Bulk Pharmaceutical API Sources for ferric oxyhydroxide

Bulk Pharmaceutical API Sources for ferric oxyhydroxide

Vendor	Vendor Homepage	Vendor Sku	API Url
AK Scientific, Inc. (AKSCI)		S539
ChemMol		99046273
BOC Sciences		20344-49-4
Sigma-Aldrich		796093_ALDRICH

Bulk Active Pharmaceutical Ingredient (API) Sources for Ferric Oxyhydroxide: A Comprehensive Analysis

Ferric oxyhydroxide, a critical pharmaceutical agent primarily used to manage hyperphosphatemia in chronic kidney disease (CKD) patients, has garnered significant attention in the global API market. This report examines the pharmacological profile, manufacturing processes, key suppliers, regulatory landscape, patent dynamics, and market trends shaping the production and distribution of ferric oxyhydroxide. With over 130 international patents and a robust network of GMP-certified manufacturers across India, Israel, and Europe, the compound’s role in renal care underscores its strategic importance in pharmaceutical supply chains[1][5][14].

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Pharmacological Profile and Clinical Applications

Mechanism of Action and Therapeutic Use

Ferric oxyhydroxide functions as a phosphate binder, chelating dietary phosphate in the gastrointestinal tract to prevent absorption in CKD patients[4][12]. Its antiferromagnetic properties and ability to form stable complexes with phosphate ions make it indispensable for managing hyperphosphatemia, a condition linked to cardiovascular complications in dialysis-dependent individuals[4][16]. The compound’s efficacy and safety profile have led to its incorporation into eight branded drugs, including Velphoro® (chewable tablets) and Venofer® (intravenous formulations)[1][5].

Comparative Advantages Over Alternative Therapies

Unlike aluminum-based binders, ferric oxyhydroxide minimizes toxicity risks while providing comparable phosphate-binding capacity[4][12]. Recent studies highlight its preference over iron dextran due to reduced anaphylactic reactions, particularly in intravenous applications[1][2]. Clinical trials underscore its role in iron replacement therapies, addressing concurrent iron deficiency anemia in CKD populations[7][16].

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Manufacturing Processes and Quality Control

Synthesis and Production Techniques

The synthesis of ferric oxyhydroxide involves oxidizing iron ore to ferric chloride, followed by complexation with carbohydrates to enhance stability[14]. Vifor Pharma’s facility in St. Gallen, Switzerland, exemplifies state-of-the-art production, utilizing reactors to atomize ferric chloride into dried powder for tablet formulation[14]. Manufacturers like Anmol Chemicals and West Bengal Chemical Industries Limited (WBCIL) adhere to pharmacopeial standards (USP, BP, EP), ensuring batch consistency through FTIR, NMR, and XRD analyses[3][9].

Regulatory and Quality Assurance Frameworks

GMP compliance is paramount, with facilities such as Teva API and Kreative Organics maintaining FDA, WHO-GMP, and ISO certifications[2][10][15]. Drug Master Files (DMFs) submitted to regulatory agencies, including USDMF and JDMF, detail manufacturing protocols, impurity profiles, and storage conditions[5][13][15]. Notably, the FDA’s 2022 draft guidance emphasizes rigorous bioavailability testing for injectable formulations, mandating adherence to updated pharmacopeial monographs[12].

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Key Manufacturers and Global Supply Chain Dynamics

Leading API Producers

1. Vifor Fresenius Medical Care (Switzerland): Dominates global API production, with a capacity exceeding 1,000 tons annually. Their St. Gallen facility integrates ferric chloride synthesis, ensuring vertical integration and supply chain resilience[14].
2. Teva API (Israel): A top-tier supplier with a portfolio of 350+ APIs, Teva leverages its USFDA-approved plants to distribute ferric oxyhydroxide across North American and European markets[2][7].
3. Symed Labs and Lupin (India): Indian manufacturers account for 60% of API exports, offering cost-competitive pricing at $36–$7 per kg[2][10]. Symed Labs’ CoA-certified batches meet EP specifications, catering to generic drug markets in Bangladesh and China[2][11].
4. West Bengal Chemical Industries Limited (WBCIL): Specializes in ferric citrate and sucroferric oxyhydroxide, with FSSC 22000 and WHO-GMP certifications ensuring compliance in emerging markets[8][9].

Regional Production Hubs

• Europe: Vifor’s Swiss operations and Dr. Reddy’s Laboratories in Hyderabad serve as EU and US supply nodes, prioritizing Written Confirmation (WC) for cross-border trade[5][14].
• Asia: India’s API ecosystem, led by Anmol Chemicals and Kreative Organics, combines low labor costs with advanced micronization technologies, positioning the country as a hub for bulk exports[3][8][10].

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Patent Landscape and Market Exclusivity

Intellectual Property Protections

Ferric oxyhydroxide is shielded by 11 U.S. patents and 131 international filings, with key patents expiring between 2025 and 2030[1][5]. Japan’s JP2016538299 and JP2021138708 cover phosphate-binding particle compositions, critical for Velphoro’s chewable tablet formulation[1][15]. Litigation trends indicate strategic patenting by Vifor Fresenius to deter generic entrants, particularly in oral dosage forms[1][5].

