Biotech Basics: Fundamental Principles
of the Biotechnology Industry
Module 1: Basic Biotech Principles
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Course Author
This ISPE course was developed by Jeffery Odum, a globally recognized instructor in the areas of
facility design, GMP compliance, and aseptic manufacturing. Take a moment to get to know Jeff
Odum by selecting the More Information icon. When you are ready, select Next to continue with the
introduction.
Jeffery Odum,
Instructor
More Information
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Course Resources
• “Biopharmaceutical Manufacturing in the Twenty-First Century – the Next Generation Manufacturing
Facility.”
• ISPE Baseline Guide: Pharmaceutical Engineering Guides for New and Renovated Facilities:
Volume 6, Biopharmaceutical Manufacturing Facilities.
• “Trends in Biopharmaceutical Manufacturing Facility Design: What’s Hot!”
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Basic Biotech Principles
Welcome to Basic Biotech Principles, Module 1 in Biotech
Basics: Fundamental Principles of Biotechnology Industry.
This module focuses on the basic scientific principles of
biotechnology and the bioprocess as well as providing an
understanding of the basic elements of biology important to
biotechnology.
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Module 1 Learning Goals
•
Recognize basic biotechnology principles
•
Review the science of biotechnology
•
Understand the basic elements of biology important to
biotechnology
•
Discuss the basic scientific principles of the bioprocess
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Lesson 1:
Recognize Basic Biotechnology Principles
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SME: Please confirm that the phrase “use products”
is correct in the screen text and VO.
What is Biotechnology?
While the science as we know it is new, the basic principles have been around for a very long time.
Biotechnology is the culmination of over 8,000
years of human experience using living organisms
and the process of fermentation to make use
products for mankind.
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Modern Biotechnology
Modern biotechnology was first identified over 90 years ago. Karl Ereky was a Hungarian
architect/engineer who envisioned a biochemical age similar to the stone age and iron ages.
Biotechnology is “all lines of work by which products
are produced from raw materials with the aid of
living things.”
-- Karl Ereky,1919
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Useful Products from Biotech Applications
Beer
Wine
Biotech
Applications
Cheese
Bread
Biopharmaceutical
Drugs
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Biotechnology Definition
Although this is a more modern definition, it is interesting that even this definition seems to be
changing rapidly as the technologies continue to develop and advance within the industry.
Biotechnology is a combination of advances in our
understanding of molecular and cell biology and
human genetics, and how the human immune
system fights disease.
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Bioscience Subsectors
Therapeutics
Industrial Products
Devices
Research and Development
The industrial biotechnology applications listed below are particularly important.
•
•
•
•
•
•
•
Industrial organic chemicals
Agricultural chemicals
Human health care
o Detection and treatment of diseases
o Human growth
o Vaccines
Forensics
Veterinary science
Organic chemicals
Fuels
•
•
•
•
Agriculture
o Crop yields
o Pesticides
o Fertilizers
Food processing
Aquaculture
Waste management
o Wastewater treatment
o Bio-remediation
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Knowledge Check Directions
[placeholder for standard knowledge check directions]
Knowledge Check
The basic principles of biotechnology are relatively new
concepts.
a)
b)
True
False
Submit
Select the best response and then select Submit.
Knowledge Check
Which of the following are subsectors of the biosciences?
a)
b)
c)
d)
e)
Therapeutics
Industrial products
Devices
Research and development
All of the above
Submit
Select the best response and then select Submit.
Lesson 2:
Review the Science of Biotechnology
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Cell Structure
This image is a cutaway of a mammalian cell.
Cells have a common, basic structure. As you will
see, the components of the cell are important to
the understanding of the science.
Roll over each term to identify the cell structure.
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The Cell as a Manufacturing Plant
In simple cells like bacteria there are thousands of different pieces of “equipment” that must be
linked together, regulated, and work in harmony for the cell to grow and reproduce.
Not only does this “chemical plant” make products, but it regularly replicates itself in rapid
manner by dividing. Select each term to learn more about its function in the cell.
Polysomes
Mitochondrion
“The production
plant” of the cell.
Endoplasmic reticulum
Vesticle
The “power station”
of the cell.
Nucleus
Pore
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The “roadways” of
the cell.
The Cell as a Manufacturing Plant
In simple cells like bacteria there are thousands of different pieces of “equipment” that all must
be linked together, regulated, and work in harmony for the cell to grow and reproduce.
Not only does this “chemical plant” make products, but it regularly replicates itself in rapid
manner by dividing. Select each term to learn more about its function in the cell.
