IC8 Recombinant DNA & Biosimilars

Question 1

There are 4

What is the impact of recombinant DNA tech on biopharmaceutical products?

Answer 1

1. Overcomes limitations e.g. source availability, natural sources can be rare and expensive
2. Allows production of safer biopharmaceuticals
   a. Not using natural sources e.g. taking blood-borne pathogens HIV from infected sources (which can eliminate transmission of virus)
3. Alternative way to obtain protein-based products (compared to direct extraction from inappropriate sources e.g. urine, placenta)
4. Gene of interest can be synthetic
   a. Researchers can design desirable mutations
   b. E.g. longer shelf life, longer circulation half-life, efficacy

Question 2

What makes a good quality biopharmaceutical Product?

Answer 2

• Every transfected cell (bacteria/host) is different from another e.g. number of copies of recombinant DNA transfected
• Use transfected cell with the
  o 1) best cell growth properties
  o 2) highest protein yield
• Protein isolation, concentration and purification steps, and viral inactivation steps in downstream processing –> ensure impurities and contaminants are excluded from final biopharmaceuticals

Question 3

What are biosimilars?

Answer 3

Biosimilars:
A biologic that is almost an identical alternative version to the innovator/reference biologics
(Similar to chemical drugs –> proprietary drug VS generic drug)

• Variabilities present even between different batches of the same product, due to
  o Biological expression system
  o Manufacturing process (upstream and downstream processing)

Question 4

How identical can chemical drugs, biosimilars with low MW and MABs be to their proprietary drug/innovator biologics?

Answer 4

1. Chemical Drugs
   a. Can be identical
   b. Based on chemical compositions
2. Biologics of small MW/size
   a. Possible to be identical
   b. More straightforward
   c. E.g. insulin, erythropoietin, filgrastim, human growth factors
3. Monoclonal antibodies (MABs, large MW/size)
   a. Impossible to be 100% identical
   b. Many steps and factors present
   i. e.g. post-translational modification
   ii. –> pattern and amount of glycosylation of Fc domain of MABs
   iii. –> in turn can affect structure and function of Fc domain of MABs
   iv. Different mutant CHO cells and the culture medium / nutrients can influence this

Question 5

What needs to be done by the company for approval of Biosimilars by US FDA, Canada and European Medicines Agency (EMA)?

Answer 5

Approval of Biosimilars by US FDA, Canada and European Medicines Agency (EMA)

1. Extensive in vitro studies that show biosimilar is similar to reference biologics
2. Non-clinical and clinical studies that show similar PK profile, clinical efficacy, safety and immunogenicity

• Methods/assays used must be sensitive and specific to be able to detect the differences between biosimilars and innovator biologics
• Issues:
  o Can biosimilars be automatic alternatives to innovators biologics / interchangeably used?
  o Can biosimilars that have been studied to be efficacious and safe for 1 indication be used for other indications that the innovator biologic covers or was approved for?