Suppliers and packagers for generic pharmaceutical drug: lutetium lu-177 vipivotide tetraxetan

lutetium lu-177 vipivotide tetraxetan

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

Applicant	Tradename	Generic Name	Dosage	NDA	NDA/ANDA	Supplier	Package Code	Package	Marketing Start
Novartis	PLUVICTO	lutetium lu-177 vipivotide tetraxetan	SOLUTION;INTRAVENOUS	215833	NDA	Advanced Accelerator Applications USA, Inc	69488-010-61	1 VIAL, GLASS in 1 PACKAGE (69488-010-61) / 7.5 mL in 1 VIAL, GLASS	2022-03-23

Suppliers for the Pharmaceutical Drug Lutetium Lu-177 Vipivotide Tetraxetan

The radiopharmaceutical Lutetium Lu-177 vipivotide tetraxetan (Pluvicto™) has emerged as a pivotal therapy for metastatic castration-resistant prostate cancer (mCRPC). Its supply chain relies on a network of specialized manufacturers and collaborators, including ITM Isotope Technologies Munich SE, Novartis, and certified API suppliers such as piCHEM Forschungs- und Entwicklungs GmbH. Critical agreements, regulatory milestones, and infrastructure expansions—such as Novartis’s FDA-approved Indianapolis facility—have stabilized production despite intermittent challenges. This report examines the global supplier ecosystem, manufacturing protocols, and strategies addressing scalability and quality control.

---

Key Suppliers and Manufacturing Partnerships

ITM Isotope Technologies Munich SE as a Core Isotope Supplier

ITM Isotope Technologies Munich SE (ITM) is the primary supplier of no-carrier-added (n.c.a.) lutetium-177 (EndolucinBeta®), the radioisotope integral to Pluvicto™. Under a long-term agreement with Novartis subsidiary Advanced Accelerator Applications (AAA), ITM has supplied n.c.a. 177Lu since the drug’s clinical trials and continues to support commercial production through 2035[1][3][8]. The partnership, formalized in 2020, ensures industrial-scale production with an emphasis on purity and reliability[1]. ITM’s infrastructure includes GMP-compliant facilities in Germany, which specialize in radiometals for targeted therapies[1].

Steffen Schuster, CEO of ITM, emphasized the strategic alignment: “Our role extends beyond supply—we enable partners to scale precision oncology treatments globally”[1]. This collaboration highlights the interdependence between radiopharmaceutical developers and isotope specialists, particularly for therapies requiring ultra-pure radioisotopes with short half-lives.

Novartis’s Vertical Integration and Production Network

Novartis, through its acquisition of Endocyte in 2018, internalized Pluvicto™’s development and commercialization[3]. The company operates a global manufacturing network spanning Millburn (USA), Zaragoza (Spain), Ivrea (Italy), and the newly approved Indianapolis (USA) facility[4][12]. The Indianapolis site, approved by the FDA in January 2024, is Novartis’s largest radioligand therapy (RLT) production hub, designed to produce 250,000 annual doses and address prior supply shortages[4][7][13].

Novartis President of Operations Steffen Lang noted: “Precision manufacturing ensures patients receive therapies within hours of production”[4]. The facility’s automation and proximity to US treatment centers reduce logistical bottlenecks, critical for a drug with a five-day viability window[10]. By 2025, Novartis plans additional sites in Sasayama (Japan) and Haiyan (China), further decentralizing production to meet regional demand[4][13].

---

API Manufacturers and Regulatory Compliance

piCHEM Forschungs- und Entwicklungs GmbH

Austria-based piCHEM is a leading API manufacturer of Lutetium-177 vipivotide tetraxetan, holding an active Type II Drug Master File (DMF 35625) with the FDA[2][5][11]. Its GMP-certified facilities produce bulk powder formulations (1 mg/mg strength) under the NDC code 72775-001, with marketing authorization extending to December 2025[2][5]. PharmaCompass lists piCHEM as a compliant supplier adhering to USDMF, JDMF, and CEP/COS standards, crucial for international distribution[5][11].

PharmaCompass’s Supplier Ecosystem

PharmaCompass catalogs over 20 global suppliers, though only piCHEM currently holds validated regulatory filings[2][5][14]. The platform facilitates connections between developers and API manufacturers, emphasizing transparency in pricing and compliance. Lutetium-177 vipivotide tetraxetan API prices fluctuate based on production scale, GMP audits, and regional demand, with suppliers often negotiating long-term contracts to stabilize costs[2][5].

