Suppliers and packagers for generic pharmaceutical drug: AZELAIC ACID

AZELAIC ACID

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

Applicant	Tradename	Generic Name	Dosage	NDA	NDA/ANDA	Supplier	Package Code	Package	Marketing Start
Leo Pharma As	FINACEA	azelaic acid	AEROSOL, FOAM;TOPICAL	207071	NDA	LEO Pharma Inc.	50222-303-50	1 CAN in 1 CARTON (50222-303-50) / 50 g in 1 CAN	2018-10-01
Leo Pharma As	FINACEA	azelaic acid	AEROSOL, FOAM;TOPICAL	207071	NDA	LEO Pharma Inc.	50222-303-91	1 CAN in 1 CARTON (50222-303-91) / 15 g in 1 CAN	2018-10-01
Almirall	AZELEX	azelaic acid	CREAM;TOPICAL	020428	NDA	Almirall, LLC	16110-869-30	1 TUBE in 1 CARTON (16110-869-30) / 30 g in 1 TUBE	2018-09-24
Almirall	AZELEX	azelaic acid	CREAM;TOPICAL	020428	NDA	Almirall, LLC	16110-869-50	1 TUBE in 1 CARTON (16110-869-50) / 50 g in 1 TUBE	2018-09-24
Actavis Labs Ut Inc	AZELAIC ACID	azelaic acid	GEL;TOPICAL	208011	ANDA	Actavis Pharma, Inc.	0591-2131-55	1 TUBE in 1 CARTON (0591-2131-55) / 50 g in 1 TUBE	2018-11-19
Encube	AZELAIC ACID	azelaic acid	GEL;TOPICAL	208724	ANDA	Encube Ethicals, Inc.	21922-038-14	1 TUBE in 1 CARTON (21922-038-14) / 50 g in 1 TUBE	2023-11-30

Azelaic Acid Pharmaceutical Drug Supply Chain Analysis

Last updated: February 19, 2026

This report analyzes the global supply landscape for azelaic acid, a dicarboxylic acid utilized in pharmaceutical formulations for its anti-inflammatory and antibacterial properties. The analysis focuses on key manufacturers, their production capacities, regulatory compliance, and potential supply chain risks. Azelaic acid is primarily used in dermatological treatments for acne and rosacea.

Who Are the Leading Manufacturers of Pharmaceutical-Grade Azelaic Acid?

The pharmaceutical-grade azelaic acid market is characterized by a limited number of specialized manufacturers. Production requires specific synthesis processes and stringent quality control to meet pharmacopeial standards.

• Global Producers: The primary manufacturers are located in Europe and Asia. Key players include:

  • BorsodChem Zrt. (Hungary): A significant producer with established manufacturing capabilities.
  • KRAHN Chemie GmbH (Germany): While primarily a distributor, KRAHN Chemie represents and supplies azelaic acid from various manufacturers, indicating a strong market presence.
  • Sintetica S.A. (Switzerland): A producer known for its active pharmaceutical ingredient (API) manufacturing.
  • Boccon-Chem Co., Ltd. (China): An emerging player in the API market, including azelaic acid.
  • Qingdao Enfine Biotechnology Co., Ltd. (China): Another Chinese entity involved in the production of specialty chemicals, including azelaic acid.
  • Yichang Tianyuan Group Co., Ltd. (China): A diversified chemical producer with azelaic acid in its product portfolio.

• Production Scale: Manufacturers vary in scale from large-volume industrial producers to more specialized API suppliers. Production capacity data is often proprietary, but market reports indicate a sufficient global supply to meet current pharmaceutical demand, with potential for expansion. For instance, European producers often leverage integrated chemical manufacturing complexes, allowing for economies of scale. Asian manufacturers, particularly those in China, have rapidly increased their production capacity for APIs across various therapeutic categories.

What Are the Key Manufacturing Processes and Quality Standards for Azelaic Acid?

The synthesis of azelaic acid for pharmaceutical use involves specific chemical processes to ensure purity and minimize impurities. The two primary methods are:

1. Ozonolysis of Oleic Acid: This is a common and established method. Oleic acid, typically derived from vegetable oils (e.g., sunflower oil, olive oil), is reacted with ozone. The ozonolysis cleaves the double bond in oleic acid, yielding azelaic acid and pelargonic acid (nonanoic acid) as byproducts. Subsequent purification steps are critical to isolate pharmaceutical-grade azelaic acid.
2. Oxidation of Cyclododecanone: This alternative method involves the oxidation of cyclododecanone, a cyclic ketone, to produce azelaic acid. This process may offer different impurity profiles compared to the oleic acid route.

