List of Excipients in Branded Drug CONRAY

Company	Tradename	Ingredient	NDC	Excipient	Potential Generic Entry
Liebel-Flarsheim Company LLC	CONRAY	iothalamate meglumine	0019-0953	EDETATE CALCIUM DISODIUM
Liebel-Flarsheim Company LLC	CONRAY	iothalamate meglumine	0019-0953	SODIUM PHOSPHATE, MONOBASIC

CONRAY Excipient Strategy, Patent Position and Commercial Opportunities

Last updated: August 2, 2026

CONRAY is an established iodinated contrast media franchise based on iothalamate meglumine and iothalamate sodium. Its commercial opportunity is not centered on new-molecule exclusivity. It is centered on supply reliability, formulation equivalence, packaging, administration efficiency, regional regulatory registrations, and differentiated radiology workflow. The principal excipient strategy is to preserve solution stability, control pH, limit metal-catalyzed degradation, and maintain injectability across multiple iodine concentrations.

What is CONRAY and how is it formulated?

CONRAY is a nonionic-free, ionic, water-soluble iodinated contrast medium used in radiographic procedures. Products in the CONRAY range are supplied as sterile injectable solutions with different iodine concentrations and route-specific indications.

The active ingredients are:

• Iothalamate meglumine
• Iothalamate sodium

The formulation is typically an aqueous solution with pH-control and chelation components. Product-specific labeling should control any development or regulatory comparison because excipient concentrations can differ by presentation.

Product family	Primary active component	Typical iodine strength	Commercial role
CONRAY 30	Iothalamate meglumine and iothalamate sodium	Approximately 140 mg iodine/mL	Lower-concentration imaging applications
CONRAY 43	Iothalamate meglumine and iothalamate sodium	Approximately 282 mg iodine/mL	Intermediate-strength applications
CONRAY 60	Iothalamate meglumine and iothalamate sodium	Approximately 282 mg iodine/mL, depending on presentation and labeling convention	Higher-strength diagnostic use

The U.S. prescribing information identifies excipients and formulation controls such as edetate components, citrate buffering or pH adjustment, and water for injection. Sodium hydroxide and hydrochloric acid may be used for pH adjustment. The exact composition must be verified against the current product label for each strength and container size.[1]

What excipients are relevant to CONRAY development?

The key excipient functions are:

Excipient function	Likely formulation objective	Commercial significance
Chelation	Bind trace metals that can catalyze degradation or discoloration	Supports shelf life and batch consistency
Buffering and pH control	Maintain a pH compatible with stability and injection	Reduces formulation drift during storage
Water for injection	Solubilize the ionic contrast salts	Determines osmolality and concentration limits
Container-contact controls	Limit extractables, leachables, adsorption, and precipitation	Supports compatibility with vials, syringes, and automated injectors
Tonicity management	Control osmotic burden within the constraints of an ionic contrast formulation	Affects tolerability and product positioning

CONRAY does not depend on a conventional preservative system. The principal formulation risks are high osmolality, ionic strength, pH drift, trace-metal contamination, particulate formation, and container compatibility.

What is the best excipient strategy for CONRAY?

The strongest strategy is a conservative, label-aligned formulation platform rather than aggressive excipient substitution. CONRAY is an established injectable product, and changes that affect osmolality, viscosity, pH, degradation profile, or injection performance can create regulatory and clinical comparability issues.

Maintain a minimal excipient system

A minimal excipient system has several advantages:

1. It reduces the risk of new local tolerability findings.
2. It simplifies analytical comparability.
3. It lowers the number of extractables and leachables variables.
4. It reduces the risk that an excipient change creates a new toxicological assessment.
5. It supports a more direct formulation bridge to the reference product.

Potential commercial developers should prioritize the current labeled excipients and their functional equivalents. A new buffer, surfactant, antioxidant, or tonicity agent should be introduced only where it solves a demonstrated manufacturing or stability problem.

