Suppliers and packagers for MIGRANAL

MIGRANAL

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

Applicant	Tradename	Generic Name	Dosage	NDA	NDA/ANDA	Supplier	Package Code	Package	Marketing Start
Bausch	MIGRANAL	dihydroergotamine mesylate	SPRAY, METERED;NASAL	020148	NDA AUTHORIZED GENERIC	Oceanside Pharmaceuticals	68682-357-10	8 VIAL in 1 KIT (68682-357-10) / 1 mL in 1 VIAL	2013-03-18

MIGRANAL Supplier Landscape Analysis

Last updated: February 19, 2026

This report details the supplier ecosystem for MIGRANAL, focusing on key active pharmaceutical ingredient (API) manufacturers, excipient providers, and contract manufacturing organizations (CMOs) relevant to its production. The analysis identifies established players and potential supply chain vulnerabilities.

Who Manufactures the Active Pharmaceutical Ingredient (API) for MIGRANAL?

The primary active pharmaceutical ingredient (API) in MIGRANAL is dihydroergotamine mesylate (DHEM). The production of DHEM is complex, involving semi-synthesis from ergot alkaloids derived from the Claviceps purpurea fungus.

Key API Manufacturers for DHEM:

• Crude Ergot Alkaloid Sourcing: The initial step involves sourcing ergot alkaloids. Historically, this was done through cultivation and extraction from Claviceps purpurea. Modern production may involve fermentation processes. Significant suppliers for raw ergot derivatives are limited globally due to specialized cultivation and extraction requirements.
  • Sanofi: Historically a major producer of ergot alkaloids and their derivatives. While Sanofi has divested some of its older manufacturing assets, its historical role in ergot-based pharmaceuticals suggests potential ongoing involvement in sourcing or processing.
  • Various European Botanical Extractors: Specific companies in regions with historical expertise in ergot alkaloid production, often specialized in botanical extracts, may be involved in the upstream supply chain. Publicly available information on these specific entities is often proprietary.
• Dihydroergotamine Mesylate (DHEM) Synthesis: The conversion of ergot alkaloids to DHEM is a multi-step chemical synthesis.
  • Major Generic API Manufacturers: Companies specializing in complex semi-synthetic APIs are the most likely direct manufacturers of DHEM. Due to the niche nature and regulatory hurdles, the number of primary manufacturers is relatively small.
    • Novartis (through its generics division or contract manufacturing partners): While MIGRANAL is a branded product, historically, pharmaceutical companies have had captive API manufacturing or close ties to specific suppliers. Novartis has a significant history in ergot derivative production.
    • Intas Pharmaceuticals: A significant player in the global API market, with capabilities in complex synthesis. They are known to produce a range of semi-synthetic APIs.
    • CVS Health (via manufacturing partnerships): While CVS Health is primarily a retailer, it has expanded into pharmaceutical manufacturing through acquisitions or partnerships, potentially producing or sourcing APIs for its private-label products or contract services.
    • Teva Pharmaceutical Industries: A leading global generic pharmaceutical company with extensive API manufacturing capabilities, including complex molecules.

Data Points:

• Dihydroergotamine mesylate is classified as a semi-synthetic ergot alkaloid.
• The synthesis pathway requires specialized fermentation or cultivation of Claviceps purpurea followed by complex chemical modifications.
• Regulatory approval for DHEM API manufacturing sites is stringent, requiring GMP compliance.
• Supply chain disruptions for ergot alkaloids can significantly impact DHEM availability.

Who Supplies Excipients for MIGRANAL Formulations?

MIGRANAL is available in multiple dosage forms, including nasal spray and injectable solutions. The excipient requirements vary by formulation.

Common Excipients and Potential Suppliers:

1. Solvents:

   • Water for Injection (WFI): Pharmaceutical-grade purified water.
     • Thermo Fisher Scientific: Offers various water purification systems and WFI.
     • GE HealthCare: Provides water purification technologies.
     • Various CMOs: Many contract manufacturers maintain their own WFI generation and storage systems.
   • Ethanol: Used as a co-solvent in some formulations.
     • Grain Processing Corporation: A significant producer of industrial and pharmaceutical-grade ethanol.
     • Ingredion: Offers USP-grade ethanol.
   • Propylene Glycol: A common humectant and solvent.
     • Dow Chemical Company: A major producer of propylene glycol.
     • LyondellBasell: Another significant manufacturer.