• Quality Control: Pharmaceutical-grade azelaic acid must comply with stringent quality standards. Key pharmacopeias that set these standards include:

  • United States Pharmacopeia (USP): Specifies limits for impurities, heavy metals, and assay requirements. USP monographs detail testing procedures.
  • European Pharmacopoeia (Ph. Eur.): Similar to USP, Ph. Eur. defines purity criteria and analytical methods for azelaic acid.
  • Japanese Pharmacopoeia (JP): Provides national standards for drug substances.

• Impurity Profile: Critical impurities to monitor include residual starting materials (e.g., oleic acid, cyclododecanone), reaction byproducts (e.g., pelargonic acid), and heavy metals. The level of these impurities is tightly regulated, with typical limits for assay being not less than 99.0% and not more than 101.0% on the dried basis, and specific limits for individual impurities below 0.1%.

What is the Regulatory Landscape for Azelaic Acid API Manufacturers?

Regulatory compliance is paramount for API manufacturers supplying the pharmaceutical industry. This involves adherence to Good Manufacturing Practices (GMP) and obtaining relevant certifications.

• Good Manufacturing Practices (GMP): Manufacturers must operate under cGMP guidelines as defined by regulatory bodies such as the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA). GMP ensures that products are consistently produced and controlled according to quality standards. This includes:

  • Robust quality management systems.
  • Well-trained personnel.
  • Adequate facilities and equipment.
  • Comprehensive documentation and record-keeping.
  • Rigorous testing and validation protocols.

• Drug Master Files (DMFs): API manufacturers often submit DMFs to regulatory agencies (e.g., FDA, EMA). A DMF is a submission to the agency containing detailed information about the facilities, processes, or articles used in the manufacturing, processing, packaging, and storing of human drugs. This allows drug product manufacturers to reference the DMF in their marketing applications without having to disclose proprietary API manufacturing details.

  • FDA DMFs: A significant number of azelaic acid manufacturers have active DMFs on file with the FDA, facilitating its use in approved drug products in the U.S.
  • European Drug Master Files (ASMFs): Similar to DMFs, Active Substance Master Files (ASMFs) are used in Europe.

• Inspections and Audits: Pharmaceutical companies routinely audit their API suppliers to ensure ongoing compliance with GMP. Regulatory agencies also conduct inspections of manufacturing facilities. Non-compliance can lead to product recalls, import alerts, and loss of market access. For example, a recent trend has seen increased scrutiny of API manufacturing sites in emerging markets by Western regulatory bodies.

What Are the Potential Supply Chain Risks and Mitigation Strategies?

The azelaic acid supply chain, like many pharmaceutical ingredient supply chains, faces several risks that could impact availability and pricing.

• Geopolitical Instability: Concentration of manufacturing in specific regions, particularly China, can expose the supply chain to risks from trade disputes, export restrictions, or political instability.

  • Mitigation: Diversifying the supplier base across different geographical regions (e.g., Europe, North America, and Asia) can reduce reliance on any single country or region. Establishing dual sourcing for critical raw materials and APIs is a common strategy.

• Raw Material Volatility: The primary feedstock, oleic acid, is derived from agricultural products (vegetable oils). Fluctuations in crop yields, weather events, and global demand for vegetable oils can impact the price and availability of oleic acid, directly affecting azelaic acid production costs.

  • Mitigation: Long-term supply contracts with oleic acid suppliers, hedging against commodity price fluctuations, and exploring alternative oleic acid sources can provide some buffer.

• Quality and Regulatory Non-Compliance: A single instance of non-compliance by a manufacturer can disrupt supply for multiple drug products that rely on that API. Strict regulatory enforcement and product recalls are costly and damaging.

  • Mitigation: Conducting thorough due diligence on all potential suppliers, including site audits and a review of their regulatory history. Implementing robust incoming material testing and quality agreements. Maintaining strong relationships with multiple qualified suppliers.

• Logistics and Transportation Disruptions: Global shipping delays, port congestion, or unexpected events (e.g., pandemics, natural disasters) can impact the timely delivery of raw materials and finished APIs.

  • Mitigation: Working with reliable logistics providers, maintaining adequate inventory levels (balancing cost with risk), and exploring alternative transportation routes.

• Increased Environmental Regulations: Growing global emphasis on environmental sustainability may lead to stricter regulations on chemical manufacturing processes, potentially increasing production costs or requiring capital investment for process modifications.

  • Mitigation: Partnering with manufacturers who have demonstrated commitment to environmental compliance and sustainable practices. Staying abreast of evolving environmental regulations in key manufacturing regions.

How is Azelaic Acid Formulated in Pharmaceutical Products?

Azelaic acid is primarily used in topical dermatological preparations. Its effectiveness stems from its anti-inflammatory, antibacterial, and keratolytic properties.

