SUMMARY OF PRODUCT CHARACTERISTICS Doc. No. SPC/71108 Ver.1 1. NAME OF THE MEDICINAL PRODUCT Varicella vaccine (live), Freeze-dried 2.QUALITATIVE AND QUANTITATIVE COMPOSITION After reconstitution, each 0.5ml per dose of varicella vaccine includes: Composition Name Quantitative Active Oka strain 3.4Lg PFU Fucose 0.0175g Sorbierite 0.0025g Inactive L-Arginine 0.006g Monosodium Glutamate 0.003g Dextran 0.015g 3. PHARMACEUTICAL FORM Freeze-dried. 4. CLINICAL PARTICULARS 4.1 Therapeutic indications The product can induce immunity against varicella-zoster virus in recipients following immunization. It is used to prevent Varicella. 4.2 Posology and method of administration 1) Reconstitute the vaccine with the stated amount of sterile water for injection and shake the vial till the content is reconstituted completely before use. 2) Inject 0.5ml s.c. the reconstituted vaccine at deltoid insertion area of the lateral upper arm. 3) The alcohol and other disinfectant can inactivate the attenuated virus in the vaccine, therefore the vaccine can be injected immediately after the disinfector is evaporated completely from the skin. 4.3 Contraindications The vaccine should not be used under the following conditions: [1] Those who had hypersensitivity history to the vaccine or any component of the formulation. [2] Those who are pregnant. 32
[3] Those who had serious diseases (including acute or chronic infection), at the period of acute attack of chronic disease and fever. [4] Those who had immunodeficiency, low immune function or in the period of receiving immunosuppressive therapy. [5] Those who had a history of innate immunity defects or contacting with family members who suffer the innate immunity defects. [6] Those who had a history of encephalopathy, epilepsy and other nervous system disease. 4.4 Special warnings and precautions for use [1] Use the product with caution in case of: the family or individual with history of convulsions, chronic disease, epilepsy, allergic reaction, or pregnant women. [2] Epinephrine or other aid measures should be available at all time to avoid rare allergic reaction after injection of the vaccine. The recipients should be observed for at least 30 minutes after injection. [3] S.C is recommended, intradermal injection can not be used, and intravenous injection is forbidden. [4] Care should be taken to avoid contacting the vaccine by disinfectant during the vial opening and injection. The immunization of Varicella Vaccine (live), Freeze-dried should be done as soon as possible after reconstitution. [5] Do not use the vaccine if any leakage of vial, foreign matters on the label, or turbidity of content is found. [6] The individuals susceptible to varicella and especially those with skin reaction within 2 or 3 weeks after inoculation should avoid contacting with pregnant women and the patients of leukemia who are very susceptible to varicella as well as those who are receiving immunosuppressive therapy, and especially avoid the contact with the women in the first three months of pregnancy. [7] After the inoculation of Varicella Vaccine (live), Freeze-dried, women of childbearing age should be contracepted for at least three months. [8] It belongs to the attenuated live vaccine, thus it is not recommended to inoculate during the popular season of such disease. There should be a one-month interval between the inoculation of other live attenuated vaccines. [9] Do not apply the medication of whole blood, plasma or immunoglobulin within 5 months prior to the injection or within three weeks after injection because it will decrease the effect of the product. [10] Avoid the use of drugs such as salicylates within 6 weeks after inoculation of the vaccine. 4.5 Interaction with other medicinal products and other forms of Interaction Do not apply the medication of whole blood, plasma or immunoglobulin within 5 months prior to the injection or within three weeks after injection because it will decrease the effect of the product. Avoid the use of drugs such as salicylates within 6 weeks after inoculation of the vaccine. There should be a one-month interval between the inoculation of other live attenuated vaccines. 4.6 Pregnancy and lactation After the inoculation of Varicella Vaccine (live), Freeze-dried, women of childbearing age should be contracepted for at least three months. 33