---

Production Challenges and Quality Control

2022 Manufacturing Halt and Recovery

In May 2022, Novartis temporarily suspended Pluvicto™ production due to potential quality issues at its Ivrea and Millburn facilities[6]. The halt affected clinical trials and commercial supply, underscoring the fragility of centralized production[6]. By July 2022, the company resumed operations after implementing enhanced QC protocols, prioritizing patients mid-treatment[6][10].

Scalability Through Multi-Site Expansion

Novartis’s Indianapolis facility exemplifies lessons learned from prior shortages. The site’s approval in 2024 diversified production risks, enabling parallel manufacturing across time zones[4][7][13]. With four active sites by 2025, Novartis projects capacity for 250,000 annual doses, sufficient to meet demand as Pluvicto™ enters earlier-line prostate cancer trials[12][13].

---

Regulatory and Market Dynamics

FDA and EMA Oversight

Pluvicto™’s approval required rigorous radiopharmaceutical validation, particularly for n.c.a. 177Lu sourcing[1][3]. The FDA’s 2024 endorsement of Indianapolis hinged on automated production lines and real-time purity testing, mitigating contamination risks observed in 2022[4][6][13]. Similarly, the EMA mandates batch-level traceability for radiometals, enforced through ITM’s and piCHEM’s documentation practices[1][5].

Competitive Landscape

While Novartis dominates Pluvicto™’s supply chain, emerging competitors like Point Biopharma and Telix Pharmaceuticals are advancing PSMA-targeted therapies. However, their reliance on third-party isotope suppliers (e.g., NorthStar Medical Radioisotopes) highlights ITM’s moat in n.c.a. 177Lu production[1][3].

---

Conclusion

The supply ecosystem for Lutetium Lu-177 vipivotide tetraxetan balances vertical integration (Novartis), specialized isotope production (ITM), and API manufacturing (piCHEM). Strategic facility expansions and stringent QC have stabilized access post-2022, though geographic diversification remains critical. Future suppliers must prioritize modular production and real-time logistics to accommodate radiopharmaceuticals’ unique constraints.

References

1. https://www.itm-radiopharma.com/news/press-releases/press-releases-detail/itm-provides-nca-lutetium-177-as-long-term-supplier-for-recently-approved-novel-radiotherapeutic-in-metastatic-prostate-cancer-377/
2. https://www.pharmacompass.com/manufacturers-suppliers-exporters/177-lu-labeled-psma-617
3. https://pmc.ncbi.nlm.nih.gov/articles/PMC9099330/
4. https://www.biospace.com/novartis-expands-production-of-pluvicto-with-addition-of-its-largest-and-most-advanced-radioligand-therapy-manufacturing-facility-in-indianapolis
5. https://www.pharmacompass.com/manufacturers-suppliers-exporters/lutetium-177lu-vipivotide-tetraxetan
6. https://www.targetedonc.com/view/production-of-2-fda-approved-radioligand-agents-for-prostate-cancer-temporarily-halts
7. https://www.appliedradiationoncology.com/articles/novartis-to-increase-radioligand-therapy-production-with-new-manufacturing-facility
8. https://www.itm-radiopharma.com/news/press-releases/press-archive/itm-provides-nca-lutetium-177-as-long-term-supplier-for-recently-approved-novel-radiotherapeutic-in-metastatic-prostate-cancer-377
9. https://www.novartis.com/us-en/news/media-releases/novartis-expands-production-pluvicto-addition-its-largest-and-most-advanced-radioligand-therapy-manufacturing-facility-indianapolis
10. https://www.cbsnews.com/news/pluvicto-short-supply-advanced-prostate-cancer-novartis/
11. https://www.pharmacompass.com/manufacturers-suppliers-exporters/lutetium-lu-177
12. http://www.urotoday.com/recent-abstracts/urologic-oncology/prostate-cancer/147668-novartis-confirms-unconstrained-supply-for-pluvicto-and-continues-to-significantly-expand-the-number-of-treatment-centers.html
13. https://www.pharmaceutical-technology.com/news/novartis-fda-pluvicto-plant/
14. https://www.pharmacompass.com/manufacturers-suppliers-exporters/lutetium-chloride-lu-177