Polysomes
Mitochondrion
The “storage tank” of
the cell.
Endoplasmic reticulum
Vesticle
Nucleus
The “command
center” of the cell.
Pore
Select each term and then select Next to continue.
The “gateway” of the
cell.
DNA, Proteins, and Genes
In addition to knowing the parts and functions of a cell, we also need to review three additional
elements: DNA, proteins, and genes. We will address each topic in greater depth in this lesson.
DNA
Proteins
DNA is genetic material that
is contained in every living
thing. All cells are
programmed by DNA, which
is basic genetic material.
Proteins are the building
blocks of DNA and the major
structural and regulatory
molecules essential for life.
Proteins are made up of 20
amino acids and each has
its own chemical properties.
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Genes
A gene contains the entire
set of blueprints,
specification, and
procedures necessary to
carry out life.
DNA
•
DNA is the basic genetic material.
•
DNA consists of:
o
Sugar
o
Phosphate
o
Four nitrogen bases
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The Four Nucleotide Bases of DNA
Adenine
Thymine
Hydrogen bonds
Guanine
Cytosine
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DNA Structure
1
2
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The DNA Language
The DNA
alphabet has
four letters:
A, G, C, T
Information
determined by
letter
sequence
Sequence
broken into
three-letter
“words,” or
codons
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The codon
specifies 1 of
the 20 amino
acids
The DNA Code
A string of bases in DNA may look something like this:
AGCTTCCGATCGGTA
However, our DNA language is read in three-letter combinations. So the above bases would be read
like this:
AGC, TTC, CGA, TCG, GTA
Each of the three letter words above is a codon that defines an amino acid:
Serine, Phenylalanine, Arginine, Serine, Valine
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DNA and Proteins
•
DNA is universal code.
•
Three-letter codon is the code for an amino acid. Same
triplet of letters is always the code for the same amino
acid.
•
Amino acids used to build proteins, which are the
building blocks of DNA.
•
There are 20 amino acids, each with its own chemical
properties.
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Chemical Properties and Protein Structure
2
Specific sequence of
nucleotides
Specific sequence of
amino acids
Chemical
properties of
a protein
3
Chemical interactions
between amino acids
The way the amino acid
chain is twisted and
folded in the three
dimensional shape
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Roles of Proteins
Proteins have four major roles. Select the role below to learn more about what proteins do.
Provide structure
Provide transport
Act as catalysts
Control cellular processes
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Therapeutic Applications of Proteins
•
The value of human proteins in treating disease has long
been known.
o
For example, some proteins are useful
therapeutically and diseases caused by a protein
deficiency can be treated with the human protein
itself.
•
Only tiny quantities can be extracted from human tissue.
•
The goal of biotechnology is to produce sufficient
amounts of human protein of high quality.
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Denatured Proteins
•
The chemical bonds that hold a protein
together are weak and can easily be broken or
altered by environmental conditions such as
temperature, pH, and salt concentration.
•
If a protein becomes denatured (loses its
proper structure), then the protein product is
ruined!
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The “Language of Life”
Language
The analogy of DNA to language
makes it easier to understand the
science.
Just like language has certain
attributes, such as letters, words,
and sentences, so does DNA with
its nitrogen bases, amino acids,
and genes.
Letters
DNA
Nitrogen bases
(AGCT)
Words
Amino Acids
Sentences
Genes
Book
Proteins
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History of Genetic Engineering
Today
Scientists become “editors” to
create solutions that target
disease.
1962
1944
Scientists discover
genetic information
is stored in the DNA.
Francis Crick, James
Watson, and Maurice
Wilkin received The
Nobel Prize in
Physiology or
Medicines.
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Genetic Engineering
Genetic engineering uses recombinant DNA technology
to transplant and/or combine genetic information from one
organism to another.
While every cell in an individual organism has the same DNA
units, different segments of DNA coding tell individual cells
how to differentiate (what to do or what to produce, such as
proteins, enzymes, etc.).
Coding the human genome was so important because
scientists now know what each gene does, making genetic
engineering possible.
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Knowledge Check
Cells have a common basic structure.
a)
b)
True
False
Submit
Select the best response and then select Submit.
Knowledge Check
Proteins are the major structural and regulatory molecules
essential for life.
a)
b)
True
False
Submit
Select the best response and then select Submit.
Knowledge Check
Proteins are made up of ______ amino acids and each has
its own chemical properties.
a)
b)
c)
d)
e)
20
100
32
4
56
Submit
Select the best response and then select Submit.
