Testing times

The Central Research Institute in Kasauli faces an uncertain future after its licence to produce vaccines is suspended.

in Kasauli

AT Kasauli in Himachal Pradeshs Solan district, the Central Research Institute (CRI), whose role in the national immunisation programme has been acknowledged, faces the threat of closure of its production units following the suspension of its licence for reasons that are best understood by the Ministry of Health and Family Welfare.

In taking the action, the Central Licensing Approving Authority (CLAA), a body that comes under the Drugs Controller General of India (DCGI), Union Ministry of Health and Family Welfare, has concluded that the institute failed to comply with the conditions of licence as stipulated under the Drugs and Cosmetics Rules. It states that the institute does not have adequate number of staff and plants and its premises are also not big enough. The good manufacturing practice (GMP) standards as laid down in Schedule M of the Drugs and Cosmetics Rules have also not been complied with, the CLAA says.

The licence was suspended on the basis of two inspections, one on August 13 and 14, 2007, and the other on January 7 and 8, 2008. After the first inspection, the CRI was given a show-cause notice, in December 2007. Its request that it be given one to one and a half years to establish new facilities was not considered.

The institute has never been in such a dire situation in its 103-year history, one that the Pasteur Institute of India (PII) in Coonoor, Tamil Nadu, and the BCG Vaccine Laboratory in Chennai are also in. All three institutes have been told to stop forthwith the supply of stocks, procurement of raw materials, and production.

On January 15, 2008, the CRI received a letter informing it that its licence had been suspended. According to informed sources, the first inspection team, which included observers from the World Health Organisation (WHO) and two State drug control officers, one from the north zone and the other from Himachal Pradesh, visited mainly the Diphtheria and Pertussis block and pointed out lacunae in quality assurance, documentation and hygiene. It concluded that the vaccine manufacturing facility at the CRI did not comply with GMP requirements and that it had to go a long way in meeting the current regulatory expectations. The team recommended that the Licensing and Central Licensing Authority may review and take action deemed fit in this case.

The two-member inspection team that visited the CRI on January 7 and 8 made a total of 65 observations. Its report noted that improvements in testing, documentation and training of personnel were observed in the Quality Control Division (QCD) and that quality assessment functions were in the process of being implemented. The team also noted that the CRI had made proposals for a new facility for the manufacturing of vaccines, which were to be considered by the Ministry.

Neither team recommended that the CRI be converted into a testing laboratory, which is what the government is planning, say sources in the CRI.

On several occasions between August and January, and specifically after receiving the show-cause notice on December 14, the CRIs Director, K.R. Mani, conveyed to the Central government the requirements of the institute and made clear that the solution to its infrastructure problems lay with the Central government. Informed sources said the CRI had repeatedly submitted detailed proposals regarding the upgrading of its infrastructure and asked for more time from the government.

In a letter to the DCGI on January 4, 10 days before the axe fell, Mani said:[T]he interests of the CRI could not be safeguarded all these years because of government procedures and other prevailing norms of the Government of India from time to time. It is disheartening and unfortunate that the Central Licensing Approving Authority has taken a decision to either suspend or cancel the manufacturing licence based on the recent WHO-NRA [National Regulatory Authority] assessment.

In fact, the main target of the inspection teams at the CRI was the Diphtheria Pertussis Tetanus centre. The CRI has been the main contributor of the DPT group of vaccines to the Expanded Programme of Immunisation (EPI), now called the Universal Immunisation Programme (UIP), for the past 25 years. In 2006-2007, the CRI not only met the vaccine target but also wiped out the backlog.

Ironically, the CRI had been asked to supply more quantities of vaccines for the EPI programme as the PII could not supply the quantities allocated to it. The CRI agreed to supply 15 lakh doses each of DT (diphtheria-tetanus) and TT (tetanus toxoid) vaccines, in addition to the allocated doses of DT and TT for the year 2007-08.

Anticipating a renovation of the existing production facilities, different components of DPT, TT and DT were produced in bulk using extra manpower so that when renovation started the stock could be converted into final lots to be supplied for the EPI programme.

The CRI started production of the Japanese encephalitis vaccine in 1982, and in 2001, after the epidemic in Andhra Pradesh, it stepped up production to meet any emergency. Scientists were trained in Japan and the CRI committed itself to continued production of the vaccine in order to build a stock to face fresh outbreaks.

The CRI is also the only organisation in South-East Asia to produce the yellow fever vaccine for people visiting South American and African countries. Very recently, the Health Ministry of the Government of Egypt came forward to sign a memorandum of understanding with the Ministry of Health and Family Welfare for the transfer of technology from the CRI to produce the yellow fever vaccine.

