U.S. FDA Finds 'Gap In Data Integrity Program' At Aurobindo Facility
Aurobindo Pharma has been issued a ‘Form 483’ with 10 observations, at the end of the inspection.
The U.S. drug regulator has highlighted the gap in the data integrity programme at Aurobindo Pharma Ltd.'s active pharmaceutical ingredient manufacturing facility in Sangareddy district of Telangana.
The Food and Drug Administration also flagged the company's failure to identify root cause of out-of-specification results, market complaints, and use of materials in manufacturing even after they have crossed the retest date which determines their suitability, among other issues, according to a copy of the observations obtained by BQ Prime's queries.
On Nov. 19, the U.S. drug regulator had flagged 10 quality lapses at the facility. The company, in its exchange filine, had said that the "observations are procedural in nature and not related to data integrity", in its exchange filing.
At the end of the inspection, Aurobindo Pharma was issued a ‘Form 483’ with 10 observations. It is issued when investigators have observed any condition that may constitute a violation of the Federal Food, Drug and Cosmetic Act and related acts.
The unit had been classified as 'official action initiated' on May 17, 2019, the company said in the filing. The U.S. FDA authorities reinspected the facility.
Aurobindo Pharma had said that it will respond to the U.S. FDA within the stipulated timeline and would work closely with the agency to address the observations at the earliest.
The pharma company's shares had declined after the company disclosed the observations in its exchange filing.
Key Highlights From U.S. FDA Observations
Investigations initiated by the quality unit in response to out-of-specification results, laboratory incidents and market complaints relating to testing of intermediates manufactured are deficient and fail to identify root cause of issue. Six instances were noted.
Process validation executed to validate use of reprocessed input material used in manufacturing process is deficient to demonstrate that the manufacturing process can reproducibly manufacture an API intermediate to ensure that quality attributes, such as impurity, are met.
Firm failed to ensure that analytical test methods and cleaning analytical methods are scientifically sound and appropriate to ensure that raw materials and API intermediates conform to established standards of quality and purity. Six instances were noted where testing procedures were deficient.
Four incidents were noted where written procedures (SOPs) for cleaning and maintenance of equipment validation were deficient. The cleaning procedures were not effective or adequate to consistently remove residues of previous product to acceptable levels.
Laboratory control mechanisms were not adequate; especially, while performing chromatographic purity analysis, system precision was not established thus giving no assurance on the accuracy of reported results.
Responsibilities and procedures applicable to the quality control unit are not in writing and fully followed. Supervisory oversight over laboratory electronic systems and data is deficient. Five separate shortfalls in procedures were highlighted.
Storage of key starting materials, raw materials and intermediates are not adequate. Physical location of material storage did not match with the locations mentioned on the white board of the warehouse facility. Four deviations were also noted with respect to lack of adequate control in receiving, storage and issuance of materials.
Materials and intermediates are not always reevaluated as appropriate to determine their suitability for use after an established retest date. Three instances were noted where the materials were missing the retest label or used in manufacturing after crossing the retest date.
Schedules and procedures established for preventive maintenance of equipment were not adequate. Deviations were noted with respect to timely preventive maintenance scheduling and operations.
Computer systems used in testing of drug substance are not of appropriate design to facilitate operations for intended use. No adequate written procedures in place for qualification of laboratory equipment and softwares used. Connectivity errors were noted during audit trials of listed equipment. The firm has not demonstrated to understand different circumstances which may lead to test injection interruptions during chromatography testing operations.
The U.S. FDA said, as part of the observation, that this discrepancy in the "firm's ability to review, document and investigate all electronic data is a gap in your data integrity program".
Aurobindo Pharma has yet to respond to BQ Prime’s emailed queries on the implications of the observations, impact on existing revenue from the facility, steps being taken to address the issues, expected timelines for resolution, whether there are pending approvals from the facility and would they get impacted.
Shares of Aurobindo Pharma were trading 0.27% higher, as of 3:05 p.m., compared with a 0.73% decline in the Sensex.