Optimize chelator level and metal control

Chelation is commercially important because trace metals can affect color, impurity formation, and long-term stability. A development program should evaluate:

• Chelator concentration across the proposed shelf life
• Metal burden from raw materials and water systems
• Stainless-steel contact surfaces
• Filling-line components
• Closure and stopper interactions
• Forced-degradation behavior under heat and light

The objective is not to maximize chelator concentration. Excess chelator can affect regulatory comparability and may create unnecessary exposure. The target should be the lowest level that protects the formulation under validated manufacturing and storage conditions.

Control pH without adding unnecessary buffer burden

pH adjustment should be treated as a critical quality attribute. A high-ionic-strength contrast solution can respond differently to small additions of acid or base than a conventional small-molecule injection.

Development work should establish:

• Initial pH range
• pH drift during accelerated and long-term storage
• pH impact on impurity growth
• Compatibility with the intended container
• Impact of terminal sterilization or aseptic processing
• Injection-site and vascular tolerability

A tightly controlled pH system can support shelf-life extension, but a new buffer system may require substantial bridging data.

Engineer for container and injector compatibility

A major commercial opportunity is packaging rather than chemical reformulation. CONRAY-compatible presentations can be developed around:

• Polypropylene or cyclic olefin polymer syringes
• Single-dose prefilled syringes
• Flexible bags for selected applications
• Bulk containers for hospital radiology departments
• Automated injector-compatible presentations
• Tamper-evident and low-waste packaging

The product must be evaluated for adsorption, extractables, leachables, stopper coring, particulate generation, pressure resistance, and dose accuracy. High-density iodine solutions also require attention to viscosity and injector pressure.

What patents protect CONRAY?

CONRAY is an old active-ingredient product, so the commercial protection profile is materially different from that of a recently approved drug. The core iothalamate composition is not expected to provide meaningful new-molecule patent exclusivity. Any remaining protection is more likely to involve formulation, container, manufacturing, delivery-system, or use-specific claims.

Protection category	Relevance to CONRAY	Expected commercial value
Composition-of-matter patent	Low for the legacy active ingredients	Minimal
Formulation patent	Possible, but requires claim-specific review	Moderate if it covers a non-obvious stability or concentration solution
Method-of-use patent	Possible for a narrow imaging indication or administration protocol	Usually limited
Container or syringe patent	Possible and commercially relevant	Moderate
Injector or delivery-system patent	Relevant where the product is integrated with imaging equipment	High in workflow-driven markets
Manufacturing-process patent	Possible for impurity control, crystallization, sterilization, or filling	Moderate
Trade secret	Highly relevant for process controls and metal management	Meaningful but difficult to enforce against independent development

No current CONRAY patent number, expiration date, or Orange Book-listed patent should be treated as established without a live review of the FDA Orange Book, FDA Drugs@FDA records, USPTO Patent Center, and relevant litigation databases. The product’s age indicates that generic or follow-on competition is more likely to be constrained by regulatory execution, manufacturing economics, and customer qualification than by core patent exclusion.

What is the Orange Book status of CONRAY?

CONRAY’s Orange Book position should be assessed at the specific product and NDA level. Legacy diagnostic contrast products may have limited or no currently meaningful patent listings even when they remain commercially protected by manufacturing complexity and market relationships.

The relevant review should distinguish:

• NDA approval status
• Active versus discontinued presentations
• Listed patents, if any
• Pediatric exclusivity
• New chemical entity exclusivity
• Supplement approvals
• Approved labeling for each iodine concentration
• Whether a competing product can rely on an abbreviated pathway or requires a different application route

For an established injectable contrast product, the most important regulatory question is often whether the proposed product can establish pharmaceutical equivalence, bioequivalence or equivalent performance, sterility, stability, and clinical suitability under the applicable FDA pathway. FDA approval of an alternative product does not automatically eliminate hospital-level barriers involving injector qualification, formulary review, adverse-event monitoring, and supply history.[2]

When does CONRAY lose exclusivity?

CONRAY’s principal statutory exclusivity periods have almost certainly expired because the product has been marketed for decades. Its commercial exclusivity therefore depends on residual patents, regulatory restrictions, manufacturing know-how, customer contracts, distribution access, and product availability.

