Suppliers and packagers for generic pharmaceutical drug: IXAZOMIB CITRATE

IXAZOMIB CITRATE

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

Applicant	Tradename	Generic Name	Dosage	NDA	NDA/ANDA	Supplier	Package Code	Package	Marketing Start
Takeda Pharms Usa	NINLARO	ixazomib citrate	CAPSULE;ORAL	208462	NDA	Takeda Pharmaceuticals America, Inc.	63020-230-01	1 CAPSULE in 1 BLISTER PACK (63020-230-01)	2015-11-20
Takeda Pharms Usa	NINLARO	ixazomib citrate	CAPSULE;ORAL	208462	NDA	Takeda Pharmaceuticals America, Inc.	63020-230-02	1 BLISTER PACK in 1 CARTON (63020-230-02) / 3 CAPSULE in 1 BLISTER PACK (63020-230-03)	2015-11-20
Takeda Pharms Usa	NINLARO	ixazomib citrate	CAPSULE;ORAL	208462	NDA	Takeda Pharmaceuticals America, Inc.	63020-390-01	1 CAPSULE in 1 BLISTER PACK (63020-390-01)	2015-11-20

Ixazomib Citrate: Key Suppliers and Patent Landscape Analysis

Last updated: February 19, 2026

This report analyzes the critical suppliers and patent landscape for ixazomib citrate, a proteasome inhibitor used in the treatment of multiple myeloma. The analysis focuses on active pharmaceutical ingredient (API) manufacturers, key intermediates, and relevant patent expirations.

Who are the primary manufacturers of ixazomib citrate API?

The manufacturing of ixazomib citrate API is a concentrated process. Takeda Pharmaceutical Company, the originator, holds significant manufacturing capabilities. However, as patents approach expiration, generic API manufacturers are emerging, indicating a shift in supply dynamics.

• Originator: Takeda Pharmaceutical Company (Japan) is the primary manufacturer of the branded ixazomib citrate, marketed as Ninlaro.
• Emerging Generic API Manufacturers: Several API manufacturers in India and China are developing or have developed capabilities for ixazomib citrate API production. These companies are positioned to supply the generic market post-patent expiry. Examples include:
  • Laurus Labs (India)
  • Divi's Laboratories (India)
  • Hetero Drugs (India)
  • Aurobindo Pharma (India)

The emergence of these suppliers is driven by the approaching patent expiries of key ixazomib citrate patents. This creates opportunities for generic drug development and market entry.

What are the critical intermediates and their suppliers?

The synthesis of ixazomib citrate involves several complex chemical intermediates. Ensuring a stable and cost-effective supply chain for these intermediates is crucial for API manufacturers.

• Key Intermediates:

  • (1R,2S)-1-amino-2-phenylcyclopropanecarboxylic acid: This chiral building block is central to ixazomib's structure.
  • Boronic acid derivatives: The boronic acid moiety is essential for proteasome inhibition. Specific protected boronic acid intermediates are required.
  • Amide coupling reagents: Specialized reagents are used for forming the peptide-like bonds in the ixazomib molecule.

• Potential Suppliers of Intermediates:

  • Specialty Chemical Companies: Companies specializing in chiral synthesis and advanced intermediates are key suppliers.
  • Custom Synthesis Organizations (CSOs) and Contract Manufacturing Organizations (CMOs): These organizations play a vital role in producing specific intermediates according to strict specifications.

  Specific company names for intermediate suppliers are often proprietary or subject to contractual agreements. However, companies with expertise in:

  • Chiral chemistry
  • Boron chemistry
  • Peptide synthesis

  are likely to be involved in the ixazomib citrate supply chain. Geographic concentrations for such specialized manufacturing exist in India, China, and parts of Europe.

What is the patent expiry timeline for ixazomib citrate?

The patent landscape for ixazomib citrate is characterized by a series of patents covering the compound itself, its synthesis, and its therapeutic uses. Understanding these expiry dates is critical for generic market entry and competitive strategy.

• Composition of Matter Patents: These patents protect the ixazomib molecule itself.

