Suppliers and packagers for generic pharmaceutical drug: AVIBACTAM SODIUM; CEFTAZIDIME

AVIBACTAM SODIUM; CEFTAZIDIME

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

Applicant	Tradename	Generic Name	Dosage	NDA	NDA/ANDA	Supplier	Package Code	Package	Marketing Start
Abbvie	AVYCAZ	avibactam sodium; ceftazidime	POWDER;INTRAVENOUS	206494	NDA	Allergan, Inc.	0456-2700-10	10 VIAL, SINGLE-DOSE in 1 CARTON (0456-2700-10) / 1 POWDER, FOR SOLUTION in 1 VIAL, SINGLE-DOSE (0456-2700-01)	2014-12-26

AVIBACTAM SODIUM AND CEFTAZIDIME SODIUM: GLOBAL SUPPLY CHAIN ANALYSIS

Last updated: February 19, 2026

Avibactam sodium, a novel beta-lactamase inhibitor, and ceftazidime sodium, a third-generation cephalosporin antibiotic, are co-formulated in the fixed-dose combination drug known as avibactam/ceftazidime. This combination targets a broad spectrum of gram-negative bacterial infections, including those caused by multidrug-resistant (MDR) pathogens. The reliable and cost-effective sourcing of both active pharmaceutical ingredients (APIs) is critical for the consistent global supply of this essential medicine.

KEY MANUFACTURING REGIONS AND SUPPLIERS

The manufacturing of avibactam sodium and ceftazidime sodium involves complex chemical synthesis processes. Major production hubs are concentrated in Asia, particularly China and India, due to cost advantages and established chemical manufacturing infrastructure. Europe also hosts key players, often focusing on specialized intermediates or final API purification.

AVIBACTAM SODIUM SUPPLIERS

Avibactam sodium synthesis is a multi-step process requiring specialized expertise. The primary suppliers are located in China and India, with a smaller presence in Europe.

• China: This region dominates avibactam sodium intermediate and API production. Key manufacturers include:
  • Wuhan Fortuna Chemical Co., Ltd.
  • Jinan Lide Pharmaceutical Co., Ltd.
  • Shandong Xinhua Pharmaceutical Co., Ltd.
  • Hec Pharm (Hubei) Co., Ltd.
• India: Indian pharmaceutical companies have increased their capacity for complex API manufacturing, including avibactam sodium. Notable suppliers include:
  • Aurobindo Pharma Ltd.
  • Dr. Reddy's Laboratories Ltd.
  • Divi's Laboratories Ltd.
• Europe: While less prominent in bulk API manufacturing, some European entities may be involved in the production of advanced intermediates or specialized processing.

CEFTAZIDIME SODIUM SUPPLIERS

Ceftazidime sodium is a more established API with a broader supplier base. Production is spread across China, India, and Europe.

• China: A significant source of ceftazidime sodium API.
  • North China Pharmaceutical Group Corporation (NCPC)
  • Zhejiang Medicine Co., Ltd.
  • Shanxi Ciyuan Biotechnology Co., Ltd.
• India: Indian manufacturers are major global suppliers of ceftazidime sodium.
  • Sun Pharmaceutical Industries Ltd.
  • Lupin Ltd.
  • Cipla Ltd.
  • Torrent Pharmaceuticals Ltd.
• Europe: European manufacturers often emphasize quality control and regulatory compliance, catering to highly regulated markets.
  • Fresenius Kabi (part of Fresenius SE & Co. KGaA) - primarily a formulator but has significant API sourcing and quality control.
  • Teva Pharmaceutical Industries Ltd. - while a global entity with manufacturing across regions, has European production capabilities for certain antibiotics.

PRODUCTION PROCESS AND QUALITY CONTROL

The synthesis of both avibactam sodium and ceftazidime sodium requires stringent process controls to ensure purity, potency, and the absence of harmful impurities.

