Streamlined and safeguarded fill and finish ADC production

Not unlike a Trojan horse, antibody drug conjugates (ADCs) are calculating and tactical cancer-fighting drugs and they require complex and highly sophisticated manufacturing facilities to produce them. With NNE’s support to ensure safety and financial security, Roche began the design of its high potent fill and finish facility in 2014.

A true first mover, Roche’s ADC fill and finish facility in Mannheim, Germany is the first of its kind – and it comes with its own unique challenges. A miniscule amount of product contamination can put manufacturers at risk.

Due to the highly toxic nature of the active pharmaceutical ingredients (API) used in ADCs, completely closed processes are required for the fill and finish lines. NNE investigated and designed highly sophisticated isolators throughout the entire process of the facility.

After stopping the initial project for one year for internal reasons, NNE did a 100% ramp-up of the complete project team within four months. This is not typical for an engineering contractor.

Rebeca Julia Lenkersdorf, Project Manager at Roche

“NNE proved a highly valuable project partner for our challenging project” says Rebeca Julia Lenkersdorf, Project Manager at Roche. “After stopping the initial project for one year for internal reasons, NNE did a 100% ramp-up of the complete project team within four months. This is not typical for an engineering contractor, and has shown to Roche that NNE is able to react very flexible according to our requirements.”

Managing contamination and financial risk

The vial isolator filling line for liquid and lyophilised products quickly became the project focal point for the facility. Beyond general containment improvements such as disposable single use systems, bags and fluid paths, NNE helped optimise primary and secondary levels of containment after a thorough health, safety and environment risk analysis.

NNE Global Technology Partner Hartmut Schaz, who worked with the facility, elaborates:

“For the primary containment, either a closed process operation (such as a closed vessel) or a local containment (such as an isolator) was necessary to avoid product contamination in the working area of the operators. In case of a primary containment or operator failure, the secondary containment prevents the spreading of the contamination to adjacent rooms or technical areas.”

Not only did Roche face an increased risk for contamination, but also a financial risk. Antibody drug conjugates are highly specialised drugs and these custom cures are substantial investments. A single vial retails up to EUR 3,000, which means that losing one batch can be more costly than purchasing a new freeze dryer. Therefore, process safety and redundancy where applicable were considered within the equipment design to avoid such incidents in the technically best possible way.

The world's most sophisticated ADC facility

“This is the first ADC manufacturing facility in the world that is this sophisticated,” Schaz says. “It is a true showcase of the most advanced containment and isolation technologies the pharmaceutical production industry has to offer. Facilities such as these will never be a pre-packaged project; at NNE we ensure that everything is custom to fit a customer’s individual demands.”

The complex project is moving along smoothly, and Rebeca Julia Lenkersdorf is pleased with the fruitful collaboration with NNE. “NNE’s competences benefitted us since the beginning of the project and is the cornerstone of our joint success. NNE has both expert knowledge and the necessary "back office" capabilities, which is essential to execute this complex project with such success. We are looking very much forward for future cooperation following the completion of this successful project in 2018.”

 

Quick facts

Customer
Roche

Country
Germany

 

Project duration
Sep. 2013 – May 2018

Facility/site
Mannheim

Services provided
Conceptual design, basic design, detailed design, construction management and
commissioning