Corruption and scams are not new in any business but is it ethically right to have corruption in industry like pharma where a drug which if approved incorrectly can impact thousands of lives. A new bribery case against CDSCO officials including Joint DCGI, intermediary agencies and a Biocon official has unsurfaced the wrongdoings in government regulatory offices and pharma industry and because it is related to biotech drug we are covering this story in this cover article. The intensity of wrongdoing by regulators and intermediaries can be felt by the fact that they were not caught red handed by any ordinary police but Central Bureau of Investigation (CBI).
Sudhir choudhary of Zee News had covered the story in his show DNA. This article has taken excerpts of Mr Sudhir as he covered this news very nicely with precise information. At the same time we had contacted Biocon spokesperson who denied the bribery allegations against the company and its officials as well as manywrong claims made in Zee news story.
Let us first see what has been reported by news agencies. The CBI had arrested, Easwar Reddy and Animesh Kumar who are officials of a Drug Authority of the Government of India i.e. Central Drugs Standard Control Organization (CDSCO) along with Dinesh Dua, Guljit Sethi, and associate vice president of Biocon Biologics L. Praveen Kumar on June 21 in a case of alleged bribery to the tune of Rs 9 lakh; Praveen Kumar, an official of Biocon Biologics was arrested later and brought to Delhi from Bangalore. Upon preliminary hearing, a special court had sent all the five accused, to judicial custody at Tihar Prison after they were arrested for alleged bribery of Rs 4 lakh to waive phase-3 clinical trial of ‘Insulin Aspart’ injection of Biocon Biologics to manage Type 1 and Type 2 diabetes. In bail plea lower court has denied application of all five on July 18, 2022. All of them are in Tihar prison.
According to Sudhir Choudhary, the name of the company with which this whole matter is related is Biocon Biologics, a subsidiary of Biocon Limited. This company manufactures medicines and at present its medicines are exported to 120 countries of the world.
CBI has arrested officials of CDSCO. The data related to the new medicines that are made in India is examined by CDSCO. These officers are alleged to get the drugs approved by taking bribe. Employees of the famous Biopharma Company Biocon have also been arrested in this scam. Seeing the advertisements of all the big pharma companies, you buy their medicines with great confidence. The most important thing is that this medicine was for diabetes.
In this case CBI has made total five arrests: Joint Drug Controller S. Eswara Reddy, Dinesh Dua, director at Synergy Network India Private Limited, Guljit Sethi alias Guljit Chaudhary Director, Bioinnovat Research Services Private Limited, Delhi; who used to look after regulatory work for Biocon Biologics, like many other pharma companies, Animesh Kumar, Assistant Drug Inspector (ADI), CDSCO, New Delhi and L. Praveen Kumar, Head-National Regulatory Affairs (NRA), Biocon.The CBI has alleged that the regulatory work of Biocon Biologics was looked after by Guljit Sethi of Bioinnovat Research Services Private Ltd. Bioinnovat and Synergy Network have business dealings hence Mr. Dua agreed to make the bribe payment.
So we have seen that CBI has arrested people in this case and it is not possible for them to make arrest without any concrete proofs. Although Sudhir chaoudhary has covered this public related matter with great details but Biotech spokesperson said that he has misinterpreted some things. A couple of points need to be noted. First is the drug is not substandard or adulterated because it has been already approved in Canada and Europe. Secondly, it is the middlemen that has been caught red handed and not Biocon employee.
Although Biocon has denied the allegations but it cannot be ignored that arrests have been made and government and intermediary officials were caught red handed, but as a responsible media we are presenting story of both sides and will wait for more truth which will come out subsequently. As of now we will see what other things have been interpreted from current case.
Biocon drug is awaiting approval by US FDA
The company says that it has done phase 1 and phase 3 trials in Germany and America respectively. And this is true, but it is equally true that the Drug Regulator Agency (FDA) of America has issued a CRL for this drug. The US FDA has issued a Complete Response Letter (CRL) for the Biologics License Application (BLA) for Insulin Aspart, however it did not identify any outstanding scientific issues with the product. The regulator had asked for some additional information. Biocon has responded to the CRL in April 2022 with the information asked, and its submission is awaiting review by the regulator. It is hoped it will accord approval to Biocon’s BLA soon.
The Ethnicity factor
This company did the first, and third phase trials of this drug not in India but in Germany and America and so the studies related to ethnicity need to be evaluated in Indian population. It is written in the FIR that on the basis of approval in other countries, this company wanted that it should be exempted from the third phase trial in India and this drug should be granted marketing authorization so that this company can sell this medicine in the Indian market.
However, this is in keeping with international best practices. As per the ICH E5 guidance, for Insulin Aspart, there is no evidence through published literature and trial data that there are ethnic or population differences between Caucasians and Indian patients to suspect that the drug may have difference in safety or efficacy. The label and dosing/titration regimen of Aspart is identical in Europe, US, and India, Biocon spokesperson said.
Why a Diabetes drug is lucrative?
There are more than 70 million patients of diabetes in India. At present, after China, India has the highest number of 770 million patients of diabetes. That is, one out of every 6 patients of diabetes in the world is from India. And from this you can understand how serious and important this news is.
The approval procedure
Biocon Biologics said in its statement that “all our product approvals are backed by science and clinical data. Our biosimilar Insulin Aspart has undergone full Global Clinical Trials and is approved by global regulatory agencies like EMA and Health Canada”.
