【Drug Name】
Generic Name: Quadrivalent Influenza Virus Subunit Vaccine
Commodity name: Huierkangxin
English name: Quadrivalent Subunit Influenza Vaccine
Hanyu Pinyin: Sijia Liugan Bingdu Yadanwei Yimiao
【Ingredients】
This product is made by inoculating chicken embryos with influenza A and B (referred to as influenza) virus strains recommended by the World Health Organization (WHO), and then cultured, harvested viral fluid, ultrafiltration concentration, virus lysis centrifugation, purification, virus inactivation, and repurification to harvest hemagglutinin and neuraminidase. Free of preservatives and antibiotics.
This product contains egg ingredients.
Active ingredients: Hemagglutinin of various types of influenza virus strains used that year. This product contains per 0.5ml:
A/Victoria/2570/2019(H1N1)pdm09-like virus 15µghemagglutinin
A/Darwin/9/2021(H3N2)-like virus 15µghemagglutinin
B/Phuket/3073/2013(B/Yamagata lineage)-like virus 15µghemagglutinin
B/Austria/1359417/2021(B/Victoria lineage)-like virus 15µghemagglutinin
Excipients: sodium dihydrogen phosphate, anhydrous disodium hydrogen phosphate, sodium chloride.
【Properties】
This product is an injection and is a slightly milky white liquid.
【Vaccination target】
This product is used for people aged 3 and above; It is especially recommended for susceptible people and people who are prone to related complications, such as children, the elderly, the frail, and people in influenza-endemic areas.
【Function and use】
After vaccination with this product, it can stimulate the body to produce immunity against influenza virus. It is used to prevent influenza caused by vaccine-related influenza viruses.
【Specifications】
0.5ml per vial. The human dose is 0.5ml per 1 time, and the hemagglutinin containing various types of influenza virus strains should be 15μg.
【Immunization Procedure and Dosage】
(1) Intramuscular injection into the deltoid muscle on the lateral side of the upper arm.
(2) Vaccination before or during the influenza season. People aged 3 years and older receive 1 dose, each dose is 0.5ml.
【Adverse reactions】
According to the classification of the incidence of adverse reactions recommended by the International Committee of Medical Science Organizations (CIOMS): very common (≥ 10%), common (1%-10%, including 1%), occasional (0.1%-1%, including 0.1%), rare (0.01%-0.1%, including 0.01%), very rare (<0.01%), the summary safety information is described as follows:
(1) Clinical trials of this product
Two clinical studies of this product have been carried out in China. A total of 3,240 subjects aged 3 and over were enrolled, of which 1,619 subjects were inoculated with at least one dose of this product. The safety observation of this product system is from the beginning of vaccination to 30 days after the full vaccination, and the long-term safety observation is from 31 days to 180 days after the full vaccination.
systemic adverse reactions
Common: fever, cough;
Occasionally: headache, runny nose, chest pain, fatigue, nausea, vomiting, abdominal pain, diarrhea, arthralgia, myalgia, maculopapular rash;
Rare: loss of appetite, pain in extremity.
local adverse reactions
Common: pain, swelling;
Occasionally: erythema, pruritus, induration;
Rare: cyanosis.
(2) Domestic and overseas clinical trials of similar products
In addition to the above adverse reactions, the following adverse reactions were also observed in domestic and overseas clinical trials of similar products:
systemic adverse reactions
Very common: malaise, gastrointestinal symptoms, lethargy, irritability;
Common: chills;
Occasionally: dyspnea, dysphagia, nasopharyngitis, tonsillitis, allergy, dizziness, lymphadenopathy;
Rare: palpitations, macular rash, constipation, hypersensitivity reactions, pruritus, nasal congestion, increased sputum production, throat irritation, hyperhidrosis, allergic purpura.
local adverse reactions
Very common: redness;
Uncommon: ecchymosis;
Rare: rash, pallor, discoloration.
(3) Post-launch monitoring of similar products overseas
In addition to the safety information in clinical trials, the safety data obtained from post-market monitoring of similar overseas products (generated by spontaneous reports from a population of unknown size, cannot accurately estimate the incidence of symptoms or effectively evaluate the correlation between symptom occurrence and vaccine use) The summary is as follows:
Digestive: Abdominal pain/discomfort, swelling of the mouth/throat/tongue;
Blood and lymphatic system: transient thrombocytopenia;
Infections and invasive diseases: injection site cellulitis;
Nervous system: convulsions, encephalomyelitis, facial paralysis, Guillain-Barré syndrome, myelitis, neuritis, paresthesias, syncope;
Respiratory system: asthma, bronchospasm;
Cardiovascular system: tachycardia, vasculitis;
Skin system: angioedema, Stevens-Johnson syndrome, sweating, urticaria;
Eyes: conjunctivitis, eye pain/redness/swelling, eyelid swelling;
Immune system: anaphylactic shock, serum sickness.
