FDA Form 483: Calibration of Analytical Instruments

Observations made by the inspector during an FDA inspection are listed on the FDA Form 483. The FDA regularly publishes some of these reports under "Frequently requested or proactively posted compliance records" on the FDA homepage.

On 29 November, a new FDA Form 483 that goes back to an inspection from 19 to 27 October 2023 at Dr. Reddy's Laboratories Ltd. in India was published. The 23-page report lists a total of 10 observations.

Analytical Instruments

One of the observations described in the report is related to laboratory instruments, apparatus and recording devices. The FDA investigator writes that "major laboratory equipment including but not limited to HPLCs, GCs, and UV Spectrophotometers that are actively used in commercial release and stability analysis were observed not meeting the calibration specifications." The report describes several examples in detail.

Furthermore, the authority criticizes the firm's SOP on "Management of Laboratory Equipment and Instrument". The FDA Form 483 states that this SOP "requires preventive maintenance be done on the equipment prior to routine calibration. During preventive maintenance (PM), potentially the equipment is opened apart and parts are changed as needed. After PM the equipment calibration is performed. However, by this practice the equipment is potentially altered just before the calibration and a conclusive assessment can not be made if the equipment was performing accurately and precisely during the entire calibration cycle."

Furthermore, "appropriate controls were not exercised over the Laboratory Information Management System (LabWare LIMS) that changes are instituted only by authorized personnel." For example, samples and tests in LIMS were cancelled without adequate controls in place and LIMS samples were created without justification and entries were not reviewed.

Further Observations

The form also lists a number of other deviations, related to the following:

• Major production equipment was not appropriately cleaned and maintained to prevent contamination.
• The responsibilities and procedures were not fully followed. There was a lack of adequate evaluation of equipment conditions upon preventative maintenance, equipment cleaning, and line clearance.
• The determination of conformance to written specifications were deficient for TAMC (Total Aerobic Microbial Count) test and TYMC (Total Yeast and Mold Count) test conducted for purified water and drug products.
• The quality unit failed to investigate deviations and investigations as well as consumer complaints thoroughly.
• The accuracy, sensitivity, specificity and reproducibility of test methods have not been established.
• Core processing areas were not maintained adequately to prevent mix up and or contamination.
• The firm failed to establish and/or follow adequate written gowning procedures pertaining to the core manufacturing areas.