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Drugs Controller General of India (DCGI) has given approval to Pune-based Serum Institute to conduct the second and third phases of clinical trials simultaneously of the potential COVID-19 vaccine Covishield developed by the Oxford University-AstraZeneca collaboration in the UK. This is the third vaccine candidate that has received approval for clinical trials from the DCGI in quick succession. Earlier approved ones, Covaxin and ZyCov-D, potential vaccines developed by Hyderabad-based Bharat Biotech and Ahmedabad-based Zydus Cadila respectively, are undergoing simultaneous Phase I and II clinical trials in various centres across the country at the moment. The companies are hoping that if everything goes well, they may be ready for the commercial launch of a COVID-19 vaccine in less than a year.
ON FAST TRACK
The speed at which all three vaccines have reached the clinical trial stage in India is unprecedented. The companies have been working overtime to zero in on the most promising vaccine candidate, and the regulator has wasted no time in granting necessary clearances. The permission to conduct simultaneous trials has also helped cut short time as, under normal conditions, approvals for each phase would have been only on the basis of the outcome of the previous phase of clinical trials.
For instance, the first vaccine project to take off, the partnership project of Bharat Biotech International Ltd (BBIL) and Indian Council of Medical Research (ICMR) to develop Covaxin, started with ICMR's National Institute of Virology (NIV) in Pune isolating the COVID-19 virus in their lab early this year, in the very initial stages of the pandemic itself. It was handed over to BBIL to identify and develop a vaccine candidate, a whole virus inactivated vaccine. The company, which has the country's only BSL-3 (bio-safety level) containment facility in the private sector to conduct such research, came out with a potential vaccine candidate within the next two to three months. The research work happened 24x7, and pre-clinical tests carried out in animals showed the vaccine is safe and it produces anti-bodies. The results were submitted to the DCGI and got cleared to be taken to the next level - the clinical trials in human volunteers. The hospitals or clinical trial sites were identified, they were asked to get their protocols ready, volunteers recruited, to begin clinical trials.
At the same time, BBIL sent samples of the vaccine candidate to Central Drugs Laboratory, Kasauli, where samples from every batch of vaccine - not just experimental vaccines, but even the ones that have obtained manufacturing licenses, gets tested for quality on a routine basis. The test results from Kasauli, which can take months depending on their workload, got prioritised and hence were completed within days. All the administrative procedures, which would have taken several years in a non-pandemic situation, thus got over within months.
ZyCov-D development has also followed a similar fast track. Pankaj R Patel, chairman of Zydus Cadila, has publically acknowledged the support of National Biopharma Mission, BIRAC, Department of Biotechnology, Government of India, ICMR and DCGI in the development of ZyCoV-D vaccine candidate. Zydus launched its accelerated vaccine development programme for COVID-19 in February 2020. The first human dosing as part of the adaptive Phase I/ II human clinical trials of ZyCoV-D, a plasmid DNA vaccine, happened on July 15. The DNA vaccine platform, on which ZyCoV-D is developed, uses non-replicating and non-integrating plasmid carrying the gene of interest, making it safer to handle.
Serum Institute, the production partner of Oxford University-AstraZeneca vaccine Covishield will also thank the regulator as the pre-clinical (based on studies of experimental animals) and Phase I clinical trial data generated outside India was considered while allowing the company to initiate the next levels (Phase II and III) of clinical trials in the country.
Phase I clinical trial is conducted to demonstrate safety of the vaccine. Once that is done, a Phase II trial to prove the efficacy of the vaccine takes place. After that is also successfully done, comes the Phase III to demonstrate efficacy of the vaccine in larger number of volunteers across multiple sites. The actual involvement of human volunteers and drawing of blood samples in the first and second phases gets over within a month each. It was the pandemic situation, and the urgency to fast track clinical trials, that made DCGI permit clinical trial sites to carry out Phase I+II trials, which means to conduct the first and second phases of clinical trial in parallel. Assuming that all clinical trial sites start administering the vaccine doses to the volunteers according to the protocols approved by the DCGI today (in the case of Covaxin and ZyCoV-D its already on), within a month, the samples collected at all the sites during the clinical trials can be sent to a NABL-approved diagnostic laboratory for testing. By then the Principal Investigators would have observed whether the vaccine is safe or not to the volunteers by observing them and checking whether they are developing any adverse reaction or effects (Phase I results).
The results of the second phase will indicate if the vaccine promoted development of antibodies. Depending on the urgency, the test results can come within 48 hours. The analysis of this data and preparation of final report by the clinical trial investigators for submission to the DCGI is the next step. This gathering of data, writing the reports and their submission, etc. to the DCGI can sometimes take months as the investigators involved are also busy medical professionals. ICMR had made an appeal to the investigators to prioritise these works and if it is heeded, reports can be prepared and submitted to the DCGI in a couple of weeks, instead of six months or more. The role of DCGI will then be to go through these reports and decide on the next regulatory step towards release of the vaccine for use.
Depending on the data of the Phase II vaccine trials, DCGI can permit the third phase of clinical trials. In the case of Covishield, the results of Phase III clinical trials along with its Phase II results may see DCGI even giving marketing approval. If there are no delays in clearances and preparation of protocols, enrolments, tests and reports, and if the results are robust, India can hope for a vaccine within a year.
READYING FOR THE LAUNCH
Indian vaccine makers are not the only ones who are working on COVID-19 vaccines. In fact, the World Health Organisation (WHO) itself is spearheading the global efforts to initiate as many accelerated vaccine development projects as possible. As on July 31, 26 vaccine candidates (including Covishield, Covaxin and ZyCoV-D) are in Phase III or Phase II stage of clinical trials. Another 139 candidate vaccines are undergoing pre-clinical evaluation. Indian companies may not be the frontrunners, but there is nothing much to complain about when it comes to their preparedness to launch the product, once it is found to be successful. But what differentiates India from other countries, especially the developed world, is the absence of any financial commitment from the government towards securing the vaccine on a priority basis once the vaccine becomes a reality.
Several developed nations have already committed billions of dollars to ensure the availability of vaccine. Deals are being signed with pharmaceutical companies like AstraZeneca and Pfizer to ensure that the vaccine doses are reaching their citizens in sufficient quantity. The US, which tops the list of COVID-19 infections with over 48 lakh cases, has made this commitment. India, where every day over 50,000 new cases are registered and is third in the global list of COVID-19 affected countries with over 18 lakh cases, is yet to make its plan clear. Any attempts to fast track the development will have to be matched with efforts to make the vaccine available at affordable costs.
Serum Institute promoter Adar Poonawalla has said that the company's newly built COVID-19 vaccine production facility can set aside half of its production capacity for domestic use, but the government is yet to have its mass vaccination plans in place. Though the priority targets for vaccination - the vulnerable population like frontline healthcare workers, people with other health conditions, etc. - have been more or less spelt out.
With COVID-19 cases increasing day by day, it is time for a vaccination plan. At least a blueprint that can suggest the way for the vaccine industry to firm up their India plans.
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