CEPiA WHITE PAPERS
OEB 5 COMPOUNDS
CEPiA WHITE PAPERS
OUSTANDING FACILITIES
ISO 7 CLASSIFICATION
HIGHLY ACTIVE PHARMACEUTICALS
HIGHLY SKILLED TEAMS
Sanofi is one of the top five pharmaceutical companies in the world and a leader in pharmaceutical sciences. Sanofi excellence in pharmaceutical sciences is based on its experience with industrial development of all kinds of projects and bringing new chemical entities to market. The industrial organization within Sanofi known as Industrial Affairs includes a business unit dedicated to third-party activity named CEPiA (Commercial & External Partnership, Industrial Affairs). One of CEPiA’s missions as a Contract Manufacturing Organization within Sanofi is to provide manufacturing solutions for Active Pharmaceuticals Ingredients (API) to external customers. A key activity is the manufacturing of highly active pharmaceutical ingredients (HAP) and cytotoxic compounds. This activity stems from Sanofi’s expertise gained through the manufacturing of taxanes (Docetaxel, Taxotere® and Cabazitaxel, Jevtana®) and in the development of other drugs for oncology. CEPiA is glad to present to customers its dedicated equipment and facilities for highly active products manufacturing. Customer HAP projects will be managed by the same experts who have developed and launched Taxotere® and Jevtana®. Our high level of expertise has been acquired handling cytotoxic compounds for more than twenty years and is based on five major principles:
• • • • •
Extensive knowledge in Chemistry State of the art facilities Highly trained personnel Environment, Health and Safety experts High standards in Quality
The extensive knowledge in Chemistry is part of an ability to adapt to the requirements of an ever moving pharmaceutical world. Driven by the search of always better compounds with increased potency Sanofi chemists have been forced to adapt their ways of working and develop their processes to achieve successful scale-up and industrial production with respect to product quality and production staff. The handling of highly active products is more complex and limited to a small number of companies. Although there has been a growing number of organizations advertising their HAP handling capabilities, only a few have demonstrated a real ability in this segment of API manufacturing. A reason being is the amount of financial investment to design, operate and maintain highly contained workshops and buildings.
www.cepia-sanofi.com
OEB 5 COMPOUNDS
CEPiA WHITE PAPERS
OUSTANDING FACILITIES
ISO 7 CLASSIFICATION
All companies dealing with commercial HAPs know that an isolator itself is not the definition of a high containment facility. There are multiple parameters that need to be considered in the manufacture of HAPs beyond the isolator. It is risky to rely on a company that would claim capabilities in HAP handling using isolators installed in workshops and which were not designed or upgraded with appropriate air flow and containment measures beyond the isolators.
HIGHLY SKILLED TEAMS
Sanofi’s operating and safety philosophy in the HAP field is based on the concept of highly contained workshops including with the weighing room for starting materials, to the isolators and reactors, to the filtration equipment and the packaging room. For these reasons, CEPiA Sanofi is truly a leader among CMOs for highly actives and cytotoxics.
On the same site located near Paris (France), a kilo lab and two production units are suitable for process development activity, small scale production and large industrial scale manufacturing. All production units are equiped with the latest technologies in isolators, glove boxes, vessels and drying equipment. Suites are fully or partially segregated with restricted access with personnel entrance and exit through airlock systems satisfying the most stringent requirements for products and personnel protection. Production units operate in ISO 7 classification/class 10000 for OEB 4 and OEB 5 compounds and are regularly inspected by Health Authorities (FDA, EMA and PMDA).
www.cepia-sanofi.com
OEB 5 COMPOUNDS
CEPiA WHITE PAPERS
OUSTANDING FACILITIES
ISO 7 CLASSIFICATION
HIGHLY SKILLED TEAMS
A total of almost 40 reactors ranging from 5L to 1000L (glass, glass-lined, stainless steel, and Hastelloy) are dedicated to this activity, as well as multiple filtration options (filters dryers and Nutsch filters) with material compatibility (stainless steel, Hastelloy). Additionally, chromatography equipment with two preparative HPLC columns (Ø 450mm and 200mm) is used for purification of high potent compounds (OEB 5).
www.cepia-sanofi.com
OEB 5 COMPOUNDS
CEPiA WHITE PAPERS
OUSTANDING FACILITIES
ISO 7 CLASSIFICATION
Furthermore, a development unit for physical properties and crystallization of highly actives is available. Milling equipment installed in isolators in a contained building allows us to provide milling and micronization services for OEB 5 compounds.
HIGHLY SKILLED TEAMS
As important as state-of-the-art equipment and facilities, manpower and specialized training are very important key parameter in a company’s ability to safely handle highly active compounds. Working in a contained environment requires a staff well trained in areas of personal protective equipment, operating procedures in industrial hygiene, quality procedures for cleanings, decontamination, adaptation to new equipment and many others that are ruled by operating procedures continuously updated from latest industry trends in technology or trends in quality and hygiene. The total staff for the Sanofi HAP unit is 80, working in one or two shifts.
