Impurity Thresholds (ICH Q3A/Q3B) for a Whole Impurity List
The Attachment 1 thresholds for your dose, and every impurity through the decision tree.
Try before you buy.
- Free preview: the method, the limits that apply and the verdict for your input; computed figures stay hidden until the pass.
- Locked until you unlock it: download and print.
- Unlock: Ultimate pass, ₹1,199 for 30 days or ₹449 for 1 week, a one-time payment unless you choose automatic renewal. Unlock: Ultimate pass, $24.99 for 30 days or $9.99 for 1 week, a one-time payment unless you choose automatic renewal.
Ways to unlock shows how to get the full result.
Printing this result is locked in the free preview.
Thresholds and impurities
Locked in the free preview. Opens the ways to unlock this result.
Locked in the free preview. Batch runs unlock with a pass.
Locked in the free preview. Query results unlock with a pass.
About the Impurity Thresholds (ICH Q3A/Q3B) for a Whole Impurity List
Works out the reporting, identification and qualification thresholds of ICH Q3A(R2) (impurities in a new drug substance) or Q3B(R2) (degradation products in a new drug product) for your maximum daily dose, and checks every impurity of a chromatogram or a specification against them. Where Attachment 1 gives a percentage or a total daily intake, whichever is lower, the lower one at your dose applies, and each result is evaluated the way Attachment 2 shows: reported to the right decimals, an intake compared after rounding to the threshold’s own decimals.
Each impurity gets its step in the decision tree of Attachment 3 — report it, identify it or reduce it, qualify it or reduce it, or reduce it to a safe level when it has known human relevant risks — and the report lists the specification lines: each specified identified and unidentified impurity, any unspecified impurity with its criterion, and the total. Paste the list or open the Excel export of the HPLC impurity calculation. The free preview shows the thresholds that apply, every verdict and step, the specification lines and the method; the reported results, the intakes and the total stay hidden, and the PDF, Excel and Print record opens with an Ultimate pass.
How to use it
- Choose Q3A(R2) for a drug substance, Q3B(R2) for the degradation products of a drug product, or your own justified thresholds, and enter the maximum daily dose.
- Paste the impurities, one per line — name; result % — or open a CSV or Excel file; add yes or no for “identified” and “known risk”, the level your safety data qualify, and your proposed limit where you have them.
- Read the thresholds that apply, each impurity’s verdicts and next step, and the specification lines.
- Without a pass the report stays a free preview with its computed figures hidden; the PDF, Excel and Print record unlocks with an Ultimate pass.
Examples
Impurity at 0.1649 %, identified, safety data to 0.2 %
Reported 0.16 %: above the identification (0.10 %) and qualification (0.15 %) thresholds; qualified at this level by your safety data
Impurity at 0.124 %
The qualification threshold is the 1.0 mg intake (lower than 0.15 %): 0.12 % is 0.96 mg, rounded to 1.0 mg, so not above it
Degradation product at 0.550 %
Reported 0.6 %: 300 µg a day, above the 200 µg qualification threshold
Common uses
- Drafting the impurities section of a specification for a new drug substance or product.
- Checking a batch’s impurity profile at release or on stability against the thresholds of its dose.
- Seeing at once which peaks of a chromatogram need identification or qualification.
- Recomputing the thresholds when the maximum daily dose of a product changes.
Q3A(R2) Attachment 1: new drug substances
- Maximum daily dose of 2 g a day or less: reporting 0.05 %; identification 0.10 % or 1.0 mg per day intake, whichever is lower; qualification 0.15 % or 1.0 mg per day intake, whichever is lower.
- Above 2 g a day: reporting 0.03 %, identification 0.05 %, qualification 0.05 %.
Results below 1.0 % are reported to two decimals, at and above 1.0 % to one.
Q3B(R2) Attachment 1: new drug products
- Reporting: 0.1 % up to 1 g a day, 0.05 % above.
