Suppliers and packagers for ERLOTINIB HYDROCHLORIDE

ERLOTINIB HYDROCHLORIDE

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

Applicant	Tradename	Generic Name	Dosage	NDA	NDA/ANDA	Supplier	Package Code	Package	Marketing Start
Alembic	ERLOTINIB HYDROCHLORIDE	erlotinib hydrochloride	TABLET;ORAL	214719	ANDA	Alembic Pharmaceuticals Limited	46708-565-30	30 TABLET, FILM COATED in 1 BOTTLE (46708-565-30)	2021-07-09
Alembic	ERLOTINIB HYDROCHLORIDE	erlotinib hydrochloride	TABLET;ORAL	214719	ANDA	Alembic Pharmaceuticals Limited	46708-565-90	90 TABLET, FILM COATED in 1 BOTTLE (46708-565-90)	2021-07-09
Alembic	ERLOTINIB HYDROCHLORIDE	erlotinib hydrochloride	TABLET;ORAL	214719	ANDA	Alembic Pharmaceuticals Limited	46708-566-30	30 TABLET, FILM COATED in 1 BOTTLE (46708-566-30)	2021-07-09
Alembic	ERLOTINIB HYDROCHLORIDE	erlotinib hydrochloride	TABLET;ORAL	214719	ANDA	Alembic Pharmaceuticals Limited	46708-566-90	90 TABLET, FILM COATED in 1 BOTTLE (46708-566-90)	2021-07-09

Erlotinib Hydrochloride: Key API and Excipient Suppliers

Last updated: February 19, 2026

Erlotinib hydrochloride, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor used in the treatment of non-small cell lung cancer and pancreatic cancer, relies on a specialized supply chain for its Active Pharmaceutical Ingredient (API) and essential excipients. Key manufacturers of erlotinib hydrochloride API include those in India and China, with significant production capacity and regulatory compliance. Excipient suppliers are vetted for quality, consistency, and adherence to Good Manufacturing Practices (GMP) to ensure drug safety and efficacy.

Who are the primary manufacturers of erlotinib hydrochloride API?

Primary manufacturers of erlotinib hydrochloride API are concentrated in India and China, leveraging established chemical synthesis expertise and large-scale production capabilities. These manufacturers supply both generic drug producers and, in some cases, support originator drug supply chains.

• Indian Manufacturers:

  • Divi's Laboratories: A significant player in the global API market, Divi's Laboratories produces a wide range of APIs, including oncology drugs. The company operates multiple WHO-GMP, USFDA, and EDQM-certified manufacturing facilities. [1]
  • Laurus Labs: Known for its focus on generics and intermediates, Laurus Labs has a strong presence in oncology APIs. Its facilities are accredited by major regulatory bodies including the USFDA. [2]
  • Aarti Industries: This company is a leading manufacturer of specialty chemicals and pharmaceuticals in India, with a portfolio that includes APIs for various therapeutic areas, including cancer. [3]
  • Lupin: While primarily a finished dosage form manufacturer, Lupin also produces APIs. Its API division adheres to stringent international quality standards. [4]

• Chinese Manufacturers:

  • Zhejiang NHU Company: A large chemical and pharmaceutical enterprise, Zhejiang NHU produces a diverse range of APIs. The company emphasizes R&D and quality control in its manufacturing processes. [5]
  • Hengdian Group: This diversified conglomerate includes pharmaceutical manufacturing arms that produce APIs. They operate facilities compliant with international regulatory requirements. [6]
  • WuXi AppTec: While primarily a Contract Research, Development and Manufacturing Organization (CRDMO), WuXi AppTec provides API manufacturing services, including for complex molecules like erlotinib hydrochloride, adhering to global regulatory standards. [7]

These manufacturers are typically assessed based on their production volume, regulatory approvals (USFDA, EDQM, PMDA), intellectual property (IP) landscape, and ability to meet the stringent quality requirements of pharmaceutical companies worldwide.

What are the critical excipients required for erlotinib hydrochloride formulations?

