AZ has applied for domestic approval of COVID-19 vaccine

Clinical data conducted in the UK and Brazil were submitted, under the condition of two doses of 18 years of age or older

The MFDS announced today (4th) that AstraZeneca Korea's application for item approval for COVID-19 vaccine (code name: AZD1222) has been received.

 

This vaccine is a 'viral vector vaccine' manufactured by putting COVID-19 surface antigen gene into a chimpanzee adenovirus vector.

 

Viral vector vaccines are manufactured by inserting viral antigen genes that cause infectious diseases into other viral genes used as carriers and mass-producing them.

 

AstraZeneca vaccine uses adenovirus, which only infects chimpanzees, as a carrier to deliver COVID-19 surface antigen gene into human cells, and the delivered COVID-19 antigen gene synthesizes antigen proteins in the body to induce the production of neutralizing antibodies.

 

US Johnson & Johnson (Janssen) vaccine was developed using a viral vector method.

 

The expected target of AstraZeneca’s vaccine is 18 years of age or older, and the expected dosage is administered twice 4 to 12 weeks after one vaccination.

 

This is the same as indications and dosages approved for emergency use in the UK, and the storage conditions are 2-8℃.

 

AstraZeneca is currently conducting phase III clinical trials in 10 countries including the UK, Brazil and the US.

 

The clinical trial was discontinued (September 6, 2020) due to an unexpected AEFI (one case of transverse myelitis).

 

As a result of safety review, clinical trials were resumed (October 23, 2020, USA, and September 12, 2020, UK) because there was no direct relationship with the vaccine.

 

Transverse myelitis is an inflammatory syndrome that affects the spinal cord and can be caused by a viral infection.

 

However, no direct association with the vaccine was found in this study.

 

The UK confirmed the preventive effect of 11,636 people in the vaccine clinical trial of AstraZeneca and made an Emergency Use Authorization on December 30, and the European Medicines Agency (EMA) has been conducting a preliminary review since October last year.

 

AstraZeneca Korea applied for the approval for products that are consigned to SK Bioscience, a domestic pharmaceutical company, and for products manufactured overseas such as Italy.

 

Item approval/examination data include non-clinical trials, clinical trials, quality, risk management plans, and manufacturing/quality control data.

 

Non-clinical data is a verification of toxicity and effectiveness through animal testing prior to administration of a drug to humans.

 

Clinical trial data confirm the effectiveness and safety when administered to humans.

 

Unlike the clinical evaluation of general medicines that show therapeutic effects, it is important to evaluate the effectiveness of vaccines to prevent infection after vaccination in healthy people.

 

The prophylactic effect (%) in the clinical trial is calculated based on the proportion of infected people who developed each after vaccination in the vaccination group and placebo group.

 

For example, in a phase III clinical trial in which 10,000 people each vaccinated and placebo vaccinated, 10 confirmed cases out of the vaccinated group and 100 confirmed cases out of the placebo vaccinated group occurred, the probability of infection of the vaccinated group Is 1/10 compared to the placebo group, so the effect of preventing COVID-19 infection is calculated as 90%.

 

Looking at the WHO's considerations for COVID-19 vaccine evaluation, it is recommended that the standard of preventive effect of COVID-19 vaccine be at least 50%.

 

The safety is checked and evaluated whether abnormal cases occur after vaccination, and the safety of the vaccine is collected through long-term tracking such as serious abnormal cases.

 

In the 'Guidelines on clinical evaluation of vaccines' by the WHO, it is recommended to follow up for at least 6 months for general vaccines and at least 12 months for vaccines containing immune boosters.

 

It is recommended to perform follow-up observation for at least 1 year in the case of COVID-19.

 

Quality data are data related to the manufacturing process control of the drug and'standards and test methods' for quality control.

 

In addition, the risk management plan (RMP) is data on a comprehensive safety management plan that includes measures to minimize the occurrence of hazards for safety management after marketing.

 

Risk Management Plan (RMP) refers to a comprehensive safety management activity plan that is carried out to collect, investigate, test, and minimize risk occurrence of information on safety and effectiveness over the entire cycle before and after drug approval and marketing.

 

GMP implementation status evaluation data are 10 kinds of data, including facility·environmental management and quality assurance system related to the item for which the license is applied.

 

Good Manufacturing Practice (GMP): Refers to the standards that pharmaceutical manufacturers must comply with throughout facilities, equipment and production processes in order to manufacture excellent pharmaceuticals with guaranteed quality.

 

In addition to general GMP evaluation data, AstraZeneca’s vaccine will be evaluated according to the characteristics of the virus carrier vaccine, such as management of biological raw materials and genetically modified organisms used in manufacturing, and biological safety level (BSL), the MFDS explained.

 

AstraZeneca’s vaccine is planned to be produced in the US, UK, and Italy, as well as SK Bioscience in Korea.

 

As for the quality data, SK Bioscience is currently submitting additional quality data on the original vaccines and finished drugs produced in Korea under consignment from AstraZeneca Company to the AstraZeneca headquarters.

 

AstraZeneca, the original developer, reviews the data to analyze and verify the quality equivalence between the vaccine used in the clinical trial and the vaccine consigned to SK Bioscience in Korea.

 

AstraZeneca prepares data including the results of quality equivalence evaluation between manufacturing sites, and AstraZeneca Korea plans to quickly submit the data to the MFDS.

 

Among the clinical trial data, additional data obtained by collecting and analyzing vaccine adverse events through a planned 12-month follow-up will be submitted, which is the same worldwide.

 

The clinical trial data submitted by AstraZeneca are data from phase I to III being conducted in the UK and Brazil, and the trial is still ongoing for the safety evaluation of the vaccine and is expected to be completed in September 2021.

 

The safety evaluation method of the vaccine is applied to other vaccine methods in the same way, and Pfizer’s vaccine and Moderna’s vaccine will be equipped with additional long-term safety data through follow-up.

 

The MFDS has announced that it will thoroughly verify the safety and effectiveness through the screening of experts in each field and external experts of COVID-19 vaccine and treatment license examination team so that the public can receive a safe and effective COVID-19 vaccine.

 

The MFDS aims to shorten the existing processing period (180 days or more) and process it within 40 days for the rapid approval and review of COVID-19 vaccine and treatment, including the product for this approval.

 

The MFDS is conducting a preliminary review on non-clinical and quality data (non-clinical 10.6~, quality 12.18~) at the request of AstraZeneca Korea and requested data supplementation for nonclinical data.

 

In addition, it is reported that the AstraZeneca vaccine, commissioned and manufactured by SK Bioscience, is preparing for the nation's lot release the fastest.

 

It is explained that the manufacturer's detailed test method was obtained at the end of August last year, and the test method was established at the end of December after receiving reagents such as standard products in November.

 

Vaccines used in the pandemic of infectious diseases are subject to rapid lot release and will be treated preferentially over lot release drugs in other countries, and they plan to quickly complete the national lot release within 20 days, which usually takes 2-3 months or more.