Ponesimod is a selective sphingosine-1-phosphate (S1P) receptor modulator used as an active pharmaceutical ingredient in medicines for relapsing forms of multiple sclerosis. The API is chemically identified as (2Z,5Z)-5-[3-chloro-4-[(2R)-2,3-dihydroxypropoxy]benzylidene]-3-(2-methylphenyl)-2-(propylimino)-1,3-thiazolidin-4-one. Ponesimod has the molecular formula C23H25ClN2O4S and a molecular weight of 460.97 g/mol. Its CAS Number is 854107-55-4. The FDA describes ponesimod as having one chiral center with the absolute R configuration.
Ponesimod is the active pharmaceutical ingredient in PONVORY, an oral medicine approved for the treatment of relapsing forms of multiple sclerosis, including clinically isolated syndrome, relapsing-remitting disease and active secondary progressive disease in adults. The current FDA labeling identifies PONVORY as an S1P receptor modulator, with a recommended maintenance dosage of 20 mg once daily following the required dose-titration regimen.
Ponesimod is a synthetic small-molecule API with a thiazolidinone-based chemical structure containing chlorine, sulfur, nitrogen and oxygen functional groups. Its stereochemical configuration is important because the molecule contains a single chiral center. Regulatory characterization has included elemental analysis, infrared spectroscopy, UV spectroscopy, proton and carbon NMR, mass spectrometry and single-crystal X-ray analysis to establish its structure and absolute configuration.
According to the EMA assessment report, the active substance is a white to light yellow, non-hygroscopic crystalline powder. Different polymorphic forms were identified during development, while the commercial manufacturing process routinely produces the intended commercial polymorphic form.
FDA product information describes ponesimod as a white to light yellowish powder that is practically insoluble or insoluble in water. The EMA assessment also identifies ponesimod as photosensitive and states that it is stored protected from light.
Ponesimod API is primarily used in the manufacture and development of pharmaceutical products intended for:
The approved PONVORY product contains ponesimod in multiple tablet strengths ranging from 2 mg to 20 mg, with 20 mg once daily being the recommended maintenance dose after titration.
Ponesimod is a relatively complex non-compendial API for which regulatory quality specifications are established through the product's approved pharmaceutical dossier rather than a publicly available universal pharmacopoeial monograph.
The EMA assessment report confirms that the active-substance specification follows ICH Q6A and includes appearance, IR identification, residue on ignition according to Ph. Eur., residual solvents by GC, impurities by HPLC, assay by HPLC and particle-size distribution by laser light diffraction. Impurity limits were established according to ICH Q3A.
Importantly, the public EMA report does not disclose the numerical acceptance limits for the active-substance assay, individual impurities or total impurities because confidential specification information has been removed. Therefore, unsupported values should not be represented as official Ponesimod API release specifications.
A Ponesimod API manufacturer in India should maintain strong control over stereochemical purity, polymorphic form, related substances, residual solvents and assay. Regulatory development information confirms that the commercial manufacturing process consistently delivers the intended polymorphic form and that analytical methods for the active substance were appropriately validated.
Manufacturing and quality-control programs should therefore incorporate validated chromatographic methods, appropriate reference standards, controlled environmental conditions and suitable packaging. Because ponesimod is photosensitive, protection from light is an important consideration during storage and handling.
Ponesimod API should be packaged in a suitable pharmaceutical-grade, tightly closed container that protects the material from light and environmental contamination. The EMA assessment reports that ponesimod is non-hygroscopic and photosensitive, with the active substance stored protected from light.
Commercial packaging and storage conditions should ultimately follow the validated stability data and the applicable approved API specification.
Typical documentation for Ponesimod API can include:
Ponesimod is an established S1P receptor modulator with a defined pharmaceutical application in relapsing multiple sclerosis. Its well-characterized chemical structure, CAS Number 854107-55-4, defined R stereochemistry and established regulatory quality-control framework make it a specialized API for controlled pharmaceutical manufacturing.
For pharmaceutical companies sourcing Ponesimod API from India, key quality considerations include identity, assay, chromatographic purity, residue on ignition, residual solvents, particle-size distribution, polymorphic form and protection from light.
| Parameter | Specification |
|---|---|
| Appearance | white to off-white crystalline powder |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | 98.0% – 102.0% |
| Loss on Drying | NMT 0.5% |
| Residue on Ignition | NMT 0.1% |
| Individual Impurity | NMT 0.5% |
| Total Impurities | NMT 1.0% |
| Water Content | NMT 0.5% |