Potency-Adjusted Batching & Recipe Control

This topic is part of the SG Systems Global potency, assay and batch-control glossary.

Updated December 2025 • Potency basis, assay-driven charge weights, LOD & percent solids, in-process assay, stability-driven overages, yield reconciliation & MES integration • Pharma, Biotech, Supplements, Nutrition, Agrochemicals, High-Value Chemicals

Potency-adjusted batching is where your “100 mg per dose” promise either holds or falls apart. It’s the step where you stop pretending every lot is 100 % label claim, read the real assay, and change the recipe so the batch still lands on-target. When this logic is weak or manual, you get a familiar mess: failed assays, out-of-spec content uniformity, unexplained yield losses, unstable products and pricing that quietly erodes margin.

In regulated manufacturing, none of that is acceptable. Regulators expect you to show how you’ve turned assay, LOD and percent solids into actual charge weights and setpoints — not that you “usually get about the right result”.

• QA and Regulatory want traceable, validated calculations and clean batch records.
• Operations want simple, guided workflows, not spreadsheet acrobatics at the weigh bench.
• Finance wants predictable yields, not “potency mysteries” every time vendors change.

“If your potency maths live in someone’s personal spreadsheet, you’re one laptop crash away from failing an inspection.”

1) Where potency goes wrong — common failure modes

Most potency issues don’t arise because people don’t know the assay; they arise because nobody systematically uses it. Typical failure modes:

Every one of these failure modes is preventable if the potency concepts in your glossary are actually embedded into recipes, weigh-and-dispense and eBMR — instead of living in validation reports and Excel.

2) Potency basis, batch-specific assay & the analytical lot link

It starts with agreeing what “potency” even means for each material:

• Potency Basis defines whether you express strength on anhydrous, as-is, salt-equivalent, free-base or other basis.
• Batch-Specific Potency recognises that each lot has its own assay — you cannot assume 100 % label claim.
• Analytical Lot Link is the glue between LIMS/CoA results and the material master / batch recipes that actually use them.

In a V5-style environment, that means:

• Storing potency basis and required fields in the material master.
• Pulling assay, LOD and related data directly from CoAs or LIMS into MES via the Analytical Lot Link, not via manual retyping.
• Using that data to automatically compute Potency Adjustment Factors and corrected actives for each lot.

That design turns “please remember to look at the CoA” into “you can’t create the job until assay data are present”, which is a meaningful upgrade from a regulatory and data-integrity standpoint.

3) LOD, percent solids & solvent content — why as-is weights lie

Many actives and concentrates are not neat powders or simple solutions. Moisture and solvent content matter:

• LOD Adjustment corrects for water lost on drying or ignition.
• Percent Solids Basis handles slurries, suspensions and solutions where only the solids carry active.
• Solvent Content Correction addresses variable solvent loads in concentrates that dilute actives.
• Corrected Active Content combines assay and these corrections into a single “true” active value for calculations.

The practical takeaway: weighing 10.00 kg “as is” is rarely the same as adding 10.00 kg of active. The system needs to know, per material, whether to:

• Use assay alone (e.g. dry API with minimal water).
• Use assay + LOD (e.g. hygroscopic powders).
• Use assay + percent solids (e.g. suspension concentrates).
• Use assay + solvent correction (e.g. variable-solvent intermediates).

Embedding those rules into MES and weigh-and-dispense — using your glossary definitions — means operators see charge weight, not an abstract potency formula. They weigh what the system tells them, and the system owns the maths and its audit trail.

4) Potency Adjustment Factor, dynamic scaling & concentration-adjusted charges

Once you have corrected active content, you can calculate how much material to add to hit a target theoretical quantity:

• Potency Adjustment Factor expresses the ratio between nominal and actual strength (e.g. 1.05 if assay is 95 % and you want 100 units).
• Dynamic Recipe Scaling scales recipes using these factors, batch sizes and available-lot constraints.
• Concentration-Adjusted Charge is the final number: “weigh this many kg of this lot”.
• Active-Equivalent Consumption keeps track of how much active you burned, not just how many kg of wet material you used.

This is where the spreadsheet temptation is strongest. The right pattern is:

• Pre-define recipe equations in a validated function library inside MES/QMS, not in ad hoc files.
• Use Analytical Lot Link data to compute Potency Adjustment Factors and Concentration-Adjusted Charges automatically per job/lot.
• Send those charge weights directly to Weigh-and-Dispense Automation, so operators see a single target, tolerance and label — not an equation.
• Record Active-Equivalent Consumption for yield and cost analysis.

That approach moves potency logic into your validated systems, where it belongs, and dramatically reduces “blue-pen corrections” in batch records that inspectors always notice.

5) In-Process Assay Gates & test-driven setpoint adjustment

Some products can’t rely on raw-material assay alone; in-process testing is needed to confirm that the overall system landed in the right window.

• In-Process Assay Gate defines decision points where you stop, test and either proceed, adjust or reject.
• Test-Driven Setpoint Adjustment uses in-process results to adjust remaining additions or process settings within defined, validated bounds.

Examples:

• Granulation solids content: adjusting binder or solvent addition based on measured moisture/solids.
• Potent liquid blend: adjusting a finishing addition to pull assay from “acceptable” toward “target”.

In V5-style MES, that looks like:

• Enforced pause steps waiting for lab or PAT results at defined points.
• Validated adjustment calculators that propose modified setpoints, with QA/technical approval where needed.
• Audit-trailed application of those new setpoints to the remainder of the batch.

