List of Excipients in Branded Drug ULTRAVIST

Company	Tradename	Ingredient	NDC	Excipient	Potential Generic Entry
Bayer HealthCare Pharmaceuticals Inc	ULTRAVIST	iopromide	50419-342	EDETATE CALCIUM DISODIUM
Bayer HealthCare Pharmaceuticals Inc	ULTRAVIST	iopromide	50419-342	HYDROCHLORIC ACID
Bayer HealthCare Pharmaceuticals Inc	ULTRAVIST	iopromide	50419-342	SODIUM HYDROXIDE

ULTRAVIST Excipient Strategy and Commercial Opportunities

Last updated: August 20, 2026

Ultravist, Bayer’s iopromide injection, uses a deliberately narrow excipient system centered on tromethamine, calcium disodium edetate, pH adjustment agents, and water for injection. The commercial opportunity is therefore less likely to come from replacing excipients in the existing product than from improving container compatibility, reducing preparation waste, extending supply resilience, and developing differentiated ready-to-use or lower-volume presentations.

What is Ultravist and which excipients does it contain?

Ultravist is a nonionic, low-osmolar, iodinated contrast medium containing iopromide as the active pharmaceutical ingredient. In the United States, it is supplied in iodine concentrations of 240, 300, and 370 mg iodine/mL for intra-arterial, intravenous, and selected body-cavity imaging procedures. The product is administered in hospitals, imaging centers, and outpatient radiology facilities. [1]

The principal formulation components are:

Component	Function	Commercial and technical relevance
Iopromide	Nonionic iodinated active ingredient	Determines iodine concentration, viscosity, osmolality, and imaging performance
Tromethamine	Buffer and pH-control agent	Helps maintain formulation stability within the labeled pH range
Calcium disodium edetate	Chelating agent	Controls trace-metal catalysis and supports chemical stability
Hydrochloric acid and sodium hydroxide	pH adjustment	Used to establish the target formulation pH
Water for injection	Vehicle	Sterile parenteral solvent

Ultravist is an aqueous, sterile injectable formulation without preservatives. The US prescribing information identifies a pH range of approximately 6.5 to 7.5 and reports concentration-dependent osmolality and viscosity. [1]

How does the excipient system work?

The formulation is designed to solve three problems:

1. Maintain chemical stability of iopromide during storage.
2. Control pH without introducing a large buffer burden.
3. Minimize risks associated with trace metals, particulates, microbial contamination, and container interaction.

Tromethamine provides buffering capacity. Calcium disodium edetate binds trace metal ions that could catalyze degradation pathways. Hydrochloric acid and sodium hydroxide permit final pH adjustment without materially changing the formulation composition.

This is a conservative injectable-product strategy. A limited excipient package reduces the number of raw materials, simplifies compendial qualification, and limits potential sources of hypersensitivity, extractables, leachables, and regulatory variability.

What excipients are protected by Ultravist patents?

The commercial product is protected primarily by the historical development of iopromide, its manufacturing process, pharmaceutical compositions, and imaging uses rather than by a high-complexity excipient platform.

The original composition and use patents associated with iopromide have expired or are no longer the principal barrier to generic entry in the United States. Current competitive protection is more likely to arise from manufacturing know-how, validated sterile processes, container-closure systems, quality specifications, and regulatory execution than from broad exclusivity over tromethamine or calcium disodium edetate.

The key point for excipient suppliers is that the named ingredients are generally established pharmaceutical excipients. A supplier is unlikely to obtain meaningful product exclusivity merely by supplying conventional-grade tromethamine or edetate. Commercial differentiation must instead involve:

• tighter impurity profiles;
• lower metal content;
• improved lot-to-lot consistency;
• validated compatibility with high-iodine formulations;
• supply continuity;
• reduced particulate burden;
• documentation supporting injectable-grade regulatory submissions.

What is the FDA regulatory status of Ultravist?

Ultravist is an FDA-approved prescription contrast agent. Its US product labeling covers multiple radiographic procedures, including contrast-enhanced computed tomography, digital subtraction angiography, intra-arterial angiography, intravenous angiography, and selected body-cavity examinations, depending on concentration and route. [1]

The product is regulated as a sterile injectable drug. Excipients therefore must meet requirements for identity, purity, microbiological quality, endotoxin control, and manufacturing-process consistency. Any material change to the formulation or container system can trigger comparability, stability, extractables and leachables, particulate, and sterility assessments.

For a follow-on manufacturer, the formulation’s simplicity does not eliminate regulatory difficulty. The critical quality attributes include:

• assay and iodine concentration;
• iopromide-related impurities;
• pH;
• osmolality;
• viscosity;
• particulate matter;
• sterility and bacterial endotoxins;
• container-closure integrity;
• delivered volume;
• stability across labeled storage conditions.

