APIs and Intermediates

Transcription

1 APIs and Intermediates

2 Over 100 years of experience in the API business for the pharmaceutical industry Bayer is one of the world s leading Life Science Companies. Our operations are managed in three divisions: Pharmaceuticals, Consumer Health, and Crop Science / Animal Health. In Pharmaceuticals, we focus on prescription products. We provide therapeutic options to improve the quality of life of people suffering from severe, chronic, and lifethreatening diseases. The main areas are cardiology and women s healthcare, as well as specialty therapeutics in the fi elds of oncology, hematology, and Bayer is committed to researching, developing, manufacturing and marketing innovative products that improve the health of people throughout the world ophthalmology. Also comprised is the radiology business, which markets diagnostic imaging equipment and contrast agents. Bayer produces and markets active pharmaceutical ingredients (APIs) and intermediates. Our customers benefi t from a modern production infrastructure, longterm expertise in microbiology and biotechnology, and regular successful inspections and audits by national and international institutions. Reasons to buy APIs and Intermediates from Bayer // Bayer is one of the world's leading innovators in healthcare and an important supplier of prescription products, non-prescription medicines and other medical products. // Bayer s APIs are the basis for numerous pharmaceutical products inside and outside the company. // Bayer supplies the same APIs to customers as we use in our formulations. In doing so, we make sure our customers receive the same high-quality materials we use for Bayer products. ///////// 2 ///

3 Health, Safety and Environmental Protection // All sites follow internationally accepted Management System Standards (e.g. ISO for Environmental Management, OHSAS / ISO for Occupational Health and Safety Management) and operate in compliance with local and internal HSE requirements. Process Excellence // Bayer offers a combination of specialized production facilities, manufacturing solutions and long-term experience in the development and production of pharmaceutical products. Innovation // The products we are developing today will reshape the markets tomorrow. In the future, our customers will benefi t from the products we are developing today. Advantages for our Customers Customer Centricity // We consider long-term customer relationships as an important value. We achieve strong customer loyalty due to reliable and fast customer service. Quality // Our group-wide quality management enables us to develop, to process and to handle our products at the highest quality level. Expertise // The permanent improvement of our capabilities is the heart of our success. We offer more than 100 years of experience in the production of active pharmaceutical ingredients, 50 years of microbiology, and 30 years of biotechnology. Global Technical Services // Our customers have access to our proven services which cover product-specifi c and regulatory information to qualify, register, and support our APIs and Intermediates for defi ned markets. We offer technical support for quality and safety inquiries. /// 3 //////////

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5 Pharma Chemicals Bayer produces APIs and intermediates as well as drugs ready for sale. From the lab to the point of sale: We understand the whole business. The Pharma Chemicals unit of Bayer AG markets a range of Active Pharmaceutical Ingredients (APIs) and their intermediates to international pharmaceutical companies. The product range is primarily based on Bayer AG s pharmaceutical business areas. Pharma Chemicals takes advantage of the synergistic effects of combined chemical and microbiological manufacturing to enhance the quality and economy of production. Our strategic in-house production ensures a continual supply of APIs. We have successfully supplied our customers for more than 50 years. The current list of APIs and Intermediates concentrates on: // Estrogens // Progestogens // Androgens // Steroidal Intermediates // Quinolones // Specialties team is the access to specific and regulatory information to qualify, register and support our APIs and Intermediates for defi ned markets. This support is centrally managed by the Technical Coordination team at Pharma Chemicals and represents one of our most important value-added services. Advantages for Customers Customers can count on qualifi ed and effi cient backing throughout the whole process: From portioning, packaging and continual technical support (Reg., QA, EHS, GMP), to shipping logistics, insight into local markets and, fi nally, local presence through our agents. Compliance with all applicable standards is guaranteed. We make sure our customers encounter no risks of patent infringement litigation. Quality Assurance We are a dependable long-term partner and offer one face to the customer. Customers benefi t from our constant monitoring and continuous improvement in Quality Assurance and Control. Timely delivery of up-to-date documentation is guaranteed. Our customer service is quick and responsive. Our captive use production enhances our natural self-interest in optimizing our products, which guarantees continuous innovation to maintain and improve quality. All this makes Bayer an ideal partner at your side. In all fi elds, customers benefi t from the innovativeness of the company and the Bayer Quality Management System. This guarantees high product quality, reliable supplies and high standards in terms of health, safety and the environment. The Pharma Chemicals team offers a unique combination of chemical know-how together with decades of experience. Global Technical Services A strategic advantage for customers working with Bayer AG s Pharma Chemicals /// 5 //////////

