A replication experiment was performed to validate a stream sampling method for a pharmaceutical powder blend. A 1.5 kg powder blend was prepared and an in-house developed feeder was used to divide into six sub-samples of approximately 250 g. Each 250 g sub-sample (1/6 total blender lot volume) was deposited along a rig of 3 meter length. A validated near infrared (NIR) spectroscopic method was used to determine the drug concentration as the powder deposited in the rig moved at a linear velocity of 10 mm/sec. The depth of penetration of the NIR radiation was 1.2 mm and the sample volume analysed was approximately 180 mg. The MPE (minimum practical error) obtained with the system was 0.04% w/w acetaminophen (APAP), which was considered excellent for the system. The replicate analysis of the powder deposition provided 390 measurements of drug concentration, with a mean APAP concentration of 14.93% (w/w) and a relative standard deviation (RSD) of 5.20%. Replicate measurements (n = 650) of the powder deposited along a single rig of 3 m length ×10 provided an RSD of 2.23%, attributable to deposition (outflow) heterogeneity. Finally, static replicate analysis of the measurement error alone amounted to an RSD of 0.14%. The embedded replicate experiments elucidated all sources of variation in a sampling system for pharmaceutical powder blends, and proved reliable and highly sensitive in identifying areas of non-acceptable residual heterogeneity (dead zones).