Bulk Pharmaceutical API Sources for QUIZARTINIB DIHYDROCHLORIDE

Bulk Pharmaceutical API Sources for QUIZARTINIB DIHYDROCHLORIDE

Vendor	Vendor Homepage	Vendor Sku	API Url
Axon Medchem		1696
MolPort		MolPort-042-665-739
Chemieliva Pharmaceutical Co., Ltd		PBCM0087834
Ambinter		Amb22370186
BioChemPartner		BCP24004
Achemtek		0102-012905

API Sourcing for Quizartinib Dihydrochloride

Last updated: February 19, 2026

This report analyzes bulk active pharmaceutical ingredient (API) sourcing for quizartinib dihydrochloride, a potent and selective FLT3 inhibitor used in treating acute myeloid leukemia (AML). Key areas of focus include current manufacturers, patent landscapes, and regulatory considerations impacting API supply chain reliability and cost.

Who are the primary bulk API manufacturers for Quizartinib Dihydrochloride?

The primary bulk API manufacturers for quizartinib dihydrochloride are currently limited, with a significant portion of production concentrated among a few specialized chemical synthesis companies. This concentration reflects the complexity of synthesizing the molecule and the stringent quality control required for pharmaceutical-grade API.

• Key API Manufacturers Identified:
  • Astex Pharmaceuticals (a wholly owned subsidiary of Otsuka Pharmaceutical Co., Ltd.): As the originator company for quizartinib, Astex Pharmaceuticals likely maintains proprietary manufacturing capabilities or closely controlled contract manufacturing organizations (CMOs) for its initial supply.
  • Contract Manufacturing Organizations (CMOs) specializing in complex small molecule synthesis: Several CMOs globally possess the technical expertise and Good Manufacturing Practice (GMP) compliant facilities necessary for producing quizartinib dihydrochloride. Specific company names are often proprietary and subject to confidentiality agreements between the API manufacturer and the drug product marketer. However, common regions for such advanced API manufacturing include China, India, and parts of Europe.

The sourcing strategy for quizartinib dihydrochloride API will heavily depend on whether the drug product is for clinical trials, commercial supply, or for the generic market. For originator products, reliance on internal or closely managed CMOs is typical. For potential generic entrants, identifying and qualifying alternative API suppliers will be a critical step.

What is the patent landscape for Quizartinib Dihydrochloride API synthesis?

The patent landscape for quizartinib dihydrochloride API synthesis is dominated by the originator, Astex Pharmaceuticals (Otsuka). Patents cover the composition of matter, specific synthetic routes, polymorphic forms, and methods of use. Understanding these patents is crucial for any entity seeking to manufacture or source quizartinib dihydrochloride API.

• Key Patents and Their Implications:
  • Composition of Matter Patents: The foundational patent for quizartinib dihydrochloride (its chemical structure) is held by Astex Pharmaceuticals. This patent, and its international equivalents, typically has a long lifespan, but its primary term has likely expired or is nearing expiry in major markets. For example, US Patent 6,894,050 was granted for quizartinib.
  • Process Patents: Astex Pharmaceuticals and Otsuka Pharmaceutical have also secured patents covering specific synthetic processes and intermediates used in the manufacturing of quizartinib dihydrochloride. These patents can extend market exclusivity by protecting novel or efficient manufacturing methods. Examples include patents describing specific reaction conditions, purification techniques, or stereoselective synthesis steps.
  • Polymorph Patents: Different crystalline forms (polymorphs) of an API can have distinct physical properties, such as solubility and stability. Patents protecting specific, advantageous polymorphs of quizartinib dihydrochloride dihydrochloride can also contribute to market exclusivity. For instance, research may have identified specific hydrated or anhydrous forms with superior formulation characteristics.
  • Formulation and Method of Use Patents: While not directly API synthesis patents, patents related to specific drug formulations containing quizartinib dihydrochloride and methods for treating specific indications (e.g., FLT3-mutated AML) can indirectly impact API demand and supply strategies.

Patent Expiry Timeline: The expiry of core composition of matter patents is a critical event for the pharmaceutical industry, often paving the way for generic competition. For quizartinib dihydrochloride, the expiry of key composition of matter patents in major markets such as the United States and Europe would allow generic API manufacturers to enter the market. However, process and polymorph patents can provide continued protection for specific manufacturing methods or API forms, potentially limiting the scope of generic entry. Detailed analysis of each patent's claims and expiry dates in relevant jurisdictions is essential.

What are the regulatory requirements for sourcing Quizartinib Dihydrochloride API?

Sourcing quizartinib dihydrochloride API necessitates strict adherence to global regulatory requirements to ensure patient safety, product efficacy, and consistent quality. These requirements are primarily enforced by regulatory agencies like the U.S. Food and Drug Administration (FDA), the European Medicines Agency (EMA), and the Pharmaceuticals and Medical Devices Agency (PMDA) in Japan.

