Compensation package for clinical trial victims in the offing

India will soon quantify the amount of compensation to be paid by pharmaceutical companies, if a volunteer dies or gets injured during a clinical trial.

On October 10, the Drug Technical Advisory Board (DTAB) gave its nod to the Central Drugs Standard Control Organization (CDSCO) to prepare a "compensation chart" or extensive guidelines that will specify the amount to be paid. Ethical committees of the company will have to decide the quantum of compensation on the basis of these guidelines.

The compensation has to be paid by the trial's sponsor or its representative within 90 days of the death or injury to the victim or the next of h/his kin. In the first 30 days, the firm will have to prove to the ethics panel that the death or injury wasn't due to the drug, else it has to pay.

In India, pharma companies pay compensation "according to their will" that varies between Rs 1 lakh and Rs 10 lakhs since "no set parameters have been laid down". The CDSCO will prepare the compensation guidelines after consulting the Motor Vehicles Act, Railways and the Workers Compensation Act. Union health ministry officials say it will take another three months to notify the guidelines. "When a 70-year-old terminally ill patient dies during a clinical trial, the compensation should be less than that given to a 22-year-old in the first stage of the same ailment. The youngster could be the family's sole bread-winner and would have lived longer had it not for the adverse drug reaction. 

The guidelines will quantify who should get how much compensation," a ministry official told TOI. "Both these patients could get the same amount. However, the pharma company might have decided on an abysmally low package. Once the guidelines are in place, the division of compensation will be fair," he added. 

Families of the 22 clinical trial victims last year were paid around Rs 50 lakh by 10 pharma companies. Compensation ranged from Rs 1.08 lakh to Rs 10 lakh. Most of the families received Rs 1.5 lakh and Rs 2.5 lakh as a one-time package. Initially, the companies had not paid compensation for majority of these deaths. Then, DCGI Dr. Surinder Singh issued an ultimatum to the errant firms: pay up or all other trials would be suspended. 

The companies who paid the compensation included well-known names like Wyeth, Quintiles, Lilly, Amgen, Bayer, Bristol Mayer, Sanofi, PPD and Pfizer. Pharma companies have all along been blamed for not paying compensation to hapless clinical trial victims. The Indian Council of Medical Research recently framed draft guidelines for compensation to participants for research-related injury. Mothers, who because of clinical trials, lose or cause harm to their unborn child may be able to demand compensation from researchers conducting the trials. Compensation has to be paid, irrespective of whether injury was foreseeable/predictable, and that the research participant had freely consented in writing about participating in it.

Compensation will have to be provided to the research participants when temporary or permanent injury occurs due to participation in the clinical study. Compensation also has to be paid when the injury is caused by a procedure that has been undertaken to manage an adverse reaction occurring during the research. 

Defining "compensation", the draft says it could be in form of payment for immediate medical/surgical management of research-related injuries, compensation for research-related injuries leading to temporary or permanent disabilities or compensation to legal heir/lawful guardian in case of death. "The payment will be the responsibility of the investigator/institution," it says. Besides, the Informed Consent Document (ICD) will have to state that the research participant has the right to claim compensation in case of research-related injuries and whom to contact for it.

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Unauthorized Clinical Trials on Bhopal Victims

Ajay Shrivastav from Bhopal, the central Indian city that witnessed one of the worst industrial disasters of the world in 1984 from a deadly gas leak, is an angry man seeking justice.

A year ago, Ajay learnt that his father Ramadhar Shrivastav, a victim of the toxic gas that had engulfed Bhopal in 1984, has been subjected to clinical trials in a hospital that was meant to treat the gas victims.

"We were shocked. We are planning to move legally now against such unauthorised clinical trial," Ajay Shrivastav told IPS.

A Bhopal court last year sentenced eight former top officials of the Indian subsidiary of Union Carbide Corp (UCC) to two years imprisonment each for the 1984 gas leak that eventually killed about 20,000 and left many more incapacitated.

Several of the victims were under prolonged treatment, and some of them fell prey to unauthorised clinical trials without their knowledge.

Ramadhar Shrivastav was part of the Astra Zeneca (a global biopharmaceutical company) trial. He is too sick to speak to anyone.

"At this site in India (Bhopal), some patients were not properly consented," a spokesperson of the company told IPS, admitting that clinical trials indeed took place without patients' consent.

"These errors were discovered by AstraZeneca through monitoring processes we employ for all of our clinical studies and promptly corrected by the investigator," the spokesperson said.

"Good clinical practice requires investigators to obtain study patients' informed consent," the company said.

Earlier, Indian health activists in Bhopal gathered proof that the Bhopal Memorial Hospital and Research Centre (BMHRC), which was built with funds from Union Carbide shares confiscated as part of the criminal case on the gas leak, carried out clinical trials on gas victims without their knowledge.

Official documents show that hospital director K. K. Maudar has admitted to the Drugs Controller General of India (DCGI) that there were drug trials. The official documents show that 80 percent of those subjected to clinical trials were victims of the 1984 disaster.

"We have documents showing the details of deaths in the three trials - Fondaparinux (cardiology) and Tigicycline (gastro surgery) and Televancin trial (anaesthesiology) - that took place at BMHRC," Rachna Dhingra of the Bhopal Group for Information and Action told IPS.

"It clearly mentions that almost all people who died were gas victims."

According to the DCGI, six trials were carried out at the BMHRC while the activists say there were more such trials.

