4.1.2  Key of Production Control

4.1.2.1 Materials and Adjuvant

(1)    All the materials should reach the requirement of new version¡¯s ¡°China Medicine Dictionary¡± and ¡°China Bio-products Material Quality Standard¡±. The purity of any materials, which are not mentioned in the above requirements, should not be lower than ¡°chemical purity¡±.

(2)    All the provider of material should be inspected completely, and the sample should be examined. Providing Agreement should be signed with the approved and qualified provider.

(3)     Strict methods of management must be established and performed seriously.

4.1.2.2  Manufacture Tools

The manufacture tools should be cleaned and sterilized by high-pressure before using.

4.1.2.3 Animal for production or test

Small mouse or cavy should comply with the cleaning standard.

4.1.2.4 Bacteria seed for production should be with typical feature, cultural and bio-chemical character. The inoculation should be performed in the special equipment by strict operation to prevent any contamination. 

4.1.2.5 Freeze-dry bacteria seed should be examined completely after opening.

4.1.2.6The medium for production should be suitable for the bacteria¡¯s growing. Any

person-poisoning substances are absolutely forbidden to add in the medium.

      Collected original liquid should be examined for bacteria purity. The qualified liquid should be sterilized. After sterilizing, inoculate it in the agar and non-agar culture medium separately for 5 days in 37 ¡æ. If any live bacteria are found, repeat the examination once in double dosage. If the impure bacteria still exist, the original liquid should be abandoned.

4.1.2.8 The qualified original liquid should be merged after removing the agar and other impurity substances according to the different variety and different producing date, and appropriate phenol or other antiseptic could be added, then storing in the temperature of 2-8 ¡æ. The storage period should not be less than 4 months from collection date to application date.

4.1.3 Key of Quality Control

Divide the following process according to bacteria vaccine manufacture technique

Process A:  Bacteria seed and testing serum should be approved by CFDA. Sold by CFDA confirming agency.

Process B:  1. Should establish the record of original seed¡¯s history, source and bio-feature. 2. Establish the main-batch from original-batch, and producing-batch from main-batch. All the batches¡¯ feature should be coincident. 3. Seed batch should be tested with the following items: culture feature, serum feature, poison power test, poison type test, immune test and antigen test.

Process C:  Microbe¡¯s identification: type, purity and other special item.

Process D: Testing for microbe¡¯s purity and concentration.

Process E: Testing for Microbe¡¯s purity.

Process F: Aseptic test

Process G: Testing for Original liquid: impurity, activation, aseptic, concentration and immune power.

Process H: Original liquid should be stored in 2-8 ¡æ

Process I: Testing for half-products and full-products should be according to relative standard.