Assay-Based Charge

Assay-based charging answers the question: 'How much of this lot do I weigh to put X kg of active into the batch?' The answer is X divided by the lot's potency (with optional moisture or solvent corrections). It is the everyday work of any dispensing kiosk where the recipe expresses an active target rather than an as-is mass. 21 CFR 211.101 requires components 'weighed, measured, or subdivided as appropriate' and that 'the actual weight or measure of each active ingredient … is determined and certified by one person and independently checked'.

• Recipe target is the active mass (on an explicit basis).
• Lot assay is the lot's potency on a matching basis (with moisture/solvent corrected separately if bases differ).
• Dispensed mass = target / potency factor (with combined corrections if applicable).
• Tolerance is applied to the dispensed mass (typically ±0.5–2% depending on scale class and process).
• Verification by a second person or barcode/scale system per 211.101(c).

• Tolerance is on the corrected mass (the target after potency correction), not the nominal recipe mass.
• Scale-class limits per OIML R76: a Class II balance at 10 kg target has a much tighter resolution than a Class III at 100 kg.
• Process tolerance (±1% typical) usually wider than scale tolerance — operator stops as soon as both criteria are satisfied.
• Out-of-tolerance dispense triggers a deviation; cannot be silently accepted.
• Tolerance for actives often tighter (±0.5%) than for excipients (±1–2%).

• Two-person verification — both sign the eBR (Part 11 §11.200 e-signatures).
• System verification — automated control with barcode-driven lot selection plus calibrated scale reading and audit-trailed acceptance; FDA accepts this in lieu of second-person.
• Hybrid — system handles routine charges; second person verifies critical actives or first-of-day.
• Whichever model, the record must show who or what verified, when, and against what limits.

• Recipe target ambiguous (nominal vs label claim vs anhydrous) — every operator interprets differently.
• Operator hand-calculates correction on a separate piece of paper — opens transcription errors and is unauditable.
• Charge accepted out of tolerance with override — straight 483 unless a documented deviation is captured.
• Tolerance applied to nominal rather than corrected mass — under-dose or over-dose by the correction factor magnitude.
• Verification cancelled by the same user (signing as both performer and verifier) — Part 11 §11.200(b) violation.
• Scale not within calibration interval at time of charge — entire dispense suspect.

• Pharma OSD — actives charged on anhydrous basis with assay correction; excipients usually as-is.
• Pharma sterile — actives charged in solution; potency correction applied to the dissolved mass.
• Biopharma — bioactivity units used as target; correction relative to working reference standard.
• Cosmetics actives — same approach as pharma; less stringent tolerance.
• Food fortification — vitamin premix charged on a label-claim basis with periodic potency revalidation.
• Cannabis — cannabinoid distillate charged to deliver target THC/CBD per unit; correction critical to regulatory limits.