AVIBACTAM SODIUM SYNTHESIS

Avibactam sodium is derived from pyrrolidine derivatives. The synthesis typically involves several key stages:

1. Formation of the pyrrolidine core: This often starts with L-proline or related amino acids.
2. Introduction of the sulfonyl group: A crucial step that forms the characteristic sulfonyl moiety.
3. Attachment of the aminomethyl group: This completes the active moiety of avibactam.
4. Salt formation: Conversion to the sodium salt for improved solubility and bioavailability.

Impurities commonly monitored include unreacted starting materials, side-reaction products, and isomers. Strict adherence to Good Manufacturing Practices (GMP) is essential, with batch-to-batch consistency verified through analytical testing.

CEFTAZIDIME SODIUM SYNTHESIS

Ceftazidime sodium is synthesized from 7-aminocephalosporanic acid (7-ACA), a key cephalosporin nucleus. The process involves:

1. Acylation of 7-ACA: The side chain containing the aminothiazole ring and the carboxypropoxy group is attached to the 7-amino group of 7-ACA.
2. Introduction of the oxime ether: This step is critical for the antibiotic's spectrum of activity.
3. Salt formation: Conversion to the sodium salt.

Critical quality attributes include:

• Purity: Typically >98.0% by HPLC.
• Related substances: Limits for specific impurities (e.g., ceftazidime dimer, unreacted 7-ACA) are defined by pharmacopoeial standards.
• Water content: Controlled to ensure stability.
• pH: Within a specified range for injectability.

REGULATORY AND QUALITY STANDARDS

Manufacturers must comply with international regulatory standards, including those set by the U.S. Food and Drug Administration (FDA), the European Medicines Agency (EMA), and other national health authorities. Pharmacopoeial monographs (e.g., United States Pharmacopeia (USP), European Pharmacopoeia (Ph. Eur.)) provide detailed specifications for API quality.

• GMP Certification: All API manufacturers supplying regulated markets must hold current GMP certifications.
• Drug Master Files (DMFs): Suppliers often submit DMFs to regulatory agencies, detailing manufacturing processes, quality controls, and facility information, which formulators reference in their drug product applications.
• Audits: Pharmaceutical companies conduct rigorous audits of their API suppliers to ensure ongoing compliance and product quality.

SUPPLY CHAIN CHALLENGES AND RISKS

The global supply chain for avibactam sodium and ceftazidime sodium faces several challenges:

raw MATERIAL AVAILABILITY AND PRICING

The synthesis of both APIs relies on specific chemical intermediates and starting materials. Fluctuations in the cost and availability of these precursors, driven by geopolitical factors, environmental regulations, or manufacturing disruptions, can impact the final API price and supply stability. For instance, the production of key chiral intermediates for avibactam sodium can be a bottleneck.

GEOPOLITICAL AND ENVIRONMENTAL REGULATIONS

Increased environmental scrutiny in China and India has led to stricter regulations and occasional plant shutdowns, affecting production capacity and lead times. Trade tensions or tariffs between major manufacturing nations can also disrupt established supply routes.

QUALITY AND COMPLIANCE RISKS

Maintaining consistent quality across multiple manufacturing sites and suppliers is paramount. Any deviation from GMP standards or the emergence of unexpected impurities can lead to product recalls or regulatory actions, significantly impacting supply. The complex multi-step synthesis of avibactam sodium increases the potential for process variations.

LOGISTICAL DISRUPTIONS

Global shipping and logistics networks are susceptible to disruptions from pandemics, natural disasters, or geopolitical events. Maintaining adequate inventory levels and diversifying transportation routes are crucial mitigation strategies.

INTELLECTUAL PROPERTY AND COMPETITION

While the patent landscape for avibactam/ceftazidime is established, ongoing research and development may introduce new synthesis routes or competing products. Generic manufacturers entering the market can also influence pricing and supply dynamics.

MARKET DYNAMICS AND OUTLOOK

The demand for avibactam/ceftazidime is driven by the increasing prevalence of MDR bacterial infections. As resistance to older antibiotics grows, novel combinations like this become indispensable.

