Vaccine fiasco

Anbumani Ramadoss, Union Health Minister, said that the licences of the vaccine-producing units had to be withdrawn because of pressure from WHO.-V. SUDERSHAN

SINCE Frontline published a Cover Story last year (April 11, 2008) on the closure in January 2008 of the three public sector units that met the bulk of the requirement of primary vaccines for the countrys Universal Immunisation Programme (UIP), and its potential impact on the supply of affordable essential vaccines for childhood immunisation, several important developments have taken place.

The Drug Controller General of India (DCGI) ordered the three units to shut down on the grounds that they were not complying with current good manufacturing practice (cGMP) norms under the Indian Drugs and Cosmetic Rules (D&CR), 1945. However, Union Health Minister Anbumani Ramadoss had told Frontline that the licences of the units had to be withdrawn because of tremendous pressure from the World Health Organisation to derecognise the DCGI, which is Indias National Regulatory Authority (NRA), following the WHO-NRA assessment of the units in 2007. This was the third assessment after the ones carried out in 2001 and 2004. The DCGI is supposed to ensure that the public sector units comply with the WHOs cGMP norms if they are to be certified by the WHO for the export of vaccines for global immunisation programmes. The Indian cGMP norms are equivalent to the WHO norms. These were adopted in 2001 but notified only in 2005.

The units in question are the 103-year-old Central Research Institute, Kasauli in Himachal Pradesh; the 100-year-old Pasteur Institute of India, Coonoor in Tamil Nadu; and the 60-year-old BCG Vaccine Laboratory, Chennai. These units had been manufacturing the Bacillus Calmette-Guerin (BCG) vaccine to prevent childhood tuberculosis, the triple diphtheria-pertussis-tetanus (DPT) vaccine, the oral polio vaccine (OPV) and the measles vaccine. The apprehensions expressed in the Cover Story that this unwarranted move could lead to a shortage of vaccines in the countrywide immunisation programme have turned out to be true (see tables).

Besides these vaccines and others belonging to the DPT group, such as the diphtheria-tetanus (DT) toxoid and tetanus toxoid (TT) vaccines, these units produce non-UIP vaccines such as the anti-rabies vaccine (ARV) for animals and humans, the typhoid vaccine and, most importantly, the yellow fever vaccine. They also produce sera, including the anti-snakebite serum. The Kasauli institute is, in fact, the only unit in South-East Asia to produce the yellow fever vaccine.

A centralised vaccine park, which will have state-of-the-art infrastructure for the production of and research on both UIP and non-UIP vaccines, including new generation vaccines, was proposed to be set up in Chengalpattu near Chennai in lieu of these three units. Hindustan Latex Ltd. (HLL), a public sector undertaking of the Ministry of Health and Family Welfare, was to set up this complex. On January 11, 2008, the Ministry handed over 330 acres (1 acre is 0.4 hectare) to the HLL for the proposed complex, named MediPark.

Though the HLL is a successful profit-making unit, it has little experience in vaccine production and technology. To begin with, the company started trading in vaccines through the marketing of the hepatitis B and typhoid vaccines. Interestingly, with its entry into the vaccine business and perhaps to present a different image, the company recently changed its name to HLL Lifecare Ltd.

The HLL, in turn, envisages MediPark as a public-private-partnership (PPP) venture with an investment of Rs.500 crore, with the UIP vaccine unit alone costing Rs.160 crore. The HLL has requested the Ministry to fund this component of the park entirely. The Ministry has apparently sought direct Cabinet approval for funding this project, but now this can be considered only by the new government. The private partner is yet to be identified by the HLL. According to recent news reports, the estimated cost of the project is now Rs.900 crore, implying that the cost of the UIP vaccine unit will have correspondingly shot up.

Towards this new-found enterprise, the HLL also signed a memorandum of understanding last August with NNE Pharmaplan India Ltd., a Denmark-based multinational company, for it to be the consultant for the project. According to A.K. Singal, the managing director of NNE Pharmaplan India, as of now, the Ministry has given the go-ahead to the company to prepare the basic engineering plan only. The detailed engineering plan will be taken up once the full contract is awarded to it, he said.

Interestingly, the Parliamentary Standing Committee on Health and Family Welfare in its 27th Report (April 2008) recommended that the suspension of the manufacturing licences of all the three public sector units be revoked. In its 34th Report dated February 18, 2009, which has specifically looked at The Functioning of the Three Vaccine Producing PSUs, the Standing Committee, chaired by Amar Singh, says: In the absence of any proactive action on the part of the Ministry [in response to the recommendation], reports about shortage of vaccines in the different States kept pouring in. It therefore decided to holistically examine this sensitive issue.