"We believe that as many as 10 drug trials were carried out by BMHRC. In their own account statement which was submitted to DCGI they clearly show that they received money for 10 different trials," says Dhingra.

The trials were conducted on 215 gas victims, according to the figures mentioned in the letter of the hospital  director to the deputy drug controller of India, Dr R. Ramakrishna, on Feb. 22 this year. The letter also gives a breakdown of the drug trials.

Dr Chandra Gulhati, editor of the New Delhi-based Monthly Index of Medical Specialties, said the BMHRC was set up in 2000 to provide super-specialty care to survivors of the tragedy and carry out research on long-term effects of the methyl-isocyanate (MIC) chemical that caused the deaths.

"But instead of concentrating on MIC-related issues, the hospital became a hot spot for conducting clinical trials on untested drugs that were primarily designed to help pharma companies," he said.

According to a World Health Organisation (WHO) bulletin report in 2008 titled 'Clinical trials in India: ethical  concerns', transnational drug companies are moving their clinical trials business to India, giving a new urgency to clinical trials registry reform.

India's powerful industry association Associated
Chambers of Commerce and Industry (ASSOCHAM) says the country is set to grab clinical trials business valued at approximately 1 billion dollars by the end of 2010, up from 200 million dollars the previous year, making the subcontinent one of the world's preferred destinations for clinical trials.

FairDrugs.org, a campaign by a worldwide coalition of health organisations and scientists led by Wemos Foundation in the Netherlands, says people living in countries like India run a high risk from pharmaceutical companies testing drugs on them unethically for the Western market.

An Indian research report published in 2009 shows several pharmaceutical companies' disregard for ethical rules.

"The Indian Centre for Studies in Ethics and Rights has examined, among other things, the way GlaxoSmithKline tested a breast cancer drug on seriously ill women in India," said Annelies den Boer of the Dutch Wemos Foundation, co-commissioner of the study with the Centre for Research on Multinational Corporations (SOMO).

Sandhya Srinivasan, a researcher who along with Sachin Nikarge documented the report for the Centre for Studies in Ethics and Rights, Mumbai, said it was found that "these trials exploited the fact that most Indians do not have access to good quality and affordable care and therefore may accept offers that might provide better quality and free treatment."

Gulhati says the clinical registration process in India should be more stringent.

"The Drugs Controller General of India should make it obligatory for all trials to be registered on the Clinical Trials Registry site before permission is granted to conduct them."

He said failure to do so should carry a penalty. "In addition, while registering trials, the composition of hospital ethics committees, which approved the trial, should be disclosed. Fewer than 40 ethics committees in India are properly constituted and functioning, which means that the safety of the subjects of clinical trials is on the  back burner."

An increasing number of hospitals are now owned by drug companies, he said. "Clinical trials at such hospitals should carry a statement of disclosure about the relationship."

According to den Boer of Wemos, "time after time we see that patients in developing countries are used to test drugs that are primarily intended for the European market. Contrary to the ethical guidelines, these patients do not benefit from the research results."

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Health Min constitutes 12 new drug advisory committees to help DCGI on new drugs, clinical trial applications

The Union health ministry has formed 12 New Drug Advisory Committees (NDAC), comprising experts in the respective fields, to advise the Drugs Controller General of India (DCGI) in matters for review of applications of new drugs and clinical trials.

Each of the panels set up to advise in matters related to review and regulatory approval of clinical trials and new drugs, except for Investigational New Drugs (INDs), relating to different therapeutic areas, has ten members. The panels were formed on reproductive and urology, cardiovascular and renal, ophthalmology, vaccines, dermatology and allergy, anaesthetics and rheumatology, neurology and psychiatry, pulmonary, oncology and haematology, gastroenterology and hepatology, metabolism and endocrinology, and antimicrobial-antiparasitic-antifungal-antiviral areas.

“The committee will advise DCGI in matters to undertake in-depth evaluation of non-clinical data including pharmacological toxicological data, clinical trial data (phase I, II, III, and IV) furnished by the applicant for approval of new drug substances of chemical and biological origin to be introduced first time in the country including vaccines and r-DNA derived products,” according to an official note by the health ministry.

The panels will also evaluate data being submitted by the applicants on global clinical trials, fixed dose combinations of two or more drugs to be introduced for the first time in the country. It will help preparing guidelines for clinical research industry in evolving acceptance criteria for marketing approval of new drugs of different therapeutic categories. The panel will also define roadmap for research industry for appropriate development of new drugs relevant to Indian population.

“While considering cases of new drugs, the committee will examine essentiality and desirability of new drugs in terms of assessment of risk versus benefit to the patient, innovation vis-à-vis existing therapeutic option and unmet medical need in India,” the note said.

Application for new drugs and global clinical trials will be evaluated by the committee either through meetings or by circulation of the applications. The term of the committees is for three years. Office of the DCGI will initially examine the applications and if any data is lacking the same will be informed to the applicant within 45 working days or else the data will be forwarded to the members of the committee in the respective areas.

