Deliverable Volume Testing for Liquid Dosage Forms: A Practical Guide

Why fill volume matters

A 60 mL bottle that delivers 57 mL looks normal on the shelf: the label, carton and fill line show nothing unusual. Over a ten-day course, however, the patient receives about 5% less than every labelled dose, and across a lot of tens of thousands of bottles a fill-volume problem becomes an efficacy and compliance issue.

USP General Chapter <698>, Deliverable Volume, addresses this. It applies to oral liquids, including powders constituted to a stated volume, labelled to contain 250 mL or less, and it is not required for single-unit containers when the monograph already includes the Uniformity of Dosage Units test (<905>). The test determines whether a container, emptied as intended, delivers the labelled volume.

Multiple-unit and single-unit criteria

1. Multiple-unit containers: the usual multi-dose bottle that a pharmacist or caregiver draws doses from over days or weeks. A slightly light pour can average out over the doses, so USP <698> sets only a floor: no single container below 95% of its labeled volume, and a batch average at or above 100%. There is no upper limit, because a bottle that delivers a little more than labeled is not a patient-safety concern in the way a bottle that delivers less is.
2. Single-unit containers: a one-time-use ampoule, vial or unit-dose cup. There is no second chance to make up a shortfall, so the limit applies on both sides: every container must be within 95%–110% of labeled volume. Too little under-doses the patient, and too much can matter just as much, depending on the drug.

Calculation

% of labeled volume = (Measured volume ÷ Labeled volume) × 100

Worked example: a 60 mL batch

Suppose a QC analyst is releasing a batch of 60 mL multi-dose antihistamine syrup. Ten bottles are selected at random and their contents measured:

58.9, 61.2, 60.5, 57.3, 62.0, 59.8, 60.1, 61.5, 58.2, 60.9 mL

Converting each to a percentage of the 60 mL label and averaging gives a batch mean of 100.1%, comfortably at or above the 100% requirement. Scanning the individual values, the lowest reading is 57.3 mL, which works out to 95.5% of label. That clears the 95% floor by a narrow margin, so every container passes and the batch is released on Stage 1 with no further testing.

Now change two numbers: suppose the lowest bottle had measured 56.4 mL (94.0% of label) and the 62.0 mL bottle had measured 62.9 mL. The average is unchanged at 100.1%, but one bottle now sits in the 90%–95% borderline band. Under USP <698>, this does not fail the batch outright. Because the average still clears 100% and only one container is borderline (not below 90%), the standard permits testing 20 additional bottles and pooling all 30 results together. At Stage 2 the average of all 30 must be at least 100%, and not more than one container may be borderline.

Where a result fails outright, with no retest available, is a container below 90% of label (multiple-unit), two or more containers in the borderline band, or an average below 100% combined with a borderline container. The standard offers a retest in only two situations: the average is below 100% but no container is outside the limits, or the average is at least 100% and not more than one container is borderline. Anything else goes to an out-of-specification investigation instead.

Errors in deliverable volume testing

• Assuming a borderline result is an automatic failure. USP <698> has a retest path for isolated borderline containers. Treating every borderline unit as a hard fail wastes material and time on batches that would have passed at Stage 2.
• Evaluating the 20 additional Stage 2 containers as their own separate group instead of pooling all 30 results together. The standard requires one combined average and one combined pass/fail call across all 30 units, not two independent judgments.
• Using the single-unit tolerance window on a multi-dose container “to be safe.” This produces false failures on bottles that are perfectly compliant under the rule that actually applies to them.
• Treating a container below 90% (multiple-unit) or outside 90%–115% (single-unit) as retestable. These results are excluded from the Stage 2 pathway entirely and should route straight to an OOS investigation.
• Rounding percentages before comparing with the 95% or 90% cutoffs. A reading of 94.96% rounds to 95% on a report, but it is still below the floor. Compare the unrounded value.

Questions on deliverable volume testing

Does USP <698> apply to injectable products?

No. Chapter <698> is scoped to oral and other non-parenteral liquid dosage forms labeled at 250 mL or less. Injectable and parenteral volume requirements are covered under separate chapters with their own fill-volume and withdrawable-volume criteria.

How many containers actually need to be tested for a routine release?

Ten containers for Stage 1. Testing stops there if the batch passes outright. Only batches in the borderline zone go to Stage 2, which adds 20 more containers for a total of 30. It is not a 30-unit test for every batch.

Can a batch be released if only the average passes but a few individual containers do not?

It depends on how many containers miss the mark and by how much. One borderline container with an otherwise compliant average can still pass through Stage 2 retesting. Two or more borderline containers, or any single container below the extended retest floor, cannot be released on the strength of the average alone.

Is deliverable volume the same test as fill volume?

No, and the distinction matters. Fill volume is what was put into the container at manufacture; deliverable volume is what actually comes out when the container is used as intended, accounting for residual film left behind by viscous formulations, dead volume in the container geometry, and pour technique. A batch can have a correct fill volume and still fail deliverable volume if the formulation clings to the container walls.

What should happen if a batch fails Stage 2?

A Stage 2 failure cannot be retested under USP <698>, because there is no Stage 3. It starts a formal out-of-specification investigation to find the root cause (fill-pump calibration, container geometry, viscosity drift, closure integrity) before any decision on the batch.

The Deliverable Volume Calculator applies the Stage 1 and Stage 2 criteria described above to measured container volumes.