Question

Suppose your team are assigned with a project that requires a comprehensive design of a bioprocess
operation for production of a new bioproduct. Based on the guidelines below, prepare a PROPOSAL
detailing the whole process.
(A) Background
i) Define ONE (1) bioproduct that your team is planning to produce. Examples: enzymes,
organic acids, vaccines, antibiotics, biofuels etc.
ii) Describe the importance of the bioproduct of interest in the industrial applications.
iii) Identify potential microorganisms that will produce the bioproduct of interest. If the
microorganism is a genetically modified one, please provide the details on the background
of the strain such as the origin of the gene of interest, host, promoter etc.
iv) Determine the type of fermentation to be employed (submerged or solid state fermentation),
mode of fermentation (batch, fed batch or continuous) and platform of fermentation (types
of bioreactors) and explain the rationales for the selection of those factors.
(B) Process development
v) Identify the medium components required for the production of the bioproduct of interest.
vi) Identify the process parameters (e.g. pH, temperature, agitation speed, dissolved oxygen
(for aerobic microorganisms) etc) required for the production of the bioproduct of interest.
vii) From (v) and (vi), suppose optimisation studies are required,
- indicate which parameters will be studied. Provide at least THREE (3) parameters.
- Explain the rationale of the selection of parameters to be optimised.
- describe how the optimisation studies are performed (range chosen, method (either
one-factor-at-a-time or design of experiment) and platform of fermentation).
(C) Downstream Processing (DSP)
Upon the completion of fermentation process, identify suitable methods for the downstream
processing stage. Firstly, identify whether your bioproduct is an intracellular or extracellular product,
as that characteristic will determine the selection of the DSP methods.
viii) Identify suitable method for primary solid-liquid separation of the bioproduct of interest.
Explain the rationale of the method chosen. Describe briefly the process.
ix) Identify suitable method for primary separation of the bioproduct of interest. Explain the
rationale of the method chosen. Describe briefly the process.
x) Identify suitable method for final purification of the bioproduct of interest. Explain the
rationale of the method chosen. Describe briefly the process.

Answer 1

As we know thee is big boom of Bioproducts like monoclonal antibodies & other enzymes which really changed the dynamics of Bioproduction or Bioprocessing .

What is Bioproducts or Biosimilars

Biosimilars are “similar” to the originators’ biologics today, but consistent safety and efficacy experience combined with better tools to confirm this similarity will enable regulators to define interchangeability, and allow substitution over the coming decade—even though biologic production and analyses cannot be precisely replicated

§ Biosimilars are emerging as one of the most important sectors in the healthcare industry to curb increasing healthcare costs, primarily associated with biologics
§ Biopharma has accounted for nearly one-half of the inflation in healthcare costs in the US, primarily due to the launch of innovative biologics

§ Biosimilars are likely to sell at 80% discount to innovator biologics, lowering the healthcare cost while rapidly expanding their use via biosimilars globally and fostering next wave of innovations at the same time

§

Current and future batch of biosimilars can be grouped into three waves:

• § Wave 1 biosimilars: Cytokines, growth factors & hormones, such as filgrastim, epoetin alfa, etc.

• § Wave 2 biosimilars: Mostly monoclonal antibodies coming off patent by early 2020s, such as infliximab, tocilizumab, etc.

§ Wave 3 biosimilars: Complex monoclonal antibodies, antibody fragments, antibody drug conjugates (ADCs) and newer technologies going off patent after early 2020s, such as aflibercept, ranibizumab, ustekinumab, etc.

A Just Basic Understanding of Bioproducts or Biosimilars

How Its look and Its Complexity

What is the importance of Biosimilars and Its requirement for various treatments

Major Microorganisms Used in Bioprocessing

In bioprocess we can use various Cells for production like

A: Bacterial Cell Example - E.coli

B: Yeast Cell

C: CHO cells etc

B: Bioprocess Development & It flow Process from Upstream to Downstream

Fermentation Process : Like Fedbatch and Perfusion

As we Know industry is moving from Fedbatch to Perfusion because there is big advatanges are there .....

Perfusion culture and media

*Compress the seed train
*Maximize bioreactor utilization

*Maximize facility capacity and efficiency

*Reduce the size and number of bioreactors

*Reduce the overall upstream footprint

*Increase volumetric productivity
*Improve protein quality

Various Parameter need to be optimised

We need Optimised following things

1 Cell Line

2: Media Optimization

3: pH, Tempr, DO & CO2 Etc..

4: Process Optimization

5: Automation and other Process Engineering

Upstream Intensification and Optimization -

Integrated Upstream & Downstream Processing approach is now days widely accepted by regulators

Major Technologies for Downstream Product Purifications & suitable purificaion technologies

Additional Information on Automation -Extra knowledge for YOU ::::::::::::::

Please let know if You need any further info on same because we do have expertise on same.

Dr. Surabhi Yadav

Bioscience & Engineering