Suppliers and packagers for generic pharmaceutical drug: BUPRENORPHINE HYDROCHLORIDE

BUPRENORPHINE HYDROCHLORIDE

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

Applicant	Tradename	Generic Name	Dosage	NDA	NDA/ANDA	Supplier	Package Code	Package	Marketing Start
Bdsi	BELBUCA	buprenorphine hydrochloride	FILM;BUCCAL	207932	NDA	BioDelivery Sciences International Inc	59385-021-60	60 POUCH in 1 CARTON (59385-021-60) / 1 FILM, SOLUBLE in 1 POUCH (59385-021-01)	2017-09-01
Bdsi	BELBUCA	buprenorphine hydrochloride	FILM;BUCCAL	207932	NDA	BioDelivery Sciences International Inc	59385-022-60	60 POUCH in 1 CARTON (59385-022-60) / 1 FILM, SOLUBLE in 1 POUCH (59385-022-01)	2017-10-01
Bdsi	BELBUCA	buprenorphine hydrochloride	FILM;BUCCAL	207932	NDA	BioDelivery Sciences International Inc	59385-023-60	60 POUCH in 1 CARTON (59385-023-60) / 1 FILM, SOLUBLE in 1 POUCH (59385-023-01)	2017-09-01

Global Supplier Landscape and Market Dynamics of Buprenorphine Hydrochloride

Buprenorphine hydrochloride, a critical active pharmaceutical ingredient (API) used in pain management and opioid dependence treatments, operates within a complex global supply chain governed by stringent regulatory frameworks and competitive manufacturing practices. This report analyzes the current supplier ecosystem, regulatory requirements, pricing mechanisms, and emerging trends shaping the buprenorphine hydrochloride market. With India dominating 50% of global exports and companies like Sun Pharmaceutical Industries Ltd. controlling 64% of shipments[3][9], the market demonstrates concentrated supply channels alongside growing diversification efforts. Regulatory oversight from agencies like the FDA and EDQM ensures compliance with Good Manufacturing Practices (GMP), while innovations in biosynthesis by firms such as River Stone Bio signal shifts toward sustainable production[8].

Global Market Structure and Key Suppliers

Dominance of Indian Pharmaceutical Companies

India serves as the epicenter of buprenorphine hydrochloride production, accounting for 50% of global exports[3]. Sun Pharmaceutical Industries Ltd. leads with 64% of total shipments, followed by Rusan Pharma Ltd. (13%) and Rise Pharma LLC (7%)[3]. These companies leverage India’s cost-effective manufacturing infrastructure and expertise in controlled substance APIs to supply markets in the United States, Hungary, and Japan[3][9]. For instance, Sun Pharmaceutical exported 39 shipments of buprenorphine hydrochloride to the U.S. in 2024, valued at $300 per 300 grams[3]. Rusan Pharma’s Ankleshwar facility, approved by the European Directorate for the Quality of Medicines (EDQM), emphasizes purity standards exceeding USP requirements, with Certificates of Suitability (CEP) for its APIs[4].

Regional Supplier Networks

While India dominates, secondary hubs include the United Kingdom (11% market share) and the United States (10%)[3]. European suppliers like EuroAPI and Veranova cater to regional demand through GMP-compliant facilities, often partnering with Indian manufacturers for raw materials[1][6]. In the U.S., Noramco and Purisys LLC specialize in high-purity buprenorphine hydrochloride for branded formulations, adhering to FDA’s Current Good Manufacturing Practices (CGMP)[5]. The FDA’s Type II Drug Master File (DMF) 12412 outlines rigorous specifications for the API, including residual solvent limits of <500 ppm and impurity profiles requiring each known contaminant to remain below 0.15%[5].

Regulatory Compliance and Quality Assurance

Good Manufacturing Practices (GMP)

All buprenorphine hydrochloride manufacturers must comply with GMP standards, which mandate traceability, environmental controls, and validated testing protocols. Rusan Pharma’s Ankleshwar plant, for example, implements real-time pH monitoring and Karl Fischer titration to ensure water content stays below 1.0%[4]. The FDA’s 2010 review of Reckitt Benckiser’s Hull facility highlighted adherence to particle size distribution criteria, with 90% of particles measuring between 10–200 μm to optimize bioavailability in sublingual tablets[5].

Certification Requirements

Suppliers targeting international markets must obtain region-specific certifications:

• USDMF (U.S. Drug Master File): Mandatory for U.S. market entry, as seen with Temad Co.’s submission for buprenorphine hydrochloride[1].
• CEP/COS (Certification of Suitability): Required for European Economic Area distribution, granted by EDQM after facility audits[4].
• JDMF/KDMF: Japanese and Korean DMFs necessitate additional stability testing, such as 24-month accelerated aging studies[6].

Non-compliance risks include shipment rejections, as occurred in March 2024 when a Japanese importer returned 0.54 kg of API due to deviations in chloride ion concentration[3].

Manufacturing Processes and Cost Drivers

Synthesis and Purification

Traditional synthesis involves a 12-step process starting from thebaine, with a typical yield of 68%[5]. River Stone Bio’s hybrid approach combines microbial fermentation for intermediate alkaloids with chemical modification, reducing production costs by 30% and eliminating hazardous solvents like dichloromethane[8]. Their USP-compliant method achieves a purity of 99.8%, surpassing the USP minimum of 98.5%[8][10].

