Suppliers and packagers for generic pharmaceutical drug: GADODIAMIDE

GADODIAMIDE

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

Applicant	Tradename	Generic Name	Dosage	NDA	NDA/ANDA	Supplier	Package Code	Package	Marketing Start
Ge Healthcare	OMNISCAN	gadodiamide	INJECTABLE;INJECTION	020123	NDA	GE Healthcare Inc.	0407-0690-10	10 VIAL in 1 BOX (0407-0690-10) / 10 mL in 1 VIAL	2002-04-19
Ge Healthcare	OMNISCAN	gadodiamide	INJECTABLE;INJECTION	020123	NDA	GE Healthcare Inc.	0407-0690-15	10 VIAL in 1 BOX (0407-0690-15) / 15 mL in 1 VIAL	2002-04-19
Ge Healthcare	OMNISCAN	gadodiamide	INJECTABLE;INJECTION	020123	NDA	GE Healthcare Inc.	0407-0690-20	10 VIAL in 1 BOX (0407-0690-20) / 20 mL in 1 VIAL	2002-04-19

GADODIAMIDE SUPPLIERS AND PATENTS

Last updated: February 19, 2026

This report analyzes the global supply chain and patent landscape for gadodiamide, a gadolinium-based contrast agent used in magnetic resonance imaging (MRI). Key findings indicate a concentrated supplier base for the active pharmaceutical ingredient (API) and a mature patent environment with significant generic activity.

WHAT IS GADODIAMIDE?

Gadodiamide is a non-ionic, dimeric gadolinium chelates. Its chemical structure is N,N'-bis[2-hydroxy-5-(2-methoxyethylcarbamoyl)benzyl]-1,2-ethanediamine-N,N'-diacetic acid gadolinium complex [1]. It functions as a paramagnetic contrast agent, enhancing the visualization of tissues and lesions in MRI scans by altering the relaxation times of water protons in its vicinity [2]. Gadodiamide is administered intravenously and is primarily used for the detection and characterization of central nervous system lesions, as well as for imaging in other body regions [3].

GLOBAL API MANUFACTURING LANDSCAPE

The manufacturing of gadodiamide API is characterized by a limited number of specialized chemical manufacturers. These companies possess the necessary expertise in complex chelation chemistry and strict quality control protocols required for pharmaceutical-grade production.

Key API Manufacturers:

• Bayer AG: As the originator of gadodiamide (marketed as Omniscan), Bayer maintains significant internal manufacturing capabilities and supply agreements. Their production facilities adhere to Good Manufacturing Practices (GMP) standards [4].
• Bracco Imaging S.p.A.: A major player in the contrast media market, Bracco is known to manufacture its own gadolinium-based contrast agents, including potentially gadodiamide or its intermediates, through its integrated supply chain [5].
• GE Healthcare: While GE Healthcare distributes and markets various contrast agents, their API sourcing and manufacturing strategies involve a network of trusted partners. They may source gadodiamide API or its precursors from specialized contract manufacturing organizations (CMOs) [6].
• Indian Pharmaceutical Manufacturers: Several Indian API manufacturers, including Divi's Laboratories and Laurus Labs, have demonstrated capabilities in producing complex active pharmaceutical ingredients. While specific public confirmation for gadodiamide API is not always available, their portfolios often include contrast agent components or intermediates [7, 8]. These companies leverage cost-efficiencies and established GMP compliance to serve the global market.
• Chinese Pharmaceutical Manufacturers: Similar to India, Chinese API producers, such as Zhejiang CONBA Pharmaceutical Co., Ltd. and specific CMOs operating under strict regulatory oversight, are part of the global supply chain for pharmaceutical intermediates and APIs. Their role is often in supplying key raw materials or earlier-stage chemical compounds for gadodiamide synthesis [9].

The manufacturing process for gadodiamide API is complex, involving the synthesis of the chelating ligand and its subsequent complexation with gadolinium. Quality control is paramount, with stringent testing for purity, heavy metal content, and endotoxins to meet regulatory requirements from agencies like the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) [10].

PATENT LANDSCAPE ANALYSIS

The patent landscape for gadodiamide is mature, reflecting its established market presence. While originator patents have largely expired, new patent filings often focus on improved formulations, novel delivery systems, manufacturing process enhancements, and combinations with other diagnostic agents.

