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India’s regulatory response to COVID

These hard corona times shall pass. This hope is to a large extent rested on the development and availability of a vaccine, which is effective to combat COVID-19. India is likely to play an important role in the development of vaccine and the road to recovery of corona struck world.

The Indian government was seen to take some prompt preventive measures, including the unprecedented national lockdown, soon after the threat of COVID-19 spreading in India was realized. However, parallelly, it also undertook various affirmative regulatory steps and initiatives to ease out the regulatory process for the development of the vaccine. India is now at the forefront to develop and manufacture a COVID-19 vaccine with three front runners. The Serum Institute of India plans to undertake mass production along with UK pharma giant, AstraZeneca of a vaccine – ‘Covishield’ developed by the University of Oxford. The others in the process of development are vaccines – ‘Covaxin’ and ‘ZyCoV-D’, which are being developed by domestic pharma companies, Bharat Biotech, and Zydus Cadila, respectively.

Ironically, much-awaited regulations the “New Drugs and Clinical Trials Rules, 2019” governing clinical trials which were introduced only last year would constitute the primary regulatory framework for testing of proposed COVID-19 vaccines. These Rules also prescribe conditions and requirements with respect to clinical trials and various aspects related to a new drug. All prospective COVID-19 vaccines will be a “new drug” as defined under the New Drugs and Clinical Trials Rules and therefore, import and manufacturing of such vaccines either for clinical trials or for sale and distribution will be regulated by these Rules. The key regulatory approvals under the Rules are to be sought from the Drug Controller, India, which is within the Central Drugs Standard Control Organization (CDSCO), the national regulatory body for drugs and medical devices.

Additionally, activities relating to the development of a vaccine also require approval from the Review Committee on Genetic Manipulation (RCGM), which is set up in the Department of Biotechnology, the Ministry of Science and Technology under the Environment Protection Act, 1986. RCGM has been entrusted with the responsibility to monitor the safety-related aspects of on-going research projects and activities involving genetically engineered organisms/hazardous microorganisms, a process involved in the development of a vaccine.

The last six months have witnessed the Indian Government relaxing the regulatory approval process and filling in gaps in the existing regulatory regime with a sole aim to foster development and distribution of the COVID-19 vaccine at the earliest without compromising on related safety aspects.

As the first step, in March 2020, the Department of Biotechnology (DBT) and CDSCO came together to set up a rapid regulatory framework to fast track the regulatory approvals. This was thoughtfully undertaken to offer the availability of an accelerated approval system for clinical trials of a vaccine and import or manufacture of a vaccine for sale and distribution or testing. For this purpose, RCGM and CDSCO constituted an empowered committee, which could undertake review and examination of applications on a prioritized basis.

In continuation of the efforts made in March and with the increasing interest of certain foreign research organizations to collaborate with Indian drug manufacturers, the DBT further notified on May 23, 2020, that preclinical studies concerning a new drug already done outside India may be considered in regulatory submission and such applications be examined based on the quality of data generated. The said notification also mentioned about consideration of an abbreviated pathway for the vaccine based on scientific rationale and level of completeness of data in human trials in addition to satisfactory preclinical data. The effort here was to accelerate trial run for vaccines in relation to which study and research have already been undertaken by the foreign research organization. Based on the data available, a clinical trial may be permitted to start from phase II or III rather than starting from Phase I, which is the usual case.

Given the present conditions, CDSCO was prompt in realizing that it would be difficult to adhere to all the protocols and regulations while conducting clinical trials of the COVID-19 vaccine. On March 30, 2020, CDSCO issued a public notice in the general interest of all the stakeholders involved in the process of clinical trials to acknowledge that protocol modifications, deviations, and amendments may be necessary owing to unavoidable circumstances, but cautioned the vaccine developers that the rights or safety of the trial subjects should not be compromised in the process.

One of the biggest challenges upon an effective vaccine being developed is the scale at which it would be required to be manufactured and distributed. With an assumption of enormous commercial risk, the Serum Institute of India has initiated large scale manufacturing of the vaccine-Covishield in anticipation of clinical trials being successful. This seemed to be the only logical way to meet the urgent, huge, and essential demand of the vaccine. Given this proposition, the Indian Government extended necessary support by issuing directions under the wide powers vested under the Drugs and Cosmetic Act, 1940 to regulate the manufacturing, sale, or distribution of a drug as may be necessary for the public interest. Vide notification on May 18, 2020, the Ministry of Health and Family Welfare set up an approval system that permitted applicants to manufacture and stock the COVID-19 vaccine, which is under clinical trial. However, once the clinical trials conclude successfully, the vaccine can be sold and distributed only after the permission for the manufacture of a new drug for sale or distribution under the New Drugs and Clinical Trial Rules, 2019 has been obtained. This initiative on the part of the Indian Government was well received by the key leads involved in vaccine development in India, who perceived this move will lessen the timelines in delivering the vaccine locally in India once ready for distribution.

Accessibility to the COVID-19 vaccine being of extreme concern also led the Indian Government to bring about an amendment to the New Drugs and Clinical Trial Rules in June 2020. This amendment makes a provision for permitting import or manufacturing of a new drug for compassionate use for the treatment of patients suffering from a life-threatening disease or disease-causing serious permanent disability or disease requiring therapy for unmet medical need, where such new drug is not approved under the New Drug and Clinical Trial Rules but is under Phase-III of the clinical trial in India or any other country. Although the concept of “compassionate use of a drug” is not new to the global pharma and healthcare world, India had no provision under its regulatory framework which expressly provided for compassionate use of a drug. The above amendment in New Drugs and Clinical Trial Rules will help COVID-19 patients to get access to treatments involving drugs, which are not available in India and pending trials outside India (but could be the last stone to be unturned to save a life). The anti-viral drug namely, “Remdesivir”, which has been vastly used to treat COVID-19 patients in Europe was accessed under EU regulatory provisions providing for compassionate use of the unauthorized drug.

While the rush to reach the desired results is at its peak, the CDSCO has also prepared and notified vaccine developers of the draft “Guidelines for Development of Vaccines with Special Consideration to COVID-19 Vaccine”. These guidelines have been developed keeping in consideration those formulated by international health organizations such as WHO. These are not intended to supersede any statutory requirements but have been developed to provide a clear understanding of the regulatory requirements to the vaccine developers. Broadly, the guidelines lay out the requirements for manufacturing standards, non-clinical and clinical development of a vaccine. Specific consideration has been given to each of these aspects and standards in relation to a COVID-19 vaccine. Among many others, these standards for the COVID-19 vaccine include –

a) adequacy of data on safety against the potential risk of vaccine-associated Enhanced Respiratory Disease (ERD) (a concern that has been raised from data of studies in animal models when tested for vaccine constructs against other coronaviruses); and

b) at least 50 percent of efficacy to be achieved in the Phase-III clinical trial (which is understood to mean that the required response shows up in at least 50 percent of those vaccinated during human trials).

The extreme desire to break free from COVID-19 along with all the necessary support from the Indian Government has made way for at least three vaccines to be present at different trial stages with Covishield already in Phase III. As of today, the world is looking at India to deliver the need of the hour – an efficacious and safe vaccine to fight COVID-19 and return to the world that we understand as “normal”. The efforts and initiatives of the Indian Government to effectively and cautiously regulate the development of vaccine during these COVID times will be appreciated for years to come and hopefully be fruitful to have a vaccine developed in a short time from now.

By Ritika Ganju, Phoenix Legal. – Mondaq