• Key Regulatory Pillars for API Sourcing:
  • Good Manufacturing Practices (GMP): API manufacturers must operate under current Good Manufacturing Practices (cGMP). This is a fundamental requirement. Regulatory bodies conduct inspections to verify compliance. Key aspects of cGMP include:
    • Robust quality management systems.
    • Validated manufacturing processes.
    • Strict control of raw materials and intermediates.
    • Comprehensive testing of the final API.
    • Detailed batch record-keeping and traceability.
    • Adequate facility and equipment maintenance.
  • Drug Master Files (DMFs): API manufacturers typically submit Drug Master Files (DMFs) to regulatory agencies. A DMF is a submission to a regulatory agency that provides full information about the facilities, processes, or articles used in manufacturing, processing, packaging, and storing human drugs. It allows regulatory bodies to review confidential manufacturing details without disclosing them to the drug product applicant.
    • Type II DMF (FDA): This is common for API submissions, detailing the chemistry, manufacturing, and controls (CMC) of the API.
    • Active Substance Master File (ASMF) (EMA): The European equivalent of a DMF.
  • ICH Guidelines: The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) provides harmonized guidelines that are widely adopted by regulatory agencies. Relevant ICH guidelines for API sourcing include:
    • ICH Q7: Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients: This is the cornerstone guideline for API manufacturing.
    • ICH Q10: Pharmaceutical Quality System: Promotes a systematic approach to quality management.
    • ICH Q11: Development and Manufacture of Drug Substances: Provides guidance on the development and manufacture of drug substances, including control strategies.
  • Impurity Profiling and Control: Regulatory agencies mandate thorough identification, qualification, and control of impurities in the API. This includes genotoxic impurities, residual solvents, and degradation products. Manufacturers must develop and validate analytical methods for detecting and quantifying these impurities according to ICH Q3A (Impurities in New Drug Substances) and ICH M7 (Assessment and Control of DNA Reactive (Mutagenic) Impurities).
  • Stability Studies: API manufacturers must conduct comprehensive stability studies to determine the re-test period or shelf-life of the API under various storage conditions, as per ICH Q1A(R2). This ensures the API remains within its quality specifications throughout its intended storage period.
  • Supply Chain Security and Auditing: Drug product manufacturers are responsible for qualifying and auditing their API suppliers. This involves rigorous due diligence to ensure the supplier's reliability, quality systems, and compliance with regulatory standards. Audits typically cover all aspects of manufacturing, quality control, and documentation.

What are the critical quality attributes (CQAs) for Quizartinib Dihydrochloride API?

Critical Quality Attributes (CQAs) are physical, chemical, biological, or microbiological properties or characteristics that should be within an appropriate limit, range, or distribution to ensure the desired product quality. For quizartinib dihydrochloride API, CQAs are paramount for ensuring the safety and efficacy of the final drug product.

• Key Critical Quality Attributes:
  • Assay/Purity: The chemical purity of quizartinib dihydrochloride is a primary CQA. This refers to the percentage of the active drug substance present. Typically, high purity levels (e.g., >98.5% or >99.0%) are required, as determined by validated analytical methods such as High-Performance Liquid Chromatography (HPLC).
  • Identification: Confirmatory tests to ensure the identity of the API. This can involve spectroscopic methods like Infrared (IR) spectroscopy, Nuclear Magnetic Resonance (NMR) spectroscopy, or Mass Spectrometry (MS), and chromatographic retention time matching.
  • Related Substances/Impurities: This is a critical CQA encompassing all organic and inorganic impurities, as well as residual solvents. Specific limits are set for:
    • Specified Identified Impurities: Known process-related impurities or degradation products with established limits.
    • Specified Unidentified Impurities: Impurities detected and quantified but whose structure is not fully elucidated, with specific limits.
    • Unspecified Impurities: Limits for any single impurity not otherwise specified.
    • Total Impurities: An overall limit for all impurities combined.
    • Genotoxic Impurities: Strict controls and very low limits (often parts per million, ppm) are required for impurities with potential genotoxic activity, based on risk assessments.
    • Residual Solvents: Limits for solvents used in the manufacturing process, as defined by ICH Q3C guidelines.
  • Water Content: The amount of water present in the API. This is particularly important for salts like dihydrochloride and can affect stability and handling. Determined by Karl Fischer titration.
  • Particle Size Distribution (PSD): For solid oral dosage forms, the PSD of the API can significantly influence dissolution rate, bioavailability, and manufacturing processability (e.g., flowability, compressibility). Techniques like laser diffraction are used for measurement.
  • Polymorphic Form: If specific polymorphic forms are patented or possess advantageous properties, control over the polymorphic form is a critical CQA. Techniques such as X-ray Powder Diffraction (XRPD) and Differential Scanning Calorimetry (DSC) are used for characterization and control.
  • Chiral Purity (if applicable): If quizartinib dihydrochloride has chiral centers and a specific enantiomer is the active form, enantiomeric purity would be a critical CQA.
  • Heavy Metals: Limits for heavy metal contamination are typically set to ensure safety.
  • Microbial Limits: If the API is prone to microbial contamination or intended for sterile drug products, microbial testing (e.g., total viable aerobic count, absence of specified objectionable microorganisms) is a CQA.

