With the increasing supervision of drug production by the national drug regulatory authorities, biopharmaceutical and vaccine manufacturers are increasingly demanding product safety management, and the use of raw materials without animal source components in the vaccine production process is growing. The demand trend, but at present, most of the vaccine production is inseparable from the addition of serum components during cell culture, but the use of serum must face the series of problems and shortcomings brought by serum:
1. Large difference between batches: Each batch of serum may be suitable for certain cell lines, and the serum batch number should be extensively tested. Mass storage will increase the cost, and it is difficult to standardize the large-scale production process, and also affect the vaccine to some extent. Batch stability
2. Risk of contamination: Serum is often contaminated by viruses. Although it is harmless to most cell cultures, it increases the factors that cannot be controlled. Once the problem occurs, it takes a considerable amount of time, materials and labor costs to solve;
3. Uncertainty: The serum contains a wide range of unknown trace components, and its role is still far from clear, and it also increases the difficulty of purification and vaccine quality control;
4. High cost: high quality serum supply is insufficient, global serum is tight, and the price is still rising, the cost is often several times the cost of cell culture medium, which brings considerable cost pressure to vaccine manufacturers;
Therefore, how to reduce the amount of serum used in vaccine production, thereby reducing the risk and high cost of using serum, is an important issue for vaccine manufacturers to pay attention to and seek solutions.
Compared with traditional high serum content cell culture, low serum cell culture can not only reduce the risk of vaccine safety, but also improve the production efficiency of the enterprise. The vaccine production is carried out using low serum medium, and the cells are domesticated and adapted to the traditional Compared with the culture method, the number of cells is significantly improved, the cell length is shortened, the ratio of division and virus titer are also improved, and the labor intensity is reduced, thereby greatly improving the production efficiency of the enterprise and, most importantly, reducing The overall cost of a vaccine manufacturing company.
Beijing Ximeijie Technology Co., Ltd. (hereinafter referred to as Ximeijie) introduces KERRY, a high-quality plant-derived protein hydrolysate and complex non-animal-derived additive system, to the vaccine client. Ultrafiltration yeast powder and recombinant low endotoxin albumin have served the global vaccine manufacturers and medium production enterprises for nearly 70 years, and have solved the problems caused by serum for the majority of vaccine customers. At present, KERRY series products have been widely used in vaccine production of BHK, VERO, SF-9, MDCK, MRC5 and other cell lines. The vaccines listed include: foot-and-mouth disease vaccine, hepatitis E vaccine, influenza vaccine, etc. From 10% to 3%, a small number of customers have achieved complete serum-free culture.
Using the KERRY Sheff-VAX system for VERO cell down-regulation

Figure 1. Vero cell growth morphology comparison. (A) Control group: 10% fetal bovine serum; (B): Experimental group: 0% fetal bovine serum + 2 g/L Sheff-VAX ACF. According to observation, there was no difference between the Vero cells in the A control group and the cells in the B experimental group. All pictures were taken with a 100X Leica microscope.


Figure 2. The growth curve of Vero cells in a medium containing 10% fetal bovine serum was used as a control group, and the control cells were added to the Sheff-Vax supplement for cell wear with a gradual decrease in serum. DMEM was used as the basic medium. (i) 10% fetal bovine serum; (ii) 7.5% fetal bovine serum; (iii) 5% fetal bovine serum; (iv) 2.5% fetal bovine serum; (v) 1.5% fetal bovine serum; (vi) 1% Fetal bovine serum; (vii) 0.5% fetal bovine serum; (viii) 0.25% fetal bovine serum; (ix) 0.1% fetal bovine serum; (x) 0% fetal bovine serum. Serum-free culture of Vero cells can be achieved by gradually reducing serum. During the same medium time, cells in the additive medium reached half of the peak of the control cell density. However, by prolonging the culture time, a higher peak of cell density can be obtained.

Recommended vaccine production cell culture additives series product introduction:
1. The world's exclusive non-animal composite additive Sheff-VAX series
Item number
Product name
5X00426
SHEFF-VAX ACF
5X00484
SHEFF-VAX PLUS ACF
5X01143
SHEFF-VAX PF ACF
5X00512
SHEFF-VAX PLUS PF ACF
PF is protein free and plus is trace elements
2. Non-animal source Hypep series
Item number
Product name
5X99023
HYPEP 1510 (soy source)
5X00713
HYPEP 4601N (wheat bran source)
5X00794
HYPEP 5603N (rice source)
5X00001
HYPEP 7504 (cottonseed source)
5X00213
HYPEP YE (yeast source)
5X00214
ULTRAPEP YE (yeast source)
3. Other related products
Item number
Product name
5X01090
SHEFF-VAX Plus PF ACF VP is used in the toxin production stage to increase virus production
5X01302
Sheffield rAblumin LE recombinant low endotoxin albumin
30624799
Sheffield rTrypsin ACF recombinant trypsin
20460791
Sheffield Trypsin 1:250 Pig Source Trypsin
30650974
Sheffield TrypStop ACF Trypsin Inhibitor
Since the low serum medium differs from the basal medium in the distribution ratio, the pH, osmotic pressure and sodium bicarbonate addition of the culture medium are changed, as well as the cell growth rate, the ratio of the seed, the time of the poisoning, and The number of times and the like are different from the previous experience and habits of the user, and it is easy to cause certain difficulties for the user when using the low serum medium. Therefore, in order to use low serum media, users must break the habits that have been formed in the past and recognize low serum media in a new posture.

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A seedbed or seedling bed is the local soil environment in which seeds are planted. Often it comprises not only the soil but also a specially prepared cold frame, hotbed or raised bed used to grow the seedlings in a controlled environment into larger young plants before transplanting them into a garden or field. A seedling bed is used to increase the number of seeds that germinate.

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