CLEAR
Once a cell line is developed for the biosimilar, the candidate molecule is analyzed and carefully compared to the reference drug using a number of characteristics called critical quality attributes (CQAs). CQAs are features associated with the reference drug that can impact safety, potency, pharmacokinetics, and overall quality. CQAs can include post-translational modifications to a protein. One example is the addition of oligomannose glycans, which impact pharmacokinetic properties and reduces clearance time. Other post-translational modifications can alter the immunogenicity of a protein, impacting patient safety and efficacy.1-5
References: 1. US Food and Drug Administration. Guidance for industry: Q8(R2) pharmaceutical development. www.fda.gov/media/71535/download. Accessed October 29, 2019. 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 October 29, 2019. 3. Blauvelt A, Cohen AD, Puig L, Vender R, van der Walt J, Wu JJ. Biosimilars for psoriasis: preclinical analytical assessment to determine similarity. Br J Dermatol. 2016;174:282-286. 4. Alessandri L, Quellette D, Acquah A, et al. Increased serum clearance of oligomannose species present on a human IgG1 molecule. mAbs. 2012;4:509-520. 5. Shapiro M. USFDA Advisory Committee. 2012. www.fda.gov/downloads/advisorycommittees/committeesmeetingmaterials/drugs/advisorycommitteeforpharmaceutical scienceandclinicalpharmacology/ucm315764.pdf. Accessed October 29, 2019.