Twelve labs were informed by the Indian Council for Medical Research (ICMR) on Thursday that they would be carrying out clinical trials of COVAXIN, India's first vaccine for COVID-19 that has been approved for human trials. However, the ICMR has also set a public launch deadline of August 15 this year, and this has raised concerns regarding whether a vaccine can be pushed for public use after barely a month of trials. This indigenous vaccine (BBV152 COVID vaccine) was developed by ICMR in partnership with Bharat Biotech International Limited (BBIL). ICMR will have a meeting with the selected labs on Saturday, but the labs are yet to get complete details about the project. Four of the twelve labs selected are based in south India. Preparations on for Phase 1 Usually, Phase 1 is a clinical trial in small group, and is to ascertain the safety profile of the vaccine. When it progresses to phase 2, the sample size is increased, and it looks at immune responses. In phase 3, this is done on a much larger scale with many more participants. Phase 3 is not even mentioned in the document. Jeevan Rekha Hospital in Belagavi and the Nizam’s Institute of Social Sciences in Hyderabad, which have both been selected, said that they received the communication regarding the trials on Thursday, and expect to start work next week. Dr Amit Bhate from the Jeevan Rekha Hospital in Belagavi, which will be conducting the trials, said, “We received communication yesterday [Thursday] that we have to start with the trials. I got the news 10 days back that we are going to do the trials. We are partnered with the CMS laboratory, which is in Delhi, and they have a tie-up with Bharat Biotech. We have done similar trials for vaccines for diseases such as for typhoid and Japanese encephalitis,” he said. Dr Bhate said that they will be receiving the vaccine next week, and expect to work with 150-200 individuals. “We will be doing all the trials and submitting the data. On that basis, the immune response of the patients to the vaccine and the success will be seen. After that, further steps will be taken,” he said. All the samples will be collected and sent to the main lab in Delhi. Dr Manohar Reddy, the director of the Nizam’s Institute of Medical Sciences (NIMS) in Hyderabad, said that they will be carrying out the trials on at least 60 participants. The vaccine trials, according to the Clinical Trial Registry of India (CTRI), will comprise 1,125 healthy individuals between the ages of 18 and 55, with no comorbidities in phase 1. The people selected for the trial will be given two doses – one on day zero and one of day 14. NIMS in Hyderabad is yet to receive approval from its institutional ethics committee, which it expects to get tomorrow. “Once we get the approval, the principal Investigator will start work registering the participants. The real project will kick off from Monday onwards," Dr Manohar said. Phase 1, he said, will go on for a month. Once phase 1 is evaluated for safety, immunogenicity (the ability of cells or tissues to provoke an immune response), etc., ICMR will decide about how to proceed for phase 2, he said. According to CTRI, there will be three groups with 375 participants in each group, which will receive formulations of the vaccine in phase 1. These results will be sent to the Central Drugs Standard Control Organisation for progressing clinical development. “The ultimate goal is the selection of a safe, well-tolerated, and immunogenic intramuscular vaccine, which will be further evaluated in the phase 2 study,” the CTRI stated. However, the outcomes mentioned in the registry in phase 1 and 2 look at timelines of 194 days (over 6 months), and estimated duration of the trial has been put at 1 year and 3 months. Concerns regarding fast-tracking Speaking to TNM, Dr Anant Bhan, a bioethics and global health researcher, raised concerns over the Independence Day deadline owing to safety and efficacy concerns. “The concern is – is there enough time given to carry out this kind of research? Is expediting the process way too fast? And will this cause issues with the efficacy and adequate oversight perspectives? Regarding the phase 1 and phase 2 studies — which are safety and immunogenetic studies, we really do not have enough data or information on the efficacy. Only after you have the efficacy data, you know if it’s going to work. If all that has to be done by August 15, then it’s very ambitious and unprecedented with regards to vaccine development,” he said. He, however, said the urgency is understandable given the times of pandemic. “But that does not mean you will skip your requirements. There can be ways of doing things more efficiently but you would need data to be presented in the right manner and make sure that you are covering all the bases while developing the vaccine. While you want to do things faster, you don’t want to do that at the cost of safety or efficacy standards,” he explained. He further added that even with an aggressive timeline of August 15, they may be able to finish phase 1, and the best-case scenario is they’ll be able to finish phase 2 as well. “But beyond that, to finish the third phase by August 15 it is highly unlikely. With regard to this, we need further details from the ICMR and the biotech company about what exactly they are doing and what is the sample size they are looking at,” he added. He also said some amount of information about phase 1 and phase 2 trial data and some part of their pre-clinical trial data needs to be shared in the public domain. Bhan also said in India, there have been no such expedited vaccine trials like these in the last two decades. And if there is any lapse in process, it could lead to a problem of its own. ICMR's letter to the 12 labs also said that non-compliance "will be viewed very seriously. Therefore, you are advised to treat this project on highest priority and meet the given timelines without any lapse." Bhan expressed his reservations about the “threatening tone” of this letter, sent by the ICMR DG. “The tone is a bit surprising. Any research of this kind is a form of a partnership and in order to do it effectively, you need to work closely with them. Care must be taken in order to maintain strict timelines and that due processes are not compromised,” he told TNM. Oommen C Kurian, a Senior Fellow & Head of Health Initiative at the Observer Research Foundation, said that having a vaccine by August 15, 2020, is an impossibility, and the only possibility is that it was typing error in the ICMR letter. "A vaccine, who's pre-clinical data isn't even published yet, cannot be rushed like this without its efficacy or safety is proven using sufficiently long trials. Only possibility is that there's a typing error, and August 2021 was typed in as August 2020. That will certainly be a realistic timeline," he said. "Normally, after preclinical animal testing, there can be up to four phases of trials which decide if the vaccine is efficacious and safe. Here we seems to have decided it is both, and the trial is being presented as is it is a mere bureaucratic requirement. I hope it is a typing error, else, it will diminish ICMR's credibility globally. Let's pause to remind ourselves that the ex chief of ICMR, Dr Soumya Swaminathan, is one of the most important names in global vaccine development as the chief scientist of WHO. A credible,safe vaccine by 15 August 2020 is a pipe dream," he added.
