The Drugs Controller General of India (DCGI) has constituted an Independent Expert Committee on Oncology for examination of reports of serious adverse events (SAEs) of deaths occurred during clinical trials in the country. Dr Arun Agarwal, Professor of ENT, Maulana Azad Medical College, New Delhi is the chairman of the expert committee.
The committee will function under the provisions as specified in Appendix XII of the Schedule Y of the Drugs & Cosmetics Rules.
The chairman of the committee will receive reports of serious adverse events of death from investigators, sponsors or his representatives whosoever had obtained permission from the DCGI for conducting the clinical trial and the ethics committee. The committee will examine the reports of serious adverse events of death, to determine the cause of death and if the cause is due to reasons which are considered as clinical trial related death , then it will give its recommendation to the DCGI.
The committee will examine whether the death has been happened due to adverse effect of investigational products; due to violation of the approved protocol, scientific misconduct or negligence by the sponsor or his representative or the investigator; whether it is due to the failure of investigational product to provide intended therapeutic effect; due to use of placebo in a placebo-controlled trial; due to adverse effects due to concomitant medication excluding standard care, necessitated as part of approved protocol; for injury to a child in-utero because of the participation of parent in clinical trial; and due to any clinical trial procedures involved in the study.
In case of clinical trial related death, the committee will also give recommendation to the DCGI the quantum of compensation to be paid by the sponsor or his representative.
Dr YK Gupta of AIIMS New Delhi; Dr Renuka Kulkarni-Munshi of TN Medical College and BLY Nair Charitable Hospital, Mumbai; Dr Hemant Malhotra of SMS Medical College, Rajasthan; Dr SD Banavali of Tata Memorial Hospital, Mumbai; Dr TN Sagar of Cancer Institute, Adayar, Chennai; Dr Kishore Singh of Maulana Azad Medical College, New Delhi; and Dr S Kataria of Safdarjung Hospital are the other members of the 8-member expert committee.
The apex committee on clinical trials, constituted by the Union health ministry on the directive of the Supreme Court to monitor the clinical trial sector in the country, has cleared a total of 41 new proposals, 26 proposals of global clinical trials and 15 in other areas. These trials were approved by new drug advisory committees (NDACs) and thereafter the technical committee, another high-level panel formed by the ministry on this purpose.
According to senior officials in the ministry, the apex committee in its 14th meeting held on June 17 deliberated in detail on the new proposals and ratified the recommendations made by the technical committee. Earlier, the technical committee in its two meetings had evaluated and recommended for 41 proposals of various categories of clinical trials.
As per the direction of the Supreme Court made in its order April 21, 2014, the proposals of global clinical trials/ clinical trials of NCEs are required to be evaluated with regard to three parameters like the assessment of risk versus benefit to the patients; innovation vis-à-vis existing therapeutic option; and unmet medical need in the country.
Out of the total 41 cases, 26 cases were global clinical trials/ clinical trials of NCEs and the rest 15 cases were related to clinical trials for approval of new drugs including fixed dose combinations, subsequent new drugs and biologicals.
Headed by union health secretary Lov Verma, other members of the apex committee are DHR secretary Dr VM Katoch, DGHS Dr Jagdish Prasad and Arun Panda, joint secretary, health ministry. DCGI Dr GN Singh and the RK Jain, additional secretary, health ministry are the special invitees of the apex committee.
Pfizer (Pregabalin, Lyrica), Bristol-Myer Squibb (Dapagliflocinpro panediol), PSI CRO Pharma India (Eravacycline, TP 434), GSK Pharma (Herpes zoster gE recombinant protein adjuvanted with AS01B adjuvant system), Spectrum Clinical Research (Apitox purified honeybee (Apismellifera) venom), Sanofi Pasteur India (Meningococcal (groups A, C, Y and W-135) polysachharide diphtheria Toxoid conjugate vaccine Menactra), Pfizer (PF-05280014, trastuzumab), Novartis Healthcare (INC424, Ruxolitinib), Cliantha Research (Bevacizumab biosimilar, BEVZ-92) are some of the companies who applied for global clinical trials and got the approval.
Acting on the reports of the Prof Ranjit Roy Chaudhury committee which had recommended to ban all the hazardous and irrational drugs in the pharmaceutical market in the country, the Union health ministry has decided to ban the continued marketing of such drugs in the country which were banned by two or more countries in the world.
“It has been decided that if two or more countries remove a drug from their market on grounds of efficacy and safety, then the continued marketing of the drug in the country will be considered for examination and appropriate action”, the health ministry said.
Earlier in February last year, the ministry had constituted an expert committee under the chairmanship of Prof Ranjit Roy Chaudhury to formulate policy and guidelines for approval of new drugs, clinical trials and banning of drugs. After much deliberations, the committee submitted its recommendations in September, 2013, recommending sweeping changes in all these sectors.