Erlotinib hydrochloride formulations require specific excipients to ensure stability, bioavailability, and manufacturability. The selection of these excipients is critical and must comply with pharmacopeial standards (e.g., USP, EP, JP) and regulatory guidelines.

• Diluents/Fillers: These add bulk to the tablet formulation.
  • Lactose Monohydrate: Commonly used due to its good compressibility and flow properties.
  • Microcrystalline Cellulose (MCC): Provides binding and disintegration properties.
• Binders: These hold the tablet ingredients together after compression.
  • Povidone (Polyvinylpyrrolidone, PVP): A widely used binder that enhances tablet hardness and integrity.
• Disintegrants: These help the tablet break apart in the digestive tract, releasing the API.
  • Croscarmellose Sodium: A superdisintegrant that swells rapidly when exposed to water.
  • Sodium Starch Glycolate: Another effective disintegrant that promotes rapid tablet disintegration.
• Lubricants: These prevent tablet ingredients from sticking to the punches and dies during compression.
  • Magnesium Stearate: A common lubricant that reduces friction between the tablet and the die wall.
• Glidants: These improve the flowability of the powder mixture.
  • Colloidal Silicon Dioxide: Enhances powder flow and prevents segregation.
• Coating Agents: Used for aesthetic purposes, taste masking, and protection of the API.
  • Hypromellose (Hydroxypropyl Methylcellulose, HPMC): A common film-coating agent.
  • Titanium Dioxide: Used as an opacifier and colorant in coatings.
  • Polyethylene Glycol (PEG): Used as a plasticizer in film coatings.

Key Excipient Suppliers:

Major global suppliers of pharmaceutical excipients include:

• Ashland: Offers a broad range of binders, disintegrants, and coating agents, including Povidone, Croscarmellose Sodium, and HPMC. [8]
• JRS Pharma: Specializes in excipients such as Microcrystalline Cellulose (VIVAPUR®) and Sodium Starch Glycolate (DICEL®). [9]
• BASF: A large chemical company providing pharmaceutical ingredients, including Lactose (LUMISORB®) and Povidone. [10]
• Evonik Industries: Offers functional excipients for drug delivery systems and tablet formulations. [11]
• Colorcon: A leading supplier of film coatings and excipients for solid dosage forms. [12]

The choice of excipient supplier is influenced by their ability to provide consistent quality, detailed documentation (e.g., Drug Master Files or excipient master files), and adherence to global regulatory standards.

What is the regulatory landscape for erlotinib hydrochloride API and finished product manufacturing?

The manufacturing of erlotinib hydrochloride API and its finished drug products is subject to rigorous regulatory oversight by health authorities worldwide. Compliance ensures the safety, efficacy, and quality of the drug.

• Active Pharmaceutical Ingredient (API) Regulations:

  • Good Manufacturing Practices (GMP): API manufacturers must adhere to GMP guidelines established by regulatory bodies such as the U.S. Food and Drug Administration (FDA), the European Medicines Agency (EMA), and the Pharmaceuticals and Medical Devices Agency (PMDA) in Japan. [13]
  • Drug Master Files (DMFs): API manufacturers typically submit DMFs to regulatory agencies. These confidential documents contain detailed information about the manufacturing process, facilities, quality control, and stability of the API. [14]
  • ICH Guidelines: The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) provides harmonized guidelines on quality, safety, efficacy, and multidisciplinary topics, which are essential for global API manufacturing. Key guidelines include ICH Q7 (Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients). [15]
  • Inspections and Audits: Regulatory agencies conduct routine inspections of API manufacturing sites to verify compliance with GMP and other applicable regulations. Pharmaceutical companies also conduct audits of their API suppliers.

• Finished Drug Product Regulations:

  • Marketing Authorization Applications (MAAs): Companies seeking to market erlotinib hydrochloride finished products must submit comprehensive dossiers to regulatory authorities. These dossiers include detailed information on the API, formulation, manufacturing process, quality control, stability data, and clinical trial results.
  • Post-Approval Changes: Any changes to the API supplier, manufacturing process, or formulation require regulatory notification or approval, depending on the significance of the change.
  • Pharmacovigilance: Manufacturers are responsible for ongoing monitoring of the drug's safety profile once it is on the market.

