title: Evaluation of compounded bevacizumab prepared for intravitreal injection.
abstract: OBJECTIVE
  Bevacizumab acquired from compounding pharmacies for intravitreal injection may cause infectious and noninfectious inflammation. In addition to safety issues, the drug itself may have variable efficacy associated with product aliquoting, handling, and distribution.
  
  
  OBJECTIVE
  To conduct surveillance cultures, evaluate endotoxin levels, and assess protein concentrations of bevacizumab obtained from compounding pharmacies in the United States.
  
  
  METHODS
  Prospective in vitro study of syringes containing intravitreal preparations of bevacizumab from compounding pharmacies. This study was conducted at a university-based, good manufacturing practice facility and academic ophthalmology practice.
  
  
  METHODS
  Microbial culture growth, endotoxin levels, and quantity and binding affinity of protein in each sample.
  
  
  RESULTS
  There were no microbial contaminants or endotoxin detected in any of the samples. Of the 21 compounded samples of bevacizumab obtained from 11 pharmacies, 17 (81%) had lower protein concentrations (mean [SD], 22.2 [4.9] mg/mL; range, 19.2-24.5 mg/mL) compared with bevacizumab acquired directly from Genentech (25 mg/mL; P < .05). In 3 of 10 compounding pharmacies where more than 1 sample was available, there were statistically significant differences in the protein concentration between samples from the same compounding pharmacy.
  
  
  CONCLUSIONS
  Test results from intravitreal preparations of bevacizumab acquired from compounding pharmacies were negative for microbial contaminants and endotoxin. However, there were significant variations in protein concentration that appear in general to be lower than bevacizumab acquired directly from Genentech. The clinical implications of these variable protein levels remain uncertain.
authors.affiliation: Department of Ophthalmology, Weill Cornell Medical College, New York, New York.
authors.forename: Nicolas A
authors.initials: NA
authors.lastname: Yannuzzi
authors.affiliation: Department of Ophthalmology, Weill Cornell Medical College, New York, New York.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Klufas
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College, New York, New York.
authors.forename: Lucy
authors.initials: L
authors.lastname: Quach
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College, New York, New York.
authors.forename: Lauren M
authors.initials: LM
authors.lastname: Beatty
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College, New York, New York.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Kaminsky
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College, New York, New York.
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Crystal
authors.affiliation: Department of Ophthalmology, Weill Cornell Medical College, New York, New York.
authors.forename: Donald J
authors.initials: DJ
authors.lastname: D'Amico
authors.affiliation: Department of Ophthalmology, Weill Cornell Medical College, New York, New York.
authors.forename: Szilárd
authors.initials: S
authors.lastname: Kiss
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000737:chemistry*; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000737:chemistry*; D001419:Bacteria / Q000302:isolation & purification; D000068258:Bevacizumab; D015153:Blotting, Western; D004339:Drug Compounding / Q000592:standards*; D004340:Drug Contamination; D004341:Drug Evaluation; D004349:Drug Packaging / Q000592:standards*; D004591:Electrophoresis, Polyacrylamide Gel; D004731:Endotoxins / Q000032:analysis; D006801:Humans; D058449:Intravitreal Injections; D009883:Ophthalmic Solutions / Q000008:administration & dosage / Q000737:chemistry; D010316:Particle Size; D004364:Pharmaceutical Preparations / Q000737:chemistry; D011446:Prospective Studies; D011506:Proteins / Q000032:analysis
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D004731:Endotoxins; D009883:Ophthalmic Solutions; D004364:Pharmaceutical Preparations; D011506:Proteins; D000068258:Bevacizumab