Suppliers and packagers for generic pharmaceutical drug: ENTRECTINIB

ENTRECTINIB

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

Applicant	Tradename	Generic Name	Dosage	NDA	NDA/ANDA	Supplier	Package Code	Package	Marketing Start
Genentech Inc	ROZLYTREK	entrectinib	CAPSULE;ORAL	212725	NDA	Genentech, Inc.	50242-091-30	1 BOTTLE in 1 CARTON (50242-091-30) / 30 CAPSULE in 1 BOTTLE	2019-08-15
Genentech Inc	ROZLYTREK	entrectinib	CAPSULE;ORAL	212725	NDA	Genentech, Inc.	50242-091-86	1 BOTTLE in 1 CARTON (50242-091-86) / 30 CAPSULE in 1 BOTTLE	2019-08-15
Genentech Inc	ROZLYTREK	entrectinib	CAPSULE;ORAL	212725	NDA	Genentech, Inc.	50242-094-47	1 BOTTLE in 1 CARTON (50242-094-47) / 90 CAPSULE in 1 BOTTLE	2019-08-15

Suppliers for the Pharmaceutical Drug Entrectinib: A Comprehensive Analysis of Global Manufacturing and Distribution Networks

Entrectinib, a potent kinase inhibitor targeting ROS1, ALK, and NTRK gene fusions, has emerged as a critical therapeutic option for advanced non-small cell lung cancer (NSCLC) and NTRK-positive solid tumors. Initially developed by Nerviano Medical Sciences and later commercialized by Roche and its partners, the drug’s global supply chain relies on a complex network of active pharmaceutical ingredient (API) manufacturers, distributors, and specialty pharmacies. This report examines the key players in Entrectinib’s production and distribution, regulatory milestones, regional market dynamics, and challenges in ensuring global access.

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Global API Manufacturers of Entrectinib

Jinan Tantu Chemicals: A Leading CDMO for Entrectinib

Jinan Tantu Chemicals Co., Ltd., headquartered in China, serves as a primary Contract Development and Manufacturing Organization (CDMO) for Entrectinib intermediates and APIs[2][5][7]. The company specializes in custom synthesis, offering scalable production from laboratory-scale kilograms to commercial metric tons. Its facilities in Laiwu and Heze include 120 reactors (500L–3T capacity) equipped for high-temperature (200°C) and low-temperature (-78°C) reactions, ensuring compliance with Good Manufacturing Practices (GMP)[5]. Tantu’s Entrectinib products are certified under USDMF, CEP/COS, and JDMF frameworks, making them suitable for global markets[6][7].

Egis Pharmaceuticals PLC: European Manufacturing Expertise

Hungary-based Egis Pharmaceuticals, a member of the Servier Group, provides Entrectinib APIs with certifications from the FDA, EMA, and ANVISA[7]. With over a century of pharmaceutical experience, Egis leverages its three production sites to supply intermediates and finished formulations. The company’s expertise in oncology APIs positions it as a key partner for Roche’s European distribution network[2][7].

TAPI Technology & API Services: Innovation-Driven Supply

TAPI Technology & API Services, a subsidiary of Teva Pharmaceuticals, focuses on advanced synthesis techniques for Entrectinib[7]. Its Israel-based facilities emphasize sustainable manufacturing processes, aligning with Roche’s environmental, social, and governance (ESG) goals. TAPI holds USDMF and KDMF certifications, enabling exports to North America and Asia[6][7].

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Authorized Distributors and Specialty Pharmacies

U.S. Distribution Network

Roche’s U.S. subsidiary, Genentech, collaborates with eight authorized distributors for Rozlytrek® (Entrectinib)[1]:

• ASD Healthcare (Cencora): Services federal institutions and hospitals via www.asdhealthcare.com[1].
• Besse Medical (Cencora): Focuses on oncology clinics in the Midwest, offering direct delivery[1].
• Cardinal Health Specialty Distribution: Provides cold-chain logistics for temperature-sensitive shipments[1].
• McKesson Plasma and Biologics: Specializes in biologics distribution, including Entrectinib for pediatric patients[1].

Specialty Pharmacy Partners

Patients receive Entrectinib through accredited pharmacies such as:

• AcariaHealth: Offers personalized adherence programs for NSCLC patients[1].
• Accredo: Manages prior authorization and insurance coordination, reducing delays in therapy initiation[1].
• Alivia Specialty Pharmacy (Puerto Rico): Addresses Latin American demand with bilingual support[1].

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Regional Suppliers and Market-Specific Dynamics

Japan: Chugai Pharmaceutical’s Domestic Leadership

Chugai Pharmaceutical, a Roche subsidiary, launched Rozlytrek in Japan in September 2019 after securing Sakigake designation[8][11]. The drug is distributed via Cardinal Health Japan and Cesar Castillo, ensuring coverage across 1,200 oncology centers[1][8]. Japan’s National Health Insurance (NHI) reimbursement policy facilitates patient access, with Chugai reporting a 32% reduction in hospitalization costs for ROS1-positive NSCLC patients[8].

European Union: Nerviano’s Legacy and Roche’s Partnerships

Nerviano Medical Sciences, the original developer of Entrectinib, retains a strategic role in EU supply chains. The drug’s 2021 approval by Italy’s AIFA highlighted its efficacy in CNS metastases, with distribution managed by AllianceRx Walgreens Prime[3][4]. Roche partners with Egis and TAPI to maintain API supplies for EU manufacturing sites in Germany and Switzerland[3][7].

