This document discusses continuous processing versus traditional batch processing in pharmaceutical manufacturing. Some key advantages of continuous processing include reduced footprint, capital and operational costs, lower raw material and intermediate inventories, and less complex scale-up. However, continuous processing also faces challenges like not being suitable for every process, requiring dedicated equipment and advanced process control approaches. The document emphasizes that process analytical technology (PAT) will play an important role in continuous manufacturing by enabling online measurement and process monitoring to ensure product quality.

1. The Impact On Continuous
Processing
By Prandeep Borah
MSF Pharmacy, GFSU

2. • Batch processing :
FDA’s current definition of a batch as ‘a
specific quantity of a drug or other material that
is intended to have uniform character and quality,
within specified limits, and is produced according
to a single manufacturing order during the same
cycle of manufacture’.
• The production volumes for most drugs are
relatively small; tens of tonnes per annum rather
than thousands of tonnes.
• The control systems associated with such batch
plant tend to be generic rather than specific to
any particular molecule.

3. Disadvantages of Batch Manufacturing:
• Defined batch size (output quantity driven by batch
size)
• Multiple, sequential process steps
• Many interruptions between/during process steps
• Long waiting times between single process steps
• Numerous transport steps between process steps
• Lengthy throughput times from start to finish
• High levels of raw material and intermediate
inventories
• Extensive validation and scale-up activities needed
• Quality measured by in-process sampling and end-
product testing

5. Continuous processing
• It Can lead to significant benefits compared with
batch processing.
– It aims to produce highly efficient reaction and processing
systems through the use of system configurations that
significantly reduce reactor sizes and maximise catalytic
and mass and heat-transfer efficiencies.
• Two important concepts are key to process
intensification.
– the chemistry itself must be telescoped as far as possible,
that is, isolation of intermediates reduced to a minimum.
– the system must be designed for ‘right first time’
processing, allowing redundancy in the plant to be
removed

6. Advantages of Continuous Manufacturing:
• Integration of compliance/quality within the process
• Reduction of systems’ footprint (40-90%)
• Reduction in capital costs (25-60%)
• Reduction of operational costs (25-60%)
• Reduction of raw material and intermediate inventories
• Less complex scale-up
• Reduction of drug substance and drug product
development times
• Reduced time to market

8. Vision of an Automated Plant

10. • Disadvantages/Challenges of CM:
• Not right for every process
• Dedicated equipment and facilities required
• Process technology under-developed
• Advanced & robust PAT and control approaches
required
• Many sensors do not exist (e.g., powder flow
rate, impurities, etc.)
• Single point of failure that can bring down the
whole plant
• Exceptional events management required
• Regulatory framework is under-developed

11. Process Analytical Technology
PAT is a system for designing, analysing
and controlling manufacturing through timely
measurement (i.e. during processing) of
critical quality and performance attributes of
raw and in-process materials and processes,
with the goal of ensuring final product quality.

12. Analytical strategies
• Batch processes:
the role of analysis in the traditional
development of batch processes has been
essentially laboratory based, univariate and
off-line.
– One advantage of laboratory-based analytical data
is that the quality of the results can be checked at
every stage of their production, from validation of
the method, through the use of system suitability
checks to ensure fitness for purpose at the time of
use to final checking and transcription of the data.

14. Continuous processes
The analytical strategy for a continuous process is
necessarily predominantly online

15. THANK YOU