Quality, safety and regulatory · Quality and safety
“The extractables study produced a long peak list, and for most peaks we have neither a name nor an assessment.”
Extractables and leachables assessment: identification to toxicology
An E&L study quickly produces more peaks than a team can identify and assess. CovaSyn assigns the signals in your MS data to known additives, degradation products and monomers and gives a toxicological pre-assessment for each compound. Your lab and your toxicologist review and sign off the report.
Starting point
When you need this
- A primary packaging material, a single-use system or a component in the product path is being qualified or changed.
- The extractables screen shows peaks above the analytical evaluation threshold that nobody can assign.
- Leachables appear in the stability study and need to be matched against the extractables.
- The authority or the client asks for a toxicological justification for individual compounds.
Result
What you get
Identified compounds
Peaks assigned to structure proposals from accurate mass, isotope pattern and fragments, with a note on typical origin such as antioxidants, plasticisers or their degradation products.
Extractables and leachables correlation
Which leachables can be traced back to extractables and which are new, so you know where to look more closely.
Toxicological pre-assessment
For each compound, structural alerts, ICH M7 classification and an applicability domain check, as the basis for assessment against the safety threshold.
Report for sign-off
Identity, confidence of the assignment and toxicological notes per compound, prepared so your experts can review and approve them.
Three ways
Yourself, together, or done for you
Run it yourself
Draw the molecule in the sketcher or use the tools through the CovaSyn MCP directly in Claude, ChatGPT or Cursor.
Go to MCPLearn it together
In a workshop your team learns how to answer questions like this with AI, cleanly and traceably.
See workshopsDone for you
We run the evaluation with our tools and deliver the finished report. Your expert reviews and signs off.
See Done-for-You
CovaSyn
The tools behind it
Deterministic calculations instead of guessed answers: the same tools we use for Done-for-You work are available to you directly.
Covams
Extractables and leachables evaluation, unknown peak analysis, molecular formula, isotope pattern, fragment annotation, compound class and database search.
Covatox
ICH M7 classification, structural alerts, toxicological endpoints, applicability domain check, safety summary and report.
Audience
Who it is for
For analytical, quality assurance and regulatory affairs teams at contract labs, CDMOs, generics manufacturers and packaging suppliers, wherever E&L data are generated faster than they can be assessed.
What the computation does not replace
- Identification from MS data stays preliminary without a reference standard; for critical compounds we recommend confirmation in the lab.
- The toxicological pre-assessment does not replace assessment by a qualified toxicologist, for example the derivation of a PDE.
- Amounts without suitable calibration are estimates; different response factors can shift the assessment against the threshold.
Insights
Read on
Extractables and Leachables: A Screening Workflow
A structure-first extractables leachables screening workflow: match peaks to known additives, set the AET, then hand structures to toxicological triage.
Read articleUnknown Impurity Identification by LC-MS/MS
Unknown impurity identification by LC-MS: formula from accurate mass, RDBE, isotope pattern and MS/MS fragment logic, with real CovaMS tool output and its.
Read articleICH M7 Classification: Class 1 to 5, by Example
ICH M7 classification explained class by class, with the dual (Q)SAR assessment and five real impurities scored live by CovaTox, including NDMA.
Read articlePDE vs TTC in Cleaning Validation: The Genotoxic Case
PDE vs TTC cleaning validation: when a health-based PDE applies, when ICH M7 forces the 1.5 µg/day TTC, and how to check the residue is even cleanable.
Read articleApplicability Domain in QSAR: When a Model Says I Don't Know
What the applicability domain in QSAR is, how Tanimoto, feature range and leverage methods define it, and how CovaTox downgrades out-of-domain predictions.
Read article
Questions
Common questions
How does an extractables and leachables study work?
First the material is extracted under exaggerated conditions and screened, usually by LC-MS, GC-MS and ICP-MS. The extractables found are identified and assessed toxicologically, then the product is tested for leachables over its shelf life. USP <1663> and <1664> provide orientation; CovaSyn supports identification and assessment of the organic compounds in your MS data.
Who can assess extractables and leachables for us?
CovaSyn does this as Done-for-You: you describe material, product and data in the intro call, we agree on scope, and you typically receive the report within 5 working days once we have your data. Handled confidentially from the start.
What is the analytical evaluation threshold (AET)?
The AET converts a toxicological safety threshold in micrograms per day into a concentration in the extract or product above which a compound must be identified and assessed. It depends on daily dose, number of doses and an uncertainty factor for response. CovaSyn helps identify the peaks above this threshold and classify them toxicologically.
What should I do if many peaks in the E&L screen stay unknown?
Prioritise by concentration relative to the AET and by structural classes of concern. CovaSyn derives structure proposals from accurate mass and fragments, links them to typical polymer additives and their degradation products and flags where confirmation with a reference standard adds the most.
How are leachables assessed toxicologically?
Each compound is checked for mutagenic structural alerts and, where available, assessed with literature data; this yields a permitted daily amount against which the measured amount is compared. Covatox provides alerts, ICH M7 classification and endpoint predictions as the basis; your toxicologist makes the final assessment.
Can I run this assessment myself?
Yes. In the sketcher you draw candidate structures and see core data instantly; the MS and toxicology tools are available through the CovaSyn MCP directly in your AI assistant.
Quality, safety and regulatory
Related problems we solve
Next step
Tell us about your E&L question.
30 minutes on Microsoft Teams with the CovaSyn team. If it is not a fit, we will say so.