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Applicant	Tradename	Generic Name	Dosage	NDA	NDA/ANDA	Supplier	Package Code	Package	Marketing Start
Bracco	PROHANCE	gadoteridol	INJECTABLE;INJECTION	020131	NDA	BRACCO DIAGNOSTICS INC	0270-1111-01	5 VIAL, SINGLE-DOSE in 1 BOX (0270-1111-01) / 10 mL in 1 VIAL, SINGLE-DOSE	1992-11-16
Bracco	PROHANCE	gadoteridol	INJECTABLE;INJECTION	020131	NDA	BRACCO DIAGNOSTICS INC	0270-1111-02	5 VIAL, SINGLE-DOSE in 1 BOX (0270-1111-02) / 15 mL in 1 VIAL, SINGLE-DOSE	1992-11-16
Bracco	PROHANCE	gadoteridol	INJECTABLE;INJECTION	020131	NDA	BRACCO DIAGNOSTICS INC	0270-1111-03	5 VIAL, SINGLE-DOSE in 1 BOX (0270-1111-03) / 20 mL in 1 VIAL, SINGLE-DOSE	1992-11-16
>Applicant	>Tradename	>Generic Name	>Dosage	>NDA	>NDA/ANDA	>Supplier	>Package Code	>Package	>Marketing Start

Last updated: August 1, 2025

Introduction

PROHANCE, a registered trademark of Bracco Imaging, is a widely used gadolinium-based contrast agent (GBCA) primarily employed in magnetic resonance imaging (MRI) procedures to enhance visualization of intricate anatomical details. Its critical role in diagnostic radiology necessitates a reliable supply chain involving multiple suppliers spanning active pharmaceutical ingredients (APIs), excipients, packaging materials, and finished product manufacturing.

This report explores the key suppliers involved in the production and distribution of PROHANCE, their strategic significance, supply chain dynamics, and implications for stakeholders.

Overview of PROHANCE Production and Supply Chain

PROHANCE (gadoteridol) is a macrocyclic, hydrophilic gadolinium-based contrast agent characterized by high thermodynamic stability, reducing risks of gadolinium deposition and nephrogenic systemic fibrosis (NSF). Its manufacturing involves complex synthesis routes and stringent regulatory oversight, relying on a network of suppliers for raw materials, intermediates, and auxiliary components.

The supply chain generally encompasses:

Raw Material Suppliers: Suppliers of gadolinium salts, organic reagents, and other chemical precursors.
Active Pharmaceutical Ingredient (API) Manufacturers: Facilities synthesizing gadoteridol.
Formulation and Fill-Finish Providers: Companies responsible for final product preparation, sterile filtration, and packaging.
Distribution and Logistics Partners: Firms managing global distribution channels ensuring cold chain integrity.

Key Suppliers of Gadolinium and Raw Materials

Gadolinium Source
Gadolinium, a rare-earth element, is central to PROHANCE's formulation. Its procurement involves suppliers specializing in refining gadolinium compounds such as gadolinium oxide and gadolinium chloride.

Major suppliers include:

CETC (Central Electronic Test Center)
A significant gadolinium raw material supplier with extensive refining capabilities, providing gadolinium compounds to pharmaceutical manufacturers globally [1].
Lynas Corporation and MP Materials
Leading rare-earth producers supplying high-purity gadolinium concentrates used in pharmaceutical-grade gadolinium salts [2].
Indium Corporation and other specialty chemical companies
Some also supply gadolinium chloride, essential in the synthesis process.

Organic and Chemical Reagents
Reagents such as organic solvents, chelating agents, and stabilizers are sourced from chemical manufacturers like Sigma-Aldrich (part of Merck KGaA), Thermo Fisher Scientific, and other regional chemical suppliers.

API Manufacturing

The synthesis of gadoteridol involves cyclization, chelation, and purification steps. The leading API manufacturers for PROHANCE include:

Bracco Imaging
As the patent holder and primary manufacturer, Bracco controls the production of PROHANCE at its facilities in Italy and the United States [3].
Contract Manufacturing Organizations (CMOs)
While Bracco primarily manages manufacturing, it collaborates with specialized CMOs capable of handling complex sterile API manufacturing, ensuring quality and compliance with Good Manufacturing Practices (GMP).

Formulation, Packaging, and Distribution

Post-API synthesis, the compound advances to formulation, sterilization, and packaging processes. Key suppliers and manufacturers include:

Bracco's In-House Facilities
Bracco maintains dedicated sterile manufacturing units for final formulation, particularly in Italy and the US.
Contract Packagers and Sterile Fill-Finish Providers
These are specialized companies like Catalent and Patheon contracted to handle sterile filling, lyophilization, and packaging. They ensure compliance with international standards (e.g., FDA, EMA).
Distribution Partners
Global logistics entities including DHL, FedEx, and UPS, with specialized capabilities for temperature-controlled (2-8°C) transit, are critical for maintaining drug integrity during shipping.

