Ioversol Production Cost Reports

The report provides detailed analysis essential for establishing an ioversol production plant. It encompasses all critical aspects necessary for ioversol production, including the cost of ioversol production, ioversol plant cost, ioversol production costs, and the overall ioversol production plant cost. Additionally, the study covers specific expenditures associated with setting up and operating an ioversol 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.

Ioversol Market Analysis: Demand and Supply Analysis, and Sourcing

Ioversol is a non-ionic, low-osmolality iodinated contrast agent, with iodine accounting for almost half of its mass. Its chemical name is N,N'-bis(2,3-dihydroxypropyl)-5-[N-(2-hydroxyethyl)glycolamido]-2,4,6-triiodoisophthalamide. This structure consists of a benzene ring with three iodine atoms and three sugar-like arms. These arms allow the heavy, iodine-rich molecule to dissolve in water at concentrations above 125% weight by volume without ionizing. Mallinckrodt developed ioversol and marketed it under the brand name Optiray. The molecule has been used clinically since the 1980s. Its structure includes three iodine atoms, two amide arms, a glycolamido group, and a hydroxyethyl tail, all designed to support its intended function.

Demand for ioversol comes from diagnostic imaging and depends more on scanner installations and procedure volumes than on disease prevalence. Computed tomography, angiography, urography, venography, and interventional procedures all require iodinated contrast injections. The volume used per procedure can be substantial. A single bottle holds 500 milliliters at a concentration of up to 741 milligrams of ioversol per milliliter, containing approximately 370 grams of active ingredient. Contrast media are therefore among the highest-volume active ingredients in the pharmaceutical industry. Scanner numbers, procedure mix, injection protocols, bolus volume, repeat studies, and single-use policies collectively determine demand. Imaging activity is the main demand driver.

Supply is divided between the original manufacturer and a growing group of Asian suppliers. Trade databases list 10 ioversol API suppliers, with five US drug master files, no Certificates of Suitability, and 117 finished-product dossiers. Named suppliers include Guerbet, Mallinckrodt, Jiangsu Hengrui Medicine, Divi's Laboratories, Hainan Poly Pharm, Brother Enterprises, and Sandoo Pharmaceuticals. Country-level figures place six of the 10 suppliers in China, two in Ireland, one in France, and one in India. Starry Pharmaceutical has also registered an ioversol injection in China. Originator supply, Chinese generic APIs, Indian custom synthesis, and integrated contract manufacturing groups now compete in the same tenders, making the supplier landscape more competitive than before.

An ioversol demand and supply analysis must consider iodine prices, iodination yield, sterile filling capacity, and hospital tender behavior. Iodine prices establish the basic cost level and are among the most important cost factors. Recent assessments place iodine prices at approximately US$72,000 to US$73,000 per tonne across North America, Japan, Chile, and China. Upon receipt, buyers check identity using infrared spectroscopy and HPLC, along with assay, free iodide, free aromatic amine, individual and total related substances, residual solvents, heavy metals, and water content. Free iodide receives particular attention because it can indicate that the molecule is breaking down. Color, pH, heavy metals, elemental impurities, bacterial endotoxins, and water content also have specified limits that must be documented on the certificate of analysis. Given the high concentration of the active ingredient, specifications are expressed in grams rather than milligrams.

Summary of the Product, Grades, and Uses

Ioversol has the molecular formula C18H24I3N3O9, a molar mass of 807.11 g/mol, and the CAS number 87771-40-2. Iodine accounts for approximately 47.17% of its total mass, making it the most important factor in the cost model. The solid has a melting range of 186 to 198 degrees. Its water solubility exceeds 125% weight by volume, allowing concentrated injections to be prepared at all strengths. At the 320 strength, the formulated solution has a density of approximately 1.371 at body temperature. Formulators consider melting range, density, viscosity, osmolality, and solubility when developing the product. All these properties are influenced by its high iodine content.

Ioversol has one pharmaceutical grade, with strict specifications in absolute terms. The material is supplied according to the relevant monograph and supported by a drug master file. These limits are particularly important because patients may receive hundreds of grams of the substance. An impurity level of 0.1% can represent several hundred milligrams administered during a single study. Specifications cover appearance, identity, assay, free iodide, free aromatic amine, related substances, residual solvents, heavy metals & water content, and bacterial endotoxin. Reference standards and impurity standards form a separate, smaller product category. Hospitals use ioversol in its finished dosage form. Commercial packaging includes bottles, bulk packages for imaging, prefilled syringes, injector cartridges, and bulk containers. The 500-milliliter package is the most widely used format.

