알코낙스 - samboi.kr

1 [ ] Pharmaceutical cleaning validation Method References For Alconox, Inc. Detergents 1. ( ) . (Worst Case) .. (matrix) .. , . , .. , , (dose) ( ), / , (batch) .. Identifying residues Selecting a residue detection method Selecting a sampling method Setting residue acceptance criteria Validating residue detection methods Conducting recovery studies Writing procedures and training operators.

2 , . , .. (1) Identifying Residue .. , , , , . (2) Selecting a residue detection method (specific) (non-specific) .. , HPLC, ion selective electrodes, flame photometry, derivative UV spectroscopy, enzymatic detection and titration .. , (TOC), pH, (conductivity) . FDA , .. ( .) (3) Selecting a sampling method (rinse water sampling), swabbing surfaces, coupon sampling (placebo sampling) .. (swabbing).

3 (WFI) (swab) , (multi-pass) , . 10 , 10 . 10 . TOC (TOC vial) . TOC (low background) Wipes, . (Texwipe) Alpha Swab 714A 761 .. UV-visible analyzer (0) (swab blank) Texwipe TX 762 . (Quartz glass fiber filter papers) . (coupon sampling) . ( 5 ) , (batch) . (4) Setting residue acceptance criteria (potential residues) , , , , Bioburden (endotoxin).

4 , .. , , .. , ( g/cm2), ( g g/mL), (mg g) ( g/mL) .. (internal action level) , (process control level) . (Acceptable Daily Intake. ADI), 50(LD50) (1/1000 ) (safety factor) , . (batch) (Carryover) 10ppm 10 ppm . mg/cm2 mg/mL (safety based limit) . Limit (mg/cm2 or L) = [ADI carryover, see below (mg) X Smallest Next Batch (kg)]/ [Size of Shared Equipment (cm2 or L) X Biggest Daily Dose or of Next Batch (kg)] (mg/cm2 or L) = [ , (mg) x (batch) (kg)]/ [ (cm2 or L) x (Batch) (kg)] ADI carryover (mg) = [LD50 by administration route (mg/kg) X body weight (kg) X (1/ 10,000 or 1/1000*)] (mg) = [ LD50 (mg/kg) x (kg) x (1/ 10,000 or 1/1000*)] * (conversion safety factor,), Medical Device cleaning validation 10 ppm.

5 Limit (mg/cm2) = [10 mg residue on just cleaned surface X Next Batch Size (kg or L)]/ [1 (kg or L) of next product X Size (cm2 or L) shared equipment] (mg/cm2) = [ 10 mg x (batch) (kg L)]/ [ 1 (kg L) x (cm2 L)] , (visual detection limit) 1 ~ 4 ug/cm2 . LD50 5 g/kg 70 kg 1000 350mg (5 g/kg x 70 kg / 1000) . 2000 kg (batch) 1000 kg , (batch) 100,000 cm , kg 700 mg/cm (350mg x1000 kg/(100,000 cm2 x kg) . , (batch) 10 ppm 100 g/cm2 (10 mg x 1000 kg/(1 kg x 100,000 cm2) x 1000 g/mg . 4 g/cm2 .. 350 mg.))

6 , . 350 mg (batch) . 100 g/cm2 , 100 L , 100 mg/L( mg/cm2 x 100,000 cm2/100 L) . 50% 25 cm2 20 mL 10% TOC TOC g/mL ppm . [(25 cm2 x 100 g/cm2) x 50% x 10% TOC/20 mL].. (5) validation methods and implementing recovery Accuracy, Linearity, Reproducibility, Selectivity, ( ) Specificity, Limit of Detection, Limit of Quantitation . (spike) . 50%, 100% 150%.

7 % .. , . % . , 100 g (spike) , (swabbing), 90 g 90% . (recovery factor) . 90 g 90% 100 g . (wipe) (rinse) .. , . , . , (surface active agent), (surfactants) .. (interface) , .. , 10,000 ppm.

8 TOC . , (bioburden)/ .. (6) .. ( , , .) .. , . Alconox 8A . A. HPLC, , B. HPLC C. (direct UV/Vis) D. E. F. G. H. , (derivative UV/Vis) I. IC J. GC , . FDA, ICH EU.

9 (USP) 1225 . (TOC) . , , 95% . , FDA (action limit) (acceptance limit) . TOC . TOC .. 8B. ANALYTICAL methods validation CONDITIONS Method Accuracy Precision (Repeatability) Linearity Reproducibility Selectivity Specificity LOD LOQ Ruggedness HPLC X X X X X X X X X GC X X X X X X X X X TLC X X X X X X X X X IC X X X X X X X X Wet methods X X X X X X X X X UV-Vis X X X X X X X X TOC X X X X X X X HPLC : high performance liquid chromatography, GC : gas chromatography, TLC : thin layer chromatography, IC : ion chromatography, UV-Vis : ultraviolet visible spectroscopy, TOC : total organic carbon, Wet methods : titrations/assays.

10 , .. , ( : ). (Annual Product Review, APR) .. , .. ( validation Report) , . GMP , .. Lot traceability of the cleaners Certificates of Analysis for the cleaners Consistent manufacturing Ingredient disclosures under confidentiality Cooperation with audits and quality questionnaires Ingredient toxicity data Ingredient reactivity information to help determine degradations and interactions Cleaner shelf life information Residue detection method information Residue sampling information Acceptance limits information Recovery information Residue detection methods validation information Assistance with written cleaning procedures Alconox , 1.