CLEAR
Once a cell line is developed for the biosimilar, the candidate molecule is analyzed and carefully compared to the reference product using a number of characteristics, called critical quality attributes (CQAs).1 CQAs are features associated with the drug product that can impact safety, potency, pharmacokinetics, and overall quality.2-4 CQAs can include post-translational modifications to a protein. One example is the addition of oligomannose glycans, which impacts pharmacokinetic properties, reducing clearance time.3 Other post-translational modifications can alter the immunogenicity of a protein, impacting patient safety and efficacy.5,6
References: 1. McCamish M, Woollett G. The state of the art in the development of biosimilars. Clin Pharmacol Ther. 2012;91:405-417. 2. US Food and Drug Administration. Guidance for Industry: Quality Considerations in Demonstrating Biosimilarity of a Therapeutic Protein Product to a Reference Product. www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm291134.pdf. Accessed December 21, 2018. 3. Alessandri L, Ouellette D, Acquah A, et al. Increased serum clearance of oligomannose species present on a human IgG1 molecule. MAbs. 2012;4:509-520. 4. US Food and Drug Administration. Guidance for Industry: Q8(R2) Pharmaceutical Development. www.fda.gov/downloads/drugs/guidances/ucm073507.pdf. Accessed December 21, 2018. 5. Shapiro M. USFDA Advisory Committee. www.fda.gov/downloads/advisorycommittees/committeesmeetingmaterials/drugs/advisorycommitteeforpharmaceuticalscienceandclinicalpharmacology/ucm315764.pdf. 6. Mellstedt H, Niederwieser D, Ludwig H. The challenge of biosimilars. Ann Oncol. 2008;19:411-419.