 <0.132 < low dye% <0.191 <0.132 < <0.191 <0.132 < < <0.191 <0.132 < medium dye% <0.191 <0.132 < <0.191 <0.132 < < <0.191 <0.132 < high dye% < <0.191 <0.132 < <0.191 <0.132 <0.0309

10 Testing of Aluminum Lakes Test Results Target Maximum Limits (ppm) Product Batch No Aluminum Arsenic Barium Cadmium Iron Lead Zinc Mercury Expected Target Maximums > Method Reference EPA 6010B EPA 7471B Method Detection Limit Reporting / Quantitation Limit FD&C RED #40/ALLURA RED AC ALUMINUM LAKES low dye% <0.191 <0.132 < <0.191 <0.132 < < <0.191 <0.132 < low dye% <0.191 <0.132 < <0.191 <0.132 < < <0.191 < medium dye% <0.191 <0.132 < <0.191 <0.132 < medium dye% <0.191 <0.132 < high dye% < <0.191 <0.132 < < <0.191 <0.132 <0.0309

11 Testing of Aluminum Lakes Test Results Target Maximum Limits (ppm) Product Batch No Aluminum Arsenic Barium Cadmium Iron Lead Zinc Mercury Expected Target Maximums > Method Reference EPA 6010B EPA 7471B Method Detection Limit Reporting / Quantitation Limit FD&C BLUE #1/BRILLIANT BLUE FCF ALUMINUM LAKES < <0.191 <0.132 < low dye% <0.191 <0.132 < <0.191 <0.132 < <0.191 <0.132 < medium dye% <0.191 <0.132 < <0.191 <0.132 < < <0.191 < high dye% <0.191 <0.132 < <0.191 <

12 Testing of Aluminum Lakes Test Results Target Maximum Limits (ppm) Product Batch No Aluminum Arsenic Barium Cadmium Iron Lead Zinc Mercury Expected Target Maximums > Method Reference EPA 6010B EPA 7471B Method Detection Limit Reporting / Quantitation Limit FD&C BLUE #2/INDIGO CARMINE ALUMINUM LAKES <0.191 <0.132 < low dye% < <0.191 <0.132 < < <0.191 <0.132 < <0.191 <0.132 < medium dye% <0.191 <0.132 < <0.191 <0.132 < < <0.191 <0.132 < high dye% < <0.191 <0.132 < <0.191 <0.132 <0.0309