BARYCELA inj. is a lyophilized formulation containing live attenuated varicella virus.

[Composition]
Each 0.5ml of reconstituted vaccine contains,
API: Live attenuated varicella virus (Virus strain: MAV/06, cell line: MRC-5)….. ≥ 3,800 PFU
Buffering agent: Potassium dihydrogen phosphate …………………………………………… 0.06 mg
Dibasic sodium phosphate hydrate ………………………………………………………………… 1.14 mg
Sodium L-glutamate hydrate ………………………………………………………………………….. 0.40 mg
Sucrose …………………………………………………………………………………………………….. 18.21 mg
L-cysteine ……………………………………………………………………………………………………. 0.18 mg
Glycine ……………………………………………………………………………………………………….. 1.82 mg
Disodium edetate hydrate ……………………………………………………………………………… 0.18 mg
Urea …………………………………………………………………………………………………………… 0.87 mg
Gelatin (Animal-derived ingredient: derived from porcine skin) …………………………… 8.74 mg

Enclosed solvent: Sterile water for injection (diluent) ……………………………………….. 0.7 mL

[Description]
This vaccine is a white lyophilized formulation for injection contained in a colorless and transparent vial, and appears colorless or light yellow when reconstituted with the enclosed solvent.

[Indication and usage]
This vaccine is indicated for active immunization for the prevention of varicella in children from 12 months to 12 years of age.

[Dosage and administration]

1. Recommended Dose
   The entire quantity of this vaccine (approximately 0.5 mL) shall be subcutaneously injected once on the upper arm (brachia lateral). Do not administer this product intravascularly or intramuscularly.

2. Reconstitution Instructions
   To reconstitute this vaccine, fill a syringe with the entire quantity of the enclosed diluent, and inject it into the vial containing the lyophilized vaccine. Then, agitate the vial to mix completely. Fill a syringe with the entire quantity of this solution, and then inject the entire quantity (approximately 0.5 mL) subcutaneously on the brachia lateral. To minimize the loss of potency, this drug must be administered immediately after preparation, and it must be discarded if it is not used within 30 minutes after preparation.

[Precautions for Use]

1. This vaccine is contraindicated to the following patients:
   1. Patients who have hypersensitivity reactions to the component of this vaccine, such as gelatin;
   2. Patients who are in a state of primary and acquired immunodeficiency due to the following conditions:
      Acute and chronic leukemia, lymphoma or other conditions affecting the bone marrow/lymphatic system, immunosuppression due to HIV/AIDS, cell-mediated immunodeficiency;
   3. Patients receiving immunosuppressive therapy (Since BARYCELA inj. is a live attenuated varicella vaccine, rash or disseminated disease may manifest more severely if it is administered to patients with immunodeficiency, patients receiving immunosuppressive therapy, and patients being administered immunosuppressive doses of corticosteroids.);
   4. Patients with untreated active tuberculosis;
   5. Pregnant women and women of childbearing potential (see section “5. Administration in pregnant women and nursing mothers”);
   6. Patients with febrile respiratory disease or other febrile infections.
2. Adverse drug reactions (ADR)

1. The information on adverse drug reactions obtained from the safety evaluation of this vaccine in 484 pediatric subjects from 12 months to 12 years of age is shown below. After vaccination, adverse drug reactions occurred in 275 subjects (56.8%).
2. Local reactions: Reactions such as pain, tenderness, and erythema/redness may occur.
3. Systemic reactions: Systemic reactions such as cough, fever, and anorexia/loss of appetite may be shown after vaccination.
   ①Solicited local site/systemic adverse drug reaction that were observed for 7 days after vaccination with this drug are as follows:

② Unsolicited adverse drug reactions observed for 42 days after this vaccination were reported in 70 subjects (14.5%) out of 484 pediatric subjects from ≥ 12 months to ≤ 12 years of age. Adverse drug reactions related to infections and infestations were most prevalent with 48 cases in 46 subjects (9.5%). ADRs related to general disorders and administration site conditions, ADRs related to gastrointestinal system disorders, and ADRs related to skin and subcutaneous tissue disorders were shown in 11 cases in 11 subjects (2.3%), 10 cases in 9 subjects (1.9%), and 11 cases in 10 subjects (2.1%), respectively. The adverse drug reactions occurred as shown below. (rarely: 0.1 to < 5%)