Knowledge Check
Proteins:
a)
b)
c)
d)
e)
Provide structure.
Provide transport.
Act as catalysts.
Control cellular processes.
All of the above.
Submit
Select the best response and then select Submit.
Lesson 3:
Understand the Basic Elements of Biology
Important to Biotechnology
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What are Biologics?
Biologics are biological therapeutic products that generally encompass any protein, virus, vaccine,
blood product, or gene transfer product.
We are going to focus on human therapeutics.
Therapeutic proteins are proteins that are
produced in biological organisms or in
recombinant DNA technology.
These proteins include:
• Monoclonal antibodies.
• Cytokines.
• Growth factors.
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Biologics vs. Small Molecule Drugs
It is important that we understand the difference between biologics and pharma-derived products.
Most of you will have never taken a biologic drug, so your frame of reference will be tablets and pills.
Select each type of product below to learn more about how they are different.
Small Molecule Drugs
Biologics
•
Very fragile molecules that easily
degrade in the digestive system
•
Compromise most traditional
pharmaceutical drugs
•
Injected into bloodstream
•
Developed via chemical synthesis
•
Designed to interact with
molecules outside the cell
•
Taken orally
•
Absorbed through the intestine walls
into the bloodstream.
•
Usually designed to block targets
•
Typically more difficult and costly
to manufacture
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So, Why Biologics?
1
2
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Developing a Recombinant Protein
Mix
recombinant
plasmid with
Create
recombinant host cells so
transformplasmid
ation and
cloning
occur.
Grow small
scale cell
culture.
Conduct
assay
development
and animal
testing.
Grow large
scale cell
culture.
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Conduct
product
recovery,
formulation,
and quality
control.
Conduct
aseptic
filtration and
processing
for
contaminati
n control.
Create Recombinant Plasmid
1
3
2
Recombinant
plasmid.
Transformation
and cloning.
Small scale cell
culture.
Assay
development and
animal testing.
Large scale cell
culture.
Listen to the audio and then select Next to continue.
Product recovery,
formulation, and
quality control.
Aseptic filtration
and processing for
contamination
control.
Transformation and Cloning
Recombinant
plasmid.
Transformation
and cloning.
Small scale cell
culture.
Assay
development and
animal testing.
Large scale cell
culture.
Listen to the audio and then select Next to continue.
Product recovery,
formulation, and
quality control.
Aseptic filtration
and processing for
contamination
control.
Small Scale Cell Culture
1.
Recombinant
plasmid.
Transformation
and cloning.
Small scale cell
culture.
Assay
development and
animal testing.
Large scale cell
culture.
Listen to the audio and then select Next to continue.
Product recovery,
formulation, and
quality control.
Aseptic filtration
and processing for
contamination
control.
Assay Development and Animal Testing
1.
Recombinant
plasmid.
Transformation
and cloning.
Small scale cell
culture.
Assay
development and
animal testing.
Large scale cell
culture.
Listen to the audio and then select Next to continue.
Product recovery,
formulation, and
quality control.
Aseptic filtration
and processing for
contamination
control.
Large Scale Cell Culture
1.
Recombinant
plasmid.
Transformation
and cloning.
Small scale cell
culture.
Assay
development and
animal testing.
Large scale cell
culture.
Listen to the audio and then select Next to continue.
Product recovery,
formulation, and
quality control.
Aseptic filtration
and processing for
contamination
control.
Product Recovery, Formulation, and Quality Control
1.
Recombinant
plasmid.
Transformation
and cloning.
Small scale cell
culture.
Assay
development and
animal testing.
Large scale cell
culture.
Listen to the audio and then select Next to continue.
Product recovery,
formulation, and
quality control.
Aseptic filtration
and processing for
contamination
control.
Contamination Control
Contamination is the presence of unwanted
microbes that can have an adverse impact on
the product. Contamination must be prevented
in aseptic processing.
Recombinant
plasmid.
Transformation
and cloning.
Small scale cell
culture.
Assay
development and
animal testing.
Large scale cell
culture.
Listen to the audio and then select Next to continue.
Product recovery,
formulation, and
quality control.
Aseptic filtration
and processing for
contamination
control.
Aseptic Filtration and Processing
Aseptic Processing
Aseptic Filtration
•
Recombinant
plasmid.
Used to sterilize products that cannot be terminally sterilized in their final
container.
Transformation
and cloning.
Small scale cell
culture.
Assay
development and
animal testing.
Large scale cell
culture.
Select each tab then select Next to continue.
