Ups and downs of Kasauli's Central Research Institute

Twenty years after the World Health Organisation (WHO) recommended that countries should transition from the Tetanus Toxoid (TT) vaccine to the Tetanus and Adult Diphtheria (Td) vaccine, the Kasauli-based Central Research Institute (CRI) rolled out this indigenously developed vaccine on February 21. The development also put the spotlight on the institute — founded by David Semple, a British army officer and bacteriologist in 1905 — and its fluctuating fortunes.Diphtheria is a potentially fatal upper-respiratory tract infection caused by the toxigenic strains of gram-positive bacillus Corynebacterium diphtheriae. Likewise, tetanus is also a major public health concern in India, having a high morbidity and mortality rate, prompting the government to launch this vaccine.The National Technical Advisory Group on Immunisation (NTAGI), Ministry of Health and Family Welfare, has recommended replacing the TT vaccine with the Td vaccine in India’s immunisation programme for all age groups, including pregnant women. “This transition is aimed at extending and strengthening protection against diphtheria in addition to tetanus, while sustaining the gains achieved in maternal and neonatal tetanus elimination and routine immunisation activities,” an official of the CRI said.The Kasauli institute started developing this vaccine in 2019. It successfully completed developmental studies, obtained a test licence, secured waivers for preclinical studies and Phase I, II, and III clinical trials, received marketing authorisation and licence for manufacture and sale, initiated commercial manufacturing, and obtained release from the Central Drugs Laboratory, Kasauli.“Since it is a combination of existing components which are in use, comprising tetanus toxoid and a reduced dose of diphtheria toxoid, a waiver was sought for the clinical trials from the scientific committee as the trial itself takes years,” said an official.“The institute will supply 55 lakh doses to the universal immunisation programme (UIP) by April, with production expected to scale up progressively in subsequent years,” observed Dr Dimple Kasana, Director, CRI. This achievement, she said, marks a major milestone in advancing India’s vaccine self-reliance “as this vaccine will play a critical role in protecting people against tetanus and diphtheria — both of which are serious yet preventable diseases”.Even though CRI is a key institute contributing to the national UIP, which aims at reducing under-5 mortality by providing free vaccinations, the lack of finances and the abysmally slow process to upgrade to the latest technologies have marred its development.Considering the need to keep pace with advances in regulatory requirements and technological developments, CRI upgraded to the current-Good Manufacturing Practices (c-GMP) protocols leading to the production of the Diphtheria, Tetanus and Pertussis (DPT) group of vaccines in 2016. This was the last upgrade the institute could achieve.Even as CRI prides itself as being the first Central Government institute to fulfil this stipulation, the Ministry of Health and Family Welfare has made adherence to the Revised Schedule M mandatory in December 2023. While transition to a higher technology or new product is abysmally slow at the institute, limited resources and other procedural hassles have stalled its plans on more than one occasion.The institute now manufactures DPT vaccines for the UIP but states are opting for the primary Pentavalent vaccine, which is a ‘5-in-1’ injection protecting infants against five diseases: diphtheria, tetanus, pertussis (whooping cough), Hepatitis B, and Haemophilus influenzae type b (Hib).The institute was supposed to supply the bulk of DPT vaccine components for HLL Biotech Limited (HBL), Chengalpattu, Tamil Nadu, to manufacture the integrated Pentavalent vaccines.The project, conceived after CRI’s revival in 2010, however, did not take off and the institute ended up supplying DPT vaccines as a booster dose for the UIP. It has manufactured 4.61 crore doses since 2019 and was unable to cater to the entire requirement. Plans to switch over to Pentavalent are yet again riddled with official red tape. “Since vaccines manufactured for the UIP are made available to the government at a much lower price than its manufacturing cost, the institute’s financial distress continues to escalate,” said an official.For more than a century, CRI-Kasauli has been a cornerstone of India’s public health system. The institute has been delivering life-saving vaccines, strengthening infectious disease surveillance, providing critical antisera for snakebite, rabies and diphtheria, and supplying DPT, TT and Japanese Encephalitis vaccines for national health programmes.Its role in training microbiologists and supporting national reference laboratories has been shaping India’s scientific and public health landscape. It has 385 employees on its rolls at present.The institute was originally established with a mandate of research work in the field of medical and public health, manufacturing of vaccines and antisera, human resource development, and to act as a national referral centre for public health problems.CRI was once the lone public sector institute that manufactured yellow fever (YF) and Japanese Encephalitis (JE) vaccines before its manufacturing licence was suspended in 2008. A Ramadoss, the then Union Health and Family Welfare Minister, had suspended its licence along with that of public sector institutes like BCG Vaccine Laboratory and Pasteur Institute of India, Coonoor, on the grounds that they did not comply with WHO’s norms of good manufacturing practices.This was a key turning point in the history of CRI. Two years later, the Union government, exercising its powers under sub rules (3) of Rule 85 of the Drugs and Cosmetics Rules, 1945, ordered revocation of the suspension in February 2010. These institutes were directed to upgrade to the WHO standards within three years. The upgrade, however, was much delayed for want of adequate funds and this eliminated their market, which was captured by the private sector.The production of vaccine for yellow fever, an acute mosquito-borne viral disease found in tropical areas of Africa and South America, was suspended in 2011. Though the institute made efforts to revive its production, it failed to secure requisite funds.It produced 35,000-40,000 doses as against the national annual demand of about 1.2 lakh doses before its production was halted. India now imports the entire stock. This vaccine is recommended for people going to Africa and South America. Since a large number of armed forces personnel, labourers and animal safari enthusiasts visit these countries, they have to get vaccinated before leaving the country.The institute also manufactured the Japanese Encephalitis vaccine earlier in view of the hundreds of deaths reported annually from Uttar Pradesh and Assam. Its production was also halted due to glitches in the redundant machinery.The first ever National Vaccine Policy 2011 strongly advocated the need for making the country self-reliant and self-sufficient in the development and manufacture of vaccines listed under UIP. With adequate funding and timely upgrade, the institute — credited with immunisation of troops during the Second World War — is confident that it can once again reach its prime and contribute optimally to the nation’s healthcare.

Ups and downs of Kasauli's Central Research Institute

Once the only Central undertaking manufacturing life-saving vaccines, the Himachal institute had its licence revoked for not meeting WHO norms in 2008. Its recent rollout of an indigenously developed vaccine shows its potential, and limitations

Ambika Sharma

Ups and downs of Kasauli's Central Research Institute

Once the only Central undertaking manufacturing life-saving vaccines, the Himachal institute had its licence revoked for not meeting WHO norms in 2008. Its recent rollout of an indigenously developed vaccine shows its potential, and limitations

Ambika Sharma

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