Key Regulatory Authorities:

• U.S. Food and Drug Administration (FDA): Regulates drugs marketed in the United States. [16]
• European Medicines Agency (EMA): Oversees drug approvals for the European Union. [17]
• Pharmaceuticals and Medical Devices Agency (PMDA): Japan's regulatory body. [18]
• Other National Authorities: Include Health Canada, Therapeutic Goods Administration (TGA) in Australia, and national drug regulatory bodies in other countries.

The supply chain for erlotinib hydrochloride must demonstrate robustness and compliance across all stages, from API synthesis to the final drug product manufacturing and distribution, to meet global regulatory standards.

How do intellectual property rights impact the supply of erlotinib hydrochloride?

Intellectual property (IP) rights, primarily patents, significantly shape the market dynamics and supply of erlotinib hydrochloride. Patents protect the innovation behind the drug, granting exclusive rights to the patent holder for a defined period.

• Composition of Matter Patents: The initial patent typically covers the erlotinib molecule itself. This patent provides the strongest protection, preventing any unauthorized manufacturing or sale of the drug substance. For Tarceva (the originator brand of erlotinib hydrochloride), this patent has long since expired in major markets, paving the way for generic competition. [19]

• Process Patents: These patents protect specific methods or processes used to synthesize erlotinib hydrochloride. Generic manufacturers must develop non-infringing synthesis routes to avoid IP challenges. Innovation in process chemistry by generic API manufacturers can lead to more cost-effective and environmentally friendly production methods.

• Formulation Patents: Patents may also cover specific drug formulations, such as particular tablet compositions, coatings, or drug delivery systems designed to improve efficacy, safety, or patient compliance.

• Patent Expirations and Generic Entry: The expiration of key patents for erlotinib hydrochloride has led to the entry of multiple generic manufacturers. This competition typically results in:

  • Price Reductions: Increased supply from generic sources drives down the overall cost of the drug.
  • Expanded Access: Lower prices can make the drug more accessible to a larger patient population.
  • Supply Chain Diversification: Pharmaceutical companies may source erlotinib hydrochloride API from multiple qualified generic suppliers, reducing reliance on a single source.

• Patent Litigation and Paragraph IV Filings (U.S.): In the U.S., generic companies can challenge existing patents by filing Abbreviated New Drug Applications (ANDAs) that certify that the relevant patents are invalid, unenforceable, or will not be infringed. This process, known as a Paragraph IV certification, often leads to patent litigation. Successful challenges by generic manufacturers before patent expiry can accelerate market entry. [20]

• Global Patent Strategies: Originator companies often pursue multiple patents in different countries covering various aspects of the drug. Generic companies must conduct thorough freedom-to-operate (FTO) analyses in each target market to ensure their products do not infringe on any valid IP.

The IP landscape for erlotinib hydrochloride is dynamic, with expired composition of matter patents opening the door for a competitive generic market. However, ongoing process and formulation patents, as well as potential new IP filings for improved delivery systems or combination therapies, can continue to influence supply and market access.

How is the quality and consistency of erlotinib hydrochloride API ensured?

Ensuring the quality and consistency of erlotinib hydrochloride API is paramount for patient safety and therapeutic efficacy. This is achieved through a multi-faceted approach involving stringent manufacturing controls, robust analytical testing, and regulatory oversight.

• Good Manufacturing Practices (GMP):

  • Process Validation: API manufacturers must validate their synthesis and purification processes to ensure they consistently produce API meeting predetermined specifications. This involves prospective, concurrent, or retrospective validation studies. [13]
  • Change Control: Any changes to the manufacturing process, equipment, or materials must be managed through a formal change control system, assessing the potential impact on API quality and requiring regulatory approval if necessary.
  • Batch Records: Detailed batch manufacturing records document every step of the production process, ensuring traceability and accountability for each lot of API.
  • Facility and Equipment Qualification: Manufacturing facilities and equipment must be qualified and maintained to prevent contamination and ensure consistent performance.