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Pharma companies must compensate victims of clinical trial errors

Drug companies looking to test their experimental drugs on Indians will not find human lives cheap any more. According to an amendment to the relevant law being planned by the health ministry, the onus of proving that clinical trials did not cause death or injury will now lie with the drug company concerned. Further, in case of death or injury from such trials, the company will have an explicit legal obligation to financially compensate the victims. Currently, India has no clear, enforceable law that mandates a drug company to provide financial compensation to the affected party or his or her dependents in case of injury or death during clinical trials. Neither the Indian Council of Medical Research’s Ethical Guidelines for Biomedical Research nor the Good Clinical Practices guidelines that deal with the subject have the status of law. These guidelines spell out the obligation of the trial sponsor in case the participant incurs physical or psychological injury, but do not delve into how to deal with complications that might arise in such cases.

According to sources, the health ministry is set to mandate payment of compensation to volunteers participating in clinical trials in case of a trial-related death or injury by amending the Drugs and Cosmetics Rules.

“Under the proposed rule, it would be the responsibility of the trial sponsor on behalf of the pharma company to prove before the ethics committee that the injury or death is not on account of clinical trial within 30 days of receiving the report of the injury or death from investigator, failing which the sponsor shall be liable to pay the compensation within 60 days or as decided by the ethics committee,” a health ministry official said. The amount of compensation will be decided on a case-to-case basis by the ethics committee.

The Drug Controller General of India’s (DCGI) office has already proposed the policy changes to make drug companies and other agencies accountable in conducting clinical trials. Further, the Drug Technical Advisory Board (DTAB), the highest decision-making body on such matters, has also endorsed the proposal to make companies liable to duly compensate people suffering from trial related injuries. The DTAB, however, added that DCGI should also consider the feasibility of setting up a tribunal comprising physicians, retired judges and civil society members to decide on disputes and fix the minimum compensation. Also, the time-frame for claiming compensation could also be determined, the board suggested. The health ministry move follows an investigation earlier this year by the ministry which found that most firms undertaking clinical trials had not paid compensation to the relatives of the persons who died during the trials. Of the 671 reported deaths during clinical trials in 2010, compensation was paid only in three cases. Subsequently, the ministry sent show cause notices to over 40 drug firms including Pfizer, Bayer, Novartis and Eli Lilly seeking an explanation. When the DCGI summoned some of these firms to explain their cases in June, they reportedly opted to pay up. While most drug companies which FE contacted refused to come on record on the issue, saying it would be inappropriate to comment on a law which is still in the making, three MNCs said they adhered to internal protocols to decide the compensation once it is proven that a death or injury resulted from the trial and most cases of alleged non-payment was due to oversight of ethics committees. One of them, however, objected to the move to shift the burden of proof to the companies. “There are times when terminally ill patients enroll themselves for such trials after intimation from doctors about the seriousness of their illness. In those cases, it may become very difficult for us to establish a causal relation (between the clinical trials and the death of the patient).”

The Indian clinical research market is estimated to be between $300 to $500 million in 2010. The Indian clinical trial market which offers 30-40% savings to pharma companies compared to the US and EU (E&Y estimate of 2005), is projected to grow annually at a rate of 20%, according to Visiongain, which sees it becoming one of the most-favoured clinical trial destinations along with China by 2015.

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CHAOS IN CLINICAL RESEARCH

The recent irregularities reported in conducting of clinical trials by Axis Clinicals, a Hyderabad based CRO, in Andhra Pradesh has once again brought to focus the questionable ways in which clinical trials are being done in India by the pharmaceutical companies and their agents. The report said that the CRO conducted bio-equivalence studies for an anti cancer drug on poor women early this year without securing their informed consent. The episode came to light only last month when some women belonging to this group complained of severe body ache, joint and chest pain and extreme weakness after taking the drug. A few of them even had difficulty in walking. The office of the DCGI raided the premises of the CRO after report came in the media and suspended its license. Axis also will be disallowed from conducting all bio-availability and bio-equivalence studies at their centre for some time now. Investigation carried out by the DCGI officials found irregularities in procedures such as recruitments of subjects and in taking their informed consents. The DCGI also found that the ethics committee at the centre was not functioning independently as required under the existing ICMR guidelines. Many such violations by CROs while conducting clinical trials in India were reported in the recent past and actions were taken against the offenders. But, these offences keep occurring in various parts of the country and very few of them get reported in the media.

After the action taken against the Hyderabad CRO, the office of the DCGI decided to audit all CROs in the country to ensure that the bio-availability and bio-equivalence studies are performed strictly in accordance with the regulatory provisions and prescribed guidelines. The DCGI office has already completed auditing of CROs in Andhra Pradesh and Mumbai. The basic problem with the clinical research in the country is that the sector is not at all effectively regulated. The health ministry has been working for last ten years to put in place a set of comprehensive rules to regulate clinical research with huge flow of contract research jobs into the country. But that has not happened yet. Ethics Committees at most of the trial sites are not active with no monitoring of the trials. What the country has a set of guidelines after amendment of the Schedule Y of Drugs & Cosmetics Act and it is not yet notified. That is what emboldens the MNCs and CROs to conduct trials as they do it now. Now in the case of CROs, a set of draft rules for their mandatory registration was issued by the DCGI some time in July 2009 after it was approved by the Drug Technical Advisory Board. But the registration process is still not in place. The move to make registration mandatory for CROs was taken after finding a spate of irregularities in conducting trials in the past. In short, the slow decision making process in the health ministry is the prime reason for the whole chaos in clinical research front. The matter has to be taken up by the health minister seriously and urgently if this critical sector of the pharmaceutical industry has to function with some order.

