Concentration-Adjusted Charge — Dosing Liquids and Solutions by True Strength

This topic is part of the SG Systems Global regulatory & operations glossary.

Updated November 2025 • Batch-Specific Potency, Potency Basis, % Solids Basis, Test-Driven Setpoint Adjustment • Liquids, Concentrate, Dose, GMP

Concentration-adjusted charge is the amount of liquid, solution, slurry or concentrate that must be added to a batch after taking account of its actual concentration or potency. Instead of dosing a fixed volume or mass regardless of strength, the system adjusts the charge so that the batch receives the correct amount of active substance. In regulated environments, concentration-adjusted charging is essential for APIs in solution, enzyme concentrates, syrups, botanical extracts and other materials whose strength is driven by assay, % solids and dilution rather than a simple “% w/w” of powder.

“A litre is not a dose. A concentration-adjusted charge turns ‘1 L of something’ into ‘exactly this much active’.”

1) Definition and Purpose

In many processes, key ingredients enter the batch as liquids or slurries: API solutions, enzyme concentrates, vitamin syrups, botanical extracts, emulsions and pastes. Their strength is defined by concentration (e.g. mg/mL, IU/mL, % w/w on solids basis), not by a simple “100 % potency” assumption used for dry powders. If the plant always charges the same volume of a solution, the active dose will drift whenever concentration changes.

A concentration-adjusted charge prevents this. For each batch, the target volume or mass of liquid to be charged is calculated from the required active dose and the current measured concentration of the lot. The operator sees a concrete target (for example, “Charge 13.9 kg” or “Charge 40.2 L”), but behind that target is a calculation based on assay, solids, density and sometimes temperature or dilution. The result is consistent corrected active content even when concentrates vary in strength within their specification window.

2) Relationship to Batch-Specific Potency and Potency Basis

For liquids and semi-solids, batch-specific potency is typically defined in units such as mg/mL, g/L, g/kg or IU/mL. This potency is itself based on a declared potency basis, often tied to % solids basis or a validated dilution recipe. Once batch-specific potency is known, concentration-adjusted charges become an application of that potency to a specific batch demand.

In formula terms, if a batch requires a certain amount of active substance (for example, 5.0 kg), and the lot potency is 0.36 kg active per litre of concentrate, the system can calculate the required volume of concentrate straightforwardly. The key is that the potency value used in the calculation has already incorporated assay, solids, LOD and basis decisions. Concentration-adjusted charge is therefore the execution-layer reflection of the potency management work done upstream in laboratory, specifications and master data.

3) Basic Calculation: From Required Active to Charge Volume

At its simplest, a concentration-adjusted charge follows the logic:

• Required active (kg) comes from the batch formula or target dose.
• Potency (kg active per L or kg) comes from batch-specific potency for the liquid lot.
• Required charge = Required active ÷ Potency.

For example, if the batch needs 3.0 kg of active and the lot potency is 0.25 kg active per L, the required volume is 3.0 / 0.25 = 12.0 L. If the batch needs 3.0 kg of active and the potency is 0.30 kg active per kg of solution, then the required mass is 3.0 / 0.30 = 10.0 kg.

In practice, the system may also incorporate TNE, process losses or stability-driven overage into the “required active” figure. It may also apply a potency adjustment factor if the formulation is written at a reference concentration or basis different from the one used by the lab. The core idea remains the same: charge targets are proportional to the required active dose and inversely proportional to the measured potency of the lot.

4) When Dosing by Mass vs Dosing by Volume

Concentrates can be charged by mass (kg, g) or by volume (L, mL). In a concentration-adjusted charge, the choice matters because it determines whether density must be part of the potency calculation.

• Mass-based dosing: potency is typically expressed as kg active per kg of solution. Corrected active content = Mass × Potency (kg/kg).
• Volume-based dosing: potency is expressed as kg active per L or mg/mL. Corrected active content = Volume × Potency (kg/L or mg/mL).

If the batch is controlled volumetrically (for example, peristaltic pump with flow meter), but potency is naturally expressed per unit mass (due to how the lab tests the sample), the system must use density to translate between the two. In either case, concentration-adjusted charging hides the complexity from the operator; they see a single target unit (kg or L), while the system performs the mass–volume conversions using current density data.

5) Integrating % Solids, Assay and Density

For many liquid and semi-solid ingredients, potency is determined by a combination of % solids basis, assay on solids basis and density. A typical chain might be:

• % solids (non-volatile solids per unit mass of liquid);
• assay on solids basis (active per unit of solid);
• density (mass per unit volume).

