Freeze-Dried Rabies Vaccine For Human Use->aspalthic products

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Changchun Changsheng Life Sciences Ltd.

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Freeze-Dried Rabies Vaccine For Human Use

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Chemicals->Chemical->aspalthic products

Freeze-Dried Rabies Vaccine For Human Use

Product Specification

Model No:	0.5ml/vial,0.5ml/syringe

Country	CN
Minimum Order	5000
Payment Term	L/C,T/T

Product Detail

Rabies vaccine is a freeze-dried preparation made from the inactivated rabies fixed virus. The virus grows in Vero cells. After cultivation, harvest and concentration, the virus suspension is inactivated, purified and then lyophilized to make the vaccine after the addition of a suitable stabilizer. It is used to prevent rabies.
1 Basic requirements
The facilities, source and subsidiary materials,water. apparatus and animals used for production and control tests shall comply with the requirements set forth in the General Notices.
2 Manufacturing
2. 1 Cell substrates for vaccine production
Vero cells shall be used for the vaccine production
2. 1. 1 Management and control tests on cell substrates.
It complies with the Requirements for Preparation and Control of Animals Cell Substrates Used for Production of Biologics. The maximum passage number of the cells from cell banks at every level shall not exceed the approved limit.
2. 1. 2 Cell substrate preparation
The cells from one or more containers of the working cell bank are resurrected to expand by serial
subculture up to a quantity enough for making one lot of vaccine. The quantity of the cells can be
defined as a cell batch. During the subculture of the cells, trypsin or other suitable digestion solution at an appropriate concentration is added onto the monolayer cell cultures to disperse cells. The dispersed cells are suspended evenly with suitable growth medium and distributed into culture bottles. Incubate the cells at 370C to form confluent monolayers.
2. 2 Virus seeds
2. 2. 1 Name and origin of virus strains
Rabies fixed virus CTN-1V strain and aGV strain or other approved Vero cell-adapted rabies fixed
virus strain can be used as the seed for the vaccine production.
2. 2. 2 Establishment of virus seed lot system
It complies with the Requirements for Bacterial and Viral Strains/Seeds Used for Manufacture and Quality Control of Biologics. The passage number of every seed lot shall not exceed the approved limit. The subculture of CTN-1V strain in Vero cells to establish the working virus seed lot shall not exceed 35 passages. The subculture of aGV strain in Vero cells to establish the working virus seed lot shall not exceed 15 passages.
2. 2. 3 Control tests on
The master seed lot virus seed lots shall be subjected to comprehensive control tests described below and the working seed lot shall be subjected to the tests described in Sections 2.2.3.1-2.2.3.4 at least.
2. 2. 3. 1 Identity test
Intracerebral neutralization test in mice is employed to identify the specificity of the virus
seed. The virus seed lot is 10-fold serially diluted. The virus suspensions at appropriate dilutions are mixed respectively with an equal volume of the rabies virus specific immune serum as the test group and with an equal volume of the rabies virus negative serum as the control group. Inoculate i.c. each mouse weighing 11-13 g with 0. 03 ml of each dilution of the test group and with that of the control group, respectively. Six mice are inoculated for each dilution. Observe the test mice daily for 14 days. The mice that die within 3 days after inoculation shall be excluded in the final evaluation of the test and for the test to be valid, not more than 20 % of total test mice shall die. The neutralization index shall be not less than 500.
2. 2. 3. 2 Virus titration
Dilute the virus seed 10-fold serially. Take 0.03ml respectively from the suitable dilutions to inoculate i. c. individual six mice each weighing 11-13g for each dilution. The mice that die within 3 days after inoculation shall be not included in the final evaluation of the test, and for the test to be valid, not more than 20 % of total test mice shall die. Observe the test mice daily for 14 days. The titer of the virus shall be not less than 7.5 lg LD50/ml.
2. 2. 3. 3 Sterility test
It complies with the test for sterility (Appendix XII A) .
2. 2. 3. 4 Tests for mycoplasmas
It complies with the test for mycoplasmas (Appendix XII B).
