The future processes and facilities will be driven by the product, and by economic
Maik W. Jornitz
Chief Operating
Officer
G-CON
Manufacturing LLC
College Station,
Texas
With an increasing diversity of therapies and drug product ranges, facility designs also require diver- sification. Inevitably, the facility designs of the future will not be a legacy of the known, but a utilization of different tools from the toolbox of facility layouts.
The therapeutic drug manufacturing industry has realized that
change is needed; flexibility in clinical material and full-scale
production is necessary to become more efficient and agile.
The topic of flexible facilities has become a hot button issue
and has received attention from industry experts and conference organizers alike. Flexibility, though, is often used in combination with modular, which does not necessarily mean what
the industry expects. This article will review different facility
layouts and flexible design opportunities.
ent options to fully understand whether it meets the requirements or not. Flexibility needs to be defined by the end-user
and only then appropriate choices can be made, including
total cost and purpose.
The need for flexibility
Facility flexibility has become a frequent discussion point
over the last few years1, 2, 3 and the question arises: “Why
the focus on flexibility?” The answer for this demand lies
within a multitude of factors, one certainly being the need to
increase capacity utilization to reduce the cost of goods sold
(COGS). Other reasons are to ramp capacity up and down in
accordance to demand or to utilize the process environment
for patient-by-patient basis treatments. More biopharmaceutical drug product manufacturers are looking into entering specific global regions with smaller production facilities
instead of utilizing a central large-scale site and shipping the
product under cold chain scrutiny to different global regions.
Others want to secure raw material supplies, like excipients
or active ingredients, and therefore build sites instead of
relying on sub-suppliers. Or think about mobile sites, which
could be deployed from location to location, depending on
the demand base. All of these needs would be easier fulfilled
when the facility shows flexibility in purpose, design, deployment, and implementation. Flexibility does not necessarily
mean one looks solely at the cost per cleanroom area, but the
total cost of a facility, time-to-run, repurposing, and product
life cycles. In addition, the typical one drug product classification industry is switching to other drug treatment possibilities and looks into the future – for example, cell therapies. The spread of facility designs is widening to fulfill the
different application requirements. The end-users requested
new choices in facility layouts and vendors developed such
choices, from classical large scale brick and mortar facilities
to small-scale isolator solutions. However, when looking for
flexibility in a facility layout, one should consider the differ-
The multitude of facility designs
Brick and mortar environments are nowadays called “
traditional facilities” and often represent large-scale, one product
facilities. These facilities are dedicated to a single product or
product line, even to the point that the facility has only one
product lifespan. Sometimes it is said that such-and-such
product financed the site,—i.e., the site is commonly built
when the product is close to approval. It can then take up to
four years to have the facility up and running. There are alternative facility architectures available—for example, modular
container and modular stick-built. These facility systems
have the advantage to have a time-to-run of half the time of
a traditional facility. The container solutions are planned and
equipped off-site and assembled at the future facility location.
Once assembled, these production site systems convert very
much into a traditional site. Similarly, modular stick-built
facilities, which are built by framing and wall-paneling a specific area, resemble a traditional production site format. The
stick-built cleanroom area can be erected in an inexpensive
shell space, which allows fast track implementation. For this
Flexibility does not mean one looks solely at the cost
per cleanroom area, but the total cost of a facility,
time-to-run, repurposing, and product life cycles.
approach, the time consuming activity becomes the validation
of the area and the HVAC superstructure. Other, newly introduced cleanroom options are isolator based or autonomous
unit based systems. When one describes flexible cleanroom
designs, these two options are easily scalable with the potential
for multi-product use.
All of these designs have their purpose, benefits, and disadvantages. Most of these designs do not represent a single,
optimal solution, but are utilized in a hybrid mode. In some of
the applications, focus is on containment to protect the environment and personnel. In these instances, a hybrid of isolators
within an autonomous unit or modular environment would be
most suited. In other instances, process stream and space utilization optimization is required, which can be done by segregation
forms and interconnections between the individual spaces. Once
