The reality is that the depth of information needed to engineer an optimal manufacturing solution is very similar whether
an operation is in batch or continuous mode. Historically though, the industry has not invested in the knowledge gathering
required to optimise production; in part because of the lack of relevant analytical tools and, arguably, because of the regulatory
structure. Once a batch operation was fixed, there was little the operators could do to accommodate variability in incoming
raw material because the scope for process development and/or process optimisation was limited.
So the current vision is a big one that will have major implications for process development. The aim is a transition from
empirical batch to knowledgebased continuous processing; the commercialisation of processes that compensate for upstream variation
rather than simply translating it through to the product, with responsive processing inside the design space rather than fixed
manual operation according to instruction.
How are the pharmaceutical industry's analytical requirements changing as a result of increased emphasis on continuous manufacture?
There are two strands to the changing requirement for analysis. Firstly, the focus on efficient continuous production increases
the demand for analytical instruments that provide process-relevant information. In the powder testing area, for example,
many of the traditional techniques simply cannot meet this need and so newer methods are gaining popularity. Powder rheometry
measures powder under conditions that simulate what the powder observes during manufacturing, quantifying powder properties
that directly correlate with in-process behaviour; for example, performance in a tableting press, mixing efficiency, dispersion
from a dry powder inhaler, rather than simply classifying a powder according to a somewhat arbitrary scale.
Beyond this, there is a need for analytical solutions that meet the new requirements for process monitoring and control—process
analytical technology (PAT). Such solutions add considerable value during process development and at the pilot stage, as well
as in largescale production.
The confluence of current trends in manufacturing has prompted the narrow definition of PAT as being based on real-time, on-
or in-line technologies, but this is debatable. More efficient manufacture relies on pinpointing those parameters that need
to be controlled and identifying the technology that can measure these. This could involve the more sensitive offline analysis
of feeds prior to their introduction into the plant,the intelligent use of soft sensors, at-line systems and, of course, realtime
in-process measurement (2). The key is to focus on the information requirement and then identify the analytical solution that
best meets it.
References
1. H. Evans, Pharm. Technol. Eur.
22 (2), 42–44 (2010).
2. N. C. Chakrabarti, "Virtual sensors for advanced pharmaceutical control,"
http://www.pharmamanufacturing.com/, accessed Oct. 14, 2011.
For a recent article on academic and industry trends in continuous manufacturing, please visit http://PharmTech.com/continuousprogress
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