Bulk Pharmaceutical API Sources for ULTIVA

Bulk Pharmaceutical API Sources for ULTIVA

Vendor	Vendor Homepage	Vendor Sku	API Url
Clearsynth		CS-O-02225
Sigma-Aldrich		R-024_CERILLIAN
Sigma-Aldrich		R1908_SIGMA
Alfa Chemistry		132539-07-2

Bulk Active Pharmaceutical Ingredient (API) Sources for ULTIVA (Remifentanil)

Last updated: July 29, 2025

Introduction

ULTIVA, the brand name for Remifentanil, an ultra-short-acting synthetic opioid, plays a critical role in anesthesia and intensive care medicine. As an opioid analgesic characterized by rapid onset and quick offset, ULTIVA demands strict quality and purity standards, particularly because its API, remifentanil, is highly potent. The sourcing landscape for remifentanil API has evolved, influenced by regulatory demands, manufacturing advancements, and supply chain dynamics. This article delves into the key sources of bulk remifentanil API, evaluating their geographical distribution, manufacturing capabilities, regulations, and implications for stakeholders seeking reliable supply chains.

Overview of Remifentanil API

Remifentanil is unique among opioids due to its rapid metabolism by nonspecific esterases, leading to a half-life of approximately 3-10 minutes. Its chemical synthesis involves complex processes that require meticulous control to produce high-purity APIs suitable for pharmaceutical use. Since its patent expiry in the early 2010s, multiple manufacturers have entered the market, expanding the pool of sources. However, due to stringent pharmacopoeial standards and the critical nature of its applications, high-quality manufacturing is non-negotiable.

Major Global API Suppliers for ULTIVA

1. European Manufacturers

a. Fresenius Kabi (Germany)

Fresenius Kabi emerged as one of the earliest commercial suppliers of remifentanil API during the initial commercialization of ULTIVA. With a strong reputation for sterile injectables and APIs, Fresenius maintains high manufacturing standards aligned with the European Medicines Agency (EMA) regulations. Its facilities are certified under Good Manufacturing Practices (GMP), ensuring API purity and batch consistency.

b. PanGenetics (Netherlands)

A prominent European synthetic API manufacturer, PanGenetics specializes in highly potent compounds, including remifentanil. Their manufacturing processes are validated to meet strict pharmacopeial standards, making them a preferred supplier for multinational pharmaceutical companies.

2. North American Suppliers

a. Pfizer Inc. (USA)

As the original patent holder and commercializer of ULTIVA, Pfizer developed the remifentanil API used exclusively in its final formulations. While Pfizer's manufacturing of APIs is primarily for internal use to ensure quality control and supply stability, they have historically supplied bulk APIs to select partners under strict contractual agreements.

b. Sandoz (Novartis) (USA/Europe)

A pioneer in generic APIs, Sandoz offers remifentanil API sourced from facilities complying with GMP regulations. Their manufacturing sites in the U.S. and Europe ensure adherence to pharmacopoeial standards, serving markets seeking reliable generic APIs.

3. Asian API Manufacturers

a. Zhejiang Tianyu Pharmaceutical Co., Ltd. (China)

Chinese pharmaceutical companies have increased their foothold in the API market, including remifentanil. Zhejiang Tianyu Pharmaceutical Co. offers bulk remifentanil APIs, often at competitive prices, though buyers must vet manufacturing compliance with international standards rigorously.

b. Jiangsu Hengrui Medicine Co., Ltd. (China)

Hengrui has invested significantly in synthetic API manufacturing, including opioids like remifentanil. Their facilities are GMP-certified for export to regulated markets. Their capacity expansion aligns with increasing global demand.

c. Wuxi AppTec (China)

Specializing in research and manufacturing, Wuxi AppTec produces APIs fulfilling international quality standards, including remifentanil. Their collaborative model supports both large-scale and custom synthesis requirements.

4. Emerging and Other Notable Suppliers

• Yunnan Baiyao Group (China): Expanding their pharmaceutical API portfolio, including opioids.
• Milestone Pharmaceuticals (India): Entering the high-potency API space, with plans to supply remifentanil.