“The rationale for seeking a waiver of Phase 3 clinical trials for Insulin Aspart in India, was based on the Indian regulatory guidance: Similar Biologics Guidelines 2016 & New Drugs and Clinical Trials 2019 (GSR 227 E). These guidelines provide a framework for waiver of Phase 3 clinical trials to be conducted in India based on a commitment to undertake a Phase 4 trial, the design of which should be approved by the Central Licencing Authority.
Similarly, in the document of the meeting, it is written in front of the fourth point that the Subject Expert Committee has decided that it exempts the Biocon company from the third phase trial of its drug in India and after this decision, this company will also sell this medicine in the Indian markets. Apart from this, it is also written in it that this company will have to tell how it will conduct the fourth phase trial. For this, the word “Submit The Protocol” has been used. This is the reason why the word “protocol” replaced the word “data” as without the drug being launched in India, “data” from a Phase 4 trial in India cannot be presented.
This recommendation for approval by SEC without a phase 3 trial in India has been in line with the Indian drug regulations outlined in Similar Biologics Guidelines 2016 & New Drugs and Clinical Trials 2019 (GSR 227 E. Also, there are past instances of similar waiver of phase 3, trials given to other multinational pharma companies, who launched their product with a commitment to do a phase 4 marketing surveillance study.
Now, on the confusion between the use of word data and protocol, Biocon Spokesperson clarified that Phase 4 trials are conducted post marketing, hence it is impossible for any company to submit phase 4 data before the launch of the product. As such, Biocon Biologics needs to submit the protocol of Phase 4 trials before launching the product and later submit the Data generated post marketing study.
Biotech Express would like to clarify here that phase 4 clinical study is a post marketing study, many prior companies have used these provisions and agreed for phase 4 study, in lieu of doing phase 3 study in India.
Earlier Incidences of Pharma Corruptions
In July 2012, Parliamentary standing committee on health and family welfare said there was a “nexus between drug companies and regulatory officials” in clearing new drugs.
It said the Drug Controller General of India (DCGI) approved 31 new drugs between January 2008 and October 2010 despite mandatory clinical trials on patients in India not being conducted. The panel further alleged that medical opinions on the drugs were written by the “invisible hands of manufacturer ..and experts merely signed them” .
One of the examples outlined in its report was that of a drug called Clevudine, made by Pharmasset, a subsidiary of the $8.1 billion Gilead Sciences. The report points out how three experts in Delhi, Gulbarga and Kolkata wrote identical letters of recommendation to market the drug without clinical trials in India.
The legislators also looked at a random sample of 42 medicines from the list of new drugs uploaded by CDSCO on its website, accounting for just 2% of the 2,167 new drugs approved by the Drug Controller General of India (DCGI) during January 2001-November 2010. They found that, of these 42 products, 33 had been approved without clinical trials being conducted on Indian patients from January 2008 to October 2010.
Of the 42 drugs picked up randomly for scrutiny, the Health Ministry was unable to provide the Committee with any documents on three – the fluoroquinolone antibacterials pefloxacin, lomefloxacin and sparfloxacin – on the grounds that their files were non-traceable. All these drugs had been approved on different dates and different years, creating doubt if disappearance was accidental, said the report.
It adds: “strangely, all these cases also happened to be controversial drugs – one was never marketed in the US, Canada, Britain, Australia and other countries with well-developed regulatory systems, while the other two were discontinued later on
Of the 39 drugs on which information was available: – for 11, the mandatory Phase III clinical trials had not been conducted; – for two, clinical trials were conducted on 21 and 46 patients respectively, against the statutory requirement of at least 100 patients; – in one case, trials were conducted at two hospitals, against the legal requirement of three to four sites; and – in the case of four drugs, not only were the mandatory Phase II trials not conducted, but the opinion of experts was not sought – the decision to approve the drugs was taken solely by the non-medical staff of the CDSCO.
There is no scientific evidence to show that the 33 drugs approved without clinical trials are safe and effective in Indian patients, say the legislators, who had questioned the Health Ministry on the matter. Ministry officials had replied that the DCGI has the power to approve drugs without such trials if it is in the public interest. But, said the panel, no explanation was available as to what constitutes public interest.
In August 2019, CBI, arrested Dr. Naresh Sharma, Dy. Drug Controller and another CDSCO official —Drug Inspector, CDSCO, Baddi, Solan— and four executives of an Amritsar or New Delhi-based pharma company in a Rs 1 lakh bribery case.It was alleged that the public servant demanded a bribe of Rs. 1 lakh in lieu of closure of file related to the said private firm and favourable action as the samples of dobutamine injection manufactured/ processed by the said firm were collected by CDSCO for testing and the said samples got failed during testing. The CBI said it “caught” the inspector accepting the bribe and that, later on, the firm’s executives were also arrested.
Where there’s smoke there’s fire. Since the accused have been caught red handed it will be interesting to see whether they will come out clean or not. Even after all if they succeed the public servant will never be able to come back in the organization as we have seen in the case of Dr Naresh Sharma and a bribe will destroy the life of Eswara Reddy as well.
Though the corruption in drug business is not endemic to India only but as a responsible citizen we need to look for more transparency and ethical practices while serving the most reputed sector which saves life of people. The bribery offered by Pharma companies can attract huge business for the company but may put in danger life of people if the drug poses adverse events.
Source: Recommendations of the SEC (Endocrinology & Metabolism) made in its 87thmeeting held on 18.05.2022 at CDSCO (HQ), New Delhi.