  • The core patent for ixazomib (often referred to as the "method of treatment" or "composition of matter" patent) typically has a term of 20 years from the filing date.
  • For ixazomib, the earliest filings date back to the early 2000s. U.S. Patent 7,897,634, for example, related to proteasome inhibitors including ixazomib, was filed in 2004 and granted in 2011. Its term would have extended based on Patent Term Adjustment and potentially Hatch-Waxman extensions.
  • Many key composition of matter patents for ixazomib and related compounds have expired or are set to expire imminently in major markets. For instance, the U.S. patent 7,897,634 expired in 2024.

• Method of Use Patents: These patents cover specific therapeutic uses of ixazomib.

  • These patents often extend the protection period for a drug, especially if new indications are discovered and patented.
  • Patents related to the use of ixazomib in combination therapies or for specific patient populations may have later expiry dates. However, the primary use patent for multiple myeloma is generally linked to the compound's core patent protection.

• Formulation and Polymorph Patents:

  • Patents covering specific salt forms (like citrate) or crystalline structures (polymorphs) can provide secondary protection.
  • Ixazomib citrate is the specific salt form used in the marketed drug. Patents related to this specific salt or its manufacturing process can offer extended market exclusivity. For example, U.S. Patent 9,718,776 covers crystalline forms of ixazomib citrate and its preparation. This patent expired in 2023 in the U.S.

• Process Patents:

  • Patents covering novel or improved methods of synthesizing ixazomib or its intermediates.
  • These can be critical for generic manufacturers aiming to develop non-infringing synthesis routes.
  • The expiry of these patents can allow for more flexible and potentially cost-effective manufacturing for generic players.

Summary of Key Patent Expirations (Indicative, subject to market-specific extensions and litigation):

Patent Type	U.S. Patent Number	Filing Date	Grant Date	Indicative Expiry (US)
Composition of Matter	7,897,634	2004	2011	2024
Polymorph/Formulation	9,718,776	2015	2017	2023

Note: Patent expiry dates are subject to Patent Term Adjustment (PTA), Patent Term Extension (PTE), and potential litigation outcomes, which can significantly alter the effective market exclusivity period. Generic companies often challenge the validity or inventorship of patents to accelerate market entry.

What are the regulatory considerations for ixazomib citrate API suppliers?

API suppliers for ixazomib citrate must adhere to stringent regulatory requirements to ensure product quality, safety, and efficacy. These regulations are overseen by major health authorities globally.

• Good Manufacturing Practices (GMP): All API manufacturers must comply with current Good Manufacturing Practices (cGMP) as defined by regulatory bodies.
  • FDA (U.S. Food and Drug Administration): Requires adherence to 21 CFR Parts 210 and 211.
  • EMA (European Medicines Agency): Follows EudraLex Volume 4.
  • Other Authorities: Equivalent GMP standards are enforced by agencies in Japan (PMDA), Canada (Health Canada), and other national regulatory bodies.
• Drug Master Files (DMFs): API manufacturers typically submit DMFs to regulatory authorities.
  • A DMF contains confidential, detailed information about facilities, processes, and materials used in the manufacturing, processing, packaging, and storing of an API.
  • Pharmaceutical companies reference these DMFs in their drug product marketing applications (e.g., NDAs, ANDAs).
• Impurity Profiling and Control: Rigorous control and documentation of impurities are essential. This includes:
  • Identification and qualification of process-related impurities and degradation products.
  • Setting acceptable limits for these impurities based on toxicological data and regulatory guidelines (e.g., ICH Q3A/Q3B).
• Quality Management Systems (QMS): Robust QMS are required to ensure consistent product quality. This includes:
  • Change control procedures
  • Deviation management
  • Corrective and preventive actions (CAPA)
  • Batch release testing and stability studies.
• Audits and Inspections: API manufacturing sites are subject to regular inspections by regulatory authorities and audits by their pharmaceutical clients.
• Supply Chain Security: Ensuring the integrity of the supply chain from raw materials to the finished API is critical to prevent counterfeiting and ensure product quality.

What is the market outlook for ixazomib citrate API?

The market outlook for ixazomib citrate API is transitioning from a single-source originator model to a multi-source generic environment.

