Chapter - 2

Biotech drug products

 Biotech drug products
 Biotechnology-based pharmaceutical products as an essential portion of
the marketed therapeutic agents that are continuously evolving due to
the increased number of approved products as well as products
entering clinical trials.
 Biotechnology involves the use of a living organism or their products
for human use including medical purposes. The Production is a
complex multistep process that requires careful considerations in
various aspects including the understanding of the differences between
biotechnology-based drugs and conventional drugs.
 Currently, different classes of therapeutic agents are produced via
biotechnology, such as antibiotics, enzymes, vaccines, and
monoclonal antibodies.
 Cont.…
Red biotechnology is the use of biotechnology in the
medical and pharmaceutical industries, and health
preservation.
This branch involves the production of   vaccines  
and antibiotics, regenerative therapies, creation of
artificial organs and new diagnostics of diseases. 
As well as the development of hormones, stem
cells, antibodies and diagnostic tests.
 Cont.…
 In medicine, modern biotechnology has many applications in
areas such as pharmaceutical drug discoveries and
production, pharmacogenomics, and genetic testing
(or genetic screening).
 Biotechnology has contributed to the discovery and
manufacturing of traditional small molecule pharmaceutical
drugs as well as drugs that are the product of biotechnology
– biopharmaceutics.
 Modern biotechnology can be used to manufacture existing
medicines relatively easily and cheaply.
 Cont...
The first genetically engineered products were medicines designed to
treat human diseases. To cite one example, in
1978 Genentech developed synthetic humanized insulin by joining its
gene with a plasmid vector inserted into the bacterium Escherichia
coli.
Insulin, widely used for the treatment of diabetes, was previously
extracted from the pancreas of abattoir animals (cattle or pigs).
The genetically engineered bacteria are able to produce large
quantities of synthetic human insulin at relatively low
cost. Biotechnology has also enabled emerging therapeutics
like gene therapy.
 2.1 What is Pharmaceutical Technology?

Pharmaceutical technology: is the multidisciplinary

science of preparing pharmaceutical dosage forms.
It Combines knowledge and understanding of active
ingredients, excipient substances, technological
processes and equipment and plays a key role in
developing new drugs.
 Is one of the essential blood protein that plays a role in aiding the blood to
clot in response to injury.
 Opportunities of Pharmaceutical In-
dustry in Ethiopia
 Huge demand for the products: great market potential with high
population density in Ethiopia and in East Africa.

 Access to regional market: export promotion program by the government

 Stable political Climate

 Existence of untapped market for product with large market potential

in Eastern Africa: anti-retroviral, anti-malarial, and anti-tubercular which
are highly demanded locally as well as by neighboring countries
 CONT.
Production of medicines: huge demand and supply gap

 Production of raw materials: almost all raw materials

are imported and just capsuled or tableted. High opportunity
to produce raw material for local as well as export.

 Production of medical supplies: large amount of medical

supplies such as disposable syringes and latex gloves
 List of Ethiopian Pharmaceutical
Manufacturers
Name Products Sales No. of Em- Location
(1000 EUR) ployee
APF-Addis Pharm. Human drugs 14,900 566 Adigrat, Tigray
Asmi Industry Medical supplies 400 50 Dukem, Oromia
Cadilla Pharm. Human drugs 5,500 308 Akaki, Oromia
East African Pharm. Human drugs 3,190 127 Addis Ababa
Veterinary drugs
EPHARM-Ethiopian Human drugs 7,120 579 Addis Ababa
Pharm
Fawes Pharm. Human drugs 330 60 Addis Ababa
Pharmacure Intravenous fluids 1,000 107 Addis Ababa
National Veterinary Veterinary vaccines 4,260 180 Debre Zeit, Oro
Rx Africa Human drugs 600 55 Addis Ababa
Sino-Ethiopia Gelatin capsules 1,080 102 Gelan City, Oro
 2.2. Drug Formulation Development

It is related to the science of transforming an Active

Pharmaceutical Ingredient (API) into a quality Drug
Product, in a specific dosage form, by developing an
appropriate formula and process.

API is the basic drug itself with the desired pharmaceutical

properties.
Formulation is basic step in the drug design process.
 Pharmaceutical manufacturing occurs in
two general steps:
1) FIRST, FIRMS CONVERT RAW MATERIALS INTO
ACTIVE PHARMACEUTICAL INGREDIENTS
(APIs).
 API production is a highly sophisticated, technically
demanding chemical and biochemical fermentation and/or
synthesis process.
 Cont....
2) THE SECOND STEP IS THE FINAL FORMULATION
OF THE DRUGS.
 During this process, firms first mix APIs and excipients (other
non-active ingredients), then either press the mixture into pills
and tablets or prepare powders for solutions or filling of
capsules, and finally, package the product for the public or
private market.
Drug Discovery and Development

How are drugs discovered and developed?

Discovery=>finding a new active structure/molecular target

Development=>converting/bringing the active structure to a useful drug
 Why To Formulate a Drug Substance?

Clinical need:
Dosage form adapted to the indication → clinical efficiency
Patient needs:
Improve the test, add a color and reduce the number of daily
intake → patient compliance
Industrial needs:
Improve the flowability, density and compressibility of API →
productivity
 Main steps of formulation development

Pre-formulation:
 Characterization of API (Solubility, Melting Point, Density….)
Formulation:
 Choosing the quantitative formula and its process of
fabrication
Scale-up and process validation:
 Transferring the process from laboratory to industrial scale
 1.3. General Procedure Of Drug Development
1. Choose a disease
2. Choose a drug target
3. Identify a “bioassay”
 bioassay = A test used to measure the pharmacological activity of
new or chemically undefined substances, as well as to determine
side-effect profiles, including toxicity.

4. Find a “lead compound”

“lead compound” = structure that has some activity against the chosen
target, but not yet good enough to be the drug itself.
5. If not known, determine the structure of the “lead compound”
 Cont.

6. Synthesize analogs of the lead

7. Identify Structure to Activity, Relationships (SAR’s)

8. Identify the “pharmacophore”

PHARMACOPHORE: the structural features directly
responsible for activity
9. Optimize structure to improve interactions with target

10. Determine toxicity and efficiency in animal models.

 Cont.
11. Determine pharmacodynamics and pharmacokinetics of the
drug.
Pharmacodynamics explores what a drug does to the body,
whereas;
Pharmacokinetics explores what the body does to the drug.
12. Patent the drug
 Continue to study drug metabolism
 Continue to test for toxicity
13. Design a manufacturing process
14. Carry out clinical trials
 Clinical testing (trials)
 Phase I – Human pharmacology (healthy volunteers – 20 ‐50
subjects)
To determine safe clinical dose range.
If drug is expected to have significant toxicity, volunteers
with that disease are taken rather than healthy volunteers,
( e.g. anti‐cancer)
Phase II :
Drug is tested on small group of patients with the target
disease.
 Clinical testing (trials)…
Phase III: Drug is tested on much larger group of patients
and compared with existing treatments and with an inert
control.
These are randomised double‐blind trials.
Takes 5‐6 years for completion.
Results analysed statistically in the end.
Phase IV :
Drug is placed on the market and patients are
monitored for side effects