Lies, shredded documents and a trashcan dowsed in acid: Intas Pharmaceuticals’ new write-up from the FDA is a textbook example of what not to do when investigators come knocking. It also offers a stark reminder of the consequences when manufacturers try to pull the wool over the agency’s eyes.
The FDA has flagged a laundry list of production problems at Intas’ plant in Gujarat, India, despite certain employees’ alleged efforts to obscure the truth. The facility earned an 11-observation Form 483 from the regulator following an inspection between Nov. 22 and Dec. 2, 2022.
FDA Forms 483 are handed down when investigators suss out “objectionable conditions” at a facility that could lead to potential manufacturing violations. If a drugmaker in receipt of a Form 483 fails to clean up its act, the regulatory wrist slap could escalate to a Warning Letter.
Aside from seeing through Intas’ smokescreen, the FDA dinged the company for lapses in record-keeping, poorly defined procedures and controls, plus issues pertaining to microbial contamination risk and environmental monitoring, among other problems.
Intas’ write-up begins innocently enough, detailing the sort of incomplete lab records and shoddy procedures common to many FDA citations. The company didn’t accurately count environmental monitoring samples, for one, nor did it have a procedure in place for integration events entered by hand, FDA investigators wrote.
But it was Intas’ quality control unit where the regulator discovered a “cascade of failure” related to lack of oversight on the control and handling of critical production documents.
On the first day of its inspection, the FDA noticed Intas staffers from the company’s quality control lab, as well as its production and engineering department, destroying documents “pertaining to original records and raw data” by “tearing it into pieces.” The employees then chucked the scraps inside Intas’ quality control lab and general parenteral scrap areas, the FDA explained.
The FDA further pointed out in its Form 483 that the areas in question support manufacturing and testing for Intas medicines sold in the U.S.
Intas’ obfuscation didn’t stop there, either.
“Additionally, we found a truck full of transparent plastic bags containing shredded documents and black plastic bags mostly containing documents torn randomly into pieces by hand mixed with other scrap materials,” the FDA continued in its citation.
That same day, FDA investigators turned up more document scraps inside a “large black plastic bag that was hid under the staircase.” Upon opening the bag, the investigators noticed “a very strong smell of chemical spread across the area,” adding that the documents inside the trash bag were wet.
A general manager explained to investigators that another employee had spilled an acid solution on the floor, which was cleaned up using tissue papers that were then discarded along with other waste.
But a quality control officer had a different story to tell investigators, alleging another employee—upon learning investigators were on the way—”immediately rushed and tore apart balance printouts along with Auto Titrator spectrums and threw the torn pieces into the small trash container,” which the employee then doused with an acid solution in a bid to “destroy the evidence of tests” with potentially damning results.
Further problems FDA raised included subpar procedures to prevent microbial contamination of sterile drugs, poorly-monitored aseptic processing areas, as well as lackluster process validation, stability testing, investigations of failures or deviations, and unsecured computers and software.
The FDA’s final observation criticized Intas for dropping the ball on establishing the “accuracy, sensitivity, specificity and reproducibility” of its testing methods.
After an inspectional slowdown spurred by COVID-19 travel restrictions, the FDA has started to dish out inspectional write-ups at a steady clip. Many of those citations have gone to India-based operations like Intas and Lupin, with the latter company recently disclosing some four compliance reprimands from the FDA in just a little over two months—each for a different site in India.
Elsewhere, Catalent’s Belgian manufacturing operations suffered a second Form 483 from the agency in October, after receiving an initial wrist slap there in 2021. In the latest write-up of the prominent CDMO, inspectors highlighted problems with Catalent’s air filters in aseptic areas, plus deficient changes to the HVAC system, and other equipment-related issues.