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Technologies and methods for new and refurbished manufacturing facility construction expand capacity for new modalities and to ease shortages.
Drug shortages of common injectable drugs have been blamed partly on lack of manufacturing capacity and on quality problems at aging facilities. And as cell and gene therapies move through the pipeline and into commercialization, there is an urgent need for GMP manufacturing capacity for these products. Pharmaceutical Technology interviewed Maik Jornitz, president and CEO of G-CON, about current trends in facility construction.
PharmTech: In 2017, the Parenteral Drug Association (PDA) published Points to Consider for Aging Facilities (1) to help companies recognize when action is needed to modernize aging facilities. You co-chaired the industry expert team that wrote this technical report. What has taken place since then?
Jornitz (G-CON): A resulting task force from the work on aging facilities is the Post-Approval Change Innovation for Access to Medicine (PAC iAM) Task Force. This group is working on easing the post-approval change scrutiny to allow new technologies to be implemented faster into processes and also to lower the hesitance to bring new technologies and improvements to facilities. This task force is making good progress, and hopefully we will see the outcome of lower post-approval burdens and possible acceptance of the review of one major regulator by the majority of regulators.
PharmTech: How is industry addressing the lack of manufacturing capacity/manufacturing quality as it relates to drug shortages?
Jornitz (G-CON): We see the move away from the traditional design-and-build mode for facilities and processing areas. Vast amounts of time are consumed by lengthy design phases, designing the same facility over again. Furthermore, traditional facility construction is sequential, meaning first the building is constructed, then the utilities and cleanroom infrastructure, followed by the equipment placement. All in all, an onsite sequential construction can take up to three years before product leaves the door. New, offsite-build cleanroom modalities allow the parallel construction of the shell building, utility modules, cleanrooms, and equipment to bring it all together in eight to 12 months. This approach is especially valid when the design phase is abbreviated by utilizing a standardized, turnkey facility solution. An example for this is iCON from IPS and G-CON.
In aseptic fill/finish, we see the need for much faster deliveries of isolator-based fill systems. Right now, the delivery time can range up to one and a half to two years, although there are new isolator/robotic-based standardized fill systems which can be supplied off the shelf. The isolator-based fill line can now be placed and prequalified in a mobile cleanroom unit, which allows more rapid buildup of filling capacity.
PharmTech: For what facility or location types are modular construction or prefabricated cleanrooms best suited?
Jornitz (G-CON): Modular and prefabricated cleanroom infrastructures are replacing the traditional stick-built structures, due to the speed of build and the higher quality of the materials used. Some larger pharma companies have decided to stop using stick-built, as the underlying weaknesses of the wall materials and potential mold contamination represented too high a risk. Moreover, companies investing into new or refurbished facilities require reliable delivery times and cost budgets. The traditional infrastructures could not meet these requirements, and the majority of end-users see time to completion shifts and cost budget drift to painful degrees. The modular and prefabricated cleanroom systems can be used in applications including bioprocessing, vaccines, continuous oral solid dosage processing, fill/ finish, compounding pharmacies, and most certainly the cell and gene therapy segments.
We see a major demand within the cell and gene therapy industry for manufacturing space, as the contract manufacturing organizations do not have the capacity and the wait time for a capacity slot can be two years. Since a lot of these products are now mature and reaching the clinical, if not commercial phase, demand for fast-track-built facilities is rapidly rising. In addition, the cell therapy processing space and facility layout are much different of what we have seen in classical pharma and biopharma. The batch processed within cell therapy is a patient, which means the volumes are so small that the processing space can be a lab size, but the containment has to be extremely robust to avoid any contamination. We believe this facility segment will experience the highest growth.
PharmTech: In what situation might a company choose to refurbish vs. build new?
Jornitz (G-CON): It depends on the application. Large-scale applications will most commonly be a greenfield site, as it is much more difficult to push such large projects into a brownfield system. However, smaller volume, newer therapy applications are utilizing existing mothballed sites; companies gut them, use the existing utilities, and then bring in cleanroom infrastructure. Large shell buildings with some existing infrastructure are ideal for off-site fabricated cleanroom infrastructure, as the time-to-run will be reduced further.
PharmTech: When choosing new construction, what are some of the key factors in designing the facility and choosing the equipment?
Jornitz (G-CON): Again, it depends on the application. If the application is mature, such as monoclonal antibodies, there will not be a lot of surprises in regard to the process and equipment, which determine the layout and footprint of the facility. However, with newer processes, such as viral vector production, new innovations and productivities are needed. These processes are ‘in flux,’ therefore, the cleanroom space around these processes must be flexible and configurable.
Energy efficiency is certainly another topic when one looks at cleanroom space, as the air handling is a major energy consumer. There have been initiatives to reduce the air circulation rate when there are no personnel present in the cleanroom, to change from single-pass to recirculation, or the reclassification of cleanrooms to a lower grade due to functionally closed single-use processes.
1. PDA, Points to Consider for Aging Facilities (July 2017).