What are the market drivers and challenges for Quizartinib Dihydrochloride API sourcing?

The market for quizartinib dihydrochloride API is primarily driven by its therapeutic application and faces specific challenges related to its complex nature and market status.

• Market Drivers:

  • Oncology Market Growth: The global oncology market continues to expand, with a sustained demand for innovative treatments for hematological malignancies like AML. Quizartinib's targeted mechanism of action addresses specific genetic mutations in AML, driving its adoption.
  • Clinical Trial Demand: Ongoing clinical trials investigating quizartinib for various AML subtypes and in combination therapies generate demand for clinical-grade API.
  • Potential Generic Entry Post-Patent Expiry: As key patents approach expiration, the prospect of generic versions entering the market will create demand for alternative API sources from generic manufacturers. This will increase competition and potentially drive down API prices.
  • Precision Medicine Adoption: The increasing focus on precision medicine, which tailors treatments based on individual genetic profiles, favors targeted therapies like quizartinib.

• Market Challenges:

  • Complex Synthesis: The multi-step synthesis of quizartinib dihydrochloride involves sophisticated chemical reactions and stringent purification steps, making API production technically challenging and potentially costly.
  • Limited Number of Qualified Suppliers: Due to the technical complexity and regulatory hurdles, the number of qualified GMP API manufacturers capable of producing quizartinib dihydrochloride may be limited, especially in the initial stages of the drug's lifecycle. This can lead to supply chain vulnerabilities.
  • Regulatory Scrutiny: Stringent regulatory requirements for API manufacturing, including impurity control and process validation, demand significant investment and expertise from API producers, posing a barrier to entry.
  • Intellectual Property Landscape: The existence of unexpired process and polymorph patents can restrict the ability of new manufacturers to enter the market even after the composition of matter patent expires.
  • Supply Chain Disruptions: Geopolitical events, raw material availability, and logistical challenges can disrupt the supply of complex APIs like quizartinib dihydrochloride. Ensuring supply chain resilience is critical.
  • Cost of Production: The intricate synthesis and rigorous quality control contribute to a high cost of production for quizartinib dihydrochloride API, which can impact the overall cost-effectiveness of the treatment.

Key Takeaways

• Quizartinib dihydrochloride API manufacturing is currently concentrated among specialized CMOs and the originator.
• The patent landscape is dominated by Astex Pharmaceuticals/Otsuka, with patents covering composition, synthesis routes, and polymorphs.
• Strict adherence to cGMP, DMF submissions, and ICH guidelines are mandatory for API sourcing.
• Critical Quality Attributes include purity, impurity profiles, water content, and polymorphic form.
• Market drivers include oncology demand and precision medicine, while challenges stem from complex synthesis, IP, and regulatory hurdles.

FAQs

1. What is the typical lead time for qualifying a new quizartinib dihydrochloride API supplier? The qualification process for a new API supplier typically spans 6 to 18 months, depending on the supplier's existing regulatory standing, the complexity of the API, and the extent of required audits and analytical method transfers. This includes site audits, quality agreement finalization, and potentially process validation batches.
2. Are there any known risks associated with specific impurity profiles in quizartinib dihydrochloride API? Risks are primarily associated with potentially genotoxic impurities and other process-related impurities exceeding defined thresholds. Regulatory agencies require thorough risk assessments and control strategies for all impurities, particularly those with mutagenic potential, to ensure patient safety.
3. What impact does the polymorphic form of quizartinib dihydrochloride API have on its use? The polymorphic form can affect API stability, solubility, dissolution rate, and bioavailability. If a specific polymorph is protected by patent or offers significant manufacturing or therapeutic advantages, controlling and verifying this specific form becomes a critical quality attribute for API sourcing.
4. How does the stability of quizartinib dihydrochloride API influence its storage and handling requirements? Stability data, determined through ICH-compliant studies, dictates the recommended storage conditions (e.g., temperature, humidity, light protection) and the re-test period or shelf-life of the API. This directly impacts logistics, inventory management, and packaging requirements.
5. What is the regulatory pathway for a generic drug product manufacturer to use a non-originator quizartinib dihydrochloride API? A generic drug product manufacturer must demonstrate pharmaceutical equivalence and bioequivalence to the reference listed drug. This involves submitting an Abbreviated New Drug Application (ANDA) to the FDA, which includes a detailed assessment of the API, often referencing a Type II DMF or ASMF submitted by the API manufacturer. The generic manufacturer must also show that the chosen API is manufactured according to cGMP and meets all specified quality attributes.

Citations

[1] U.S. Patent No. 6,894,050 (granted 2005). [2] International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use. (2000). ICH Q7: Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients. [3] International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use. (2013). ICH Q3A(R2): Impurities in New Drug Substances. [4] International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use. (2016). ICH M7(R1): Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk. [5] International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use. (2003). ICH Q1A(R2): Stability Testing of New Drug Substances and Products.