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Clinical trials: DCGI faults 9 more CROs

HYDERABAD: Nearly a month after the licence of Axis Clinicals was suspended for irregularities in conducting trials on poor illiterate women, officials of the Drug Controller General of India (DCGI) found similar violations by nine Clinical Research Organizations (CROs) in the state. Highly-placed sources said that there are glaring violations in the recruitment process of `subjects' and in taking their informed consent in almost all these organizations, where the gullible are becoming guinea pigs.

In fact, Actimus Bio Sciences, Visakhapatnam, which is the latest to get embroiled in the clinical trial controversy, was one among the eight CROs recently inspected by the DCGI officials.

It was after Axis Clinicals was found to have administered anti-cancer drug to poor women from Piduguralla in Guntur district without securing their consent in June this year, DCGI had decided to investigate the working of all bioavailability and bioequivalence study centres in Andhra Pradesh within a period of two months to ensure that such studies are performed strictly in accordance with the applicable regulatory provisions and prescribed guidelines.

The officials, who are yet to submit the final report to DCGI, Delhi, revealed that they concentrated on the issues pertaining to the recruitment process and the ethical committee's approval process adopted by these CROs during their course of investigations. "None of them is fully following either the guidelines of the Indian Council for Medical Research or the rules framed in the Schedule Y, which are necessary for manufacturing new drugs," said an official adding that some documents were seized during the investigation.

Besides, the Standard Operating Procedure drafted for every study was given a go by. "They should practise and follow what is there in the SOP. Further, if video recording of subjects is done prior to the study, it would be beneficial for these organizations though it's not mandatory. None of them is adopting this practice," said the official adding that more than 50 studies are being done annually by these CROs.

Aizant, Sipra, Bio Serve, Vimta, CR Bio, Nicholas Piramal, GVK Bio are the other CROs operating in the state. The DCGI officials said that the final report would be submitted to DCGI in about a week or so. He added that a team would again visit Actimus Bio Sciences in Visakhapatnam on Wednesday to study the case of two students who were subjected to clinical tests for two days.

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Clinical trials in AP come under scanner

Good food, old Telugu movies and handsome money is what 25 women at Pidiguralla town in the coastal district of Guntur were promised in return for vials of their blood. But what they had not bargained for was severe body ache and hospitalisation.

The women, most of whom are poor quarry workers, were unaware that they were being used for trials conducted by Hyderabad-based firm Axis Clinicals for a breast cancer drug.

The Andhra Pradesh government has now directed the district health officials to probe the incident. “There is no illegality about clinical trials but there has to be proper monitoring,” said Andhra Pradesh health minister DL Ravindra Reddy. The state government is also awaiting a compliance report from the Drug Controller General of India (DCGI) on this matter.

Axis Clinicals is engaged in bio-availability (BA) and non-equivalence (BE) studies and has a facility that includes a clinical pharmacology unit as well as a bio-analytical laboratory for drug analysis. When contacted, Business Development AGM Abhijit Chowdhary said the company was never involved in any trials for new drugs. “We were only conducting BE studies on healthy volunteers for a generic drug and not trials for any new drug. However, he refused to give any further details about the drug or the pharmaceutical company’s name for which the BE trials were being conducted.

“We were conducting these trials with the prior permission from DCGI and now we are cooperating with them for any kind of clarifications or reports,’’ Chowdhary said.

Andhra Pradesh Drug Control Administration head RP Meena said the state had no power to regulate clinical trial research organisations (CROs). The CROs are supposed to form an ethical committee which should meet frequently to discuss the type of clinical trials being undertaken, the side-effects if any, and keep a record of who the subjects are and what precautions have been taken to do away with any side-effects.

But the so-called ethical committee remains only on paper, and a large number of innocent patients are becoming guinea pigs for all kinds of clinical trials. “The ethical committee is not functioning properly,” said a top official from a pharmaceutical company. “The missing links in the trial registry have to be plugged through necessary rules and regulations and effective implementation,” the official said.

There are several reasons why drug companies are drawn to India. These include a technically competent workforce, patient availability and a friendly drug-control system. However, the booming clinical trial industry is raising concerns because of a lack of regulation of private trials and proper ethics review, says a WHO report. More than 650 clinical trials are currently taking place in the country and all the leading global pharmaceutical companies have started moving their key trials to India. The country has a large number of patients in areas for clinical research, such as diabetes, cardiovascular disease, HIV and oncology.

The global clinical research market is pegged at around $20 billion with India’s share being about $485 million. The latter is projected to cross the $1-billion mark by 2015, a Frost & Sullivan report says. Clinical trials are needed and new medicines are imperative, but more than the investment that would come in, the bigger task at hand is to ensure safety of volunteers and generate quality data, adds the report.

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Anti-Anxiety drug to be banned in India

The government is planning to ban a popular Anti-Anxiety drug that has been commonly used in India for over a decade. The drug is used without any clinical trials and despite the fact it is banned in several other countries. 

TIME magazine describes this decade as the "Age of Anxiety" and 4 out of 10 Indians suffer from anxiety related disorders according to the Indian Council of Medical Research.The Health Ministry is considering a ban on the commonly-used anti-anxiety drug Deanxit, for potential addiction and because it can sometimes provoke suicidal thoughts and nightmares.Psychiatrist, Bombay Hospital Dr Sharita Shah, said "In India, its not just psychiatrists who are using it, there are a lot of other doctors, like the GP, cardiologists, everyone prescribes it. So, it is popular, and patients also tend to overdose, once you write a prescription, the patients tend to take the drug on their own, and don’t come back to the doctors."