– Infections and infestations

Occasionally: Adenoviral conjunctivitis, bronchitis, infectious diarrhea, viral gastritis, gastroenteritis, viral gastroenteritis, herpangina, impetigo, nasopharyngitis, pharyngitis, bacterial tonsillitis, upper respiratory tract infection, varicella, viral infection, viral pharyngitis

– Systemic disorders and administration site conditions
Occasionally: Fever, injection site reaction

– Skin and subcutaneous tissue disorders
Occasionally: Dermatitis, atopic dermatitis, rash, papular rash, vesicular rash- Gastrointestinal system
Occasionally: Diarrhea, food poisoning, gastrointestinal inflammation, vomiting

– Respiratory system
Occasionally: Epistaxis

– Vascular disorders
Occasionally: Hypertension

③ After this vaccination, 40 cases (1 case each of diarrhea, gastrointestinal inflammation, influenza-like illness, and fever; 8 cases of bronchitis; 1 case of infectious croup; 1 case of infectious diarrhea; 4 cases of gastroenteritis; 1 case of rotaviral gastroenteritis; 1 case of viral gastroenteritis; 1 case of hand-foot-mouth disease; 1 case of flu; 1 case of pharyngitis; 4 cases of pneumonia; 1 case of bacterial pneumonia; 1 case of respiratory syncytial virus pneumonia; 4 cases of viral pneumonia; and 1 case each of tonsillitis, bacterial tonsillitis, viral pharyngitis, accidental exposure to drugs, accidental exposure to drug packaging materials, and laceration) of serious adverse events occurred in 36 subjects (7.4%) out of 484 subjects during a period of 6 months. Among the serious adverse events that occurred, there were 4 cases (1 case each of gastrointestinal inflammation, infectious diarrhea, viral gastroenteritis, and viral pharyngitis) of serious adverse drug reactions that were related to this drug.

④ During a period of 42 days after this vaccination, one or more varicella-like rash occurred in a total of 9 subjects (1.9%) out of 484 subjects.

In the case of the varicella-like rash that occurred during a period of 42 days after vaccination, samples were taken from the subjects’ lesion sites and VZV genotyping was performed. The results were “not detectable” for 7 subjects and 1 subject was confirmed as having wild type. VZV genotyping was not performed for the remaining 1 subject since only a phone call visit was made and a blister swab could not be collected.

1. General precautions

1. The duration of prophylaxis of this vaccine against varicella infection is unknown.
2. Efficacy has not been established for multiple injections of this vaccine. The necessity for a second vaccination is unclear.
3. As with other vaccines, this vaccine does not have prophylactic effects in every vaccinated individual.
4. As with other vaccines, appropriate emergency measures, including epinephrine injections (1:1000), shall be available for immediate use since anaphylaxis/anaphylactoid reactions may be shown after vaccination.
5. If acute conditions such as fever exceeding 38℃ are shown, postponement of vaccination shall be considered.
6. If blood or plasma was transfused, or if immunoglobulins or varicella-zoster immunoglobulins were administered, this vaccine shall be administered after a minimum vaccination interval (3 to 11 months) has passed, depending on the type and dose of the blood or immunoglobulin formulation.
7. This vaccine must not be administered concomitantly with immunoglobulins, including varicella-zoster immunoglobulins. In addition, immunoglobulins must not be administered for 2 months after this vaccination, unless the benefits of administration of all immunoglobulins including varicella-zoster immunoglobulins outweigh the benefits of the vaccination.
8. As Reye’s syndrome has been reported after the use of salicylate for natural varicella infection, the vaccinated individual shall avoid using salicylate for 6 weeks after vaccination.

