Sadettin S. Ozturk, Ph.D.
Cell Culture Process for Recombinant
Protein Production
Lecture 1:
Cell Culture Technology
by
Sadettin S. Ozturk, Ph.D
1
1
Sadettin S. Ozturk, Ph.D.
Outline
•
Biopharmaceuticals: Medicines from recombinant DNA
technology
•
Host cell options and microbial systems
•
Cell culture technology
•
Complexities and challenges in cell culture systems
•
Alternatives to cell culture systems
•
Cell culture: current state-of-the-art
•
New directions in cell culture
2
2
Sadettin S. Ozturk, Ph.D.
Insert DNA
into host cell line
The Industry of Biopharmaceuticals Started with
Recombinant DNA Technology in 1980s
Grow cells in
Bioreactors
Separate
cells out,
collect
product
Purify
Product
Host Cell
Identify the
gene and DNA
to treat the
disease
Formulate
and Fill
3
3
Sadettin S. Ozturk, Ph.D.
Since 1980s Many Biopharmaceuticals Got
Approval as Medicines
4
4
Sadettin S. Ozturk, Ph.D.
Biopharmaceuticals are now a Major Player
in Pharmaceutical Industry
5
Small molecules
Biopharmaceuticals
5
Sadettin S. Ozturk, Ph.D.
Small Molecules vs. Biopharmaceuticals Sales:
US Market
6
6
Sadettin S. Ozturk, Ph.D.
Global Biopharmaceuticals Sales were
$380 Bln in 2019
CAGR: Compound Annual Growth Rate
7
7
Sadettin S. Ozturk, Ph.D.
Worldwide Revenues: 7 of the top 10 Drugs are
Biopharmaceuticals
8
CEN News, Volume 93 Issue 48, p. 19, Issue Date: December 7, 2015
8
Sadettin S. Ozturk, Ph.D.
Biopharmaceutical Market is Concentrated in the
Western World, because People can Afford Expensive
Medicines
9
9
Sadettin S. Ozturk, Ph.D.
Medical Treatment using
Biopharmaceuticals is Very Expensive
10
10
Sadettin S. Ozturk, Ph.D.
Why are Biopharmaceuticals Very Expensive:
They
are More Complicated than Chemical Drugs, More Difficult
to Make
Aspirin
180 daltons
mAb
150,000 daltons
Factor VIII
~250,000 dalton
Insulin
5,700 daltons
11
11
Sadettin S. Ozturk, Ph.D.
Why are Biopharmaceuticals Very Expensive: The Drug
Development Process is Very Long, Expensive, and Risky
12
Review
Approval
Reg.
Filing
Phase III Clinical Trials
Submit BLA
Early Clinical Development
Phase II Clinical
Trials
Manufacturing Activities
Late Clinical Development
Clinical and Product Development Activities
Ph I Batch
Process Validation
Launch
Preparation
Year
-2
Year
1
Year
2
Year
3
Year
4
Year
5
Preclinical
Studies
Target
Research
Phase I Clinical
Trials
Submit IND
BLA
Prep
Tox
Mat
Ph II Batch
Ph III Batch
Process Development Activities
Process
Characterization
Late Phase
Process Dev
Early
Phase Process
Development
Tech Transfer
BLA Prep Support
Year
0
Year
6
IND: Investigational new drug application (first in human) (Clinical Trial Application, CTA in EU)
BLA: Biologics license application (Marketing Authorization Application, MAA in EU)
12
Sadettin S. Ozturk, Ph.D.
Genetic Engineered Organisms to Produce
Biopharmaceuticals:
Host Options
13
13
Sadettin S. Ozturk, Ph.D.