It is not known whether the vaccine is excreted in human milk, because many drugs are excreted in human milk. Cautions should be paid to women in lactation period. 4.7 Effects on ability to drive and use machines It is not known whether the vaccine whether the vaccine may effect the ability to drive and use machines, cautions should be paid. 4.8 Undesirable effects Common adverse reactions: 1) Redness, swelling, pain, itching etc. at the site of injection within 24 hours following the injection may be found, which could generally be relieved spontaneously within 2 or 3 days. 2) Temporal fever reaction may be found within 1 to 3 weeks after inoculation. It is mostly slight (ranging between 37.1~37.5 o C) and can be relieved spontaneously after one or two days. No specific treatment is necessary. If necessary, taking more rest and more water to prevent secondary infection. For moderate fever (ranging between 37.6~39.0 o C) or fever lasting for more than 48 hours, physical treatment or medication can be taken when necessary. 3) Interspersed rash or blebs may appear to few recipients probably within two weeks after injection. No special treatment is necessary. Symptomatic treatment could be helpful in case of need. Rare adverse reactions: Serious fever (body temperature above 39 o C): Physical treatment or medication is needed to avoid febrile seizures. Very rare adverse reactions: 1) Allergic skin rash: Urticaria allergic reaction may appear to several individuals within 72 hours after inoculation, and at this time immediate antiallergic therapy should be given. 2) Allergic purpura: It may appear to very rare individuals. Timely therapy should be given properly with Cortico-Steroids drug. Improper therapy may induce purpura nephritis. 3) Occasional thrombocytopenic purpura may appear to several recipients. 4.9 Overdose Not confirmed until now. 5. PHARMACOLOGICAL PROPERTIES 5.1 Pharmacodynamic properties ATC code: J07BK 5.2 Pharmacokinetic properties Not applicable. 5.3 Preclinical safety data 34
Test aims Review and evaluate the animal safety of the Varicella Vaccine (Live), Freeze-dried with produced by Changchun Changsheng Life Science Limited Test materials The Varicella Vaccine (Live), Freeze-dried with batch number of 20050503, 20050504 and 20050605 which produced by Changchun Changsheng Life Science Limited are the industrial scale test products with consecutive three batches in our laboratory. 1. Acute toxicity test: Taking 5 mouse with body weight around 18 to 20 grammers, giving 0.5ml Varicella Vaccine (Live), Freeze-dried after dissolved by Sterilization Water for Injection to each mouse by tail mainline injection, observing for 30 minutes, no acute toxicity reaction, the mouse which body weight increase after observation of 7 days will be treated as qualified. 2. Abnormal toxicity test: 1). Mouse test: Taking 5 mouse with body weight around 18 to 22 g, giving 0.5ml Varicella Vaccine (Live), Freeze-dried after dissolved by Sterilization Water for Injection to each mouse by Intraperitoneal Injection, observing for 7 days. The mouse should survive without any abnormal reaction in the whole period of observation, and the mouse which body weight increase after the observation will be treated as qualified. 2). Guinea Pig test: Taking 2 Guinea Pigs with body weight around 250 to 350 g, giving 5.0ml Varicella Vaccine (Live), Freeze-dried after dissolved by Sterilization Water for Injection to each Guinea Pig, observing for 7 days. The Guinea Pigs should survive without any abnormal reaction in the whole period of observation, and the Guinea Pig which body weight increase after the observation will be treated as qualified. Test result: 1. The Acute Toxicity of mouse The result of the Acute Toxicity Test of the mouse is qualified, for the test result, see Graph 1. 35
Graph 1, the result of Acute Toxicity Test Batch number 20050503 20050504 20050605 Acute toxicity None None None reaction after 30 minutes of injection Body weight (g) of 19.5, 18.6, 20.0, 19.0, 19.0, 19.6, 20.0, 19.0, the mouse before 18.2 18.2 observation Body weight (g) of 26.8, 26.2, 27.3, 27.1, 26.6, 27.3, 27.7, 26.2, the mouse after the 26.0 26.0 observation for 7 days Conclusion Qualified Qualified Qualified 19.1, 18.2, 18.9, 18.3, 20.1 26.0, 24.8, 25.2, 25.9, 27.5 2. Abnormal toxicity test 1). The result of the Abnormal Toxicity Test of the mouse is qualified, for the test result, see Graph 2. 2). The result of the Abnormal Toxicity Test of the Guinea Pig is qualified, for the test result, see Graph 3. Graph 2, The result of Abnormal Toxicity Test of mouse Batch number 20050503 20050504 20050605 Abnormal None None None Toxicity reaction Body weight (g) 18-22 18-22 18-22 of the mouse before observation Body weight (g) of the mouse after 27 28 26 26 27 26 27 27 26 25 26 27 27 26 27 the observation for 7 days Conclusion Qualified Qualified Qualified Graph 3, The result of the Abnormal Toxicity Test of the Guinea Pig Batch Number 20050503 20050504 20050605 36