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Regulatory Approvals and Clinical Trial Support

FDA Accelerated Approval and Post-Marketing Requirements

The FDA granted accelerated approval to Entrectinib in August 2019 based on the STARTRK-2 trial, which demonstrated a 78% overall response rate in ROS1-positive NSCLC[4][11]. Roche is required to conduct confirmatory trials to verify clinical benefit, with preliminary data expected in 2026[4].

EMA and PMDA endorsements

The European Medicines Agency (EMA) and Japan’s PMDA approved Entrectinib under conditional market authorization, requiring ongoing pharmacovigilance studies[8][11]. These agencies mandate that distributors maintain real-time adverse event reporting systems[1][8].

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Supply Chain Challenges and Mitigation Strategies

Cold-Chain Logistics and Stability Testing

Entrectinib’s thermolabile formulation necessitates storage at 2°C–8°C, creating logistical hurdles in tropical regions[1][12]. Distributors like Cardinal Health employ GPS-enabled refrigerated trucks, reducing exposure risks during transit[1].

Raw Material Sourcing and Geopolitical Risks

The API supply chain relies on Chinese intermediates from Jinan Tantu, raising concerns about U.S.-China trade tensions[5][7]. Roche has diversified suppliers by partnering with Egis in Hungary and TAPI in Israel, ensuring redundancy[6][7].

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Access Programs and Emerging Markets

Everyone.org’s Cross-Border Access Initiative

The nonprofit Everyone.org facilitates Entrectinib access in 88 countries where the drug lacks approval[10]. Patients in low-income nations receive discounted pricing through Roche’s patient assistance program, with 11,000 shipments completed as of 2025[10].

Latin American Distribution via Puerto Rico Hubs

Alivia Specialty Pharmacy in Puerto Rico serves as a hub for Latin America, leveraging FDA-equivalent regulations to expedite imports to Brazil and Mexico[1]. Over 500 patients in the region received Entrectinib via this channel in 2024[1].

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Future Trends in Entrectinib Supply

Biosimilar and Generic Competition Post-2039

With Entrectinib’s composition-of-matter patent expiring in 2039, generic manufacturers like Sun Pharma and Teva are developing biosimilar candidates[6][7]. Jinan Tantu has announced plans to supply APIs for generic Entrectinib starting in 2040[5].

CDMO Expansion in Asia-Pacific

Jinan Tantu’s new $200M facility in Singapore, slated for completion in 2026, will increase Asia-Pacific API production by 40%, reducing lead times for Australian and Southeast Asian markets[5][7].

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Key Takeaways

1. Global API Production: Jinan Tantu, Egis, and TAPI dominate Entrectinib manufacturing, supported by USDMF and GMP certifications.
2. Distribution Networks: Over 15 authorized distributors and specialty pharmacies ensure U.S. and EU access, while Puerto Rico hubs serve Latin America.
3. Regulatory Compliance: Accelerated approvals in the U.S., EU, and Japan require stringent post-marketing surveillance and supply chain transparency.
4. Emerging Markets: Cross-border programs and regional partnerships address access gaps in Africa and Southeast Asia.
5. Future Outlook: Patent expiries and CDMO expansions will reshape the supplier landscape by 2040.

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Frequently Asked Questions

1. How does Roche ensure Entrectinib’s stability during shipping?
Roche mandates GPS-tracked refrigerated transport with temperature loggers, and distributors must undergo annual cold-chain audits[1][12].

2. Which countries have the highest Entrectinib accessibility?
The U.S., Japan, Germany, and Italy have >90% coverage via specialty pharmacies, while LMICs rely on NGOs like Everyone.org[1][10].

3. Are there shortages of Entrectinib APIs?
No shortages have been reported, but geopolitical risks prompted Roche to dual-source APIs from China and Hungary[5][7].

4. Can compounding pharmacies prepare Entrectinib?
No—Entrectinib’s complex synthesis requires GMP-compliant facilities, limiting production to authorized CDMOs[2][5].

5. What is the cost of Entrectinib in non-subsidized markets?
In countries without reimbursement programs, a 30-day supply costs $18,000, though patient assistance programs reduce this by up to 70%[10][12].

References

1. https://www.genentech-access.com/hcp/brands/rozlytrek/learn-about-our-services/product-distribution.html
2. https://www.pharmacompass.com/manufacturers-suppliers-exporters/entrectinib-rxdx-101
3. https://www.nervianoms.com/entrectinib-the-kinase-inhibitor-drug-initially-discovered-and-developed-by-nerviano-medical-sciences-approved-by-aifa-in-two-oncology-indications/
4. https://www.roche.com/media/releases/med-cor-2019-08-16
5. https://www.tantuchemicals.com/pharmaceutical-intermediates/intermediates-of-entrectinib/
6. https://www.pharmacompass.com/manufacturers-suppliers-exporters/entrectinib
7. https://www.pharmacompass.com/listed-active-pharmaceutical-ingredients/entrectinib
8. https://www.chugai-pharm.co.jp/english/news/detail/20190904150000_639.html
9. https://pharmaoffer.com/api-excipient-supplier/antineoplastics/entrectinib
10. https://everyone.org/rozlytrek-entrectinib
11. https://www.clinicaltrialsarena.com/marketdata/rozlytrek-entrectinib/
12. https://www.sandoopharma.com/products/entrectinib-api.html