In a recent warning letter, an Indian pharmaceutical manufacturer was cited for failure to maintain manufacturing equipment. The FDA during the facility inspection identified holes and corrosion in three pieces of equipment used in manufacturing. Previously, FDA received a compliant concerning metal embedded in a tablet from this manufacturer. Although the manufacturer replaced the equipment, they did not perform a retrospective review to determine the potential impact of the poorly maintained equipment on drugs manufactured and distributed prior to replacing the equipment. 21 CFR 211.67 addresses maintenance of the equipment to prevent malfunctions or contamination of the drug product.
Additionally, the firm admitted that they had not performed process validation for the manufacturing of Isoxsuprine hydrochloride tablets. Process validation is a requirement per 21 CFR 211.110a, yet a [redacted] number of batches of this product were shipped to the US that were manufactured using an un-validated manufacturing process. The firms formal response was that they “were not currently manufacturing” this product. Which of course the FDA took exception with as the firm had not provided any information on the validation of the manufacturing process, nor a retrospective risk assessment on the batches that were produced with an un-validated manufacturing process and subsequently released.
Based on the information in the warning letter, the firm apparently did not maintain the equipment properly which lead to metal contamination of the drug product that went undetected.