APIs and Intermediates

2

Over 100 years of experience

Bayer is one of the world’s foremost innova-

tors in health care and a leading supplier

of prescription products, non-prescription

medicines and medical products. Bayer

Pharmaceuticals is the Pharmaceutical Divi-

sion of Bayer. Its headquarter company is

Bayer AG, Berlin.

At Pharmaceuticals, our largest segment in

terms of sales, we focus on researching, de-

veloping and marketing specialty-focused

innovative medicines that provide signifi cant

clinical benefi t and value, primarily in the

therapeutic areas of cardiology, oncology,

gynecology, hematology and ophthalmolo-

gy. In this way, we are addressing the grow-

ing requirements of patients, physicians,

health care payers and regulatory agencies.

Bayer provides inno vative products for both

the treatment and prevention of acute dis-

eases across a broad range of illnesses.

These products are prescribed by both gen-

eral practitioners and medical specialists.

Bayer developed the fi rst direct oral Factor

Xa inhibitor for the prevention and treatment

of life-threatening blood clots and offers a

product for the treatment of two different

forms of life-threatening pulmonary hyper-

tension.

Bayer offers innovative therapeutic options

to improve the quality of life for people suf-

fering from severe, chronic and life-threaten-

ing diseases like multiple sclerosis or hemo-

philia A. Crucial improvements have been

achieved in targeted cancer treatments such

as advanced renal cell carcinoma, unresect-

able hepatocellular carcinoma, metastatic

colorectal cancer, gastrointestinal stromal

tumors and in the treatment of castration-

resistant prostate cancer with symptomatic

bone metastases and no known visceral

metastatic disease.

In Ophthalmology Bayer launched a drug

for the treatment of wet age-related macular

degeneration, which also has been approved

for the treatment of several other disorders

of the back of the eye like diabetic macular

edema.

In the fi eld of Women’s Health, the com-

pany is concentrating on the three areas:

contraception, menopause management

and the development of gynecological

treatments. Bayer is a leading company in

the fi eld of female hormonal contraception.

In Men’s Health the division offers a range

of therapeutic options including treatments

for erectile dysfunction and testosterone

defi ciency.

The pharmaceutical products are primarily

distributed through wholesalers, pharma-

cies and hospitals, products are also co-

developed and co-marketed in partnerships

with other companies.

With more than 100 years of experience

in the production of active pharmaceuti-

cals ingredients, 50 years of microbiolo-

gy and 30 years of biotechnology, regu-

larly successful inspections and audits

by national and international institutions,

and a modern chemical and biological

production infrastructure Bayer AG is the

ideal partner at your side.

of experience of experience


of experience




of experience of experience of experience



medicines and medical products. Bayer






100 years of experience








Pharma Chemicals

The Pharma Chemicals unit of Bayer AG

markets a range of Active Pharmaceutical

Ingredients (APIs) and their intermediates to

international pharmaceutical companies. We

have successfully supplied our customers

for more than 50 years.

The Pharma Chemicals product range is

primarily based on Bayer AG’s pharma-

ceutical business areas. Other products and

technologies are the result of custom manu-

facturing activities, where Pharma Chemi-

cals cooperates with a variety of

selected customers. Pharma Chemicals

also takes advantage of the synergistic

effects of combined chemical and microbio-

logical manufacturing to enhance the quality

and economy of production. Our strategic

in-house production ensures a continual

supply of APIs. Today, production at the

Pharma Chemicals unit concentrates on:

• Estrogens

• Progestogens

• Androgens

• Steroidal Intermediates

• Quinolones

• Specialties

In all fi elds you can benefi t from the innova-

tiveness of Bayer AG 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 experi-

ence. We look forward to discussing your

specifi c requirements and answering any

further queries you may have.

Production of APIs and Intermediates

Bayer AG’s production and corresponding

development facilities for Pharma Chemi-

cals are located at four different sites. Each

of these sites offers specifi c production

capabilities, which add together to fulfi ll our

customers’ requirements today and in the

future. All sites are regularly audited by local

or foreign governmental authorities such as

the FDA, EMAS, EMA, customers and HSE

auditors (e.g., ISO 14001). All production

sites meet the highest cGMP and environ-

mental standards.

Custom Manufacturing

Should the standard range of products

offered by Pharma Chemicals not cover

the requirements of our customers, we can

also enter into long-term partnerships in

order to meet the individual and specifi c

needs of our customers using our tech-

nology.

Global Technical Services

GMP and regulatory requirements are be-

coming stricter and more comprehensive.