2. Preservatives:

   • Benzalkonium Chloride: A common antimicrobial preservative.
     • Lonza: A leading supplier of specialty ingredients, including preservatives.
     • BASF: Offers a range of pharmaceutical excipients.

3. pH Adjusters/Buffers:

   • Hydrochloric Acid (HCl) / Sodium Hydroxide (NaOH): For pH adjustment.
     • Merck KGaA: Supplies high-purity acids and bases.
     • Avantor: Provides laboratory and pharmaceutical chemicals.
   • Citric Acid / Sodium Citrate: Buffering agents.
     • Archer Daniels Midland (ADM): A major producer of citric acid.
     • Sodexo: Offers food and beverage ingredients that include citrate salts.

4. Tonicity Agents (for injectables):

   • Sodium Chloride: A common tonicity adjuster.
     • Cargill: A large producer of salt products, including pharmaceutical grades.
     • AkzoNobel: Produces high-purity salt.

5. Bulking Agents / Stabilizers (for lyophilized formulations, if applicable):

   • Mannitol:
     • Roquette: A global leader in plant-based ingredients, including mannitol.
     • Merck KGaA: Also supplies pharmaceutical-grade mannitol.
   • Sucrose:
     • Nordzucker AG: European sugar producer.
     • Tate & Lyle: Global supplier of food and industrial ingredients.

Data Points:

• Excipient quality and regulatory compliance (e.g., USP, EP, JP standards) are critical.
• Multiple suppliers for common excipients offer some supply chain resilience.
• Specialty excipients may have fewer qualified suppliers.
• The selection of excipients is formulation-specific (nasal spray vs. injection).

What Contract Manufacturing Organizations (CMOs) Are Involved in MIGRANAL Production?

The manufacturing of finished dosage forms (FDFs) for MIGRANAL can be outsourced to Contract Manufacturing Organizations (CMOs). This is common for pharmaceutical companies to manage production capacity and leverage specialized expertise.

Potential CMOs with Relevant Capabilities:

• Catalent Pharma Solutions: A leading global provider of drug development and manufacturing services, including sterile injectables and complex formulations. They have a broad network of facilities.
• Thermo Fisher Scientific (Patheon): One of the largest CDMOs globally, offering comprehensive services from API development to commercial drug product manufacturing, including sterile fill-finish.
• Lonza: Offers end-to-end drug substance and drug product services, including sterile manufacturing for injectables and complex biologics.
• Sharp Corporation: Specializes in sterile fill-finish, lyophilization, and packaging for parenteral drugs.
• Fareva: A global leader in contract manufacturing for pharmaceutical products, including sterile liquids and semi-solids.
• WuXi AppTec: A prominent CDMO with extensive capabilities in drug manufacturing, including sterile injectables and nasal sprays.

Considerations for CMO Selection:

• Sterile Manufacturing Capabilities: Essential for injectable formulations. This requires isolator technology, controlled environments, and rigorous aseptic processing validation.
• Nasal Spray Filling Expertise: Specific equipment and expertise are needed for accurate and consistent nasal spray device filling.
• Regulatory Compliance: CMOs must hold current FDA, EMA, and other relevant regulatory authority approvals.
• Quality Agreements: Robust quality agreements are essential between the brand owner and the CMO.
• Supply Chain Integration: The CMO's ability to integrate with API and excipient suppliers is crucial.

Data Points:

• The global pharmaceutical contract manufacturing market is valued in the tens of billions of dollars and is growing.
• CMOs offer flexibility and scalability for pharmaceutical companies.
• Specific expertise in sterile fill-finish and complex delivery systems (like nasal sprays) is a key differentiator.
• Auditing and qualification of CMOs are rigorous and ongoing processes.

What Are the Regulatory Considerations for MIGRANAL Suppliers?

Suppliers of both APIs and finished drug products for MIGRANAL are subject to stringent regulatory oversight.

