Inspectors from the World Health Organisation’s (WHO) Prequalification Team revealed a number of deviations from Good Clinical Practice (GCP) and Good Laboratory Practice (GLP) at Quest’s facilities in Chennai, India during a visit last October while it was investigating HIV treatments Lamivudine, Zidovudine and Nevirapine dispersible tablets for drugmaker Micro Labs.
Quest responded in April, but the Agency has, “after due consideration of the critical issues,” now issued the contract research organisation a Notice of Concern (NOC) and recommended that the study in question be rejected.
The NOC cited failures in the data integrity of clinical trial records, including the observation that over two-thirds of electrocardiograms (ECGs) were duplicates of each other.
“Subject details and dates had been changed by the company, in the majority of cases, to make the ECGs appear as if they were from each of the different subjects who had participated in the study.”
In another example, “a number of forms relating to the LAZ/032/13 study were in the process of being completed during the inspection as they had not been filled at the time of the activity. As inspectors entered the bioanalytical laboratory, laboratory staff members were seen in the process of completing records, some of them back-dated.”
Outsourcing-Pharma.com attempted to contact both Quest and the sponsor, Micro Labs (itself a subject of a WHO NOC from May 2014), but neither company responded at the time of going to press.
Regulatory consultant Anders Fuglsang from Fuglsang Pharma, however, expressed his concern at the data integrity issues the WHO inspectorate observed:
“[The WHO’s] inspectors are very experienced and they are among the most competent people I ever worked with,” he told Outsourcing-Pharma.com. “When they raise a concern of this type I believe there is every credible reason to raise an eyebrow and be potentially worried.”
European regulators recommended the suspension of a number of drugs tested at fellow Indian CRO GVK Bio back in January, after concerns about data were raised from its site in Hyderabad. The EMA has recently re-affirmed its recommendation after re-examinating evidence at the request of marketing authority holders.
Following the publication of this article, Outsourcing-Pharma was contacted by Quest Life Sciences with the following statements:
"The audit conducted by WHO in October was a joint audit along with USFDA wherein USFDA had issued 5 483s which were immediately complied with and that particular audit has been closed and an EIR issued last month. Following this we have had yet another USFDA audit in June 2015 where only 1 minor 483 was issued.
"This issue of “Duplicate ECGs” pointed out by WHO was not part of the original audit findings but was a retrospective finding and we did not have an opportunity to defend it on site. We had taken safety of subjects as the primary concern and provided a detailed CAPA which included demonstrating that the subjects involved in the study had no underlying cardiac problem but unfortunately WHO has not accepted it and have issued a notice of concern. This issue was raised regarding a clinical study which was conducted in mid 2013 at our facility. However right from Dec 2013, we have changed the ECG machine to a completely 21 CFR Part 11 compliant machine.
"Though WHO has issued an NOC, the fact that they have indicated that lifting of the NOC would be done on submission of a repeat study shows that as such bioequivalence was indeed established. Based on the necessary action suggested by WHO we are in the process of conducting the entire clinical study again at our own cost to ensure that the NOC is lifted at the earliest.
"Over the past couple of years, we have upgraded our quality and systems tremendously and our global expansion plans are underway. Apart from WHO we have been audited by various other regulatory agencies on a regular basis and this isolated event would not be affecting the warm relationship we share with our customers."