[Press Release, Jan 21, 2021 / unofficial translation ]


Updates on the approval and review of COVID19 therapeutics and vaccines (2)


1. Current status of Approval/Review of COVID-19 Therapeutics

□ The Ministry of Food and Drug Safety (MFDS, Minister Kim Ganglip) completed a survey of the manufacturer and clinical trial site (medical institution) concerning the approval of Regkirona Inj.. which Celltrion has applied for. Currently, the MFDS is conducting an additional review of nonclinical, clinical trial data and the quality data.


<< Document Review (Quality) >>
□ Quality data demonstrates the management of the therapeutic’s manufacturing process and quality, among others, and includes data on the physicochemical and biological characteristics of the drug substance and the finished product, manufacturing methods, specifications and analytical procedures (including evidence), reference standards, containers, and packaging.
○ Moreover, considering the candidate treatment is recombinant, MFDS evaluate data for management of drug substance, separation/purification for each process, stability data for establishing storage condition and shelf life.

<< Inspection of the Clinical Trial Site (Medical Institution) >>
□ MFDS checked the compliance of regulations throughout the clinical trial to ensure the safety of the clinical trial subjects and the reliability of the test results, e.g. the compliance of patient consent forms, the management of medicines for the clinical trial, and the management of electronic data through document review and on-site inspection (January 12?15).
○ In addition, the MFDS thoroughly reviewed whether overseas medical institutions conducted clinical trials in accordance with the reliability and international ethical standards of clinical trials through document reviews.


2. Current status of Approval/Review of COVID-19 Vaccine
□ MFDS has completed a inspection of the manufacturing site concerning AstraZeneca Korea has applied for the approval of AstraZeneca COVID-19 Vaccine Inj.. Currently MFDS is currently conducting a review of nonclinical, clinical trial data and the evaluation of quality data.

<< Document Review (Clinical Trials) >>
< Efficacy >
○ The preventive effect of the vaccine is analyzed and evaluated through the proportion of infected patients in the vaccine group (test group) and the placebo group (control group) when the number of patients infected with COVID-19 among clinical trial participants reaches the target number.
* recommendation of World Health Organization (WHO) : primary efficacy endpoint estimate of a COVID-19 should be at least 50%.

< Safety >
○ The MFDS evaluates the safety of vaccines by combining the results of four clinical trials conducted in the United Kingdom (UK; two cases), Brazil, and South Africa.
- By concurrently monitoring the vaccine and placebo groups, the MFDS compares and evaluates all solicited* or unsolicited adverse events that occur within 28 days after vaccination (A long-term follow-ups should be one year after vaccine administration).
* solicidated adverse events: pain at the injection site, nausea, fever, headaches, muscle pain, joint pain, etc.
- The MFDS intensively reviews life-threatening or serious adverse events, such as anaphylaxis and death.
- The causal relationship between the adverse event and the vaccine is evaluated, and in the case that a causal relationship is determined, the MFDS will examine whether to manage the adverse event as an intensive safety review item.
○ The MFDS compares the vaccine group and the placebo group to search for any safety information that requires special attention for the elderly over 65 years of age.
- For reference, the proportion of elderly patients over 65 years of age in 4 clinical trials evaluated at the time of emergency use approval in the UK is approximately 10% of the people subject to safety assessments.
○ MFDS will conducted comprehensively the nonclinical and clinical trial data, which will be reflected in the precautions for authorization.

<< Documetn Review (Quality) >>
□ Quality data are the information on the manufacturing process management and quality management of the therapeutics. In particular, the MFDS reviews data on the physicochemical and biological properties, manufacturing methods, standards and test methods, standard products, containers, and packaging of raw material medicines and finished medicines.
○ Moreover, the MFDS is reviewing the impurity removal verification data for each process, and safety test data to establish storage methods and use periods.

<< Evaluation of Good Manufacturing Practices (GMPs) >>
□ To ensure that the vaccine manufacturer has the suitable facilities and quality assurance system to produce the vaccines with consistent quality, the MFDS conducted an on-site inspection (January 18?20) of the manufacturing facility (SK Bioscience).
○ This approval application product is a viral vector vaccine, which uses a virus (as a carrier), unlike general vaccines. As such, the MFDS has additionally confirmed the matters related to the management of genetically modified organisms (GMO) and the biosafety level (BSL) in the manufacturing facility.
○ Given that the vaccine is a sterile injectable, the MFDS has conducted an on-site inspection to confirm whether the manufacturing site has facilities and the environment to prevent contamination from fine particles and microorganisms and maintain the required level of cleanliness.
○ In addition, the MFDS monitored the actual manufacturing records and quality inspection records for the finished medicines that have already been produced and the undiluted solution in the raw material stage, as well as reviewed data reliability.

□ The MFDS’s GMP evaluation and management capabilities for domestic vaccine manufacturers are internationally recognized through the prequalification (PQ) certification of WHO.
○ Currently, 19 vaccines from 5 Korean domestic companies have received PQ certification from WHO and are internationally supplied to UN-affiliated organizations, such as the United Nations International Children’s Emergency Fund (UNICEF).
- In 2016, a Memorandom of Understanding was signed between the MFDS and WHO, replacing WHO’s field inspection based on the GMP due diligence report provided by the MFDS.


3. Plans for Approval and Evaluation
○ (Therapeutics) The MFDS requested (January 20) Celltrion to provide quality data on the Celltrion’s Regkirona Inj., that have not yet been submitted. Upon submission, the MFDS will continue the evaluation.
- The MFDS will synthesize the evaluation results and receive advice from the Central Pharmaceutical Advisory Committee, a legal advisory body of the MFDS, on the safety, efficacy, and matters to be considered during the approval process on January 27 (Wed). Then, the MFDS will announce the results on the same day.
○ (Vaccine) In relation to AstraZeneca’s AstraZeneca COVID-19 vaccine, the MFDS requested (January 15) AstraZeneca to submit additional data necessary for evaluation, such as nonclinical, clinical, and quality data. As soon as the data are submitted, the MFDS will review the efficacy, feasibility, and safety of the applied dose and dosage and focus on the assessment of the quality for national lot release.
- Concerning the clinical trial data, the MFDS will hold the Advisory Committee for the Safety and Efficacy Assessment of COVID-19 Vaccine meeting on January 31 (Sun) and announce the results on February 1 (Mon).

□ The MFDS will thoroughly and scientifically verify the safety and efficacy of COVID-19 therapeutics and vaccines and continue to exert its best efforts to ensure objectivity and transparency by collecting various opinions from experts.