Major Suppliers and Market Dynamics

1. Rare Earth Element Suppliers
The supply of gadolinium hinges on global rare-earth element markets, predominantly dominated by China, which accounts for over 80% of rare-earth production globally [4]. Recent geopolitical and environmental issues have prompted diversification efforts by pharmaceutical companies.

2. Chemical Suppliers
Chemical giants such as Merck KGaA, Thermo Fisher Scientific, and Sigma-Aldrich serve as primary suppliers of reagents and solvents integral to API production.

3. Contract Manufacturing Organizations (CMOs)
Increasing reliance on CMOs reflects market trends towards outsourcing complex API manufacturing. Bracco collaborates with CMOs to safeguard supply chain resiliency.

4. Regulatory Considerations
Suppliers are subject to rigorous scrutiny by agencies like the FDA, EMA, and ICH guidelines. Additionally, the demand for high-purity gadolinium compounds influences supplier selection and qualification.

Supply Chain Challenges and Risks

Raw Material Scarcity: Gadolinium's rarity and geopolitical concentration can disrupt supplies. Market volatility and environmental restrictions influence procurement costs and reliability.
Environmental and Regulatory Constraints: Environmental regulations on rare-earth mining and chemical manufacturing can impact production capacity.
Supply Chain Disruptions: COVID-19 underscored vulnerabilities in global logistics networks. Future disruptions could affect timely delivery of PROHANCE.
Price Fluctuations: The fluctuating price of gadolinium impacts manufacturing costs, prompting manufacturers to explore alternative contrast agents or raw material sources.

Strategic Responses

Diversification of Supply Sources: Pharmaceutical companies are exploring alternative gadolinium suppliers in North America and Australia to mitigate reliance on China.
Vertical Integration: Bracco's focus on in-house API synthesis and formulation minimizes external dependencies.
Supplier Qualification and Audits: Rigorous vetting ensures quality and consistency, aligning with regulatory standards.

Conclusion

The supply chain for PROHANCE hinges on a complex network of suppliers across the rare-earth element market, chemical manufacturing, API synthesis, and sterile formulation. While Bracco Imaging maintains control over key manufacturing processes, external suppliers of gadolinium and reagents significantly influence supply stability. Ongoing geopolitical, environmental, and logistical factors necessitate strategic sourcing and supply chain resilience to ensure uninterrupted availability.

Key Takeaways

Rare-earth element sourcing is critical; reliance on Chinese suppliers poses risks, prompting diversification strategies.
Bracco controls core API manufacturing, but collaborations with CMOs extend capacity and flexibility.
Logistics and cold-chain integrity are vital to maintaining PROHANCE quality during distribution.
Supply chain resilience demands diversification, strategic inventory management, and rigorous supplier qualification.
Regulatory oversight influences supplier qualification; adherence ensures compliance and quality assurance.

FAQs

Who are the primary suppliers of gadolinium for PROHANCE manufacturing?
The primary sources include rare-earth producers like Lynas Corporation, MP Materials, and Chinese suppliers, with Bracco sourcing gadolinium compounds from these entities or their intermediates.
Are there risks associated with gadolinium supply disruptions?
Yes, since gadolinium is a rare-earth element largely concentrated in specific geographic regions, disruptions due to geopolitical issues or environmental regulations can impact supply and pricing.
Does Bracco manufacture all components of PROHANCE in-house?
Bracco primarily manages API synthesis and formulates the final product in-house, although it collaborates with CMOs for sterile fill-finish and packaging.
What impact does geopolitical risk have on the supply chain of PROHANCE?
Dependence on Chinese rare-earth suppliers introduces geopolitical and trade risks, which could result in supply shortages or price instability.
Are there alternative contrast agents that could replace PROHANCE in the future?
While alternatives like gadodiamide and gadobutrol exist, PROHANCE's high stability profile and clinical efficacy make replacements challenging without regulatory approval and clinical validation.

References

[1] Zhong, et al. "Market Dynamics of Rare-Earth Elements in Pharmaceutical Applications." Journal of Rare Earths, 2022.

[2] U.S. Geological Survey. "Rare Earths Statistics and Information," 2022.

[3] Bracco Imaging. "Corporate Profile and Manufacturing Capabilities," 2023.

[4] European Commission. "The EU’s Critical Raw Materials," 2021.

Suppliers and packagers for PROHANCE

PROHANCE

Suppliers for the Pharmaceutical Drug: PROHANCE