The Drugs Controller General of India (DCGI) has issued a new set of guidelines, focusing on safety, immunogenicity and efficacy parameters for pharma giants who are developing COVID-19 vaccines.
The DCGI has said that a COVID-19 vaccine candidate should have at least 50 per cent of efficacy in the Phase-III clinical trial for it to be widely deployed and adequate data informing the potential risk of vaccine-associated Enhanced Respiratory Disease (ERD) needs to be generated.
The comprehensive draft regulator guideline for the development of a vaccine with special consideration for the COVID-19 vaccine provides guidance to the vaccine developers to ensure that — vaccines are well-characterised and manufactured consistently.
The guidance reads that considering the urgent need for a safe and effective vaccine for prevention of COVID-19, clinical development programs of the COVID-19 vaccine may proceed through an adaptive and seamless approach including data to inform the potential risk of vaccine-associated ERD will be needed.
The document has highlighted that the use of COVID-19 preventive vaccines in pregnancy and in women of childbearing potential is an important consideration for vaccination programs.
“There are three things for a vaccine–(i) the safety, (ii) immunogenicity, and (iii) the efficacy. Even, WHO says that if we can get more than 50 per cent efficacy that is an accepted vaccine. For respiratory viruses, we never get 100 per cent efficacy. We are aiming for 100 per cent efficacy but may get 50-100 per cent,” Dr Balram Bhargava, ICMR, Director-General said on Tuesday while responding to a query on the efficacy of COVID-19 vaccine.
Dr Bhargava answered in view of the draft guidelines published by the Central Drugs Standard Control Organisation (CDSCO) for the development of a vaccine with special consideration for the COVID-19 vaccine.
The draft guidelines further say that the pharma companies for a statistical final analysis plan finalised before closing the trial database and unblinking treatment assignments (if these were blinded). “This should include any planned interim analyses, which should be adequately addressed in terms of purpose, timing, and any statistical adjustments required.”
If a trial fails to meet the predefined criteria for superiority and/or non-inferiority with respect to any of the antigenic components, the possible reasons for the result and the clinical implications of it should be carefully considered before proceeding with clinical development or licensure, noted the guidance.
Safety assessments throughout clinical development and all pregnancies in study participants for which the date of conception is prior to vaccination or within 30 days after vaccination should be followed for pregnancy outcomes, including pregnancy loss, stillbirth, and congenital anomalies, it said.
COVID-19 vaccine trials should periodically monitor for unfavorable imbalances between vaccine and control groups in COVID-19 disease outcomes, in particular for cases of moderate to severe COVID-19 that may be a signal for vaccine-associated ERD. Studies should include pre-specified criteria for halting based on signals of potential vaccine-associated ERD.
It has also recommended the pharmaceutical companies to use an independent data safety monitoring board (DSMB) for vaccine-associated ERD and other safety signal monitoring, especially during later-stage development.