Deanxit enjoys a Rs 35 crore annual market in India itself. But what is disturbing, given those serious side-effects is that India is one of the few countries to even allow its usage.

Deanxit is banned for use in the country of it’s origin, Denmark. The US FDA, Drug Authorities in UK , Canada, Australia or Japan , have not approved this drug either. For such a drug, no clinical trials were carried out in India.

Taking note of these points, the Health Ministry has NOW setup a panel of medical experts to probe the side effects of this drug. But the bigger question is, who is responsible for the health of those patients who took this medicine for all this while?

Drug Expert, Editor MIMS Dr CM Gulati said “Why on Earth did the DCGI approve it? What were they thinking? Plus it is highly immoral and unethical on the drug company's part to sell a drug in India, which is banned in it’s country of origin! So, two major violations took place here.”

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Clinical trial reporting guidelines made stricter

The Drug Controller General of India has made it mandatory for pharma companies and clinical research organisation in the country to submit information on serious adverse reactions during clinical trials within 14 days of occurrence in a standardised format.

The drug controller has asked the drug firms to clearly mention whether a specific adverse effect is related to the clinical trials, whether it has resulted in fatality of the volunteer and whether compensation for the injury or death has been provided. This comes in the backdrop of the civil societies and drug experts raising concerns on the laxity in implementation of protocols by pharma firms, CROs in clinical trials across the country.

While the law already provides for reporting of such incidents through schedule Y of Drug and Cosmetic Act, it is the strict implementation of the Act that DCGI is aiming at. The drug regulator also made it compulsory.

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New Guidelines by DCGI for Clinical Trials

Clinical trials are an indispensable part of medical R&D to test the safety and efficacy of a new drug, treatment or a diagnostic technique in humans. While these are essential in the fight for better health, India has been shockingly lax in enforcing strict guidelines, and indeed even in evolving a stringent protocol for the same. Serious questions were raised about rules and regulations related to clinical trials when four girls died in Andhra Pradesh last year, after being administered a vaccine for human papiloma virus to prevent cervical cancer. While a committee has concluded that the deaths were most likely unrelated to the vaccine, it nonetheless put into sharp focus the existing protocol and safeguards for volunteers.

The Drug Controller General of India (DCGI) has finally come out with new draft guidelines that make it mandatory for all companies conducting critical trials to take the written consent of the volunteer. This provision has been arbitrary until now, leading to allegations that “informed consent” is a fallacy since volunteers are seldom given a full picture of the trial or of the risks involved. The socio-economic status of the volunteer too has to be mentioned: this could set the alarm bells ringing if there’s any widespread exploitation of any particular section of society. Equally importantly, the guidelines require the companies to report to the DCGI any serious adverse effect during the conduct of the trial, the reasons for that and details of compensation given.

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Sparsha Pharma to launch 3 transdermal products soon, got DCGI nod for marketing one

Sparsha Pharma International, the lone manufacturer of transdermal patches, a medicated adhesive patch that is placed on the skin to deliver a specific amount of drug through skin and into the bloodstream, is planning to launch three products in a couple of months.

The Hyderabad-based company already has a product, fentanyl transdermal patch, in the market. Fentanyl is a potent synthetic narcotic analgesic with a rapid onset and short duration of action. It was given to Dr Reddy’s Laboratories with exclusive rights for one year to sell in the domestic market in 2009 and Dr Reddy’s is marketing the product under the brand name, Finrid. Later, after the expiry of the exclusivity period Sparsha launched the product in the domestic market last year under the brand name, Fen-Touch.

“We are planning to launch two more products in a couple of months and we have already received approval from the Drugs Controller General of India (DCGI) for one of the products. Both the products are for pain management. Another product, which is for the treatment of asthma, is in clinical trial stage and will launch in a few months”, Dange Veerapaneni, managing director, Sparsha Pharma International, told Pharmabiz.

The company has a technology collaboration agreement with Japan-based leading transdermal patches manufacturer. Sparsha, with a manufacturing capacity of 1.5 crore transdermal patches per annum, is planning to invest Rs.60 crore in two phases as a part of expansion of its existing facility near Hyderabad. Sparsha is also mulling options to engage in contract manufacturing services

Commenting on the advantages of transdermal delivery, Dange Veerapaneni said that it avoids stomach upset common to orally administered drugs, side effects are less as the drug does not travel to all parts of the body and the drug is not subject to degradation during the first-pass effect as compared many oral drugs.

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Max Neeman International Responds to New India Clinical Research Guidelines

The Drug Controller General of India (DCGI) has formed new Regulatory and ICH GCP guidelines.  These guidelines include: recommendations regarding structure and format of genomic biomarker regulatory submissions; the Development Safety Update Report (DSUR), intended to be a common standard for periodic reporting on drugs under development among ICH regions.

In response to the new guidelines, Max Neeman (leading Indian-based CRO) trained the Quality Assurance team and incorporated required changes into SOPs to carry out trials for biomarkers and stem cell trials.  Extensive, timely, up-to-date training in response to India regulatory bodies provides for an exceptional level of knowledge regarding the most current Indian Clinical Trial Regulations, ICH GCP guidelines and ISO and ISMS standards.

