Recent 483 observations make it clear that FDA expects a “Belt and Suspenders” approach when it comes to instrument calibration. It seems that having a stand-alone calibration program is not enough. A firm was cited for failing to establish a system to double-check the calibration records of critical process equipment while being used in the manufacturing process. The specific observation reads as follows:
Specifically, your firm’s production batch records for the OTC drug products …are deficient because they do not include specific clear instructions on how to perform the manufacturing steps, does not provide for the identification of the equipment used, for the verification of the line clearance, for the identification of critical process parameters, for the verification of the calibration status of the instruments used to measure critical process parameters, for the documenting the actual and theoretical yield, and for the documentation of the in-process test results. The batch records also lack complete laboratory records and do not include all labeling.
To avoid this 483, the critical questions that must be incorporated into the batch record are: Does this instrument have a calibration sticker? Is it in calibration? When does the calibration expire?
Knowledge concerning 483 trends is critical for all aspects of a sound quality manufacturing system. A firm could have a solid calibration system and still get in trouble with FDA. While the specific guidance described in 21 CFR 211 Sub Part F “Production and Process Controls” does not specifically reference calibration it could be implied by the all-encompassing language below emphasis added
§ 211.100 Written procedures; deviations.
(a) There shall be written procedures for production and process control designed to assure that the drug products have the identity, strength, quality, and purity they purport or are represented to possess. Such procedures shall include all requirements in this subpart.
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