Main End-Uses of Ioversol

Contrast-enhanced computed tomography is the largest end-use segment for ioversol because of its high iodine content. Iodine strongly absorbs X-rays, allowing vessels and organs filled with the contrast agent to stand out against surrounding soft tissue. Optiray is available in strengths of 300, 320, and 350 milligrams of iodine per milliliter. These correspond to 636, 678, and 741 milligrams of ioversol per milliliter, respectively. Radiologists select the appropriate strength based on the type of study, scanner, catheter, and injection rate. Body weight, renal function, scan timing, the target vessel, and scanner generation also influence this choice.

Angiography and interventional procedures form the second-largest end-use segment, where viscosity is an important practical consideration. Ioversol's osmolality ranges from approximately 700 to 790 milliosmoles per kilogram, well below that of older ionic contrast agents. However, higher iodine concentrations also increase viscosity. The 350 strength has a viscosity of approximately 14 centipoise at room temperature and 9 centipoise at body temperature, making it routine to warm the bottle before injection. Power injectors, catheter size, and flow rate must all account for this viscosity. Warming cabinets, larger-bore catheters, higher injection pressure, shorter tubing, and slower injection ramps can help manage the thicker solution. High viscosity is the trade-off for achieving a high iodine concentration.

Urography, venography, and specialized imaging studies form the third end-use segment, generally requiring smaller volumes per case. Excretory urography, peripheral venography, cerebral angiography, and contrast-enhanced head studies all use the same product. Reference standards and analytical testing account for another portion of demand, while veterinary imaging contributes a small amount. Analytical quantities are used for method validation, impurity profiling, stability studies, and proficiency testing.

Ioversol Market Risks

Iodine availability and pricing, rather than technology, are the main commercial constraints for ioversol. Its manufacturing chemistry has been established since the 1980s, with few major technical secrets remaining. Iodine is sourced mainly from Chilean caliche deposits and Japanese brine, with SQM, Cosayach, Godo Shigen, and Iochem being important suppliers. These two countries effectively influence the price of the main raw material, and manufacturers cannot replace iodine with another element. Caliche grades, production decisions in Chile, Japanese brine output, inventory levels, and freight costs all affect iodine prices. This is why contracts often include price adjustment clauses to pass on changes in raw material costs.

Commercial and technical risks also affect the market, with competitive tender pricing being a major challenge. Iohexol, iopamidol, iopromide, and iodixanol compete for the same procedures, so hospitals often compare products based on price per bottle. The rapid growth of manufacturing capacity in China and India has put further pressure on margins. Supply concentration is another concern, as plant shutdowns have previously caused shortages in this product category. Clinical risks, including contrast-associated kidney injury & thyroid effects, and hypersensitivity reactions, also require continued attention to product labeling. The main risks include plant shutdowns, sudden increases in iodine prices, lost tenders, regulatory findings, and new competitor launches. A shutdown at a single manufacturing site can be enough to cause supply shortages.

Ioversol Production Process and Main Cost Drivers

Ioversol is made from triiodinated aminoisophthalic acid by amidation with an aminodiol, then elaboration of the amine into a glycolamido hydroxyethyl side chain.

1. By Amidation and Side Chain Elaboration of Triiodoaminoisophthalic Acid: The main inputs are 5-amino-2,4,6-triiodoisophthalic acid, thionyl chloride, 3-amino-1,2-propanediol, sodium carbonate, acetic anhydride, pyridine, glycolic acid, acetyl chloride, 2-chloroethanol, caustic soda, solvents including ethyl acetate, dimethylformamide, dimethylacetamide, toluene and methanol, chromatography media, and packaging.

The iodinated core is the main cost driver in ioversol production because of its high iodine content. The starting acid already contains three iodine atoms attached to one benzene ring, accounting for roughly half its weight. At current iodine prices, the iodine alone in one kilogram of finished ioversol is worth approximately US$34 before accounting for any production losses. The acid is manufactured upstream from isophthalic acid through nitration, reduction, and ring iodination. Few ioversol manufacturers would establish this entire production chain for a single product. The upstream process requires isophthalic acid, nitric acid, a reduction system, an iodinating reagent, and an iodine recovery loop. As a result, the iodinated core is already expensive before it enters ioversol production.

Building the two amide arms comes next, and the published route is unforgiving. The acid is converted to its di-acid chloride with thionyl chloride, isolated, then treated with 3-amino-1,2-propanediol in a polar aprotic solvent over a base. The four hydroxyls are then masked with acetic anhydride, because the next step attacks an amine and will not tolerate free alcohols. Protection and deprotection are pure cost with no product gain. Acetic anhydride, pyridine, ethyl acetate, acid washing, and brine washing all belong to that detour.

