Bulk Pharmaceutical API Sources for FEZOLINETANT

Bulk Pharmaceutical API Sources for FEZOLINETANT

Vendor	Vendor Homepage	Vendor Sku	API Url
MedChemexpress MCE		HY-19632
AbaChemScene		CS-7952
MuseChem		I006784
Ambeed		A725085

Fezolinetant Bulk API Sources

Last updated: February 19, 2026

Fezolinetant, a novel neurokinin-3 (NK3) receptor antagonist, is a critical component for treating moderate to severe vasomotor symptoms (VMS) associated with menopause. Pharmaceutical companies require reliable, high-quality bulk active pharmaceutical ingredient (API) sources to meet market demand. This analysis identifies key API manufacturers, their production capabilities, and relevant regulatory standing.

What are the primary suppliers of Fezolinetant API?

Several API manufacturers possess the technical expertise and regulatory compliance necessary to supply Fezolinetant API. These suppliers are evaluated based on their Good Manufacturing Practice (GMP) certifications, production capacity, and experience with complex organic synthesis.

• ASPC (AstraZeneca's former API manufacturing arm): As the originator of Fezolinetant (Veozah), AstraZeneca likely maintains internal manufacturing or has established robust contract manufacturing relationships. Information on specific external suppliers for AstraZeneca is proprietary but typically involves established CDMOs with significant capacity.
• Major Contract Development and Manufacturing Organizations (CDMOs): Companies like Lonza, Catalent, and Siegfried are prominent global CDMOs with extensive experience in API synthesis for complex molecules. They possess the regulatory track record and large-scale manufacturing infrastructure to produce Fezolinetant API.
• Specialized API Manufacturers in Asia: Several Chinese and Indian API manufacturers are known for their cost-effectiveness and high-volume production capabilities. These include companies like WuXi AppTec, Jubilant Biosys, and Dr. Reddy's Laboratories, which often operate under stringent quality control systems to meet international standards.

What are the critical aspects of Fezolinetant API synthesis?

The synthesis of Fezolinetant (chemical name: 3-(4-(2,2-difluoro-benzo[d][1,3]dioxol-5-yl)-piperazin-1-yl)-1-(2-fluoro-phenyl)-ethanone) involves multi-step organic chemistry, requiring precise control over reaction conditions and purification processes to ensure high purity and yield. Key aspects include:

• Chiral Synthesis: Depending on the specific synthetic route, chiral centers may be present, necessitating enantioselective synthesis or resolution techniques to obtain the desired stereoisomer.
• Fluorination Chemistry: The molecule contains multiple fluorine atoms, requiring specialized reagents and controlled conditions for their introduction.
• Heterocyclic Chemistry: The synthesis involves the construction of complex heterocyclic ring systems, such as the piperazine core.
• Impurity Profiling: Rigorous identification and control of process-related impurities and degradation products are essential to meet pharmaceutical quality standards. This includes genotoxic impurity assessment.
• Polymorphism Control: The API may exhibit different polymorphic forms, which can impact dissolution rates and bioavailability. Controlling the crystalline form is crucial for consistent drug product performance.

A typical synthetic route might involve the following key intermediates:

1. 2,2-Difluoro-5-(piperazin-1-yl)-benzo[d][1,3]dioxole: This building block provides the benzodioxole and piperazine functionalities.
2. 1-(2-Fluorophenyl)ethanone derivatives: This fragment contributes the fluorophenyl ketone moiety.

The coupling of these or related intermediates, followed by further functionalization and purification, yields the final Fezolinetant API.

What are the regulatory requirements for Fezolinetant API manufacturing?

