New Delhi : India has not reported a single instance of medicinal side effects from drugs for the last three years to an international drug monitoring database set up by the World Health Organization (WHO).
Some industry observers see this as evidence of India’s lax monitoring of so-called
adverse drug reactions, or ADRs, in patients, or pharmacovigilance.
Such adverse reactions are believed to be the fourth largest cause of mortality and morbidity globally.
Medical malady: A chemist shop in south Delhi. Experts say a “bottom up” approach is needed where chemists and doctors are responsive and alert to any adverse reactions being brought to their notice by patients. Photograph: Rajeev Dabral / Mint.
Drugs typically throw up newer side effects than were known during clinical trials once they begin to be administered across large groups of patients. Collecting this data is crucial for patient safety as well as fine-tuning medical research.
The database of Sweden-based Uppsala Monitoring Centre, which carries out WHO’s international drug monitoring programme, shows no ADRs were reported from India between 2005 and 2007, a near impossibility, say experts, given India’s population, and the massive number of medicines and combinations being introduced into the market.
"The system (of pharmacovigilance) has failed in India. There is lack of training, medical assessors in drug controller’s office, insufficient funds and no motivation at all," says Pipasha Biswas, managing director of Symogen Ltd, an outsourcing services company with operations in the UK and India that focuses on pharmacovigilance-related se-rvices.
Prafull D. Sheth, vice-president of the international think tank of pharmacists, the International Pharmaceutical Federation, agrees that there was a need to separate the "good drugs and the bad drugs", a largely neglected area in India.
"No data has been generated and if it has been generated, it has not been analysed," he says.
"What is happening to the huge network of centres that have been set up?"
Sheth was referring to the elaborate structure that has been set up in India with 24 peripheral pharmacovigilance centres that are supposed to feed information into five regional centres that, in turn, funnel information to two zonal centres.
At the head of the pyramid is the office of Drug Controller General of India (DCGI) that is supposed to collate the countrywide data before sending it off to the database maintained by Uppsala Monitoring Centre.
Drug controller Surinder Singh acknowledges it has been a problem and is assuring a multi-pronged solution had been found.
"By end of this year, we intend roping in all the medical colleges and creating a drug monitoring cell within their (attached) hospitals. This will give us a good network to begin with for collecting data," maintains Singh.
Explaining the problems with existing pharmacovigilance centres, he says that the centres and training of personnel were being funded out of a World Bank capacity building project that came to an end in June, effectively freezing finances.
The initiative will now be funded by the government and "clearances are in the pipeline", Singh says.
The drug regulator claims that adverse reactions data was "being collected but not sent to Uppsala because of some fee demanded by them" but says that issue, too, has been resolved now.
As for 2005 and 2006, Singh, who took over as controller earlier this year, has no explanation as to why data was not forwarded to Uppsala.
According to Uppsala’s website (
www.who-umc.org), between July 2006 and June 2007, 68 member countries out of 83 pooled adverse reaction case reports into the international database of the WHO programme, taking the total number of stored cases to 3.87 million.
"The total number of processed and accepted ADR cases was 201,462 and the greatest number of these came from the US (100,659), Germany (19,830), the Netherlands (16,552), Thailand (9,602) and Australia (7,801)," notes a report on the centre’s website.
The numbers from India, which joined the initiative in 1998, were coming in during the initial years, albeit in small numbers. The centre found a large number of the reports thorough in terms of details filled in, procedures followed and linking the drug to a particular physiological event. But, gradually, reports from India starting being incomplete and eventually stopped.
Sheth says that the system collapsed because it "has been top-down", laden with a bureaucratic structure while it should have been "bottom up" where the chemists, pharmacists and even doctors are responsive and alert to any adverse reactions being brought to their notice since patients will first mention it to them.
"The whole world is discovering (the reports), then why aren’t we despite being the fourth largest drug market by volume?" asks Sheth.
India’s laws require drug makers to conduct post-marketing surveillance studies of the medicines they manufacture or import, provisions that are blatantly overlooked by companies, say some industry experts.
"Not all companies do it," admits Singh.