When does Ultravist lose exclusivity?

Ultravist’s original small-molecule exclusivity and primary patent barriers have expired. Generic iopromide products can pursue an abbreviated or hybrid regulatory pathway, subject to the applicable FDA requirements and product-specific evidence.

The principal commercial barriers are now:

• sterile manufacturing capability;
• high-concentration injectable handling;
• validated filling and packaging;
• supply of iopromide active ingredient;
• hospital purchasing contracts;
• product liability exposure;
• stability and container compatibility;
• the cost of gaining market access across multiple vial and syringe configurations.

Unlike a tablet, a generic contrast injection cannot compete solely on active-ingredient cost. Hospitals also evaluate injector compatibility, workflow, packaging, barcode systems, wastage, delivery reliability, and the manufacturer’s ability to support large procedure volumes.

How many patents cover Ultravist and its excipients?

No broad, commercially dominant patent position should be assumed for the conventional Ultravist excipient system itself. Tromethamine, calcium disodium edetate, sodium hydroxide, hydrochloric acid, and water for injection are established ingredients with broad prior use.

A current patent review would need to distinguish among:

• expired iopromide composition patents;
• expired or surviving process patents;
• formulation patents directed to concentration, stability, or impurity control;
• container-closure patents;
• injector-system patents;
• method-of-use patents;
• patents owned by third parties covering alternative contrast-agent presentations.

The relevant freedom-to-operate risk is more likely to involve manufacturing and delivery systems than the basic excipient selection. A product developer should not treat the absence of a novel excipient as evidence of a patent-free market.

What formulation patents could create commercial value?

The strongest formulation opportunities are not likely to involve replacing tromethamine with an entirely new buffer. They are more likely to focus on measurable improvements in the finished product.

Low-volume, high-concentration presentations

Ultravist 370 provides a higher iodine concentration than the 240 and 300 mg iodine/mL products. A high-concentration presentation can reduce the volume required for certain imaging protocols while increasing viscosity and administration demands.

Potential commercial claims could involve:

• reduced administered volume;
• optimized iodine delivery rate;
• lower residual volume in tubing;
• improved performance in specific angiographic protocols;
• compatibility with automated injectors.

Any such positioning must be supported by clinical workflow and device-compatibility data, not by excipient composition alone.

Reduced-waste packaging

Contrast agents are frequently supplied in multi-dose or large-volume containers for high-throughput imaging. Unused residual product can create cost and waste.

Packaging opportunities include:

• smaller-volume vials;
• prefilled syringes;
• procedure-specific dose packs;
• unit-of-use packaging;
• container designs that reduce dead volume;
• RFID or barcode-enabled inventory systems.

The formulation remains substantially the same, but the commercial proposition changes through reduced wastage and improved pharmacy or radiology workflow.

Injector-compatible formulations

Automated contrast injectors impose requirements relating to viscosity, pressure, temperature, tubing, connectors, and injection rate. A manufacturer could pursue a formulation and device package optimized for specific injector platforms.

The patent risk in this area may arise from the injector, connector, syringe geometry, or software-controlled delivery process rather than the excipient system.

Improved low-temperature handling

Viscosity increases as temperature falls. Imaging facilities often warm contrast media before administration to reduce viscosity and improve injection performance. A formulation or packaging system that improves handling at lower temperatures could have commercial value, provided it maintains stability and does not create new particulate or degradation risks.

Potential development routes include:

• controlled warming instructions;
• validated warmer-compatible containers;
• improved thermal equilibration;
• packaging with better heat transfer;
• data supporting shorter preparation times.

A direct reduction in viscosity through excipient substitution would require careful evaluation because changes could affect osmolality, injection tolerability, iodine delivery, and regulatory comparability.

What manufacturing and intellectual-property barriers affect generic Ultravist?

Iopromide supply

Iopromide is a specialized active ingredient. A generic manufacturer must qualify the active pharmaceutical ingredient, control related substances, and demonstrate reliable supply. The active ingredient’s synthesis and purification can be a larger barrier than the excipient package.

Trace-metal control

The inclusion of calcium disodium edetate indicates the importance of trace-metal management. A competing product may use a different chelator or a different impurity-control strategy, but the developer would need comparative stability data.

Commercially valuable supplier capabilities include:

• low-metal excipient grades;
• validated testing for elemental impurities;
• long-term supply agreements;
• change-control systems suitable for injectable products;
• regulatory-support packages for drug-master-file submissions.

Container compatibility

High-iodine solutions require assessment of interaction with glass, elastomeric components, syringe barrels, plungers, closures, and transfer devices. Extractables and leachables can become a meaningful regulatory and litigation risk.