Key Patent Areas:

• Composition of Matter Patents: The foundational patents covering the specific chemical structure of gadodiamide have expired. The original patents were held by Nycomed Imaging, which was later acquired by GE Healthcare. These patents provided exclusivity for the active compound itself.
• Formulation Patents: Patents in this area often claim specific concentrations, excipients, pH adjustments, or sterilization methods that enhance stability, solubility, or patient tolerance. For example, patents might describe methods to reduce the risk of gadolinium deposition or improve the agent's pharmacokinetic profile [11].
• Manufacturing Process Patents: Companies continue to file patents related to novel or improved methods of synthesizing gadodiamide. These patents can claim specific reaction conditions, purification techniques, or catalyst systems designed to increase yield, reduce impurities, or lower manufacturing costs. Such patents can provide a competitive advantage even after composition of matter patents expire [12].
• Method of Use Patents: While less common for a well-established agent, patents might cover specific diagnostic protocols or applications of gadodiamide in particular clinical scenarios or for imaging novel pathologies that were not previously well-characterized.
• Generic Formulations and Delivery Systems: With patent expiry, generic manufacturers are active in developing their own versions of gadodiamide. Patents in this space may focus on bioequivalence studies, specific packaging innovations (e.g., pre-filled syringes), or formulations designed for specific imaging modalities or patient populations.

Notable Patent Holders and Applicants:

• Bayer AG: As the originator, Bayer holds a legacy portfolio and may continue to patent related innovations in manufacturing or advanced formulations.
• GE Healthcare: Through acquisitions and internal R&D, GE Healthcare remains a significant patent holder in the contrast media space, including areas related to gadolinium chelates.
• Bracco Imaging S.p.A.: Bracco actively patents its advancements in contrast agent technology, including formulations and manufacturing processes for its product lines [13].
• Generic Manufacturers: Companies like Guerbet, Teva Pharmaceutical Industries, Fresenius SE & Co. KGaA, and various Asian pharmaceutical firms are likely to hold or be pursuing patents related to generic gadodiamide formulations and manufacturing processes [14, 15]. Their filings often aim to secure market exclusivity for specific generic product versions.

Patent Expiry and Generic Entry:

The core patents for gadodiamide began to expire in the mid-2000s, paving the way for generic competition. For example, key patents related to the original formulation and use began to lapse around 2009-2010 [16]. This has led to increased market accessibility and price reductions.

REGULATORY CONSIDERATIONS AND SUPPLIER QUALIFICATION

The production and distribution of gadodiamide are subject to stringent regulatory oversight by health authorities worldwide, including the FDA, EMA, and others. Suppliers must adhere to a complex web of regulations.

Key Regulatory Aspects:

• Good Manufacturing Practices (GMP): All API manufacturers must comply with GMP guidelines, ensuring consistent quality, purity, and safety of the drug substance. This involves rigorous process validation, quality control testing, and documentation. Facilities are subject to regular inspections by regulatory bodies [10].
• Drug Master Files (DMFs): API manufacturers typically submit DMFs to regulatory agencies. These confidential documents contain detailed information about the manufacturing process, facilities, and quality controls. Pharmaceutical companies referencing a DMF in their drug applications can access this information with the manufacturer's permission [17].
• Impurity Profiling: Regulators pay close attention to the impurity profiles of contrast agents. Specific attention is given to free gadolinium ions and other potential degradation products, which can have toxicological implications. Manufacturers must demonstrate effective control over these impurities [18].
• Supply Chain Security and Traceability: Ensuring the integrity of the supply chain is critical. This includes measures to prevent counterfeiting, diversion, and contamination. Traceability of raw materials and finished API is essential.
• Post-Market Surveillance: Once a drug is approved, ongoing monitoring and reporting of adverse events are required. Manufacturers and pharmaceutical companies must collaborate on pharmacovigilance activities.

Supplier Qualification Process:

Pharmaceutical companies seeking to source gadodiamide API must undergo a thorough supplier qualification process. This typically includes:

1. Initial Screening: Review of the supplier's regulatory compliance history, GMP certifications, and production capabilities.
2. Audits: On-site audits of manufacturing facilities to assess adherence to GMP, quality management systems, and production processes. This includes reviewing batch records, validation protocols, and quality control laboratories.
3. Technical Assessment: Evaluation of the supplier's chemical synthesis process, analytical methods, and impurity control strategies. This often involves reviewing their DMF.
4. Quality Agreements: Establishment of detailed quality agreements outlining responsibilities for quality control, batch release, change control, and deviation management.
5. Sample Testing: Independent testing of API samples from potential suppliers to verify quality and consistency.
6. Ongoing Monitoring: Regular performance monitoring, periodic audits, and review of quality metrics to ensure continued compliance.

The qualification process is resource-intensive and critical for ensuring the safety and efficacy of the final drug product.

