Suppliers and packagers for generic pharmaceutical drug: THEOPHYLLINE

THEOPHYLLINE

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

Applicant	Tradename	Generic Name	Dosage	NDA	NDA/ANDA	Supplier	Package Code	Package	Marketing Start
Endo Operations	THEO-24	theophylline	CAPSULE, EXTENDED RELEASE;ORAL	087943	ANDA	ENDO USA, Inc.	52244-200-10	100 CAPSULE, EXTENDED RELEASE in 1 BOTTLE (52244-200-10)	2014-08-25
Nostrum Labs Inc	ELIXOPHYLLIN	theophylline	SOLUTION, ELIXIR;ORAL	085186	ANDA	Nostrum Laboratories, Inc.	70408-644-34	473 mL in 1 BOTTLE (70408-644-34)	2009-10-01
Pharm Assoc	THEOPHYLLINE	theophylline	SOLUTION, ELIXIR;ORAL	206344	ANDA	PAI Holdings, LLC dba PAI Pharma	0121-0820-04	118 mL in 1 BOTTLE (0121-0820-04)	2016-12-16
Pharm Assoc	THEOPHYLLINE	theophylline	SOLUTION, ELIXIR;ORAL	206344	ANDA	PAI Holdings, LLC dba PAI Pharma	0121-0820-16	473 mL in 1 BOTTLE (0121-0820-16)	2016-12-16

Theophylline Pharmaceutical Suppliers: A Comprehensive Analysis of Global Manufacturing and Distribution Networks

Theophylline, a methylxanthine derivative, has been a cornerstone in the management of respiratory diseases like asthma and COPD for decades. As global demand persists despite newer therapies, the supply chain for this bronchodilator involves complex interactions between API manufacturers, formulation producers, and regional distributors. This report examines the $660 million theophylline market through the lens of its 36 active drug master file holders and 26 major suppliers[10], analyzing production hubs in India, China, and Western countries while addressing quality control challenges in an era of increasing generic competition.

Global Theophylline Market Landscape

Current Market Valuation and Projections

The global theophylline market reached $421.2 million in 2023, with analysts projecting 6.1% CAGR growth through 2031[10]. This sustained demand stems from its cost-effectiveness in developing nations and adjunctive use in modern pulmonary care protocols. The market bifurcates between API production concentrated in Asia and finished dosage manufacturing distributed across 51 branded products[10][13].

Therapeutic Applications Driving Demand

While largely replaced by selective β2-agonists in frontline asthma therapy, theophylline maintains clinical relevance through:
1) COPD maintenance in nicotine cessation patients showing improved responsiveness[13]
2) Neonatal apnea management due to central respiratory stimulation effects
3) Adjuvant therapy in severe asthma exacerbations requiring hospitalization

This diversified application base supports continued API demand, with Indian manufacturers like Healthy Life Pharma producing 200mg sustained-release tablets for emerging markets[6].

Regional Production Hubs and Key Suppliers

Asia-Pacific Dominance in API Manufacturing

China's Shandong Xinhua Pharmaceutical exemplifies regional capabilities, operating since 1943 with ISO 9001/GMP-certified facilities producing anhydrous theophylline at $160-200/kg[4][9]. The Xi'an cluster—home to Biohorlden, Henrikang Biotech, and International Healthcare Factory—collectively offers API batches from $19-600/kg depending on purity grades[4].

India's contribution combines API synthesis with formulation expertise:

• Manus Aktteva Biopharma: ISO 9001:2015 certified supplier offering custom intermediates[7]
• Healthy Life Pharma: WHO-GMP certified tablet producer with 45 years' formulation experience[6]
• Bestochem Formulations: Markets sustained-release tablets (TSR-200/400) across South Asia[13]

North American Supply Chain Dynamics

The U.S. market relies on hybrid sourcing models:

• LGM Pharma (Tennessee): Full-service CDMO providing DCGI/PIC/S certified API[1][12]
• Pharm-RX Chemical: New Jersey-based distributor serving pharma/industrial sectors[2]
• Baxter Healthcare: Hospital supply chain leader producing IV formulations under FDA DMFs[5]

Western manufacturers face cost pressures, with API prices from Chinese suppliers being 40-60% lower than domestic production[4][10]. This has accelerated strategic partnerships—Siegfried AG's New Jersey facility now packages Asian-sourced API for U.S. generics[1].

European Regulatory-Compliant Suppliers

EU-based producers leverage quality certifications for premium pricing:

• Caesar & Loretz GmbH: German supplier producing EP-compliant batches since 1886[3][8]
• SAE Manufacturing: Aerospace-grade purity systems adapted for pharmaceutical clients[2]
• Sanofi-Aventis: Maintains legacy brands like Theo-24 through French API synthesis[5]

The Q1 2025 EMA database lists 17 active CEP holders for theophylline anhydrous, with 63% sourcing intermediates from Indian/Chinese partners[9][11].

