US drug regulator issues warning letter to Sun Pharma on CGMP

HQ Team

January 11, 2023: Indian drug major Sun Pharmaceutical’s western Indian facility of Halal has been issued a warning letter by the FDA for not conforming to Current Good Manufacturing Practices (CGMP).

In a letter dated December 15, the US drug regulator stated that it had inspected the facility from April 26 to May 29 last year and found the drug products from the facility were “adulterated.”

The impurity was because the company’s methods, facilities, or controls for manufacturing, processing, packing, or holding do not conform to CGMP, and drug products were adulterated under the section of the Federal Food, Drug, and Cosmetic Act.

“Additionally, your capsules … are adulterated under the FD&C Act … for failure to conform to compendial standards for strength, quality, or purity,” Francis Godwin, the FDA’s director at the Office of Manufacturing Quality, wrote to Sun Pharma’s managing director Dilip Shanghvi.

The CGMP regulations for drugs contain minimum requirements for the methods, facilities, and controls used in manufacturing, processing, and packing a drug product.

Microbiological contamination

During the inspection, Godwin wrote, Sun Pharmaceutical failed to establish and follow appropriate written procedures designed to prevent microbiological contamination of drug products purporting to be sterile, including validation of all aseptic and sterilization processes.

“Your media fills failed to simulate commercial operations accurately,” he wrote in the letter.

A media fill is the performance of an aseptic manufacturing procedure using a sterile microbiological growth medium in place of the drug solution.

It tests whether the aseptic procedures are adequate to prevent contamination during actual drug production.

“Our inspection found the aseptic operations simulated during your media fills were not sufficiently representative of commercial aseptic manufacturing operations for medroxyprogesterone acetate injectable suspension USP, 150 mg/mL, 1 ml prefilled syringes and vials.”

Poor aseptic techniques

Media fill and smoke studies of your manually intensive aseptic (free from contamination) operations, such as dispensing sterile API and adding clean API to the compounding tank, revealed poor aseptic techniques by the company’s operators.

According to the warning letter, the company had a significant media fill failure in November 2021, revealing severe operational flaws and risks. Sun Pharma waited five months to initiate a recall of its drug products affected by the deficiencies.

The ISO 5 cleanroom areas used for aseptic compounding and filling were poorly designed and lacked adequate protection, according to the letter. The FDA asked for a thorough evaluation, independent reviews, and risk management to be in place.

The FDA alleged that Sun Pharma failed to investigate any unexplained discrepancy or failure of a batch or its components to meet any of its specifications, whether or not the batch had already been distributed.

The FDA stated that Sun Pharma had failed to adequately clean and maintain drug product manufacturing equipment to prevent malfunctions or contamination.

The regulator also stated that “significant findings in this letter demonstrate that your firm does not operate an effective quality system in accordance with CGMP.”

“In response to this letter, provide a comprehensive, independent assessment of your overall system for investigating deviations, discrepancies, complaints, out-of-specification results, and failures.”