# mAb Production Modeling and Design Space Evaluation Including Glycosylation Process

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## Abstract

**:**

## 1. Introduction

## 2. Methods

#### 2.1. Kinetic Model Building

#### 2.2. Design of Experiment

#### 2.3. Kriging and Dynamic Kriging Model Building

#### 2.4. Feasibility Analysis with Adaptive Sampling

## 3. Results and Discussion

#### 3.1. Prediction of Temperature and pH Effect Using the Kinetic Model

_{p}decreases, regardless of the shift in pH. However, inconsistency is still observed in the trend of Man5 and G2FS1, as shown in Table 1.

#### 3.2. Kriging and Dynamic Kriging

#### 3.2.1. Regular Kriging vs. Dynamic Kriging

#### 3.2.2. Prediction of Temperature Effect from Dynamic Kriging Model

#### 3.3. Feasibility Analysis and Design Space

## 4. Conclusions

## Supplementary Materials

## Author Contributions

## Funding

## Conflicts of Interest

## References

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**Figure 1.**Dynamic change in (

**a**) viable cell density, (

**b**) glucose concentration and (

**c**) mAb concentration under different temperatures. (

**d**) Dynamic change in mAb concentration under different pH values.

**Figure 2.**Glycan fractions under different temperature (

**a**) G0, (

**b**) G0F, (

**c**) G1F, (

**d**) G2F, (

**e**) G1, (

**f**) G2FS1.

**Figure 3.**Glycan fractions under different pH values: (

**a**) G0, (

**b**) G0F, (

**c**) G1F, (

**d**) G2F, (

**e**) G1, (

**f**) G2FS1.

**Figure 4.**Prediction of viable cell (

**a**), glucose (

**b**), and mAbs (

**c**) from dynamic kriging. Prediction of glucose concentration (

**d**) from regular kriging.

**Figure 5.**Prediction of different glycan fractions from dynamic kriging: (

**a**) Man5, (

**b**) G0F, (

**c**) G2F, (

**d**) G2FS1.

**Figure 6.**The prediction of glycan fractions under different temperatures from dynamic kriging: (

**a**) G0, (

**b**) G0F, (

**c**) G1, (

**d**) G1F, (

**e**) G2F, (

**f**) G2FS1.

**Figure 7.**(

**a**) High mannose, (

**b**) afucosylation, (

**c**) GI fractions within the defined operating ranges. The color variation represents glycan fractions.

**Figure 8.**Glycosylation index predicted by dynamic kriging: (

**a**) high mannose, (

**b**) afucosylation, (

**c**) GI, (

**d**) FI.

**Figure 9.**Feasible operating region obtained from adaptive sampling. Contour plot for feasibility function values under different pH values and temperatures. Zero line represents the feasible region’s boundary. Initial sampling points are shown as blue dots and red circles are adaptive sampling points.

Protein | pH Range | qp | Glycan Fraction | Ref |
---|---|---|---|---|

mAb | $\downarrow $ pH 7.15–6.70. | $\downarrow $ | Reduced: G0F, G0, Man5 Increased: G1F, G2F, G2FS1 | [16] |

mAb | $\downarrow $pH 7.2–6.9 | - | Reduced: G0 | [37] |

mAb | $\downarrow $pH 6.9–6.7 | $\downarrow $ | Increased: G1F+G2F, Man5, galactosylation Reduced: Sialylation | [36] |

$\uparrow $pH 6.9–7.3 | $\downarrow $ |

Conditions | Titer | G0 | G0F | G1/G2 | G1F/G2F | G2F1S |
---|---|---|---|---|---|---|

pH shifted down | $\downarrow $ | $\downarrow $ | $\downarrow $ | $\downarrow $ | $\uparrow $ | $\uparrow $ |

Temperature shifted down | $\uparrow $ | $\uparrow $ | $\uparrow $ | $\downarrow $ | $\downarrow $ | $\downarrow $ |

Glycan Fractions | Man5 | G0 | G1 | G1F | G2F | G2FS1 |
---|---|---|---|---|---|---|

Day 5 | 0.029 | 0.004 | 0.027 | 0.088 | 0.073 | 0.088 |

Day 1 | 0.018 | 0.004 | 0.017 | 0.072 | 0.044 | 0.0510 |

Glycan Index | Afucoyslation | ManX | GI | FI |
---|---|---|---|---|

MRSE | 0.0121 | 0.0186 | 0.0025 | 0.0026 |

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**MDPI and ACS Style**

Yang, O.; Ierapetritou, M.
mAb Production Modeling and Design Space Evaluation Including Glycosylation Process. *Processes* **2021**, *9*, 324.
https://doi.org/10.3390/pr9020324

**AMA Style**

Yang O, Ierapetritou M.
mAb Production Modeling and Design Space Evaluation Including Glycosylation Process. *Processes*. 2021; 9(2):324.
https://doi.org/10.3390/pr9020324

**Chicago/Turabian Style**

Yang, Ou, and Marianthi Ierapetritou.
2021. "mAb Production Modeling and Design Space Evaluation Including Glycosylation Process" *Processes* 9, no. 2: 324.
https://doi.org/10.3390/pr9020324