On December 6, 2008, T.K. Rangarajan, a Rajya Sabha member from the Communist Party of India (Marxist), made a representation to Prime Minister Manmohan Singh on the vaccine unit closure issue. He raised 10 questions and sought the Prime Ministers urgent intervention in the matter.

The questions related to the additional financial expenditure incurred on the procurement of vaccines since the closure of the units, the total estimated additional expenditure until 2012 when the vaccine park is likely to become operational, a comparison of this with the cost of upgrading the units to cGMP norms, the Ministrys strategy for making the vaccines available in the interim, the impact on the immunisation programme because of the closure, and so on. Rangarajan also met Manmohan Singh, who apparently gave him a patient hearing.

The Prime Ministers Office, in turn, asked the Ministry of Health and Family Welfare on December 23 to respond to the queries by December 29. But Rangarajan is yet to receive any response from the Prime Ministers Office or the Ministry.

However, in reply to a question in the Lok Sabha, Anbumani Ramadoss stated on February 18 that an expert committee under the chairmanship of the DCGI had been constituted in April 2008 to study, inter alia, the existing infrastructure/facilities available with these institutes and explore the feasibility of converting these facilities into testing laboratories, utilising the existing facilities for setting up residential training facilities and having some of the vaccines/anti-sera production at these institutes in compliance with cGMP. Though the expert committee has submitted its report, ironically, its terms of reference never included exploring ways to upgrade the existing units to make them cGMP compliant for primary vaccines.

This suggests that the Ministry never had any intention of upgrading them to meet cGMP norms and that the decision to shut them down was perhaps taken in 2004 itself. If one goes by the remarks of M. Ayyappan, the chairman and managing director of the HLL, to a news agency, the first project report was prepared in 2004 itself and the green signal was given in 2006. According to Anbumani Ramadoss statement, the expert committee recommended the production of tissue culture anti-rabies vaccine (TCARV) and anti-sera at the Pasteur Institute. The institute will also be developed into a central testing laboratory for medical devices and a training centre for the production and testing of anti-sera.

Recommendations for the Kasauli unit include new manufacturing facilities for the yellow fever vaccine, the influenza vaccine (seasonal and pandemic), the acetone-killed typhoid vaccine and the TCARV; a new anti-sera facility; a centre for measles, flu and rabies surveillance in addition to the existing polio surveillance; expansion and modernisation of the existing animal house into a national animal breeding centre; and the expansion of the Central Drugs Laboratory at Kasauli to have separate wings for bacterial and viral vaccines.

The recommendations for the Chennai unit include its conversion into a BCG vaccine-testing laboratory under the Central Drugs Laboratory, setting up a training centre for BCG production and testing, developing a central testing laboratory for cosmetics, and expanding and modernising the existing animal house.

Given the limited and very specific terms of reference, these recommendations are not surprising. Indeed, the Parliamentary Standing Committee report states: The scope and TOR [terms of reference] of the EC [expert committee] are self-revealing. [They] indicate that the Ministry had already taken a decision for final stoppage of vaccine production at the institutes despite the fact that the manufacturing licence remained suspended till the time discrepancies notice were finally removed. The Committee expresses its serious reservation on this development. The report further says that certain critical aspects about the functioning of the three units remain unclear even after an analysis of the Ministrys Status Note and the expert committees report, requiring complete examination of the whole issue by the Standing Committee.

The most significant and the damning observation of the Standing Committee is the following: [N]either the joint inspection team of WHO-NRA nor the subsequent team from the DCGIs office had made any recommendation regarding stopping production of vaccines by these units or closing down these units.

The report also points out that in the last evaluation of the units, carried out in 2007, the three units had been asked to rectify certain deficiencies in cGMP compliance that were noticed but the institutes were neither given sufficient time nor adequate budgetary support to rectify the deficiencies pointed out by the inspection team.

The Standing Committee has pointed out that the major shortcomings pointed out by the WHO inspection team had already been rectified by the institutions concerned and what remained were a few drawbacks pertaining mainly to infrastructure, which could have been easily removed with positive support from the Ministry. Citing Rule 85 (1) of the Drugs and Cosmetics Rules, the Standing Committee stated that the licences of the three units should have only been suspended for a specific period.

This period, says the report, could have been utilised for removal of all the shortcomings in a time-bound manner under the overall supervision of the Ministry.

