Proven acceptable range

When given the active substance characteristics determined during development acceptance criteria for the validation studies can be established. These criteria will demonstrate the consistency of the dried material processed within a proven acceptable range in the development phase and adequacy of the scale-up to manufacturing. To be comprehensive in this presentation, numerous aspects, although not necessarily applicable to all products, are presented as illustrations in the following sections. 

Table 7 Varied Process Parameters for a Proven Acceptable Range...

Another useful concept is the proven acceptable range (PAR) [4], which includes all values of a given control parameter that fall between established high and low worst-case conditions. 

Consequences of exceeding the Proven Acceptable Range and the action required... 

Table 5 Critical process parameter boundary conditions for a proven acceptable range...

Fig. 4 Lyophilization proven acceptable range lysozyme model preparation.

We typically use two levels—high and low—to conduct initial experiments. This correlates with Chapman s proven acceptable range (PAR) approach (35) Each end of each PAR must be supported by documented evidence otherwise, is not a proven range. However, some authors believe that looking at five to 10 factors each at two levels requires them to study... 

APIs batches are produced by a modified process (e.g., a validated process goes outside the proven acceptable range of a critical operating parameter and the batch is subjected to intensive analytical tests). 

Proven acceptable range (PAR) Upper/lower worst-case conditions outer or control limits/control parameter range characterization, tolerance, or design space range product quality acceptable... 

---