Suppliers and packagers for generic pharmaceutical drug: DIATRIZOATE MEGLUMINE; DIATRIZOATE SODIUM

DIATRIZOATE MEGLUMINE; DIATRIZOATE SODIUM

Listed suppliers include manufacturers, repackagers, relabelers, and private labeling entitities.

Applicant	Tradename	Generic Name	Dosage	NDA	NDA/ANDA	Supplier	Package Code	Package	Marketing Start
Bracco	RENOGRAFIN-60	diatrizoate meglumine; diatrizoate sodium	INJECTABLE;INJECTION	010040	NDA	BRACCO DIAGNOSTICS INC	0270-0149-57	10 BOTTLE in 1 PACKAGE (0270-0149-57) / 300 mL in 1 BOTTLE	1970-11-03
Bracco	RENOGRAFIN-60	diatrizoate meglumine; diatrizoate sodium	INJECTABLE;INJECTION	010040	NDA	BRACCO DIAGNOSTICS INC	0270-0149-60	10 BOTTLE in 1 PACKAGE (0270-0149-60) / 100 mL in 1 BOTTLE	1970-11-03
Bracco	RENOGRAFIN-60	diatrizoate meglumine; diatrizoate sodium	INJECTABLE;INJECTION	010040	NDA	BRACCO DIAGNOSTICS INC	0270-1410-30	10 BOTTLE in 1 PACKAGE (0270-1410-30) / 300 mL in 1 BOTTLE	1982-11-09
Bracco	RENOGRAFIN-76	diatrizoate meglumine; diatrizoate sodium	INJECTABLE;INJECTION	010040	NDA	BRACCO DIAGNOSTICS INC	0270-0149-57	10 BOTTLE in 1 PACKAGE (0270-0149-57) / 300 mL in 1 BOTTLE	1970-11-03
Bracco	RENOGRAFIN-76	diatrizoate meglumine; diatrizoate sodium	INJECTABLE;INJECTION	010040	NDA	BRACCO DIAGNOSTICS INC	0270-0149-60	10 BOTTLE in 1 PACKAGE (0270-0149-60) / 100 mL in 1 BOTTLE	1970-11-03
Bracco	RENOGRAFIN-76	diatrizoate meglumine; diatrizoate sodium	INJECTABLE;INJECTION	010040	NDA	BRACCO DIAGNOSTICS INC	0270-1410-30	10 BOTTLE in 1 PACKAGE (0270-1410-30) / 300 mL in 1 BOTTLE	1982-11-09

Diatrizoate Meglumine; Diatrizoate Sodium Supply Chain Analysis

Last updated: February 19, 2026

This report analyzes the supply chain for Diatrizoate Meglumine and Diatrizoate Sodium, key components in radiopaque contrast media. The analysis focuses on critical raw material suppliers, manufacturing capabilities, patent landscapes, and regulatory considerations impacting supply stability and market access. Identifying reliable suppliers and understanding associated intellectual property are paramount for pharmaceutical companies developing or marketing products containing these agents.

What Are the Key Raw Materials and Their Suppliers?

The synthesis of Diatrizoate Meglumine and Diatrizoate Sodium relies on specific chemical precursors. The primary synthetic route involves iodination of a substituted benzoic acid derivative.

• 3,5-Diaminobenzoic Acid: This is a foundational intermediate. Suppliers for this compound include:

  • BASF SE: A global chemical producer with extensive capabilities in fine chemical synthesis. Their product portfolio often includes complex organic intermediates.
  • Merck KGaA: Operates a significant chemical division, supplying a range of reagents and intermediates for pharmaceutical manufacturing.
  • WuXi AppTec: A contract research, development, and manufacturing organization (CRDMO) that offers custom synthesis services, including complex intermediates like 3,5-diaminobenzoic acid.
  • Various Chinese Manufacturers: Numerous chemical synthesis companies based in China are key suppliers, often offering competitive pricing for bulk intermediates. Examples include Zhejiang NHU Co., Ltd. and Jiangsu Liansheng Chemical Co., Ltd., though direct supply chain verification for specific pharmaceutical grades is essential.

• Iodine Source (e.g., Iodine Monochloride, Sodium Iodide): Iodine is essential for the iodination step.

  • SQM S.A. (Sociedad Química y Minera de Chile): A leading global producer of iodine, primarily from caliche ore in Chile. Their production capacity and quality control are critical for pharmaceutical-grade iodine.
  • Chilean Iodine Producers: Beyond SQM, other Chilean companies contribute to global iodine supply.
  • Japanese Iodine Producers: Companies such as Ishihara Sangyo Kaisha, Ltd. are also significant iodine suppliers.
  • Distributors of Iodine Compounds: Specialized chemical distributors handle various iodine-based reagents for laboratory and industrial use.

