L2: Process design, Economy and Unit operations

Question 1

What are the two main activities in process design for bioproduct manufacturing?

Answer 1

Process synthesis: Selecting and arranging unit operations to produce a product at acceptable cost and quality.

Process analysis: Comparing and analyzing different process solutions to optimize effectiveness and cost.

Question 2

What is the general purpose of process synthesis within process design?

Answer 2

To determine an efficient combination of steps (unit operations) that achieve the desired product quality and cost.

Question 3

Why is the chance of commercialization generally low (1-3%) at the initial stages of process design?

Answer 3

Because initial designs are speculative, often without proof of commercial feasibility, and many processes do not meet economic or technical viability at scale.

Question 4

How much does it typically cost to develop a new drug compared to the actual development cost? Why is there such a difference?

Answer 4

The average cost is $500 million to $1 billion, but actual development expenses are around $50-100 million due to costs spread across trials, regulatory processes, and high failure rates.

Question 5

What are some environmental and economic challenges associated with wastewater treatment in bioprocessing?

Answer 5

Increased costs due to stringent disposal regulations.

Need for advanced treatments to remove residual biological and chemical compounds.

Green chemistry principles aim to reduce these impacts through sustainable waste management.

Question 6

What is the primary difference in process requirements between high-value, low-volume products and commodity biochemicals?

Answer 6

• High-value, low-volume products are often processed in batch mode.
• Commodity biochemicals are typically produced in continuous processes due to their lower value and higher volume.

Question 7

Why is it generally easier to recover extracellular products compared to intracellular products in bioprocessing?

Answer 7

Extracellular products are already secreted into the medium, reducing the amount of cell debris and impurities, whereas intracellular products require cell lysis to release them.

Question 8

What percentage of production costs for recombinant DNA products is associated with downstream processing (DSP)?

Answer 8

80-90% of production costs are due to DSP for recombinant DNA products, as these require high purity and complex purification steps.

Question 9

How can integrating unit operations help improve process yield in downstream processing?

Answer 9

Integration can minimize losses between steps, increase efficiency, and reduce handling, all of which help to maintain higher yields.

Question 10

What factors can influence the product concentration in fermentation broth?

Answer 10

• Fermentation conditions, such as pH and nutrient availability.
• The metabolic efficiency of the organism.
• Volume and duration of fermentation.

Question 11

How is the productivity of a fermentation process measured, and why is this metric important?

Answer 11

Productivity is measured as grams of product per liter of fermentation broth per hour (g/L/h).

It’s crucial for ensuring that the process is quick enough to meet demand and prevent product degradation.

Question 12

What concentration of small molecules in fermentation broth is typically required for high, medium, and low product cost categories?

Answer 12

• High-cost products: 50 g/L.
• Medium-cost products: 150 g/L.
• Low-cost products: 300 g/L.

Question 13

Define the W-factor in DSP and explain its importance in process economics.

Answer 13

The W-factor represents the amount of water per kilogram of product (kg water/kg product). A lower W-factor reduces water handling and treatment costs, making the process more economical.

Question 14

What are the main applications and challenges of filtration in bioprocesses, particularly when filtering cells and proteins?

Answer 14

Applications: Separation of cells and proteins from liquid, often as a concentration method.

Challenges: Membrane fouling, high-pressure needs, and limited membrane lifespan.

Question 15

Describe two types of filtration commonly used in biomass removal for DSP.

Answer 15

• Rotary vacuum filtration: Often used for large-scale cell separation.
• Membrane filtration: Used for finer separations, such as protein concentration, but requires high pressure.

Question 16

What advantages does centrifugation offer in biomass removal, and what are some of its limitations?

Answer 16

Advantages: No need for filter aids and effective separation of cells.

Limitations: Shear forces may damage cells, and the process can be noisy and expensive.

Question 17

How does liquid-liquid extraction work, and in what situations is it most useful for DSP?

Answer 17

It separates compounds by transferring them into a water-immiscible solvent. It’s especially useful for extracting small molecules or proteins into separate phases.

Question 18

What are some considerations when selecting an organic solvent for liquid-liquid extraction in DSP?

Answer 18

• Environmental impact and safety of the solvent.
• Compatibility with the product.
• Ease of recycling the solvent for cost efficiency.

Question 19

Explain the process of protein precipitation in DSP and list one major challenge associated with this technique.

Answer 19

• Process: Proteins are precipitated by adjusting solubility (e.g., changing pH or salt concentration), separated from the liquid phase, and collected.
• Challenge: Accurate solubility data is required, and very small precipitate particles can be challenging to separate.

Question 20

What role does distillation play in DSP, and what are some limitations when working with water-based solutions?

Answer 20

Distillation separates components based on boiling points, but water’s high boiling point makes it energy-intensive, and high temperatures can damage sensitive molecules.

Question 21

Why is sedimentation relatively rare in bioprocesses, and what are its main applications when it is used?

Answer 21

Sedimentation is slow, especially for microbial cells with density close to water.
It’s used primarily for dense, large particles or sometimes in liquid-liquid separations.

Question 22

What principle does chromatography use to separate products, and why is it important in the purification of similar proteins?

Answer 22

Chromatography separates based on molecular interactions with a stationary phase. It’s essential for purifying similar proteins due to its high specificity.

Question 23

List two challenges associated with scaling up chromatography in DSP.

Answer 23

1. Pressure drops: Increased pressure with larger columns.
   2.Distribution issues: Ensuring uniform flow across wider columns.

Question 24

Explain the cost-yield trade-offs involved in choosing chromatographic media for DSP.

Answer 24

High-cost media offers better purity but may reduce yield, while less expensive media might sacrifice purity. The right balance is crucial for cost efficiency.

Question 25

Why is downstream processing considered a more significant cost factor for high-purity products like monoclonal antibodies?

Answer 25

These products require extensive purification steps to achieve high purity, which increases DSP costs significantly.

Question 26

How can DSP costs be optimized through process design, particularly for products with low market value?

Answer 26

By simplifying the number of steps, integrating unit operations, and selecting cost-effective materials, DSP costs can be minimized.

Question 27

What is the significance of unit operation topology in the design of a DSP flowsheet?

Answer 27

Topology helps organize the sequence and connectivity of unit operations, impacting process efficiency and cost.

Question 28

Describe the difference between upstream and downstream operations in a typical bioprocessing workflow.

Answer 28

• Upstream: Involves preparing and cultivating the biological material.
• Downstream: Involves recovering, purifying, and formulating the final product.

Question 29

What is the impact of product concentration on the scale and type of unit operations required in DSP?

Answer 29

Higher product concentration allows for smaller, more efficient unit operations, reducing water usage and costs.

Question 30

How does DSP for industrial enzymes differ from DSP for high-purity recombinant DNA products?

Answer 30

Industrial enzymes require less stringent purity, allowing simpler and more cost-effective DSP, while recombinant DNA products require complex, high-cost purification.