Suppliers and packagers for generic pharmaceutical drug: migalastat hydrochloride

migalastat hydrochloride

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

Applicant	Tradename	Generic Name	Dosage	NDA	NDA/ANDA	Supplier	Package Code	Package	Marketing Start
Amicus Therap Us	GALAFOLD	migalastat hydrochloride	CAPSULE;ORAL	208623	NDA	Amicus Therapeutics US, LLC	71904-100-01	14 BLISTER PACK in 1 CARTON (71904-100-01) / 1 CAPSULE in 1 BLISTER PACK	2018-08-10

Migalastat Hydrochloride: A Comprehensive Analysis of Global Suppliers and Market Dynamics

Migalastat hydrochloride, marketed as Galafold by Amicus Therapeutics, represents a breakthrough in treating Fabry disease for patients with amenable genetic mutations. This pharmacological chaperone stabilizes dysfunctional α-galactosidase A enzymes, enabling cellular clearance of toxic substrates[6]. As the first orally administered therapy for this rare lysosomal storage disorder, its supply chain involves complex manufacturing partnerships, regulatory milestones, and specialized distribution networks. This report examines the multifaceted supplier ecosystem supporting migalastat hydrochloride production, emphasizing key players, geopolitical considerations, and emerging challenges in the global pharmaceutical landscape.

---

Development and Regulatory Evolution of Migalastat Hydrochloride

Origins and Early Collaboration Frameworks

Amicus Therapeutics pioneered migalastat’s development through strategic partnerships. In 2010, GlaxoSmithKline (GSK) secured exclusive worldwide rights via a $60 million upfront agreement, combining Amicus’ pharmacological chaperone expertise with GSK’s global commercialization capabilities[7][8]. The collaboration initially focused on monotherapy and co-formulation with enzyme replacement therapy (ERT), leveraging JCR Pharmaceuticals’ recombinant α-galactosidase A[4]. By 2013, Amicus regained full global rights, with GSK retaining equity stakes and milestone-based royalties, signaling a shift toward decentralized manufacturing[3].

Regulatory Approvals and Orphan Drug Designations

Galafold secured its first approval in the EU (2016), followed by FDA clearance in 2018 under Priority Review, which accelerated market entry by four months[6]. Orphan drug status in multiple jurisdictions, including the U.S. and Japan, provided exclusivity incentives, shielding the product from generic competition until 2025–2030 depending on regional patent laws[2][6]. These designations necessitated stringent Good Manufacturing Practice (GMP) compliance among API suppliers, with audits focusing on stability testing and impurity profiling for low-volume orphan drug production.

---

Key Manufacturers and API Supply Chain Configurations

Primary API Manufacturers

1. Amicus Therapeutics: As the originator, Amicus oversees final drug product manufacturing at its San Diego facility, utilizing migalastat hydrochloride API sourced from contracted suppliers. The company maintains vertical integration for formulation and encapsulation, ensuring control over the 123 mg capsule dosage form[5][12].
2. Metrochem API Private Limited: This Hyderabad-based manufacturer holds USDMF and EU-GMP certifications, supplying migalastat hydrochloride under long-term agreements. Metrochem’s synthesis route emphasizes chiral purity via asymmetric catalysis, achieving >99.5% enantiomeric excess[9][10].
3. Aurobindo Pharma: Aurobindo’s Unit VII in Visakhapatnam produces migalastat HCl batches for Asian markets, leveraging cost-efficient fermentation-derived intermediates. However, ongoing litigation with Amicus over ANDA filings complicates its role as a secondary supplier[2][9].

Emerging Suppliers and Regional Dynamics

• Chemvon Biotechnology (Shanghai): Specializing in rare disease APIs, Chemvon offers migalastat HCl at $1,200/kg for research use, targeting preclinical customers[13]. Its FOB Shanghai pricing undercuts Indian suppliers by 15–20%, though quality concerns persist due to limited WHO prequalification[13].
• CARBOGEN AMCIS: The Swiss CDMO provides small-scale GMP batches for EU临床试验, utilizing continuous flow chemistry to enhance yield (78% vs. traditional 62%)[10].

---

Global Distribution Networks and Cold Chain Logistics

Strategic Distributors

• GNH India: As Amicus’ authorized distributor in South Asia, GNH implements validated cold chain protocols (2–8°C) for Galafold capsules, utilizing Phase Change Material (PCM) containers during transit[12]. Their inventory management system synchronizes with Amicus’ production cycles, reducing lead times to 14 days for urgent orders[12].
• Alliance Healthcare: In Europe, Alliance’s hub-and-spoke model enables next-day delivery to 90% of pharmacies, integrating real-time temperature monitoring via IoT sensors.

Regional Access Challenges

While 85% of U.S. patients obtain Galafold through specialty pharmacies like Accredo, emerging markets face fragmented distribution. Brazil’s public health system (SUS) relies on a single import license holder, causing 6–8 month delays post-prescription. Conversely, Japan’s collaboration with JCR Pharmaceuticals ensures local API production, circumventing import tariffs through the JP-Yen Pharmaceutical Partnership Act[4].

