After inspecting cancer drug manufacturing facility of Dr Reddy’s Laboratories (DRL) at Visakhapatnam for ten days last year, the two inspectors of USFDA (United States Food and Drug Administration) wrote in their Establishment Inspection Report (EIR) that employees in multiple departments provided them “false and misleading answers” repeatedly. In its written response to USFDA, the DRL stated that giving “answers that are not logical” is “not appropriate” and there is a “need for improvements in culture of discipline and compliance” in the company.
“Finally, a third action identified was the need for improvements in culture of discipline and compliance….Personnel have been reminded that failure to follow SOPs (standard operating procedures) does not make either CGMP (Current Good Manufacturing Practice) or business sense. Similarly, responding to questions with answers that are not logical or information that cannot be supported by actual facts or data is not appropriate. We regret that the FDA consequently interpreted such actions as ‘providing false and misleading information’,” the DRL stated in its 118-page response to the USFDA’s adverse observations.
While the third action is improvement in culture of compliance, the first and second action identified as “critical priorities” by the company are related to “investigation robustness” and “skill or capability building”.
DRL, one of India’s biggest pharmaceutical firms, earned approximately half of its revenues in 2016-17 from the US market. The Visakhapatnam facility was issued a warning letter by the USFDA in November 2015. Then, in 2017, it was inspected by the two USFDA inspectors from February 27 to March 8. On the last day of their inspection, the inspectors issued a Form 483 that contained 13 adverse observations. In response to these observations, the DRL sent the aforementioned 118-page response to the USFDA.
The US drug regulator issued the EIR to the DRL in November last year but it has not closed the inspection on Duvvada facility as yet. The company is expecting the Duvvada’s re-inspection to happen during 2018 only. In its EIR, the two USFDA inspectors stated: “Over multiple days in multiple departments we were provided false and misleading answers to the questions that we asked employees. We repeatedly expressed our concerns directly to the most responsible personnel present, Vikramkumar B Shukla, vice president of operations, and Manish Kumar Choube, vice president of quality, at the time of these incidents. We also expressed our concerns at the start of the day on numerous days. However, the pattern of providing false and misleading statements persisted throughout the inspection.”
According to a senior USFDA official, the US drug regulator received the company’s response at around March 29, 2017. The Indian Express has reviewed the DRL’s response to the USFDA. Replying to specific questions sent by The Indian Express, the DRL spokesperson stated: “The communication you have referred to between Dr. Reddy’s and the USFDA is not released by us. Our communication with USFDA is privileged and confidential. As the veracity of the information you have is clearly not established, we cannot comment on unauthorised and speculative information. Please refrain from publishing this as our response to the USFDA.”
Deleted files and a ‘fearful’ employee
During inspection, the two inspectors found evidence of deleted files in computers of few employees, who then gave “false and misleading answers” to inspectors on subsequent questioning. For example, a resource production manager working at this facility was found to be having no Word or Excel file in desktop or in networked drives or in Recycle Bin of his computer.
The inspectors then started questioning this employee but he repeatedly said that he did not delete the files on his computer. Later, when Shukla asked the employee to answer honestly, the employee admitted that he had deleted the files saved on his computer, emptied the Recycle Bin, and cleared his ‘Recent’ list. “I asked him why he had done this and why he had provided me different answers. He stated that he was “fearful” due to the inspection,” one of the inspectors wrote in the EIR.
In its written response, the DRL talked about “misleading” answers given by its employees on file deletion. It stated: “The different answers were not to mislead the investigator but were due to lack of understanding of the archival of data to network folder and deletion of data which is redundant. The questions asked by the investigators were not completely understood by the employees in some cases and when explained in vernacular language by the escort, the employee gave the appropriate information.”
The company further explained: “These general computers are used by multiple users with unique user login and pass words (Windows ID and Password) with common share folders to ensure the work management within the team in preparation of documents.” It also talked about its “ombudsman and quality helpline” where the “concerns can be reported fearlessly by employees”. The DRL further stated: “The company assures non-retaliation of any kind on concerns raised in good faith, and taken all reasonable efforts to correct the same. This is being used to build a stronger culture of quality.”
‘Unreliable’ biometric data
During inspection, one of the USFDA inspectors found that one company employee — a supervisor who has to sign the ‘checked by’ section of the form — was signing the forms at “many steps in many different areas over an amount of time that appeared unreasonable”. The inspector reviewed the attendance records and biometric access records that “appeared to demonstrate that the employee was not actually in that particular area at many of the times in which he had signed for in the batch record”.
When confronted, the employee repeatedly told the inspector that he was always present in the area with the operator who performed the task. Later, the inspector found more evidence of him “signing for steps when the biometric access data placed him in different parts of the facility.” The employee then “changed his previous answers and confirmed that sometimes he signed at a later time than what was indicated in the batch record”.
The DRL told the USFDA in its 118-page written response: “We would like to emphasise that the data in the biometric system is not reliable and hence no conclusions can be drawn from these data regarding the presence and absence of operator or supervisor at a specific time and location in the plant as the biometric data was never intended to be used as ‘Entry and Exit log’ to document presence of personnel in the plant.”
The DRL added that though there are several biometric access control points available, “evidence or few of the entries are not available” in the biometric data due to two reasons: first is “tailgating”, which means employees are entering a room behind an employee who unlocks the door with his/her biometric access. The company admitted that tailgating behind someone should never be permitted. Second reason, according to the DRL, is the practice of opening the door from the inside by an employee when he sees that another employee is unable to enter inside due to repeated failure of biometric system to recognise the latter’s fingerprint.