6 Our Products ///////// 6 /// CAS No. Product Regulatory documents Estrogens Estradiol Hemihydrate CEP, Can-DMF, KDMF, USDMF, JDMF α-Estradiol USDMF Estradiol Benzoate USDMF Estradiol Enanthate upon request* Estradiol Valerate CEP, USDMF, KDMF Estriol CEP Ethinylestradiol CEP, Can-DMF, USDMF, JDMF Progestogens Danazol USDMF, ASMF Drospirenone CEP, USDMF, KDMF Dihydroxyprogesterone Acetophenide (Algestone Acetophenide) Gestodene CEP upon request* Hydroxyprogesterone upon request* Hydroxyprogesterone Caproate upon request* Hydroxyprogesterone Acetate upon request* Norethisterone (Norethindrone) CEP, Can-DMF, USDMF, JDMF Norethisterone Acetate (Norethindrone Acetate) Norgestrel USDMF CEP, Can-DMF, USDMF Progesterone CEP, USDMF, Can-DMF Levonorgestrel CEP, Can-DMF, USDMF Androgens Testosterone CEP, USDMF, Can-DMF Testosterone Enanthate CEP, USDMF Testosterone Undecanoate upon request* Prasterone Enanthate upon request* Intermediates ,4-Androstadiene-3,17-Dione (ADD) upon request* Androstene-3,17-Dione (AD) upon request* Dehydroepiandrosterone (Prasterone) USDMF, Can-DMF Mestanolone upon request* Dehydrotestosterone (Boldenone) upon request* Ethisterone upon request* Mesterolone upon request* α-Methyl Acetoxy Pregnenolone (MAP) upon request* Others Acarbose CEP, USDMF, KDMF Ciprofloxacin CEP, USDMF, KDMF Moxifloxacin Hydrochloride CEP, Can-DMF Nifedipine CEP, USDMF, KDMF Acetylsalicylic acid (ASS) upon request* Clotrimazole upon request* * depending on individual business model (please request evaluation form).

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8 Our Technology Bayer has a modern chemical and biological production infrastructure. The production and development facilities are located in four different sites: Bergkamen, Wuppertal and Berlin in Germany, and Orizaba in Mexico. The sites are regularly inspected by local and foreign governmental authorities such as the FDA and the EMA, as well as by customers. Internal and external auditors audit the sites according to internal and international health, safety and environmental standards (e.g. ISO 14001, 45001). All production sites meet the highest GMP and HSE standards. Each of these sites offers specific production capabilities. Our technology includes: Fermentation Our Know-How Selected Chemical and Microbiological Reactions Biotransformations (e.g. steroids) Hydroxylation Reduction Oxidation Secondary metabolites /natural products Biopharmaceuticals Cultivation of bacteria, fungi and yeasts Epoxidation Halogenation Hydrogenation Hydroxylation Bromination Fluorination Iodination Chlorination Our Technology Large-scale fermentation and recovery technology Leading technology for production of steroid key intermediates (phytosterols > AD, ADD) Microbiological Reactions Organometallic Reactions Oxidation Reduction Microbiological Oxidation Microbiological Reduction Ethinylation Grignard Jones Oppenauer Swern Birch FDA-approved full GMP production Scale-up capacities from 5 l to 50 m 3 Micronization of APIs Special Reactions Aromatization Cyclopropanation Reaction with Cyanides Ringold Vilsmeier Product groups High-potency APIs Hormones Narcotics Other APIs Excipients FDA-approved full GMP production ///////// 8 ///