• Meglumine: Used to form the meglumine salt of diatrizoic acid.

  • Merck KGaA: Offers meglumine as part of its pharmaceutical excipient and fine chemical offerings.
  • Evonik Industries AG: A specialty chemicals company with a portfolio that includes amino-sugars like meglumine.
  • Chinese Pharmaceutical Chemical Manufacturers: Several Chinese companies specialize in producing pharmaceutical-grade meglumine.

• Sodium Hydroxide / Sodium Carbonate: Used for salt formation and pH adjustments. These are commodity chemicals with numerous global suppliers, including Dow Inc., Olin Corporation, and various regional chemical producers. Pharmaceutical grades are readily available from major chemical distributors.

Table 1: Key Raw Materials and Potential Suppliers

Raw Material	Primary Function	Potential Suppliers
3,5-Diaminobenzoic Acid	Core aromatic intermediate	BASF SE, Merck KGaA, WuXi AppTec, Zhejiang NHU Co., Ltd., Jiangsu Liansheng Chemical Co., Ltd.
Iodine Source	Iodination reagent	SQM S.A., Other Chilean Producers, Ishihara Sangyo Kaisha, Ltd., Chemical Distributors
Meglumine	Counter-ion for meglumine salt	Merck KGaA, Evonik Industries AG, Chinese Pharmaceutical Chemical Manufacturers
Sodium Hydroxide/Carbonate	Salt formation, pH adjustment	Dow Inc., Olin Corporation, Regional Chemical Producers, Pharmaceutical Chemical Distributors

Supplier qualification for pharmaceutical active pharmaceutical ingredients (APIs) requires rigorous auditing for Good Manufacturing Practices (GMP), consistent quality, and supply chain transparency.

What Are the Manufacturing Processes and Key Manufacturers?

The synthesis of Diatrizoate Meglumine and Diatrizoate Sodium involves multiple steps, primarily centered around the iodination of 3,5-diaminobenzoic acid and subsequent salt formation.

1. Iodination: 3,5-diaminobenzoic acid is reacted with an iodinating agent, typically in a solvent under controlled conditions, to introduce iodine atoms at the 2, 4, and 6 positions of the benzene ring. This yields 3,5-diamino-2,4,6-triiodobenzoic acid (diatrizoic acid).
2. Salt Formation:
   • Diatrizoic Acid: The free acid can be purified.
   • Diatrizoate Sodium: Reacting diatrizoic acid with a sodium source (e.g., sodium hydroxide or sodium carbonate) forms the sodium salt.
   • Diatrizoate Meglumine: Reacting diatrizoic acid with meglumine forms the meglumine salt. Often, Diatrizoate Meglumine solutions also contain Diatrizoate Sodium, creating a mixed salt formulation.

Key Manufacturers of Diatrizoate Meglumine and Diatrizoate Sodium APIs and Finished Products:

• General Electric Healthcare (formerly part of Amersham, Nycomed): A major producer of radiopaque contrast media, including products based on diatrizoate salts. Their integrated supply chain likely includes captive manufacturing or long-term contracts with API suppliers.
• Bayer AG: Markets contrast media products under various brand names. Bayer has significant pharmaceutical manufacturing capabilities.
• Lupin Ltd.: An Indian multinational pharmaceutical company that manufactures and markets a range of APIs and finished dosage forms, including some contrast agents.
• Bracco Imaging S.p.A.: A significant player in the diagnostic imaging market, Bracco develops and manufactures contrast agents.
• E-Life Sciences (China): A growing presence in API manufacturing, including intermediates and APIs for contrast media.
• Various Generic API Manufacturers: Numerous companies, particularly in India and China, produce generic APIs. These manufacturers must meet stringent regulatory requirements (e.g., FDA, EMA). Examples include:
  • Syntho Pharmaceuticals Pvt. Ltd. (India)
  • Zydus Cadila (India)
  • Anuh Pharma Ltd. (India)

The manufacturing of contrast media APIs and finished products requires specialized facilities capable of handling potent compounds and ensuring high purity and sterility, especially for injectable formulations. GMP compliance is non-negotiable.

What Is the Patent Landscape?

