Real Time Release

Real time release is the ability to evaluate and ensure the acceptable quality of in-process and/or final product based on process analytical data. Typically, the PAT component of real time release can include a validated combination of assessed material attributes (in-process and/or product at final process stage), process controls, process end-points, and other critical process parameters. Material attributes can be assessed using direct and/or indirect (e.g., correlated) process analytical methods. The combined process analytical measurements and other test data gathered during the manufacturing process can serve the basis for real time release of the final product and would demonstrate that each batch conforms to established regulatory quality attributes. We consider real time release testing to be an example of alternative analytical procedures for final product release.

Real time release as defined in this guidance builds on parametric release for heat terminally sterilized drug products, a practice in the United States since 1985. In real time release, material attributes are measured and controlled along with process parameters. Real time release as defined in this guidance may fulfill the requirements of parametric release for all dosage forms as defined by other regulatory authorities.

The Agency's approval should be obtained prior to implementing real time release for final products. Process understanding, control strategies, plus on-, in-, or at-line measurement of critical attributes that relate to product quality can provide a scientific risk-based approach to justify how real time quality assurance may be equivalent to, or better than, laboratory-based testing on collected samples. Real time release as defined in this guidance meets the requirements of testing and release for distribution (21 CFR 211.165).

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.