Without that structure, you get tribal “seasoning” of batches — which may rescue a few, but cannot be defended under data-integrity and QRM scrutiny.

6) Stability-driven overages & potency-normalised yield

Sometimes you deliberately charge more than the label claim to guarantee that product stays within spec over shelf-life. The difference between good and bad overages is documentation and maths.

• Stability-Driven Overage ties overage percentages to real stability data and degradation kinetics.
• Potency-Normalised Yield expresses yield not just in kg or litres, but in “kg of declared active” at release and over time.
• Batch Balancing and Batch Yield Reconciliation close the loop on what went where (product, scrap, samples, rework).

Execution-wise, that means:

• Overages are parameterised in recipes and justified in stability files, not “a scoop extra because we always do that”.
• Potency-normalised yield is part of management reviews and PQRs, not just theoretical batch-size vs fill counts.
• Losses are tracked in active equivalents, so you can tell whether you’re losing solvent or actives when things go wrong.

This level of thinking is increasingly expected in higher-risk segments: it’s not enough to say “we add 3 % extra”; you need to show that 3 % was derived from data and is maintained within bounds by the control system.

7) Weigh-and-dispense, MES & eBMR — turning potency into behaviour

All the potency logic in the world is worthless if it isn’t what operators actually do. This is where:

• Weigh-and-Dispense Automation and Weighing & Dispensing Component Control guide identity checks, charge weights and labels at the scale.
• MES orchestrates batch steps, in-process tests, setpoint adjustments and holds.
• eBMR captures the entire potency story in a way QA and inspectors can follow.

Practically, a potency-aware weigh-and-dispense operator never has to:

• Manually copy assay or LOD values into a calculator.
• Guess which equation to use for a given API or concentrate.
• Hand-write “corrected” charge weights into the batch record.

They see: “Material X, Lot Y, Assay/LOD/solids pre-filled; Target [kg]; Tolerance [±]; Weigh now.” The system does the rest and keeps the audit trails. That is the only sustainable way to keep potency under control across shifts, sites and CMOs.

FAQ — Potency-Adjusted Batching & Recipe Control

Q1. Do we need full potency-adjustment logic for every material?
No. A risk-based approach is expected. Focus full assay/LOD/solids-based adjustment on actives, critical excipients and high-variability materials. Low-impact, low-variability materials can often be controlled on a simpler basis, provided the rationale is documented in your QRM and process-validation work.

Q2. Is it acceptable to run potency maths in Excel if we lock the spreadsheet?
Locked spreadsheets with change control are better than nothing, but they still create parallel logic outside your core MES/eBMR. Regulators increasingly question critical calculations that live off-system. The direction of travel is clear: move potency logic into validated system functions wherever feasible, use spreadsheets only as a transitional or backup tool, and make sure the audit trail is just as strong as it would be in MES.

Q3. How do we decide when in-process assay or test-driven adjustment is required?
Use risk and process understanding: products with narrow therapeutic index, complex reactions, highly variable intermediates or sensitive release specifications are good candidates for in-process assay gates. Process-development and validation work should explicitly state whether raw-material assay is sufficient or in-process checks are required, and how any adjustments will be calculated and controlled.

Q4. How does potency-normalised yield help in practice?
Potency-normalised yield strips out “noise” from variable active strengths and shows you how much declared active you really got into saleable units. It separates “we lost solvent or excipient” from “we lost active”, making root-cause analysis, pricing and process-improvement discussions far clearer. It also avoids blaming validation or QC when the real problem is raw-material variability that nobody has accounted for yet.

Q5. How do we bring CMOs and co-packers into this potency framework?
By pushing the same logic and expectations through quality agreements, tech-transfer packages and data exchanges. That means: clearly specifying potency basis and adjustment rules; providing or requiring Analytical Lot Link equivalents; mandating weigh-and-dispense controls that enforce calculated charge weights; and requiring eBMR or equivalent records that show all potency-related calculations. “We assumed the CMO handled potency” is not an acceptable position once your name is on the label.

Q6. What’s a pragmatic starting point if our potency adjustment is mostly “rule-of-thumb” today?
Start with a single high-risk or high-cost active. Map how assay and LOD data are used today, where spreadsheets sit and where errors or deviations have arisen. Build a simple, validated potency-calculation function into MES or weigh-and-dispense for that active, using your glossary concepts as the spec. Prove that it stabilises potency, reduces review pain and makes yield more predictable — then expand to the next set of actives. Small, well-chosen steps beat a “big bang” potency project every time.

Related Reading (Glossary)
• Potency & Basis:
Potency Basis |
Batch-Specific Potency |
Analytical Lot Link |
Corrected Active Content
• LOD, Solids & Concentration:
LOD Adjustment |
Percent Solids Basis |
Solvent Content Correction
• Dynamic Recipes & In-Process Control:
Potency Adjustment Factor |
Dynamic Recipe Scaling |
Concentration-Adjusted Charge |
Active-Equivalent Consumption |
In-Process Assay Gate |
Test-Driven Setpoint Adjustment
• Overages, Yield & Balancing:
Stability-Driven Overage |
Potency-Normalised Yield |
Batch Balancing |
Batch Yield Reconciliation
• Execution & Records:
Weighing & Dispensing Component Control |
Weigh-and-Dispense Automation |
MES – Manufacturing Execution System |
Electronic Batch Record (eBMR)