The original patents for diatrizoic acid and its salts have long expired. However, the patent landscape relevant to Diatrizoate Meglumine and Diatrizoate Sodium includes:

• Formulations: Patents may cover specific ratios of Diatrizoate Meglumine to Diatrizoate Sodium in formulations, excipient combinations, or novel drug delivery systems that improve solubility, stability, or administration.
• Manufacturing Processes: Novel or improved synthetic routes for producing the APIs or intermediates with higher purity, yield, or reduced environmental impact can be patented. This includes specific purification methods or crystallization techniques.
• Medical Uses/Indications: While the primary uses are established, patents might exist for new diagnostic applications or administration methods for specific medical imaging procedures.
• Polymorphs and Crystal Forms: Discovery of new crystalline forms of the API with improved physical properties (e.g., stability, dissolution rate) can be patented.

Key Patent Holders and Areas of Interest:

• Bracco Imaging S.p.A.: Holds numerous patents related to contrast media, including formulations and delivery systems. For example, patents may address stability improvements or specific imaging applications.
• General Electric Healthcare: Has a historical and ongoing interest in contrast media technology, reflected in its patent filings related to formulations and applications.
• Bayer AG: Also actively patents in the diagnostic imaging space, potentially covering novel formulations or therapeutic combinations involving contrast agents.
• Academic Institutions and Smaller Biotech Firms: May hold patents on specific synthesis methodologies or novel applications that could be licensed to larger manufacturers.

Example of Patent Focus: A patent might claim "A pharmaceutical composition comprising diatrizoate meglumine and diatrizoate sodium in a weight ratio of 1:2 to 2:1, wherein the composition further comprises tromethamine and a chelating agent." Such patents aim to protect specific product characteristics.

To conduct a thorough patent search, databases like Google Patents, Espacenet, USPTO Patent Full-Text and Image Database, and commercial patent analytics platforms are utilized. Key search terms include "diatrizoate meglumine," "diatrizoate sodium," "contrast media," "radiopaque agent," and specific CAS numbers (e.g., 131-49-7 for Diatrizoic Acid, 131-51-1 for Diatrizoate Meglumine, 3119-15-1 for Diatrizoate Sodium).

What Are the Regulatory Considerations and Standards?

The manufacture and sale of Diatrizoate Meglumine and Diatrizoate Sodium are subject to stringent regulatory oversight by health authorities worldwide.

• Good Manufacturing Practices (GMP): Manufacturers of APIs and finished pharmaceutical products must adhere to GMP guidelines established by regulatory bodies like the U.S. Food and Drug Administration (FDA), the European Medicines Agency (EMA), and the World Health Organization (WHO). These standards ensure product quality, safety, and efficacy through controlled manufacturing processes, facility design, and quality management systems.
• Drug Master Files (DMFs) / Active Substance Master Files (ASMFs): API manufacturers typically submit DMFs (in the U.S.) or ASMFs (in Europe) to regulatory agencies. These confidential documents contain detailed information about the manufacturing process, quality control, and facilities for an API. Pharmaceutical companies reference these filings in their drug applications.
• Pharmacopeial Standards: Diatrizoate Meglumine and Diatrizoate Sodium must meet the specifications outlined in major pharmacopeias, such as the United States Pharmacopeia (USP), European Pharmacopoeia (Ph. Eur.), and Japanese Pharmacopoeia (JP). These monographs define identity, purity, strength, and quality attributes. For example, the USP monograph for Diatrizoate Meglumine Injection specifies requirements for appearance, identification, assay, pH, osmolality, and limits for impurities.
• Impurity Profiling: Regulatory agencies require thorough identification and control of impurities, including related substances, residual solvents, and potential genotoxic impurities. The synthetic route dictates the likely impurity profile, and robust analytical methods are needed for their detection and quantification.
• Excipient Regulations: For finished drug products, all excipients used must also comply with pharmacopeial standards and regulatory requirements.
• Product Registration: Finished drug products containing Diatrizoate Meglumine and Diatrizoate Sodium require marketing authorization from national regulatory authorities before they can be sold. This involves submitting comprehensive dossiers demonstrating safety, efficacy, and quality.
• Supply Chain Security and Traceability: Regulations are increasingly focused on ensuring the integrity of the pharmaceutical supply chain, including measures to prevent counterfeiting and ensure traceability from raw material to finished product.

Key Regulatory Bodies:

• U.S. Food and Drug Administration (FDA)
• European Medicines Agency (EMA)
• Pharmaceuticals and Medical Devices Agency (PMDA) - Japan
• Therapeutic Goods Administration (TGA) - Australia
• Health Canada
• National Medical Products Administration (NMPA) - China

Companies must maintain active communication with regulatory authorities and be prepared for site inspections to ensure ongoing compliance.

What Are the Market Dynamics and Competitive Landscape?

