Bioprocess Engineering Fundamentals

Question 1

What are general procedures in bioprocessing?

Answer 1

• Single vial of the working cell bank (WCB system)
• Cultivation of cells in a bioreactor at different scales (human body is the best bioreactor- that we are trying to recreate).
• Separation of cells for recovery of a target product
• Purification process for final product: purity and yield
• Analysis of final product (QC)
• Formulation & packaging.

Question 2

What is upstream processing?

Answer 2

from gene/cell to cell cultivation process resulting in initial generation of target product.

Question 3

What is downstream processing?

Answer 3

cell harvesting, lysing, isolating, purification of a target product and generation of finished product format followed by sealing of the final product containers.

Question 4

Steps in bioprocess engineering process?

Answer 4

STEP 1: Fermentation/ cell culture (upstream processing)

• Order and test all raw materials.
• Equipment and materials sterilized to avoid bacterial and other contamination to the cell cultures.
• Original cell culture started in small bottles (large soda)
• As the cells grow and multiply, they are introduced into a small bioreactor.
• Eventually they are grown in large bioreactors which can be several stories tall.
• The product is then created
• For pharmaceutical, there are chemical processes involved (chemical synthesis)
• For biopharmaceuticals, cell culture or fermentation is involved
• The product is referred to as the ‘active ingredient’ - chow cells to active ingredient ( insulin would be called the active ingredient here).

STEP 2: Purification (downstream processing)

• After the active ingredient is synthesized, it must be purified.
• Purification involves removing the chemicals used in the process.
• For biopharmaceuticals, purification involves separating the cells from cellular nutrients and the byproducts they grew in.
• Based on chemical/physical properties:
• Interactions with other molecules (chromatography)
• Size (filtration)
• Solubility (precipitation)
• The end result is called the bulk product- it may be sold as it is or processed further at the same plant or shipped to another plant for further processing.

STEP 3: Formulation

• Getting the bulk product into its final form.
• Chemical mixing operations to blend the active ingredient with other substances such as fillers, needed in the final form.
• The final form may be solid (tablet or capsule), liquid, gels/creams or aerosols.
• Biopharmaceuticals usually are sold as sterile liquids or powders (longer shelf-life)

STEP 4: Final dosage form preparation

• The formulated preparation is made into its final form
• The final form is dispensed into containers
• The containers are labeled and packaged.

Question 5

Active ingredient of chow cells?

Answer 5

Insulin! (product)

Question 6

Departments to ensure quality?

Answer 6

Companies must conform to Good Manufacturing Practice (GMP) regulations established by the FDA

Quality control- quality of product (QC), Quality assurance- quality of process (QA), Validation.