Suppliers and packagers for generic pharmaceutical drug: VORINOSTAT

VORINOSTAT

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

Applicant	Tradename	Generic Name	Dosage	NDA	NDA/ANDA	Supplier	Package Code	Package	Marketing Start
Msd Sub Merck	ZOLINZA	vorinostat	CAPSULE;ORAL	021991	NDA	Merck Sharp & Dohme LLC	0006-0568-40	120 CAPSULE in 1 BOTTLE (0006-0568-40)	2006-10-06

Vorinostat Drug Suppliers and Manufacturing Landscape

Last updated: February 19, 2026

Vorinostat, a histone deacetylase (HDAC) inhibitor marketed as Zolinza, is approved for the treatment of cutaneous T-cell lymphoma (CTCL). The manufacturing and supply chain for vorinostat involves specialized chemical synthesis and adherence to stringent pharmaceutical quality standards. Key suppliers are involved in the production of active pharmaceutical ingredients (APIs) and intermediates.

What is the Chemical Structure and Synthesis Route for Vorinostat?

Vorinostat is chemically known as N-hydroxy-N'-phenyloctanediamide. Its synthesis typically involves a multi-step process, often starting with simpler chemical building blocks.

Key Synthesis Steps:

1. Amide formation: A common route involves reacting 4-phenylamino-4-oxobutanoic acid with hydroxylamine to form the hydroxamic acid moiety.
2. Coupling: The resulting intermediate is then coupled with octanedioic acid or a reactive derivative thereof.
3. Purification: Rigorous purification steps are essential to achieve the required pharmaceutical grade purity.

Specific synthesis routes can vary between manufacturers and are often protected by process patents.

Who are the Primary API and Intermediate Suppliers for Vorinostat?

The supply chain for vorinostat API and its key intermediates is characterized by specialized chemical manufacturers. Due to the proprietary nature of drug manufacturing, precise supplier lists are not publicly disclosed by brand-name drug manufacturers. However, general industry knowledge and patent literature point to certain types of suppliers and established players in custom synthesis and API manufacturing.

Identified and Potential Suppliers:

• Symrise AG: This German company, through its Symrise Cosmetic Ingredients division, has been associated with the development and supply of ingredients relevant to cosmetic applications, some of which may overlap with intermediates for pharmaceutical synthesis. Their expertise in fine chemicals and custom synthesis is a key capability [1].
• Major API Manufacturers: Global API manufacturers with expertise in complex organic synthesis and Good Manufacturing Practices (GMP) are primary candidates for supplying vorinostat API or critical intermediates. Companies like Lonza, Siegfried AG, and Dr. Reddy's Laboratories possess the necessary infrastructure and regulatory compliance for such production.
• Custom Synthesis Organizations (CSOs) and Contract Manufacturing Organizations (CMOs): Pharmaceutical companies often outsource API production to CSOs and CMOs. These organizations specialize in developing and scaling up chemical synthesis processes. Examples of major CMOs include Catalent, Thermo Fisher Scientific (Patheon), and WuXi AppTec. These entities are capable of producing vorinostat according to specific client requirements and regulatory standards.
• Specialty Chemical Providers: Suppliers of specific reagents and starting materials essential for vorinostat synthesis are also part of the broader supply chain. This can include companies providing specific amines, carboxylic acids, and coupling agents.

The selection of a supplier depends on factors such as manufacturing capacity, quality control systems, regulatory compliance (e.g., FDA, EMA audits), cost, and the supplier's ability to handle specific chemical reactions and purification techniques.

What are the Regulatory Requirements for Vorinostat Manufacturing?

The manufacturing of vorinostat, like all pharmaceuticals, is subject to stringent regulatory oversight from health authorities worldwide.

Key Regulatory Frameworks:

• Good Manufacturing Practices (GMP): All manufacturing facilities must adhere to cGMP standards 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 requirements for facilities, equipment, personnel, documentation, and quality control.
• Drug Master Files (DMFs): API manufacturers typically submit DMFs to regulatory agencies. A DMF contains confidential detailed information about facilities, processes, or articles used in the manufacturing, processing, packaging, and storing of human drugs. It allows regulatory agencies to review the information in support of an application without disclosure to the applicant [2].
• ICH Guidelines: International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines provide harmonized standards for pharmaceutical development and registration, including quality, safety, and efficacy. ICH Q7, for instance, details GMP for APIs.
• impurity Profiling and Control: Manufacturers must identify, quantify, and control impurities in the API. This includes process-related impurities, degradation products, and residual solvents, all of which must be within acceptable limits.
• Stability Testing: Comprehensive stability testing is required to establish the shelf-life of the API and finished drug product under various storage conditions.

Compliance with these regulations is critical for any supplier intending to produce vorinostat API or intermediates for commercial drug products.

How does Patent Exclusivity Impact Vorinostat Supply?

Patent exclusivity plays a significant role in the commercial supply of pharmaceutical drugs like vorinostat.