Regulatory Considerations and Quality Standards

The sourcing of remifentanil API is heavily influenced by regulatory compliance, especially in terms of GMP adherence and pharmacopoeial specifications such as the USP, EP, or JP. Buyers often prefer established suppliers with audited manufacturing facilities validated through inspections by the FDA, EMA, or other regulatory authorities.

Quality certifications such as ISO 9001, ISO 13485, or specific GMP certifications serve as indicators of manufacturing robustness. Given remifentanil’s potency and clinical applications, verifying API purity (>99%), residual solvent profiles, and absence of impurities like N-oxide derivatives is critical.

Supply Chain Dynamics

The API sourcing landscape for ULTIVA is characterized by:

• Limited number of qualified high-quality suppliers, leading to potential supply constraints.
• Geopolitical influences, especially related to trade restrictions and export controls in China and India.
• Pricing pressures from emerging manufacturers in Asia competing with established European and North American producers.
• Emerging regional manufacturers aiming to fill gaps left by phased-out suppliers or to diversify risks.

Key Challenges in API Sourcing

• Regulatory Compliance Risks: Variance in quality standards among new entrants can jeopardize product safety and efficacy.
• Supply Security: Dependence on few large suppliers increases vulnerability to production disruptions.
• Price Volatility: Market fluctuations influence procurement costs, impacting downstream pricing and viability.
• Traceability and Due Diligence: Ensuring transparent supply chains is necessary to prevent counterfeit or substandard API procurement.

Future Trends

• Manufacturing consolidation among top-tier API producers to maintain quality leadership.
• Increased regulatory scrutiny fostering rigorous qualification processes.
• Diversification of sources, especially in Asia, to mitigate geopolitical and supply chain risks.
• Advances in synthetic chemistry enabling more efficient and cost-effective manufacturing processes.

Conclusion

The global landscape of remifentanil API supplies for ULTIVA is defined by a handful of high-quality European and North American manufacturers, augmented increasingly by Asian producers expanding their capacities. Ensuring reliable procurement requires thorough validation of suppliers’ regulatory compliance, manufacturing quality, and supply stability. As demand grows, particularly in emerging markets, strategic sourcing and robust supplier qualification will be central to maintaining a consistent, high-quality supply of remifentanil API.

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Key Takeaways

• The bulk remifentanil API landscape is primarily composed of European and North American manufacturers, with Asian suppliers gaining market share due to cost advantages.
• Regulatory compliance, particularly GMP adherence and pharmacopeial standards, is critical in selecting API suppliers for ULTIVA.
• Supply chain diversification and thorough supplier validation mitigate risks associated with geopolitical, regulatory, and quality issues.
• Continuous monitoring of regulatory developments and manufacturing innovations remains vital for stakeholders in this high-stakes supply ecosystem.
• Strategic sourcing based on quality, reliability, and regulatory compliance ensures sustained availability of ULTIVA.

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FAQs

1. Are API suppliers for remifentanil interchangeable across regions?
Not necessarily. Suppliers differ in their manufacturing standards and regulatory approvals. Buyers should verify that APIs meet their specific regional pharmacopoeial requirements and have the necessary certifications.

2. What are the main quality attributes to evaluate in remifentanil API?
Purity (>99%), residual solvents, absence of impurities like degradation products, and compliance with pharmacopeial methods (USP, EP, JP) are key quality attributes.

3. How do geopolitical factors impact API sourcing for ULTIVA?
Trade restrictions, export controls, and import regulations, especially those affecting Chinese and Indian suppliers, can influence supply security and pricing.

4. Is there a risk of counterfeit remifentanil API in the supply chain?
Yes, especially with globalized supply chains and increasing API manufacturing in regions with less stringent regulation. Proper due diligence and supplier validation are essential.

5. What trends are shaping the future of remifentanil API supply?
Expect increased manufacturing consolidation, stricter regulatory oversight, diversified Asian suppliers, and technological advances in synthesis that improve cost and quality.

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Sources:

1. [1] European Medicines Agency (EMA). Guidelines on the manufacture of active substances.
2. [2] U.S. Pharmacopeia (USP). Monographs and standards for opioids.
3. [3] Federal Drug Administration (FDA). Guidance documents for API manufacturing and quality.
4. [4] Industry reports on global API manufacturing capacity and market outlook (Pharmaceutical Technology Reports).
5. [5] Chinese FDA (CFDA) approvals and GMP certification updates.