GROWTH DRIVERS

• Antimicrobial Resistance (AMR): The urgent global need for effective treatments against MDR pathogens.
• Hospital-Acquired Infections (HAIs): The high incidence of serious HAIs caused by gram-negative bacteria.
• Pipeline Development: Continued clinical trials and regulatory approvals for new indications or patient populations.

COMPETITIVE LANDSCAPE

The primary branded product is Vabomere (in the U.S.) and Zavicefta (in Europe), marketed by Pfizer. The market is expected to see increased generic competition as patents expire, which will likely drive down API costs but increase overall API demand from a broader range of manufacturers.

SUPPLY CHAIN RESILIENCE

Pharmaceutical companies are increasingly focused on building more resilient supply chains. This includes:

• Dual Sourcing: Establishing relationships with multiple qualified suppliers for critical APIs and intermediates.
• Geographic Diversification: Reducing reliance on single manufacturing regions.
• Inventory Management: Strategic stockpiling of raw materials and finished APIs.
• Vertical Integration: Some larger pharmaceutical companies may consider backward integration into key intermediate manufacturing.

KEY TAKEAWAYS

The global supply of avibactam sodium and ceftazidime sodium is primarily anchored in China and India, with European manufacturers playing a role in specialized segments. Ensuring the consistent availability of these critical APIs requires navigating complex synthesis pathways, stringent quality control measures, and a dynamic global regulatory and geopolitical environment. Supply chain resilience, driven by dual sourcing, geographic diversification, and robust inventory management, is essential for meeting the growing demand for treatments against multidrug-resistant bacteria.

FREQUENTLY ASKED QUESTIONS

1. What are the primary chemical intermediates required for avibactam sodium synthesis? The synthesis of avibactam sodium typically requires derivatives of L-proline and various reagents for sulfonyl group and aminomethyl group introduction. Specific intermediates are proprietary and vary by manufacturing route, but often include protected pyrrolidine structures and sulfonylating agents.

2. Are there any major differences in the quality standards for avibactam sodium API compared to ceftazidime sodium API? Both APIs must meet stringent pharmacopoeial standards for purity, potency, and impurity profiles (e.g., USP, Ph. Eur.). However, the complexity of avibactam sodium synthesis, involving more novel chemical transformations, may necessitate more extensive process validation and analytical method development to control specific impurities compared to the more established synthesis of ceftazidime sodium.

3. What is the impact of regulatory actions on API suppliers in China and India on the global supply? Regulatory actions, such as plant shutdowns due to environmental non-compliance or GMP violations, can lead to significant disruptions in API supply. These events can cause shortages, price increases, and force pharmaceutical companies to expedite the qualification of alternative suppliers, which is a time-consuming and costly process.

4. How does the patent expiration of the avibactam/ceftazidime combination drug affect the API market? Patent expiration typically leads to increased competition from generic manufacturers. This increased demand from generic players can drive higher volumes for API suppliers. It also generally results in downward pressure on API pricing as multiple suppliers vie for market share.

5. What strategies are being employed by pharmaceutical companies to mitigate supply chain risks for these antibiotics? Companies are pursuing multi-sourcing strategies, diversifying manufacturing locations geographically, increasing buffer stock of APIs and critical raw materials, and conducting more frequent supplier audits. Some are also exploring strategic partnerships or long-term supply agreements to secure capacity and pricing.

CITATIONS

[1] Pfizer Inc. (n.d.). Zavicefta. Retrieved from [Official Product Information Website - Example, actual URL would be specific]

[2] U.S. Food and Drug Administration. (n.d.). Drug Master Files (DMFs). Retrieved from [FDA Official Website - Example, actual URL would be specific]

[3] European Medicines Agency. (n.d.). Guidance Documents. Retrieved from [EMA Official Website - Example, actual URL would be specific]

[4] United States Pharmacopeia. (n.d.). Pharmacopeial Information. Retrieved from [USP Official Website - Example, actual URL would be specific]

[5] European Pharmacopoeia. (n.d.). Ph. Eur. Publications. Retrieved from [EDQM Official Website - Example, actual URL would be specific]