U.S. FDA Flags Procedural Lapses At Lupin’s Nagpur Facility
The company said it will address the observation at the earliest and gain approval for injectable manufacturing for the U.S.
The U.S. drug regulator flagged procedural lapses at Lupin Ltd.’s injectable manufacturing facility in Nagpur, Maharashtra.
“US FDA inspected Lupin’s Nagpur Unit-2 injectable manufacturing facility from Oct. 17 through Oct. 29, 2022," the company said in an Oct. 30 exchange filing. "The inspection was a pre-approval inspection of the injectable facility. The inspection closed with issuance of a Form-483 with five observations.”
A Form 483 is issued when investigators have observed any condition that in their judgment may constitute violation of the Food Drug and Cosmetic Act and Related Acts.
“We are committed to addressing the observations at the earliest, and gaining approval for injectable manufacturing for the U.S.,” the company said.
BQ Prime has obtained a copy of the observations from the FDA.
These are:
Aseptic processing areas are deficient. Interior surfaces where vessels used for filling operations are placed had missing pieces, raised surfaces and deep scratches, stains near stopper assembly and chipped paint on metal footing. Also, disinfectant effectiveness was not conducted.
Procedures designed to prevent microbiological contamination of drug products purporting to be sterile were not established and followed. Personnel were not glove or gown monitored, eye covers were not worn during certain procedures, operator's hands were directly used to open vial covers. Also, monitoring of high-efficiency particulate absorbing or HEPA filters value indicated a zero value that could be an indication of damage.
Procedures designed to prevent microbiological contamination of drug products purporting to be sterile did not include adequate validation of aseptic process. Some batches did not meet temperature and time requirement. There were issues with stoppering functions. Decontamination qualification of vial filling did not include place of biological and chemical indicators.
Aseptic monitoring areas are deficient regarding system for monitoring environmental conditions. No personnel monitoring for gloves and gowns of those who operate in aseptic filling operations and set up for sterile components is not monitored for total particulates. No active air monitoring and anaerobic monitoring of manufacturing environment.
Failure to review unexplained discrepancy or failure of batch or its components to meet specifications whether the batch is distributed or not. Temperature excursions were observed. Impact of temperature excursion on testing parameters for the shelf life duration was not evaluated and proper procedures were not followed when "very high alarm" excursion was noted on monitoring of return loop. Also, there was failure to complete sterility testing for test samples collected from vial filling lines as per procedures.
Lupin has yet to respond to BQ Prime’s emailed queries on the implications of the observations, any impact on existing revenues and the impact on the pending approvals and launch timelines. It’s also yet to comment on the steps being taken to address these issues and the expected timelines for resolution.
Shares of Lupin were trading 0.05% higher as of 1:54 p.m., compared with a 0.26% decline in the Sensex.