- Identification: below 1 mg, 1.0 % or 5 µg TDI; 1 mg to 10 mg, 0.5 % or 20 µg TDI; above 10 mg up to 2 g, 0.2 % or 2 mg TDI (whichever is lower); above 2 g, 0.10 %.
- Qualification: below 10 mg, 1.0 % or 50 µg TDI; 10 mg to 100 mg, 0.5 % or 200 µg TDI; above 100 mg up to 2 g, 0.2 % or 3 mg TDI (whichever is lower); above 2 g, 0.15 %.
Results below 1.0 % are reported to the decimals of the reporting threshold, at and above 1.0 % to one.
The decision tree (Attachment 3)
Above the identification threshold: if the structure is not identified, identify it or reduce it to not more than the threshold; if it is identified and has known human relevant risks, reduce it to a safe level; otherwise, above the qualification threshold, reduce it to not more than that threshold or qualify it with safety data. A level adequately tested in safety or clinical studies, or a significant metabolite, is qualified.
Sources
- ICH Quality guidelines — Q3A(R2) Impurities in New Drug Substances and Q3B(R2) Impurities in New Drug Products: Attachment 1 (thresholds), Attachment 2 (evaluating reported results) and Attachment 3 (decision tree)
Limitations
- Organic impurities and degradation products only: residual solvents (ICH Q3C), elemental impurities (ICH Q3D) and mutagenic impurities (ICH M7) have their own limits.
- The guidelines do not cover biological and biotechnological products, peptides, oligonucleotides, radiopharmaceuticals, fermentation and semi-synthetic products, herbal products or crude products of animal or plant origin.
- Lower thresholds can apply to an unusually toxic impurity and higher ones need a scientific justification: enter them as your justified thresholds.
- Up to 500 impurities at a time, checked on your device in a moment.
- MySmartCoPilot is not affiliated with or endorsed by ICH. This record applies the thresholds of the guideline you choose; your QA approves the specification.
Privacy
On this device: nothing is sent
Your results stay in this browser and are never sent anywhere. The PDF and Excel files are made on your device.
Frequently asked questions
What do I get without a pass?
Without a pass, Impurity Thresholds (ICH Q3A/Q3B) for a Whole Impurity List shows the method, the limits that apply and the verdict for your input; computed figures stay hidden until the pass. Until you unlock it, the result can’t be downloaded or printed. An Ultimate pass, a one-time payment unless you choose automatic renewal, unlocks the full result. The pricing page lists the passes and their prices.
What does the Ultimate pass add here?
This tool in full, and every other Pro, Premium and Ultimate tool, for 7 days, 30 days or a year (a pass bought with PayPal leaves out email-address extractors). The pass is a one-time payment unless you choose automatic renewal.
What is the identification threshold for a dose of 1.5 g a day?
Under Q3A(R2) it is 0.10 % or 1.0 mg per day intake, whichever is lower. At 1.5 g a day, 1.0 mg is about 0.067 % of the dose, so the 1.0 mg intake applies: an impurity is above it when its reported result, converted to an intake and rounded to one decimal, is more than 1.0 mg.
How is a result compared with a threshold?
A threshold in % is compared with the reported result rounded to the threshold’s decimals; a threshold given as an intake with the reported result converted to an intake (result × maximum daily dose) and rounded to the threshold’s decimals. A result equal to a threshold does not exceed it.
Do I report a result of 0.044 % against a 0.05 % threshold?
No: rounded to two decimals it is 0.04 %, which is not above the 0.05 % reporting threshold. A result of 0.0963 % is reported as 0.10 %.
What goes into the specification?
Each specified identified impurity, each specified unidentified impurity above the identification threshold, any unspecified impurity with an acceptance criterion not more than the identification threshold, and the total. Each criterion is set no higher than the level its safety data qualify.
Can I open the export of the HPLC impurity calculation?
Yes: open its Excel file and the list is read from its Impurities sheet (the peak names and the calculated results).