• Analytical Testing and Specifications:

  • Identity, Purity, and Potency: Each batch of erlotinib hydrochloride API undergoes comprehensive analytical testing to confirm its identity, assess its purity (including related substances and residual solvents), and determine its potency.
  • Pharmacopeial Standards: API must meet the specifications outlined in official pharmacopeias, such as the United States Pharmacopeia (USP), European Pharmacopoeia (EP), and Japanese Pharmacopoeia (JP). These monographs define required tests, analytical methods, and acceptance criteria.
  • In-house Specifications: Manufacturers often establish more stringent in-house specifications to ensure an even higher level of quality.
  • Analytical Methods Validation: All analytical methods used for testing must be validated according to ICH Q2(R1) guidelines to ensure they are accurate, precise, specific, and reliable. [21]

• Stability Testing:

  • Long-term and Accelerated Studies: API is subjected to stability studies under various temperature and humidity conditions (ICH Q1A(R2)). This data establishes the retest period or shelf-life of the API and identifies potential degradation products. [22]
  • Stress Testing: Forced degradation studies are conducted to understand the API's degradation pathways under conditions such as heat, humidity, light, acid, base, and oxidation. This helps in developing stability-indicating analytical methods.

• Supplier Qualification and Audits:

  • Quality Agreements: Pharmaceutical companies establish quality agreements with their API suppliers. These agreements define the responsibilities of each party regarding quality control, change notification, and issue resolution.
  • Supplier Audits: Regular audits of API manufacturing sites by the pharmaceutical companies are crucial to verify ongoing compliance with GMP and the terms of the quality agreement.

• Regulatory Submissions and Inspections:

  • Drug Master Files (DMFs): Detailed information on the API manufacturing process and controls is submitted to regulatory agencies via DMFs.
  • Regulatory Inspections: API manufacturing sites are subject to inspection by regulatory authorities (e.g., FDA, EMA) to assess compliance with GMP.

By implementing these rigorous quality control measures, the consistency and quality of erlotinib hydrochloride API are assured, forming the foundation for safe and effective finished drug products.

Key Takeaways

• India and China are the primary geographic hubs for erlotinib hydrochloride API manufacturing, with companies like Divi's Laboratories, Laurus Labs, Aarti Industries, Zhejiang NHU, and Hengdian Group being significant producers.
• Critical excipients include diluents (lactose, MCC), binders (povidone), disintegrants (croscarmellose sodium), lubricants (magnesium stearate), glidants (colloidal silicon dioxide), and coating agents (HPMC, titanium dioxide). Major global excipient suppliers include Ashland, JRS Pharma, and BASF.
• The manufacturing of erlotinib hydrochloride API and finished products is heavily regulated, requiring adherence to GMP, submission of DMFs, and compliance with ICH guidelines, overseen by agencies such as the FDA and EMA.
• Intellectual property, particularly patent expirations, has enabled significant generic competition for erlotinib hydrochloride, leading to increased supply and reduced prices.
• API quality and consistency are maintained through stringent GMP, comprehensive analytical testing against pharmacopeial standards, validated analytical methods, stability studies, and robust supplier qualification processes.

Frequently Asked Questions

1. What is the typical batch size for erlotinib hydrochloride API production? Batch sizes can vary significantly depending on the manufacturer's capacity and market demand, often ranging from tens of kilograms to several metric tons for established APIs like erlotinib hydrochloride, particularly from large-scale generic manufacturers.

2. How long does it take to qualify a new erlotinib hydrochloride API supplier? The qualification process for a new API supplier typically takes 6 to 18 months. This includes initial assessments, technical reviews of DMFs, site audits, and potentially the evaluation of pilot or validation batches.

3. Are there any specific impurities that regulatory agencies scrutinize for erlotinib hydrochloride? Regulatory agencies scrutinize impurities such as related substances (process impurities and degradation products), residual solvents, and genotoxic impurities. Specific focus is placed on impurities that exceed established thresholds (ICH Q3A/Q3B) or pose a toxicological risk. [23]

4. What is the typical shelf-life assigned to erlotinib hydrochloride API? The retest period or shelf-life for erlotinib hydrochloride API is generally determined by stability studies and can range from 2 to 5 years when stored under recommended conditions. Specific assignments vary by manufacturer and are detailed in their regulatory filings.

