Cyanocobalamin

The FDA specifically chided Zydus for failing to suss out the cause of cross contamination incidents—including with glass particulates—as well as poor safeguards against microbial contamination and subpar production and process controls. Last week, Zydus Lifesciences confirmed the receipt of an FDA warning letter at its Waghodia plant in Gujarat, India, marking the latest in a string of production reprimands for the Indian drugmaker.Now, more details about what FDA investigators uncovered have come to light.The warning letter, which was posted to the FDA’s website on Tuesday, outlines three major manufacturing slights turned up during an inspection in April of this year. Zydus received the Warning Letter after previously being slapped with an FDA Form 483, which the company responded to in mid-May.The FDA specifically chided Zydus for failing to suss out the cause of cross-contamination incidents—including with glass particulates—as well as poor safeguards against microbial contamination and subpar production and process controls.On the first observation, FDA inspectors noted that Zydus failed to sufficiently investigate glass particulate contamination in multiple batches of its cyanocobalamin injection, which is used to treat and prevent a lack of vitamin B12.Zydus relied on visual inspections of the drug vials in question and ultimately released batches of the product without identifying the root cause of the issue, “even though there was potential for glass contamination,” the FDA said.To make matters worse, Zydus’ operators that carried out the visual inspections on the cyanocobalamin vials “were not adequately qualified for their ability to identify these defects,” the FDA continued.Zydus informed the FDA that it stopped manufacturing the vitamin deficiency injection in August of 2022, adding that it had not received any complaints about glass found in the product.Still, the FDA viewed Zydus’ response as inadequate, arguing that a “lack of customer complaints alone is neither a verification of a robust quality system nor indication that you have appropriate process controls in place.” Zydus also failed to tie up other cross-contamination concerns beyond the glass snafu, according to the FDA.For instance, Zydus suffered "multiple cross-contamination events” largely tied to products manufactured with shared equipment that wasn’t adequately cleaned, the regulator said. The agency specifically flagged a July 2024 recall tied to cross-contamination at the drugmaker.As for Zydus’ microbial contamination oversights, the FDA dinged the drugmaker for “poor aseptic behavior,” with investigators flagging “multiple instances” of poor aseptic techniques during the start-up and filling of certain injectable drug batches.Given the nature of Zydus’ production shortfalls, the FDA has recommended the company enlist a consultant to help bring its manufacturing standards up to par.Zydus’ warning letter marks the latest writeup in a string of manufacturing wrist-slaps for the company. In early May, the FDA hit Zydus’ site in Gujarat with a Form 483, citing 10 observations around poor production protocols.Three weeks prior to that rebuke, Zydus’ facility in Matoda, India, received a separate Form 483 that yielded four observations, including the company’s failure to clean and maintain equipment. 

Indian generic manufacturer Zydus Lifesciences was hit with an FDA warning letter on Tuesday after it shipped vitamin B injections containing glass particles. An inspection from April 15 to April 23 at Zydus’ facility in Waghodia, a town in Gujarat, India, uncovered three major issues. The FDA inspectors found the company distributed batches of cyanocobalamin injection, used to treat vitamin B deficiency, that could contain glass particles as small as 150 micrometers. Zydus didn’t locate the source of the glass and only used visual inspections to determine if injections were safe or not. In response, Zydus said it had no customer complaints and that it stopped manufacturing the cyanocobalamin injections in August 2022, yet the FDA said this was “inadequate.” The company had to recall batches of the injections this past June. Further, the FDA found issues related to cross-contamination that had been ongoing for three months. Surfaces and equipment weren’t properly cleaned, causing some product contact surfaces to be “stickier” than usual. The company then shipped drug batches that were related to other contaminated batches. Inspectors also saw workers stretching over sterile vials and failing to properly conduct airflow studies to avoid contamination. Finally, the FDA found problems in the company’s process performance qualifications for its manufacturing, stating there weren’t proper written instructions for employees to follow and certain data weren’t collected. The agency has recommended that Zydus hire a third-party consultant and has given the drugmaker 15 days to respond. If the company fails to remedy the manufacturing problems, the FDA could prevent any of Zydus’ products from entering the US. Zydus did not immediately respond to a request for comment.