【Taboo】
(1) Those who are known to be allergic to any ingredients contained in this product, including eggs, excipients, formaldehyde, and Triton N-101.
(2) Suffering from acute disease, severe chronic disease, acute exacerbation of chronic disease, cold and fever.
(3) Those with uncontrolled epilepsy and other progressive neurological diseases, and those with a history of Guillain-Barré syndrome.
【Precautions】
(1) Use with caution in the following situations: family and personal history of convulsions, chronic diseases, history of epilepsy, allergies.
(2) Prefilled syringes with cracks, unclear or invalid labels, turbid vaccines, lumpy flocs that cannot be shaken, and other abnormal appearances are not allowed to use.
(3) This product is strictly forbidden to be frozen, and it is strictly forbidden to use in divided doses. The prefilled syringe should be used immediately after opening.
(4) This product should not be mixed with other medical products and injected together in a syringe.
(5) For patients with thrombocytopenia or bleeding disorders, intramuscular injection of this product may cause bleeding.
(6) Intravenous injection is strictly prohibited.
(7) Adrenaline and other drugs should be prepared for emergency use in case of occasional severe allergic reactions. Recipients should be observed on site for at least 30 minutes after injection.
(8) Those who inject immunoglobulin should be inoculated with this product at least one month apart to avoid affecting the immune effect.
(9) Those who have any nervous system reaction after injection are prohibited from using it again.
(10) This product must be used within the validity period.
(11) Those who are immunocompromised or have any questions before use should consult and listen to the doctor's advice.
[Pregnant and lactating women medication]
There are no clinical trial data on the use of this product in pregnant and lactating women. If this group of people needs to use this product, it is recommended to make a decision after joint benefit/risk assessment with the doctor.
【medicine interactions】
At present, no clinical research has been conducted on the joint use of this product with other vaccines or drugs. There are no data to evaluate the effect of this product when used concurrently with other vaccines or drugs.
The use of immunosuppressants may reduce the body's immune response to this product.
If you are currently or have recently used any other vaccines or drugs, in order to avoid possible drug interactions, it is recommended to consult a professional physician before inoculating this product.
【Clinical Trials】
In a randomized, blinded, positive-controlled Phase III pivotal registration clinical trial completed in China, a total of 3,000 subjects aged 3 and above were enrolled, 800 subjects aged ≥65 years old, and 700 subjects aged 18-64 years old , 700 people in the 9-17-year-old group, and 800 people in the 3-8-year-old group. The subjects in each age group were randomly inoculated with 1 dose of this product or the quadrivalent influenza virus split vaccine at a ratio of 1:1. Blood samples were collected before and 28 days after immunization, and the titer of influenza virus HI antibody in the subject's serum was detected by the micro-hemagglutination inhibition test method.
The post-influenza virus HI antibody GMT in the whole study group were as follows: H1N1 type 400.39, H3N2 type 436.71, BY type 267.60, BV type 77.80 (see Table 1 for details), and the positive conversion rate of post-free antibody was 82.71% for H1N1 type, 91.22% for H3N2 type, 88.36% for BY type and 84.96% for BV type (see Table 2 for details). The protection rates of post-antibody (≥1:40) were 96.60% for H1N1 type, 97.96% for H3N2 type, 95.92% for BY type and 89.45% for BV type (see Table 2 for details). FAS results are consistent with PPS.
