Modeling and Optimization of Continuous Viral Vaccine Production

Round 1

Reviewer 1 Report

Title-Modeling and Optimization of Continuous Viral Vaccine Production by Caitlin S. Morris et al 2022.

Summary of Article- In the present work, author proposed mathematical model provides a versatile, comprehensive platform that can be tailored to various viral cultures with or without a latent phase.

Here, author revealed that the production of Defective Interfering Particles (DIPs) highly depends on the number of cells introduced to the viral reactor. A flowsheet model was created to optimize the continuous platform, including the number of cells supplied to the viral reactor. The model presented in this paper provides a robust model for the continuous production of a viral vaccine.

Furthermore, a sensitivity analysis was performed to investigate the effects of each input on each output.

 

Comments- This is very important study to understand the model captures the lag observed during the early production of viruses in culture and explains later phase growth dynamics. The results of the analyses presented herein indicate that the model that has been developed is a versatile model with enhanced accuracy. Several conclusions could be drawn through parameter estimation, model fitting, and optimization. Additionally, this model has proven versatile, so it may 428 be used to develop platforms for various viral vaccines. Article accepted with few small corrections mentioned as below-

 

 

1.     The experimentally various viral vaccines Production is challenging and deviate from Modeling data due to type of infectious agents and their biological mechanism for adaptation and production. Author also emphasizes this in discussion section if there are similar studies with similar-approx. Mathematical models available. please mention.

2.     No. of references is less in the article. Many statements or content should be justified by reference to understand it more proper way by wide readers.

3.     What is significance of study. Importance and future prospect of the study should be mentioned in the separately from the discussion and conclusion section.

 

Acceptance- Yes

Decision- Minor revision

 

Author Response

Thank you very much for your time and consideration. 

Author Response File: Author Response.docx

Reviewer 2 Report

The authors developed a method related to an important topic in the pharmaceutical industry. They propose a mathematical model that considers the latency period parameter, in this way this model could be applied to the production of viral vaccines.

I only have a few comments.

Line 101  This sentence could be included… Each parameter is defined in Table 1.

Line 117: K2 was included in equation 1c, it is not included in equation 1b. So, the explanation for equation 1b should be rewritten.

Lines 187, 243, 298, 207, 301  Citation for software gPROMS is needed

Line 221  Citation is in a different format.

Lines 234 - 235  Citations should be included.

Line 294  You can use DIPs instead of defective interfering particles.

Author Response

Thank you very much for your time and consideration.

Author Response File: Author Response.docx