From flubbing data to performing aseptic processing with torn and stained gowns, Brassica Pharma’s recent warning letter from the FDA reads like a textbook example of what not to do when the U.S. regulator comes knocking at your facility.
After inspecting Brassica’s Tarapur manufacturing plant in Maharashtra, India, from Jan. 15-19, the agency this month handed down a scathing four-observation production write-up—despite Brassica already receiving a wrist-slap in the shape of a Form 483 earlier this year.
Brassica’s manufacturing slights run the gamut from widespread and routine data falsification to substandard environmental monitoring meant to ensure the sterility of drugs, according to the FDA’s July 11 warning letter, which was published Tuesday.
Given the severity of Brassica’s infractions, the FDA has advised the Indian company to enlist a manufacturing consultant. Brassica in February pledged to suspend manufacturing and distribution of all drugs bound for the U.S. market following the FDA’s initial visit, according to the letter.
The warning letter starts off innocently enough, noting that Brassica failed to test every batch of its drug products for sterility.
Things took a turn when the FDA interviewed Brassica’s “sole analyst” trained in the testing procedures, who revealed that it was his “routine practice” to not test all batches and fabricate records for samples not tested.
To make matters worse, during the inspection, the FDA observed four failed sterility tests, including one for a U.S.-bound product.
Brassica also failed to collect samples for environmental and personnel monitoring. Once again, interviews with the company’s microbiology staff revealed that it’s Brassica’s “routine practice to fabricate records and results for samples that were not taken,” the FDA said.
In response to the data falsification observations, Brassica said it would open an investigation and roll out a code of conduct for data integrity. That internal probe failed to include a retrospective review of all data recorded or a review of data recording practices outside of the microbiology laboratory, according to the warning letter, so it failed to meet the FDA’s standards for remediation.
The FDA also chided Brassica for failing to establish proper procedures to prevent microbiological contamination of its sterile drug products.
Agency investigators specifically saw operators “touching the inside of empty sterile tubes,” leaning over the filling line with their heads and torsos, leaning over bulk drug product to manually check product fill level and working with exposed skin in cleanrooms.
Further, the gowning worn by operators during aseptic processing was observed to be “stained and torn,” according to the FDA.
Brassica’s facility itself was subpar as well, with the FDA noting that the company’s aseptic processing equipment design and cleanroom layout were “inadequate.”
Given Brassica’s prior U.S. marketing suspension, the FDA now wants the company to specify in its response to the warning letter whether it plans to resume manufacturing drugs for the U.S. market at its Tarapur facility.
Before the firm can get to that point, however, it must ensure it’s fixed all “deficiencies and systemic flaws” flagged in the FDA’s report to make sure it can meet current good manufacturing practices.
Brassica, which has been in operation for 20 years, makes sterile eye ointments and gels as well as prefilled syringes, dermatologicals and liquid orals, according to its website.