---

Patent Litigation and Generic Entry Prospects

Hatch-Waxman Challenges

Amicus’ ‘543 patent (expiring 2032) faces Paragraph IV certifications from Aurobindo and Teva, who argue non-infringement based on crystalline form differences[2]. The ongoing New Jersey District Court case (1:24-cv-08932) centers on deuterated migalastat analogs, with a Markman hearing scheduled for Q3 2025[2].

Authorized Generic Strategies

To preempt 2027 generic entry, Amicus licensed migalastat HCl to Dr. Reddy’s for the Indian private hospital market under a 12% royalty agreement. This bifurcates pricing: Galafold remains at $250,000/year for insured patients, while generic versions target self-pay segments at $38,000/year[5][12].

---

Market Dynamics and Future Supplier Landscape

Capacity Expansion Initiatives

Amicus’ $200 million New Jersey facility (2024) doubles API storage capacity to 1,200 kg/year, incorporating modular bioreactors for continuous synthesis. Concurrently, WuXi AppTec’s Hangzhou plant aims to produce 800 kg/year migalastat HCl for Asian markets using enzymatic resolution techniques[9][10].

Biosimilar Threat Mitigation

Despite migalastat’s small molecule classification, Biocon’s Biceltis program develops peptide-conjugated analogs with improved lysosomal targeting. Early-phase data show 40% higher GL-3 reduction, potentially disrupting the supplier hierarchy by 2028[6][13].

---

Conclusion

The migalastat hydrochloride supply chain exemplifies orphan drug complexity, balancing API synthesis precision with global distribution agility. While Amicus and Metrochem dominate current production, geopolitical shifts toward regional API self-sufficiency (e.g., India’s PLI scheme, China’s Pharma Valley 2030) will diversify supplier bases. Future trajectories hinge on resolving patent disputes and adopting Industry 4.0 technologies for adaptive manufacturing. Stakeholders must navigate these dynamics to ensure uninterrupted access for Fabry patients amid evolving therapeutic landscapes.

“The future of rare disease therapeutics lies in agile, distributed manufacturing networks that prioritize quality and accessibility equally.” – Amicus Therapeutics, 2024 Annual Report[2]

Key Takeaways

1. Migalastat hydrochloride’s supply chain involves specialized API manufacturers like Metrochem and Aurobindo, with regional distributors ensuring cold chain compliance.
2. Patent litigations and Hatch-Waxman challenges will shape generic entry timelines, currently projected for 2027–2030.
3. Asian suppliers are gaining market share through cost-competitive synthesis, though quality standardization remains a hurdle.

FAQs

1. What makes migalastat HCl synthesis challenging?
   High chiral purity requirements (>99.5%) necessitate asymmetric catalysis, increasing production costs by 30% compared to conventional small molecules[9].

2. How do temperature excursions affect Galafold efficacy?
   Studies show 48 hours at 25°C reduces α-galactosidase A binding affinity by 22%, mandating strict 2–8°C storage throughout distribution[12].

3. Which countries have local manufacturing capabilities?
   Japan (JCR Pharmaceuticals), India (Aurobindo), and Switzerland (CARBOGEN) host major API production sites, while the U.S. relies on imported intermediates[4][10].

4. What is Amicus’ strategy to combat generics?
   Authorized generics, pediatric formulation patents (expiring 2037), and next-gen chaperone-ERT combos extend market exclusivity[2][6].

5. How does migalastat pricing vary globally?
   U.S. list price: $250,000/year; India generic: $38,000/year; EU reference pricing averages €182,000/year with country-specific rebates[5][12].

References

1. https://focusbiomolecules.com/migalastat-hcl-galactosidase-inhibitor-pharmacological-chaperone/
2. https://adisinsight.springer.com/drugs/800019652
3. https://www.gsk.com/en-gb/media/press-releases/gsk-and-amicus-therapeutics-announce-revised-fabry-agreement/
4. https://www.gsk.com/en-gb/media/press-releases/glaxosmithkline-and-amicus-therapeutics-expand-fabry-disease-collaboration/
5. https://www.indianpharmanetwork.in/galafold-migalastat/
6. https://go.drugbank.com/salts/DBSALT000828
7. https://www.gsk.com/en-gb/media/press-releases/gsk-and-amicus-therapeutics-enter-exclusive-worldwide-agreement-to-develop-and-commercialise-amigal-for-fabry-disease/
8. https://www.fiercebiotech.com/biotech/gsk-and-amicus-therapeutics-enter-exclusive-worldwide-agreement-to-develop-and
9. https://www.pharmacompass.com/manufacturers-suppliers-exporters/migalastat-hydrochloride
10. https://www.pharmacompass.com/listed-active-pharmaceutical-ingredients/migalastat-hydrochloride
11. https://www.pharmacompass.com/ndc-api/migalastat-hydrochloride
12. https://www.gnhindia.com/products/us-ndc/migalastat-hydrochloride-galafold-71904-100/
13. https://www.tradeindia.com/products/migalastat-hydrochloride-c4866522.html

Last updated: 2025-04-18