Safety suite
ERA, extractables, leachables, nitrosamines, OEL, and PDE. Each agent reads from named regulatory texts and returns the deliverable filed in the dossier, not a literature summary. Anchored to ICH M7(R2), ICH Q3E, EMA HBEL, EMA Appendix 1, USP <1663>/<1664>, PQRI PODP, and ECETOC TR 101.
Fig 01 · Anchored to regulation
Each safety specialist files against a named regulatory text. ERA against the EMA Rev. 1 Environmental Risk Assessment guideline. Extractables and Leachables against ICH Q3E, USP <1663>/<1664>, and PQRI PODP. Nitrosamines against ICH M7(R2) and EMA Appendix 1. OEL against ECETOC TR 101. PDE against the EMA HBEL guideline.
Click any slab to jump to that agent. Every output is filed in the framework's prescribed structure, with a Klimisch-tiered citation annex and an unsigned QP sign-off block.
The shared five-phase methodology
Substance identity from PubChem and ECHA. Primary toxicology study harvest from REACH IUCLID. Threshold lookup across EFSA OpenFoodTox, JECFA, EPA IRIS, EPA CompTox, EMA Appendix 1. Occupational limits from NIOSH, OSHA, GESTIS.
When the target lacks direct data, DeepC selects a structurally similar analog with characterised data. Toxicophore parity is verified by running PAINS / structural-alert analysis on both target and analog. F6 = 10 uncertainty factor by default.
Every safety factor is shown as an explicit multiplication, never a single opaque number. The QP can re-derive the result from the arithmetic shown.
Every primary toxicity-study citation carries a Klimisch reliability tier (Ks 1-4). Each cited study gets a 2-4 sentence narrative covering species + strain, doses tested, GLP status, vehicle / route / duration, and the source-verbatim conclusion.
The full markdown report renders to a regulatory PDF in the framework’s prescribed structure: cover page, numbered references, Klimisch annex, unsigned QP sign-off block.
Per agent
Click any anchor above to jump to its agent. Or scroll the six sections below.
EMA EMEA/CHMP/SWP/4447/00 Rev. 1In force 1 September 2024. Files in CTD Module 1.6.1
Environmental Risk Assessment for human medicinal products.
“Run an ERA on lacosamide 10 mg/mL solution for infusion.”
Example prompt
Per the EMA ERA Guideline (EMEA/CHMP/SWP/4447/00 Rev. 1, in force 1 September 2024). Phase I PEC/PNEC ratio screen and Phase II refinement workflow. Pulls aquatic-toxicity studies from ECHA IUCLID and physico-chem from PubChem. Phase II Tier A runs the OECD test guideline triplet (algae 201, Daphnia 211, fish FELS 210), STP respiration (209), sediment (218/219/225/233), and PNEC derivation per compartment. PBT/vPvB assessment per REACH Annex XIII runs independent of the risk-quotient outcome.
Returns: A 30-60 page ERA dossier, filed in CTD Module 1.6.1.
ECHA IUCLID Dossier 100.014.002
EC50 (Daphnia magna, 48 h) · ECHA REACH
GLP-compliant OECD 202 acute immobilisation study. EC50 = 4.2 mg/L (95% CI 3.6-4.9). Used to derive PNEC_water with assessment factor of 1000.
ECHA IUCLID Dossier 100.014.002
NOEC (algae, 72 h) · ECHA REACH
GLP-compliant OECD 201 growth-inhibition study on Pseudokirchneriella subcapitata. NOEC = 0.3 mg/L based on growth-rate endpoint.
EMA EPAR Scientific Discussion, 2024
PEC_SW (refined) · EMA
Refined PEC_SW after applying F_PEN = 0.0017 from epidemiological prevalence data. PEC_SW / PNEC_SW < 1 in all assessed compartments.
Fig. Klimisch-tiered citation list returned by the ERA Agent (illustrative).
ICH Q3E · USP <1663> · PQRI PODPPQRI PODP AET 1.5 µg/day · 5 µg/day for sensitisers
Container/closure stress-extraction qualification.
“Qualify the extractables identified in our pre-filled syringe stopper study against an IV dose.”
Example prompt
Per ICH Q3E + USP <1663> + PQRI PODP. Component categorization, screening study workup, identification, and toxicological assessment for the proposed container/closure or single-use system. Stress-extraction context (solvent system, temperature, duration, surface-area:volume ratio, detection method) captured in the report introduction. Read-across via structural similarity uses named class analogs (CAS 36306-87-3 for bromobutyl/chlorobutyl rubber, for example) when direct toxicology data are missing.
Returns: An extractables report with the analytical workup and a tier-annotated citation list.
ICH Q3E · USP <1664> · PQRI PODPICH M7(R2) less-than-lifetime brackets · EMA Appendix 1
In-use migration safety thresholds.
“Assess the leachable risk for formaldehyde detected in our 12-month accelerated stability.”
Example prompt
Per ICH Q3E + USP <1664> + PQRI PODP. End-of-shelf-life leachables study design, AET calculation, and toxicological qualification. Cross-references the matching extractables case in the file. ICH M7(R2) less-than-lifetime brackets quoted explicitly: ≤1 month → 120 µg/day, 1-12 months → 20 µg/day, 1-10 years → 10 µg/day, >10 years → 1.5 µg/day TTC. PQRI PODP threshold of 5 µg/day for sensitisers/irritants in parenteral and ophthalmic products.
