title: Stability, potency, and preservative effectiveness of epoetin alfa after addition of a bacteriostatic diluent.
abstract: The stability, potency, and preservative effectiveness of two dilutions of epoetin alfa containing a bacteriostatic diluent were studied. Epoetin alfa 10,000 units/mL in single-use vials was diluted 1:1 and 1:1.5 with bacteriostatic 0.9% sodium chloride injection. USP tests of preservative effectiveness were performed on samples from two batches each of the 1:1 and the 1:1.5 dilutions. Appearance assessment, Western blot analysis, radioimmunoassay, and bioassay were used to determine the stability or potency of samples from three batches of each dilution that were stored at 5 degrees C or at 30 degrees C for 12 weeks. Both batches of the 1:1.5 dilution (epoetin alfa 4,000 units/mL with 0.54% benzyl alcohol) met the USP criteria for preserved solutions, while one batch of the 1:1 dilution (epoetin alfa 5,000 units/mL with 0.45% benzyl alcohol) did not. Epoetin alfa 10,000 units/mL diluted either 1:1 or 1:1.5 with bacteriostatic 0.9% sodium chloride injection and stored at 5 degrees C or at 30 degrees C remained stable and potent for 12 weeks. The addition of 1.5 mL of bacteriostatic 0.9% sodium chloride injection to a vial containing 1 mL of epoetin alfa 10,000 units/mL makes a solution of epoetin alfa 4,000 units/mL that meets the USP criteria for preservative effectiveness and remains stable and potent for 12 weeks at 5 degrees C.
authors.affiliation: R. W. Johnson Pharmaceutical Research Institute, Raritan, NJ 08869.
authors.forename: D C
authors.initials: DC
authors.lastname: Corbo
authors.forename: R L
authors.initials: RL
authors.lastname: Suddith
authors.forename: B
authors.initials: B
authors.lastname: Sharma
authors.forename: R B
authors.initials: RB
authors.lastname: Naso
mesh_terms: D000818:Animals; D015153:Blotting, Western; D004344:Drug Incompatibility; D004355:Drug Stability; D004912:Erythrocytes / Q000378:metabolism; D004921:Erythropoietin / Q000097:blood / Q000737:chemistry* / Q000494:pharmacology; D007501:Iron / Q000097:blood; D051379:Mice; D011310:Preservatives, Pharmaceutical; D011863:Radioimmunoassay; D011994:Recombinant Proteins / Q000097:blood / Q000737:chemistry / Q000494:pharmacology; D012965:Sodium Chloride / Q000494:pharmacology
chemical_list: D011310:Preservatives, Pharmaceutical; D011994:Recombinant Proteins; D004921:Erythropoietin; D012965:Sodium Chloride; D007501:Iron