Most people in pharmaceutical industries feel relaxation when a batch reconciles above 100% like at 100.7%. But the fact is that they should not be happy as theoretical yield is the max value that the dispensed materials can possibly give, so a result above 100% cannot be real.It is a signal that a number is wrong & something is added that the calculation does not know about, or that two things that should have been kept apart were mixed. Auditors know this, and a yield above 100% is treated like a yield that is too low,it needs an explanation before the batch moves on.
This article lists seven real causes of a yield above 100%, with a simple check for each one, so that you can find the reason in an organised way instead of guessing.
Why a yield above 100% is a problem
A reconciliation proves that every kilogram or every unit is accounted for. If the BMR shows more than theoretical then the accounting is not reliable, and that raises questions about the rest of the batch record. It can also hide a real quality problem, such as another product’s residue in the batch or an unrecorded addition of rework. The right reaction is to hold the batch, check, and document.
Percentage Yield Calculator, which compares actual with theoretical yield and shows the loss
Coating Reconciliation, which compares core with coated tablets on a count basis.
Cause 1
Moisture or solvent
This is the most frequent reason for granulation and drying. If the theoretical yield is on a dry basis but the granules are weighed with moisture still in them, the actual figure looks too high. Hygroscopic blends can also take up water while they wait in a drum on a humid day.
Example
The theoretical dry weight of a granulation is 130.0 kg. The granules weigh 131.0 kg, which looks like 100.77 %. The loss on drying is 4.0%, so the dry-equivalent weight is 131× 0.96 = 125.76, and the yield on a dry basis is 125.76 ÷ 130 = 96.74%. The batch did not gain material. It carried water.
Cause 2
The wrong theoretical quantity
The theoretical quantity must be built from what was really dispensed. If extra API was weighed to correct for the assay, but the theoretical was calculated from the label claim, then the actual quantity will include that extra material and the yield will be too high. In the case of an API with an assay of 98.5%, the correction adds about 1.5% more API mass, so a result near 101.5% would not be a surprise. The API Requirement Calculator shows how the gross weight is found.
Check: recalculate the theoretical from the dispensing record, and confirm that it uses the same potency and overage as the master formula.
Cause 3
Weighing error
A balance that has drifted, a tare weight value that was not reset, a drum weighed with its lid on one time and off on another, or two different balances used at two stages can all move the total by a percent or more.
Check: look at the calibration status and the last daily check of each balance used, confirm the tare weights of the containers, and weigh one of the drums again on a second balance.
Cause 4
Wrong average weight in a count-based yield
Stages that are tracked in tablets or capsules convert weight into a count by dividing by the average unit weight. A small error in that average moves the count. Suppose 98.0 kg of coated tablets are counted, and the theoretical is 240,000 tablets. With the true average coated weight of 412 mg the count is 237,864, which is a yield of 99.11%. If a sample of lighter tablets suggests an average of 405 mg, the count becomes 241,975, which is 100.82%. The batch has not changed, only the average has.
Check: measure the average on a larger sample, taken from different parts of the batch, and use the same balance that was used for the bulk weight. See Coating Reconciliation for the count-based method.
Cause 5
Carry-over or a mix-up
Residual product left in a hopper, a blender or a coating pan from the previous batch will be swept into the next one, and its weight appears as a yield gain. A drum from another batch put on the wrong pallet has the same effect.
Check: review the line clearance and the cleaning records for the equipment, and confirm that no other batch of any product was handled in the same area at the same time. If there is a doubt about identity, this is a quality event, not just a calculation problem.
Cause 6
Rework or returned material counted twice
Material that was rejected, collected as sweepings or sent for rework may be added back later. If it was already counted in the actual yield at an earlier stage, then its weight is counted a second time.
Check: go through the rework register and the returns log, and match each container to one entry in the batch record.
Cause 7
An arithmetic or unit error
A kilogram entered as a gram, a decimal point in the wrong place, a number carried over from the wrong line of the record, or a rounded value used too early are all common. They are also the easiest to find, so check them first.
Check: have a second person repeat the calculation from the raw data. The Percentage Yield Calculator gives an independent answer in seconds.
Quick reference
| Possible cause | First check |
|---|---|
| Moisture or solvent in the material | Loss on drying (LOD) of the weighed material, and the moisture basis of the theoretical |
| Wrong theoretical quantity | Recalculate it from the quantities actually dispensed, including assay correction |
| Weighing error | Balance calibration, tare values, and a re-weigh of a sample drum |
| Wrong average weight in a count calculation | Re-measure the average weight on a larger, representative sample |
| Carry-over or a mix-up | Line clearance, cleaning records and any other batch handled in the same equipment |
| Rework or returns counted twice | Rework register, and every container of returned material |
| Arithmetic or unit error | A second person recalculates, with attention to kg and g, and to decimals |
What to do when it happens
- Do not change the numbers to make the result fit. Record the figures exactly as measured.
- Hold the batch, and follow your deviation procedure for a result outside the limit.
- Work through the seven checks above, starting with the easy ones: arithmetic, units and the theoretical.
- Write down what was checked and what was found, including the checks that found nothing.
- If the cause is not found, escalate it to QA as an unexplained discrepancy. The steps in How to Investigate a Batch Reconciliation Failure apply in the same way.
Frequently asked questions
Is a yield above 100% acceptable?
No. It is outside what is physically possible for the dispensed materials, so it needs an explanation, even if the limit in the batch record does not mention an upper figure.
Can I round 100.4% to 100%?
Not without a reason. Round only as your procedure says, and always record the unrounded result. The better answer is to find the cause.
Why does the yield change between stages?
Each stage has its own losses and its own measurement points. A figure that looks right at one stage may include a moisture effect or an average-weight error that only shows at the next.
What upper limit should I use?
Use the limit in your approved batch record. Any upper limit has to come from your own validated process and approved procedures, not from a general rule, and a result above 100% still needs an explanation.