9. The viral transmission of the vaccine was unknown in the clinical trials on this vaccine. However, in the case of a similar vaccine, post-marketing study verified that the virus can be transmitted through contact between healthy vaccinated individuals showing a varicella-LIKE rash and healthy but susceptible individuals in rare cases. In addition, transmission of the virus from vaccinated individuals who do not manifest a varicella-LIKE rash has been reported. Thus, if possible, vaccinated individuals shall avoid close contact with highly susceptible individuals for 6 weeks. If contact with individuals having high-risk susceptibility cannot be avoided, the potential risks of viral transmission due to the vaccine and the risks of acquisition and transmission of natural varicella virus shall be compared. Individuals with high-risk susceptibility are as follows:
   ● Immunocompromised persons;
   ● Pregnant women without medical history of varicella or evidence of infection based on clinical test results;
   ● Newborns of pregnant women without medical history of varicella or evidence of infection based on clinical test results.

1. Drug Interactions

1. Refer to section “3. General precautions” for matters regarding immunoglobulins, salicylate, and transfusions.

1. Administration in pregnant women and nursing mothers

1. The safety of this vaccine when administered to pregnant women has not been evaluated. However, pregnant women shall not be given this vaccine since naturally occurring varicella-zoster virus infection is sometimes known to have harmful effects on the fetus. In addition, pregnancy shall be avoided for 3 months after vaccination (see section “1. This vaccine must not be administered to the following patients”).
2. It is unknown whether live attenuated varicella virus is secreted in human milk. However, since some viruses are secreted in human milk, caution shall be taken when administering this vaccine to nursing mothers.

1. Administration in children
   This vaccine shall not be administered to children aged < 12 months since its safety and efficacy have not been established for children of this age.
2. Administration in the elderly
   This vaccine shall not be used in adults including the elderly for the purpose of prophylaxis against varicella.
3. Precautions for application

1. This vaccine shall be stored under refrigeration. It shall be taken from the refrigerator and prepared immediately prior to vaccination, and once dissolved, it shall be used within 30 minutes. The prepared vaccine must not be frozen.
2. Separate sterile needles and syringes shall be used for each individual to prevent transmission of infectious diseases. Once used, the needles must not be reused and must be appropriately discarded.
3. When preparing this vaccine, it must be dissolved with its own enclosed solvent since there are concerns of virus inactivation if preservatives or antiviral substances are present in the solvent.

1. Precautions for storage and handling

1. Placing the vaccine in a different container may be the cause of accidents and is undesirable in terms of maintaining quality.
2. This vaccine must not be used by being dissolved together or mixed with other drugs, including other virus vaccines.

1. Precautions for use by specialists

1. Information on pharmacological action
   As a live attenuated varicella vaccine made of the varicella-zoster virus (attenuated MAV/06 strain), this vaccine induces immune response to varicella infection.
2. Information on clinical trial
   The immunogenicity of this vaccine was evaluated in a randomized, double-blind, multicenter, multinational, active-controlled, non-inferiority study in healthy children aged from 12 months and to 12 years, 515 children were randomized and received either BARYCELA(N=258) or active control (N=257).. The results of performing an evaluation of the primary immunogenicity in 478 subjects included in the per protocol set (PPS) showed that the seroconversion rate assessed by the fluorescent-antibody-to-membrane-antigen (FAMA) assay for antibody titer satisfied the non-inferiority criterion.
   The following table shows the statistical analysis of non-Inferiority in seroconversion rate at 42days post-vaccination in a phase 3 clinical trial.

1. Information on nonclinical trial
   No significant findings that may be of particular interest to humans were identified in the results of repeat-dose toxicity and local tolerance studies performed on this vaccine.

[Storage Method and Shelf Life]
Store under refrigeration at 2–8°C in a light-shielded, airtight container. The shelf life is 24 months from the date of manufacture.

[Packaging Unit]
1, 10 vial/box (≥ 3,800 PFU), Enclosed diluent vial (0.7 mL)

GC Biopharma Corp.
40, Sandan-gil, Hwasun-eup, Hwasun-gun,Jeollanam-do, Korea