Quality Assurance forms an integral part of drug development to maintain the integrity of clinical trials.  Max Neeman continually trains employees to keep current with new DCGI, ICH GCP guidelines and to seek out the most effective actions to correct and prevent issues.  Company QA auditors have years of hands-on experience working as CRCs and CRAs which allows for in-depth knowledge of operational aspects.  Based on this and strong SOPs, the team can provide insightful recommendations, helping to ensure compliance and high quality results.

In addition to a comprehensive internal Quality Assurance program, Max Neeman provides stand alone service to sponsors and clients.  A full range of clinical audit services exist from SOP preparation to advice on trial implementation in order to maintain the highest standard of conformance to ICH GCP regulations.  Indeed, Max Neeman has successfully completed a 5th external regulatory audit for highest enrollment globally.

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Ban on anti-anxiety drug Deanxit in pipeline

The Government may soon ban the controversial anti-anxiety drug Deanxit, a combination of two psycho-active agents being frequently prescribed by private doctors in India. A Government panel has pointed out the addictive potential of the drug as harmful side effects.

The technical panel of the Drug Controller General of India in its latest report to be discussed on May 5 has said that it (Deanxit) has potential for addiction (among users). The panel comprising medical experts also said that it has side effects such as drowsiness or dizziness, dry mouth, constipation, weakness or tiredness, excitement, anxiety or nightmares.

The finding will be reviewed by the Drugs Technical Advisory Board (DTAB), the highest decision-making body under the Union Health Ministry on technical matters related to health issues.

Sources said the panel without making any specific recommendations has pointed that the combination of flupentixol and melitracen produced by a firm Lucdbeck from Denmark is used widely by private sector for treating depression and anxiety.

Interestingly, the medical fraternity dealing with the psychiatric cases is divided over the health impacts of Deanxit which is banned in its country of origin, Denmark, but is being freely sold here.

What’s more, even though no mandatory clinical trial has been done on melitracen — one of its two ingredients- in India, it is touted as a “wonder drug” by the private psychiatrists who have been prescribing it at the drop of hat for treating anxiety cases.

However, doctors from Government hospitals do not recommend its usage. Dr Rajesh Sagar, Additional Professor of Psychiatry, AIIMS, says that he never ever prescribed the medicine to his patients. “In fact, in AIIMS no one is prescribing this drug as no proper trial has been done on it. Moreover, anti-psychotic drugs should not be given for anxiety symptoms.”

He was of the view that the drug is being aggressively marketed by the company among non-psychiatric doctors who are prescribing it at the cost of health of the patients.

The medicine has no presence in Government-run hospitals such as GB Pant Hospital and Institute for Human Behaviour and Allied Science (IHBAS) in Delhi, known for best psychiatric treatment in the country.

Dr Deepak Kumar (Psychiatric) from IHBAS said the drug is banned in many nations due to its health hazards. “There are no clinical trials in India. Moreover, one of the two ingredients, melitracen is not approved yet in the country. The drug is freely available in India, even though the fixed-dose combination has been banned in advanced countries due to health hazards. It’s strange why it’s still being sold in the country.”

Dr Chandra Gulati, editor of MIMS India, a drug Journal, too maintained, “Interestingly, melitracen is not approved in India. So how can you approve a combination of which one of the ingredients is not approved?”

“Also, this drug is made in Denmark. However, it is not approved for use in Denmark itself. According to rule 30B in the Drugs Act, any drug not approved in the country of origin cannot be used in India. Moreover, its sale is prohibited in the UK, US, Australia, Canada and Japan. Then how come it is beneficial for the patients in India,” he argued.

Gulati said that the drug is being aggressively promoted for a wide range of known and unknown disorders such as psychogenic depression, depressive neuroses, masked depression, menopausal depression, dysphoria in alcoholics and drug addicts.

The DGCI should have banned it long ago but for unknown reasons, it has cleared the combination drugs without mandatory clinical trials in India, he added.

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DCGI asks state drug controllers to immediately cancel licenses for Artemisinin

The Drugs Controller General of India (DCGI) has asked the state drug controllers to immediately cancel the manufacturing licenses of oral single drug formulations of Artemisinin and its derivatives, and also to ensure that no consignment of oral single drugs fonnulations of Artemisinin and its derivatives is exported from India with immediate effect.

The DCGI's order comes in the wake of WHO reports that continued use of Artemisinin derivatives as monotherapy for the deadly disease malaria is one of the main factors which contributes to the development and spread of drug resistance.

The WHO had some time back written to the DCGI stating that there is increasing evidence that the continued use of the Artemisinin derivatives as monotherapy is one of the main factors which contributes to the development and spread of resistance. Resistance to Artestinate was first reported in 2009 in limited geographical area at the Thai-Cambodian border, where Artemisinin have been used alone as monotherapies for many years, especially in the private sector.

Artemisinin based combination therapy is-the first line of treatment for all P. Falciparum malaria cases around the world. Monotherapy with the Artemisinin has been withdrawn in India also.

Earlier, the question of phasing out of oral single drug formulations of Artemisinin and its derivatives from the market was considered in the 39th meeting of the Drugs Consultative Committee held on December 10, 2008 at the DCGI office.  The committee after deliberations agreed that oral single drug formulations of Artemisinin derivatives like Artesunate and Artemether should be withdrawn from the market in a phased manner by July 2009.

