USFDA issued warning letter to Semler research, Banglore :Fact and Learn

:Photo upload from Semler official website.

In Apr 2016 USFDA declare the inspection for the submitted study in Semler, Banglore.

According to the information , USFDA select the 30 projects for audit to check the data intigrity of the projects.
During facility round one lead inspector found excel sheet on data server of one employees regarding the concentration data of the particular projects.

According to the information the spreadsheet contain concentration data regarding Test and reference product of the submitted projects. That employee even don't know what he save on server and what was the impact.
The spreadsheet contain the subjects number that plasma samples were replaced with already analysed other subjects sample.
Site was not disclose the name of the employee who save the spreadsheet. USFDA verify the subject concentrations data and existing data and found that significant differences in 90% CI value.

Image source: Google image.

USFDA was questioning of all study (NDA, ANDA) related results that were submitted to the USFDA in past.

During this USFDA issued warning letter (Form 483) to the Semler for the sample replacement issue.
However, the agency is requiring that sponsors of approved applications repeat the bioequivalence/bioavailability studies using a company other than Semler.

Dear members, what we learn from the Semler issue?

A. Do not manipulate any data. It's should be define in the quality policy of the company . For Quality system every employee is responsible and have to flow in your blood as well as in act. It should be reflect from your act so no one has to dare to do falsification of the data even your will think before doing like this.
If anybody have forcing you to do manipulate any data then report to the higher authority as well as to mmanagement. They will definitely help you out.

B. "Ethics" is most important things when you are working with CRO.

Because you can't work without considering ethics that whatever I do is the compliance with GxP or not ?
If I am doing any manipulation (you don't have to do) then what will happened if  this manipulation is  found by any regulatory agency and what will ther impact on the organization?
This type of questioning asked to yourself again and again like a self assessment.

If every employee will do work like that then no one have any questioning on your work. Please oblong your work. Management has to awarded if any employee troubleshoot any problem or any employee has report directly to their HOD or management if anyone forcing them to do any corrections in original generated data.

C. Do not save any unwanted files/ folder in the server as well as on desktop. You don't have any personal folder within your circle because company is company and personal work is personal.
Always clean your recycle bin at every interval.

Think over it guy's... Feedback any more suggestions.

Thank you.

Untitled Letter USFDA (Pdf)

USFDA Warn to Semler CRO, India and GVK Bioscience, Hyderabad

USFDA Warn to Semler CRO, India

You guys all known about the recent USFDA inspection at Semeler CRO, Bnaglore plant. The main concern about the data intigrity, that the truthfull ness of the the data. The significant concern was adressed to the Mr. Krathish Bopanna- CEO and president of Semlor. Data intigrity issues are not new for the Indian CRO, Hyderbad based Indian CRO GVK biosciences.  They did the ECG falsification in total 9 projects which were select for the inspection.



The data integrity issue for an India CRO is not the first, with accusations of false electrocardiogram data last year by Hyderabad-based CRO GVK Biosciences leading to a European Medicines Agency suspension of more than 700 drugs tested there. This case hit many of India's leading generic drug makers in a price tag estimated at $1 billion in sales.

Details are here  EMA opens investigation into India’s GVK Bio over ECG falsifications By Zachary Brennan+, 26-Sep-2014.

 GVK BIO has refuted news reports that Germany’s drug regulator had banned the sale of 80 generic medicines due to ‘insufficient’ clinical trials conducted by it. In a statement released by the company, Manni Kantipudi, Chief Executive Officer, GVK BIO stated, “The regulatory authorities have themselves stated, “This decision is taken out of precaution. No element at this stage has led to establish a true risk for human health or a lack of efficacy of these drugs.” continue statement from the Mr.Kantipudi “We believe that the conclusions of the France’s National Security Agency of Medicines and Health Products (ANSM) and the subsequent actions by the EMA are highly disproportionate to the actual risk posed to human health. At the same time, we respect and honour the conclusion made by the European regulators and are working with our clinical development customers to provide new data that meets all regulatory requirements.”

In next statments publish with further deatils  the statement revealed that in May 2014, a regulatory inspector from ANSM visited its clinical development facility at Hyderabad. His inspection focused on nine studies that had ‘check-out’ ECGs. Based on his inspection, he concluded that some of the employees had taken print outs of ECGs from one volunteer and used them for other volunteers. To counter this finding, GVK BIO sought the opinion of four independent cardiologists. The reports from these cardiologists indicated that the ECGs could belong to multiple volunteers and it was difficult to conclude that the ECGs belong to the same volunteer.

Unfortunately EMA’s Committee for Medicinal Products for Human Use (CHMP) concluded that though the ‘check-out’ ECGs may have no direct relevance to the quality of the testing of drugs, they believe that since some of the same employees involved in check-out ECGs could be involved in other critical activities, left an element of doubt on the Bio-equivalence results. Hence authorities have concluded that the BE studies conducted at our Hyderabad clinical development facility since 2008-20014 are not sufficient to support Marketing Authorization Holders (MAHs) for the approved products.

According to the statement, check-out ECGs are ECGs conducted before the volunteers leave the clinic merely as an additional safety test, and they do not form part of any international clinical trial guidelines; the requirement for the ECGs vary depending on the trial protocol followed for each drug. It is intended to ensure that the volunteer is safe on key health parameters and is not a drug efficacy parameter.

As a precautionary measure, the regulators have recommended suspension of marketing authorization of
those products. The ANSM has said on its website: “This decision is taken out of precaution. No element at this stage has led to establish a true risk for human health or a lack of efficacy of these drugs.”
According to the statement, GVK BIO’s clinical development unit has been inspected over 25 times by various regulatory agencies including UK-MHRA, ANSM, USFDA, DCG of India, ANVISA (Brazil), WHO, MOH Turkey, with no reported critical findings.

From these issue, it is clearly mentioning that, for taking any ECG at the time of chek-out was not to fall under any International guideline. ECG is important for the any to predicts any likely or possible relationship with the the Investigational products and also the for the determination of the relationship. 

From these issue, all the CRO has to aware that the each and every step they are done on site at everywhere. So be prepare for the regulatory inspection.

Untitled letter by USFDA (Pdf)

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