Ensitrelvir Fumaric Acid is a non-covalent, non-peptidic oral 3CL protease inhibitor developed for antiviral drug formulation. The molecule features a multi-ring heterocyclic structure comprising indazole, 1,2,4-triazole, and 1,3,5-triazinone cores, synthesized via a convergent coupling pathway. The active pharmaceutical ingredient selectively binds to the viral main protease to halt replication. Production parameters focus on stereochemical control and impurity elimination to meet current Good Manufacturing Practice standards for clinical trials and commercial scale-up.
Technical Specifications
|
Parameter |
Specification |
Test Method |
|
Assay (Purity) |
≥ 99.0% (anhydrous basis) |
High-Performance Liquid Chromatography |
|
Individual Impurity |
≤ 0.10% |
Gradient HPLC with Diode-Array Detection |
|
Total Impurities |
≤ 0.50% |
HPLC |
|
Water Content |
≤ 1.0% |
Coulometric Titration |
|
Residue on Ignition |
≤ 0.1% |
Gravimetric Analysis |
|
Heavy Metals |
≤ 10 ppm |
Inductively Coupled Plasma Mass Spectrometry |
|
Residual Solvents |
Compliant with ICH Q3C limits |
Headspace Gas Chromatography |
|
Appearance |
White to off-white crystalline powder |
Visual Inspection |
|
Solubility |
Soluble in DMSO; slightly soluble in polar organic solvents |
USP/EP Monograph |
Manufacturing and Supply Parameters
Synthetic Route: Convergent multi-step synthesis utilizing optimized coupling steps for indazole and triazole intermediates without heavy metal catalysts.
Crystallization: Controlled cooling parameters achieving uniform particle size distribution (D90 < 50 µm) without excessive milling.
Cleanroom Environment: Crystallization, isolation, and drying performed under ISO Class 8 conditions utilizing automated closed-system filtration.
Batch Capabilities: Pilot scale ranging from 10 kg to 50 kg per batch, scaling to commercial validation batches exceeding 300 kg with documented consistency.
Supply Stability: Routine stock maintenance for sample requests from 100g to 1kg alongside scheduled multi-ton annual supply arrangements.
Regulatory Documentation
Drug Master File: Comprehensive ICH CTD format documentation available for regulatory filing support.
Analytical Data: Certificate of Analysis, HPLC chromatograms, mass spectrometry, proton nuclear magnetic resonance, and elemental analysis provided with every batch.
Compliance Reports: TSE/BSE-free declarations, residual solvent testing reports, genotoxic impurity risk assessments, and elemental impurity profiling per ICH Q3D.
Stability Data: Accelerated (40°C / 75% RH) and long-term (25°C / 60% RH) testing reports confirming solid-state stability.
Packaging and Storage
Primary Packaging: Double-layer medical-grade low-density polyethylene bags, heat-sealed under a conditioned nitrogen atmosphere.
Secondary Packaging: Rigid fiber drums or tamper-evident aluminum-laminated tins providing mechanical protection during freight transport.
Traceability Labeling: Outer packaging displays nomenclature, CAS number, batch number, net weight, gross weight, manufacturing date, re-test date, and storage instructions.
Storage Conditions: Store in a dry, dark environment between 2°C and 8°C.
Pharmaceutical Applications
Oral Antiviral Formulations: Serves as the primary active substance for formulating antiviral tablets targeting 3CL protease activity. Precise particle sizing ensures high content uniformity in direct compression and wet granulation processes, supporting predictable dissolution kinetics and bioavailability.
Analytical Reference Standard: Utilized by quality control laboratories to establish validated HPLC assay methods and system suitability tests. High chemical purity minimizes baseline interference for precise quantification of degradation products.
Impurity Profiling: Applied as a benchmark substance to stress-test stability chambers and evaluate degradation pathways under diverse thermal and humidity conditions.
Process Development: Deployed in pilot plant environments to optimize downstream processing parameters, powder flowability, and excipient compatibility. Optimized crystal morphology reduces static accumulation during powder handling.
FAQ
Q: What is the certified purity level for commercial orders?
A: The standard commercial grade maintains an HPLC purity of ≥ 99.0% with individual known impurities controlled below 0.10%.
Q: What documentation supports regulatory drug applications?
A: A complete CTD-format Drug Master File, including synthetic routes, impurity profiles, analytical validation reports, and stability data, is accessible under confidentiality agreements.
Q: What are the recommended storage conditions?
A: Store in airtight, nitrogen-purged containers protected from light and moisture, maintained at 2°C to 8°C.
Q: Is analytical reference data included with initial sample shipments?
A: Every sample shipment includes a batch-specific Certificate of Analysis alongside complete NMR, HPLC, and IR spectra verification records.
Q: What is the standard lead time for batch deliveries?
A: Sample quantities dispatch within 3 to 5 business days, while commercial tonnage orders follow scheduled manufacturing lead times specified in supply contracts.
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