The market for radiopaque contrast media, including those based on diatrizoate salts, is mature but essential for diagnostic imaging.

• Established Product: Diatrizoate-based contrast agents have been in use for decades. They are well-characterized and are often considered cost-effective options for various imaging procedures.
• Competition from Newer Agents: The market faces competition from newer generations of contrast agents, such as iohexol, iopamidol, and iodixanol, which offer different physicochemical properties, lower osmolality, or improved safety profiles for certain patient populations. However, diatrizoate formulations remain competitive due to their established efficacy and lower cost.
• Geographic Market Segmentation: Demand is driven by the availability and utilization of advanced diagnostic imaging equipment (CT, angiography). Developed markets in North America, Europe, and parts of Asia represent significant demand centers. Emerging markets are expected to show growth as healthcare infrastructure expands.
• Key Market Drivers:
  • Aging population and increasing prevalence of chronic diseases requiring diagnostic imaging.
  • Technological advancements in imaging modalities.
  • Growing demand for minimally invasive procedures.
• Key Market Restraints:
  • High cost of newer contrast agents, leading to a preference for established, lower-cost options like diatrizoate in some regions.
  • Concerns about iodine-induced nephropathy, although this is generally more pronounced with older, higher-osmolality agents.
  • Increasing competition from biosimil or generic contrast agents in some markets.
• Consolidation and Partnerships: The industry has seen consolidation, with larger players acquiring smaller competitors or forming strategic partnerships to expand their product portfolios and market reach.

The competitive landscape is characterized by a few large, integrated players and numerous generic API and finished product manufacturers. Price sensitivity is a factor, especially in tendering processes for hospital supplies.

Key Takeaways

• The supply chain for Diatrizoate Meglumine and Diatrizoate Sodium is underpinned by a network of global chemical manufacturers for key intermediates such as 3,5-diaminobenzoic acid and iodine sources, alongside specialized suppliers for meglumine.
• Manufacturing is concentrated among established pharmaceutical companies and a significant number of generic API producers, particularly in India and China, all operating under strict GMP regulations.
• While foundational patents have expired, ongoing patent activity focuses on novel formulations, manufacturing process improvements, and specific medical applications.
• Regulatory compliance, including adherence to pharmacopeial standards and GMP, is critical for market access and supply chain integrity.
• The market for diatrizoate-based contrast media is mature but stable, facing competition from newer agents but maintaining its position due to cost-effectiveness and established efficacy.

FAQs

1. What is the primary advantage of Diatrizoate Meglumine and Diatrizoate Sodium over newer contrast agents? Their primary advantage is cost-effectiveness and a long history of established efficacy and safety for a broad range of diagnostic imaging procedures.

2. Are there specific challenges associated with sourcing 3,5-diaminobenzoic acid? Challenges can include ensuring consistent pharmaceutical-grade quality, secure supply agreements with manufacturers capable of meeting GMP standards, and managing potential price volatility of intermediate chemicals.

3. How do regulatory bodies assess the quality of Diatrizoate Meglumine and Diatrizoate Sodium APIs? They assess quality through review of DMFs/ASMFs, pharmacopeial compliance, impurity profiling data, and GMP audit reports of manufacturing facilities.

4. What is the typical shelf-life for injectable formulations of Diatrizoate Meglumine and Diatrizoate Sodium? Injectable formulations typically have a shelf-life of 2 to 3 years when stored under recommended conditions, as specified by the manufacturer and approved by regulatory authorities.

5. Can a single supplier provide both Diatrizoate Meglumine and Diatrizoate Sodium APIs? Yes, larger pharmaceutical chemical manufacturers or specialized contrast media API producers may offer both salts, simplifying procurement for finished product manufacturers.

Citations

[1] United States Pharmacopeia. (n.d.). Diatrizoate Meglumine Injection. In United States Pharmacopeia. Retrieved from [Specify access method if applicable, e.g., USP-NF Online database] [2] European Pharmacopoeia. (n.d.). Diatrizoic Acid. In European Pharmacopoeia. Retrieved from [Specify access method if applicable, e.g., Ph. Eur. Online database] [3] Global Health Intelligence. (Year of publication, if available). Contrast Media Market Analysis. [Report details, if publicly available] [4] Patent databases (e.g., Google Patents, Espacenet, USPTO). (Ongoing access). Search for patents related to diatrizoate meglumine and diatrizoate sodium. [5] Chemical industry directories and company websites (e.g., BASF SE, Merck KGaA, SQM S.A., Evonik Industries AG, Bracco Imaging S.p.A., GE Healthcare, Bayer AG). (Ongoing access).