2. 2. 3. 5 Tests for adventitious viruses
It complies with the tests for adventitious viruses (Appendix XII C).
2. 2. 3. 6 Test for immunogenicity
Prepare the original vaccine with the master seed virus to immunize i. p. mice each weighing 12-14 g. Each mouse receives 0. 5 ml twice at an interval of 7 days as the test group. The unimmunized mice of the same batch shall be served in parallel as the control group. On the 14th day after the first inoculation, challenge i. c. the immunized and unimmunized mice individually with 0.03 ml of each dilution of the 10-fold serially diluted rabies challenging virus CVS strain. Ten mice are challenged with each dilution of the challenging virus. The mice that die within 3 days after inoculation shall not be included in the final evaluation of the test, and for the test to be valid,not more than 20 % of total test mice shall die. Observe the test mice daily for 14 days and evaluate the result at the the protective index shall end of observation, and be more than 100.
2. 2. 4 Storage of virus seed lots
Store at or below -60℃.
2.3 Bulk
2. 3. 1 Cell substrate preparation
See Section 2. 1. 2.
2. 3. 2 Culture medium
MEM and medium199, containing a quantity of inactivated new-born calf serum or other suitable medium can be used for culture medium. The quality of new-born calf serum shall comply with the related requirements (Appendix XIII D).
2. 3. 3 Tests for adventitious viruses in control cells
It complies with the tests for adventitious viruses (Appendix XII C).
2. 3. 4 Virus inoculation and cultivation
The cell cultures with confluent monolayer are selected. Inoculate rabies virus seed at 0.01-0.1MOI onto the confluent monolayer of cell cultures (with the same MOI for the same virus working seed lot). Incubate the cell cultures at an appropriate temperature for a period of time. And then discard the culture medium and wash the monolayers thoroughly with sterile PBS or other appropriate rinsing solution to remove calf serum.Then a quantity of maintenance medium is added to continue the cultivation process at 33-35℃.
2. 3. 5 Virus harvest
After incubation for a period of time, the virus suspension can be harvested. Multiple harvests can be carried out after further cultivation with replacing maintenance medium if the quality of cells is good enough. After being qualified in control tests, the virus suspensions harvested at the same time from the same cell batch can be pooled and defined as a single virus harvest.
2. 3. 6 Control tests on single virus harvests
See Section 3. 1.
2. 3. 7 Storage of single virus harvests
Store at 2-8℃ for not more than 30 days.
2. 3. 8. Pooling and concentration
After being qualified in control tests, the several single virus harvests derived from the same cell batch can be pooled, which can be concentrated through ultrafiltration or other appropriate method to the prescribed range of protein content.
2. 3. 9 Virus inactivation
After being concentrated, the single virus harvests shall be inactivated by adding ß-propiolactone in a proportion of 1:4000 at an appropriate temperature for a period of time. The inactivated virus suspension shall be kept at an appropriate temperature for a period of time to make ß-propiolactone hydrolyzed totally. A sample shall be taken immediately from each virus inactivation container at the end of inactivation process for the respective validation of inactivation.
2. 3. 10 Purification
The inactivated virus suspension shall be purified by means of chromatography or other appropriate methods. The bulk is prepared after the addition of an amount of human albumin or other appropriate stabilizer.
2. 3. 11 Control tests on bulk
See Section 3. 2.
2. 4 Final bulk
2. 4. 1 Formulation
The bulk shall be formulated based on the prescribed protein and antigen content so as to make the total protein content to be not more than 80 µg per single human dose, and the final bulk is made after adding appropriate stabilizer.
2. 4. 2 Control tests on final bulk
See Section 3. 3.
2. 5 Final product
2. 5. 1 Defining batches
It complies with the Requirements for Defining Batches of Biologics.
2. 5. 2 Filling and lyophilization
It complies with the Requirements for Filling and Lyophilization of Biologics.
2. 5. 3 Specifications
o.5 ml or l.0 ml of reconstituted vaccine per container as the stated value. 0. 5 ml or l. 0 ml per single human dose each time. The potency of rabies vaccine shall be not less than 2. 5 IU.
