Cells should ideally be passaged during:
Growth curve of cultured cells comprises lag adaptation, exponential log proliferation, plateau where division balances loss, and death where loss predominates. Ideal timing for passaging aligns with transition from late log to early plateau when cultures achieve sufficient density providing high yield of cells for splitting but before deleterious effects of overconfluence arise. At this point confluence typically 70-80% for adherent fibroblasts and epithelial lines, or suspension density half of maximal sustainable concentration, providing many cells yet maintaining health with active DNA synthesis fraction and intact surface receptors for reattachment. Passaging during lag would be premature leading to dilution of autocrine growth factors and prolonged lag in next vessel, while passaging in deep plateau or death phase captures cells already stressed releasing proteases, danger signals, and senescence-associated secretory phenotype factors that impair recovery. Standard operating procedures therefore schedule subculture at onset of plateau to ensure rapid resumption of exponential growth within 12 hours, preserving doubling time and minimizing selection for transformed clones.
Ref: Freshney Ch.14 Passaging at plateau late log; Alberts MBoC Ch.17 Growth regulation subculture timing before overconfluence stress.