5. How does the geographic origin of API suppliers influence supply chain risk? Reliance on API suppliers from specific geographic regions can introduce risks related to geopolitical stability, trade policies, natural disasters, and differing regulatory enforcement levels. Diversifying suppliers across multiple regions can mitigate these risks.

Citations

[1] Divi's Laboratories. (n.d.). APIs. Retrieved from https://www.divislabs.com/apis [2] Laurus Labs. (n.d.). APIs. Retrieved from https://www.lauruslabs.com/products/apis/ [3] Aarti Industries. (n.d.). Pharmaceuticals. Retrieved from https://www.aarti-industries.com/pharmaceuticals [4] Lupin. (n.d.). API Business. Retrieved from https://www.lupin.com/business/api-business/ [5] Zhejiang NHU Company. (n.d.). Products. Retrieved from https://www.zje.nhu.com/products [6] Hengdian Group. (n.d.). Pharmaceuticals. Retrieved from https://www.hengdiangroup.com/business/pharmaceuticals/ [7] WuXi AppTec. (n.d.). API Manufacturing. Retrieved from https://www.wuxiapptec.com/services/small-molecule-drug-substance-manufacturing [8] Ashland. (n.d.). Pharmaceutical Excipients. Retrieved from https://www.ashland.com/industries/pharmaceuticals/excipients [9] JRS Pharma. (n.d.). Products. Retrieved from https://www.jrspharma.com/products/ [10] BASF. (n.d.). Pharmaceutical Ingredients. Retrieved from https://www.basf.com/global/en/markets/pharmaceuticals.html [11] Evonik Industries. (n.d.). Health & Care. Retrieved from https://www.evonik.com/en/business-units/specialty-additives/health-care [12] Colorcon. (n.d.). Products. Retrieved from https://www.colorcon.com/products-services [13] U.S. Food and Drug Administration. (2022, March 3). Current Good Manufacturing Practice (CGMP) Regulations. Retrieved from https://www.fda.gov/drugs/pharmaceutical-quality-regulation/current-good-manufacturing-practice-cgmp-regulations [14] U.S. Food and Drug Administration. (2023, March 15). Drug Master Files (DMFs). Retrieved from https://www.fda.gov/drugs/development-approval-process-drugs/drug-master-files-dmfs [15] International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use. (n.d.). ICH Harmonised Tripartite Guideline Q7: Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients. Retrieved from https://www.ich.org/page/quality-guidelines [16] U.S. Food and Drug Administration. (n.d.). Drugs. Retrieved from https://www.fda.gov/drugs [17] European Medicines Agency. (n.d.). Medicines. Retrieved from https://www.ema.europa.eu/en/medicines [18] Pharmaceuticals and Medical Devices Agency. (n.d.). About PMDA. Retrieved from https://www.pmda.go.jp/english/about-pmda/01.html [19] U.S. Food and Drug Administration. (n.d.). Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations. Retrieved from https://www.accessdata.fda.gov/scripts/cder/ob/ [20] U.S. Food and Drug Administration. (2023, May 17). Abbreviated New Drug Applications (ANDAs) - Paragraph IV Certifications. Retrieved from https://www.fda.gov/drugs/abbreviated-new-drug-applications-andas-paragraph-iv-certifications [21] International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use. (n.d.). ICH Harmonised Guideline Q2(R1): Validation of Analytical Procedures: Text and Methodology. Retrieved from https://www.ich.org/page/quality-guidelines [22] International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use. (n.d.). ICH Harmonised Guideline Q1A(R2): Stability Testing of New Drug Substances and Products. Retrieved from https://www.ich.org/page/quality-guidelines [23] International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use. (n.d.). ICH Harmonised Guideline Q3A(R2): Impurities in New Drug Substances. Retrieved from https://www.ich.org/page/quality-guidelines