Pibrentasvir Production Cost Reports

The report provides a detailed analysis essential for establishing a pibrentasvir production plant. It encompasses all critical aspects necessary for pibrentasvir production, including the cost of pibrentasvir production, pibrentasvir plant cost, pibrentasvir production costs, and the overall pibrentasvir production plant cost. Additionally, the study covers specific expenditures associated with setting up and operating a pibrentasvir production plant. These encompass production processes, raw material requirements, utility requirements, infrastructure needs, machinery and technology requirements, manpower requirements, packaging requirements, transportation requirements, and more.

Pibrentasvir is a strong NS5A (multifunctional phosphoprotein) inhibitor that is used in combination with glecaprevir. It is utilised as a fixed-dose oral therapy for treating acute and chronic hepatitis C virus (HCV) infections across all genotypes. It is utilised in adults and pediatric patients aged 3 years and older, including those without cirrhosis, with compensated cirrhosis. It is used in prior treatment failures to NS5A or NS3/4A inhibitors, HIV co-infection, severe renal impairment or on dialysis, and post-liver or kidney transplant recipients. It supports shorter 8-week durations for treatment-naïve, non-cirrhotic patients, thereby expanding treatment access without genotype-specific dosing. Its common side effects include headache, fatigue, nausea, itching, diarrhoea, and weakness, mostly mild with low discontinuation rates.

The pibrentasvir market is fuelled by growing hepatitis C virus (HCV) infections around the world. The rising incidence in high-risk groups like those with HIV co-infection, post-transplant patients, and pediatric populations aged 3 years and older contributes to its market growth. The expanding regulatory approvals, like the U.S. FDA, make it useful as a first-line pan-genotypic therapy for both acute and chronic cases boosts its demand. The technological advancements in direct-acting antivirals (DAAs) and increasing healthcare investments in developing markets support its market. The industrial pibrentasvir procurement is affected by supply chain dependencies on API manufacturers, raw material volatility, and regulatory compliance for Good Manufacturing Practices (GMP).

Raw Material for Pibrentasvir Production

According to the pibrentasvir production plant project report, the key raw materials used in the production of pibrentasvir include aryl halide precursors, 3,5-difluoro-4-(4-(4-fluorophenyl)piperidin-1-yl)aniline, tris(dibenzylideneacetone)dipalladium, and toluene.

Production Process of Pibrentasvir

The extensive pibrentasvir production cost report consists of the following major industrial production process:

1. From aryl halide precursors and  3,5-difluoro-4-(4-(4-fluorophenyl)piperidin-1-yl)aniline: The production of pibrentasvir involves initial coupling of key aryl building blocks. This is followed by reaction with 3,5-difluoro-4-(4-(4-fluorophenyl)piperidin-1-yl)aniline via extraction and silica gel chromatography. After that, a palladium-catalysed coupling using tris(dibenzylideneacetone)dipalladium takes place, followed by purification through chromatography. Then deprotection proceeds via filtration through Celite and toluene and acetic acid treatment with chromatography. This is followed by Boc deprotection in 1,4-dioxane, which yields the penultimate amine after partitioning with NaOH, and final pibrentasvir assembly occurs through amide coupling, to give pibrentasvir.

Pibrentasvir has the molecular formula of C57H65F5N10O8 and an average molecular weight of 1113.2 g/mol. It contains 8 defined stereocenters (absolute stereochemistry) and 5 fluorine atoms. It appears as a white to off-white solid powder with low aqueous solubility, typical of lipophilic antivirals. Its structure includes a 19-membered macrocycle with imidazo[1,2-a]pyridine and fluorophenyl-pyrrolidine moieties linked by amide bonds, exhibiting high potency. It shows moderate metabolic interactions via UGT1A1/ABCB1/ABCG2 transporters, with a polar surface area and rotatable bonds supporting oral bioavailability in fixed-dose glecaprevir combinations despite its large size. All these physical and chemical properties make it useful as an NS5A inhibitor.