Pharmaceutical Calculation Suite
The USP <905> acceptance-value calculation — the conditional reference value M, the staged 10- and 30-unit testing plan, and the individual-unit window that moves with the batch mean.
Uniformity of dosage units per USP <905> ensures each unit in a batch carries a drug substance content within a narrow range around the label claim. The chapter offers two methods — Content Uniformity (assay of individual units, applicable in all cases) and Weight Variation (permitted for specific dosage forms when the drug constitutes ≥25 mg and ≥25% of the unit, per the chapter's Table 1). This calculator implements the Content Uniformity acceptance-value calculation. <905> is harmonized with the European and Japanese Pharmacopoeias.
The reference value M is not fixed. It tracks the mean inside a band and clamps at the band edges:
Case 1 — T ≤ 101.5:
98.5% ≤ X̄ ≤ 101.5% → M = X̄, so AV = ks
X̄ < 98.5% → M = 98.5%, so AV = (98.5 − X̄) + ks
X̄ > 101.5% → M = 101.5%, so AV = (X̄ − 101.5) + ks
Case 2 — T > 101.5 (products with an approved overage):
98.5% ≤ X̄ ≤ T → M = X̄
X̄ < 98.5% → M = 98.5%
X̄ > T → M = T%
Staged testing. Select not fewer than 30 units. Stage 1: assay 10 units; the requirement is met if AV ≤ L1. If AV > L1, Stage 2: assay the next 20 (n = 30, k = 2.0); the requirement is met if AV ≤ L1 and no individual unit falls outside [1 − 0.01·L2]·M to [1 + 0.01·L2]·M — that is, 0.75·M to 1.25·M with the default L2 = 25. Note the individual-unit window is centred on M, not on label claim, so it moves with the batch mean within the band. The window is a Stage 2 criterion only; at Stage 1 the calculator shows it for information, and the Stage 1 verdict rests on AV ≤ L1 alone.
| Symbol | Variable | Description |
|---|---|---|
| X̄ | Mean of individual contents | Mean of the assayed individual unit contents, as % of label claim. |
| s | Sample standard deviation | n − 1 form, on the individual contents. |
| k | Acceptability constant | 2.4 at n = 10 (Stage 1); 2.0 at n = 30 (Stage 2). |
| T | Target content per dosage unit at time of manufacture | As % of label claim; 100.0% unless otherwise stated or the approved target differs. Selects Case 1 vs Case 2 of the M definition. A calculator input — leave blank for 100.0, or enter your approved target (e.g. 105) to invoke Case 2. |
| M | Reference value | Defined conditionally from X̄, T and the 98.5–101.5 band (see the cases above). Never simply fixed at 100. |
| L1 | Maximum allowed acceptance value | 15.0 unless otherwise specified — at both stages. A calculator input: leave blank for 15.0, or enter the monograph's value. |
| L2 | Maximum allowed deviation of any unit from M | 25.0 unless otherwise specified; defines the Stage 2 individual-unit window 0.75·M–1.25·M. A calculator input: leave blank for 25.0. |
Worked example A — mean inside the band. Ten units (% LC): 98.2, 99.1, 100.4, 101.2, 99.6, 98.8, 100.9, 99.9, 100.7, 99.4. T = 100.0%.
Worked example B — mean below the band. Same spread, mean shifted down: X̄ = 97.92, s = 0.977, T = 100.0%.
PharmaCalc returns your Acceptance Value with the Stage 1 / Stage 2 decision already made. It is computed server-side against the published method and written into a GMP PDF report with the inputs, formula chain, references, document control and signature pages — traceable to the software release that produced it.
Open the Content Uniformity calculator — free demo