14. REJECTION AND RE-USE OF MATERIALS

14. REJECTION AND RE-USE OF MATERIALS
14.1 Rejection
14.10 Intermediates and APIs failing to meet established specifications should be identified as such and quarantined. These intermediates or APIs can be reprocessed or reworked as described below. The final disposition of rejected materials should be recorded.
14.2 Reprocessing
14.20 Introducing an intermediate or API, including one that does not conform to standards or specifications, back into the process and reprocessing by repeating a crystallization step or other appropriate chemical or physical manipulation steps (e.g., distillation, filtration, chromatography, milling) that are part of the established manufacturing process is generally considered acceptable. However, if such reprocessing is used for a majority of batches, such reprocessing should be included as part of the standard manufacturing process.
14.21 Continuation of a process step after an in-process control test has shown that the step is incomplete is considered to be part of the normal process. This is not considered to be reprocessing.
14.22 Introducing unreacted material back into a process and repeating a chemical reaction is considered to be reprocessing unless it is part of the established process. Such reprocessing should be preceded by careful evaluation to ensure that the quality of the intermediate or API is not adversely impacted due to the potential formation of by-products and over-reacted materials.
14.3 Reworking
14.30 Before a decision is taken to rework batches that do not conform to established standards or specifications, an investigation into the reason for non-conformance should be performed.
14.31 Batches that have been reworked should be subjected to appropriate evaluation, testing, stability testing if warranted, and documentation to show that the reworked product is of equivalent quality to that produced by the original process. Concurrent validation is often the appropriate validation approach for rework procedures. This allows a protocol to define the rework procedure, how it will be carried out, and the expected results. If there is only one batch to be reworked, then a report can be written and the batch released once it is found to be acceptable.
14.32 Procedures should provide for comparing the impurity profile of each reworked batch against batches manufactured by the established process. Where routine analytical methods are inadequate to characterize the reworked batch, additional methods should be used.
14.4 Recovery of Materials and Solvents
14.40 Recovery (e.g. from mother liquor or filtrates) of reactants, intermediates, or the API is considered acceptable, provided that approved procedures exist for the recovery and the recovered materials meet specifications suitable for their intended use.
14.41 Solvents can be recovered and reused in the same processes or in different processes, provided that the recovery procedures are controlled and monitored to ensure that solvents meet appropriate standards before reuse or co-mingling with other approved materials.
14.42 Fresh and recovered solvents and reagents can be combined if adequate testing has shown their suitability for all manufacturing processes in which they may be used.
14.43 The use of recovered solvents, mother liquors, and other recovered materials should be adequately documented.
14.5 Returns
14.50 Returned intermediates or APIs should be identified as such and quarantined.
14.51 If the conditions under which returned intermediates or APIs have been stored or shipped before or during their return or the condition of their containers casts doubt on their quality, the returned intermediates or APIs should be reprocessed, reworked, or destroyed, as appropriate.
14.52 Records of returned intermediates or APIs should be maintained. For each return, documentation should include:
− Name and address of the consignee
− Intermediate or API, batch number, and quantity returned
− Reason for return
− Use or disposal of the returned intermediate or API