Bulk Pharmaceutical API Sources for alatrofloxacin mesylate

Bulk Pharmaceutical API Sources for alatrofloxacin mesylate

Vendor	Vendor Homepage	Vendor Sku	API Url
NovoSeek		5282517
ABI Chem		AC1NR071
ISpharm		I14-17256
AKos Consulting & Solutions		AKOS015904299

Alatrofloxacin Mesylate Bulk API Sourcing: Patent Landscape and Supply Chain Analysis

Last updated: February 19, 2026

This report analyzes the patent landscape and identifies potential bulk active pharmaceutical ingredient (API) sources for alatrofloxacin mesylate, a broad-spectrum fluoroquinolone antibiotic. Patent expirations and ongoing litigation impact market access and pricing for this critical therapeutic agent.

What is Alatrofloxacin Mesylate?

Alatrofloxacin mesylate is the water-soluble prodrug of trovafloxacin. Trovafloxacin is a synthetic fluoroquinolone antibiotic effective against a wide range of Gram-positive and Gram-negative bacteria, including many resistant strains. It was primarily developed for the treatment of community-acquired pneumonia, intra-abdominal infections, and complicated skin and skin structure infections.

The mesylate salt form enhances the solubility and bioavailability of trovafloxacin, allowing for intravenous administration. Alatrofloxacin was marketed by Pfizer under the brand name Trovan.

Mechanism of Action

Alatrofloxacin, upon administration, is rapidly converted in vivo to its active form, trovafloxacin. Trovafloxacin inhibits bacterial DNA gyrase (topoisomerase II) and topoisomerase IV, enzymes essential for bacterial DNA replication, transcription, repair, and recombination. This inhibition leads to bacterial cell death.

Therapeutic Indications

Trovafloxacin demonstrated activity against:

• Staphylococcus aureus (including methicillin-resistant strains)
• Streptococcus pneumoniae
• Haemophilus influenzae
• Moraxella catarrhalis
• Escherichia coli
• Klebsiella pneumoniae
• Proteus mirabilis
• Bacteroides fragilis
• Clostridium perfringens

The drug was approved in the United States in December 1997 for specific indications but was later withdrawn from the market due to safety concerns, particularly hepatotoxicity.

Patent Landscape of Alatrofloxacin Mesylate

The patent landscape for alatrofloxacin mesylate is critical for understanding market exclusivity, potential for generic entry, and freedom to operate for API manufacturers. Key patents primarily cover the compound itself, its therapeutic uses, and manufacturing processes.

Composition of Matter Patents

The foundational patents for trovafloxacin and its salts, including alatrofloxacin mesylate, have expired.

• US Patent 4,704,458 (issued November 3, 1987) to Pfizer Inc. covers fluoroquinolone compounds, including trovafloxacin. This patent has expired.
• US Patent 5,187,175 (issued February 16, 1993) to Pfizer Inc. covers processes for preparing fluoroquinolones, potentially including methods relevant to alatrofloxacin synthesis. This patent has expired.

The expiration of these core patents opens the door for generic manufacturers to produce and market alatrofloxacin mesylate, provided they can navigate manufacturing process patents and regulatory requirements.

Manufacturing Process Patents

While the composition of matter patents have expired, specific novel or improved synthetic routes for alatrofloxacin mesylate may still be protected by process patents. These patents could dictate specific steps, reagents, or purification techniques. Identifying these patents is crucial for API manufacturers to avoid infringement.

• US Patent 5,270,321 (issued December 14, 1993) to Pfizer Inc. relates to processes for preparing specific fluoroquinolone intermediates.
• US Patent 5,338,752 (issued August 16, 1994) to Pfizer Inc. describes methods for preparing crystalline forms of fluoroquinolones.

These examples illustrate the types of process patents that could influence manufacturing. A thorough freedom-to-operate analysis would require a comprehensive search of the USPTO and international patent databases for all active patents claiming methods of synthesizing alatrofloxacin mesylate or its key intermediates.

Litigation and Market Withdrawal

The market presence of alatrofloxacin was significantly impacted by safety concerns. In March 1999, Pfizer voluntarily withdrew Trovan (alatrofloxacin mesylate for injection) and its oral counterpart, Trovan (trovafloxacin), from the U.S. market due to reports of severe liver damage, including fatalities [1]. This withdrawal, despite the expiration of primary patents, has had a chilling effect on market re-entry and the development of generic versions.

The legal and regulatory landscape surrounding alatrofloxacin mesylate is complex due to its history of market withdrawal. While patent expiry theoretically allows for generic production, the drug's safety profile and the potential for liability may deter manufacturers and limit its therapeutic reintroduction.

Bulk API Sourcing for Alatrofloxacin Mesylate

Sourcing bulk API for alatrofloxacin mesylate requires identifying manufacturers capable of synthesizing the compound according to stringent quality standards, particularly given its historical safety issues. The market for this API is likely to be small and specialized, catering to niche applications, research, or potential reintroduction under strict controls.

Manufacturing Challenges and Considerations

Synthesizing alatrofloxacin mesylate involves multi-step chemical processes. Key considerations for API manufacturers include:

1. Chiral Purity: Fluoroquinolones can exist as enantiomers. Ensuring the correct stereochemistry of the active isomer is critical for efficacy and safety.
2. Impurity Profiling: Rigorous control of process-related impurities and degradants is essential, especially given the drug's history of hepatotoxicity.
3. Salt Formation: Precise control over the mesylate salt formation to achieve desired physicochemical properties like solubility and stability.
4. Regulatory Compliance: Manufacturing must adhere to Good Manufacturing Practices (GMP) standards set by regulatory bodies like the FDA, EMA, and others. This includes robust quality control, documentation, and validation.

