Instructor: Nguyen Hoang Khue Tu, Ph.

D, Pharm
 Objectives

 Overview the development of pharmaceutical biotechnology

 Introduce
 course objectives
 syllabus
 assessment scheme
 Revise essential concepts of pharmaceutical biotechnology
 Assessment

Midterm test: 30%

Practical: 20%
Assignment: 10%
Final examination: 40%
 Overview
① Introduction
② Manufacturing processes of Biotech compounds
used in Pharmaceutical and Biopharmaceutical
fields
③ Pharmaceutical 　 Development Strategies
④ Gene therapy
⑤ Formulation for a pharmaceutical and
biopharmaceutical
Chapter I: INTRODUCTION
What is Pharmaceutical?

 Pharmaceutical substances form the backbone of modern 　　

　　　　
medicinal therapy

 Most traditional pharmaceuticals are low molecular weight

organic chemicals (Table 1.1).

 A range of pharmaceutical substances (e.g. hormones and 　

blood products) are produced by/extracted from biological
sources.
Table 1.1 Sometraditional pharmaceutical substances that are generally
produced by direct chemical synthesis

Drug Molecular Therapeutic

Molecular mass
formula indication
Acetaminophen
C8H9NO2 151.16 Analgesic
(paracetamol)
Katharine C13H16C/NO 237.74 Anesthetic
Levamisole C11H12N2S 204.31 Anathematic
Diazoxide C8H7C/N2O2S 230.7 Antihypertensive
Acyclovir C8H11N5O3 225.2 Antiviral agent
Zidovudine C10H13N5O4 267.2 Antiviral agent
Anti-inflammatory and
Dexamethasone C22H29FO5 392.5
Immunosuppressive agent
Misoprostol C22H38O5 382.5 Anti-ulcer agent
Cimetidine C10H16N6 252.3 Anti-ulcer agent
What is Biopharmaceutical?

 ‘Biopharmaceutical’ and ‘Products of pharmaceutical biote

chnology’ or ‘Biotechnology medicines’

 ‘Biologic’ refers to any pharmaceutical product produced b

y biotechnological endeavour. In pharmaceutical circles, ‘biolo
gic’ generally refers to medicinal products derived from blood,
as well as vaccines, toxins and allergen products.

‘Biotechnology’ has a much broader and long-established me

aning. Essentially, it refers to the use of biological systems (e.g.
cells or tissues) or biological molecules (e.g. enzymes or 　 anti
bodies) for/in the manufacture of commercial products.
 Pharmaceutical Biotechnology
 Modern biotechnology have had major impact on Pharmaceutical and
Biopharmaceutical fields.
 Cultivation of cells used in pharmaceutical and biopharmaceutical
fields.
 Gene Disruption
 Expression of Genes
 Mutasynthesis
 Recombinant DNA technology
 Hybridoma technology
 X-crystallization application
 Formulation for a pharmaceutical and biopharmaceutical
 Gene therapy
What is the Impact of Pharmaceutical Biotechnology on the
Drug Development Process?

Reducing cost

Accelerating the Drug Development Process: development and

manufacture of therapeutic proteins and nucleotides.

Maintaining High Standards in Quality Assurance

 The age of biopharmaceuticals

Biomedical research continues to broaden our understanding of the mo

lecular mechanisms underlining both health and disease.

Research undertaken since the 1950s has pinpointed a host of proteins

produced naturally in the body that have obvious therapeutic application
s.

Example

 Interferons and interleukins (which regulate the immune response)

 Growth factors, such as erythropoietin (EPO; which stimulates 　
　　 red blood cell production)
 The age of biopharmaceuticals

The pharmaceutical potential of regulatory molecules was generally

appreciated, 　 their widespread medical application was in most cases
rendered impractical due to the tiny quantities in which they were nat
urally produced.

The advent of recombinant DNA technology (genetic engineering) a

nd monoclonal antibody technology (hybridoma technology) overcam
e many such 　 difficulties, and marked the beginning of a new era of t
he pharmaceutical sciences.
 The age of biopharmaceuticals

Recombinant DNA technology has had a fourfold positive impact

upon the production of 　 pharmaceutically important proteins:

It overcomes the problem of source availability.

It overcomes problems of product safety.
It provides an alternative to direct extraction from
inappropriate/dangerous source material.
It facilitates the generation of engineered therapeutic proteins
displaying some clinical advantage over the native protein
product.
 Biopharmaceuticals: current status and future prospects

By mid 2006, some 160 biopharmaceutical products had gai

ned marketing approval in the USA and/or EU (Table 1.3)

 Protein-based therapeutic agents: 　 hormones, blood fac

tors and thrombolytic agents, as well as vaccines and mon
oclonal antibodies.

 Nucleic-acid-based products: ‘Vitravene’, an antisense oli

gonucleotide, and ‘Macugen’, an aptamer.
Biopharmaceuticals: current status and future prospects

Many of the initial biopharmaceuticals approved were simple

replacement proteins (e.g. blood factors and human insulin).

The vast majority of approved recombinant proteins have bee

n produced in the bacterium E. coli, the yeast S. cerevisiae or in
animal cell lines (most notably Chinese hamster ovary (CHO) cel
ls or baby hamster kidney (BHK) cells.
Biopharmaceuticals: current status and future prospects

Although most biopharmaceuticals approved to date are intended for

human use, a number of products destined for veterinary application
have also come on the market.

 Recombinant bovine GH (Somatotrophin), which was approved in the

USA in the early 1990s and used to increase milk yields from dairy
cattle.

 Veterinary biopharmaceuticals include a range of recombinant vaccines

and an interferon-based product.
Table 1.3 Summary categorization of biopharmaceuticals approved for
general medical use in the EU and/or USA by 2006
What can you do by the end of this course?

Overview the development of pharmaceutical biotechnology

Outline the applications of biotechnology in pharmaceutical
and biopharmaceutical fields
Understand how to drug design and drug development
Understand the Regulations in pharmaceutical manufacturing
What topics will be covered?
Pharmaceutical and Biopharmaceutical production
Pharmaceutical practice
Manufacturing processes of Biotech compounds used in Pharmaceutical

and Biopharmaceutical fields

Pharmaceutical 　 Development Strategies
Nucleic-acid and cell-based therapeutics
REVISIONS
 Procaryotic and Eucaryotic Cells 　 in Biotech Production

 Fermentation of microorganisms or the use of yeast and plants in

the production of important pharmaceuticals has been well established.

 The promises of genomics in drug discovery and drug production,

which were eagerly embraced in the mid-1990s, have now been fulfilled
in many areas.

 A systematic integration of technologies results in a superior output

of data and information, and thereby enhances our understanding of
biological function – drug discovery and development is hence facing a
new age.
 Procaryotic and Eucaryotic Cells in Biotech Production

 Bacterial strains, especially Actinomycetes have been used in biotech prod

uction and drug discovery for years.

 The productivity of yeast and other fungi in a variety of different processe

s has improved significantly since genetic methods have been introduced.

 Transgenic plant Biotech

Figure 1. Convergence of genomic and clinical knowledge in po
stgenomic new drug development and healthcare
The overall discovery/development process can be divided into
four convenient steps

Target Selection and Validation

Choice Between Small-molecule and Macromolecule Platforms
Definition of Target Product Profile
Drug Discovery and Development