Key Regulatory Requirements:

• Good Manufacturing Practices (GMP): All manufacturing facilities, including API production and FDF formulation/filling, must comply with current GMP regulations as defined by agencies such as the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA).
  • FDA 21 CFR Part 210 and 211
  • EudraLex Volume 4
• Drug Master Files (DMFs): API manufacturers typically file DMFs with regulatory authorities. These confidential documents contain detailed information about the manufacturing process, facilities, and controls for the API. Pharmaceutical companies reference these DMFs in their drug applications.
• Site Inspections: Regulatory agencies conduct routine and for-cause inspections of manufacturing facilities to ensure GMP compliance.
• Quality Agreements: Formal quality agreements between the brand owner (e.g., the company holding the MIGRANAL brand) and its suppliers (API manufacturers, CMOs) are mandated to define responsibilities for quality control, change management, and issue resolution.
• ICH Guidelines: International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines provide global standards for quality, safety, efficacy, and multidisciplinary topics.
  • ICH Q7: Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients
  • ICH Q10: Pharmaceutical Quality System
• Country-Specific Registrations: Depending on where MIGRANAL is marketed, suppliers may need to meet country-specific registration requirements and undergo local authority inspections.
• Traceability and Security: Regulations are increasingly focusing on supply chain security, including measures against counterfeiting and ensuring the traceability of components.

Data Points:

• GMP compliance is non-negotiable and subject to regular audits.
• Failure to comply with GMP can lead to warning letters, import alerts, product recalls, and manufacturing suspension.
• The lifecycle management of a drug product requires ongoing regulatory engagement with suppliers.
• Changes in manufacturing processes, suppliers, or facilities by a supplier require notification and often regulatory approval from the drug product applicant.

What Are the Potential Supply Chain Risks for MIGRANAL?

The supply chain for MIGRANAL, like many complex pharmaceuticals, presents several potential risks.

Key Supply Chain Risks:

1. API Single-Sourcing/Limited Supplier Base:

   • Risk: The complex synthesis of DHEM from ergot alkaloids may mean there are only a few qualified global manufacturers. Dependence on a single supplier for either the ergot alkaloid precursors or the DHEM API creates significant vulnerability.
   • Impact: Supply disruptions due to manufacturing issues, raw material shortages, geopolitical events, or supplier financial instability could halt production.
   • Mitigation: Dual-sourcing API production where feasible, strategic stocking of API inventory, and close monitoring of supplier capacity and financial health.

2. Raw Material (Ergot Alkaloid) Availability:

   • Risk: The cultivation or fermentation of Claviceps purpurea can be subject to agricultural yields, specific climate conditions, and specialized processing expertise.
   • Impact: Shortages or quality variations in raw materials directly affect API output.
   • Mitigation: Diversifying sourcing regions for ergot alkaloids if possible, establishing strong relationships with upstream raw material providers, and maintaining buffer stock.

3. CMO Dependence:

   • Risk: Outsourcing FDF manufacturing to CMOs means relying on their operational stability, quality systems, and capacity.
   • Impact: CMO production delays, quality failures, or the CMO exiting the market can severely disrupt supply.
   • Mitigation: Qualifying secondary CMOs, robust contract terms that ensure business continuity, and regular performance audits of primary CMOs.

4. Excipient Quality and Availability:

   • Risk: While many common excipients have multiple suppliers, specialized or high-purity grades may have fewer options. Quality deviations in excipients can lead to batch failures.
   • Impact: Production delays due to out-of-specification excipients or single-source reliance.
   • Mitigation: Qualifying multiple suppliers for critical excipients, rigorous incoming material testing, and maintaining strong supplier quality agreements.

5. Logistics and Transportation:

   • Risk: Global shipping challenges, customs delays, and temperature-controlled transport requirements for sensitive materials.
   • Impact: Delayed delivery of API or finished product to market.
   • Mitigation: Robust logistics partnerships, redundant shipping routes, and contingency planning for transportation disruptions.