Castigating the Ministry for its total inaction, the Parliamentary Standing Committee states: [I]t is astonishing to find that the building structures of these old institutions have continued to remain in their original set-up. Ideal position would have been to revamp the existing structures so as to ensure normal functioning as well as further expansion/strengthening in accordance with the changing times/requirements. The Committee is not aware whether any initiative, whatsoever, was taken by the Ministry or the Director-General of Health Services (DGHS) to draw up an action plan and take follow-up action in a time-bound manner. The Committee fails to understand as to how the Ministry would ensure cGMP compliance in the private institutes when it cannot enforce the same in its own institutes.

But more serious is the charge by the Standing Committee that the WHO had offered to upgrade the technology of these units but the Ministry had declined the offer and instead preferred to cancel their vaccine-producing licences.

Interestingly, the Standing Committee has found that a proposal to convert the DPT manufacturing laboratory at the Kasauli unit into a cGMP-compliant structure was made way back in 1997-98, and the contract was awarded to Noida-based HSCC.

However, after nine years and spending Rs.11.86 crore, the firm, in December 2006, expressed its inability and disinterest in completing the project. [This] epitomises the cavalier fashion with which the Ministry has treated the issue. The Committee views with serious concern the admission on the part of M/s HSCC about their not having any expertise to construct a scientific structure to cGMP standards. The Committee is of the firm opinion that the Ministry is responsible to a large extent for the prevailing unsatisfactory situation in the three institutes thereby leading to shortage of life saving vaccines with serious impact on UIP and child health care programmes in the country.

As reported earlier in Frontline, besides suspension of production, the DCGI also ordered the destruction of held-over stocks, in particular at the Chennai unit, the sole manufacturer of BCG in the country, stating that products manufactured at the institute could not be used owing to non-conformity with cGMP standards. This, according to the Standing Committee, was done on February 20, 2008.

Until the inspections were carried out, the institute had been meeting the requirements of BCG vaccine for the entire countrywithout any reports of any adverse effects. If the vaccines supplied under the UIP conformed to the standards of safety, efficacy and quality, then what could be the logic to order the destruction and writing off of the stock by the DCGI? the Standing Committee asked.

It also noted with dismay that, in the wake of the closure of the units, there have been vaccine shortages for the UIP across the country. The demand-supply gap following vaccine procurement from private suppliers in 2008-09 is given in Table 1.

Significantly, the Standing Committee said that the cGMP status of these private suppliers was not known and that it would like to be apprised by the Ministry about it. The committee has also commented that once the private sector becomes the source of vaccines, there is every likelihood of the cost of the vaccines going up, defeating the very objective of providing essential vaccines at an affordable price. Indeed, the Minister recently confirmed this unfortunate development to a television channel. Though private sector units had made a commitment to the Ministry on paper, they were now demanding a much higher price.

As regards the proposed vaccine park, the Standing Committee noted that with the three vaccine-manufacturing public sector units already functioning for so many decades the right course of action would have been to make sincere efforts to revamp them.

Vaccine park coming up at the cost of already existing units cannot be justified from any point of view. This project could take a couple of years before manufacturing and supply of vaccines could actually take place. In conclusion, the committee recommends that the Ministry revoke the suspension of the vaccine-manufacturing licences at the earliest.

Until such time that new infrastructure is built conforming to D&CR norms, these institutes should be allowed to continue production in the old structures after carrying out the rectifications either fully or to the extent possible, the report states.

Another significant development in the matter is that on February 21, a Supreme Court Bench comprising Chief Justice K.G. Balakrishnan and Justice P. Sathasivam admitted a public interest litigation (PIL) filed by S.P. Shukla, former Special Secretary to the Ministry of Health and Family Welfare and a former Member of the Planning Commission, and non-governmental organisations against the government, including the Health Minister, the Health Secretary, the DCGI, the directors of the three public sector units and the respective State governments.

The bench, in turn, issued notices to the respondents. The Parliamentary Standing Committee report strengthens the petitioners prayers significantly.

The petition asked the court to make recommendations to ensure the availability of essential vaccines at affordable prices, including directing the government to restart production at the public sector units. Drawing the courts attention to media reports that alleged improper and illegal arrangements between some of the public sector units producing vaccines and various private firms, especially Green Signal Bio Pharma, a company owned by P. Sundaraparipoornan and registered in 2005, the PIL asked the court to constitute a committee of experts to investigate these allegations. The scope of the Standing Committees report, unfortunately, neither included these aspects nor some of the questions raised by Rangarajan.

However, according to sources, the Prime Ministers Office has taken a strong view of the entire issue and has directed the Ministry to seek clearance from the Expenditure Finance Committee for the vaccine park proposal before bringing it up to the Cabinet. The Ministry will be directed to submit a detailed report to the Finance Committee on all the outstanding issues in the matter, the sources said.

The Committee feels that the the Ministry is responsible for the prevailing situation in the three units.