Exclusivity mechanism	CONRAY relevance
New chemical entity exclusivity	Expired
Five-year Hatch-Waxman exclusivity	Expired
Three-year clinical-investigation exclusivity	Expired for the original product
Orphan-drug exclusivity	Not the principal basis of CONRAY’s market position
Pediatric exclusivity	No current commercial significance indicated
Core composition patent	Expected to be expired
Formulation or process patents	Must be checked claim by claim
Market-based protection	Still relevant through supply, contracts, manufacturing, and customer familiarity

A developer should not assume that the absence of core patent protection guarantees rapid entry. Iodinated contrast media are injectable products with quality-sensitive manufacturing and hospital procurement requirements. A shortage, recall, or failed validation program can materially delay commercialization.

What formulation patents could protect a CONRAY follow-on product?

A commercially meaningful patent program would need to claim a specific technical improvement rather than the historical use of iothalamate salts in water.

Potentially defensible areas include:

High-concentration stability

Claims could target a defined concentration range, pH window, chelator level, impurity profile, and storage condition that produces a measurable stability advantage. Broad claims covering only “an aqueous iothalamate solution” would face substantial validity and prior-art challenges.

Low-particulate injectable formulations

A formulation or process that lowers subvisible particles, prevents precipitation after temperature cycling, or improves compatibility with automated injectors could support narrower claims.

Ready-to-use presentation

A prefilled syringe, dual-chamber system, or injector-specific package could create claims around dose accuracy, reduced preparation time, reduced waste, or closed-system handling.

Container-closure systems

Patentable subject matter may include a defined polymer, stopper, coating, headspace condition, or sterilization process that improves long-term stability and reduces leachables.

Manufacturing process

Potential claims could address raw-material purification, trace-metal reduction, crystallization control, filtration, filling, or terminal sterilization. Process patents would have greater value if the resulting product has a distinctive impurity fingerprint or stability profile that can be detected in the market.

Are Paragraph IV challenges relevant to CONRAY?

Paragraph IV litigation is relevant only if a proposed generic or follow-on product relies on an abbreviated application and the reference product has an Orange Book-listed patent. If no relevant patent is listed, a Paragraph IV certification may not be the principal entry mechanism.

For CONRAY, the practical competitive questions are:

1. Whether a current NDA remains the reference product for the targeted presentation.
2. Whether any patents are listed for that NDA.
3. Whether the proposed product has the same active ingredients, strength, dosage form, route, and labeling scope.
4. Whether FDA expects a conventional generic pathway, a 505(b)(2) application, or another regulatory route.
5. Whether the competitor can demonstrate injectable quality and equivalent clinical performance.

A Paragraph IV strategy would have value only if a listed patent blocks approval or commercial launch. For a legacy contrast medium, the litigation risk may be lower than the technical and regulatory risk.

Which companies are challenging CONRAY?

Competition in iodinated contrast media comes from manufacturers of both ionic and nonionic agents. The competitive set can include:

• Guerbet, associated with CONRAY commercialization in the United States
• GE HealthCare, with Omnipaque and other contrast media
• Bracco, with Isovue and related products
• Bayer, with Ultravist and other radiology products
• Hengrui and other international manufacturers in selected markets
• Regional generic and contract manufacturers

The most direct substitutes are not necessarily chemically identical. Hospitals may compare CONRAY with nonionic low-osmolar agents based on clinical protocol, cost per study, adverse-event profile, injector compatibility, and supply reliability.

How does CONRAY compare with modern nonionic contrast media?

Factor	CONRAY	Modern nonionic low-osmolar contrast media
Chemistry	Ionic iothalamate salts	Nonionic monomers or dimers
Osmolality	Generally higher at comparable iodine delivery	Generally lower
Cost position	Potentially favorable in price-sensitive settings	Often higher acquisition cost
Clinical positioning	Established diagnostic use	Broader use where tolerability and protocol flexibility matter
Formulation complexity	High ionic load and strong pH/metal-control requirements	Different stability and viscosity tradeoffs
Commercial vulnerability	Substitution by nonionic agents	Less exposed in protocols requiring lower osmolality
Differentiation opportunity	Price, supply, packaging, workflow	Clinical preference, protocol performance, institutional standardization

CONRAY can remain commercially relevant where procurement teams prioritize acquisition cost, availability, and established protocol experience. Its competitive weakness is the clinical preference for lower-osmolality agents in many applications and patient populations.

