The science and the regulatory framework behind vaccination has come a long way since Edward Jenner discovered the first ever vaccine in 1796. Today, we have a plethora of regulations for every step of vaccine development, its approval and distribution. The regulatory framework aims to address the medico-ethical concerns that are inherent to the process of vaccine development and its administration amongst the general public. These concerns pertain to the safety of the research subjects of vaccine trials and recipients of the vaccines.
In the context of the COVID-19 pandemic, the fundamental premise underlying the regulatory framework is to strike a balance between the immediate necessity for fast tracked development of vaccines and the need for protection of its beneficiaries from fatal adverse reactions. In this context, this article attempts to simplify the legal compliances required for this process while also analysing recent developments as India nears the completion of the first phase of its COVID-19 vaccination drive.
- VACCINE DEVELOPMENT
In India, the vaccine development and registration procedure starts with clinical trials that are conducted under the aegis of Central Drugs Standard Control Organisation (CDCSO) and the Drug Controller General of India (DCGI). Vaccine development also requires approval from the Review Committee on Genetic Manipulation (RCGM) which is set up by the Department of Biotechnology (DBT) under the Environment Protection Act, 1986. The RCGM primarily looks into the safety-related concerns of activities involving genetically engineered organisms, including vaccines. The CDCSO accepts the application for a clinical trial only after it receives a No Objection Certification (NOC) from the RCGM, post examination of data from pre-clinical studies.
The clinical trials for development of the COVID-19 Vaccine are regulated under the New Drugs and Clinical Trial Rules, 2019 (NDCT Rules) and the COVID-19 vaccines are defined as “new drugs” under these Rules. The Rules define a “clinical trial” as a systematic study of a new drug to generate data for discovering or verifying its, clinical or pharmacological adverse effects, with the objective of determining the safety, efficacy or tolerance of such new drug. The clinical trials are divided into the following three stages:
The results from the clinical trials are then submitted to the CDCSO for initiating the vaccine approval process.
In March 2020, the RCGM and the CDCSO set up a rapid response regulatory framework to fast track the regulatory approvals of vaccine applications. To further fasten the process, the Government via a notification in May 2020, allowed applicants to manufacture and stock potential vaccines which could be sold and distributed post the success of clinical trials. The CDCSO also released the “Guidelines for Development of Vaccines with Special Consideration to COVID-19 Vaccine” for vaccine developers, which provided a framework similar to ones developed by international organisations like the WHO. With this rapid action framework in place, around 30 companies entered the race to produce the COVID-vaccine. More information about the present status of different vaccines can be found here.
- FINAL VACCINE APPROVAL
CDCSO is the National Regulatory Authority for giving approval to drugs and vaccines in India. The CDCSO reviews the results of clinical trials, and if approved by CDCSO, the Central Licensing Approval Authority (CLAA) gives its approval which commences the PHASE-IV or the post-marketing surveillance. Entire procedure for approval under the NDCT Rules can be found here.
As a part of India’s vaccination drive, approval has been given to the following vaccines – the Oxford-AstraZeneca COVISHIELD vaccine, manufactured by the Serum Institute of India Limited, and the COVAXIN shot developed by Bharat Biotech International Limited in collaboration with the Indian Council of Medical Research (ICMR) and National Institute of Virology (NIV). The CDCSO has granted emergency-use authorisation (EUA) for restricted use in an emergency situation to both the COVISHIELD and COVAXIN Vaccines. The approval is restricted in the sense that those who are administered this vaccine will be monitored the same way as volunteers in clinical trials.
Emergency Use Authorization (EUA) is a mechanism used to facilitate the administration of vaccines to groups that are at high risk of infection, morbidity, and mortality during public health emergencies. It includes a review of phase I, phase II data as well as a follow-up and interim analysis of the phase-III data. The Vaccine Task Force (VTF) and the National Expert Group on Vaccine Administration for COVID-19 (NEGVAC) are the administrative bodies regulating the EUA and pricing of the vaccines.
