50 pc efficacy in phase 3 trials needed for COVID-19 vaccine approval: Drug authority's draft guidelines

A COVID-19 vaccine candidate should show at least 50 per cent efficacy during phase III of clinical trials for it to be widely deployed, according to a draft guidance document for vaccine developers issued by central drug authority.

However, equate data informing about potential risk of vaccine-associated Enhanced Respiratory Disease (ERD) will need to be generated, Central Drugs Standard Control Organisation (CDSCO) said in its draft 'Regulatory Guidelines for Development of Vaccines with Special Consideration for COVID-19 Vaccine'.

It said people with a history or laboratory evidence of prior vel coronavirus infection should be allowed to participate in trials if y did t have acute COVID-19 or or acute infectious illness.

draft guidelines have been uploed on CDSCO's website. It is seeking comments and feedback from public until October 12.

"To ensure that a widely deployed COVID-19 vaccine is effective, primary efficacy endpoint point estimate for a placebo-controlled efficacy trial should be at least 50 per cent...," guidelines said.

Considering urgent need for a safe and effective vaccine for prevention of COVID-19, clinical development programs of COVID-19 vaccine may proceed through an aptive and seamless approach.

"However, as applicable for any vaccine, regardless of wher clinical development programs proceed in discrete phases with separate studies or via a more seamless approach, an equate data, including data to inform potential risk of vaccine-associated Enhanced Respiratory Disease (ERD) will be needed," y said.

Consideration may be needed for conducting more than one vaccine efficacy trial in case different subs of a pathogen are involved, guidelines underlined.

In such cases, efficacy trials may be required to be conducted in different regions where certain subs are kwn to predominate.

It is anticipated that equately powered efficacy trials for COVID-19 vaccines will be of sufficient size to provide an acceptable safety database for younger ult and elderly populations, provided that significant safety concerns arise during clinical development that would warrant furr pre-licensure evaluation.

Speaking at a press conference on Tuesday, Dr Balram Bhargava, director-general, Indian Council of Medical Research, said all vaccines for respiratory viruses are t 100 per cent effective.

"re are three things for a vaccine -- first safety, second immugenicity and third efficacy. 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." According to CDSCO guidelines, as it is possible that a COVID-19 vaccine "might be much more effective in preventing moderate to severe versus mild COVID-19", consideration should be given for powering efficacy trials for formal hyposis testing on a severe COVID-19 endpoint.

Regardless, moderate to severe COVID-19 should be evaluated as a secondary endpoint (with or without formal hyposis testing) if t evaluated as a primary endpoint, guidelines said.

Establishing vaccine safety and efficacy in SARS-CoV-2 naïve individuals is critical, y ded.

Vaccine safety and COVID-19 outcomes in individuals with prior SARS-CoV-2 infection who might have been asymptomatic are also important to examine because pre-vaccination screening for prior infection may t be feasible in practice when COVID-19 vaccine is approved and introduced in market.

"refore, subjects with history or laboratory evidence of prior COVID-19 infection should t be excluded from  COVID-19 vaccine trial. However, subjects with acute COVID-19 or or acute infectious illness should be excluded from such trials," guidelines said.

Evaluation of vaccine safety and efficacy in phase III clinical trial in ults should include equate representation of elderly individuals and individuals with comorbidities, y said.

Furr, productive and developmental toxicity data should be re as per requirements specified in New Drugs and Clinical Trials Rules, 2019 to support inclusion of pregnant women and women of childbearing potential, y ded.

It is important for COVID-19 vaccines to plan for pediatric assessments of safety and effectiveness considering pandemic in accordance with New Drugs and Clinical Trials Rules, 2019.

After approval of a vaccine, it is essential to monitor vaccine safety in routine use, guidelines underscored.

y also recommended use of an independent Data Safety Monitoring Board (DSMB) for vaccine-associated ERD and or safety signal monitoring, especially during later st development.

In general, all vaccines, including those against coronavirus infection manufactured or imported into country, are required to comply with requirements and guidelines for chemistry, manufacturing and controls (CMC) specified in Drugs and Cosmetics Rules, 1945 and New Drugs and Clinical Trials Rules, 2019.

All vaccines are required to be characterised and manufactured in compliance with good manufacturing practices as prescribed in rules.