1. Scope
To generate a guideline document which
¸ Identifies the principles of continuous processing for manufacture of pharmaceutical products
¸ Shows how continuous processing is both consistent with and supportive of the GMP principles set out in the FDA publications regarding GMPs for the 21st Century and PAT
¸ Reviews current regulatory requirements and identifies specific potential regulatory concerns which may need to be resolved by virtue of :
o Explanation or amplification of the intent of the current regulatory requirements.
o New regulatory principles approach specific to continuous processing .
o Recognition of improvements in currently available technology
o Generation of improvements in technology to address current shortfalls
¸ Gives guidelines for the traceability of pharmaceutical products made continuously
The production of pharmaceutical drug products has traditionally used batch based processes and techniques which are essentially scaled up versions of the methods used in the laboratory during the development of the product.
Unlike the chemical and food industry, in-process measurement and control has been limited by both the availability of suitable sensors, but also by a significant lack of understanding of the relationship between the process conditions and/or in-process material characteristics and the quality of the final product.
Control of product quality by virtue of ôprocess validationö is based on repeating processes using conditions which have been previously shown to give a satisfactory result assuming that all other inputs to the process, typically physical properties of input materials, or environmental conditions remain unchanged or do not influence the process.
In general terms, product quality control strategies could be characterised as ôfixed recipesö with no in-process feedback as opposed to closed loop control strategies used in other industries which maintain output product quality by adjusting key process conditions on the basis of in process measurements.
Recent FDA guidance on PAT and Risk based GMPs has highlighted the need for better understanding of process dynamics and the implementation of measurements and closed loop control strategies which actively control key process parameters in order to maintain product quality.
However, implementation of closed loop control strategies is significantly easier in continuous , time invariant , processes, (particularly those with low entrained process mass) where the relationship between process disturbances and corrective control actions is much more visible against the background of normal steady state process conditions, rather than having to be decoupled or extracted from the more complex time variant data produced by the natural progression of a batch ( non steady state ) process.
However, concerns over process stability and on ensuring that any off specification product could be fully isolated (without risk of cross contamination) have previously caused the industry to shy away from continuous processes for production of drug products.
The goal of this guidance document is to identify the potential concerns associated with the transition between batch processing and continuous processing and to assist in the preparation of regulatory submission, which demonstrated that the issues have been addressed in a suitable manner such that the replacement of batch processes with continuous processing actually reduces the risk of off spec., which requires subsequent reprocessing or scrapping.
Keywords
PAT
The title and scope are in draft form and are under development within this ASTM Committee.
Citing ASTM Standards
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