COVID-19 Vaccine Development and HSA's Pandemic Special Access Route

Overview of Vaccine Development

Vaccines typically take several years to develop, register and enter the market due to the fact that vaccine developers typically follow a linear sequence of steps for the following:

• Vaccine candidate selection;

• Preclinical studies;

• Phase I-III clinical trials;

• Final large-scale commercial manufacturing; and

• Filing to regulators for marketing authorisation

• Marketing

• Post-market follow-up

Vaccine developers follow the steps listed under standard vaccine development, but these have been compressed and accelerated in under a year due to these factors:

• Global cooperation through sharing of genetic information and research developments since early January 2020;

• Knowledge gained from the previous severe acute respiratory syndrome (SARS) enabled more targeted research in vaccine development;

• Large investments in vaccine developments worldwide, regardless of the potential outcome;

• Pharmaceutical companies in consultation with regulators have adopted innovative and efficient trial designs to conduct multiple trials concurrently while maintaining the scientific rigour; and

• Some companies have also leveraged international clinical trial networks to select trial sites with high infection rate, enabling rapid enrolment into the trials.

Pre-Clinical Testing

Once vaccines are developed in the laboratory, they must go through pre-clinical testing in animals to ensure they are safe for use, before they enter clinical trials to be tested on humans.

Clinical Trials

Clinical trials of vaccines in humans comprise three phases:

• Phase I trials usually involve small groups of healthy volunteers (e.g. 20-100) using a range of doses to ensure the vaccine is safe for use in humans, find out if the vaccine elicits the intended immune response (i.e. stimulates the body to produce antibodies) in humans, and assess the safest doses for further testing in Phase II trials.

• Phase II trials involve a larger group of people (e.g. >100) with characteristics (e.g. age, physical health) similar to the population for whom the vaccine is intended, to further evaluate the vaccine’s safety and ability to produce the intended immune response in a more diverse group of people.

• Phase III trials include thousands of people to confirm its efficacy and safety in the intended population.

Clinical trials are traditionally conducted sequentially, with each phase building on the results of the previous phase.

Clinical trials have been designed to be innovative and efficient, enabling the companies to conduct multiple trials in parallel or to combine different phases of a clinical trial, while maintaining the scientific rigour. Such regulatory agility and flexibility allow for speedier development and evaluation.

Some companies have also leveraged international clinical trial networks to select trial sites with high infection rate, enabling rapid enrolment into the trials.

HSA's Review & Evaluation

For routine vaccine registration purposes, the manufacturer will need to make an application to HSA to register the products with the complete pre-clinical, clinical and manufacturing data to substantiate the quality, safety and efficacy of the products at the point of application and demonstrate that the benefits outweigh the known risks for use in our population.

Under PSAR, companies can submit data on a “rolling”, or staggered basis and continue their clinical trials and development while HSA reviews the submitted data concurrently, instead of waiting for the full data set to be submitted before starting evaluation.

Hence, evaluation can potentially be completed in a shorter time, by working expeditiously on the available rolling data. As with other new vaccines undergoing routine registration, data submitted by companies under PSAR will be robustly and thoroughly reviewed by HSA’s regulators, in accordance with international scientific standards during the evaluation.

Although companies can start submitting data from the early development stages, HSA will only grant PSAR authorisation if there is reasonable quality, safety and efficacy data suggesting that the potential benefits outweigh the known risks.

HSA also consults with and presents our assessment and recommendations to our Medicines Advisory Committee and Panel of Infectious Diseases Experts before granting any interim authorisation.

Ongoing data must continue to be submitted post-authorisation to transition the status of the vaccine from PSAR interim authorisation to full registration.

Vaccine Safety Monitoring

Following regulatory approval and registration of a vaccine, HSA’s post market surveillance programme allows for the continual monitoring of the safety profile to ensure that the benefit continues to outweigh the known risks after the vaccine has been in use in wider clinical setting.

In addition to the existing pharmacovigilance system that is already in place, HSA will actively monitor the safety profiles of the COVID-19 vaccine and use data analytics to detect safety signals. This will enable HSA to take swift regulatory actions should any safety concern emerge.