Emergency response and expedited pathways for regulatory approval do not find specific mention in the Drugs and Cosmetics Act 1940 and Rules 1945, but do so in the NDCT Rules 2019. Sub-clause 2(ii)(A) of clause (1) of the Second Schedule of the NDCT Rules provide for “accelerated approval” and “relaxation, abbreviations, omission or deferment of data” in “special situations” that are “life threatening or serious disease conditions or rare diseases and for drugs intended to be used in the diseases of special relevance to Indian scenario or unmet medical need in India” such as the pandemic or when remarkable efficacy is observed with a defined dose in the Phase II clinical trials. Such an accelerated approval is finally granted by CDCSO headed by the DCGI.
The restricted emergency approval given to COVAXIN in clinical-trial mode has especially come to face a lot of flak as clinical trial data for phases I and II has not been made public yet. Moreover, the approval has been given without completion of its phase III trials which test efficacy of the vaccine. A regulatory pitfall that arises here is usage of undefined terms for giving the EUA. COVISHEILD has been given approval for ‘restricted emergency use’ and COVAXIN has been granted approval for ‘restricted use in emergency situation in public interest as an abundant precaution, in clinical trial mode’. However, the difference in application of these terminologies and the restrictions under which the EUA has been provided, have not been specified by the regulatory authorities. Moreover, these terms, including ‘emergency use authorisation’, ‘restricted emergency use’ or ‘use in a clinical trial mode’ have not been defined under the NDCT Rules or the Drugs and Cosmetics Act, 1940. Thus, though the accelerated approval process is legitimate under law in context of a medical emergency, it has not been carried out in a transparent way and there exist regulatory pitfalls in giving such approvals.
The manner of giving the EUA has been criticized as it also goes against the draft Science, Technology, and Innovation Policy (STIP) released by the central government to promote the ethos of “Open Science”. As per this policy, scientific data should be transparent, accessible and should transfer knowledge between producers and users of such knowledge. However, the manner in which COVAXIN has been given the approval, creates a disparity between the policy and practice.
- VACCINE DISTRIBUTION
Two vaccines are being given as two doses as a part of India’s vaccination drive at present – the COVISHIELD or the COVAXIN vaccine. Though there is no specific legal framework for regulation of vaccine distribution, the Ministry of Health and Family Welfare has released Operational Guidelines for vaccine distribution which calls for an equitable distribution of vaccines across the country.
The national inoculation drive was launched on January 16, 2021 and 20.29 lakh beneficiaries have been vaccinated as of January 27, 2021 through 36,572 sessions. The drive is being managed using the Covid-19 Vaccine Intelligence Network, or Co-WIN. The IT platform is being used for rolling out and scaling up distribution for end-to-end management of vaccine distribution. The drive is being undertaken in three stages as of now – the first phase, is to vaccinate healthcare workers, the second phase includes essential services workers and the third phase includes people deemed susceptible to the coronavirus.
- POST VACCINATION LIABILITY
The Vaccine Manufacturers Association of India has written to the Indian government seeking indemnity from lawsuits during the pandemic period, citing the examples of USA and UK. USA has limited the liability of the Pfizer and Moderna vaccines under the Public Readiness and Emergency Preparedness Act 2005 (PREP Act). Recipients of these vaccines can seek compensation under a fund administered by Department of Health and Human Services. UK under its Human Medicines Regulations of 2012 has also limited civil liability of vaccine manufacturers and health care workers.
However, we are yet to see how this would translate in the Indian scenario in the absence of any express legal provisions for either indemnity or immunity. In India, the remedies to vaccine recipients might come under the Consumer Protection Act, 2019 or the Drugs and Cosmetics Act, 1954. The Vaccination Act, 1880 or the NDCT Rules do not provide for vaccine manufacturer accountability. Moreover, under the CDCSO Act 2019, compensation rules are limited to the clinical trial related remedy only.
A possible solution that has been proposed is a global, centralized no-fault-compensation fund to be set up under the COVAX Facility, an international partnership of countries to financially support vaccine development and accessibility, especially for lower-income countries. This fund could be funded either by higher-income countries or by charging manufacturers a per-dose tax to support its purpose. This would reduce the burden on lower or middle-income countries who would be unable to provide indemnity or immunity to vaccine manufacturers.
India needs to build a more robust regulatory framework that specifies the rights and responsibilities of the recipients, manufacturers and administrators, to ensure that the humongous population is inoculated in an efficient manner, especially given that India is also exporting the vaccines to other countries.