table1. The whole study population was free of after-antibodiesGMTandGMIAnalysis (.PPSset)
Type of antibody |
Constituencies
|
Number of detections
|
antibodyGMT（95%CI）
|
GMTRatio (95%CI）
|
antibodyGMI（95%CI）
|
|
H1N1
|
Experimental group
|
1469
|
400.39(377.13~425.09)
|
1.201(1.107~1.303)
|
11.84(11.06~12.67)
|
|
Control group
|
1480
|
333.46(315.49~352.46)
|
|
9.90(9.24~10.61)
|
|
H3N2
|
Experimental group
|
1469
|
436.71(410.88~464.16)
|
1.137(1.043~1.240)
|
16.66(15.70~17.68)
|
|
Control group
|
1480
|
384.13(361.25~408.45)
|
|
14.05(13.21~14.95)
|
|
B(Y)
|
Experimental group
|
1469
|
267.60(251.98~284.19)
|
1.481(1.362~1.611)
|
12.58(11.85~13.35)
|
|
Control group
|
1480
|
180.63(170.32~191.57)
|
|
8.45(7.99~8.93)
|
|
B(V)
|
Experimental group
|
1469
|
77.80(73.50~82.36)
|
1.146(1.058~1.241)
|
9.76(9.28~10.27)
|
|
Control group
|
1480
|
67.90(64.21~71.81)
|
|
8.34(7.92~8.77)
|
Note: The virus strain types contained in the vaccines of the experimental group and the control group: H1N1 type is A/Brisbane/02/2018 (H1N1) pdm09-like virus strain, H3N2 type is A/Kansas/14/2017 (H3N2)-like virus strain, B(Y) type is B/Phuket/3073/2013-like virus (B/Yamagata/16/88 lineage) strain, Type B(V) is a B/Colorado/06/2017-like virus (B/Victoria/2/87 lineage) strain.
If the antibody GMT ratio (experimental group/control group) is 95%, the lower CI limit is not less than 0.67, and the non-inferior efficacy test is established.
table2. Full studyAnalysis of antibody-positive conversion rate and protection rate in population（.PPSset)
Type of antibody |
Constituencies
|
Number of detections
|
Antibody positive conversion rate%（95%CI）
|
Poor positive conversion rate%（95%CI）
|
Antibody protection rate (≥1:40）%（95%CI）
|
|
H1N1
|
Experimental group
|
1469
|
82.71（80.68~84.61）
|
4.06(1.21~6.91)
|
96.60（95.54~97.46）
|
|
Control group
|
1480
|
78.65（76.47~80.71）
|
|
96.01（94.89~96.95）
|
|
H3N2
|
Experimental group
|
1469
|
91.22（89.65~92.62）
|
1.89(-0.24~4.03)
|
97.96（97.10~98.62）
|
|
Control group
|
1480
|
89.32（87.64~90.85）
|
|
97.36（96.42~98.12）
|
|
B(Y)
|
Experimental group
|
1469
|
88.36（86.61~89.96）
|
6.40(3.85~8.95)
|
95.92（94.77~96.87）
|
|
Control group
|
1480
|
81.96（79.90~83.89）
|
|
94.26（92.95~95.39）
|
|
B(V)
|
Experimental group
|
1469
|
84.96（83.02~86.75）
|
3.87(1.17~6.58)
|
89.45（87.76~90.97）
|
|
Control group
|
1480
|
81.08（78.99~83.05）
|
|
87.50（85.71~89.14）
|
Note: The virus strain types contained in the vaccines of the experimental group and the control group: H1N1 type is A/Brisbane/02/2018 (H1N1) pdm09-like virus strain, H3N2 type is A/Kansas/14/2017 (H3N2)-like virus strain, B(Y) type is B/Phuket/3073/2013-like virus (B/Yamagata/16/88 lineage) strain, Type B(V) is a B/Colorado/06/2017-like virus (B/Victoria/2/87 lineage) strain.
Yang conversion: with 1:10 serum as the lowest dilution, the pre-immunization HI antibody <1:10 post-immunization HI antibody titer ≥1:40 is positive conversion, or pre-immunization HI antibody ≥ 1:10, the post-immunization HI antibody titer increases 4 times to positive conversion.
Yang conversion rate: the rate at which HI antibodies reach positive rotation after exemption; Protection rate: ratio of post-HI antibody titer ≥ 1:40.
If the antibody positive conversion rate is poor (experimental group-control group), 95%, the lower CI limit is >-10%, and the non-inferior efficacy test is established.
For safety data obtained in the above clinical trials, please refer to [Adverse Reactions].
【Storage】Store and transport at 2~8 °C in the dark.
【Packing】Prefilled syringe, 1pcs/box.
【Validity】12 months.
【Executive standard】YBS00362023
【Approval number】Sinopharm S20230029【Marketing Authorization Holder】
Name: Jiangsu Zhonghui Yuantong Biotechnology Co., Ltd
Registered address: No. 32, Xinglin Road, Taizhou Pharmaceutical High-tech Zone
Zip code: 225300
Phone number: 4006080059
Fax number: 0523-82205726
URL: http://www.abbbio.com
【manufacturer】
Company name: Jiangsu Zhonghui Yuantong Biotechnology Co., Ltd.
Production address: No. 32, Xinglin Road, Pharmaceutical High-tech Zone, Taizhou City
Zip code: 225300
Phone number: 4006080059
Fax number: 0523-82205726
URL: http://www.abbbio.com
