In March this year, PharmaCompass had shared the observations made by the US Food and Drug Administration (FDA) investigators — Latorie S. Jones and Massoud Motamed — during their inspection of Divi’s Labs Unit II, located in Visakhapatnam (in Andhra Pradesh, India) from November 29 to December 6, 2016.
The inspection resulted in the Divi’s facility being placed on an Import Alert. The FDA had also issued a warning letter to the site. The facility manufactures active pharmaceutical ingredient (APIs).
This month, the agency’s inspectors were back at Divi’s Labs Unit II. Based on the Form 483 issued to Divi’s by inspectors Erika V. Butler and Tsedenia Woldehanna, it is apparent that the compliance turnaround that was being expected by the FDA, has not occurred at the concerned site.
Concerns over Divi’s product quality linger on
During the last inspection, FDA investigators had highlighted concerns over Divi’s product quality — in over 30 batches a “known impurity was integrated as part of a desired peak”. This known impurity was “not considered in the calculation of total impurities”.
In the recent inspection, from September 11 to 19, 2017, investigators uncovered multiple instances where Divi’s had “failed to test individual batches of final API for conformity with all appropriate specification such as purity, strength and identity”.
Lab chemist’s ‘unhygienic hands’ led to product failure!
During their last visit, Jones and Motamed had raised concern over a colored residue commingled with the product. Divi’s could not explain how the cross contamination of the colored residue with the API was overlooked.
During the recent visit, it was found that when the laboratory reported a failing product result, due to contamination by another product manufactured at the site, Divi’s invalidated the result without an adequate investigation.
The Form 483 mentions that the same cross-contamination, which Divi’s investigation concluded had occurred in the laboratory, was found in 17 previous batches.
Divi’s further went on to invalidate the original results and released the batches using the retest results.
In another case where product contamination was found, the investigation concluded that the contamination came from unhygienic hands of an analyst (who hadn’t washed his hands). Even though the analyst stated he performed the activity in a “clean and dedicated location,” he had wiped his hands and “did not observe any product on his hands”.
over equipment cleaning
In the past, Divi’s had received complaints over abnormally colored/stained material along with dark particles in the product supplied by them. During the last inspection, the agency also noted
that equipment deficiencies were observed throughout the inspection.
The recent FDA observations highlight that the firm had failed to ensure its cleaning procedures were “effective for the removal of the build-up of contaminants, degradants and microbes”. The batch cleaning record did not have the detailed step by step instructions on how to clean the equipment.
Data integrity concerns at Divi’s
In the warning letter issued to Divi’s, the FDA had found that the files provided by Divi’s weren’t the original records. In other instances, Divi’s provided the investigators only a subset of the requested records.
The recent inspection mentions two instances where documents were completed while the operation had not been performed.
Butler and Woldehanna also raised concern over several incidents where the “sample injection sequence was completed but results were not calculated and/or compared to specification” in order to ensure failing results were not obtained.
The Form 483 issued to Divi’s highlights that the company needs to do a lot more to convince the FDA that data integrity is a non-issue at its Visakhapatnam site, that its product failure investigations in the laboratory are conducted thoroughly and that contamination in its products is no longer an area of concern.
In short — it’s a long haul for Divi’s, insofar as a compliance turnaround is concerned.