How Do You Calculate Content Uniformity (AV) per USP <905>?

If you work in pharmaceutical quality control, you've likely faced the question: “Does this batch meet the content uniformity requirement?” The answer comes from a single calculated value — the Acceptance Value (AV) — defined in USP <905> Uniformity of Dosage Units. This article explains what it is, how to calculate it, and how to use the free tool at 6sq.

What It Is

Content uniformity is a pharmacopeial test that ensures each dosage unit (tablet, capsule, etc.) contains the active ingredient within a narrow range around the labeled claim. USP <905> provides two approaches: Content Uniformity (CU) for most products and Weight Variation (WV) for certain cases. The test result is expressed as the Acceptance Value (AV), which must not exceed a specified limit (usually L1 = 15.0) for the batch to pass.

How It Works / Formula

The AV calculation is defined in USP <905> as:

AV = | M – X̄ | + k × s

Where:

• X̄ = mean of individual contents (as % of label claim)
• s = sample standard deviation (of the % label claim values)
• k = a constant from the USP table (depends on sample size n)
• M = reference value, which depends on X̄:

- If 98.5 ≤ X̄ ≤ 101.5, then M = X̄ (i.e., the term |M – X̄| = 0)
- If X̄ < 98.5, then M = 98.5
- If X̄ > 101.5, then M = 101.5

The k values from USP <905> are:

Sample size (n) | k

• 10 | 2.4
• 30 | 2.0

Acceptance criteria (first stage, n = 10):

• AV ≤ 15.0 → pass
• If AV > 15.0, test 20 more units (total 30) and use the second-stage criteria (AV ≤ 15.0 with k = 2.0, and no unit outside 75%–125% of label claim).

A Worked Illustrative Example

Example data (illustrative only):
Suppose you test 10 tablets and obtain the following individual contents (% of label claim):

99.2, 98.7, 100.5, 101.0, 99.8, 100.2, 98.9, 101.3, 99.5, 100.8

Step 1 – Calculate mean (X̄):
X̄ = (sum of all values) / 10 = 999.9 / 10 = 99.99%

Step 2 – Calculate standard deviation (s):
Using the sample standard deviation formula, you get s ≈ 0.89%

Step 3 – Determine M:
Since X̄ = 99.99 (within 98.5–101.5), M = X̄, so |M – X̄| = 0.

Step 4 – Find k:
For n = 10, k = 2.4 (from USP table).

Step 5 – Calculate AV:
AV = |0| + 2.4 × 0.89 = 2.14

Decision: AV = 2.14 ≤ 15.0 → Pass USP <905> content uniformity.

Common Pitfalls

1. Using the wrong k value – k = 2.4 is only for n = 10; for the 30-unit stage, use k = 2.0.
2. Forgetting the M adjustment – If your mean is below 98.5 or above 101.5, you must set M to 98.5 or 101.5, respectively. This adds a penalty to the AV.
3. Confusing standard deviation – Use the sample standard deviation (n – 1 denominator), not the population version.
4. Ignoring the second stage – A failure at n = 10 does not mean batch failure; you are allowed to test 20 additional units.

Free Tool

To avoid manual calculation errors, use the free, USP <905>-compliant calculator at:
https://www.6sq.com/tools/usp905/ – simply enter your individual assay values, and it will compute the AV and give you an immediate pass/fail verdict.