Product recovery,
formulation, and
quality control.
Aseptic filtration
and processing for
contamination
control.
Aseptic Filtration and Processing
Aseptic Processing
Aseptic Filtration
•
Designed to achieve a sterile product, but this may not always be the end
result.
•
Techniques are often associated with the formulation, filling, and sealing of
the drug product into its final delivery means.
Recombinant
plasmid.
Transformation
and cloning.
Small scale cell
culture.
Assay
development and
animal testing.
Large scale cell
culture.
Select each tab then select Next to continue.
Product recovery,
formulation, and
quality control.
Aseptic filtration
and processing for
contamination
control.
Knowledge Check
Biologics are biological therapeutic products that generally
encompass any:
a) Protein.
b) Virus.
c) Vaccine.
d) Blood or gene transfer product.
e) All of the above.
Submit
Select the best response and then select Submit.
Knowledge Check
Match the terms with their correct description.
o
Biologics
o
Small Molecule Drugs
o Very fragile molecules that easily degrade in the
digestive system and are injected into the
bloodstream.
o Most traditional pharmaceutical drugs; taken orally.
Submit
Drag each term to the best response and then select Submit.
Knowledge Check
Aseptic processing is designed to achieve a final sterile
product.
a)
b)
True
False
Submit
Select the best response and then select Submit.
Lesson 4:
Discuss the Basic Scientific Principles of the
Bioprocess
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SME: Please review slide and VO text to ensure it is
accurate. Changed to ensure clarity.
The Industrial Process
Like all industrial processes, the manufacture of biologic products requires inputs and activities
to manufacture the product. The corresponding output will produce some form of waste.
Listen to the audio and then select Next to continue.
Biotech Process Steps
Non-engineers will need to understand what a process is and how the unit operations
integrate to produce the product. All biotech manufacturing processes have a general
composition.
1
2
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Choosing the Right Material
Choosing the right starting material is vital to success. In a perfect world, the starting material should
fit the following criteria, though not all production cell lines display all of these characteristics:
Stable in
culture
Grow fast
Able to
make the
product in
large
quantities
Grow on
inexpensive
nutrients
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Examples of Choosing the Right Material
Companies spend significant amounts of R&D money to make sure they select the right starting
material. The right starting material is dependent upon the product being manufactured.
For example:
E. coli bacteria are given the
gene to make human insulin
so that now diabetics no
longer rely on insulin purified
from animal carcasses.
Chinese hamster ovary (CHO)
cells grow well in culture and are
used to manufacture many
products such as human interferon
(a protein).
Select Next to continue.
Cell Growth Process
Culture
Stock selection & testing
(covered in this lesson)
Media
preparation
Food material for cell growth
(covered in this lesson)
Cell Growth
Production growth
(covered in this lesson)
Recovery
Removal of spent biomass
(covered in module 2)
Purification
Purify product
(covered in module 2)
Formulation
Final dosage form
(covered in module 2)
Select each item then select Next to continue.
Culture: Processing the Cell Line
Cell Line Selection
Cell Bank Development
Scale-up
To promote the expected level of growth, cell lines need to:
•
Be easily reproducible.
•
Grow fast.
•
Use inexpensive medium.
This does not mean that every cell line meets these criteria. But the majority of cell lines
that we see used in the industry:
•
Produce high quality product.
•
Grow in inexpensive medium.
Culture
Media
preparation
Cell growth
Recovery
Select each tab then select Next to continue.
Purification
Formulation
Culture: Processing the Cell Line
Cell Line Selection
Cell Bank Development
Scale-up
Testing
• The quality and viability of the cell line must be confirmed through testing.
• Cell lines will be categorized as “master” and “working.”
o Using the original master cell line, subsequent working cell lines will be used to
continue the manufacturing operations for years.
o The working cell banks are genetic equals of the master.
Storage
• The storage and security of these cell banks is important. Millions of dollars have been
spent to genetically develop the master cell line.
• Protection of this investment is not only good business, it is also a regulatory
requirement.
Culture
Media
preparation
Cell growth
Recovery
Select each tab then select Next to continue.
Purification
Formulation
Culture: Processing the Cell Line
Cell Line Selection
Cell Bank Development
Scale-up
•
The processing of the cell line begins at a very small scale; a few milliliters of material
are used to begin the growth process.
•
As volumes grow, the scale of the process increases.
•
With each scale-up step, the process grows closer to reaching the maximum volume
needed to support the overall process.