Together, these yield a batch-specific potency such as “0.36 kg active per L”. The concentration-adjusted charge then uses that potency to determine how many litres to add. If % solids drifts due to evaporation or dilution, or assay on solids basis changes across lots, batch-specific potency and therefore the required charge will change accordingly, even though the underlying recipe still calls for the same amount of active per batch.

Integrating these variables is much easier if % solids, assay and density are captured as structured data in LIMS and combined into potency via a validated calculation, rather than leaving that work to ad-hoc spreadsheets. Concentration-adjusted charges then become a straightforward application of the resulting potency value rather than a fresh calculation challenge for every batch.

6) Corrected Active Content for Concentration-Adjusted Charges

Just like solid additions, liquid additions need to be captured as both gross quantity and corrected active content. For a concentration-adjusted charge, this is trivial once potency is known:

• Corrected active content = Charge quantity × Potency (active per unit).

For example, if the system instructs the operator to add 12.0 L of concentrate at 0.36 kg active per L and the final volume is 12.1 L within tolerance, the corrected active content is 12.1 × 0.36 ≈ 4.36 kg. This value can be compared to the target active requirement, used in mass balance across the process, and fed into potency-normalised yield reporting and active-equivalent consumption postings.

From a regulatory perspective, this dual view is crucial. It shows that liquid additions were not simply “12 L of something”, but a specific, potency-normalised amount of active substance that can be tied back to specifications, label claim and validation studies.

7) Hard-Gating and Batch Weighing for Liquids

Concentration-adjusted charges fit naturally into a potency-aware batch weighing and dosing framework. Instead of presenting static targets, MES can:

• retrieve batch-specific potency for the selected liquid lot;
• compute the concentration-adjusted charge required for the batch;
• apply appropriate tolerances to the gross quantity (mass or volume);
• enforce hard-gating so the step cannot complete outside tolerance.

For mass-based dosing, integrated load cells and flow weigh systems can be controlled in exactly the same way as solid scales. For volume-based dosing, Coriolis meters or other flow meters can provide the “net volume” equivalent. The operator still sees simple “target” and “actual” fields, but behind them is a validated chain from lab potency to concentration-adjusted charge to corrected active content recorded automatically in the electronic batch record (eBMR).

8) Concentration-Adjusted Charges in Test-Driven Setpoint Adjustment

In more advanced strategies, concentration-adjusted charges form part of test-driven setpoint adjustment. Here, in-process tests such as assay, % solids, density or titer are performed on an intermediate or concentrate, and the results are used to recalculate the required charge for a downstream batch step.

For example, a bioreactor harvest might be tested for potency (titre IU/mL) and solids. If the material is stronger than expected, the volume required to achieve the target dose in the formulation is reduced; if it is weaker, the required volume increases, or a decision is made to scale the batch or divert the material. Concentration-adjusted charging is the execution mechanism that turns those test results into a concrete new setpoint for the pump, valve or weighing step that transfers the material into the next vessel.

When these decisions are embedded in MES logic and documented in the eBMR, regulators can see not only the test results but also the derived concentration-adjusted charges and their rationale, rather than relying on narrative explanations or standalone spreadsheets.

9) Dynamic Recipe Scaling for Concentrated Liquids

Dynamic recipe scaling goes a step further by allowing test results to influence not just the size of a concentration-adjusted charge, but the batch size or number of units produced. For example:

• If a concentrate is significantly stronger than planned, the process may reduce the volume charged and produce more units from the same batch to keep dose per unit unchanged.
• If a concentrate is weaker, the process may increase the charge volume or reduce batch size to maintain regulatory dose limits.

Concentration-adjusted charges are a central component of this approach. They define how much liquid to move given the current potency and the chosen scaling decision. The batch record can then show that, even though more or less concentrate was used and the number of units changed, the corrected active content per unit remained within specification. This aligns closely with modern expectations under QbD for managing variability through design space and adaptive control, rather than via rigid, one-size-fits-all quantities.

10) Data Integrity, LIMS Integration and Analytical Lot Links

As with other potency-based calculations, concentration-adjusted charges are only defensible if their inputs are controlled. Key inputs include:

• assay and % solids results in LIMS;
• density data, where used, from lab or process measurements;
• links between analytical results and material lots via an analytical lot link;
• validated calculation logic in MES or master-data systems;
• secure audit trails for any changes.

From an ALCOA+ perspective, concentration-adjusted charges must be attributable (to lot and tests), legible, contemporaneous, original (system-generated) and accurate. Operators should not be expected to re-enter concentration values or run calculations manually. Instead, potency data should flow electronically from LIMS into ERP/MES, where concentration-adjusted charge targets are derived and presented to the shop floor as controlled instructions with full traceability in the eBMR.