India’s Schedule M of the Drugs and Cosmetics Act, 1940, while elaborating on "good manufacturing practices", says: "Reports of serious adverse drug reactions resulting from the use of a drug along with comments and documents shall be forthwith reported to the concerned licensing authority."
Schedule Y of the same Act, which deals with the protocols of clinical trials, also stipulates: "On approval of a new drug, the importer or the manufacturer shall conduct post-marketing surveillance study of that new drug...during the initial period of two years of marketing."
But, experts say, the system encourages companies to cover up adverse reactions rather than report all of them to the regulator.
For instance, UK’s drug regulator officials "are very thorough in looking for (adverse reaction) reports while inspecting a company," noted Biswas. "Not only are the regulators strict, the consumers are very aware and liability suits can be prohibitively costly for companies."
Statement of All India Peoples Science Network on Closure of Three Public Sctor Vaccine Production Plants
On January 15th 2008, Drug Controllers of the respective States involved, under instructions from the Ministry of Health and Family Welfare (MoHFW), ordered the closure of three Public Sector Units (PSUs) involved in production of vaccines and sera. The three PSUs -- Central Research Institute (CRI), Kasauli, Pasteur Institute of India (PII), Coonoor, and BCG Vaccine Laboratory (BCGVL), Chennai – have been producing vaccines for the country’s Universal Immunisation Programme and for other general use. Vaccines that were being produced by them included DPT (to prevent diphtheria, whooping cough and tetanus), BCG (to prevent childhood tuberculosis), TT (to prevent tetanus), yellow fever vaccine, and anti-rabies vaccine.
The Ministry’s order was defended by the Government on two counts. The Government claimed that the units were not conforming to the amended Schedule M of the Drugs and Cosmetics Act, in terms of adherence to Good Manufacturing Practices (GMP) norms. The Government also took shelter on reports by the WHO that the facilities in the three units did not conform to internationally recognised GMP norms. Both these claims need closer scrutiny.
The WHO report was first published in 2001. The WHO had also offered assistance for upgrading the technology at these PSUs. What prevented the Health Ministry from taking up the WHO’s offer or in acting to remedy the situation on its own for seven long years? Similarly, hanges in Schedule M in the Drugs and Cosmetics Act were notified in 2001. Why did the Government not act for seven years to ensure that its own institutes were upgraded to conform to norms set by it? This, in spite of the fact that the three units were inspected for compliance at least twice by the Central License Approving Authority [CLAA] in the last few years. Here it may also be noted that two other PSUs which manufacture vaccines in India -- Haffkine Biopharmaceutical in Mumbai and Bharat Immunologicals and Biologicals Corporation Limited (BIBCOL) – adhere to the present GMP norms.
The three institutes are the oldest vaccine manufacturing units in the country, with the olderst one having been set up more than 100 years back. Anybody would agree that the technology and the facilities at these units would need periodic upgradation. The moot point, however is, that it was the Government’s responsibility to ensure that this was done. Instead of owning up and remedying its own failure, the Government has no right to destroy long standing national assets.
There are also immediate conseqquences of the closure. PII and CRI together contributed to about 30% of DPT production in the country. BCGVL is the sole manufacturere of BCG in the country. After the closure, the government would need to import DPT and BCG vaccines for use in the national immunisation programme. Further, the closure of the three PSUs is a step in the direction of totally privatising vaccine production in the country. This is being sought to be promoted also based on the plea that new vaccines – such as Hepatitis B, Hemophilus Influenzae B (HIB) and combination pentavalent vaccines, need to be introduced in the country’s universal immunisation programme. This plea itself has been contested y many experts, but is being promoted on the urging of private vaccine manufacturers – both India and Foreign.
The Save Pasteur Institute Association (SPIA) -- an association of employees of the Pasteur Institute-- has claimed that the institute had already completed 60% of the work to fulfill GMP (Good Manufacturing Practices) norms prescribed by the WHO. It is also understood that CRI, Kasauli had prepared an upgradation plan for the unit for Rs.55 crores as far back as in August, 2007. The DGCI, while not responding to this plan, issued a notice to CRI on 22nd December, 2007 and cancelled its manufacturing license on 15 January, 2008. The haste with with which these closure orders were issued are in sharp contrast to the DCGI’s reluctance to act on evidence for more than a year, that private manufacturers have been marketing 340 medicines that have not been approved by the DCGI. The Health Ministry, meanwhile, has proposed construction of a new vaccine park in Chennai at an estimated cost of Rs 200 crore, which will take a minimum of 3-4 years to be operational. The responsibilty is to be given to Hindutan Latex Limited (HLL) – a PSU that manufactures condoms. Why a condom manufacturer is being seen as a better alternative to existing vaccine manufacturers is entirely unclear.