Culture
Media
preparation
Cell growth
Recovery
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Purification
Formulation
Media Preparation
Just like people, cells need a balanced diet to provide them
with energy and nutrients.
•
•
Media broth
Metabolism
Culture
Media
preparation
Cell growth
Recovery
Purification
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Formulation
Carbon-containing compounds
provide the chemical energy cells
need to function.
A Cell’s Diet
Sometimes cells can’t make all
the biomolecules they need from
raw materials. Additives such as
amino acids, vitamins, antibiotics,
and anti-fungal agents may be
necessary.
Carbon
Additives
Glucose is often the primary
energy source. Starches or other
sugars are also used.
Nitrogen
A Cell’s
Diet
Other
elements
Cells also require sodium,
potassium, and magnesium salts.
Other metals such as zinc, iron,
and manganese will also show as
trace elements.
Culture
Media
preparation
Oxygen and
Hydrogen
Cells need a nitrogen source to
make amino acids, nucleic acids,
and other molecules. Sources are
usually NH3 ( as a gas) and NH4
(solid form as a salt).
Cells get oxygen and hydrogen
from air and water and also from
carbon and nitrogen sources.
Phosphorus
These are usually supplied from
inorganic salts.
Cell growth
Recovery
Select each item then select Next to continue.
Purification
Formulation
Example of Media Recipes
Microbial (60,000L)
Culture
Mammalian (10-20,000L)
•
65% glucose solution
•
Ammonium sulfate
•
Potassium and sodium salts
•
Protein hydrolysate
•
Growth factors
•
Water
Media
preparation
Cell growth
Recovery
Select each tab then select Next to continue.
Purification
Formulation
Example of Media Recipes
Microbial (60,000L)
Culture
Mammalian (10-20,000L)
•
Amino acids
•
Soy protein hydrolysate solution (heated)
•
Salts
•
Trace elements: iron and zinc
•
Sodium hydroxide
•
Methotrexate
•
Glucose
•
Amino acids
•
Potassium phosphate
Media
preparation
Cell growth
Recovery
Select each tab then select Next to continue.
Purification
Formulation
Media Recipes – Things to Watch Out For
Culture
Media
preparation
•
Mixing mistakes can cause product failure.
•
Sequence of additions may be critical; following the
exact steps in the recipe will be a key element of
success.
•
All media must get into tank and be mixed.
•
Many mammalian media components are heat-sensitive
and must be filter-sterilized.
•
SOPs (the instructions on how to manufacture) may be
complex and must be followed.
Cell growth
Recovery
Select Next to continue.
Purification
Formulation
Media Mixing
As you can see from this graphic,
the manufacture of media
components is a major
manufacturing operation.
There are numerous steps,
extensive equipment needs, and
possibly large volumes of
materials and utilities that will be
required just to provide the cells
with the right diet. All of these
operations are considered part of
the overall product manufacturing
process and thus under
regulatory oversight.
Culture
Media
preparation
Cell growth
Recovery
Purification
Roll over each image and then select Next to continue.
Formulation
Cells Affect Their Environment
1
2
Culture
Media
preparation
Cell growth
Recovery
Purification
Listen to the audio and then select Next to continue.
Formulation
Cell Culture Life Cycle
[5]
[4]
[6]
Death
[3]
[1]
[2]
Culture
Media
preparation
Cell growth
Recovery
Purification
Listen to the audio and then select Next to continue.
Formulation
Knowledge Check
All biotech manufacturing processes have a general
composition of _________ operations and __________
operations.
Submit
Type your response in the question field, then select Submit to
continue.
Knowledge Check
____________ is the process in which cells break down
ingredients in the growth media, release energy, and reassemble elements into other molecules.
Submit
Type your response in the question field, then select Submit to
continue.
Knowledge Check
Media mixing is not a major manufacturing operation and is,
therefore, not under regulatory oversight.
a)
b)
True
False
Submit
Select the best response and then select Submit.
Knowledge Check Summary
[placeholder for knowledge check summary]
Select Next to continue.
Summary of Learning Goals for Module 1
You have completed this module.
For your review, here are the learning goals addressed in this
module and the knowledge you should be able to
demonstrate as a result:
• Recognize basic biotechnology principles
• Review the science of biotechnology
• Understand the basic elements of biology important to
biotechnology
• Discuss the basic scientific principles of the bioprocess
Listen to the audio and then select Next to continue.
Closing
If you have any questions about this module, please contact member services:
(813) 960-2105
training@ispe.org
When you are ready, navigate to Module 2 in the LMS.
Select Back to review this module or exit to the next module