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Questions and Answers on
Current Good Manufacturing Practices, Records and Reports 1. Some products, such as transdermal patches, are made using manufacturing processes with higher in-process material reject rates than for other products and processes. Is this okay? Maybe. It depends on the cause and consistency of the reject rate. Many transdermal patch manufacturing processes produce more waste (i.e., lower yield from theoretical) than other pharmaceutical processes. This should not of itself be a concern. The waste is usually due to the cumulative effect of roll splicing, line start-ups and stoppages, roll-stock changes, and perhaps higher rates of in-process sampling. This is most pronounced for processes involving lamination of rolls of various component layers. Roll-stock defects detected during adhesive coating of the roll, for example, can often only be rejected from the roll after final fabrication/lamination of the entire patch, which contributes to the final process waste stream. We expect that validated and well-controlled processes will achieve fairly consistent waste amounts batch-to-batch. Waste in excess of the normal operating rates may need (see 211.192) to be evaluated to determine cause (e.g., due to increase in sampling or higher than normal component defects... or both) and the consequences on product quality assessed. We've seen a small number of cases where unusually high intra-batch rejects/losses were due to excessive component quality variability and poorly developed processes. References:
Contact for further information:
Brian Hasselbalch, CDER 2. Do the CGMP regulations permit the destruction of an internal quality assurance audit report once the corrective action has been completed? The CGMP regulations (21 CFR 210 and 211) for finished pharmaceutical manufacturing do not specifically address the requirement to conduct, or to keep records of, internal quality assurance audits. If the report in question were from a routine audit to verify that the firm's quality system is operating as intended, then it would be acceptable if the firm elected to discard the report once all corrections have been verified. However, any documentation of corrective action as a result of such an audit would have to be retained (see 211.180 and 211.188). For example, if a routine internal audit finds a problem with a mixing step and the outcome is a change in mixing time, all affected procedures, including the master production record, are to reflect the necessary changes, and such records are subject to FDA inspection as usual. Any investigation into the impact this problem had on related batches is to be retained and also made available for inspection by FDA (see 211.192). In addition, any reports of investigations or evaluations prepared in response to, for example, a product complaint (211.198), vendor qualification (211.84), periodic review of records and data (211.180(e)), and a failure investigation (211.192) are not internal audits as discussed above. Such records are subject to FDA inspection and must be retained for at least the time specified in the CGMP regulations (see 211.180). References:
Contact for further information:
Rosa Motta, CDER Date created: August 4, 2004 |
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