Process Development and Quality by Design (QbD)

Process development refers to the exercise of creating a means to manufacture a given
product in a given quantity. It involves the selection and sequencing of process steps from a
repertoire of unit operations. Unit operations, the working tools of chemical engineers,
include such steps as mixing, heating, cooling, pumping, size reduction and chemical or
biological reactions.
The task of the R&D process development and of the chemical engineering respectively is
to extrapolate a chemical reaction discovered and researched in the laboratory to an
industrial scale, taking into consideration the economic, safety, and ecological boundary
conditions.
The starting point is the laboratory equipment and the outcome of development is the
production plant in between process development is required.
The development of chemical processes is a complex procedure therefore it does not take
place in a oneway street. Assumptions are made for the individual development stages
which are only confirmed or refuted when the next stage is being worked on. It may be
necessary, therefore to go through the individual stages several times with modified
assumptions, resulting in a cyclic pattern. The first hurdle in establishing a new process is
overcome when a promising synthetic route, usually with associated catalysts is discovered.
Process development (PD) activities should lead to the establishment of what is termed the
“design space,” which represents the multidimensional combination and interaction of input
variables (e.g., material attributes) and process parameters that have been demonstrated to
provide assurance of quality. Regulatory authorities expect process development to be
based on sound scientific methods and principles, in combination with risk management
tools which are applied throughout the development process. The current industry dogma is
that quality, which is generally expressed as identity, concentration, and purity of the
product cannot be tested, but instead should be assured through process understanding
and process control. This dogma is commonly referred to as assuring quality by design
(QbD). In general, process development studies should provide the basis for process
improvement, process validation, continuous verification, and any process control
requirements. The PD program will identify any critical and key process parameters that
should be monitored and controlled; that is, those parameters which could affect the
product critical quality attributes (CQAs) and those that will be key to process performance
from the economical perspective (that is, generally aiming for an optimization of process
yield).
The R&D process development is carried out with following stages,
. Synthetic route scouting or selection
. Products development & identification
. Optimized laboratory synthesis
. Significant changes- from Lab to production scale
. Laboratory scale up (so-called Kilo lab)

. Writing specification of process, process equipment, input materials and analysis
method
. Lab technology transfer to plant scale
. Pilot plant / Engineering batches
. cGMP manufacturing
. Validations
. Commercial production.