Modular Manufacturing Can Ease Bioprocessing Woes

This article was published in Pharmaceutical Technology Europe, Volume 30, Issue 8, August 2018

Modular manufacturing is being increasingly used in the biopharmaceutical industry where flexibility and low-cost manufacturing systems are sought out. The design of a modular system in biopharmaceutical and pharmaceutical processing can involve breaking down a manufacturing facility into smaller functional building blocks, also known as modules (1).

The term modular manufacturing is used throughout the biopharmaceutical industry in reference to modular facilities, modular processing equipment, or modular automation platforms, according to Joe Makowiecki, Enterprise Solution architect at GE Healthcare Life Sciences.

“Any of these can fit the definition in that they involve modules as the basis of design or construction. Modular is particularly attractive for its ability to provide flexibility for diverse and evolving technologies,” Makowiecki says.

In addition, a major trend in the cleanroom industry is a shift toward using modular construction, such as PODs, which are pre-assembled modules that are typically built offsite and then integrated into a facility onsite. PODs provide self-contained and autonomous cleanrooms (2).

Reduction in lead time, increased flexibility, functionality, and ease-of-cleaning are factors driving the cleanroom industry toward modular systems (2).

A critical point to consider when creating a modular manufacturing system is the biomanufacturing process that will be used with the system. To that end, GE Healthcare designed KUBio, a prefabricated, modular manufacturing facility solution based on single-use technologies, to optimize the process flow in biopharmaceutical production. The facility has been standardized to reduce facility-modelling time and offers a consistent setup in any global location.

One of the challenges in the industry today is that the the large and diverse pipeline of biologics does not largely fit the current manufacturing infrastructure, Makowiecki points out. Higher product titers, biosimilars and new personalized therapies are driving batch sizes, cost reduction, and multiproduct manufacture flexibility. 

“KUBio has been created with these drivers in mind, providing flexibility, reduced time to production, defined investment from the beginning of the project and global regulatory compliance,” Makowiecki adds.

Modular construction

POD cleanroom units differ from traditional, fixed cleanrooms in that they offer ease of scalability, are mobile, and can be repurposed once a production process reaches the end of its lifecycle (3). PODs can be applied to many types of biopharmaceutical product manufacturing, including monoclonal antibodies, vaccines, recombinant proteins, personalized medicines, cell therapies, and gene therapies. In addition, the unit can be used for laboratory work (4).

G-CON Manufacturing, a provider of autonomous cleanroom PODs, works with pharmaceutical and biotechnology companies to design POD cleanrooms that fit the specific applications required by these companies. 

Following construction of the initial box structure, G-CON would then install internal wall systems and outfit the unit with ductwork, airhandling systems, automation and controls, doors, windows, flooring, and fire alarm systems, depending on the specified design (4).

Once built and outfitted, the PODs are subjected to a factory acceptance test (FAT) to confirm that predetermined specifications are met. From there, PODs are wrapped and shipped to the onsite location, where they will be interconnected, according to G-CON. The process of constructing PODs differs from the traditional method of constructing cleanrooms because PODS require less crew member and less time to construct (4).

Integrating modular systems

Because modular systems can also be integrated into already existing facilities, it offers a less capitalintensive means to adopt modular manufacturing than having to build a new facility. As an example, GE Healthcare’s FlexFactory, a configurable, integrated, single-use biomanufacturing platform, is designed to fit a new or an existing manufacturing plant. 

“The FlexFactory is a flexible, multiproduct biomanufacturing solution that can incorporate existing, qualified technologies as well as integrate new technologies that improve costs and process efficiencies,” says Makowiecki.

The KUBio facility consists of 50–80 prefabricated modules, each module manufactured and fitted out with building services infrastructure, including heating, ventilation, and air conditioning (HVAC), electrical, and plumbing prior to shipping.

“Parallel production pathways save time; while the modules are being manufactured, the customer site is prepared, and the manufacturing equipment is secured,” according to Makowiecki.

Furthermore, a prefabricated facility like KUBio can be added to an existing site to increase manufacturing capacity or to increase production in a segregated manufacturing environment for sensitive products such as viral vectors that require an enhanced biosafety level of production.

Adding capacity is particular challenging for pharmaceutical facility planners because it involves many strategic engineering and logistical factors. Modular manufacturing is an optimal platform to address these challenges by helping facility engineers maintain timelines and cost certainty while allowing them to adhere to design specifications (5).

Modular pharmaceutical manufacturing helps mitigate the problems in older, traditional biomanufacturing buildings, many of which were designed prior to the most current cGMP regulations. These traditional facilities often have energy-inefficient heating, ventilation, and air conditioning (HVAC) systems that may not be properly isolated from other operations, according to Germfree Laboratories, a provider of custom-built biosafetly equipment.

Modular manufacturing systems offer solutions to problems such as these by providing self-contained, energy-efficient HVAC and air filtration systems. They also give engineers a new range of options and allow engineers to focus on changing product requirements, capacity demands, and new R&D initiatives during the planning and design phase (5).

“We see that there is an increasing need for flexible, multiproduct, prefabricated biomanufacturing solutions for commercial production. Today there are three KUBios and over 50 FlexFactories globally. Most of these facilities are used for clinical production, but there are also commercial sites, and the number is expected to increase in the coming years,” says Makowiecki.

References

1. R. Hernandez, BioPharm International, 28 (5) 18–25 (2015).
2. C. Lipeles and P. Genois, “Modular Cleanroom Facility Trends,” accessed 20 July, 2018.
3. G-CON Manufacturing, “G-CON PODs,” accessed 20 July, 2018.
4. S. Sarkar, “Changing the Face of Biopharmaceutical Cleanroom Infrastructures,” accessed 20 July 2018.
5. Germfree Laboratories, “Modular Pharmaceutical Manufacturing," accessed 20 July, 2018.

Article Details

Pharmaceutical Technology Europe
Vol. 30, No. 8
August 2018
Page: 30–31

Citation

When referring to this article, please cite it as F. Mirasol, “Modular Manufacturing Can Ease Bioprocessing Woes," Pharmaceutical Technology Europe30 (8) 2018.