11) Typical Use Cases Across Industries

Concentration-adjusted charging is used wherever liquids or semi-solids carry active functionality:

• Pharmaceuticals and biologics: API solutions, antibody concentrates, neutralising solutions, buffers with active excipients, oral solutions and suspensions.
• Dietary supplements: vitamin and mineral syrups, botanical tinctures, oil suspensions and probiotic concentrates where label claims are in mg or CFU per dose.
• Food and beverage: enzyme concentrates, flavour and colour concentrates, sweetener syrups, stabiliser and emulsifier slurries used at low but critical levels.
• Cosmetics and personal care: active concentrates, emulsions and gels where a defined amount of active must be delivered per batch or per unit.
• Chemicals and speciality materials: catalyst and additive solutions where performance is strongly concentration-dependent.

In all of these domains, concentration-adjusted charges are the mechanism that ensures “one pump stroke” or “one litre” does not silently translate into different doses when concentrates or intermediates vary in strength between lots, suppliers or campaign runs.

12) Common Pitfalls and Failure Modes

When concentration is not handled systematically, several recurring issues appear:

• Fixed-volume dosing: using a fixed charge volume for a solution whose concentration drifts, causing under- or over-dosing over time.
• Spreadsheet dependence: using local calculators to adjust charges without embedding the logic into validated MES or ERP systems.
• Missing density: treating mg/mL potency as if it were mg/kg (or vice versa) without proper density conversion, leading to dose miscalculations.
• Unclear basis: CoAs reporting “10 % w/w” without stating whether this is on an as-is, dry or solids basis, making the concentration-adjustment logic opaque.
• Incomplete investigations: investigating OOS results by reviewing only gross volumes charged, without checking corrected active content based on actual potency.

Many of these problems disappear once concentration-adjusted charges are formalised as part of potency management: concentrations are stored as master data, conversions are performed centrally and the eBMR shows clearly how test results influenced the amount of liquid added to each batch.

13) Practical Implementation Steps

To implement concentration-adjusted charges in a robust way, organisations typically:

• Identify which liquid or semi-solid ingredients require concentration-aware dosing.
• Standardise how concentration is defined (mg/mL, IU/mL, % w/w on solids basis) and how it is tested.
• Integrate concentration, % solids, assay and density data into batch-specific potency for each lot.
• Configure MES to calculate concentration-adjusted charge targets from required active, potency and, where relevant, overage or process-loss factors.
• Validate the calculations as part of computer system validation (CSV) and expose results clearly in the eBMR.

Once this is done, concentration-adjusted charges become a standard pattern: every time a potency-managed liquid is dosed, the system quietly ensures the batch sees the right amount of active, regardless of how the concentrate’s strength has shifted within its approved range.

FAQ

Q1. How is a concentration-adjusted charge different from a potency-adjusted solid charge?
The principle is the same – both adjust the quantity based on actual strength. The difference is that concentration-adjusted charges work with liquids and slurries using units like mg/mL, g/L or IU/mL, often involving % solids and density in the potency calculation.

Q2. Do all liquid additions need to be concentration-adjusted?
No. It is most important for liquids carrying active functionality or where label claim, safety, efficacy or critical quality attributes depend on dose. Utility streams and simple carriers may be managed with fixed charges if justified in the control strategy.

Q3. Can operators calculate concentration-adjusted charges manually?
In principle yes, but in a GxP environment the calculation should be embedded in validated systems. Manual calculations are error-prone, hard to audit and difficult to keep consistent across shifts, sites and products.

Q4. What data are essential to calculate a concentration-adjusted charge?
You need the batch’s required active dose, the lot’s batch-specific potency (often derived from assay, % solids and density) and the dosing unit (mass or volume). Additional factors like overage, process loss or guardbanding may also be included depending on the control strategy.

Q5. What is a practical first step to adopt concentration-adjusted charges?
Start with one critical liquid ingredient, document how its potency is defined and tested, configure a simple concentration-adjusted charge calculation in MES for that material, validate it, and then expand the pattern to other concentrates and solutions once the approach is proven.

Related Reading
• Potency & Basis: Batch-Specific Potency | Potency Basis | LOD Adjustment | % Solids Basis
• Liquid & Test-Driven Control: Test-Driven Setpoint Adjustment | Dynamic Recipe Scaling | In-Process Assay Gate
• Yield, Mass Balance & Records: Corrected Active Content | Mass Balance | Potency-Normalised Yield | Active-Equivalent Consumption | Electronic Batch Record (eBMR)