2. 5. 4 Packaging
It complies with the Requirements for Packaging of Biologics.
3 Control tests
3. 1 Control tests on single virus harvests
3. 1. 1 Virus titration
See Section 2. 2. 3. 2. It shall be not less than 6.0 lg LD50/ml.
3. 1. 2 Sterility test
It complies with the test for sterility (Appendix XII A).
3. 1. 3 Tests for mycoplasmas
It complies with the test for mycoplasmas (Appendix XII B) .
3. 2 Control tests on bulk
3. 2. 1 Sterility test
It complies with the test for sterility (Appendix XII A)
3. 2. 2 Validation test for effective inactivation
An amount of 25 ml of the inactivated virus suspension is inoculated onto Vero cell sheets. Each 1 ml of the inactivated virus suspension shall be inoculated onto an area of 3 cm2 monolayer cell sheet. After adsorption for 60 min at 37℃, the cell culture medium shall be added, and the quantitative proportion of the culture medium to the virus suspension shall be not more than 1 : 3. Subculture shall be carried out once every 7 days. Harvest the culture medium after 2ldays' incubation. Mix the harvested mediums, and inoculate i. c. each of 20 mice weighing 11-13 g with the mixed mediums. Each mouse receives 0.03 ml. The mice that die within 3 days after inoculation shall be not be included in the final evaluation of the test, and for the test to be valid, not more than 20 % of total test mice shall die. Observe the test animals for 14 days. All of them shall survive the observation period.
3. 2. 3 Protein content
The test sample shall be taken from the purified preparation prior to the addition of human albumin. The protein content shall be not more than 80 µg/dose (Appendix VI B, method 2).
3.2.4 Antigen content
The antigen content can be determined by ELISA. The approved standard of antigen content shall apply.
3.3 Control tests on final product
Other than the determination of the moisture content,the enclosed sterile water for injection shall be added into the final product as the stated value,and the reconstitude product shall be subjected to the following tests.
3.4.1 Identity test
Rabies viral antigen in the tese sample shall be demonstrated with ELISA.
3.4.2 Apperance
The product looks like a white crisp cake.After reconstitution,it shall turn into transparent liquid free from foreign matters.
3. 4. 3 Chemical tests
3. 4. 3. 1 pH
The pH shall be 7. 2-8. 0 (Appendix V A).
3. 4. 3. 2 Moisture content
The content of residual moisture shall be not more than 3. 0% (Appendix XII D).
3. 4. 4 Potency test
The potency of the vaccine shall be not less than 2. 5 IU/dose (Appendix XI A).
3. 4. 5 Thermostability test
Before release each lot of vaccine shall be subjected to thermostability test. The test sample is exposed at 37℃for 28 days for the determination of potency (Section 3. 4. 4) . The test vaccine which passed the thermostability test is considered satisfactory in potency test.
3. 4. 6 Test for residual bovine serum albumin
The content of residual bovine serum albumin shall be not more than 50 µg/does (Appendix XIII I).
3.4.7 Test for the content of residual antibiotics
Test for the content of residual antibiotics shall be carried out if antibiotics have been added during the production. The residual antibiotic content shall be not more than 50 ng/dose determined by ELISA.
3. 4. 8 Test for residual DNA of Vero cells
The residual DNA of Vero cells shall be not more than 100 pg/dose (Appendix IX B, method l).
3. 4. 9 Test for residual protein of Vero cells
The residual protein of Vero cells shall be not more than 4 µg/dose by ELISA.
3. 4. 10 Sterility test
It complies with the test for sterility (Appendix XII A) .
3. 4. 11 Test for abnormal
It complies with the test (Appendix XII F).
3.4.12 Test for bacterial endotoxin
The content of bacterial endotoxin shall be not more than 50EU/does.(Appendix XII E, gel-clot limit test).
4 Storage, shipping and validity period
Store and ship the product at 2-8℃,protected from light. The approved validity period shall apply starting from the date when the final bulk is made.
5 Diluent of Vaccine
Sterile water for injection used as the diluent shall comply with the specifications set forth in Volume II of the Chinese Pharmacopoeia.
5.1 Extractable Volume
5.2 Packaging
5.3 Standard for implementation
5.4 Manufacturer
5.5 Validity Period
6 Package inserts
It complies with the Requirements for Packaging of Biologics and the approved contents.ccls-vaccine.com

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