Potential API Suppliers

Given the niche nature and historical context of alatrofloxacin mesylate, identifying current, large-scale commercial suppliers is challenging. The primary market is likely to be served by:

1. Specialty Chemical and API Manufacturers: Companies focusing on complex organic synthesis and custom API production. These may include:

   • Contract Development and Manufacturing Organizations (CDMOs): These firms offer services from process development to commercial-scale manufacturing. Identifying CDMOs with experience in fluoroquinolone synthesis would be a primary step.
   • API Manufacturers Specializing in Niche or Older Drugs: Some manufacturers maintain capabilities for older drugs whose patents have expired but still have limited demand.

2. Research Chemical Suppliers: While not typically producing GMP-grade API for commercial drug products, these suppliers may offer alatrofloxacin mesylate for research and development purposes. Examples include Sigma-Aldrich (Merck), Cayman Chemical, and Santa Cruz Biotechnology. These are not suitable for pharmaceutical product manufacturing but can be a source for early-stage research material.

Due to the drug's withdrawal from major markets and the associated safety concerns, publicly listed large-scale API manufacturers solely dedicated to alatrofloxacin mesylate are uncommon. The supply chain is likely to be characterized by custom synthesis agreements with specialized CDMOs rather than off-the-shelf bulk API procurement.

Due Diligence for API Sourcing

Any company seeking to source alatrofloxacin mesylate API must conduct thorough due diligence, focusing on:

• Quality Management System (QMS): Audit the manufacturer's QMS to ensure compliance with international GMP standards.
• Manufacturing Capabilities: Verify the manufacturer's experience with fluoroquinolone synthesis, chiral control, and impurity management.
• Regulatory History: Review the manufacturer's inspection history with major regulatory bodies.
• Supply Chain Security: Assess the robustness of the manufacturer's raw material sourcing and supply chain.
• Intellectual Property: Confirm that the manufacturing process does not infringe on any active patents.

The historical safety profile of alatrofloxacin necessitates an even higher degree of scrutiny regarding API quality and consistency.

Regulatory Considerations for Alatrofloxacin Mesylate

The regulatory pathway for any alatrofloxacin mesylate product, whether for research, reintroduction, or a new indication, is significantly influenced by its history.

Past Safety Issues

The liver toxicity associated with trovafloxacin led to its market withdrawal. Any future development or manufacturing would require:

• Extensive Toxicology Studies: New, comprehensive safety studies to address concerns regarding hepatotoxicity.
• Risk Management Plans: Robust pharmacovigilance and risk mitigation strategies would be mandatory.
• Post-Marketing Surveillance: Strict monitoring of patient outcomes would be required.

Generic Drug Approval

For generic alatrofloxacin mesylate, manufacturers would need to demonstrate:

• Bioequivalence: The generic product must be bioequivalent to the reference listed drug (RLD) if one were still available and marketed. Given the withdrawal, this could be complex, potentially requiring a novel RLD designation or a comparative study against a suitable comparator.
• CMC (Chemistry, Manufacturing, and Controls): Comprehensive data on the API and finished drug product manufacturing, including stability, purity, and quality control.
• Labeling: Generic labeling must be the same as the RLD's labeling, unless specific differences are justified and approved. This includes all warnings, precautions, and contraindications.

The regulatory hurdles for reintroducing alatrofloxacin mesylate are substantial due to the drug's past safety issues.

Key Takeaways

• Key composition of matter patents for alatrofloxacin mesylate have expired, theoretically allowing for generic production.
• Pfizer voluntarily withdrew alatrofloxacin mesylate from the U.S. market in 1999 due to severe hepatotoxicity concerns, significantly impacting its commercial viability and future market entry.
• Bulk API sourcing for alatrofloxacin mesylate is likely to involve specialized CDMOs capable of complex organic synthesis and stringent quality control, rather than large, general API suppliers.
• Any future manufacturing or marketing of alatrofloxacin mesylate will face significant regulatory scrutiny due to its historical safety profile, requiring extensive safety studies and robust risk management plans.
• A thorough freedom-to-operate analysis is critical to identify and avoid infringement of any remaining process patents related to alatrofloxacin mesylate synthesis.

Frequently Asked Questions

1. Are there any active composition of matter patents for alatrofloxacin mesylate? No, the primary composition of matter patents for alatrofloxacin and its salts have expired.

2. What are the main reasons for the limited availability of alatrofloxacin mesylate API on the market? The primary reason is the drug's market withdrawal due to severe hepatotoxicity concerns, which significantly reduced demand and discouraged continued large-scale commercial production and regulatory pursuit.

3. Can a company easily manufacture generic alatrofloxacin mesylate now that patents have expired? While patent expiry removes a major barrier, regulatory approval for generic alatrofloxacin mesylate is challenging due to the drug's history of severe side effects, requiring extensive safety data and risk mitigation strategies.

4. Where can I find GMP-compliant alatrofloxacin mesylate API for pharmaceutical development? Finding GMP-compliant API is likely to require engaging with specialized Contract Development and Manufacturing Organizations (CDMOs) that have expertise in complex fluoroquinolone synthesis and a proven regulatory track record, rather than purchasing from standard catalog suppliers.

5. What are the key quality control considerations for alatrofloxacin mesylate API manufacturing? Key considerations include ensuring chiral purity, rigorous control of process-related impurities and degradants to mitigate toxicity risks, and precise control over the mesylate salt formation for desired physicochemical properties.

Citations

[1] U.S. Food & Drug Administration. (1999, March 19). FDA Public Health Advisory - Trovafloxacin (Trovan). Retrieved from [FDA Archive] (Note: Actual URL may require searching FDA archives or news releases from that period).