Korea needs to change the paradigm of vaccine development radically to shorten the development time under a global pandemic scenario, a government report said.

The Korea Health Industry Development Institute released a report on the nation’s clinical trial strategy for vaccine development to respond to the next pandemic.

According to the report, building a system to develop vaccines to respond to Covid-19 variants quickly and a pandemic of a new pathogen has emerged as a pivotal issue in global healthcare.

The international community, including Coalition for Epidemic Preparedness Innovations (CEPI), said if the world had developed a Covid-19 vaccine within 100 days of the first Covid-19 outbreak, it would have reduced 67 million Covid-19 cases to 3.8 million as of Dec. 8, 2020. It would have started vaccination on May 8, 2020, to prevent millions of deaths and economic losses.

According to the report, CEPI began a “100-day Mission” to complete vaccine development within 100 days of recognizing the need for a vaccine.

It established five goals – building a vaccine library for representative pathogens (prototypes), securing vaccine safety data against representative pathogens in advance, developing a quickly-applicable vaccine platform and analysis method, maintaining production capacities and clinical trial networks for rapid development and manufacturing of a vaccine, and building governance to form global partnerships and share financing and data.

Regarding maintaining capacities and clinical trial networks for rapid development and manufacturing of a vaccine, the KHIDI’s report introduced the rapid clinical trial strategy applied to the development of Covid-19 vaccines.

The report said Moderna’s vaccine development stirred ethical issues because Moderna skipped a preclinical trial on animals and directly began a human clinical trial.

However, the report noted that the decision was based on the judgment that if the information necessary for clinical trials was available from sources other than animal testing or if there was sufficient animal testing data for a vaccine similar to a Covid-19 vaccine candidate, the company could start a phase 1 study without animal testing in emergencies like Covid-19.

For swift vaccine development, some companies used a “seamless design,” combining phase 1 and 2, phase 2 and 3, or phase 1, 2, and 3.

By combining two or three stages of clinical trials, this strategy could save time for regulatory approval, administrative procedures, and clinical trial settings.

Pfizer used this strategy for its Covid-19 vaccine development.

While it took 19 weeks for Moderna to conduct phase 1 and 2 trials and begin a phase 3 study, Pfizer spent only 13 weeks to start a phase 2/3 trial by combining phase 1-3 studies.

Some governments also used a quick vaccine development strategy. For example, clinical trial networks through the U.S. Clinical Trials Transformation Initiative (CTTI), the U.K. Clinical Research Collaboration (UKCRC), and Europe’s Life Science Research Infrastructures (LS RIs) were actively used for Covid-19 vaccine and treatment studies.

The global clinical trial network was used for large-scale clinical trials, and the selection of institutions considering their trial capacity and Covid-19 incidence made it possible to recruit participants in the shortest time, the KHIDI’s report said.

The fast Covid-19 vaccine development was also possible because regulatory agencies revised clinical trial guidelines.

As herd immunity against Covid-19 was urgently needed, the U.S. FDA lowered the standard for vaccine efficacy, and some other regulatory agencies applied a “rolling review” process to make decisions on clinical trial approval and vaccine approval as quickly as possible KHIDI said in the report.

For a rolling review, the regulator begins evaluation in sub-fields such as preclinical, clinical, toxicology, and standard test methods as soon as it receives data from a drugmaker, rather than starting the review after receiving all the required data.

After leading pharmaceutical firms obtained approval for Covid-19 vaccines, others used a comparative clinical trial. This is because it is almost impossible to conduct a placebo-controlled trial due to ethical issues after a certain vaccine’s efficacy is disclosed or a vaccine is authorized.

A comparative clinical trial can reduce costs and time because the number of participants can be lowered from tens of thousands to thousands. However, while it solved the problem of massive recruitment when the vaccination rate was high, it also faced the problem of securing a controlled vaccine when the vaccine supply was in shortage during the Covid-19 pandemic.

AstraZeneca, Moderna, and Pfizer used placebo groups in their vaccine trials.

However, France’s Valneva obtained approval for a phase 3 comparative trial of VLA2001, using AstraZeneca’s vaccine as a control vaccine in April 2021. Then, the company won the EU’s marketing approval on June 24, 2021.

SK Bioscience also conducted a phase 3 comparative trial and scored the nod for SKYCovione from the Ministry of Food and Drug Safety on June 29.

In light of these examples, to develop a vaccine rapidly, it is necessary to apply an adaptive clinical design, develop the vaccine’s efficacy evaluation indicators early, and build a global clinical trial network, the KHIDI said.

“To prepare for a future pandemic, we should build a stable vaccine R&D infrastructure with a long-term perspective,” the KHIDI said. “Excellent studies should get the government’s research grants on a large scale. In addition, the government should thoroughly manage the research procedure to achieve good outcomes.”

The KHIDI also noted that the nation should strengthen the weak areas in vaccine development by building the capacity to identify pathogens and disease characteristics early, come up with a strategy to recruit clinical trial participants, and establish a platform to share information on benefit-risk measures.

“It is necessary to establish a strategic system, along with nurturing experts so that innovative trial methods such as adaptive studies, practical trials, and simulation research could be revitalized in Korea,” it said.