11. In the same large-volume injection production line, if there is a sterilization cabinet, multiple specifications of products (such as 250ml, 100ml) and products with different sterilization parameters (such as different sterilization temperature and time) need to be sterilized, then In the process of verification and re-verification, how to verify the design of heat distribution and heat penetration? Do various specifications and various sterilization conditions need to be verified separately?

Answer: Generally speaking, various specifications and various sterilization conditions need to be verified separately.

Sterilization of mixed loading of different specifications is not recommended unless a lot of relevant content can be confirmed.

12. During the verification or re-verification of the humid heat sterilizer, when verifying the heat distribution and heat penetration, if 12 or 16 thermocouples are installed in the cabinet for temperature testing, the cold spot found is 3 times The verification may be different. What should I do if this happens?

Answer: Generally speaking, the cold spot of no-load heat distribution should be around a certain location, otherwise it may be caused by equipment, pressure, incomplete air replacement, steam quality, etc.

For thermal penetration, the cold spot of the large volume injection (LVP, >100ml) is located at the geometric center of the product and at the bottom of the product along the longitudinal axis, but verification is required. The location of the cold spot is not typical in small volume injections, because the rate of heating of the solution is almost the same as that of the sterilizer.

Also, the orientation of the container will also affect the location of the cold spot. When the container is rotated or turned over, there may be no discernible cold spot.

If the load remains the same, the capacity is the same, there is no barrier to steam penetration, and the cold spot still cannot be reproduced, the equipment, process, pressure, steam quality, etc. should be checked for possible uncertainties.

13. What is the difference between the full-load heat distribution and the no-load heat distribution for the sterilization effect?

Answer: Both tests measure the temperature distribution of the sterilization chamber, and do not reflect the temperature and thermal benefits in the product, nor can it directly reflect the sterilization effect of the product. But the chamber condition obviously affects the situation inside the product. During the verification, the no-load heat distribution, full-load heat distribution, and product heat penetration tests are carried out in sequence. The main purpose of using this kind of test is to reveal the objective situation as much as possible with as few tests as possible. The results of the previous test provide information for the latter test.

14. Is the full load heat distribution test performed with an empty bottle or an infusion bottle with water for injection?

Answer: The full load heat distribution test is carried out with simulated samples.

15. If the loading method during verification is half-load or full-load, is it necessary to verify if it is between full-load and half-load in future production?

Answer: For the loading method between full load and half load, it is recommended to use simulated product filling to achieve full load, so as to ensure that the loading method during production is consistent with that during verification.

16. How to do the thermal penetration test?

Answer: The purpose of the heat penetration test is to determine the "coldest point" in the sterilization chamber loading, and to confirm that this point obtains a sufficient sterility guarantee value in the predetermined sterilization procedure, that is, the residual amount of bacteria ≤ 10-6 And the difference between the temperature of each detection point and the average temperature in the sterilization chamber ≤ 2.5°C. For changes in operating conditions that may affect the sterilization effect, corresponding verifications should be made to confirm the operating methods. For example: when a stainless steel cover is added to each sterilization tray, the heating time inside the actual product (solution) will be 2 minutes slower than that without the cover, so it is necessary to add 2 minutes when setting the sterilization program. The placement of the thermocouple is consistent with the full-load heat distribution test procedure, and the standard thermocouple is placed in the center of the sterilization solution.

17. What is the concept of simulated samples in the heat penetration test? Does it refer to small batch samples in the laboratory?

Answer: The simulated sample in the thermal penetration test refers to the sample with the same thermal penetration performance as the real sample, not a small batch of laboratory samples.

18. Does the type of biological indicator for the microbial challenge test need to be selected according to the variety? How to choose?

Answer: For the types and selection of biological indicators for microbial challenge tests, please refer to the Chinese Pharmacopoeia 2005 Edition Two Appendix 169 Sterilization Method.

19. How to determine the level of microbial contamination before sterilization?

Answer: Membrane filtration is the most commonly used method. It should be verified before use.

20. The microbial limit test result of the product is 0CFU, and no heat-resistant microorganisms are found. Can the Bacillus subtilis with a slightly lower D value be used as a biological indicator for verification during the verification process?

Answer: 1) There is no causal relationship between the microbial limit test results and the selection of Bacillus subtilis with a slightly lower D value as the biological indicator.

2) According to the questioner's question, it can be considered that it uses the sterilization process of the residual probability method. For the sterilization process of the survival probability method, a biological indicator can be selected for the survival probability test. It is only because the product or packaging itself cannot withstand excessive killing. Therefore, a more stringent process control is selected, plus the initial bacterial number control of the product, or more In addition to the sterilization filtration process, etc., the biological indicator is selected for sensitivity test, and the average bacterial content N0 is measured, and then the microbial limit before and after the sterilization of the products with no less than 4 gradient bacteria and sufficient batches and quantities Test (if necessary, test for different sterilization times), find and obtain state parameters that are greater than 6 logarithmic levels, and calculate the D value under the condition that the F0 value is between 8 and 12.