(1999; 168 pages) [Spanish]
7.2.2 In-process blending/mixing
Some processes require blending or mixing. Such in-process blending is acceptable provided it is adequately documented in batch production records. Examples include:
• Collection of multiple batches or continuous accumulation of batches with defined endpoint in a single holding tank (with a new batch number).
• Recycling material from one batch for further use in a subsequent batch.
• Repeated crystallizations of the same mother liquor for better yield of crystals.
• Collecting several centrifuge loads in a single drier/blender.
Incidental carry-over is another type of in-process mixing that frequently occurs. Examples include:
• Residue adhering to the wall of a micronizer used for milling the finished excipient.
• Residual layer of damp crystals remaining in a centrifuge bowl after discharge of the bulk of the crystals from a prior batch.
• Incomplete discharge of fluids, crystals or particles from a processing vessel upon transfer of the material to the next step in the process.
These residues are usually acceptable since clean-up between successive batches of the same excipient is not normally required during production. However, in the case of non-dedicated production units, complete cleaning procedures designed to prevent contamination that would alter the quality of the substance must be employed when changing from one excipient to another. Checking the effectiveness of these cleaning procedures may require the use of analytical testing for the substances involved.
In contrast to in-process blending and incidental carry-over discussed above, other blending operations should be directed towards achieving homogeneity of the finished excipient batch. Three areas in the processing of finished batches of an excipient which should be examined carefully and critically are:
- the final blending operation to produce the finished batch;
- the point in the process at which the batch number is assigned;
- the sampling procedure used to obtain the sample that is intended to be representative of the batch.
Blending of excipient batches to salvage adulterated material is not an acceptable practice.
Mother liquors containing recoverable amounts of excipients are frequently reused. Secondary recovery procedures for such excipients are acceptable, if the recovered excipient meets its specifications and if recovery procedures are indicated in batch production records. Secondary recovery procedures for reactants and intermediates are acceptable provided that the recovered materials meet suitable specifications.