ASTM E2537-08

Application of the approach described within this standard guide applies science-based concepts and principles introduced in the FDA initiative Pharmaceutical cGMPs for the 21st Century.

This guide supports, and is consistent with, elements from ICH Q8 and ICH Q9.

According to FDA Guidance for Industry, PAT, “With real time quality assurance, the desired quality attributes are ensured through continuous assessment during manufacture. Data from production batches can serve to validate the process and reflect the total system design concept, essentially supporting validation with each manufacturing batch.” In other words, the accumulated product and process understanding used to identify the Critical Quality Attributes (CQAs), together with the knowledge that the risk-based monitoring and control strategy will enable control of the CQAs, should provide the confidence needed to show validation with each batch. This is as opposed to a conventional discrete process validation approach.

1.1 This guide describes Continuous Quality Verification (CQV) as an approach to process validation where manufacturing process (or supporting utility system) performance is continuously monitored, evaluated and adjusted (as necessary). It is a science-based approach to verify that a process is capable and will consistently produce product meeting its predetermined critical quality attributes. CQV is similarly described as Continuous Quality Assurance (U.S. FDA) and Continuous Process Verification (ICH Q8).

1.2 Pharmaceutical and biopharmaceutical product manufacturing companies are required to provide assurance that the processes used to manufacture regulated products result in products with the specified critical quality attributes of strength identity and purity associated with the product safety, and efficacy. Process validation is a way in which companies provide that assurance.

1.3 With the knowledge obtained during the product lifecycle, a framework for continuous quality improvement will be established where the following may be possible: (1) risk mitigated, (2) process variability reduced, (3) process capability enhanced, (4) process design space defined or enhanced, and ultimately (5) product quality improved. This can enable a number of benefits that address both compliance and operational goals (for example, real time release, continuous process improvement).

1.4 The principles in this guide may be applied to drug product or active pharmaceutical ingredient/drug substance pharmaceutical and biopharmaceutical batch or continuous manufacturing processes or supporting utility systems (for example, TOC for Purified Water and Water for Injection systems, and so forth).

1.5 The principles in this guide may be applied during the development and manufacturing of a new process or product or for the improvement and/or redesign of an existing process.

1.6 Continuous quality verification may be applied to manufacturing processes that use monitoring systems that provide frequent and objective measurement of process data. These processes may or may not employ in-, on-, or at-line analyzers/controllers that monitor, measure, analyze, and control the process performance. The associated processes may or may not have a design space.

1.7 This guide may be used independently or in conjunction with other proposed E55 standards to be published by ASTM International.