Bulk Pharmaceutical API Sources for perflutren

Bulk Pharmaceutical API Sources for perflutren

Vendor	Vendor Homepage	Vendor Sku	API Url
ChemExper Chemical Directory		HmT@D@dDdLdJdFdAdIdEdLbdLadjjj`@@
NovoSeek		6432
ABI Chem		AC1L1MIR
ABI Chem		AC1Q4IBX
ISpharm		I14-14876
ChemMol		49416688
ChemMol		49423611

Bulk Active Pharmaceutical Ingredient (API) Sources for PERFLUTREN

Last updated: July 27, 2025

Introduction

Perflutren, marketed under brand names such as Definity, Lumason, and others, is an ultrasound contrast agent used primarily for enhancing echocardiography and other ultrasonic imaging procedures. Its active pharmaceutical ingredient (API) is perflutren lipid microspheres, a lipid-encapsulated perfluorocarbon compound. The manufacturing and sourcing of bulk API for Perflutren is a complex process, requiring adherence to stringent quality, safety, and regulatory standards due to the sensitive nature of pharmaceutical microcapsules and perfluorocarbon chemistry.

This report assesses the key sources and considerations for procuring bulk API for Perflutren, analyzing existing manufacturers, raw materials, regulatory landscape, and logistical considerations.

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Understanding the API: Perflutren Lipid Microspheres

Perflutren lipid microspheres consist of a perfluorocarbon core encapsulated within phospholipid shells, typically phosphatidylcholine derivatives, stabilized with additional lipids like phosphatidylglycerol and polyethylene glycol conjugates. The perfluorocarbon used most commonly in Perflutren is perfluoropropane (C3F8), renowned for its stability, inertness, and safety profile in medical applications.

The API's propriety formulation involves meticulous control over size distribution, shell integrity, and perfluorocarbon content, making sourcing a highly regulated activity.

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Key Sources of Raw Materials & API Components

1. Perfluoropropane (C3F8) – The Core Active Ingredient

Perfluoropropane is integral to the API, functioning as the contrast-enhancing agent. Major manufacturers include:

• Chemours: A leading producer of perfluorocarbons, including C3F8, with facilities in the USA and Belgium. Chemours supplies pharmaceutical-grade C3F8, adhering strictly to safety and purity standards (Ref. [1]).

• 3M and Other Specialty Gas Suppliers: Known for high-purity specialty gases, they supply C3F8 for medical applications, often requiring suppliers to meet ISO 13485 standards.

• DCC (Digital Chemistry Corporation): Occasionally provides custom-grade perfluorocarbons suitable for medical formulations, with emphasis on purity and stability.

2. Phospholipids (Shell Material)

Phospholipids form the lipid shell of microspheres:

• Lipoid GmbH (Lipoid): A major global supplier of pharmaceutical-grade phosphatidylcholine, phosphatidylglycerol, and related lipids. Their products comply with USP/NF standards, ensuring compatibility for injectable formulations.

• Avanti Polar Lipids: Supplies high-quality phospholipids used in pharmaceutical and research settings, with an emphasis on purity and reproducibility.

• Desirable Quality Standards: Suppliers must demonstrate compliance with pharmacopeial standards, such as USP, EP, or JP, and have documentation supporting traceability and batch-to-batch consistency.

3. Emulsifiers and Stabilizers

These include polyethylene glycol (PEG) derivatives and other stabilizing agents:

• Dow Chemical and Sigma-Aldrich: Provide pharmaceutical-grade PEG derivatives suitable for lipid microsphere stabilization.

• Application of Good Manufacturing Practice (GMP): Proper sourcing of excipients is critical to ensure safety and efficacy.

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Manufacturers Specializing in API and Contract Production

While the API for Perflutren—primarily the lipid microspheres—is not widely available from multiple commercial API producers due to proprietary technology, some contract manufacturing organizations (CMOs) and pharmaceutical companies develop and produce APIs for ultrasound contrast agents.

1. Lantheus Medical Imaging

• Role: The primary innovator and manufacturer of Perflutren-based contrast agents like Definity® and Lumason® (known as SonoVue® outside the U.S.). They control the end-to-end manufacturing of the API, maintaining proprietary formulations and processes.

• API Production: Lantheus performs in-house synthesis with proprietary lipid encapsulation technology, making their APIs unavailable for external sourcing.

2. ResMed and Bracco Group

• ResMed: Specializes in medical gases and some contrast agents, but not API production for Perflutren specifically.

