RTRT and continuous manufacturing are examples of initiatives that have been catalytic to better material and process understanding.
Both depend on a thorough understanding of material properties, beyond the tradition specification of particle-size distribution
and tapped density, for example. However, concurrently, the process must be well understood to ensure that the risk of perturbations
can be assessed and that the settings, which have traditionally been fixed by regulation, can be modified to accommodate variation
in incoming materials and still achieve output material that satisfies the quality attributes.
Advances in measurement technologies and a broadening mindset (helped by the process analytical technology and QbD initiatives)
are driving material and process understanding. There are now GMP suites for continuous manufacturing of tablets that rely
heavily on PAT and that function with real-time, closed-loop feedback on parameters, such as size, moisture content, and blend
uniformity.
For this reason, RTRT has become much more of a reality in the past couple of years. However, there are many material properties
that are still not measured routinely at-line or on-line, even though they can influence final product quality. For example,
if particle shape is not being monitored, but particle size is and the shape changes, then the powder will perform differently
in the press, causing the tablet properties (e.g., weight, hardness, dissolution, stability) to be affected. Yet, the process
and quality system may not have accounted for this effect because the material going into the press was conforming to the
inadequate specification of particle size.
RTRT is the future for efficient, safe, and competitive pharmaceutical manufacturing. It relies, however, on capturing more
information about the materials being processed and the equipment and configuration employed during manufacturing. A closer
relationship between formulators, process developers, and plant operators is essential. In addition, the extensive knowledge
that exists in manufacturing, such as which products compress well and which are always capping, can be fed back to development
to provide the design space necessary for optimal manufacturing and high product quality.
Be sure to check out the additional features related to this article on analytics and on industry and regulatory expectations
Tim Freeman is director of operations at Freeman Technology in the United Kingdom.
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