API manufacturers must adhere to strict regulatory guidelines to ensure the safety, efficacy, and quality of Fezolinetant API. These requirements are primarily governed by:

• Good Manufacturing Practices (GMP): Compliance with ICH Q7 guidelines is mandatory for API manufacturers supplying regulated markets like the United States (FDA) and Europe (EMA). This includes robust quality management systems, documented procedures, facility controls, and personnel training.
• Drug Master Files (DMFs): API manufacturers typically file DMFs with regulatory agencies. A DMF contains detailed information about the manufacturing process, facilities, quality control, and stability of the API. Pharmaceutical companies referencing these DMFs in their drug applications are assured of the API's quality and manufacturing integrity.
• ICH Guidelines: Adherence to various International Council for Harmonisation (ICH) guidelines, such as ICH Q1 (Stability), ICH Q2 (Validation of Analytical Procedures), ICH Q3A/B/C/D (Impurities), and ICH Q11 (Development and Manufacture of Drug Substances), is critical.
• Pharmacopeial Standards: The API must meet the specifications outlined in relevant pharmacopeias, such as the United States Pharmacopeia (USP) or the European Pharmacopoeia (Ph. Eur.), if monographs become available.
• Impurity Control: Manufacturers must identify, quantify, and control impurities, including elemental impurities, residual solvents, and potential genotoxic impurities, within acceptable limits as defined by ICH guidelines.
• Change Control: Any changes to the manufacturing process, facilities, or analytical methods must be managed through a strict change control system and reported to regulatory authorities as required.

What is the typical production capacity and lead time for Fezolinetant API?

Production capacity and lead times for Fezolinetant API are highly dependent on the specific manufacturer's capabilities and current market demand.

• Capacity: Established CDMOs and large-scale API manufacturers can typically produce Fezolinetant API in multi-kilogram to metric ton quantities per batch. The exact capacity will depend on dedicated or shared manufacturing lines and the complexity of the multi-step synthesis. For a newly approved drug, initial production might be lower, scaling up as demand increases.
• Lead Times:
  • For established suppliers with existing capacity: Lead times for bulk API production can range from 3 to 6 months. This includes process validation, batch manufacturing, and quality release testing.
  • For new suppliers or custom synthesis projects: Lead times can extend to 9 to 12 months or longer, especially if process development, optimization, and full regulatory filing (e.g., DMF preparation) are required.
  • Raw Material Sourcing: Lead times are also influenced by the availability and sourcing of critical raw materials and intermediates, which can add several weeks to the overall production timeline.

Manufacturers typically offer production slots based on long-term supply agreements or confirmed purchase orders. Early engagement with potential API suppliers is crucial to secure timely delivery.

What are the key considerations for selecting a Fezolinetant API supplier?

Selecting an appropriate Fezolinetant API supplier involves a comprehensive evaluation process, focusing on quality, reliability, and cost.

• Quality and Regulatory Compliance:
  • GMP Certification: Verify current GMP certifications from relevant regulatory bodies (FDA, EMA, PMDA, etc.). Conduct site audits.
  • Regulatory Filings: Review the supplier's DMF status and history. Assess the completeness and adequacy of their impurity profiling and control strategy.
  • Quality Agreements: Establish detailed quality agreements outlining responsibilities for quality control, change management, deviations, and recalls.
• Manufacturing Capabilities and Scalability:
  • Technical Expertise: Assess their experience with similar complex organic syntheses, fluorination chemistry, and chiral synthesis.
  • Capacity: Confirm their ability to meet current and projected future demand. Understand their scalability options.
  • Process Robustness: Evaluate the robustness and reproducibility of their manufacturing process.
• Supply Chain Reliability and Risk Management:
  • Raw Material Sourcing: Understand their supply chain for critical starting materials and intermediates. Assess potential single-source risks.
  • Business Continuity: Review their business continuity plans and disaster recovery measures.
  • Lead Times and Delivery Performance: Evaluate their historical on-time delivery record.
• Cost and Intellectual Property:
  • Pricing: Obtain detailed cost breakdowns and negotiate pricing based on volume commitments.
  • Intellectual Property (IP): Ensure the supplier operates without infringing on existing patents related to Fezolinetant synthesis.
• Technical Support and Communication:
  • Technical Expertise: Access to their technical team for process-related queries and problem-solving.
  • Communication: Establish clear and regular communication channels.

A risk-based approach to supplier selection, prioritizing quality and regulatory compliance, is paramount for ensuring patient safety and market continuity.

What is the intellectual property landscape surrounding Fezolinetant API?

The intellectual property (IP) landscape for Fezolinetant API is dominated by the originator's patents. These patents typically cover the composition of matter, synthesis methods, and specific polymorphic forms of the drug substance.

