Nichebusters, a New Model for Drug Development, Drives Use of Modular Biopharmaceutical Facilities

Aging populations, rising obesity levels, and the global effort to reduce the incidence of vaccine-preventable diseases is driving demand for biopharmaceutical drugs, many of which are smaller-volume, niche products for targeted patient populations. The ability to construct smaller-scale, modular biopharmaceutical production facilities with minimal set-up time while still maintaining high quality is enabling the cost-effective production of products that can meet the increased demand on a local level. Olivier Loeillot, general manager of enterprise solutions, GE Healthcare Life Sciences, spoke with Cynthia Challener, editor of the Pharmaceutical Sciences, Manufacturing & Marketplace Report, about modular biofacilities.

Need for local production

Pharmaceutical Sciences, Manufacturing and Marketplace Report: What are the drivers behind the introduction of modular-type biopharmaceutical manufacturing facilities?
Loeillot (GEHealthcare): When commissioning a new facility, biopharmaceutical manufacturers want high quality construction to help ensure a consistently high quality product, anywhere in the world, as rapidly as possible.

Most demand for such an offering comes from either large multinational companies wanting to build or expand “in-country for-country” manufacturing capacity in local markets, or governments looking to build in-country for-country local manufacturing capacity themselves. In either case, the need for additional cost-effective capacity stems from an increasing worldwide demand for biopharmaceuticals that is caused by aging populations, rising obesity levels, and the global effort to reduce the incidence of vaccine-preventable diseases.

At the same time, the age of blockbuster therapeutics has diminished, to be replaced with so-called ‘nichebusters’ that aim to address unmet clinical needs for targeted subsets of the patient population. This change in turn will lead to biopharmaceutical companies taking a new approach to manufacturing, for example, by producing smaller batches and adopting greater flexibility.

Biologics and monoclonal antibodies can be very costly to the healthcare system and to patients, making it more attractive to deploy such a modular facility for biopharmaceuticals.  As part of this approach, the speed and flexibility benefits of single-use components are now well-recognized across the industry, and the next step is harnessing this potential and packaging it for rapid deployment wherever a customer requires.

Minimizing risk and reducing set-up time

Pharmaceutical Sciences, Manufacturing and Marketplace Report: What are the critical components of such a modular manufacturing approach? What are the important factors that will lead to successful construction of a modular facility?

Loeillot (GEHealthcare): Biopharmaceutical manufacturers are looking to minimize financial and operational risks by opting for an approach that delivers shorter set-up times, scalability, quality, and the ability to maximize the use of single-use manufacturing technologies, such as bioreactors, storage and mixing tanks, and chromatography columns.

From a facility perspective, a shorter set-up time can be achieved through simplifying and standardizing the modular components as much as possible. Coupling this facility approach to a single-use manufacturing line reduces design-to-production timelines while enabling quicker validation and increasing the product manufacturing turnaround. Scalability is achieved by having a facility footprint that readily accommodates growth in production capacity as required.

Incorporating single-use technologies is also about flexibility by allowing easy switching of product if required, but also by enabling greater use of continuous processing and other opportunities to improve efficiencies.

Initial focus on monoclonal antibodies

Pharmaceutical Sciences, Manufacturing and Marketplace Report: What specifically does KUBio entail? How does it work?

Loeillot

(GE

Healthcare

)

: GE Healthcare’s KUBio is an off-the-shelf cGMP-compliant facility designed for the production of monoclonal antibodies (mAbs) for the treatment of a wide variety of diseases, such as cancer and rheumatoid arthritis, that can be assembled anywhere.

The complete production facility consists of modules that come fully fabricated for assembly at the required site. KUBio has an approximate footprint of 1200 m² and a total area of 2200 m² split over two levels: the upper level comprises gowning areas and heating, ventilation, and air conditioning (HVAC) installations and the lower area contains process and utilities rooms.

The facility includes a single-use process technology production train that is adaptable to a customer’s specific mAb process with a standard bioreactor setup of 2 x 1000-L bioreactors feeding one harvest and downstream processing line. The bioreactor size, however, can be increased or decreased if required. KUBio also has the option to be supplied with fill and finish capabilities.

We coordinate the entire project and partner with both local and global experts in process development, engineering, and construction. By cutting months off the typical construction time and streamlining the whole execution process, a mAb manufacturing facility at a fixed investment cost can be delivered in a timeframe of 14–18 months.

Pharmaceutical Sciences, Manufacturing and Marketplace Report: What types of facilities can be constructed with KUBio? Is it suited for specific biopharmaceutical manufacturing processes/scales?

Loeillot (GEHealthcare): Our initial modular facility is configured for the manufacture of mAbs and is designed to reach production volumes of over 100 kg/ mAb/year. This level has been chosen to meet most local capacity demands.

Additional solutions to come

Pharmaceutical Sciences, Manufacturing and Marketplace Report: Is GE doing further work on KUBio? What can be expected in the future as far as expanded offerings go?

Loeillot (GEHealthcare): We are in the process of designing off-the-shelf facilities for the manufacture of other biopharmaceuticals. We are also constantly evaluating customer feedback in order to design new solutions for their evolving manufacturing needs.