In CM, unit operations are close-coupled and reside in a
common production room. Although this aspect of CM is
favorable because it results in a significant reduction in cGMP
space, it becomes difficult to arrange technical equipment in an
ideal manner, with respect to desired adjacencies and proximities
to associated process equipment. The technical area becomes
a multi-operational space, similar to that of the production
suite, and minimizing pipe and cable runs and ensuring proper
accessibility and maintenance access to all equipment takes on a
new form of challenge.
Figure 2: The CM engineering services scale. The required investment in
engineering services is minimized through the application of standard
equipment platforms and modular construction.
DESIGN TOOLS AND DELIVERABLES
As illustrated by the preceding graph, the scale of engineering
hours of labor and deliverables required to execute a capital
OSD project varies depending on the level of equipment/
automation standardization and the degree to which modular
facility construction is leveraged. If standard equipment/
automation is employed, such as the GEA ConsiGma continuous
platform, then it makes sense to leverage vendor engineering,
including Piping and Instrumentation Diagrams (P&IDs), as well
as automation documentation—thereby minimizing the scope
of process engineering services required from the engineering
firm of record.
In contrast, if it is determined that some combination of
vendor offerings provides a better-suited processing system for
a particular product, then the engineering firm takes on a more
significant process integration role, thereby increasing the scope
of process engineering services required. These deliverables
will most likely include detailed P&IDs, system architecture
and connectivity diagrams, and detailed instrument, valve, and
equipment databases. At a minimum, the engineering firm must
develop sufficient documentation and data to facilitate the
integration of vendor supplied machine controls and PAT devices
with the DCS.
The magnitude of architectural and facilities engineering also
will vary depending on the building construction approach.
Modular construction will require significantly less hours of labor
than traditional stick-built construction.
In contrast to a traditional batch OSD project, the deliverables
of a CM project more closely resemble those required to design
a biotech or API chemical facility, in the sense that there is a
stronger emphasis on automation deliverables and piping details.
The CM equipment is more complex because all equipment
items in a train are connected, and any change or adjustment
to a particular machine in the stack-up will alter the entire train.
The mechanical integration, support details, and provisions for
required access and egress are significantly more challenging
than in traditional batch OSD. In CM, an optimized layout is
essential, given the interconnected nature of the train and need
for perfect synchronization of all machines in the process.
BUILDING INFORMATION MODELING
Leveraging Building Information Modeling (BIM) provides the
engineering firm with the best chance to deliver a successful
CM project. Three-dimensional equipment and piping
models should be developed to optimize the arrangement of
feeders, continuous mixer, mills, PAT, wet or dry granulation,
and compression equipment—all of which will be physically
connected. BIM provides the best opportunity to design support
structures to optimize the performance of highly-sensitive
gravimetric feeders, which are rendered ineffective when
exposed to external vibration or even air movement from a
Engineering firms must embrace their role in the ongoing CM
revolution in the OSD industry by investing in the collaboration,
education, and design tools necessary to ensure viability. The
scarcity of capital project opportunities to-date is indicative
that the rate of market adoption has been slower than
desired, especially from the standpoint of FDA CDER Director
Dr. Woodcock, who is taking every conceivable measure to
accelerate adoption. Engineering firms will get their chance.
When the opportunity arises, it will be incumbent on us to be
fully prepared to deliver the winning CM project.
1. Woodcock, Janet. “Modernizing Pharmaceutical Manufacturing
– Continuous Manufacturing as a Key Enabler” MIT-CMAC
International Symposium on Continuous Manufacturing of
Pharmaceuticals, May 20, 2014.
2. ASTM E2968-14. Standard Guide for Application of Continuous
Processing in the Pharmaceutical Industry, April 2015.