Sanofi uses the occupational exposure banding system index from 1 to 5 relative to the product toxicity, corresponding to the to the Occupational Exposure Limit (OEL) range:
OEB OEB 1 OEB 2 OEB 3 OEB 4 OEB 5
OEL range (μg/m3) 1 000 - 5 000 100 - 1 000 10 - 100 1 - 10
CEPiA WHITE PAPERS
OUSTANDING FACILITIES
ISO 7 CLASSIFICATION
HIGHLY ACTIVE PHARMACEUTICALS
HIGHLY SKILLED TEAMS
Sanofi is one of the top five pharmaceutical companies in the world and a leader in pharmaceutical sciences. Sanofi excellence in pharmaceutical sciences is based on its experience with industrial development of all kinds of projects and bringing new chemical entities to market. The industrial organization within Sanofi known as Industrial Affairs includes a business unit dedicated to third-party activity named CEPiA (Commercial & External Partnership, Industrial Affairs). One of CEPiA’s missions as a Contract Manufacturing Organization within Sanofi is to provide manufacturing solutions for Active Pharmaceuticals Ingredients (API) to external customers. A key activity is the manufacturing of highly active pharmaceutical ingredients (HAP) and cytotoxic compounds. This activity stems from Sanofi’s expertise gained through the manufacturing of taxanes (Docetaxel, Taxotere® and Cabazitaxel, Jevtana®) and in the development of other drugs for oncology. CEPiA is glad to present to customers its dedicated equipment and facilities for highly active products manufacturing. Customer HAP projects will be managed by the same experts who have developed and launched Taxotere® and Jevtana®. Our high level of expertise has been acquired handling cytotoxic compounds for more than twenty years and is based on five major principles:
• • • • •
Extensive knowledge in Chemistry State of the art facilities Highly trained personnel Environment, Health and Safety experts High standards in Quality
The extensive knowledge in Chemistry is part of an ability to adapt to the requirements of an ever moving pharmaceutical world. Driven by the search of always better compounds with increased potency Sanofi chemists have been forced to adapt their ways of working and develop their processes to achieve successful scale-up and industrial production with respect to product quality and production staff. The handling of highly active products is more complex and limited to a small number of companies. Although there has been a growing number of organizations advertising their HAP handling capabilities, only a few have demonstrated a real ability in this segment of API manufacturing. A reason being is the amount of financial investment to design, operate and maintain highly contained workshops and buildings.
www.cepia-sanofi.com
OEB 5 COMPOUNDS
CEPiA WHITE PAPERS
OUSTANDING FACILITIES
ISO 7 CLASSIFICATION
All companies dealing with commercial HAPs know that an isolator itself is not the definition of a high containment facility. There are multiple parameters that need to be considered in the manufacture of HAPs beyond the isolator. It is risky to rely on a company that would claim capabilities in HAP handling using isolators installed in workshops and which were not designed or upgraded with appropriate air flow and containment measures beyond the isolators.
HIGHLY SKILLED TEAMS
Sanofi’s operating and safety philosophy in the HAP field is based on the concept of highly contained workshops including with the weighing room for starting materials, to the isolators and reactors, to the filtration equipment and the packaging room. For these reasons, CEPiA Sanofi is truly a leader among CMOs for highly actives and cytotoxics.
On the same site located near Paris (France), a kilo lab and two production units are suitable for process development activity, small scale production and large industrial scale manufacturing. All production units are equiped with the latest technologies in isolators, glove boxes, vessels and drying equipment. Suites are fully or partially segregated with restricted access with personnel entrance and exit through airlock systems satisfying the most stringent requirements for products and personnel protection. Production units operate in ISO 7 classification/class 10000 for OEB 4 and OEB 5 compounds and are regularly inspected by Health Authorities (FDA, EMA and PMDA).
www.cepia-sanofi.com
OEB 5 COMPOUNDS
CEPiA WHITE PAPERS
OUSTANDING FACILITIES
ISO 7 CLASSIFICATION
HIGHLY SKILLED TEAMS
A total of almost 40 reactors ranging from 5L to 1000L (glass, glass-lined, stainless steel, and Hastelloy) are dedicated to this activity, as well as multiple filtration options (filters dryers and Nutsch filters) with material compatibility (stainless steel, Hastelloy). Additionally, chromatography equipment with two preparative HPLC columns (Ø 450mm and 200mm) is used for purification of high potent compounds (OEB 5).
www.cepia-sanofi.com
OEB 5 COMPOUNDS
CEPiA WHITE PAPERS
OUSTANDING FACILITIES
ISO 7 CLASSIFICATION
Furthermore, a development unit for physical properties and crystallization of highly actives is available. Milling equipment installed in isolators in a contained building allows us to provide milling and micronization services for OEB 5 compounds.
HIGHLY SKILLED TEAMS
As important as state-of-the-art equipment and facilities, manpower and specialized training are very important key parameter in a company’s ability to safely handle highly active compounds. Working in a contained environment requires a staff well trained in areas of personal protective equipment, operating procedures in industrial hygiene, quality procedures for cleanings, decontamination, adaptation to new equipment and many others that are ruled by operating procedures continuously updated from latest industry trends in technology or trends in quality and hygiene. The total staff for the Sanofi HAP unit is 80, working in one or two shifts.
Sanofi uses the occupational exposure banding system index from 1 to 5 relative to the product toxicity, corresponding to the to the Occupational Exposure Limit (OEL) range:
OEB OEB 1 OEB 2 OEB 3 OEB 4 OEB 5
OEL range (μg/m3) 1 000 - 5 000 100 - 1 000 10 - 100 1 - 10
