FDA Warning Letter - Automated System Validation

Date: 03 February 2012
Link FDA 483 (New Window)

Observation

Although this observation does not directly relate to 21CFR211.68 for computerised systems it still has an impact on the validation requirements of an automated system within a tablet manufacturing and packing line.

4. Equipment used in the manufacture, processing, packing or holding of drug products is not of appropriate design to facilitate operations for its intended use. [21 C.F.R. § 211.63) For example,

a. Our review of the equipment qualifications for multiple automated Tablet Testing System (TTS) machines, used to conduct in-process tablet testing (weight, hardness and thickness) revealed that performance qualification was not conducted to ensure the accuracy of the machine at the various available speed settings. A February 2010 investigation of OOS tablet weights for Digoxin tablets revealed that the TTSs were giving incorrect tablet weights for lighter weight ( < 200 mg) tablets when run at the default speed of (b)(4) and concluded it would give accurate results only when run at a speed of (b)(4) However, your firm failed to make a further assessment of the overall reliability of the TTS machines, including evaluating their accuracy with other products and other tablet weights at other speeds.

b. Your firm has not adequately qualified the in-line Pressure Control Device (PCD)-2 Automatic Tablet Weight Control System on the (b)(4) and (b)(4) tablet press machines. Your firm did not Qualifications (PQ) that are representative of all of the products run on the tablet presses to assure proper functioning, including evaluating the reject station timing in relation to tablet press rpm. There is no assurance that the PCD-2 system is accurately rejecting the "marked" OOS tablets throughout the compression run.