Next-Generation Biotechnology Manufacturing: Genentech Small-Batch Biologics

Summary

I had a discussion with Genentech’s Benedicte Lebreton, VP, head of Technical Development for Biologics US, about the new Genentech Clinical Supply Center for small-batch Biologics flexible manufacturing facility implementing manufacturing concepts, innovations and technologies that are models for future expansion. The Clinical Supply Center has put into practice much of what is been described by the BioPhorum Digital Plant Maturity Model as the highest level next-generation manufacturing―namely, Level 5 Adaptive Plant. Single Use Technologies are a fundamental for achieving the goals of the facility, including flexible manufacturing and environmentally sustainable production.

Genentech, a member of the Roche Group, is the founder of the biotechnology industry and pioneer of the processes and technologies used to commercially manufacture complex biologic medicines. The Clinical Supply Center is part of the Roche Global Manufacturing Network and one of three manufacturing sites in California. Globally, Roche and Genentech produce medicines at 11 sites around the world. In 2021, Genentech delivered more than 55 million vials for patients.

Clinical supply center facility

The facility serves as a new model for the fast, efficient production of therapeutics for smaller patient populations, including personalized and rare disease medicines. The new facility is designed for efficiency and sustainability, achieving globally recognized LEED Gold Certification for healthy, efficient, carbon and cost-saving green buildings.

The 78,520 sq. ft. facility supports digitalization from product definition to production with communications connecting people and equipment with over 19,000 feet of network cabling and equipment with over 1,000 digital connections, approximately one every 75 square feet.

System architecture

The digital manufacturing automation architecture integrates all systems including LIMS (Laboratory Instrument Management Systems), Drug Substance DMS (Discrepancy Management System), EDMS (Electronic Document Management System), EMS (Environment Monitoring System), CMS (Calibration Management System) PLM (Product Lifecycle Management), DCS (Distributed Control System), and BAS (Building Automation System).

Discussion

Benedicte Lebreton described the project as a success with no unexpected operational issues. She noted the project has achieved the design requirements, including:

• Rapid and seamless technology transfer from research to clinical manufacturing by using the Product Lifecycle Management system.
• Standard plug and play utility and data connections for Single Use Technology equipment.
• Integrated paperless digital manufacturing.
• The facility, equipment design and layout enable quick production reconfiguration changes.
• Parameter driven workflows allow the reuse of workflows across unit operations and molecules.
• Closed systems enabling a true ballroom configuration for the process.

A major benefit has been creating a reliable design template for building and operating flexible facilities based on the Genentech team’s learning experience.

Sustainability and efficiency

The facility furthers Genentech’s long-standing commitment with impressive sustainability and energy efficiency results proven in operation:

• 25% reduction in overall energy use
• 100% of electricity from renewable sources
• 28% less water usage compared to other facilities

A major contributor to energy conservation has been the use of less water and steam using single use technologies that do not require Clean In Place (CIP).

Single-use technologies have decreased the time between scientific discovery and clinical manufacturing, enabling delivery of new medicines to clinical trial patients quicker, while using fewer resources. Benedicte Lebreton emphasized, “But rather than disposable, we would say renewable or reusable. Nothing from the facility goes to landfill!.”

Lebreton continued, “We have a collaboration with our local waste management company to bring our solid waste to a nearby facility to incinerate for energy. The waste-to-energy process takes our waste and combusts it to generate steam for electricity generation. This process combined with our reductions in water and energy translate to a 14% lower carbon footprint. We also have several recycling programs in place for other items like gloves, and cardboard, a wash and reuse program for safety glasses, and many upcoming pilots for soft plastics to reduce our solid waste stream, etc.”

“We are very proud of another collaboration with a local hard plastic recycling company where we have established a true circular economy. Our hard plastics are sent to this company and then are converted to items like pipette tips and centrifuge tubes we repurchase for use across our organization.”

One of the Genentech sustainably partners is Polycarbin resource management company, which is dedicated to transforming the single-use scientific supply chain into the sustainable, circular economy of tomorrow. The company takes waste plastic repurposes it for other uses.

Genentech industry commitment

Genentech is a member of the Roche Group and is committed to supporting industry initiatives and organizations including NAMUR and BioPhorum, (also known as BPOG) participating in many "operating groups," which help align the industry on opportunities to improve in spaces that are not proprietary in nature. Genentech and Roche have influenced many of the white papers and outputs from BPOGs and have incorporated best practices from the BPOGs where applicable.

As a side note, Genentech has been an active contributor to the Pharmaceutical Automation Roundtable (PAR) that I have been involved and describe in articles such as: 2019 PAR Insights from the Annual Pharmaceutical Automation Roundtable and Survey.

Thoughts and observations

This is a great example of applying next-generation manufacturing concepts to achieve flexible and environmentally sustainable production.

I asked Benedicte Lebreton what was on her wish list. She said she would like more ideal sensors for single use. This is a new area, and I have talked to several companies working and refining designs for single use sensors. We both agreed that considering the short time single use field has existed, progress has been good.

It is interesting to note that in the 2019 Pharmaceutical Automation Roundtable, the consensus was that the technology wasn’t quite ready to achieve the BioPhorum Digital Plant Maturity Model Level 5 Adaptive Plant, and this Genentech project illustrates tremendous progress since that time to achieve flexible small batch production.