title: Modernization of Physical Appearance and Solution Color Tests Using Quantitative Tristimulus Colorimetry: Advantages, Harmonization, and Validation Strategies.
abstract: Color measurements, including physical appearance, are important yet often misunderstood and underappreciated aspects of a control strategy for drug substances and drug products. From a patient safety perspective, color can be an important control point for detecting contamination, impurities, and degradation products, with human visual acuity often more sensitive for colored impurities than instrumental techniques such as HPLC. Physical appearance tests and solution color tests can also serve an important role in ensuring that appropriate steps are taken such that clinical trials do not become unblinded when the active material is compared with another product or a placebo. Despite the importance of color tests, compendial visual tests are not harmonized across the major pharmacopoeias, which results in ambiguous specifications of little value, difficult communication of true sample color, and significant extra work required for global registration. Some pharmacopoeias have not yet recognized or adopted technical advances in the instrumental measurement of color and appearance, whereas others begin to acknowledge the advantage of instrumental colorimetry, yet leave implementation of the technology ambiguous. This commentary will highlight the above-mentioned inconsistencies, provide an avenue toward harmonization and modernization, and outline a scientifically sound approach for implementing quantitative technologies for improved measurement, communication, and control of color and appearance for both solutions and solids. Importantly, this manuscript, for the first time, outlines a color method validation approach that is consistent with the International Conference on Harmonization's guidance on the topic of method validation.
authors.affiliation: Small Molecule Design and Development, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, 46285.
authors.forename: Brian W
authors.initials: BW
authors.lastname: Pack
authors.affiliation: Small Molecule Design and Development, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, 46285.
authors.forename: Laura L
authors.initials: LL
authors.lastname: Montgomery
authors.affiliation: Small Molecule Design and Development, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, 46285.
authors.forename: Evan M
authors.initials: EM
authors.lastname: Hetrick
mesh_terms: D000465:Algorithms; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003124:Colorimetry / Q000295:instrumentation / Q000379:methods*; D005079:Excipients; D057230:Limit of Detection; D019999:Pharmaceutical Solutions; D012015:Reference Standards; D015203:Reproducibility of Results; D012996:Solutions; D014785:Vision, Ocular
chemical_list: D005079:Excipients; D019999:Pharmaceutical Solutions; D012996:Solutions
keywords: analysis; analytical chemistry; colorimetry; description; formulation; injectables; physical appearance; physical characterization; solid dosage form; validation