The Impact On Continuous Processing

By Prandeep BorahMSF Pharmacy, GFSU

• 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.

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

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

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

Vision of an Automated Plant

• 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

Process Analytical TechnologyPAT 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.

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.

Continuous processesThe analytical strategy for a continuous process is necessarily predominantly online

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