Side chain elaboration and purification finish the route. Acetoxyacetyl chloride, made from glycolic acid, acylates the ring amine, and the acetyl groups then come off under base. N-alkylation with 2-chloroethanol installs the hydroxyethyl group, and the crude product is purified chromatographically. Original reported yields were about eighty-three percent for the acylation and forty-eight for the alkylation. Commercial processes do far better, but every point of yield lost carries iodine with it. Chromatography media, eluent volume, fraction pooling, concentration, and drying all follow the final step. Purification is where the margin is won.

Main Factors Affecting Ioversol Production Cost

Ioversol production costs are driven primarily by iodine, which accounts for more than all other cost factors combined. At prices of around US$72,000 per tonne, the iodine contained in a single 500-milliliter bottle is worth approximately US$12 to US$13. Caliche grades, production decisions in Chile, Japanese brine output, inventory levels, and freight costs all influence this price. Iodine cannot be replaced because the imaging effect depends on the element itself. As a result, an ioversol manufacturing plant is largely an iodine-processing operation. The high value of iodine also affects inventory value, working capital, insurance, security, and hedging costs.

Iodine recovery is the next major cost factor and helps distinguish competitive plants from less efficient ones. Iodination and subsequent processing leave iodide in mother liquors, wash water, and spent reagent streams. Recovering this iodide, oxidizing it back into a usable form, and returning it to the production chain are standard practices rather than optional improvements. When iodine enters the effluent, the plant incurs both the cost of lost material and the cost of wastewater treatment. Recovery efficiency must therefore be included in any reliable cost model. The recovery loop includes iodide oxidation, extraction or adsorption, blow-out columns, filtration, and recycling. Although often overlooked by outsiders, this process is central to cost control.

The remaining costs come from production steps, solvents, and sterile filling. The manufacturing route includes acid chloride formation, bis-amidation, protection, acylation, deprotection, alkylation, and chromatography, resulting in high solvent consumption per kilogram. Dimethylformamide, dimethylacetamide, ethyl acetate, toluene, and methanol must be recovered or sent for incineration. Filling is another major cost center because the viscous solution, at a concentration of 741 milligrams per milliliter, fills slowly and is difficult to filter. Warm filling, particulate control, and terminal sterilization further increase the cost per bottle. Filtration area, filling speed, particulate limits, container-closure testing, and autoclave cycles all influence these costs.

Raw Materials for Ioversol Production Plant and its Procurement

The triiodinated acid is supplied by a limited number of manufacturers, mainly in China and India, along with integrated contrast media producers. Both iodine content and iodination quality are important. Assay, iodine distribution on the ring, free iodide, isomeric purity, and color affect the finished product and the performance of the production chain. Supply contracts therefore address lead times, iodine price adjustment clauses, minimum order volumes, audit rights, and change control.

These factors influence how a contrast media plant purchases and qualifies its raw materials. Contracts specify assay, free iodide, related substances, water content, and residue limits for the iodinated intermediate. They usually also include an iodine price adjustment clause. Supplier qualification involves audits, certificates of analysis, and trial batches that are processed into the finished active ingredient. Incoming material checks cover identity, assay by HPLC, free iodide, free amine, and residual solvents. Aminodiol and chloroethanol suppliers are qualified separately because each material has its own impurity risks. Locating the facility within an existing plant that iodinated aromatic compounds allows the sharing of iodine recovery systems and handling expertise. Iodine handling requires corrosion-resistant lines, sealed transfers, spill containment, vapor capture, and dedicated storage because iodine attacks most conventional materials.

Sustainability and Regulatory Requirements

Ioversol manufacturing has an environmental profile similar to that of an iodination plant, with halides, solvents, and salts being the main concerns. Iodide-containing wastewater is a key issue, and the iodide is recovered rather than discharged because iodine is valuable. Large volumes of spent amide solvents are generated, requiring both solvent recovery stills and licensed incineration. Thionyl chloride and acid chloride processes produce acidic vent streams that require scrubbing. Iodinated organic compounds can persist in water, and contrast media residues are increasingly being detected in treated effluent and surface water. Controlling these discharges therefore remains an active area of concern. The environmental budget includes iodide recovery, solvent recovery stills, acid scrubbers, wastewater treatment, and licensed incineration.

Pharmacopoeial requirements and licensing rules govern the product. Manufacturers submit a Type II drug master file, comply with FDA current Good Manufacturing Practice (cGMP) requirements under 21 CFR Parts 210 and 211, and meet the relevant pharmacopoeial monograph requirements for the active ingredient. Finished injections require separate approvals, with specifications for sterility, endotoxins, particulate matter, and container-closure integrity. ICH Q3A and Q3C address impurities and residual solvents, Q6A covers specification setting, and Q11 guides the control strategy. Elemental impurity testing under Q3D is particularly important because metals are used as reagents in the manufacturing process. Product labeling includes warnings about kidney injury, thyroid function, and hypersensitivity. Batch records, stability commitments, annual reporting, change filings, and pharmacovigilance requirements apply throughout the product's lifecycle.

