Suppliers and packagers for generic pharmaceutical drug: APREMILAST

APREMILAST

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

Applicant	Tradename	Generic Name	Dosage	NDA	NDA/ANDA	Supplier	Package Code	Package	Marketing Start
Amgen Inc	OTEZLA	apremilast	TABLET;ORAL	205437	NDA	Amgen Inc	55513-137-60	60 TABLET, FILM COATED in 1 BOTTLE (55513-137-60)	2020-02-26
Amgen Inc	OTEZLA	apremilast	TABLET;ORAL	205437	NDA	Amgen Inc	55513-137-95	1 BLISTER PACK in 1 CARTON (55513-137-95) / 28 TABLET, FILM COATED in 1 BLISTER PACK	2020-02-26
Amneal	APREMILAST	apremilast	TABLET;ORAL	211782	ANDA	Amneal Pharmaceuticals NY LLC	60219-1410-6	60 TABLET, FILM COATED in 1 BOTTLE (60219-1410-6)	2021-07-05
Amneal	APREMILAST	apremilast	TABLET;ORAL	211782	ANDA	Amneal Pharmaceuticals NY LLC	60219-1744-7	1 KIT in 1 KIT (60219-1744-7) * 4 TABLET, FILM COATED in 1 BLISTER PACK * 19 TABLET, FILM COATED in 1 BLISTER PACK * 4 TABLET, FILM COATED in 1 BLISTER PACK	2021-07-05

Apremilast API Suppliers: A Comprehensive Analysis of Global Manufacturers and Regulatory Considerations

Apremilast, a phosphodiesterase-4 (PDE-4) inhibitor, has emerged as a critical therapeutic agent for managing psoriatic arthritis, plaque psoriasis, and oral ulcers associated with Behçet’s disease[8]. As a small-molecule drug, its production relies on a robust supply chain of active pharmaceutical ingredient (API) manufacturers and suppliers. This report examines the global landscape of Apremilast suppliers, analyzing regional manufacturing hubs, regulatory compliance frameworks, market dynamics, and quality assurance practices. With over 40 companies worldwide producing Apremilast API, the industry reflects a blend of cost-efficient Indian manufacturers, European leaders in Good Manufacturing Practices (GMP), and specialized Chinese exporters[1][2][3]. The entry of generics, such as JAMP Pharma’s 2022 Canadian launch, underscores the growing emphasis on affordability without compromising quality[4].

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Global Supplier Landscape of Apremilast API

Regional Dominance in API Production

The production of Apremilast API is concentrated in three key regions: Asia-Pacific, Europe, and North America. India dominates the market, with over 70% of suppliers headquartered there, including Dr. Reddy’s Laboratories, Aarti Pharmalabs, and Hetero Drugs[1][3]. These companies leverage India’s cost-competitive labor, advanced synthesis capabilities, and expertise in scaling production for global markets. For instance, Dr. Reddy’s, established in 1984, operates six dedicated manufacturing facilities and has pioneered generic API development[1]. Meanwhile, European suppliers like Poland’s Polpharma emphasize GMP compliance and cater to stringent regulatory requirements. Polpharma, with over 70 years of experience, provides end-to-end solutions from process development to commercial manufacturing[1][2]. China’s role is growing, with firms such as Shandong Loncom Pharmaceutical and Senova Technology Co. expanding their API portfolios through state-of-the-art facilities in economic zones like Qihe[1][5].

Key Players and Their Capabilities

1. Dr. Reddy’s Laboratories (India): A leader in generic APIs, Dr. Reddy’s offers a diverse portfolio and robust R&D infrastructure. Its Apremilast API is produced in FDA-approved facilities, ensuring compliance with U.S. pharmacopeial standards[1][7].
2. Polpharma (Poland): As a significant European API producer, Polpharma combines cGMP manufacturing with expertise in highly potent APIs (HPAPIs). Its Apremilast is distributed globally, particularly to markets prioritizing EU-GMP certification[1][5].
3. Zhejiang Ausun Pharmaceutical (China): Specializing in high-threshold generic APIs, Ausun operates an on-site R&D center and focuses on cost-effective production for emerging markets[1].
4. Alembic Pharmaceuticals (India): Known for vertical integration, Alembic controls the entire supply chain from intermediates to finished dosages, reducing production costs by 15–20% compared to competitors[3][7].

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Regulatory Considerations for Apremilast Suppliers

Good Manufacturing Practices (GMP) Certification

GMP compliance is non-negotiable for Apremilast API suppliers. The U.S. FDA’s current GMP (cGMP) standards require rigorous documentation of manufacturing processes, quality control testing, and facility audits[3]. Indian suppliers like Neuland Laboratories and Metrochem API have invested heavily in upgrading facilities to meet these requirements. For example, Neuland’s Hyderabad plant, established in 1984, holds multiple certifications, including WHO-GMP and ISO 9001[1][3]. European suppliers adhere to the European Medicines Agency’s (EMA) GMP guidelines, which mandate annual inspections and stability testing for APIs[2][5]. Polpharma’s adherence to these standards has enabled it to supply Apremilast to over 80 countries[1].

Drug Master Files (DMFs) and Regulatory Submissions

Apremilast suppliers must submit DMFs to regulatory agencies to demonstrate API quality and manufacturing controls. The U.S. Drug Master File (USDMF) includes details on synthesis pathways, impurity profiles, and packaging[3][7]. Dr. Reddy’s USDMF for Apremilast, referenced in multiple Abbreviated New Drug Applications (ANDAs), has facilitated the approval of generic versions in the U.S.[7]. Similarly, the European Active Substance Master File (ASMF) requires suppliers to disclose data on raw materials and critical process parameters. Tenatra Chemie, an Indian exporter, has successfully navigated ASMF requirements to supply APIs to EU-based generic drug manufacturers[1][5].

