Validation of a Spectral Method for Quantitative Measurement of Color in Protein Drug Solutions.
A quantitative spectral method has been developed to precisely measure the color of protein solutions. In this method, a spectrophotometer is utilized for capturing the visible absorption spectrum of a protein solution, which can then be converted to color values (L*a*b*) that represent human perception of color in a quantitative three-dimensional space. These quantitative values (L*a*b*) allow for calculating the best match of a sample's color to a European Pharmacopoeia reference color solution. In order to qualify this instrument and assay for use in clinical quality control, a technical assessment was conducted to evaluate the assay suitability and precision. Setting acceptance criteria for this study required development and implementation of a unique statistical method for assessing precision in 3-dimensional space. Different instruments, cuvettes, protein solutions, and analysts were compared in this study. The instrument accuracy, repeatability, and assay precision were determined. The instrument and assay are found suitable for use in assessing color of drug substances and drug products and is comparable to the current European Pharmacopoeia visual assessment method.
In the biotechnology industry, a visual assessment is the most commonly used method for color characterization, batch release, and stability testing of liquid protein drug solutions. Using this method, an analyst visually determines the color of the sample by choosing the closest match to a standard color series. This visual method can be subjective because it requires an analyst to make a judgment of the best match of color of the sample to the standard color series, and it does not capture data on hue and chroma that would allow for improved product characterization and the ability to detect subtle differences between samples. To overcome these challenges, we developed a quantitative spectral method for color determination that greatly reduces the variability in measuring color and allows for a more precise understanding of color differences. In this study, we established a statistical method for assessing precision in 3-dimensional space and demonstrated that the quantitative spectral method is comparable with respect to precision and accuracy to the current European Pharmacopoeia visual assessment method.
Early Stage Pharmaceutical Development Department, Yin.Jian@gene.com.
Jian
J
Yin
Early Stage Pharmaceutical Development Department.
Trevor E
TE
Swartz
Analytical Development and Quality Control Department, and.
Jian
J
Zhang
Early Stage Pharmaceutical Development Department.
Thomas W
TW
Patapoff
Analytical Development and Quality Control Department, and.
Bartolo
B
Chen
Nonclinical Biostatistics, Genentech, Inc., South San Francisco, CA.
Joseph
J
Marhoul
Early Stage Pharmaceutical Development Department.
Norman
N
Shih
Early Stage Pharmaceutical Development Department.
Bruce
B
Kabakoff
Analytical Development and Quality Control Department, and.
Kimia
K
Rahimi
D002626:Chemistry, Pharmaceutical / Q000379:methods / Q000592:standards*; D003116:Color / Q000592:standards*; D006801:Humans; D019999:Pharmaceutical Solutions / Q000032:analysis*; D011506:Proteins / Q000032:analysis*; D015203:Reproducibility of Results; D013053:Spectrophotometry / Q000379:methods / Q000592:standards
D019999:Pharmaceutical Solutions; D011506:Proteins
Accuracy; CIE L*a*b* values; Color; Precision; Repeatability; Spectral method; Suitability