However, it has been brought to the notice of the DCGI office that some of the manufacturers are exporting the monotherapies of Artemisinin to other countries, which prompted him to act tough in this regard.

Monotherapy with Artemisinin poses a great threat to global malaria control as resistance in any part of the world can be detrimental to the use of Artemisinin-based Combination Therapy in other parts of the world, the DCGI in its order said.

Alarmed over the emerging situation in this regard, the WHO had recently warned that 'the world risks losing its most potent treatment for malaria unless steps are quickly taken to prevent the development and spread of drug resistant parasites'.

The global plan for artemisinin resistance containment outlines the necessary actions to contain and prevent resistance to artemisinins, which are the critical component of Artemisinin-based Combination Therapies (ACTs), the most potent weapon in treating falciparum malaria, the deadliest form of the disease. Resistance to artemisinins has already emerged in areas on the Cambodia-Thailand border. Although ACTs are currently more than 90% efficacious around the world, quick action is essential. If these treatments fail, many countries will have nothing to fall back on, the WHO warns.

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Drug Controller General of India to set up office in Chandigarh

In order to facilitate the pharma companies, the Drug Controller General of India (DCGI) is setting up sub zonal offices in Chandigarh, Jammu (Jammu & Kashmir) and Bangalore by the end of this year.

Besides, it has also plans to set up sub zonal offices in Guwahati, Goa and Indore next year. The facility will look after facilitation of inspections, issuing of licences, approvals and eventually managing clinical trial audits and would benefit the pharma players.”

The Chandigarh sub zonal office would be fully operational by the end of this year including the laboratory. The move by the centre is likely to benefit over 500 units located in tax free zone of Himachal Pradesh, besides Punjab, some parts of Jammu & Kashmir and Haryana, as they can get clearances and approval locally.

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CEL-SCI Gets Approval To Begin Phase III Clinical Trial Of Multikine In India for Head & Neck Cancer

CEL-SCI Corporation announced that it has received approval to begin enrolment of patients in its phase III clinical trial of Multikine in India from the Directorate General of Health Services Office of Drug Controller General of India (DCGI) - the Indian equivalent of the FDA. India is an important country for this nine country clinical trial because about 15 of the 48 clinical centres for this global trial will be located in India and because India has the greatest number of head and neck cancer cases in the world. 

It is expected that patient enrolment in India will be about 4-6 times faster than would be possible in US clinical centres. The global phase III trial for Multikine was started in the United States in late December 2010. CEL-SCI expects to commence the trial in other countries around the world within the next 30-60 days. Multikine is the company's flagship immunotherapy developed as a first-line standard of care in the treatment of head and neck cancer.

CEL-SCI's phase III clinical trial is an open-label, randomized, controlled, multi-centre study designed to determine if Multikine administered prior to current standard of care (surgery plus radiotherapy or surgery plus concurrent chemo radiotherapy) in previously untreated subjects with Advanced Primary Squamous Cell Carcinoma of the Oral Cavity/Soft Palate (Head and Neck cancer) will result in an increased overall rate of survival, versus the subjects treated with standard of care only.

CEL-SCI's 880 patient phase III trial is expected to be the largest clinical study of head and neck cancer ever conducted. It is also the first trial in which immunotherapy will be administered before any other traditional means of care are attempted. This is significant because conventional cancer therapy weakens the immune system and likely compromises the benefits of immunotherapy.

Phase II clinical trials of Multikine demonstrated that the product was safe and well-tolerated and eliminated tumours in 12% of the subjects less than a month into treatment. The Multikine treatment regimen was also shown to kill, on average, about half of the cancer cells in the subjects' tumours before the start of standard therapy. Follow-up studies of subjects enrolled in phase II trials showed a 33% improvement in the survival rate of those treated with Multikine at a median of three and a half years following surgery. The US Food and Drug Administration granted orphan drug status to Multikine in the neo-adjuvant therapy of patients with squamous cell carcinoma of the head and neck.

CEL-SCI Corporation is developing products that empower immune defenses. The lead product, Multikine is currently being tested in a global phase III clinical trial that started in December 2010. In phase II clinical trials Multikine was shown to be safe and well-tolerated and to improve the patients overall survival by 33 per cent at a median of three and half years following surgery.

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Commerce Ministry to go ahead with bar-coding of medicines

The Ministry of Commerce and Industry will go ahead with the proposal for 2D bar-coding and a unique ‘randomly generated numeric code’ on packets of medicine destined for export, a senior official said.

According to P.V. Appaji, the executive director of the Pharmaceuticals Export Promotion Council (Pharmexcil, the ministry has set March 31 as the date for receiving objections and suggestions from the Pharma industry, which is opposing the move.

“The government will go ahead with implementation of the bar coding. However, the ministry has asked the industry to come out with their problems before March 31. Bar coding is fixed and the government will implement it as per schedule,” Mr. Appaji said.

The Commerce Ministry had recently made it mandatory for all medicines manufactured and exported out of the country to have a barcode from July 1.

Department of Commerce Additional Secretary Rajeev Kher held a meeting on March 10 with the representatives of pharmaceutical companies Torrent, Lupin and Fortis India, along with officials of Pharmexcil, sources said.

The Director General of Foreign Trade (DGFT) has made it mandatory for drug-makers to print a barcode on every product exported out of the country in the wake of overseas allegations that some local firms ship out counterfeit medicines.

