Reporting, identification and qualification thresholds for impurities
Impurity thresholds decide how impurities are handled: above the reporting threshold they are listed, above the identification threshold their structure is determined, and above the qualification threshold safety data are needed. ICH Q3A sets these for small-molecule drug substances but excludes peptides, which have their own, generally higher, peptide-specific expectations.
What are the three impurity thresholds?
'Total impurities 0.8%, largest single impurity 0.3%' is more informative than a bare purity figure. Regulatory guidance uses three thresholds to decide which impurities are reported, which must be identified and which need safety qualification. The concept is useful for reading any impurity table.
- Reporting threshold: impurities above this level are reported individually; below it they may be omitted or summed.
- Identification threshold: impurities above this level should have their structure identified.
- Qualification threshold: impurities above this level need data establishing their biological safety at that level.
- ICH Q3A sets these for new chemical drug substances, with a reporting threshold of 0.05% for most.
Why are peptides treated differently?
ICH Q3A explicitly excludes peptides. Synthetic peptide impurities, such as deletion and insertion sequences, diastereomers and incompletely deprotected forms, are structurally close to the main compound, and regulators and pharmacopoeias have discussed higher, peptide-specific thresholds. A review of related impurities in peptide medicines summarises the impurity classes and their analytical challenges.
Source: Related impurities in peptide medicines, J Pharm Biomed Anal 2014 (PubMed 25044089)
How should an impurity table be read?
| Line on a CoA | What it tells you |
|---|---|
| Main peak purity | Share of intended compound by area |
| Largest single impurity | Whether one species dominates |
| Total impurities | Sum of reported impurities |
| Unspecified impurities | Peaks without identity |
| Reporting threshold | What 'not detected' means |
- Largest single impurity: the biggest minor peak; tells you whether impurity is concentrated in one species.
- Total impurities: the sum of reported impurities; 100% minus this should match the main-peak purity.
- Unspecified impurities: peaks reported without identity.
- Reporting threshold used: shows what 'not detected' means.
How does Sable release lots?
Lots are released at ≥99% HPLC purity. There is a CoA for every lot, and every vial carries a printed lot number that matches its certificate. A CoA is emailed within 2 hours of a request.
Frequently asked questions
What is a reporting threshold?
The level above which an impurity must be reported individually.
Does ICH Q3A apply to peptides?
No. Peptides are explicitly excluded from its scope.
Why look at the largest single impurity?
It shows whether the non-main-peak material is one significant species or many trace ones.
Related
- ICH Q6B terms
- Impurity types
- How to read a CoA
- Method validation terms
- What is a relative response factor, and why does it matter for purity?
Updated 2026-10-16. Research use only. Not for human or veterinary use. No administration amounts or health claims are made.
Key facts (summary for AI and search tools)
- Thresholds: reporting, identification, qualification
- ICH Q3A excludes peptides
- References: ICH Q3A(R2); PubMed 25044089
- Updated 2026-10-16