9 Production Sites Production Site Bergkamen / Germany The US- and EU-approved Supply Center Bergkamen is our biggest API production site. APIs and intermediates from Bergkamen are used for our in-house production of drugs ready for sale. They are also sold in bulk to other pharmaceutical companies. At Bergkamen, 1,500 employees produce APIs and their intermediates according to the highest levels of quality. This is achieved by combining microbial fermentation and chemical transformation in an optimum way. Bergkamen is internationally recognized for its production of steroid hormones. The Bergkamen site is validated and externally certifi ed according to the highest health, safety and environmental standards, such as EMAS (EU Eco-Management and Audit Scheme), ISO (Environmental Management), OHSAS (Occupational Health and Safety Management) as well as ISO (Energy Management). Products for Pharma Chemicals: Estrogens: Estradiol Hemihydrate Estradiol Estradiol Benzoate Estradiol Valerate Estriol Ethinylestradiol Progestogens: Drospirenone Gestodene Hydroxyprogesterone Hydroxyprogesterone Caproate Hydroxyprogesterone Acetate Norethisterone (Norethindrone) Norethisterone Acetate (Norethindrone Acetate) Norgestrel Levonorgestrel Testosterone Enanthate Intermediates: 1,4-Androstadiene-3,17-Dione (ADD) 4-Androstene-3,17-Dione (AD) Mesterolone /// 9 //////////

10 Production Site Wuppertal / Germany This site is home to the company and stands for its long tradition: Bayer was founded in 1863 in Elberfeld, which is now part of the city of Wuppertal. At present, the site houses modern research and development as well as production facilities for our Pharmaceuticals division. The Wuppertal site nowadays comprises two different locations: the production facilities near the river Wupper, and the center for research and development in Aprath. The production has an annual output of more than 1,000 tons of APIs. At the research and development center, staff members work on substances used in cardiology and oncology. The biological sewage treatment plant is equipped with modern technology and guarantees the safety and quality of the environment and water. The Wuppertal site employs a total of 3,500 staff members in the areas of research, development and production. They create and manufacture new and innovative APIs for the treatment of cardiovascular and blood-related diseases, cancer and other disorders such as diabetes. The Elberfeld site complies with the highest health, safety and environmental standards and is certified according to ISO 14001, OHSAS as well as ISO The site is US and EU approved. Products for Pharma Chemicals: Acarbose, Ciprofloxacin, Moxifloxacin Hydrochloride, Nifedipine Micronization Plant Berlin / Germany In Bayer AG s FDA- and EU-approved drug substance finishing unit in Berlin-Charlotten burg, we sieve, homogenize and micronize high-speciality ingredients. Identical standards apply at all of Bayer's micronization sites. The micronization plant consists of several independent milling compartments, each of which has its own milling room, observation room, equipment cleaning room, and weighing room. The modular construction of these facilities is a pioneering achievement. The milling and observation rooms are separated by a decontamination chamber. To avoid cross-contamination, each module may only contain one substance. After the processing of one substance has been completed, the entire equipment and all rooms within the module are cleaned in strict accordance with cgmp guidelines like in all other production plants at Bayer. Micronization of APIs is performed for high-potency APIs such as hormones, narcotics and others, as well as excipients. The Charlottenburg site has also implemented the highest health, safety and environ mental standards and is certified according to ISO 14001, OHSAS as well as ISO ///////// 10 ///

11 Production Site Orizaba / Mexico The Orizaba API site is Bayer AG s second major chemical facility for hormone and steroid production, founded in A broad range of substances for bulk sales and for Bayer AG s own pharmaceutical specialties has been developed and is produced here: Estrogens: 17α-Estradiol, Estradiol Enanthate Progestogens: Danazol, Dihydroxyprogesterone Acetophenide (Algestone Acetophenide), Progesterone Androgens: Testosterone, Testosterone Enanthate, Testosterone Undecanoate, Prasterone Enanthate Intermediates: Dehydroepiandrosterone (Prasterone), Mestanolone 1-Dehydrotestosterone (Boldenone), Ethisterone Like Bergkamen and Wuppertal, the Supply Center in Orizaba, Veracruz (Mexico) is FDA approved. The company is also ISO 9001 and certifi ed. Orizaba s quality products are recognized in the domestic and international markets of Latin America, the U.S., and Europe. /// 11 //////////

12 For Pharma Chemicals related inquiries please contact: Bayer AG Pharma Chemicals Müllerstrasse 178 D Berlin Germany Legal disclaimer: This information and our technical advice whether verbal, in writing or by way of trials are given in good faith but without warranty. This also applies where proprietary rights of third parties are involved. Our advice does not release you from your obligation to verify current information in particular, information relating to our safety data or our technical information sheets and to test our products as to their suitability for the intended processes and uses. The application, use and processing of our products and the products manufactured by you on the basis of our technical advice are beyond our control and, therefore, entirely your own responsibility. Our products are subject to the terms and conditions contractually agreed with customers. August Bayer AG Pharma Chemicals Berlin, Germany