One of the most signifi cant advantages for

any customer working with Bayer AG’s

Pharma Chemicals team is therefore access

to our proven services covering product-

specifi c and regulatory information to quali-

fy, register and support our wide range of

APIs and Intermediates. This support, which

is centrally managed within the Pharma

Chemicals team, represents one of our

most important value-added services.

3

4

Products

CAS No. Product Regulatory documents

Estrogens 35380-71-3 Estradiol Hemihydrate CEP, Can-DMF, KDMF, USDMF, JDMF 57-91-0 17α-Estradiol USDMF 50-50-0 Estradiol Benzoate USDMF 4956-37-0 Estradiol Enanthate upon request* 979-32-8 Estradiol Valerate CEP, USDMF, KDMF 50-27-1 Estriol CEP 57-63-6 Ethinylestradiol CEP, Can-DMF, USDMF, JDMF

Progestogens 17230-88-5 Danazol USDMF, ASMF 67392-87-4 Drospirenone CEP, USDMF, KDMF 24356-94-3 Dihydroxyprogesterone Acetophenide upon request* (Algestone Acetophenide) 60282-87-3 Gestodene CEP 68-96-2 Hydroxyprogesterone upon request* 630-56-8 Hydroxyprogesterone Caproate upon request* 302-23-8 Hydroxyprogesterone Acetate upon request* 68-22-4 Norethisterone (Norethindrone) CEP, Can-DMF, USDMF, JDMF 51-98-9 Norethisterone Acetate CEP, Can-DMF, USDMF (Norethindrone Acetate) 6533-00-2 Norgestrel USDMF, JDMF 57-83-0 Progesterone CEP, USDMF, Can-DMF 797-63-7 Levonorgestrel CEP, Can-DMF, USDMF, JDMF

Androgens 58-22-0 Testosterone CEP, USDMF, Can-DMF 315-37-7 Testosterone Enanthate CEP, USDMF 5949-44-0 Testosterone Undecanoate upon request* 23983-43-9 Prasterone Enanthate upon request*

Intermediates 897-06-3 1,4-Androstadiene-3,17-Dione (ADD) upon request* 63-05-8 4-Androstene-3,17-Dione (AD) upon request* 53-43-0 Dehydroepiandrosterone (Prasterone) USDMF, Can-DMF 521-11-9 Mestanolone upon request* 846-48-0 1-Dehydrotestosterone (Boldenone) upon request* 434-03-7 Ethisterone upon request* 1424-00-6 Mesterolone upon request* 564-63-6 14α-Hydroxyandrost-4-ene-3,17-dione (VAD) upon request* 1173-09-7 16α-Methyl Acetoxy Pregnenolone (MAP) upon request*

Others 56180-94-0 Acarbose CEP, USDMF, KDMF 86393-32-0 Ciprofloxacin CEP, USDMF, KDMF 186826-86-8 Moxifloxacin Hydrochloride CEP, Can-DMF 21829-25-4 Nifedipin CEP, USDMF, KDMF


Custom Synthesis and Development

* depending on individual business model (please request evaluation form).* depending on individual business model (please request evaluation form).* depending on individual business model (please request evaluation form).

521-11-9 Mestanolone upon request* 846-48-0 1-Dehydrotestosterone (Boldenone) upon request* 434-03-7 Ethisterone upon request* 1424-00-6 Mesterolone upon request*

56180-94-0 Acarbose CEP, USDMF, KDMF 86393-32-0 Ciprofloxacin CEP, USDMF, KDMF 186826-86-8 Moxifloxacin Hydrochloride CEP, Can-DMF 21829-25-4 Nifedipin CEP, USDMF, KDMF

* depending on individual business model (please request evaluation form).

56180-94-0 Acarbose CEP, USDMF, KDMF 86393-32-0 Ciprofloxacin CEP, USDMF, KDMF 186826-86-8 Moxifloxacin Hydrochloride CEP, Can-DMF 186826-86-8 Moxifloxacin Hydrochloride CEP, Can-DMF 21829-25-4 Nifedipin CEP, USDMF, KDMF

58-22-0 Testosterone CEP, USDMF, Can-DMF 315-37-7 Testosterone Enanthate CEP, USDMF 5949-44-0 Testosterone Undecanoate upon request* 5949-44-0 Testosterone Undecanoate upon request* 23983-43-9 Prasterone Enanthate upon request*