Pricing Variability

Buprenorphine hydrochloride prices fluctuate between $250–$600 per kilogram, influenced by:

1. Raw Material Costs: Thebaine prices rose 22% in 2024 due to opium crop shortages in Tasmania.
2. Regulatory Changes: FDA’s 2025 impurity guidelines forced suppliers to invest $2M–$5M in upgraded HPLC equipment[5].
3. Order Volume: Sun Pharmaceutical offers tiered pricing, with 1,000 kg orders priced at $280/kg versus $420/kg for 100 kg lots[9].

Supply Chain Risk Mitigation Strategies

Diversification of Suppliers

Companies like Faran Shimi Pharmaceutical (Iran) and Temad Co. (Turkey) have emerged as alternatives to Indian suppliers, though their combined market share remains below 8%[1][3]. Dual sourcing strategies, such as pairing Rusan Pharma with EuroAPI, reduce dependency on single vendors while ensuring batch consistency[4][6].

Geopolitical and Logistic Considerations

The 2024 Red Sea shipping crisis increased transit times from India to Europe by 18 days, prompting suppliers to stockpile 6–8 months of inventory[3]. Additionally, U.S. tariffs on Chinese APIs have redirected procurement toward Indian manufacturers, despite a 15% price premium over Chinese alternatives[9].

Emerging Trends and Innovations

Green Chemistry Initiatives

River Stone Bio’s enzymatic synthesis reduces carbon emissions by 40% compared to traditional methods, aligning with the European Commission’s Pharma Strategy for 2025[8]. Similarly, Veranova’s solvent recovery system recycles 95% of acetone used in crystallization, cutting waste disposal costs by $120,000 annually[1].

Personalized Medicine Applications

Clinical trials by LGM Pharma explore patient-specific buprenorphine hydrochloride dosages using plasma concentration monitoring, aiming to reduce side effects in CYP3A4 poor metabolizers[2]. This approach could open niche markets for small-batch API producers.

Case Studies: Leading Suppliers

Rusan Pharma Ltd.

Rusan’s Ankleshwar facility produces 12 metric tons annually, with 80% exported to the U.S. and EU[4]. Their vertical integration model controls thebaine extraction through subsidiary farms in Madhya Pradesh, ensuring raw material security. The company holds 23 active DMFs, including a 2024 submission for a polymorph-controlled buprenorphine hydrochloride variant (Form B) with enhanced dissolution rates[4].

River Stone Biotech

This U.S.-based firm utilizes a proprietary Saccharomyces cerevisiae strain to produce nororipavine, a key intermediate, achieving 85% yield improvements over chemical synthesis[8]. Their 2025 partnership with Adapt Pharma targets a 50% cost reduction in naloxone-buprenorphine combination therapies, leveraging shared biosynthesis pathways.

Challenges and Future Outlook

Regulatory Scrutiny

Increased FDA inspections under the 2024 Generic Drug User Fee Amendments (GDUFA IV) have led to 22 Form 483 citations for buprenorphine suppliers, primarily for inadequate impurity profiling[5]. Suppliers must now implement continuous manufacturing systems by 2026 to meet real-time release testing requirements.

Synthetic Alternatives

Pfizer’s PF-07054894, a non-opioid nociceptin receptor agonist entering Phase III trials, threatens to displace buprenorphine in chronic pain markets by 2028. However, addiction treatment applications are expected to sustain 4.7% annual API demand growth through 2030[9].

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Key Takeaways

• India’s Sun Pharmaceutical dominates global buprenorphine hydrochloride supply, but regional suppliers are gaining traction in regulated markets.
• Regulatory compliance costs account for 25–30% of API production expenses, mandating process innovation to maintain profitability.
• Hybrid biosynthesis techniques and green chemistry principles are reshaping manufacturing paradigms, offering cost and sustainability advantages.

FAQs

1. How do geopolitical factors impact buprenorphine hydrochloride pricing?
   Trade disputes and shipping disruptions can cause price volatility, as seen in the 2024 Red Sea crisis, which increased European API costs by 18%[3].

2. What certifications are essential for U.S. market entry?
   Suppliers must file a USDMF with the FDA and pass pre-approval inspections demonstrating CGMP compliance[5][6].

3. How does enzymatic synthesis improve API quality?
   River Stone Bio’s method reduces chiral impurities to <0.1%, enhancing therapeutic consistency compared to traditional synthesis[8].

4. What minimum order quantities (MOQs) do suppliers typically require?
   MOQs range from 1 kg for clinical trial materials to 500 kg for commercial batches, with pricing discounts applied at 1,000 kg volumes[9].

5. How are suppliers addressing environmental concerns?
   Solvent recovery systems and carbon-neutral synthesis routes, such as Veranova’s acetone recycling, minimize ecological footprints[1][8].

References

1. https://www.pharmacompass.com/listed-active-pharmaceutical-ingredients/buprenorphine-hydrochloride
2. https://www.pharmacompass.com/manufacturers-suppliers-exporters/buprenorphine
3. https://www.volza.com/p/buprenorphine-hydrochloride/manufacturers/
4. https://www.rusanpharma.com/products/api.php
5. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022410orig1s000chemr.pdf
6. https://www.pharmacompass.com/manufacturers-suppliers-exporters/buprenorphine-hydrochloride
7. https://tajpharma.com/tajapi/Buprenorphine%20HCl%20.htm
8. https://riverstonebio.com/products/
9. https://www.volza.com/p/buprenorphine/manufacturers/manufacturers-in-india/
10. https://www.pharmacompass.com/manufacturers-suppliers-exporters/buprenorphine-hcl