Patent Landscape:

• Composition of Matter Patent: The original patent for vorinostat (e.g., U.S. Patent No. 5,362,758) claimed the compound itself. This patent has expired, paving the way for generic competition.
• Process Patents: Additional patents may cover specific synthesis methods or purification techniques for vorinostat. These patents can extend market exclusivity by preventing generic manufacturers from using those particular patented processes. Generic manufacturers must develop non-infringing synthesis routes.
• Formulation Patents: Patents may also exist for specific pharmaceutical formulations of vorinostat, such as extended-release versions or specific salt forms.
• Exclusivity Periods: The Hatch-Waxman Act in the U.S. provides for periods of market exclusivity for certain approved drugs. For innovator drugs, this can include data exclusivity and orphan drug exclusivity, which can delay generic entry even after the expiration of compound patents.

The expiration of key patents generally leads to increased competition from generic manufacturers, potentially increasing demand for APIs from a broader range of suppliers.

What are the Key Considerations for Sourcing Vorinostat API?

Pharmaceutical companies seeking to source vorinostat API or its intermediates must undertake a thorough evaluation process.

Sourcing Criteria:

• Quality and GMP Compliance: The supplier must demonstrate robust quality management systems and operate under current GMP. This includes a track record of successful regulatory inspections.
• Supply Chain Security and Reliability: The ability to consistently supply the required quantities without interruption is paramount. This involves assessing the supplier's manufacturing capacity, contingency plans, and geopolitical stability of their manufacturing sites.
• Technical Expertise: The supplier should possess expertise in the specific chemistry required for vorinostat synthesis and purification, including the ability to control critical process parameters and impurities.
• Cost-Effectiveness: While quality and reliability are primary, cost is a significant factor, especially for generic drug production.
• Regulatory Support: The supplier should be willing and able to provide necessary documentation, such as DMFs and Certificates of Analysis, and support regulatory filings.
• Intellectual Property: Ensuring that the sourcing arrangement does not infringe on existing patents, particularly process patents, is crucial.

A rigorous vendor qualification process is essential to mitigate risks associated with API sourcing.

What is the Market Outlook for Vorinostat Suppliers?

The market outlook for vorinostat suppliers is influenced by several factors, primarily the transition to generic competition and potential new indications.

Market Dynamics:

• Generic Entry: The U.S. patent for vorinostat expired in 2022. This has opened the door for generic manufacturers, which are expected to increase the overall demand for vorinostat API. Generic competition typically drives down API prices due to increased supplier competition.
• New Indications and Research: While primarily approved for CTCL, ongoing research into vorinostat for other cancers (e.g., glioblastoma, breast cancer) or in combination therapies could lead to expanded indications, potentially increasing future demand. However, clinical trial outcomes dictate this.
• Manufacturing Capacity: Suppliers with existing capacity and expertise in producing complex small molecules under GMP conditions are well-positioned to serve the growing generic market.
• Supply Chain Diversification: Pharmaceutical companies often seek to diversify their API suppliers to mitigate risks. This trend favors suppliers who can demonstrate reliability and robust quality systems.

The increasing demand from the generic market, coupled with potential future therapeutic expansions, presents opportunities for qualified API and intermediate suppliers.

Key Takeaways

• Vorinostat API and intermediate supply chains involve specialized chemical synthesis manufacturers adhering to strict GMP regulations.
• Key suppliers are typically large API manufacturers or specialized Contract Manufacturing Organizations (CMOs) with expertise in complex organic synthesis.
• Regulatory compliance, including GMP and submission of Drug Master Files (DMFs), is a critical prerequisite for suppliers.
• The expiration of vorinostat's composition of matter patent has opened the market for generic manufacturers, likely increasing overall API demand.
• Sourcing decisions prioritize quality, supply chain reliability, technical expertise, and cost-effectiveness, alongside robust regulatory support.

FAQs

1. Are there any publicly listed suppliers of vorinostat API? Publicly listed, confirmed suppliers of vorinostat API for brand-name drugs are not typically disclosed due to proprietary agreements. However, companies specializing in custom synthesis and API manufacturing for a wide range of pharmaceuticals are capable of producing vorinostat.
2. What is the typical lead time for sourcing vorinostat API? Lead times for sourcing custom-manufactured APIs like vorinostat can range from 6 to 18 months, depending on the supplier's current capacity, the complexity of the synthesis, and the required scale.
3. What quality standards must vorinostat API suppliers meet? Vorinostat API suppliers must meet current Good Manufacturing Practices (cGMP) standards as mandated by regulatory agencies like the FDA and EMA. This includes rigorous quality control, impurity profiling, and adherence to ICH guidelines.
4. Can existing generic vorinostat manufacturers provide API to new entrants? While some generic manufacturers may have internal API production capabilities or long-term supply agreements, they are not typically in the business of supplying API to direct competitors. New entrants must establish their own supply chains or contract with independent API manufacturers.
5. Does vorinostat have any specific storage requirements for the API? Vorinostat API typically requires storage in tightly sealed containers, protected from light and moisture, at controlled room temperatures or as specified by stability studies to maintain its integrity and prevent degradation.

Citations

[1] Symrise. (n.d.). Symrise Cosmetic Ingredients. Retrieved from [Symrise website - Specific page not directly linked as it may change, but the division is relevant]

[2] U.S. Food and Drug Administration. (2019, February 12). Drug Master Files (DMFs). Retrieved from https://www.fda.gov/drugs/guidance-compliance-regulatory-information/drug-master-files-dmfs