Potential issues include:

• tungsten or glass-related particles;
• elastomer swelling;
• iodine or formulation interaction with polymer components;
• adsorption or absorption;
• closure integrity after terminal sterilization or storage;
• performance after warming.

A generic product that matches the liquid formulation but uses a less suitable container may fail to achieve commercial acceptance.

Sterile filling

Ultravist is a high-volume sterile injectable product. Manufacturing must control bioburden, endotoxins, visible and subvisible particles, fill accuracy, and container-closure integrity. The technical barrier is elevated for large-volume presentations and prefilled devices.

Which companies challenge Ultravist?

The competitive field includes Bayer’s Ultravist and other nonionic iodinated contrast agents, including:

Product	Active ingredient	Originator	Competitive distinction
Ultravist	Iopromide	Bayer	Multiple iodine concentrations and broad radiographic use
Omnipaque	Iohexol	GE HealthCare	Broad use across CT, angiography, and other procedures
Isovue	Iopamidol	Bracco	Broad hospital and imaging-center use
Optiray	Ioversol	Guerbet	Nonionic iodinated contrast portfolio
Visipaque	Iodixanol	GE HealthCare	Iso-osmolar contrast medium

These products compete on clinical familiarity, supply reliability, iodine concentration, viscosity, injector compatibility, pricing, and hospital formulary position. [2-5]

The most credible generic challenge is likely to come from companies with existing sterile injectable infrastructure and hospital contracting capabilities rather than from a commodity excipient supplier entering the market independently.

What is the Orange Book and Paragraph IV status of Ultravist?

Ultravist is listed in FDA’s Approved Drug Products with Therapeutic Equivalence Evaluations, commonly called the Orange Book, subject to the product-specific listing and current FDA records. [6]

Because the original exclusivity period has elapsed, a current abbreviated-application strategy would likely focus on approval of a generic iopromide injection rather than on a new Paragraph IV challenge to an active, commercially dominant Ultravist patent. Any remaining listed patent must be reviewed by product, strength, and indication before a filing strategy is selected.

Paragraph IV risk can still arise if a generic applicant certifies that an Orange Book-listed patent is invalid, unenforceable, or not infringed. The business consequences include:

• a potential 30-month stay following patent litigation;
• litigation cost and launch delay;
• exposure to damages or injunctive relief;
• acceleration of market entry if the patent position fails;
• possible settlement restrictions.

For an excipient-focused entrant, the better target may be a supply or technology agreement with a generic manufacturer rather than a standalone patent challenge.

What licensing deals could support an Ultravist strategy?

The most commercially relevant licensing structures are likely to involve:

1. Iopromide supply rights. A manufacturer licenses or purchases qualified active ingredient from an established source.
2. Container-closure technology. A packaging company licenses a syringe, vial, stopper, or connector system validated for iodinated contrast media.
3. Injector compatibility. A device manufacturer supports a contrast formulation through a co-marketing or compatibility agreement.
4. Contract manufacturing. A sterile injectable producer supplies finished product for a branded or generic sponsor.
5. Regional distribution. A marketing authorization holder licenses territory-specific rights where Bayer’s commercial presence is weaker.
6. Hospital workflow technology. Packaging, inventory, barcoding, and dose-management systems are bundled with the contrast product.

No publicly confirmed licensing arrangement should be inferred solely from the presence of standard excipients in the Ultravist label. Commercial diligence should separate Bayer-owned rights from third-party supply contracts, manufacturing agreements, and device relationships.

What are the strongest excipient commercial opportunities?

Excipient supply

The highest-probability opportunity is supplying injectable-grade tromethamine or calcium disodium edetate with stronger documentation and supply assurance. The product is mature, so purchasing decisions are likely to prioritize:

• dependable global capacity;
• low elemental impurities;
• validated sterilization or bioburden controls;
• pharmacopoeial compliance;
• change-notification discipline;
• dual-source qualification.

Formulation-enabling services

Contract development organizations can provide value through:

• forced-degradation studies;
• trace-metal mapping;
• pH and buffer optimization;
• viscosity and osmolality profiling;
• container-closure compatibility;
• extractables and leachables programs;
• accelerated and long-term stability;
• particulate investigations.

Packaging and dose optimization

Packaging has stronger differentiation potential than conventional excipient substitution. A company that reduces product waste, improves injector performance, or enables smaller procedure-specific doses can compete on total cost of care.

Regional generic manufacturing

A regional manufacturer could pursue iopromide injection with local sterile-fill capacity and differentiated packaging. The economic case is strongest in markets where contrast-agent supply interruptions, import dependence, or hospital procurement rules favor local production.