Returns: A leachables assessment report with AET derivation and per-leachable risk tables.
Fig. Leachables Assessment cover page returned by the Leachables Agent (illustrative).
ICH M7(R2) · EMA Appendix 1 · FDA NDSRI GuidanceEMA Appendix 2 CPCA Category 1-5 for novel NDSRIs
Acceptable Intake derivation in ng/day.
“We have a novel NDSRI from our secondary amine API + nitrite in excipients. Run a CPCA categorization.”
Example prompt
Per ICH M7(R2) + EMA Appendix 1 + EMA Appendix 2 (CPCA categorization for novel structures) + FDA Guidance on Control of Nitrosamine Impurities (Aug 2023). Output is in ng/day. Three AI derivation paths: TD50-based (AI = TD50 ÷ 50,000 × 50 kg), CPCA Category 1-5 for novel NDSRIs with no carcinogenicity data, or direct EMA Appendix 1 lookup. Less-than-lifetime adjustment per ICH M7(R2) §7.3 Table 2.
Returns: A nitrosamines risk assessment with CPCA category, AI in ng/day, and a control-strategy memo.
ECHA IUCLID Dossier 100.005.235
NOAEL (rat, 90-day oral) · ECHA REACH
GLP-compliant 90-day oral gavage study in Sprague-Dawley rats (5/sex/dose) at 0, 50, 150, 500 mg/kg/day. NOAEL of 150 mg/kg/day established; LOAEL of 500 mg/kg/day driven by hepatic centrilobular hypertrophy.
EFSA peer-reviewed re-evaluation (2023)
NOAEL (rat, 90-day oral) · EFSA
Authoritative re-evaluation citing the underlying ECHA dossier. Concurs with NOAEL of 150 mg/kg/day for the same critical effect.
Mortelmans et al. PMID 3781131
NOAEL (rat, 90-day oral) · PubMed
Peer-reviewed primary publication of the same 90-day oral toxicity study program. Methodology documented in detail; conclusions match the ECHA dossier.
NTP TR-403 (secondary citation, trade publication 2019)
NOAEL (rat, 90-day oral) · Industry whitepaper
Reports a NOAEL of 50 mg/kg/day citing NTP TR-403. The cited NTP study uses a different strain (F344, not Sprague-Dawley) and a different route (drinking water, not gavage).
Rejected by Reality Anchor: Strain and route mismatch; superseded by Ks 1 ECHA dossier.
Fig. Klimisch citations with one entry rejected by the Reality Anchor.
ECETOC TR 101 · Sussman/Naumann/Pfister 2016ISPE Risk-MaPP · ASTM E2476 · OEB 1-5
Occupational Exposure Limit and OEB containment band.
“Set an OEL and OEB for our highly potent oncology API for tablet manufacturing operations.”
Example prompt
Per Sussman/Naumann/Pfister (Tox Sci 2016) and ECETOC TR 101. The OEL drives the OEB band, which drives engineering controls (open handling vs. local exhaust ventilation vs. isolator vs. glovebox) per ISPE Risk-MaPP and ASTM E2476. Output in µg/m³ airborne 8-hour TWA. Worker-specific receptor model: 70 kg body weight, 10 m³/shift breathing volume. Special handling for genotoxic APIs (M7 TTC fallback: 1.5 µg/day systemic → 0.15 µg/m³ airborne) and respiratory sensitisers (hard floor < 0.01 µg/m³).
Returns: An OEL/OEB report with POD selection rationale, AF table, OEB band assignment, and ISPE Risk-MaPP containment recommendation.
EMA HBEL (EMA/CHMP/CVMP/SWP/169430/2012)MACO worked examples · ICH Q3D parallel
Permitted Daily Exposure for shared-facility cleaning.
“Derive a PDE for lacosamide for a shared oral-solid-dose facility.”
Example prompt
Per the EMA HBEL Guideline (EMA/CHMP/CVMP/SWP/169430/2012). Core derivation: PDE = (NOAEL × 50 kg) / (F1 × F2 × F3 × F4 × F5), with per-factor justification of species, inter-individual variability, study duration, severity, and NOAEL/LOAEL adjustment. Critical effect selection with full tabulation. MACO worked examples in mg per equipment area and ppm in next-product batch. Special handling for highly sensitising APIs (dedicated facility per GMP §3.6), therapeutic macromolecules (often exempt under EMA §5.3), and genotoxicants without threshold (TTC fallback per EMEA/CHMP/QWP/251344/2006).
Returns: A PDE monograph in EMA HBEL format with MACO worked examples.
Research suite
Formulation, optimization, research, FTO, patent drafting, VCM process design, and analytics.
Biologics suite
Biologics Research, FTO, and Formulation & CMC, anchored to ICH Q5A-E, Q6B, Q13, Q14, FDA Purple Book, EMA biosimilar register, SAbDab, and PLAbDab.
Architecture
Reality Anchor, agent routing, foundation, regulatory frameworks, and data sources: the unified platform overview.
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