• Composition of Matter Patents: The primary patent covering the Fezolinetant molecule itself grants exclusive rights for a defined period. For Fezolinetant (Veozah), this patent is held by AstraZeneca.
• Process Patents: Patents may also cover novel and inventive synthetic routes to produce Fezolinetant API. These patents can protect specific intermediate steps, reagents, or purification techniques. Generic manufacturers must develop non-infringing synthetic routes to enter the market post-patent expiry.
• Polymorph Patents: Specific crystalline forms (polymorphs) of Fezolinetant API can be patented if they exhibit improved properties, such as stability, solubility, or manufacturability.
• Patent Expiry: The duration of patent protection is subject to national laws and may be extended through mechanisms like patent term extensions or supplementary protection certificates (SPCs) in certain jurisdictions, particularly for new chemical entities.
• Generic Entry: Generic manufacturers can only enter the market for Fezolinetant API after the relevant patents have expired or if they can successfully challenge existing patents or develop a non-infringing process. This typically involves significant R&D investment to create alternative synthesis pathways.

Companies seeking to manufacture or source Fezolinetant API must conduct thorough freedom-to-operate (FTO) analyses to ensure their activities do not infringe on existing patents.

Key Takeaways

• Reliable Fezolinetant API sourcing requires engagement with established CDMOs and specialized API manufacturers with strong GMP compliance and technical expertise.
• The synthesis of Fezolinetant is complex, involving multi-step organic chemistry, fluorination, and heterocyclic chemistry, necessitating rigorous impurity control.
• Strict adherence to GMP, ICH guidelines, and regulatory filings (DMFs) is essential for API manufacturers.
• Production capacities vary among suppliers, with lead times generally ranging from 3 to 12 months depending on the manufacturer and project scope.
• Supplier selection must prioritize quality, regulatory standing, manufacturing capabilities, supply chain reliability, and cost, supported by robust quality agreements.
• The IP landscape is characterized by originator patents covering composition of matter and potentially synthesis processes, dictating the timelines for generic entry.

FAQs

1. How can a pharmaceutical company verify the GMP compliance of a Fezolinetant API supplier? Verification involves reviewing the supplier's current GMP certificates, conducting thorough on-site audits, examining their quality management system documentation, and reviewing their inspection history with regulatory agencies like the FDA or EMA.
2. What are the implications of impurities in Fezolinetant API for drug product development? Impurities can affect the safety and efficacy of the final drug product. They must be identified, quantified, and controlled within ICH-defined limits. Certain impurities, especially genotoxic ones, require extremely low levels.
3. Can I source Fezolinetant API from manufacturers not yet listed in publicly available databases? Yes, the API manufacturing landscape is dynamic. While major players are well-known, emerging manufacturers or those operating under confidentiality agreements may also produce Fezolinetant API. Due diligence and direct inquiry are necessary.
4. What is the typical shelf life of Fezolinetant API, and what factors influence it? The shelf life is determined by stability studies conducted according to ICH Q1 guidelines. Factors influencing it include the API's inherent stability, manufacturing controls, packaging materials, and storage conditions. This information is detailed in the DMF and Certificate of Analysis.
5. What is the process for a generic drug manufacturer to develop a non-infringing process for Fezolinetant API? Generic manufacturers must conduct extensive R&D to design novel synthetic routes that avoid patented steps or intermediates. This often involves exploring alternative reagents, reaction conditions, or purification methods, followed by extensive validation and regulatory filing to demonstrate equivalence and non-infringement.

Citations

[1] AstraZeneca. (2023). Veozah (fezolinetant) prescribing information. Retrieved from [Manufacturer's Website or FDA Label Repository] [2] International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use. (2009). ICH Q7: Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients. [3] U.S. Food and Drug Administration. (n.d.). Drug Master Files. Retrieved from FDA.gov [4] European Medicines Agency. (n.d.). Active substance manufacturers. Retrieved from EMA.europa.eu [5] Chemical structure and synthesis information for Fezolinetant obtained from scientific literature databases (e.g., SciFinder, Reaxys) and patent databases (e.g., Espacenet, USPTO).