Biotechnology and Pharmaceuticals
The Central government has to come out with appropriate strategy to overcome the trade barriers put up by the Vietnam government against Indian pharmaceutical exports in recent months. The regulatory authorities in Vietnam have been frequently finding fault with the quality of Indian pharmaceutical exports without much justification, according to some leading exporters.
This hostile attitude of the Vietnamese drug regulatory authority is resulting in issuing letters and blacklisting some Indian exporters citing compliance and quality issues. While the industry appreciated the pro activeness of the Indian government in reaching out to Vietnamese counterparts, the industry insisted that the government should take measures in interacting with the stakeholders as well to understand the ground realities.
Nipun Jain, chief executive officer, of Pharmachem stressed that Vietnam being a major export destination is an important market for the industry and thus pre-emptive measures should be taken to address the issue. To safeguard the interest of the Indian exporters, while maintaining a strong relation with the Vietnamese government, Jain who is also in the SME panel of Pharmexcil suggested that India and Vietnam should work together to collaborate on setting up a joint drug testing lab in Vietnam, which would ease up the tension and build the confidence among both the parties.
He also suggested that if not that the Vietnamese government can try to outsource the drug testing to a third party like SGS. If not that they can try adopting pre-shipment testing through a third party as being done for exports to Nigeria, where samples of drugs to be exported to the Nigerian market is tested through a third party testing laboratory in India itself before being exported.
“These are some of the practical solutions that can be adopted to address the issue. These steps will ease the exporters tension and uncertainity while exporting to Vietnam and will also help the Vietnamese authority in addressing their fears on quality issues, without affecting the exports,” Jain pointed out.
A highly placed source from the industry claimed that contrary to the claims made by the Vietnamese government, the fault does not lie with exporters alone, as the regulatory system in the country is equally to be blamed. On condition of anonymity a source revealed that there is a huge lacunae in the drug testing and regulatory system in Vietnam which is the main cause of concern for many. In fact, the source pointed that the testing labs and other facilities are not even updated and latest as per the internationally accepted guidelines.
“The ongoing situation cannot be sorted out without taking into cognizance of the deplorable state of the drug regulatory system in Vietnam, as well rather than playing the blame game they should take some constructive steps towards modernising their drug testing labs. May be then they will find out that the problem is not with the Indian drugs but is with their incapability in properly testing the products,” a source stressed.
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.
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.
Allometry, also called biological scaling, the change in organisms in relation to proportional changes in body size.
An example of allometry can be seen in mammals. Ranging from the mouse to the elephant, as the body gets larger, in general hearts beat more slowly, brains get bigger, bones get proportionally shorter and thinner, and life spans lengthen. Even ecologically flexible characteristics, such as population density and the size of home ranges, scale in a predictive way with body size. The study of allometry stems from work in the late 19th century by the Scottish zoologist D’arcy Thompson and in the early 20th century by the English biologist Julian Huxley, the latter of whom coined the term for this field of study.
The entry of a new chemical entity (NCE) into the clinical phase marks an important milestone in its development phase. Part of the planning of the first in man (FIM) study is the prediction and calculation of the first dose mainly based on the analysis of the available preclinical dataset. Some techniques of allometry are currently in use by the pharmaceutical industry, that they are based on the assumption that new characteristics that influence the NCE exposure in plasma or tissues, which were observed in animals or in vitro systems.
Although the aim of an FIM dose prediction is not to cause any adverse events in the human prabands, the 2006 incident after a single dose of Tergenero TGN1412, a monoclonal antibody, resulted in a serious health damage of the study probands. A direct consequence of this serious incidence was a currently draft guideline by Europeam Medicines Agency (EMEA 2007) entitled “Guideline on requirements for FIM clinical trials for potential high risk medicinal products.
Relationships between organ size and body size in growing animals
log y = α log x + log b
Where x is body size, y is organ size, log b is the intercept of the line on the y-axis and α is the slope of the line, also known as the allometric coefficient. When x and y are body and organ sizes at different developmental stages, the allometric coefficient captures the differential growth ratio between the organ and the body as a whole. When the organ has a higher growth rate than the body as whole, for example, the chela of male fiddler crab, α > 1, which is called positive allometry or hyperallometry. When the organ has a lower growth rate than the body as whole, α < 1, which is called negative allometry or hypoallometry. Organs that have negative allometry include the human head, which grows more slowly than the rest of the body after birth and so is proportionally smaller in adults than in children. When an organ grows at the same rate as the rest of the body, α = 1, a condition called isometry. Such an organ maintains a constant proportionate size (but not absolute size) throughout development.
References: 1. Encyclopedia Britannica, Tobias Pahler. 2. Dose finding in single dose studies by allometry.,Methods in clinical pharmacology ,3. Alexander.W Allometry study of biological scalling, Nature Education knowledge3(10):2.