In his January 4 letter to the DCGI, Mani said the CRI had attempted to comply with GMP standards since 1995 itself as the DPT group of vaccines was considered most important. A new GMP facility for the production of TT, DT and pertussis vaccines, as well as other processes, had been initiated, but it failed for reasons that did not fall in the ambit of the CRI.

Some of the reasons he cited: the selection of the GMP vendor was not considered in the beginning; scientists at the CRI did not have adequate knowledge of the GMP; the regulatory authorities did not shoulder responsibility for accomplishing the requirements of the GMP vaccine production facilities; and the regulatory personnel authorised to give suggestions did not do so.

He said the regulatory personnel did not play a constructive role save for pointing out the deficiencies. He alleged that one of the GMP experts, Dr A.K. Tahlan, who was the head of the Central Drug Laboratory (CDL), an autonomous organisation in Kasauli, did not deliver any constructive ideas to the CRI, the parent organisation. He added that Tahlan, who was transferred from the CDL to the CRI, ought not to have been assigned the responsibility of carrying out the WHO-NRA assessment as it involved a conflict of interest.

The CRI Director explained in his letter that subsequent to the WHO-NRA assessment, the institute had renovated the QCD laboratory and created a Quality Assurance Department. A proposal had been submitted to the Ministry for the renovation of the existing production facilities as long-term and short-term plans.

In fact, he said, the CRI had been asked to give a fresh proposal for the construction of new GMP facilities for the production of the DPT group of vaccines and other vaccines as well. It was estimated that it would take one to one and a half years for the construction of the new production facilities.

Informed sources in the CRI said the government wanted to convert the institute into a testing centre and stopped production activities.

As per the minutes of a meeting held on February 2 to discuss the suspension of the CRIs licence, the Union Health Secretary told the Director to collect information on the manpower available in both the CRI and the CDL and their proposed deployment to meet the changed requirement of the institutes and explore the possibility of redeploying the existing manpower to the proposed testing laboratory and other activities within the vaccine institutes itself.

The Health Secretary gave an assurance that consequent upon the stoppage of the production of vaccines in these institutions and their conversion into testing laboratories and facilities for undertaking other assigned activities, there would be no retrenchment of the existing employees.

The CRI Director explained that as the bulk of the employees, nearly 500, were employed in the C and D categories, their services would not be utilised if the production facilities were converted to lab testing or diagnostic facilities.

But on February 5, it became clear that the Ministry was intent on converting the three institutes, including the CRI, into testing centres. The institutes were asked to furnish information regarding their plans, costs, time frame and required manpower for their conversion into testing laboratories.

Meanwhile, vaccine production has come to a halt at the CRI, leaving unfinished many projects, and the fate of nearly 650 employees hangs in the balance. The institute runs a dispensary to treat dog- and snake-bite cases and has been unable to deliver sera for such cases ever since its licence was suspended.

Since 1953, the CRI has produced anti-sera products such as the anti-rabies serum, anti-diphtheria serum, anti-tetanus serum and anti-snake-bite serum. It also supplies diagnostic reagents to various organisations all over the country for research purposes.

The suspension of production is bound to have adverse effects on the public health system, which was dependent on the supply of cheap vaccines from the CRI and the other institutes in the public sector. The national immunisation programme of the government will also stand to be affected if the CRIs licence to produce is terminated.

The suspension was all the more surprising as the CRI had been given the responsibility to supply 800 lakh doses of the DPT group of vaccines as no other public or private sector manufacturing organisation was in a position to supply the vaccines for the current year.

The CRI employees association, which is spearheading an agitation over the issue, feels that the suspension of licence was a pretext to hand over production completely to private operators and at the same time downsize the staff at the CRI.

An air of gloom has descended on Kasauli as the CRI contributes a great deal to the economy of the town. We want to work. This situation is very depressing. The government says it is paying our salaries, but we dont want to be idle. We want to continue doing the work we did, said Sameera Rawat, a technical supervisor at the CRI. The majority of the employees are local people.

Naresh Attri, president of the CRI Employees Association, told Frontline that the Union Health Ministry did not give them any plan of action to improve the institute.

He wondered why the Ministry was keen to set up a vaccine park in Chengalpattu near Chennai after shutting down three vaccine-producing public sector units.

It is ironical that an institute that produces vaccines of standard drug quality is disallowed from further production, while the private vaccine manufacturers are allowed a free run, said a CRI scientist requesting anonymity.

Three years ago, in 2005, the CRI celebrated its centenary and none other than Union Health Minister Anbumani Ramadoss was the chief guest. The CRIs effort in sustaining the national vaccination programme was lauded and there was nothing to suspect that a full stop would be put to production activities.