The committee, in its report, noted with concern that in India there are unacceptably large number of formulations in the market at present, somewhere between 60000 and 85000, and many of these medicines should not have been allowed to reach the market in the first place.
Drugs which should never have been allowed to reach the market are being marketed. Many of these drugs are inherently unsafe and potentially hazardous. They do not appear in any textbook of medicine or pharmacology; nor do they find a place in the market of any country which has a well-regulated market for drugs. Such drugs must be removed from the market, the committee had noted in its report.
The committee had further noted that new drugs should be allowed to be marketed in the country only if the experts feel that the drug will have some advantages over the already existing drugs in terms of therapeutic efficacy and safety. Another consideration is whether the drug is being marketed in the country of origin. If not, then questions arise as to why this is so, and this becomes a factor in approving its release in India.
“Again, if the drug is already in the market but two or more countries remove the drug from their market on grounds of efficacy and safety, then the national drug regulatory agency should consider the possibility of removing the drug from the Indian market as well”, the panel recommended.
The Federation of Indian Chamber of Commerce and Industry (FICCI) has asked the Union health ministry to recast the adverse regulations introduced in the year 2013-14 as there is an urgent need to revive the clinical trial sector in the country to address the burden of existing and new diseases.
According to the FICCI, India has witnessed heightened activism and media sensationalism targeting clinical research resulting in a slew of new regulations. While these regulations have been well-intentioned, they have proved to be disastrous for clinical research in the country and the long-term future of pharmaceutical innovation in India. “There is an urgent need to revive the sector to address the burden of existing and new diseases. This would include recasting of adverse regulations introduced in 2013-14”, the FICCI said in its wish-list submitted recently to the new Union health ministry Dr Harsh Vardhan.
It further said that a framework of internal operating procedures should be put in place for the efficient functioning of the regulatory authority in order to maintain a high level of documentation, probity, and transparency. The functioning of the regulatory authority should be subject to regular audits. Summary audit data in appropriate format should also be available in the public domain. The regulatory authority should function at a high measurable standard of customer service with regards to research applicants. This should include time-bound review and disposal of applications. Customer service metrics should be available in the public domain in a timely manner.
Besides, the CDSCO should be strengthened through a comprehensive programme of up-gradation of qualifications, skills and experience of personnel dealing with the review of research applications within the regulatory authority. Several issues pertaining to BA-BE studies, compensation packages, long processing time due for approvals etc. needs to be streamlined for reviving clinical trials in the country.
The FICCI also demanded to the government to create awareness amongst judiciary, media and civil societies in order to enable them to take informed decisions.
Union Ministry of Corporate Affairs has put in place a set of rules to eliminate unfair business practices in the sectors like pharmaceuticals, cosmetics, healthcare, medical and pharmacy education, having a turnover of Rs.25 crore. Stringent audit regime for the purpose is already in place from June 30, 2013. It pertains to the cost records and audit rules, 2014 under section 148 of the Companies Act 2013.
All pharma companies, healthcare providers and colleges of medical and pharmacy in the country will need to adhere to this strict audit procedure. These sectors among other industries including power, defence will need to make their expenses incurred more transparent. Particularly for pharma, audit in costs incurred for manufacture, research, for hospitals on drugs purchased, services offered and colleges will need to disclose details of admissions offered and fees collected.
According to officials from the Karnataka government, the new rules enforced from June 30, 2014, will apply to medical colleges where prospective students are facing the challenge of seeking admission to MBBS and BDS besides post graduation despite their performance. The sector is marked by touts who interface between the candidate and the colleges especially in the medical education. “Such transparency through an audit on cost will keep malpractices at bay,” they added.
In a notification on June 12,2014, via Official Gazette G.S.R. 398(E) sections 173, 175, 177, 178, 179, 184, 185, 186, 187, 188, 189 and section 191 read with section 469 of the Companies Act, 2013 (18 of 2013), the Central Government has introduced the rules to amend the Companies (Meetings and Powers of Board) Rules, 2014. The rules will be referred to as the Companies (Meetings and Powers of Board) Amendment Rules, 2014.
The Companies (Meetings and Powers of Board) Rules, 2014, under rule 6, has included that public companies covered under these norms which were not required to constitute Audit Committee under section 292A of the Companies Act, 1956 (1 of 1956) would now need to form their Audit Committee within one year from the commencement of these rules or appointment of independent directors by them.
Further, the Ministry of Corporate Affairs has also mandated that public companies covered under this rule would need to constitute their nomination and remuneration committee within one year.
Now with the new rules, every company in the pharma sector, healthcare besides medical and pharmacy colleges will need to maintain cost records and which will be scrutinised at any point of time by a team of officials, said the Karnataka government sources.
According to the pharma companies, the stringent audit regime now creates an environment of transparency in operations. Such a move was long overdue and the Indian companies including drug manufacturers would now be forced to operate in a far more professional environment.