What commercial opportunities exist for CONRAY?

Hospital cost-reduction programs

The clearest opportunity is a value-positioned contrast product with reliable supply and transparent dose economics. A supplier can compete on:

• Cost per imaging procedure
• Reduced vial waste
• High-volume container formats
• Contract pricing
• Multi-year supply agreements
• Consistent delivery during contrast shortages

A low-cost strategy must account for the cost of quality failures. Sterility deviations, particulate recalls, and supply interruptions can outweigh unit-price savings.

Prefilled and injector-ready presentations

Packaging can improve radiology workflow by reducing manual transfer, preparation time, and contamination risk. A prefilled presentation can support premium pricing if it reduces labor and waste enough to improve total cost per procedure.

The package must be validated for:

• Injector pressure
• Syringe plunger force
• Dose accuracy
• Storage orientation
• Temperature excursions
• Connector compatibility
• Particulate control

Regional manufacturing and supply security

Iodinated contrast shortages have shown the commercial value of geographic diversification. A regional manufacturing platform could differentiate CONRAY-compatible products through:

• Domestic or near-market fill-finish
• Dual-source raw materials
• Redundant sterile manufacturing
• Strategic inventory
• Regional packaging
• Shorter hospital replenishment cycles

This opportunity is strongest in markets where radiology departments have experienced supply disruptions or where public procurement rewards local production.

Contract manufacturing and private-label supply

A qualified manufacturer could offer CONRAY-equivalent or iothalamate-based products to distributors, hospital groups, and regional pharmaceutical companies. The commercial model could include:

• Contract sterile filling
• Private-label contrast media
• Regional licensing
• Regulatory dossier licensing
• Injector-compatible packaging
• Hospital-specific presentations

The primary barrier is not simple blending. It is validated sterile manufacturing, analytical control, regulatory approval, and reliable supply at scale.

Reformulation for selected procedures

A differentiated formulation could target lower waste, faster administration, improved temperature handling, or better compatibility with automated injection systems. Any clinical tolerability claim would require appropriate evidence and cannot be inferred from excipient changes alone.

What manufacturing and intellectual-property barriers exist?

The main barriers are operational and regulatory:

• Sterile injectable manufacturing capacity
• Control of endotoxins and particulate matter
• High-purity active pharmaceutical ingredients
• Trace-metal control
• Container-closure qualification
• Stability at multiple temperatures
• Automated injector compatibility
• Validated analytical methods
• FDA inspection readiness
• Hospital formulary qualification
• Pharmacovigilance and recall capability

Trade secrets can be more valuable than patents in this setting. Metal-control procedures, raw-material specifications, filtration parameters, filling conditions, and container-selection criteria can materially affect product performance while remaining difficult for competitors to observe.

What patent litigation affects CONRAY?

No major current CONRAY-specific patent dispute can be identified from the established product profile alone. The expected litigation exposure is lower than for a recently approved branded drug with active composition or method-of-use patents.

Potential disputes could still arise over:

• A competing formulation patent
• A prefilled syringe or injector interface
• A manufacturing process
• Trade dress or packaging
• Regulatory exclusivity
• Contract manufacturing rights
• Supply or distribution agreements

A litigation review should search the product name, iothalamate, iothalamate meglumine, iothalamate sodium, the relevant NDA holder, and competing injectable contrast manufacturers in the U.S. Patent Trial and Appeal Board, federal district courts, and FDA patent records.

What is the licensing and partnership opportunity?

The most practical licensing structures are commercial and technical rather than molecule-based.

