When is perfusion actually worth the added complexity over fed-batch?

Short version: perfusion earns its complexity when (a) the product is labile and can’t sit in the vessel — the short residence time protects it; (b) you need very high volumetric productivity in a small footprint; or (c) demand is high and steady enough to run steady-state for long campaigns. If you’re single-product, a stable molecule and moderate demand, a well-run fed-batch is usually simpler, cheaper to validate and ‘good enough’. The hidden costs of perfusion are cell-retention hardware, media consumption and the control/validation burden — budget for those honestly before committing.