897-06-3 1,4-Androstadiene-3,17-Dione (ADD) upon request* 63-05-8 4-Androstene-3,17-Dione (AD) upon request* 53-43-0 Dehydroepiandrosterone (Prasterone) USDMF, Can-DMF 521-11-9 Mestanolone upon request* 846-48-0 1-Dehydrotestosterone (Boldenone) upon request* 434-03-7 Ethisterone upon request* 1424-00-6 Mesterolone upon request*

-Hydroxyandrost-4-ene-3,17-dione (VAD) upon request*-Methyl Acetoxy Pregnenolone (MAP) upon request*

56180-94-0 Acarbose CEP, USDMF, KDMF 86393-32-0 Ciprofloxacin CEP, USDMF, KDMF 186826-86-8 Moxifloxacin Hydrochloride CEP, Can-DMF 186826-86-8 Moxifloxacin Hydrochloride CEP, Can-DMF 21829-25-4 Nifedipin CEP, USDMF, KDMF 21829-25-4 Nifedipin CEP, USDMF, KDMF

521-11-9 Mestanolone upon request* 846-48-0 1-Dehydrotestosterone (Boldenone) upon request* 434-03-7 Ethisterone upon request* 1424-00-6 Mesterolone upon request*

521-11-9 Mestanolone upon request* 846-48-0 1-Dehydrotestosterone (Boldenone) upon request* 434-03-7 Ethisterone upon request* 1424-00-6 Mesterolone upon request* 434-03-7 Ethisterone upon request* 1424-00-6 Mesterolone upon request*

-Hydroxyandrost-4-ene-3,17-dione (VAD) upon request*-Methyl Acetoxy Pregnenolone (MAP) upon request*


-Methyl Acetoxy Pregnenolone (MAP) upon request*





Custom Synthesis and Development

FermentationOur Know-How

Biotransformations (e.g., steroids) Hydroxylation Reduction Oxidation

Secondary metabolites /natural products

Biopharmaceuticals

Cultivation of bacteria, fungi and yeasts

Our technology

Large-scale fermentation and recovery technology

Leading technology for production of steroid key intermediates (phytosterols > AD, ADD)

FDA-approved full GMP production

Scale-up capacities from 5 l to 50 m3

Micronization of APIs

Product groups High-potency APIs Hormones Narcotics Other APIs Excipients

GMP facility (FDA approved)

Selected Chemical and Microbiological Reactions

Epoxidation

Halogenation Bromination Fluorination Iodination Chlorination

Hydrogenation

Hydroxylation

Microbiological Reactions Microbiological Oxidation Microbiological Reduction

Organometallic Reactions Ethinylation Grignard

Oxidation Jones Oppenauer Swern

Reduction Birch

Special Reactions Aromatization Cyclopropanation Reaction with Cyanides Ringold Vilsmeier

5


Our technology

Large-scale fermentation and recovery

Leading technology for production of steroid key intermediates (phytosterols > AD, ADD)

FDA-approved full GMP production

Scale-up capacities from 5 l to 50 m


Oxidation


Biopharmaceuticals


Oxidation


Biopharmaceuticals


Biotransformations (e.g., steroids) Hydroxylation Reduction

6

Production Sites

Production Site Bergkamen ⁄ Germany

The US- and EU-approved Supply Center

Bergkamen is Bayer AG’s major facility for

the production of intermediates, active ingre-

dients and bulk pharmaceutical chemicals

for steroid hormones via chemical and micro-

biological synthesis. In Berg kamen, we

Production Site Orizaba ⁄ Mexico

The Orizaba API site is Bayer AG’s second

major chemical facility for hormone and ste-

roid production, founded in 1963. A broad

range of substances for bulk sales and for

Bayer AG’s own pharma ceutical specialties

has been developed and is produced here.

Like Bergkamen, the Supply Center in

Orizaba, Veracruz (Mexico) is FDA approved.

Today, a wide range of APIs and Inter-

mediates, mainly steroid hormones, is manu-

factured regularly in accordance with all reg-

ulatory and cGMP requirements. Permanent

process control and quality management

using state-of-the-art equipment ensure

quality performance in line with all interna-

tional standards. The company is also ISO

9001 and 14001 certifi ed.

manufacture products for

our own use and for third

parties. The site is

located in the industrial

Ruhr region of North

Rhine-Westphalia and has

ex cellent transport and

in frastructure links. Cut-

ting-edge production tech-

nology and highly

sophi stic ated automa-

tion – run by a team of

committed and highly

competent Bayer AG em-

ployees – guarantee excellent product quality

in full compliance with cGMP and

ICH guidelines. The Supply Center is HSE

certifi ed with ISO 14001 and OHSAS 18001

as well as the EMAS.