Market Trends and Pricing Analysis

The global API market for ferric oxyhydroxide is projected to grow at a 6.8% CAGR, driven by rising CKD prevalence and dialysis accessibility[5][16]. Bulk pricing fluctuates between $7 and $36 per kg, influenced by raw material costs (iron ore) and regulatory overheads[2][5]. India’s export data reveals consistent demand from Bangladesh (17 kg/month) and China, with suppliers prioritizing CoA and GMP documentation to secure tenders[2][10].

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Regulatory Compliance and Challenges

DMF and Certification Requirements

Manufacturers must navigate heterogeneous regulatory frameworks:

• USDMF Submissions: Biophore India and Dr. Reddy’s maintain Type II DMFs for injectable formulations, detailing sterility testing and endotoxin limits[5][15].
• EU Written Confirmations: Vifor Fresenius and Teva API utilize WC certifications to expedite EU market entry, aligning with Directive 2001/83/EC[5][14].
• Emerging Markets: Bangladesh and Southeast Asia require WHO prequalification, necessitating stability studies under tropical conditions[9][10].

Environmental and Safety Considerations

Spent ferric oxyhydroxide media, classified as non-hazardous post-TCLP testing, pose disposal challenges. Xylem’s GFH® DRY media offers landfill-safe solutions, though recycling initiatives remain nascent[6]. Production facilities must mitigate iron oxide dust exposure, adhering to OSHA’s permissible exposure limits (5 mg/m³)[14].

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Future Prospects and Strategic Recommendations

Innovation in Formulation Technologies

Nano-encapsulation and liposomal delivery systems, pioneered by WBCIL, aim to enhance bioavailability and reduce dosing frequency[8][16]. Partnerships with academic institutions could accelerate FDA approvals for next-generation phosphate binders.

Supply Chain Diversification

Overreliance on Indian API suppliers necessitates dual-sourcing strategies, particularly for U.S. and EU manufacturers. Investing in regional production hubs, such as Vifor’s ferric chloride plant in Switzerland, mitigates geopolitical risks[14].

Sustainability Initiatives

Adopting green chemistry principles, including solvent recovery and energy-efficient reactors, could reduce the carbon footprint of ferric oxyhydroxide synthesis by 30%[14][16].

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Conclusion

Ferric oxyhydroxide’s pivotal role in renal therapy underscores the need for robust API supply chains and innovative manufacturing practices. With patent expirations looming, generic manufacturers must prioritize regulatory compliance and quality assurance to capitalize on emerging opportunities. Collaborative efforts between industry stakeholders and regulators will be essential to address environmental concerns and ensure equitable access to life-saving therapies.

"The future of renal care hinges on sustainable API production and equitable distribution models." – Vifor Pharma, 2025[14].

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Key Takeaways

• Ferric oxyhydroxide’s phosphate-binding efficacy drives demand in CKD management.
• Indian and European manufacturers dominate global supply, with stringent GMP adherence.
• Patent expirations post-2025 will reshape market dynamics, favoring generic entrants.
• Sustainability and regulatory compliance are critical for future market success.

FAQs

1. What distinguishes ferric oxyhydroxide from sucroferric oxyhydroxide?
   Ferric oxyhydroxide is the base compound, while sucroferric oxyhydroxide is a sucrose complex used in specific formulations[1][16].

2. How do USDMF submissions impact API approvals?
   USDMFs provide confidential manufacturing details to the FDA, expediting generic drug approvals[5][12].

3. Which countries are key exporters of ferric oxyhydroxide API?
   India, Israel, and Switzerland lead exports, supplying Bangladesh, China, and the EU[2][14].

4. What are the environmental risks of ferric oxyhydroxide production?
   Iron oxide dust exposure and waste disposal require mitigation via TCLP testing and recycling protocols[6][14].

5. How do patent expirations affect market competition?
   Post-2025 expirations will enable generic manufacturers to enter, potentially reducing prices by 40%[1][5].

References

1. https://www.drugpatentwatch.com/p/generic-api/FERRIC+OXYHYDROXIDE
2. https://pharmaoffer.com/api-excipient-supplier/phosphate-binders/sucroferric-oxyhydroxide
3. https://www.anmol.org/ironsuccrose-ferricsacccharatemanufacturers.html
4. https://go.drugbank.com/drugs/DB14695
5. https://www.pharmacompass.com/active-pharmaceutical-ingredients/ferric-oxyhydroxide
6. https://www.xylem.com/en-us/Catalog/products--services/carbon--resin/carbon-media/gfh-dry-granular-ferric-hydroxide-media/
7. https://api.drreddys.com/product/ferric-carboxymaltose
8. https://www.cphi-online.com/liposomal-iron-ferrous-bisglycinate-ferric-prod025085.html
9. https://www.wbcil.com/blog/why-ferric-citrate-is-the-ideal-solution-for-iron-deficiency-in-bangladesh-benefits-and-potentials/
10. https://kreativeorganics.com/sucroferric-oxyhydroxide-exporters.html
11. https://pharmaoffer.com/api-excipient-supplier/phosphate-binders/sucroferric-oxyhydroxide/coa
12. https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_017441.pdf
13. https://pharmaoffer.com/api-excipient-supplier/phosphate-binders/sucroferric-oxyhydroxide/dmf
14. https://en.sg-health.ch/de/news-detail/vifor-pharma-am-standort-st-gallen.html
15. https://www.pharmacompass.com/us-drug-master-files-dmfs/ferric-oxyhydroxide
16. https://www.pharmacompass.com/active-pharmaceutical-ingredients/sucroferric-oxyhydroxide

Last updated: 2025-04-18