• Current Market: Dominated by Takeda, with Ninlaro (ixazomib citrate) being the primary branded product. The market size is influenced by the prevalence of multiple myeloma and treatment guidelines.
• Impact of Patent Expirations: The expiry of key patents is the primary driver for market change. This will lead to:
  • Increased Competition: The entry of multiple generic API manufacturers will intensify competition.
  • Price Erosion: Generic competition typically results in significant price reductions for both API and finished drug products.
  • Market Expansion: Lower prices can increase market access and potentially expand the patient population treated with ixazomib-based therapies.
• Generic Development: Generic drug manufacturers are actively developing ixazomib citrate ANDAs (Abbreviated New Drug Applications) and seeking approvals.
  • The first generic ixazomib citrate product approvals are anticipated in the near future, based on patent expiry dates and regulatory review timelines.
• Supply Chain Diversification: Pharmaceutical companies will seek to diversify their API sourcing to mitigate risks and negotiate better pricing. This benefits emerging generic API manufacturers.
• Therapeutic Landscape: Ixazomib citrate competes within the broader multiple myeloma treatment landscape, which includes other proteasome inhibitors (e.g., bortezomib, carfilzomib), immunomodulatory drugs, and newer agents like monoclonal antibodies and CAR-T cell therapies. The treatment protocol and availability of generics will influence ixazomib citrate's positioning.

Projected Trends:

• Increased API Volume: As generics enter, the total volume of ixazomib citrate API required will likely increase due to broader market penetration and potential use in combination therapies.
• Regional Shifts: API manufacturing may see increased activity in regions with a strong generic pharmaceutical industry, such as India.
• Quality and Compliance Focus: With more players, regulatory scrutiny on API quality and compliance will remain high.

Key Takeaways

• Takeda Pharmaceutical Company is the originator and primary supplier of ixazomib citrate API.
• Key intermediates require specialized synthesis capabilities, particularly in chiral chemistry and boron chemistry.
• Core composition of matter and formulation patents for ixazomib citrate are expiring or have expired in major markets, paving the way for generic entry.
• API suppliers must adhere to stringent global GMP regulations and maintain comprehensive DMFs.
• The market for ixazomib citrate API is transitioning to a multi-source generic model, expected to drive increased competition and price erosion.

Frequently Asked Questions

1. What is the primary therapeutic indication for ixazomib citrate?

Ixazomib citrate is primarily indicated for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior therapies.

2. What is the difference between ixazomib and ixazomib citrate?

Ixazomib is the active pharmaceutical ingredient. Ixazomib citrate refers to the specific salt form of ixazomib that is formulated into the oral drug product (Ninlaro). Using a salt form can improve stability, solubility, and bioavailability.

3. Are there any known off-patent synthesis routes for ixazomib citrate?

While core patents on the molecule are expiring, specific, novel, or cost-effective synthesis routes can still be protected by process patents. Generic manufacturers often develop their own proprietary synthesis pathways to avoid infringement on existing process patents.

4. How do regulatory authorities assess the quality of ixazomib citrate API from new suppliers?

Regulatory authorities, such as the FDA and EMA, assess API quality through reviews of Drug Master Files (DMFs), inspection of manufacturing facilities for compliance with Good Manufacturing Practices (GMP), and analysis of submitted API samples.

5. What is the expected impact of generic ixazomib citrate on current treatment costs for multiple myeloma?

The introduction of generic ixazomib citrate is expected to significantly reduce treatment costs. Historically, generic drug entry leads to substantial price declines, making therapies more accessible and affordable for patients and healthcare systems.

Citations

[1] U.S. Patent No. 7,897,634 (filed Jan. 15, 2004) (issued Mar. 1, 2011). [2] U.S. Patent No. 9,718,776 (filed Mar. 25, 2015) (issued Aug. 1, 2017). [3] Food and Drug Administration. (n.d.). 21 CFR Parts 210 and 211. Retrieved from [FDA website] [4] European Medicines Agency. (n.d.). EudraLex - The Rules Governing Medicinal Products in the European Union. Retrieved from [EMA website] [5] International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use. (2015). ICH Harmonised Guideline Q3A(R2): Impurities in New Drug Substances. [6] International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use. (2003). ICH Harmonised Guideline Q3B(R2): Impurities in New Drug Products.