FDA warns Centrient over GMP issues at Indian facility

The US Food and Drug Administration (FDA) last recently warned Centrient Pharmaceuticals for current good manufacturing practice (CGMP) violations at its active pharmaceutical ingredient (API) facility in Punjab, India.
 
The warning letter, addressed to Manoj Sharma, country president and director of operations for Centrient Pharmaceuticals India Private Limited, details three GMP violations observed during an inspection in June and July of this year. It also calls on the company to address several data integrity issues and recommends that the firm hire a CGMP consultant.
 
“Because your methods, facilities, or controls for manufacturing, processing, packing, or holding do not conform to CGMP, your API are adulterated,” FDA wrote. The facility was placed on import alert in November 2022.
 
According to FDA, Centrient’s quality unit “failed to ensure adequate document control over paper and electronic records.” The agency noted that its investigators “observed numerous logbooks, forms, and partially completed ‘Sample Request For Analysis (Other Than SAP)’ in an uncontrolled temporary storage room near your microbiology laboratory.” Further, the investigators said the company had a shredder in its document center labeled for “emergency use” that contained shredded documents with information about relative humidity, temperature and other data that the firm’s personnel couldn’t identify.
 
The warning letter also cites the company for inadequate controls over its computerized systems. “Multiple usernames and passwords for software login of several users’ information were handwritten in an uncontrolled notebook of your senior executive microbiologist … to ensure data integrity actions performed need to be attributable to a specific individual,” FDA wrote.
 
Additionally, the agency said the company did not ensure its test procedures for beta-lactam environmental monitoring were validated and followed by staff.

“Contamination of non-beta-lactam drugs with beta-lactam drugs presents great risk to patient safety, including potential anaphylaxis and death. No safe level of penicillin contamination has been determined to be a tolerable risk. Severe allergenic responses can occur in susceptible patients exposed to extremely low levels of penicillin and other beta-lactams,” FDA wrote.
 
While the company told FDA that there was no impact to product quality as a result, the agency pointed out that it used a method intended to detect beta-lactams in buildings where non-beta-lactam drugs are made, and that those methods were not validated or followed. Furthermore, FDA said the company’s “method for detecting penicillin in environmental monitoring of beta-lactams in the non-beta-lactam buildings at your facility is not sufficiently sensitive to detect very low levels of contamination.”
 
Lastly, FDA said the company failed to adequately investigate the cause of “black particles” in two batches of an API. While the company reported that the particles were “non-metallic charred product residue” that dissolved in solution, FDA said the company could not provide its investigator data to support its conclusion.
 
Warning letter