Abnormal Toxicity Reaction None None None Body weight (g) of the Guinea 268 275 260 280 290 295 Pig before observation Body weight (g) of the Guinea 281 288 277 296 304 310 Pig after the observation for 7 days Conclusion Qualified Qualified Qualified Conclusion Based on the study of the Acute Toxicity Test of the mouse and the Abnormal Toxicity Test of the mouse and Guinea Pig, the Varicella Vaccine (Live), Freeze-dried produced by Changchun Changsheng Life Science Limited has very good safety. 6. PHARMACEUTICAL PARTICULARS 6.1 List of excipients Name Source Specification Fucose ACROS ORGANICS,American CP standard Sorbierite North China Pharmaceutical Group Corp CP standard L-Arginine Shanghai Kangda Amino Acid Factory CP standard Monosodium Glutamate Hongmei Group CP standard Dextran Shandong Jinyang Pharmaceutical Co.,Ltd CP standard 6.2 Incompatibilities [1] Do not apply the medication of whole blood, plasma or immunoglobulin within 5 months prior to the injection or within three weeks after injection because it will decrease the effect of the product. [2] Avoid the use of drugs such as salicylates within 6 weeks after inoculation of the vaccine. 6.3 Shelf life 24 months. 6.4 Special precautions for storage Stored and transported at 2-8, protected from light. 37
6.5 Nature and contents of container Purpose Container name Specification/MODEL Manufacturer For bulk Serum bottle 10000ml Tianjin Hengming Quartz Glass For Final product Product Co., Ltd Low boron 2ml NINGBO ZHENGLI silicon glass PHARMCEUTIAL PACKING Co. Ltd antibiotic injection vial Official halogenated 13-D2 HuBei Huaqiang Sciences Co Ltd. butyl rubber plug Aluminum plastic combined cap 13.3 6.0 Heibei Jinhuan Packaging Co.,Ltd used for antibiotics(blue) Vaccine label 1.6cm 4.6 cm Beijing zhongbiao Fangyuan Anti-counterfeiting Technological Co., Ltd WFI label 1.6cm 4.6 cm Beijing zhongbiao Fangyuan Anti-counterfeiting Technological Co., Ltd Package insert 8.5 18.5 cm Beijing zhongbiao Fangyuan Anti-counterfeiting Technological Co., Ltd Small box 6.0cm 5.2cm 1.8cm Carton 36cm 23.5cm 26.5cm Beijing zhongbiao Fangyuan Anti-counterfeiting Technological Co., Ltd Jilin Hengtong Co., Ltd 38
6.6 Special precautions for disposal [1] Use the product with caution in case of: the family or individual with history of convulsions, chronic disease, epilepsy, allergic reaction, or pregnant women. [2] Epinephrine or other aid measures should be available at all time to avoid rare allergic reaction after injection of the vaccine. The recipients should be observed for at least 30 minutes after injection. [3] S.C is recommended, intradermal injection can not be used, and intravenous injection is forbidden. [4] Care should be taken to avoid contacting the vaccine by disinfectant during the vial opening and injection. The immunization of the vaccine should be done as soon as possible after reconstitution. [5] Do not use the vaccine if any leakage of vial, foreign matters on the label, or turbidity of content is found. [6] The individuals susceptible to varicella and especially those with skin reaction within 2 or 3 weeks after inoculation should avoid contacting with pregnant women and the patients of leukemia who are very susceptible to varicella as well as those who are receiving immunosuppressive therapy, and especially avoid the contact with the women in the first three months of pregnancy. [7] After the inoculation of the vaccine, women of childbearing age should be contracepted for at least three months. [8] It belongs to the attenuated live vaccine, thus it is not recommended to inoculate during the popular season of such disease. There should be a one-month interval between the inoculation of other live attenuated vaccines. [9] Do not apply the medication of whole blood, plasma or immunoglobulin within 5 months prior to the injection or within three weeks after injection because it will decrease the effect of the product. [10] Avoid the use of drugs such as salicylates within 6 weeks after inoculation of the vaccine. 7. <MARKETING AUTHORISATION> <PREQUALIFICATION> HOLDER Changchun Changsheng Life Sciences Ltd. No.1615 Yueda Road, Changchun, China 8. <MARKETING> AUTHORISATION NUMBER(S) GUOYAOZHUNZIS20083109 9. DATE OF FIRST < AUTHORISATION> / RENEWAL OF THE < AUTHORISATION> Feb. 9, 2009 39