In Silico Assessments
High-quality (Q)SAR analysis to qualify impurities in pharmaceuticals, biologics and medical devices — from ICH M7 mutagenicity to ISO 10993-18/-17 extractables & leachables risk assessment — without animal testing, whenever feasible.
Who we are
INSIAS is a Belgium-based consultancy supporting pharmaceutical and biotech companies, as well as medical device manufacturers, in the qualification of product-related impurities — while avoiding animal testing whenever feasible.
When adequate experimental data are absent, ICH M7 prescribes a structure-based (Q)SAR assessment: the impurity is evaluated with two complementary methodologies — an expert rule-based system and a statistical model. When both are negative, the impurity is considered non-mutagenic and no further testing is required. (Q)SAR models also support other endpoints — mutagenicity, genotoxicity, carcinogenicity, skin sensitization and irritation, specific organ toxicity among others — and the same weight-of-evidence approach underpins the toxicological risk assessment of medical device extractables and leachables (ISO 10993-18 / ISO 10993-17).
Ames alert · aromatic amine
4-Aminobiphenyl · C₁₂H₁₁N
Structure-based prediction
of toxicological endpoints
Services
Our core service: basic reviews and detailed (Q)SAR reports using the leading platforms — Derek Nexus, CASE Ultra and Leadscope — selected per project and endpoint, for pharmaceutical impurities (ICH M7, ICH Q3A&B) and medical device E&L (ISO 10993-18/-17). On top of that, add a certified expert review or confirmatory testing when needed.
Our core service. Submit your chemical structure (mol file, SMILES, image…) and receive a detailed report based on the two complementary methodologies ICH M7 requires — an expert rule-based and a statistical model. Both negative → the impurity is considered non-mutagenic; no further testing.
On top of the basic review, we can perform a full expert review and interpretation of the toxicity prediction. Alerting structures, out-of-domain or conflicting calls are assessed for mechanistic plausibility and analogue data (read-across), refining or justifying the conclusion — reviewed, signed by a certified toxicologist and submission-ready.
In silico predictions can be overruled by in vitro or in vivo testing. Insias has access to a network of highly experienced CROs for Ames (OECD TG 471), LLNA (OECD TG 429) and repeat-dose toxicity studies. Compound unavailable? Our prequalified, world-class synthesis labs can make it for you.
Lhasa Limited
Derek Nexus is a leading expert rule-based toxicity system with SAR knowledge for 70+ endpoints — bacterial mutagenicity (Ames), chromosome damage, carcinogenicity, skin sensitisation with LLNA EC3 potency predictions, respiratory sensitisation, and skin & eye irritation alerts. Sarah Nexus applies a statistical, machine-learning approach to mutagenicity. Together they provide the two complementary (Q)SAR methodologies required by ICH M7, with transparent reasoning that facilitates expert review. (Lhasa Limited)
MultiCASE
CASE Ultra offers validated expert rule-based and statistical models for bacterial mutagenicity — including strain-specific Ames models (TA98, TA100, TA1535, TA1537, E. coli) — built under a Research Collaboration Agreement with the US FDA, so both ICH M7 methodologies live in one system. It includes surrogate searching and tools that support expert review and final ICH M7 classification, alongside QMRF-documented models for chromosomal aberration, in vivo micronucleus, carcinogenicity, skin sensitization (LLNA and GPMT-based, with ECETOC potency categories) and skin & eye irritation. (MultiCASE)
Instem
Leadscope Model Applier combines expert alerts with a suite of 100+ statistical QSAR models, developed partly in collaboration with the US FDA. Its dedicated ICH M7 module integrates both methodologies into a documented decision framework, and its genetox suite covers bacterial mutation, in vitro chromosomal aberration and in vivo micronucleus. Sensitization models predict the LLNA outcome with ECETOC potency categories, acute toxicity models predict GHS categories, and its read-across environment — with over 400,000 curated toxicity studies, including skin & eye irritation — supports systemic endpoints and device E&L. (Instem)
How it works
Send us your impurity or NCE as a mol file, SMILES or image — or an extractables & leachables list for a given drug product or medical device.
Your compound runs through both ICH M7 methodologies — expert rule-based and statistical — for the relevant endpoints;
Positive, out-of-domain or conflicting calls are refined through read-across and mechanistic reasoning — signed by a certified toxicologist on request.
Submission-ready report with risk characterization: expected exposure versus the acceptable intake — the TTC or a compound-specific PDE. In case adequate safety margins are not reached, a follow-up safety qualification strategy is proposed.
Why in silico
When both methodologies are negative, ICH M7 considers the assessment complete — no Ames test, no in vivo studies. Fully aligned with the 3Rs.
ICH M7 for pharmaceutical impurities; ISO 10993-18/-17 for medical device extractables & leachables — hazard assessment followed by risk characterization.
Two complementary methodologies, a documented rationale and certified sign-off — conclusions built to withstand regulatory scrutiny.
Exposure assessed against the acceptable intake — the TTC (1.5 µg/day) or a compound-specific limit, with stricter limits for the cohort of concern (aflatoxin-like, azoxy and N-nitroso compounds).
Contact
Tell us about your impurity or compound and the endpoint of concern. We'll get back to you with a proposal and turnaround time.
