Patisiran is a chemically synthesized, double-stranded small interfering RNA (siRNA) active pharmaceutical ingredient designed to target transthyretin (TTR) messenger RNA. It belongs to the advanced class of RNA interference-based therapeutics and is used as a specialized oligonucleotide drug substance.
Patisiran is identified by CAS Number 1420706-45-1. The pharmaceutical active substance is generally supplied as Patisiran Sodium. FDA information gives the molecular formula as C412H480N148Na40O290P40 and molecular weight as approximately 14,304 Da.
Unlike conventional low-molecular-weight APIs, Patisiran is a large oligonucleotide requiring specialized manufacturing and analytical controls. Its production involves controlled solid-phase oligonucleotide synthesis, cleavage and deprotection, purification, duplex formation and lyophilization.
Patisiran Sodium is described as a white to off-white, hygroscopic powder. It is soluble in water and phosphate-buffered saline. Because of its oligonucleotide structure, quality evaluation requires specialized analytical techniques rather than relying only on conventional pharmaceutical API tests.
Regulatory characterization includes molecular-mass determination, duplex identity, chromatographic purity, assay, thermal melting analysis, sodium content, water determination, elemental impurity testing, residual-solvent analysis, bacterial endotoxin testing and microbiological quality assessment.
The manufacturing process for Patisiran involves several controlled stages. The oligonucleotide strands are produced through solid-phase synthesis followed by cleavage and deprotection. The crude material is then purified to remove truncated sequences, deletion products, addition products and other process-related impurities.
The complementary strands are subsequently combined through controlled duplex formation or annealing. The final active substance is subjected to further purification and lyophilization to obtain the required drug-substance form.
Due to the complexity of oligonucleotide manufacturing, specialized facilities, validated analytical procedures and tightly controlled environmental conditions are required.
Quality control for Patisiran focuses on characteristics that are particularly important for siRNA drug substances. These include identity, molecular mass, sequence integrity, duplex formation, chromatographic purity and related oligonucleotide impurities.
Regulatory analytical methods include SE-HPLC, AX-HPLC, LC-MS, thermal analysis, Karl Fischer water determination, ICP-MS or equivalent elemental analysis and GC for residual solvents.
Microbiological controls such as bacterial endotoxin and bioburden testing are also applicable to the active substance.
Patisiran is an RNA interference therapeutic that targets transthyretin (TTR) mRNA. Reduction of TTR messenger RNA results in decreased production of transthyretin protein.
The API is therefore relevant to pharmaceutical development programs involving RNA therapeutics, siRNA technology, oligonucleotide drug substances and advanced genetic medicines.
Patisiran is categorized as a specialized siRNA API, oligonucleotide API and RNA therapeutic API, rather than a conventional small-molecule pharmaceutical ingredient.
Patisiran is hygroscopic and requires controlled storage conditions. Regulatory stability information supports storage at approximately −20°C ± 5°C for the active substance.
Appropriate packaging should protect the material from moisture and maintain the required temperature throughout storage and handling.
Patisiran Sodium is a highly specialized pharmaceutical drug substance requiring expertise in oligonucleotide synthesis, purification, duplex formation and advanced analytical characterization.
For commercial pharmaceutical applications, Patisiran API should be evaluated against the applicable approved drug-substance specification and validated analytical methods. Public regulatory documents do not disclose every commercial numerical acceptance criterion, so specification-dependent values should not be replaced with generic small-molecule API limits.
| 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 1.0% |