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Quality Assurance and Impurity Control

Impurity Profiling and Analytical Standards

Daicel Pharma, a leader in impurity synthesis, produces high-purity Apremilast impurities such as O-Desmethyl Apremilast and Apremilast Amino Sulfone Impurity[8]. These reference standards are critical for validating analytical methods and ensuring API purity ≥99.5%. For instance, Daicel’s Certificate of Analysis (CoA) includes characterization data from NMR, IR, and mass spectrometry, aligning with ICH Q3A guidelines[8]. Suppliers like Metrochem API employ high-performance liquid chromatography (HPLC) to monitor impurities during synthesis, reducing batch-to-batch variability[1][3].

Stability Testing and Packaging

Stability studies under ICH Q1A conditions (25°C/60% RH) are mandatory to determine Apremilast’s shelf life. Alkem Laboratories utilizes accelerated stability testing to predict degradation pathways, ensuring APIs remain stable for 24 months in controlled environments[1][3]. Packaging in double-lined polyethylene bags with desiccants further prevents moisture ingress, a common cause of API degradation[3].

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Market Dynamics and Pricing Trends

Cost Drivers and Competitive Pricing

The average price of Apremilast API ranges from $1,200 to $1,800 per kilogram, influenced by raw material costs, regulatory compliance, and order volume[3]. Indian suppliers offer competitive pricing due to economies of scale; for example, Aarti Pharmalabs produces xanthine derivatives in-house, reducing dependency on third-party intermediates[1]. In contrast, European suppliers like Polpharma charge a 20–25% premium for EU-GMP-certified APIs, targeting markets with stringent regulatory oversight[2][5].

Impact of Generic Entrants

The 2022 launch of JAMP Pharma’s generic Apremilast in Canada disrupted the market, offering a 30% cost reduction compared to the brand-name Otezla®[4]. JAMP’s strategy includes patient support programs and bulk procurement agreements with hospitals, enhancing accessibility for nearly 1 million Canadians with psoriasis[4]. Similarly, U.S. generics from Teva and Mylan have intensified price competition, driving down API costs by 12–15% annually since 2023[5][7].

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Challenges and Future Outlook

Supply Chain Vulnerabilities

API manufacturers face challenges such as API shortages due to geopolitical tensions and reliance on Chinese intermediates. During the 2023–2024 supply crunch, Apremilast prices spiked by 40% when lockdowns in Shandong disrupted shipments from Loncom Pharmaceutical[1][5]. Diversifying production sites and stockpiling critical intermediates are now priorities for major suppliers.

Advancements in Continuous Manufacturing

To enhance efficiency, companies like Dr. Reddy’s are adopting continuous manufacturing technologies. This approach reduces production cycles from 14 days to 48 hours and minimizes waste by 30%, aligning with the FDA’s push for Industry 4.0 adoption[1][7].

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Conclusion

The Apremilast API market is characterized by a blend of cost-driven Indian manufacturers, quality-focused European suppliers, and innovative Chinese exporters. Regulatory compliance, particularly GMP and DMF submissions, remains a critical differentiator. As generics gain traction, suppliers must balance affordability with rigorous quality control. Future success will hinge on adopting advanced manufacturing technologies and mitigating supply chain risks through geographic diversification.

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Key Takeaways

1. India dominates Apremilast API production, leveraging cost efficiencies and scale.
2. Regulatory compliance (GMP, DMFs) is pivotal for market access.
3. Generic entrants like JAMP Pharma are reshaping pricing dynamics.
4. Continuous manufacturing and impurity control are emerging as competitive advantages.

FAQs

1. What certifications should I prioritize when selecting an Apremilast supplier?
   Opt for suppliers with FDA-approval, EU-GMP, or WHO-GMP certifications to ensure compliance[1][3][5].

2. How do Indian suppliers maintain cost competitiveness?
   Vertical integration, in-house intermediate synthesis, and economies of scale reduce production costs[1][3].

3. What impact have generics had on Apremilast pricing?
   Generics have driven price reductions of 12–30%, enhancing accessibility in markets like Canada and the U.S.[4][7].

4. Why is impurity profiling critical for Apremilast API?
   Impurities affect drug safety and efficacy; rigorous control ensures compliance with ICH guidelines[8].

5. How are suppliers addressing supply chain risks?
   Diversifying manufacturing sites and stockpiling intermediates mitigate disruptions caused by geopolitical issues[1][5].

"The addition of Apremilast demonstrates our expertise and strong presence in the specialty drug segment." — Louis Pilon, CEO of JAMP Pharma Group[4].

References

1. https://www.pharmacompass.com/listed-active-pharmaceutical-ingredients/apremilast
2. https://pharmaoffer.com/api-excipient-supplier/immunosuppressants/apremilast
3. https://www.pharmacompass.com/active-pharmaceutical-ingredients/apremilast
4. https://www.jamppharma.ca/en/the-jamp-pharma-group-launches-pr-jamp-apremilast-a-new-generic-alternative-for-the-treatment-of-plaque-psoriasis-and-psoriatic-arthritis/
5. https://pharmaoffer.com/api-excipient-supplier/immunosuppressants/apremilast/fda
6. https://www.otezlapro.com/-/media/Themes/Otezla/OtezlaPro-com/OtezlaPro-com/PDFs/9-0-Resource/9-5-Prescribing/APR150207b1_STARTForm_new_1-6-17
7. https://www.pharmacompass.com/us-drug-master-files-dmfs/apremilast
8. https://www.daicelpharmastandards.com/product-category/apremilast