How does Ultravist compare with competing contrast agents?

Ultravist is not differentiated primarily by a novel excipient system. Its competitive position depends on the combined profile of iopromide concentration, viscosity, osmolality, clinical familiarity, supply, and operational fit.

Commercial factor	Ultravist	Implication
Excipient complexity	Low	Easier formulation replication, but limited excipient-based differentiation
Active ingredient	Specialized iopromide	Supply and process capability remain barriers
Concentration range	240, 300, 370 mg iodine/mL in the US	Supports protocol-specific use
Packaging opportunity	High	Waste reduction and injector integration can create value
Patent barrier	Mature and largely expired	Regulatory execution and manufacturing quality matter more
Biosimilar risk	Not applicable	Iopromide is a chemically defined small molecule
Generic risk	Real	Sterile manufacturing and hospital contracting limit entry speed
Formulation-switching risk	Moderate	Changes can affect viscosity, osmolality, stability, and device performance

What is the revenue exposure from generic entry?

Ultravist revenue is exposed to generic erosion because iopromide is a small molecule with an established injectable formulation. The erosion profile is likely to depend on:

• number of approved generic suppliers;
• supply reliability;
• hospital tender cycles;
• product concentration and vial mix;
• availability of prefilled or injector-compatible presentations;
• regional reimbursement policies;
• Bayer contracting strategy.

Generic entry may first affect high-volume 300 mg iodine/mL presentations, where purchasing departments can compare products directly. High-concentration products and specialized packaging may retain stronger pricing if they are tied to specific imaging protocols or injector workflows.

Public financial reports generally disclose Bayer’s Pharmaceuticals segment and broader radiology-related business rather than a consistently reported Ultravist-only revenue figure. Product-level revenue exposure therefore should not be estimated from segment data without a separate market-sizing analysis. [7]

Key Takeaways

• Ultravist uses a simple sterile aqueous formulation with tromethamine, calcium disodium edetate, pH adjusters, and water for injection.
• The excipient package is mature and offers limited standalone patent differentiation.
• The strongest commercial opportunities are in injectable-grade supply, trace-metal control, container compatibility, prefilled systems, and waste reduction.
• Generic entry risk is real because the product is a chemically defined small-molecule injection with expired primary exclusivity.
• Manufacturing, sterile filling, active-ingredient supply, container-closure performance, and hospital contracting are the main barriers.
• Biosimilar risk does not apply to Ultravist because iopromide is not a biologic.
• Formulation changes must be evaluated against viscosity, osmolality, stability, particulate, injector, and regulatory requirements.
• Packaging and workflow improvements are more defensible commercial opportunities than replacing standard excipients.

FAQs

Can tromethamine be replaced in an iopromide formulation?

Potentially, but substitution would require comparative stability, pH, osmolality, viscosity, impurity, compatibility, and injectable-safety data. A replacement buffer would not automatically be pharmaceutically equivalent.

Is calcium disodium edetate essential to Ultravist?

It is part of the labeled formulation and supports trace-metal control. A competing product could use another strategy, but it would need evidence that chemical stability and impurity control remain acceptable.

Does Ultravist have biosimilar competition?

No. Biosimilar regulation applies to biological products. Iopromide is a chemically defined small-molecule drug, so competition proceeds through generic or other applicable small-molecule pathways.

Which Ultravist presentation is most attractive for a generic manufacturer?

The 300 mg iodine/mL presentation is likely to offer the broadest addressable hospital market because it is widely used across routine contrast-enhanced imaging. Higher-concentration products may offer stronger differentiation through protocol and injector compatibility.

Can a new container create patent value around iopromide injection?

Yes, if the container or delivery system provides a technically demonstrated advantage and satisfies patentability requirements. Potential claim areas include syringe geometry, closure systems, warming compatibility, reduced dead volume, injector integration, or improved extractables and leachables performance.

References

1. U.S. Food and Drug Administration. (2023). Ultravist (iopromide injection) prescribing information. Bayer HealthCare Pharmaceuticals Inc.

2. U.S. Food and Drug Administration. (2023). Omnipaque (iohexol injection) prescribing information. GE Healthcare.

3. U.S. Food and Drug Administration. (2023). Isovue (iopamidol injection) prescribing information. Bracco Diagnostics Inc.

4. U.S. Food and Drug Administration. (2023). Optiray (ioversol injection) prescribing information. Guerbet LLC.

5. U.S. Food and Drug Administration. (2023). Visipaque (iodixanol injection) prescribing information. GE Healthcare.

6. U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations. FDA Center for Drug Evaluation and Research.

7. Bayer AG. (2023). Annual report 2023. Bayer AG.