• Dosage Forms:

  • Gels: Commonly formulated as a 15% gel (e.g., Finacea®). Gels offer a lighter feel and are suitable for oily or acne-prone skin.
  • Creams: Available as 20% creams (e.g., Azelex®). Creams provide moisturizing benefits and are often preferred for dry or sensitive skin.
  • Foams: Less common, but some formulations exist as a foam for ease of application.

• Mechanism of Action:

  • Anti-inflammatory: Reduces inflammation associated with acne and rosacea by inhibiting neutrophil chemotaxis and inflammatory cytokine production.
  • Antibacterial: Inhibits the growth of Propionibacterium acnes (now Cutibacterium acnes), a bacterium implicated in acne development.
  • Keratolytic: Helps to normalize keratinization, preventing the clogging of hair follicles.
  • Hyperpigmentation Reduction: Can also reduce hyperpigmentation by inhibiting tyrosinase, an enzyme involved in melanin production.

• Excipients: Pharmaceutical formulations of azelaic acid require specific excipients to ensure stability, solubility, and appropriate skin penetration. These can include:

  • Gelling agents: Carbomer, hydroxyethyl cellulose.
  • Emulsifiers: Cetearyl alcohol, glyceryl stearate.
  • Solvents/Humectants: Propylene glycol, glycerin.
  • Preservatives: Benzyl alcohol, sodium benzoate.
  • pH adjusters: Sodium hydroxide, citric acid.

The choice of excipients is critical for the overall performance and tolerability of the final pharmaceutical product.

Key Takeaways

• The global azelaic acid API market is concentrated among a few key manufacturers, primarily in Europe and Asia.
• Production involves specialized synthesis routes, such as oleic acid ozonolysis, and requires strict adherence to pharmacopeial standards (USP, Ph. Eur.) and GMP.
• Regulatory compliance, including the submission of DMFs and successful GMP audits, is essential for market access.
• Supply chain risks include geopolitical factors, raw material price volatility, quality control failures, and logistics disruptions. Diversification and robust quality management are crucial mitigation strategies.
• Azelaic acid is primarily formulated into topical gels and creams for dermatological conditions, leveraging its anti-inflammatory, antibacterial, and keratolytic properties.

Frequently Asked Questions

1. What is the primary difference between pharmaceutical-grade and industrial-grade azelaic acid? Pharmaceutical-grade azelaic acid meets stringent purity requirements defined by pharmacopeias (USP, Ph. Eur.) and is manufactured under cGMP conditions, ensuring safety and efficacy for human use. Industrial-grade azelaic acid has less rigorous purity standards and is intended for non-pharmaceutical applications.

2. Are there any common impurities found in azelaic acid that are of particular concern to regulators? Regulators are concerned with residual starting materials (e.g., oleic acid), reaction byproducts (e.g., pelargonic acid), heavy metals, and any genotoxic impurities that may arise from the synthesis process.

3. What is the typical lead time for sourcing pharmaceutical-grade azelaic acid from a new supplier? Lead times can vary significantly but typically range from 3 to 9 months. This includes the supplier qualification process, site audits, quality agreement finalization, and initial order fulfillment.

4. Can the synthesis process of azelaic acid from oleic acid result in allergenic components? While azelaic acid itself is generally well-tolerated, residual impurities from the oleic acid source (e.g., vegetable oil allergens) or processing chemicals could theoretically pose a risk. Manufacturers rigorously test for and control such impurities to minimize this risk.

5. How does the cost of azelaic acid compare to other active ingredients used in topical dermatology for similar indications? The cost of azelaic acid API can be moderate compared to some highly specialized APIs but may be higher than generic topical agents like benzoyl peroxide. Pricing is influenced by manufacturing complexity, regulatory compliance costs, and market supply-demand dynamics.

Citations

[1] U.S. Food and Drug Administration. (n.d.). Drug Master Files. Retrieved from [FDA Website] (Note: Specific URL for DMF search is dynamic and best accessed via the FDA's official portal).

[2] European Medicines Agency. (n.d.). Active Substance Master File Procedure. Retrieved from [EMA Website] (Note: Specific URL for ASMF information is dynamic and best accessed via the EMA's official portal).

[3] United States Pharmacopeial Convention. (n.d.). Pharmacopeial Monographs. Retrieved from [USP Website] (Note: Access to specific monographs typically requires subscription).

[4] European Directorate for the Quality of Medicines & HealthCare. (n.d.). The European Pharmacopoeia. Retrieved from [EDQM Website].

[5] Grand View Research. (2023). Azelaic Acid Market Size, Share & Trends Analysis Report. (Note: Market research reports are proprietary and typically require purchase for full access; this citation indicates the existence and type of such reports).

[6] Various chemical supplier websites and product specification sheets (e.g., BorsodChem, KRAHN Chemie, Sintetica S.A.). (Note: Specific product details are proprietary and accessed directly from manufacturers).