World-class standards of development,

quality control, engineering, maintenance

Orizaba’s quality products

are recognized in the

domestic and international

markets, especially Latin

America, Europe and

the U.S.

and a variety of other technical services pro-

vide the latest manufacturing technology

to meet our customers’ specifi c needs.

The microbiological production facilities fea-

ture fermenters with working capacities from

0.01 to 200 m3 that convert steroidal raw

materials into a variety of intermediates and

Active Pharmaceutical Ingredients (APIs).

Bayer AG has designed its chemical works

as multipurpose units that can be intercon-

nected, which allows for bulk-scale pro-

duction of a variety of different chemicals.

Batch production can be performed in

0.5 to 8 m3 reactors and can include isol -

ation steps where required.

Our production units are equipped with

state-of-the-art process control systems.

This allows a wide range of organic chemical

reactions and subsequent physical process

technology to be performed with optimum

effi ciency and to high quality standards.

7

Production Site Elberfeld ⁄ Germany

The US- and EU-approved Supply Center

Wuppertal-Elberfeld represents Bayer’s

birth place. It was founded in 1863 in

Wuppertal, near Düsseldorf and Cologne.

Nowadays the state-of-the-art facilities

ensure time- and cost-effective production

of Active Pharmaceutical Ingredients for

internal and third-party use via chemical

and microbiological synthesis.

Cutting-edge production technology and

highly sophisticated automation – run by a

team committed to high quality and custom-

er service – guarantees top-grade quality,

reliable logistics and adherence to the high-

est safety and environmental standards. Our

highly competent Bayer AG employees’ work

environment is embedded in an established

technical infrastructure dedicated to gaining

full compliance with cGMP and ICH guide-

lines. Furthermore, the Supply Center is ISO

14001 (HSE) approved.

Our state-of-the-art equipment and qualifi ed

systems enable us to carry out highly de-

manding chemical reactions and multistep

production processes – for example, low-

temperature reactions down to -100 °C, or-

ganometallic reactions, vacuum distillations

down to 10 - 5 mbar, and separation of iso-

mers by chromatography on a technical

scale. Our well-established quality control

process, with its consistent set of operation

procedures and directives and meticulous

documentation system, meets all the require-

ments of the regulatory authorities. With

reaction scales from 1 m3 up to 8 m3 and

Micronization Plant Berlin ⁄ Germany

Pharmaceutical manufacturing requires that

most substances used must be homoge-

neously distributed and fi nely ground. In

order to accomplish this, third-party pharma

chemicals as well as Bayer AG’s own spe-

cialty ingredients are sieved, homogenized if

necessary, and / or subsequently micronized.

This production process is carried out using

jet mills in Bayer AG’s FDA- and EU-

approved drug substance fi nishing unit in

Berlin-Charlottenburg.

The modular construction of these facilities

is a pioneering achievement. The microniza-

tion plant consists of several independent

milling compartments, each of which

has its own milling room, observation

room, equipment clean-

ing room, and weighing

room. The milling

and the observation

room are separated

by a decon -ta mination

chamber.

To avoid cross-con-

tamination, each module

may only contain one

substance. After the

processing of one sub-

stance has been com-

pleted, the entire equipment and all rooms

within the module are cleaned in strict accor-

dance with cGMP guidelines.

Bayer AG has devoted considerable attention to environmentally friendly production processes in establishing the facilities

mentioned here. The new, sophisticated wastewater treatment process is one example that ensures production processes

take environmental protection as much into account as the quality and purity of our APIs and Intermediates.

fermenters up to 80 m3, we can produce

your active ingredients as you require them

– in all possible quantities and in full compli-

ance with cGMP standards.

Bayer AG

Pharma Chemicals

13353 Berlin, Germany

www.pharma.bayer.com

www.pharmachemicals.bayer.com

For Pharma Chemicals related inquiries

please contact:

Bayer AG

Pharma Chemicals

Müllerstrasse 178

D-13353 Berlin

Germany

Phone: +49 30 468 11247 or +49 30 468 12030

www.pharmachemicals.bayer.com

[email protected]

For all other inquiries related to

Bayer AG, please contact the main

switchboard: +49 30 468 1111

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 informa-tion 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 sold in accordance with the current version of our General Conditions of Sale and Delivery.July 2017.

APIs and Intermediates - Bayer Pharma...

Documents

Transcript of APIs and Intermediates - Bayer Pharma...