Table 2.

Common developability liability risks, conditions for their evaluation and likely occurrence, and mitigation strategies.

Type	Common sequence motifs/characteristics	Forced degradation/conditions	Common occurrence	Routes of mitigation
Deamidation (Asn)	NG, NN, NS, NT	Neutral/high pH, phosphate buffer	Cell culture conditions, physiological pH/temp, higher pH formulations	Corrective engineering, partial mitigation with low formulation pH
Isomerization (Asp)79	DG, DS	Low pH	Low pH conditions, formulations	Adjust formulation pH, corrective engineering
Glycation (non-enzymatic)80	K	Reducing sugars at higher temperatures (glucose, fructose)	Cell culture conditions, physiological pH/temp	Corrective engineering
Trp/Met oxidation	M, W	Light, chemical oxidizers (H2O2, tBHP, AAPH)	Light, metals, polysorbate degradation, storage, thermal stress	Corrective engineering, formulate with antioxidants, amber vials, eliminate stainless steel in process
N-glycosylation	NXS/T motif, non-consensus	None	Cell culture conditions	Corrective engineering, purification removal
Self-interaction	Structural, charge/hydrophobic patches	Concentration dependent	Higher concentrations	Viscosity modifiers, optimize pH
Aggregation	Structural, aggregation-prone motifs	Thermal, storage, low/high pH	Cell Culture, process (low pH or pH adjustment), storage, administration	Optimize pH and formulation, stabilizers, removal by purification
Clipping	Asp-Pro motif, non-consensus, enzymatic	Low/high pH, thermal	Cell Culture, process (low pH), HCP contamination, storage	Corrective engineering, removal by purification, removal of proteolytic HCPs, formulation pH
low/high pI	Excess Glu/Asp or Lys/Arg	N/A	Inherent molecular property (outside 7–9 range)	Corrective pI variants, isotype switching