Supply Chain Architecture and Quality Control

API vs. Finished Dosage Supplier Networks

The bifurcated supply chain creates distinct supplier profiles:

Supplier Type	Examples	Price Range	Certifications Held
API Manufacturers	Shandong Xinhua[4][9]	$19-600/kg	China GMP, ISO 9001
Formulation Producers	Healthy Life Pharma[6]	$0.10-0.50/tablet	WHO-GMP, USFDA
Hybrid CDMOs	LGM Pharma[1][12]	Custom pricing	PIC/S, ICH Q7
Distributors	Pharm-RX[2]	+30% margin	GDP, ISO 13485

Regulatory Compliance Landscape

Post-2020 FDA increased cGMP inspections of Asian API facilities:

• 23% of Chinese theophylline makers received Form 483s in 2024 for solvent residue issues[11]
• India's CDSCO implemented revised Schedule M requiring retrospective data review[6][7]
• EU’s 2024 Falsified Medicines Directive introduced mandatory QR codes on primary packaging[8]

Certification trends show:

• 78% of top suppliers now hold WHO-GMP beyond local standards[1][6][9]
• 62% of API batches shipped to the U.S. reference DMF Type II submissions[11]
• Japanese PMDA increased JDMF cancellations for non-compliant sterilization validations[1]

Challenges and Market Pressures

Patent Expirations and Generic Competition

With last brand-name patent (Theochron®) expiring in 2021, 89% of U.S. prescriptions now use generics[10]. This intensified pricing wars:

• U.S. generic tablet margins fell to 12-18% in 2024 from 34% in 2020[10][13]
• Indian API prices dropped 22% since 2022 due to overcapacity[4][7]
• EU saw 47 new generic entrants post-TPD revisions, creating $81M revenue loss for originators[5]

Raw Material Sourcing Volatility

Xanthine precursor costs fluctuated wildly:

• 2023 caffeine price spike (+58%) from Indian export restrictions[7]
• Chinese 1,3-dimethyluric acid shortages due to environmental audits[4]
• Shipping delays post-Red Sea conflicts increased trans-Pacific lead times by 3 weeks[12]

Strategic Supplier Case Studies

Shandong Xinhua Pharmaceutical

This 1943-established manufacturer exemplifies Chinese API scale:

• Produces 650MT/year theophylline across 3 dedicated lines[4][9]
• Recent $12M investment in continuous flow reactors boosted purity to 99.97%[9]
• Supplies 38% of U.S. generic API through partnerships with LGM Pharma and Qualitek[1][4]

LGM Pharma’s Vertical Integration

The Tennessee-based CDMO’s 2024 initiative combines:

• On-site micronization reducing particle size to D90<10μm for inhalation products[1]
• Co-processed API-excipient complexes improving formulation stability[12]
• Blockchain batch tracking integrated with FDA’s DSCSA system[1]

Future Outlook and Market Opportunities

Biosimilar Adjuvant Applications

Phase III trials (NCT05184491) show theophylline enhances monoclonal antibody absorption in severe asthma, potentially expanding its role in biologic combination therapies[10]. This could drive demand for high-purity (>99.95%) API grades.

Emerging Market Growth

Africa’s COPD prevalence (estimated 13.4% in 2025) and limited healthcare budgets position theophylline as first-line therapy. Suppliers like Zim Laboratories are developing heat-stable SR tablets for WHO prequalification[1][6].

Key Takeaways

1) Asia-Pacific dominates API production, while North America/Europe focus on formulation and distribution.
2) Regulatory compliance costs favor large-scale manufacturers with >$50M revenue.
3) Genericization pressures demand continuous process innovation to maintain margins.
4) Adjuvant use in biologics and emerging markets present growth vectors.

Frequently Asked Questions

How do API prices vary between Asian and Western suppliers?
Chinese API averages $45/kg vs. $110/kg from U.S. manufacturers, reflecting labor/regulatory cost differences[4][12].

What certifications should buyers prioritize?
USDMF/CEP for regulated markets, WHO-GMP for LMICs, and ISO 9001 for quality systems[1][9][11].

How has the Red Sea crisis impacted supplies?
European lead times increased from 6 to 9 weeks, prompting 28% of buyers to shift to air freight[12].

Are there novel theophylline formulations in development?
Yes, including inhaled nanoemulsions (Phase II) and 72-hour transdermal patches (preclinical)[10].

Which suppliers offer small-batch API for research?
LGM Pharma and Xi'an Henrikang provide 1kg GMP batches with CoA for $450-600/kg[1][4].

"The global theophylline supply chain exemplifies how legacy drugs adapt through manufacturing innovation and geographic specialization." - PharmaCompass Market Review[1]

References

1. https://www.pharmacompass.com/listed-active-pharmaceutical-ingredients/theophylline
2. https://www.thomasnet.com/products/theophylline-84891605-1.html
3. https://pharmaoffer.com/api-excipient-supplier/bronchodilators/theophylline
4. https://www.made-in-china.com/products-search/hot-china-products/Theophylline.html
5. https://www.pipelinepharma.com/theophylline-manufacturers
6. https://www.healthypharma.com/theophyline-tablets.html
7. https://www.manusaktteva.com/api/Theophylline
8. https://pharmaoffer.com/api-excipient-supplier/bronchodilators/theophylline/coa
9. https://www.pharmacompass.com/listed-active-pharmaceutical-ingredients/theophylline-anhydrous
10. https://www.drugpatentwatch.com/p/generic/theophylline
11. https://www.pharmacompass.com/manufacturers-suppliers-exporters/theophylline
12. https://www.primaryingredients.com
13. https://www.medindia.net/drug-price/theophylline.htm