Exports of pharmaceuticals from India stood at Rs. 40,000 crore last fiscal and are expected to witness a growth of 20 per cent this year.

The industry is opposing the move, saying it would incur an additional cost on the bar-coding procedure.

Any value edition to the product would affect pricing, said an official of city-based Natco Pharma.

“As it is, we have been facing serious competition from China on all fronts. Barcoding needs additional investment on manpower as well as machinery and thus puts pressure on pricing,” Natco Pharma Company Secretary and General Manager M. Adinarayana said.

Mr. Appaji said as per government estimates, bar-coding would cost 30 paisa per strip. “Putting barcode on primary packing is difficult and expensive, but secondary and outer layer of the export package will be acceptable for the industry,” he said.

The Drug Controller General of India (DCGI) recently indicated that it would make it mandatory for medicines intended for domestic supply to also bear barcodes. However, the government is yet to come out with an order in this regard.

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IP becomes first pharmacopoeia in the world to have its book of standards in DVD format

Indian Pharmacopoeia Commission (IPC) for the first time has released its IP 2010 in the DVD format at its general meeting which was held on March 4 in New Delhi. With this, IPC becomes the first pharmacopoeia in the world to have its book of standards in the DVD format. The main idea behind having it in the DVD format is to ensure that it becomes more user friendly and more accessible for people who need to refer it.

The book of Indian standards was released in DVD format by K Chandramouli, secretary, ministry of Health and Family Welfare and costs Rs.25,000. Dr G N Singh, secretary and scientific director, IPC informed, “We are very proud of the fact that we are the first country to have our book of standards i.e. the IP 2010 in DVD format. We have ensured that all the data that is being converted in the DVD is rightly protected and cannot be copied and misused.”

He pointed out that the IPC had decided to launch the DVD version so as to ensure that the users will be benefited from this so that they need not carry the bulky book when they need it. He informed for those who are interested in procuring the IP 2010 in DVD format it is available for sale at the IPC Secretariat and its distributors.

IP 2010 is the only book of standards in the world that has the distinction of being available in the DVD format. Even the British Pharmacopoeia (BP), United States Pharmacopeia (USP) are available only in the CD format.

The features of the latest edition of IP 2010, supersedes the 2007 edition and has many added features to it, with increased number of anti retroviral and protease inhibitors ie 40 drugs in the current edition. The latest addition of the IP 2010 has introduced 60 herbal drugs which include raw plants and herbal products approved by the DCGI.

Among the many firsts, the IP also has the distinction of being the first pharmacopoeia to have most detailed information on phyto pharmaceutical and herbal products. There are a total of 151 IP monographs in the IP 2010 edition, of which 89 monographs is of non biological products, 48 of biologicals and 14 of diagnostics. IPC is constantly updating all parameters keeping in view of national needs and international scenario.

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Stiff rules in offing for clinical research organizations

The noose is all set to tighten against organizations which conduct clinical trials for pharmaceutical companies. 

The Drug Controller General of India (DCGI) is all set to make it mandatory for all clinical research organizations (CROs) in India to register with it so that their activities can be closely monitored and their scientific credentials checked. The draft rules were published on January 19. A copy of the rules is available with the TOI.

What is interesting is the requirement for CROs to maintain all records for a period of five years after the final results are submitted, so that these can be scrutinized any time. New rules say, "All records such as protocols, approvals from the Central Drugs Standard Control Organization and ethics committee, audit certificates, completed and final reports, shall be maintained. All documentation and communication are to be dated and preserved safely for five years after completion of the study or submission of the data to CDSCO."

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DCGI, WHO to organise seminar on medical devices in Gujarat on March 18, 19

The Drug Controller General of India (DCGI) in collaboration with World Health Organisation (WHO) is organising a two day seminar for the regulatory authorities and stakeholders of medical device industry from March 18 to 19 in Gujarat. With this seminar the DCGI aims to sensitise not only the regulatory authorities but also other stake holders about the Medical Device Regulation Bill that is expected to be passed in the Parliament.

Once the Bill on medical devices is passed by both the houses in the parliament it will be known as The Medical Device Regulation Act. This Act will focus on consolidating laws related to medical devices and to establish the medical device regulatory authority of India for establishing and maintaining a national system of controls relating to quality, safety, efficacy and availability of medical devices that are used in India.

With the enactment of the bill, the medical devices industry's long-standing demand for creating separate guidelines and definition for medical devices will be met with. H G Koshia, commissioner, FDCA informed that this seminar will focus mainly on sensitising the industry about the medical device regulation bill.

The Gujarat Food & Drugs Control Administration, (FDCA) will be co-ordinating with the DCGI and WHO to hold this event. This is the first time that the such a training seminar for medical device industry is being organised by the DCGI in the state. 

Gujarat has 127 licensed medical device manufacturing units which is the largest in the country. Koshia informed that out of all the medical devices that are manufactured in the country more than 40 per cent including both new and old comes from Gujarat. Koshia points out, “Since Gujarat is considered as the hub of medical device industry it seems appropriate that this event be conducted here. This event targets at training the regulatory officials from different states and the stake holders across the country on the medical devises and the regulatory issues pertaining to it.”

He informed, that at present, medical devices is not considered as a separate entity and are treated as drugs under the Drug & Cosmetic Act with just nearly 20 notified devices regulated under this Act. Whereas there are still thousands of other devices that are outside the purview of D&C Act.

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