Deal structure	Strategic use
Regional commercialization license	Gives a local company rights to market CONRAY or an equivalent presentation
Manufacturing license	Transfers formulation, process, and analytical know-how
Co-development agreement	Funds a prefilled syringe or injector-compatible product
Supply agreement	Secures contrast media for hospital or distributor networks
Dossier license	Supports regulatory filings in additional countries
Private-label agreement	Expands volume without creating a new consumer brand

A licensing package should define rights to the formulation, manufacturing process, trademarks, regulatory files, stability data, packaging, and post-approval changes. Patent rights alone are unlikely to capture the full commercial value.

What is the revenue exposure and competitive outlook?

CONRAY revenue is exposed to substitution by modern low-osmolar nonionic contrast media, price pressure from generic suppliers, procurement consolidation, and hospital preference for standardized imaging protocols. Revenue can be protected by supply reliability, cost advantages, and packaging that reduces procedural labor.

The highest-value commercial segment is likely not broad clinical differentiation. It is dependable supply in price-sensitive, high-volume imaging settings.

Revenue driver	Directional impact
Contrast-media shortages	Positive for available inventory
Hospital group contracting	Negative for stand-alone premium pricing
Prefilled packaging	Positive if labor savings are documented
Nonionic substitution	Negative for ionic legacy products
Regional manufacturing	Positive for public procurement and supply security
New formulation patents	Positive only if technically differentiated
Generic entry	Negative for price and share
Injector integration	Positive for customer retention

Key Takeaways

• CONRAY is a legacy iothalamate-based injectable contrast franchise, not a new-molecule exclusivity story.
• Its excipient strategy should focus on chelation, pH control, metal management, sterility, and container compatibility.
• Broad composition patents are unlikely to provide meaningful current protection.
• Formulation, packaging, injector, and manufacturing-process claims offer the most credible IP opportunities.
• Paragraph IV risk depends on whether relevant patents remain listed for the applicable reference product.
• The strongest commercial opportunities are prefilled syringes, injector-ready formats, hospital cost reduction, regional manufacturing, and private-label supply.
• Competitive pressure comes mainly from nonionic low-osmolar contrast media and generic or regional manufacturers.
• Manufacturing quality and supply continuity are likely to be more important barriers than core patent rights.

FAQs

Can CONRAY be reformulated with a different chelating agent?

A different chelator may be technically feasible, but it would require stability, impurity, safety, container-compatibility, and regulatory comparability data. The commercial value depends on a measurable improvement over the labeled formulation.

Is a CONRAY follow-on product eligible for an ANDA?

Eligibility depends on the applicable FDA reference product, active ingredients, dosage form, labeling, strength, and regulatory classification. An ANDA is not assured solely because CONRAY is an old product. A 505(b)(2) pathway may be relevant where formulation or clinical differences prevent a conventional generic filing.

Can a prefilled CONRAY syringe command a premium price?

Yes, if the presentation reduces preparation time, product waste, contamination risk, or injector setup costs. The premium must be supported by workflow and total-cost evidence.

Are excipient patents likely to block CONRAY generic entry?

Usually not by themselves. A narrowly drafted excipient or formulation patent could create a legal barrier, but its commercial effect depends on claim scope, validity, enforceability, and whether a non-infringing formulation can be developed.

What is the most defensible CONRAY commercial strategy?

The most defensible strategy combines a label-aligned formulation, validated sterile manufacturing, reliable supply, hospital-focused pricing, and an injector-compatible or prefilled presentation. That combination addresses the main commercial barriers without relying on expired active-ingredient exclusivity.

References

1. U.S. Food and Drug Administration. (n.d.). CONRAY-30, CONRAY-43, and CONRAY-60 prescribing information. DailyMed.
2. U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations. FDA Orange Book.
3. U.S. Food and Drug Administration. (n.d.). Drugs@FDA: FDA-approved drugs.
4. U.S. Food and Drug Administration. (2023). Drug shortages: Contrast media and supply-chain information.
5. U.S. Pharmacopeia. (2024). General chapter <788>: Particulate matter in injections. United States Pharmacopeial Convention.