Suppliers and packagers for generic pharmaceutical drug: pralatrexate

pralatrexate

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

Applicant	Tradename	Generic Name	Dosage	NDA	NDA/ANDA	Supplier	Package Code	Package	Marketing Start
Acrotech Biopharma	FOLOTYN	pralatrexate	SOLUTION;INTRAVENOUS	022468	NDA AUTHORIZED GENERIC	Fresenius Kabi USA, LLC	65219-550-01	1 VIAL, SINGLE-DOSE in 1 CARTON (65219-550-01) / 1 mL in 1 VIAL, SINGLE-DOSE	2022-11-15
Acrotech Biopharma	FOLOTYN	pralatrexate	SOLUTION;INTRAVENOUS	022468	NDA AUTHORIZED GENERIC	Fresenius Kabi USA, LLC	65219-552-02	1 VIAL, SINGLE-DOSE in 1 CARTON (65219-552-02) / 2 mL in 1 VIAL, SINGLE-DOSE	2022-11-15
Acrotech Biopharma	FOLOTYN	pralatrexate	SOLUTION;INTRAVENOUS	022468	NDA	Acrotech Biopharma Inc	72893-003-01	1 VIAL in 1 CARTON (72893-003-01) / 1 mL in 1 VIAL	2009-09-24
Acrotech Biopharma	FOLOTYN	pralatrexate	SOLUTION;INTRAVENOUS	022468	NDA	Acrotech Biopharma Inc	72893-005-01	1 VIAL in 1 CARTON (72893-005-01) / 2 mL in 1 VIAL	2009-09-24

Suppliers for the Pharmaceutical Drug Pralatrexate: A Comprehensive Analysis

Pralatrexate, a novel antifolate antimetabolite, has emerged as a critical therapeutic agent for relapsed or refractory peripheral T-cell lymphoma (PTCL). Its unique mechanism of action, which involves inhibition of dihydrofolate reductase and thymidylate synthase, allows for targeted cytotoxicity in malignant cells[2][6]. As global demand for this orphan-designated drug grows, understanding its supply chain—including manufacturers, regulatory milestones, pricing dynamics, and geographic availability—becomes essential for healthcare providers and pharmaceutical stakeholders. This report provides a detailed examination of the pralatrexate supply landscape, synthesizing data from clinical trials, manufacturer profiles, and market developments.

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Development and Therapeutic Profile of Pralatrexate

Origins and Mechanism of Action

Pralatrexate originated from collaborative research at Memorial Sloan-Kettering Cancer Center and Southern Research Institute[2]. Unlike traditional antifolates like methotrexate, pralatrexate’s 10-propargyl modification enhances cellular uptake and retention, enabling potent inhibition of folate-dependent enzymes in cancer cells[3][6]. This structural innovation underpins its FDA approval in 2009 and subsequent adoption as a second-line PTCL therapy[2][8].

Clinical Efficacy and Regulatory Approvals

Clinical trials have demonstrated pralatrexate’s variable efficacy across regions. In the U.S.-based PROPEL study, the drug achieved an overall response rate (ORR) of 29% and median progression-free survival (PFS) of 3.5 months[3]. However, a registrational study in China reported superior outcomes: ORR of 52% and median PFS of 4.8 months[3]. These disparities may reflect differences in patient populations or dosing protocols. Globally, pralatrexate holds approvals in the U.S., Japan, and China, with Acrotech Biopharma leading development[2][3].

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Key Manufacturers and Suppliers of Pralatrexate

Innovator and Branded Product Suppliers

Acrotech Biopharma (previously Spectrum Pharmaceuticals) remains the primary innovator, marketing pralatrexate under the brand name Folotyn[2][6]. The drug’s production involves a network of API manufacturers and formulation partners:

• Teva API (Israel): A major supplier of pralatrexate active pharmaceutical ingredient (API), Teva leverages its 14 international plants to produce over 350 APIs under GMP compliance[9][12].
• Hetero Drugs (India): This vertically integrated manufacturer provides APIs and finished formulations, with approvals from the U.S. FDA and European EMA[1][5].
• Fresenius Kabi (U.S.): Entered the market in 2022 with a generic pralatrexate injection, available in 20 mg/mL and 40 mg/2 mL vials[4][6].

Regional Distribution Networks

• China: CASI Pharmaceuticals partnered with China National Medicines Corporation (CNMC) in 2023 to distribute Folotyn, supported by a phase III trial targeting first-line PTCL therapy[3].
• Europe: Servier and Mundipharma International handle distribution, adhering to EMA’s Written Confirmation (WC) requirements for API imports[12].

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Regulatory Compliance and Quality Assurance

Good Manufacturing Practices (GMP)

All pralatrexate suppliers must comply with GMP standards to ensure product consistency. For example:

• Apicore LLC (U.S.): Specializes in process R&D and API manufacturing, with facilities audited by the FDA[1].
• Haoyuan Chemexpress (China): Produces intermediates under ISO guidelines, catering to Asian markets[1].

Certification Landscape

Platforms like PharmaCompass and PharmaOffer enable buyers to filter suppliers by certifications:

• GMP: Hetero Labs and Teva API maintain GMP compliance for global exports[5][9].
• Written Confirmation (WC): Mandatory for EU imports, obtained by Hetero Labs through EMA inspections[12].