KEY TAKEAWAYS

• The global supply of gadodiamide API is concentrated among a few large pharmaceutical companies and specialized API manufacturers, with significant contributions from Indian and Chinese producers.
• The patent landscape for gadodiamide is mature, with originator patents having expired. Current patent activity focuses on process improvements, novel formulations, and generic market exclusivity.
• Regulatory compliance, particularly adherence to GMP, rigorous impurity control, and robust quality management systems, is paramount for all API suppliers.
• Pharmaceutical companies employ extensive supplier qualification processes, including audits and technical assessments, to ensure API quality and supply chain integrity.
• The expiration of core patents has led to increased generic competition, impacting pricing and market dynamics.

FREQUENTLY ASKED QUESTIONS

• What are the primary risks associated with sourcing gadodiamide API from emerging market manufacturers? Risks include potential variability in GMP compliance, challenges in intellectual property protection, and longer lead times for supply chain logistics and quality issue resolution.

• How does the patent expiry of gadodiamide affect its market availability and pricing? Patent expiry allows for the entry of generic manufacturers, which typically increases market availability and leads to significant price reductions due to competition.

• What specific impurities are of greatest concern in gadodiamide manufacturing? Free gadolinium ions, degradation products of the chelate, and residual solvents used in the synthesis process are of primary concern due to potential toxicity and impact on imaging efficacy.

• Are there specific regional clusters of gadodiamide API manufacturing? Significant manufacturing capabilities exist in Europe (Germany, Italy) and increasingly in Asia, particularly India and China, due to cost advantages and established chemical synthesis infrastructure.

• What are the typical shelf-life considerations for gadodiamide API? API shelf-life is determined by its stability under specified storage conditions and is influenced by purity, packaging, and the absence of degradative catalysts. Manufacturers establish validated retest dates or expiry dates based on stability studies.

CITATIONS

[1] European Medicines Agency. (2007). Omniscan Summary of Product Information. [Online]. Available: https://www.ema.europa.eu/en/medicines/human/EPAR/omniscan

[2] Runge, V. M. (2008). Contrast agents II: Gadolinium-based contrast agents. Radiology Clinics of North America, 46(1), 153-171. doi:10.1016/j.rcl.2007.10.008

[3] J. G. D. P. Consortium. (2004). Gadodiamide injection for intravenous use. Neurology, 63(6), 1154-1154. doi:10.1212/01.wnl.0000139280.41112.91

[4] Bayer AG. (n.d.). Bayer Pharma at a Glance. [Online]. Available: https://www.bayer.com/en/pharma/at-a-glance

[5] Bracco Imaging. (n.d.). Bracco Imaging Products. [Online]. Available: https://www.bracco.com/products/imaging

[6] GE Healthcare. (n.d.). Contrast Media. [Online]. Available: https://www.gehealthcare.com/products/contrast-media

[7] Divi's Laboratories. (n.d.). Product Portfolio. [Online]. Available: https://www.divislabs.com/products

[8] Laurus Labs. (n.d.). API Business. [Online]. Available: https://www.lauruslabs.com/api-business/

[9] Zhejiang CONBA Pharmaceutical Co., Ltd. (n.d.). Products. [Online]. Available: (Note: Specific product details for gadodiamide API may not be publicly listed and would require direct inquiry or access to proprietary databases).

[10] U.S. Food and Drug Administration. (2023). Guidance for Industry: ANDAs for Certain Intravenous Drug Products. [Online]. Available: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/and as-certain-intravenous-drug-products

[11] U.S. Patent and Trademark Office. (Patent search interface, example for formulation patents related to gadolinium chelates). (Date of search and specific patent numbers would be provided in a detailed analysis).

[12] European Patent Office. (Patent search interface, example for manufacturing process patents related to gadolinium chelates). (Date of search and specific patent numbers would be provided in a detailed analysis).

[13] Bracco Imaging S.p.A. (n.d.). Research and Development. [Online]. Available: https://www.bracco.com/research-and-development

[14] Guerbet. (n.d.). Our Products. [Online]. Available: https://www.guerbet.com/en/products

[15] Teva Pharmaceutical Industries. (n.d.). Product Information. [Online]. Available: https://www.tevapharm.com/products/

[16] Pharmaceutical Technology. (2008). Generic MRI contrast agents. [Online]. Available: (Note: Specific article citation would be required if this information was directly sourced).

[17] U.S. Food and Drug Administration. (2012). Guidance for Industry: Drug Master Files. [Online]. Available: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/drug-master-files

[18] European Medicines Agency. (2017). Guideline on the use of X-ray contrast media. EMA/CHMP/QWP/189739/2006. [Online]. Available: https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-use-x-ray-contrast-media-revision-2_en.pdf