• Bracco Imaging: Produces ultrasound contrast agents (e.g., SonoVue). Their manufacturing involves proprietary processes, and they usually do not externalize API sourcing.

3. Contract Manufacturing & Outsourcing

Due to proprietary formulations, most bulk APIs for Perflutren are produced in-house by patent holders. However, certain niche suppliers and CMOs may offer custom manufacturing services for research or clinical trial purposes:

• Recipharm and Patheon (Thermo Fisher Scientific): Known for contract formulation and manufacturing services, but specific API production for Perflutren remains restricted.

• Innovative Contract Manufacturing Firms in China & India: These firms may develop lipid microencapsulation APIs under license or through technology transfer agreements, subject to strict regulatory oversight.

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Regulatory & Quality Considerations

Sourcing of API components for Perflutren necessitates compliance with:

• FDA: The U.S. Food and Drug Administration enforces strict standards for APIs used in injectable contrast agents, requiring pre-approval, GMP compliance, and batch validation.

• EMA and International Standards: Similar stringent requirements are imposed by the European Medicines Agency and other regulators.

• Pharmacopeial Standards: USP, EP, JP specifications dictate purity, residual solvents, endotoxin levels, sterility, and particle size distribution.

Supply Chain & Logistics

Given the sensitive nature of perfluorocarbons and lipids, suppliers must ensure cold-chain logistics and contamination control to preserve product integrity. Batch traceability and comprehensive documentation are mandatory for regulatory approval.

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Market and Competitive Landscape

The market for bulk API sourcing for Perflutren is concentrated predominantly among established pharmaceutical players with proprietary manufacturing facilities. Smaller biotech firms and research organizations may explore custom API production for clinical trials, but commercial scale sourcing remains limited.

Limited external API supply reflects the proprietary nature of the formulations, high entry barriers, and the necessity for strict regulatory compliance. Future sourcing opportunities may stem from licensing agreements, partnerships, or emerging technology platforms capable of producing lipid microencapsulated perfluorocarbons.

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Emerging Trends & Future Outlook

• Alternative Perfluorocarbons: Innovations in eco-friendly and stable perfluorocarbon compounds could diversify supply sources.

• Advanced Manufacturing Techniques: Microfluidic and nanotechnology-based lipid encapsulation methods could lead to new API formulations, potentially opening avenues for third-party API sourcing.

• Regulatory Harmonization: As global standards mature, access to bulk API may expand if new licensed suppliers emerge.

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Key Takeaways

• Limited External API Sources: The proprietary nature of Perflutren API means most production is vertically integrated by patent holders like Lantheus. External sourcing mainly involves raw materials—perfluorocarbons and phospholipids.

• Critical Raw Material Suppliers: Chemours, Lipoid GmbH, and Avanti Polar Lipids are primary suppliers for high-purity precursors used in API fabrication.

• Regulatory Compliance: Strict adherence to GMP, FDA, EMA requirements is non-negotiable for API procurement.

• Supply Chain Management: Perfluorocarbon handling demands robust logistics, traceability, and contamination controls.

• Future Opportunities: Growing interest in alternative formulations and encapsulation technologies may diversify the supply landscape.

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FAQs

1. Can I directly purchase bulk API for Perflutren from manufacturers?
Typically, no. Due to proprietary formulations and regulatory restrictions, most companies retain control over their APIs. Raw materials like perfluorocarbons and phospholipids are available to authorized entities under strict agreements.

2. What are the main raw materials necessary for manufacturing Perflutren API?
Perfluoropropane (C3F8) for the core contrast agent, phospholipids for the shell, and stabilizing agents like PEG derivatives.

3. Which companies supply pharmaceutical-grade phospholipids suitable for Perflutren?
Lipoid GmbH and Avanti Polar Lipids are prominent suppliers of phosphatidylcholine and related phospholipids complying with pharmacopeial standards.

4. Are there regional differences in sourcing Perflutren API components?
Yes. Regulatory requirements, quality standards, and supplier availability differ; North America, Europe, and Asia have distinct suppliers, with certain regions favoring local GMP-compliant providers.

5. What future developments could affect API sourcing for Perflutren?
Emerging encapsulation technologies, alternative perfluorocarbons, and regulatory shifts toward open manufacturing may alter sourcing strategies and reduce dependency on proprietary providers.

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References:

[1] Chemours. "Perfluorochemicals." Accessed 2023.