The engineering team must approach a CM project from
a different perspective. In CM, there are many acceptable
approaches to batch definition, including run time, volume
produced, or active pharmaceutical ingredient (API) lot. It may be
acceptable to simply define batch size by throughput, and not
commit to a specific quantity of product or duration of run time.
The CM operation is characterized by throughput, typically in kg/
hr, which—in many ways—simplifies the capacity analysis. Unit
operations are close-coupled and characterized by a common
line rate of production. WIP inventory between connected unit
operations is eliminated. Weigh/dispense is replaced by loss-in-weight feeders.
The need to analyze capacity and properly consider constraints
will not be completely eliminated. A fundamental difference
between batch and CM is understanding the time to reach
steady-state, where operations are consistent “…over a period of
time where all relevant process parameters and product qualities
are not subject to variation outside of a defined range of values.”
Similar to batch operations, equipment set-up and disassembly,
as well as major and minor cleaning times, must be estimated in
order to conduct meaningful capacity studies.
As the project moves into detailed design, the level of
automation, the plant configuration, and the nature of design
deliverables look very different in a CM project, versus traditional
The following paragraphs elaborate on how engineering
firms may modify their detailed design approach for CM project
execution, and why CM projects require more sophisticated
design tools for proper execution.
The level of automation in batch OSD facilities varies greatly.
Some clients use electronic batch record systems, which
monitor critical parameters from each unit operation through
a higher level Distributed Control System (DCS). Based on the
complexity of the batch record system, unit operations may
require a permissive signal from the DCS to start operations. In
this type of highly-advanced system, each room would have a
local operator station that would interface with the DCS. Also,
all major equipment would have identified I/O interface with
the DCS over a selected communication protocol, i.e. Fieldbus,
ModBus, DH+. However, the equipment itself would still act as
an island of automation. All set points and operational queues
would be initiated from the local equipment control system.
Since a continuous manufacturing train needs to be properly
tuned and the throughput of the close-coupled unit operations
synchronized, the continuous equipment needs to not only
be monitored, but controlled by the higher level automation
system. Each unit operation will still have an independent
control system, but set points and critical parameters will be
input from the DCS and queues to delay, slow down, or pause
will all be generated from the higher level automation system.
In traditional batch operations, materials move between
unit operations in IBCs. In a continuous operation, materials
move via gravity or pneumatic transfer in a closed piping
system between unit operations. In continuous operations,
critical parameters (blend uniformity, moisture content,
particle size) are measured and analyzed in real-time between
unit operations to verify the system is operating within
predefined control limits, i.e., the process is in specification.
These measurements are collected utilizing process analytical
technology (PAT) devices, which are installed in the transition
piping between process equipment. The location of each PAT
component is critical to ensure desired functionality, as well
as accessibility for maintenance and calibration. Also, they
require power and communication wiring back to the DCS,
so determining wire-ways or conduit paths is an important
coordination step in the design process.
It is not uncommon for batch pharmaceutical facilities to
compartmentalize or group unit operations into specific
functional areas, i.e., granulation, blending, and compression.
Furthermore, to facilitate training and scheduling and promote
consistency, many organizations standardize unit operations,
as well as the rooms that house them. For example, a standard
compression module will always include the same make and
model tablet press, deduster, and metal detector. Peripheral
containers, scales, and furniture will be arranged in a standard
configuration in the room. Personnel trained in compression
operations will be familiar with all compression suites in the
facility, and possibly the entire organization. The time required
to add new modules is minimized, because standard designs and
implementation documents already exist.
As these standard modules are configured in the facility the
corresponding technical/mechanical spaces must be added
adjacent to each process room. Technical areas support the
auxiliary mechanical, electrical and plumbing (MEP) services,
including vacuum pumps, air handling units (AHU’s), and dust
collectors, as well as electrical and control panels associated with
the process equipment.
The equipment arrangement in Figure 1 illustrates the use of
standard processing rooms with adjacent technical areas in a
traditional batch OSD facility.
Figure 1: Standard
processing rooms with
areas in a traditional
batch OSD facility.