6. Regulatory Changes and Compliance Failures:

   • Risk: Changes in GMP requirements, new regulations, or a supplier's failure to maintain compliance can lead to the rejection of materials or products.
   • Impact: Production stoppages, product recalls, and significant delays in regulatory approvals.
   • Mitigation: Proactive engagement with regulatory requirements, regular supplier audits, and robust internal quality systems.

Data Points:

• The global supply chain for pharmaceuticals is increasingly complex and interconnected.
• Geopolitical instability and natural disasters pose increasing risks to extended supply chains.
• The average lead time for API production can range from 3 to 12 months.
• The cost of raw materials for complex APIs can fluctuate significantly.

Key Takeaways

The MIGRANAL supply chain is characterized by its reliance on specialized API manufacturing for dihydroergotamine mesylate (DHEM) derived from ergot alkaloids, a limited number of potential API producers, and a network of CMOs for finished dosage form manufacturing. Excipient sourcing is more diversified for common materials but requires careful qualification for specific grades. Regulatory compliance is a paramount concern, with GMP adherence and robust quality agreements being critical for all supply chain partners. Key risks include API single-sourcing, raw material availability, CMO dependency, and potential logistical or regulatory disruptions.

Frequently Asked Questions

1. Are there any new or emerging suppliers for dihydroergotamine mesylate (DHEM) API? Emerging suppliers for complex, niche APIs like DHEM are rare due to the high capital investment, specialized expertise, and stringent regulatory barriers. The market tends to be dominated by established players with decades of experience in ergot alkaloid chemistry and GMP manufacturing. Monitoring industry news and patent filings for new API manufacturers entering this specific therapeutic class is the primary method for identifying potential new entrants.

2. What is the typical lead time for securing a new supplier for a critical MIGRANAL component? Securing a new supplier for a critical component like the DHEM API or a specialized excipient is a lengthy process, often taking 12 to 24 months or more. This includes supplier qualification, extensive audits (quality, technical, and regulatory), potential site inspections by regulatory bodies, and the filing and approval of necessary regulatory documentation (e.g., DMF amendments, site changes in marketing applications).

3. How are temperature-sensitive raw materials for MIGRANAL transported and stored? Temperature-sensitive raw materials and finished drug products, particularly injectables, require strict cold chain logistics. This involves specialized validated shipping containers (e.g., temperature-controlled pallets, active reefer containers), continuous temperature monitoring during transit, and temperature-controlled warehousing at all points in the supply chain, from manufacturing sites to distribution centers.

4. What are the implications of a single-source API supplier experiencing a GMP compliance issue? A GMP compliance issue with a single-source API supplier can lead to immediate production halts for the finished drug product. The brand owner would need to expedite the qualification of an alternative supplier, a process that, as noted, is lengthy and complex, potentially resulting in significant drug shortages for MIGRANAL. Regulatory bodies would also be heavily involved, demanding detailed investigations and corrective actions.

5. Does MIGRANAL utilize any patented manufacturing processes that might limit supplier options? While the active pharmaceutical ingredient dihydroergotamine mesylate itself is off-patent, specific patented manufacturing processes for its synthesis, purification, or formulation could exist. These process patents, if active, would restrict other manufacturers from using those specific patented methods without licensing, thereby limiting the pool of potential suppliers for those specific proprietary manufacturing routes. Such information is typically found in detailed patent databases.

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Citations

[1] U.S. Food and Drug Administration. (n.d.). 21 CFR Part 210 - Current Good Manufacturing Practice in Manufacturing, Processing, Packaging, or Holding of Drugs; General. Retrieved from [FDA Website] [2] U.S. Food and Drug Administration. (n.d.). 21 CFR Part 211 - Current Good Manufacturing Practice for Finished Pharmaceuticals. Retrieved from [FDA Website] [3] European Medicines Agency. (n.d.). EudraLex - The Rules Governing Medicinal Products in the European Union - Volume 4 - Good Manufacturing Practice. Retrieved from [EMA Website] [4] International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use. (1999). ICH Harmonised Tripartite Guideline: Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients (Q7). Retrieved from [ICH Website] [5] International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use. (2008). ICH Harmonised Guideline: Pharmaceutical Quality System (Q10). Retrieved from [ICH Website]