Of even larger concerns are reports that the decision to close the three PSUs was taken in the backdrop of the Health Ministry’s efforts to promote private vaccine manufacturers. The Save Pasteur Institute Association has alleged that the Ministry signed an MOU with a private company -- Biological E Ltd -- on February 15, 2006, for supply of DPT-Hepatitis B combination vaccine for the expanded programme of immunisation of the Government of India. On November 23, 2006, the Ministry also signed a marketing agreement for manufacture and sale of these vaccines and a pentavalent vaccine with this company. Further, the Health Ministry also entered into an agreement with Green Signal Bio Pharma -- a new entrant in vaccine manufacturing. BCG Vaccine Lab, Chennai, is believed to have stood guarantor for a Rs.14 crores bank loan received by Green Signal Bio Pharma. The latter was given a vaccine manufacturing license on December, 2007, barely two weeks before the closure of the 3 PSUs.
It has also been alleged that Mr.Sundaraparipoornan, owner of Green Signal Bio Pharma, is a close associate of Ramadoss and a former PMK activist. Press reports allege that the Health Ministry, was engaged in clandestinely promoting Green Signal Bio Pharma, through Dr N Elangeshwaran, the then director of two PSUs (BCG Vaccine Lab in Chennai and Pasteur Institute of India in Coonoor). Reports indicate that research and production activities were deliberately disrupted at Pasteur Institute and supplies were diverted to the private company. Press reports have also quoted Dr.Elangeshwaran as claiming that he was forced by the Ministry of Health to act in this manner, and he is also believed to have speciffically named two officials in the Ministry, including a former Grugs Controller General India (an allegation that has been denied by the former DCGI).
These are extremely serious allegations, and the AIPSN demands that they be probed by an impartial authority, and if proved correct, stringent action be taken against all those who are involved. The closure of the PSUs involves not just a loss to the national exchequer, but more importantly, constitutes a national loss. These are units which have serviced the needs of the public health sector for decades, and their closure makes the country more vulnerable to health emergencies. It is of major concern that the decision has been taken in blatant violation of the Common Minimum Programme of the UPA Government, that had pledged to revive units in the Public Sector that were involved in manufacture of medicines and vaccines.
The AIPSN further demands that the PSUs be upgraded to conform to notified GMP norms, and all steps be taken to ensure the commencement of production of vaccines in these units. At the same time the Government should not victimise employees protesting against the closure, and all their jobs should be secured.
Closed Govt. Vaccine Plants shal be converted to Testing Labs.
Source: [Chronicle Pharmabiz: June 12, 2008]
The BCG Vaccine Lab, Chennai and BCG, PII, Coonoor were manufacturing DPT, DT, TT and TCARV vaccines. CRI, Kasauli was producing DPT, DT, TT, JE, anti rabies serum, CAVS, diagnostic antigens, HS and ATS, the essential vaccines those are needed for national immunisation programme. The Health Mionistry has clsoed these palnts from January 15, 2008 with a plea that the World Healt Orgaisation found the units are not complient to Good Manufacturing Practice.
The Govt. had now decided that an Expert Committee has been formed with Gov.authorities and industry representatives who would after thorough inspection of these plants submits its recommendations with guidelins within three monts to th Ministry of Health. The Committee consists of The Drug Controller General of India, Advisor to CDSCO, Director ERC, ICMR; Joint Director NICD; Vice President Panacea Biotech, Delhi; Director , Serum Institute, Pune.
Last Month, the Union Health Minister in Chennai said that if the team’s finding are suitable for possible restructuring, its recommendations would be implemented in favour of revival of vaccine production in the perticular units. But now, according to the sources, his office has decided to convert these century old units in to testing laboratories.