CAPEX and OPEX for an Ioversol Production Plant

An Ioversol manufacturing plant is a multi-step fine chemical facility with an iodine recovery system and a sterile filling line. Initial capital investment covers the synthesis section, including glass-lined reactors, condensers, chloride handling systems with scrubbers, filter dryers, and solvent storage. Iodine recovery requires additional equipment, such as oxidation vessels, extraction or adsorption systems, blow-out columns, and corrosion-resistant iodine handling systems. Downstream processing requires chromatography columns, crystallizers, dryers, and milling equipment for controlled processing.

For an integrated manufacturer, sterile production capacity is the largest single capital expense. This includes compounding tanks, filtration systems, a bottle filling line, autoclaves, and a controlled warehouse. Aseptic production also requires cleanrooms, air handling systems, environmental monitoring, process validation, and qualified personnel. Operating costs are mainly driven by iodine, followed by other raw materials, solvents and energy, and then labor and testing. Ioversol plant setup costs are substantial when sterile filling facilities are included but relatively moderate when the plant produces only the active ingredient. The workforce requires specialized skills in both chemical manufacturing and aseptic operations. The cost per kilogram depends primarily on iodine prices, iodine recovery efficiency, overall chemical yield, and solvent recycling rates.

Plant Location & Investment Factors

For an ioversol project, the first decision is whether to manufacture the iodinated intermediate in-house or purchase it from a supplier. Buying simplifies operations but makes the plant dependent on a supplier that captures much of the product's value. In-house production requires an iodination process, an iodine recovery system, and the capital investment needed for both. For a company that already manufactures several contrast agents, ioversol can be produced as another campaign using shared equipment. This explains why the supplier base mainly consists of contrast media specialists. The second decision is whether to produce the active ingredient or the finished injection. Active ingredient production requires competitive iodine use and strong documentation. Finished-dose production additionally requires sterile filling, bottle supply, participation in tenders, and distribution without refrigeration but with protection from light. A new entrant needs experience in iodination, iodine recovery capabilities, and the ability to operate under competitive tender pricing. The choice of site depends on iodine import logistics, wastewater discharge permits, utility costs, access to skilled labor, and access to hospital markets.

Major Ioversol Producing Regions

China accounts for most of the active ingredient manufacturing capacity, with six of the ten listed suppliers based there. India contributes through Divi's Laboratories and its broader fine chemical manufacturing base. Ireland and France represent the originator side, as Guerbet holds the brand and has registered addresses in these countries. In the United States, Liebel-Flarsheim manufactures the finished injection at its facility in Raleigh, North Carolina. Overall, China, India, Ireland, France, and the United States account for nearly all the named manufacturing capacity. Iodine, the key raw material, is sourced from entirely different locations.

Key Ioversol Producers

Guerbet

• French contrast media specialist holding the Optiray brand and franchise.
• Supplies the active ingredient and fills the finished injection through its subsidiaries.
• Competes on imaging portfolio depth, injector systems & clinical support.
• Serves radiology departments and imaging centers worldwide.

Mallinckrodt Pharmaceuticals

• American pharmaceutical company that developed Ioverol and patented the route.
• Appears twice on supplier listings for the active ingredient.
• Competes on originator process knowledge & regulatory history.
• Served the contrast media market before the franchise moved on.

Jiangsu Hengrui Medicine

• Chinese pharmaceutical group with a substantial contrast media business.
• Supplies ioversol alongside other iodinated and gadolinium agents.
• Competes on Chinese cost position & integrated manufacturing.
• Serves domestic hospitals and export customers.

Divi's Laboratories

• Indian active ingredient manufacturer with large-scale custom synthesis capability.
• Lists ioversol among its generic active ingredient portfolio.
• Competes on scale, process chemistry & regulated-market documentation.
• Serves finished dose makers in Europe and North America.

Starry Pharmaceutical

• Chinese group pursuing integration across contrast media actives and finished forms.
• Took an ioversol injection through Chinese registration with consistency evaluation.
• Competes on whole-chain integration and domestic approval progress.
• Serves Chinese hospitals and regional buyers.

Hainan Poly Pharm

• Chinese active ingredient producer listed as an ioversol supplier.
• Operates within a broader generic injectable and active ingredient business.
• Competes on manufacturing cost and responsiveness.
• Serves formulators and distributors in Asia and beyond.