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Market Dynamics and Pricing Strategies

Cost Analysis

Pralatrexate’s price varies significantly by formulation and region:

• U.S.: Branded Folotyn costs ~$4,194 per 1 mL vial, while Fresenius Kabi’s generic version is priced 30-40% lower[6][8].
• India: Hetero Labs offers API at reduced rates due to economies of scale, though exact figures are proprietary[5][9].

Factors Influencing Price Volatility

• Regulatory changes: Orphan drug exclusivity in the U.S. until 2025 limits generic competition[2][8].
• Supply chain disruptions: COVID-19-related API shortages impacted 2021–2022 inventories, prompting tiered pricing models[4][6].

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Strategic Partnerships and Future Outlook

Collaborative Ventures

• CASI-CNMC Alliance: Combines CASI’s R&D expertise with CNMC’s distribution infrastructure to penetrate China’s $1.2 billion PTCL market[3].
• Fresenius Kabi’s Biosimilar Pipeline: Plans to launch pralatrexate biosimilars by 2026 aim to reduce treatment costs in low-income countries[4][6].

Emerging Markets and Clinical Expansion

Ongoing trials explore pralatrexate’s efficacy in diffuse large B-cell lymphoma and mesothelioma, potentially expanding its supplier base[2]. Acrotech’s CRESCENDO phase III trial (NCT06072131) in the U.S. evaluates combination therapies, which may necessitate new API sourcing agreements[2][3].

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Challenges in the Pralatrexate Supply Chain

Regulatory Hurdles

• EMA’s WC Requirements: Non-EU manufacturers face lengthy audit processes to obtain written confirmations, delaying market entry[12].
• NMPA Scrutiny: China’s 2024 pharmacovigilance guidelines require suppliers to submit real-time adverse event data, increasing compliance costs[3].

Counterfeit Risks

Unauthorized API producers in Southeast Asia have exploited pralatrexate’s high cost, underscoring the need for verified supplier platforms like PharmaCompass[1][5].

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Conclusion

The pralatrexate supply chain is characterized by a mix of innovator firms, generic manufacturers, and regional distributors. While Acrotech Biopharma and Fresenius Kabi dominate Western markets, partnerships in Asia—such as CASI-CNMC—highlight the drug’s growing importance in emerging economies. Quality assurance remains paramount, with GMP and WC certifications serving as critical differentiators. Future developments, including biosimilars and expanded indications, will likely reshape supplier landscapes, emphasizing agility and regulatory compliance.

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Key Takeaways

1. Pralatrexate’s unique mechanism drives demand across U.S., EU, and Asian markets.
2. Hetero Drugs and Teva API lead API production, while Fresenius Kabi dominates generics.
3. Regulatory certifications (GMP, WC) are essential for supplier credibility.
4. Strategic alliances, like CASI-CNMC, optimize regional distribution.
5. Pricing remains volatile due to orphan exclusivity and supply chain constraints.

FAQs

1. Which companies supply pralatrexate API in India?
   Hetero Drugs and Haoyuan Chemexpress are key Indian API suppliers[1][5].

2. What is the cost difference between branded and generic pralatrexate?
   Fresenius Kabi’s generic version is ~35% cheaper than Folotyn in the U.S.[6][8].

3. How does China regulate pralatrexate imports?
   The NMPA requires real-time adverse event reporting and GMP compliance for API suppliers[3].

4. What certifications are needed to supply pralatrexate to the EU?
   Manufacturers must obtain Written Confirmation from EMA-audited facilities[12].

5. Are biosimilars of pralatrexate under development?
   Fresenius Kabi plans to launch biosimilars by 2026, pending clinical trial outcomes[4][6].

"The dosing of the first patient with FOLOTYN in China marks a significant achievement for CASI. It reflects our unwavering commitment to bringing advanced therapeutic options to patients." – Dr. Wei-Wu He, CASI CEO[3].

References

1. https://www.pharmacompass.com/listed-active-pharmaceutical-ingredients/pralatrexate
2. https://adisinsight.springer.com/drugs/800011170
3. https://www.clinicaltrialsarena.com/news/casi-initiates-lymphoma-treatment/
4. https://www.businesswire.com/news/home/20221208005257/en/Fresenius-Kabi-Introduces-Pralatrexate-Injection-for-the-Treatment-of-Relapsed-or-Refractory-Peripheral-T-cell-Lymphoma
5. https://pharmaoffer.com/api-excipient-supplier/antimetabolites/pralatrexate
6. https://www.fresenius-kabi.com/us/news-and-events/fresenius-kabi-introduces-pralatrexate-injection-for-the-treatme
7. https://www.biospace.com/fresenius-kabi-introduces-pralatrexate-injection-for-the-treatment-of-relapsed-or-refractory-peripheral-t-cell-lymphoma
8. https://www.drugs.com/price-guide/pralatrexate
9. https://pharmaoffer.com/api-excipient-supplier/antimetabolites/pralatrexate/gmp
10. https://www.pharmaexcipients.com/excipient-suppliers-list/
11. https://pharmasource.global/supplier-profiles/
12. https://pharmaoffer.com/api-excipient-supplier/antimetabolites/pralatrexate/wc