Download PRACTICAL APPLICATIONS OF BIOTECHNOLOGY

tolerance to ____________ and _____________
to environmental stresses (drought, heat, cold).
PRACTICAL APPLICATIONS OF BIOTECHNOLOGY
1. Bioprocessing technology

Uses whole living cells or components of them
to manufacture desired products.

Most common whole cells used are yeast and
bacteria (one-celled organisms).

Most common components are enzymes
(proteins that catalyze chemical reactions).

Cells isolated from animals and plants also are
used to produce desired products.
2. Genetic engineering

The technique of removing, modifying or adding
genes to a DNA molecule to change the
information it contains.

More specifically is known as recombinant DNA
(rDNA) technology.

The product of rDNA technology is known as a
genetically modified organism, or GMO.

Example: Gene for human insulin inserted into
E.coli → bacteria that make human insulin (a
biopharmaceutical).

Create disease- and insect-resistant trees to
help meet demand for wood products.
1. Agricultural applications — _____________________

Better detection of ____________

More nutritious _________

New and more effective ____________

Improved _______________ for diseases
2. Medical and Health Care Applications

________________________________
Example: quick test for strep throat

MANY new treatments for ______________
and conditions
Examples: _____________, stroke, anemia,
cystic fibrosis, hemophilia, leukemia and other
_________; hepatitis; rheumatoid arthritis;
growth deficiencies; transplant rejection
3. Chemical and Environmental Applications (Industrial
Biotechnology)
1. Agricultural applications — better crops, improved
animal health

Produce enzymes used in ___________
detergents.
2. Medical and health care applications — new tests,
vaccines, medicines

Use genetically modified microorganisms that
break down _______________________.
3. Chemical and environmental applications — better
manufacturing processes and consumer products

Develop bio-based, biodegradable plastics.

Improve manufacturing that reduces the
amount of ________________________.
1. Agricultural applications — _____________________

Improve crop yields by introducing genes that
confer __________________________,
Clinical Trials — A Closer Look
Clinical research and development
The Food and Drug Administration (FDA) is the main
consumer watchdog for numerous products: Drugs and
_____________ (prescription and over-the counter),
Food, Medical devices, ___________ feed and drugs,
Cosmetics, Radiation-emitting products (such as
___________________ and pagers)
The application to the FDA to request permission to
begin human testing is called an Investigational New
Drug application, or IND.
The evaluation of pharmaceuticals and
biopharmaceuticals is a highly _____________ process
requiring many _______ to prove a drug is safe and
effective.
This is known as the drug development process.
There are a number of steps in the new drug
development timeline.
The steps include:
► research and _____________ in the lab ►
testing in ___________ models (pre-clinical) ► several
phases of testing in ___________ (clinical trials)
Clinical trials are ____________________ designed to
distinguish a drug’s __________ from other influences.
Drugs must be thoroughly analyzed and tested in animal
models _____________ they are tested in humans.
Research and development in the lab
R&D involves initial synthesis and analysis of a
promising pharmaceutical OR development and analysis
of a biopharmaceutical produced in living cells.
On upcoming slides, the word “drug” applies both to
pharmaceuticals and to biopharmaceuticals.
Pre-clinical testing
When new drugs show promise in lab testing, studies
are designed to evaluate them further.
These studies in animals are referred to as “pre-clinical
studies.”
Pre-clinical studies help establish ________________
____________________________ of the treatment
if/when human studies begin.
Many new drugs and treatments are ______________
at this step because they are proven unsafe.
The IND permits the use of an investigational new drug
for the sole purpose of __________________________.
Phase 1 clinical trials
Drug is tested for its _____________ with the human
body.
Trials are conducted to determine the appropriate dose
range with regard to ________ and _____________
(NOT ______________).
Trials are conducted on a limited number (___-___) of
normal volunteers or patients (such as patients with
cancer or AIDS).
Phase 1 trials often take nine to 18 months to complete.
Many drugs are abandoned in Phase 1 testing because
of problems with safety or toxicity.
Phase 2 trials
Small-scale, well-controlled trials evaluate the
preliminary ________ AND ___________ in ____ to
____ patients with the disease or condition to be
treated.
May focus on dose-response, dosing schedule or other
issues related to preliminary safety and efficacy.
Often take one to three years to complete.
Additional _________ testing may be conducted at the
same time to obtain long-term safety data.
If studies show drug to be safe and useful, testing may
proceed to Phase 3.
Phase 3 trials
The most ____________ (and expensive) testing of a
drug.
These trials fully assess _________, efficacy and drug
dosage in a _________ group of patients with the
specific disease to be tested.
Conducted on larger (______s to ________s) and more
diverse groups of patients with the condition.
Make comparisons between the new treatment and a
placebo and/or the standard treatment.
Trials help to better understand the drug’s safety and
uncover any adverse effects.
Trials often take two to five years to complete.
New Drug Application (NDA)
Submitted to the FDA once all or most of the proposed
studies are completed.
Submitted if company believes adequate positive
information has been obtained to warrant a request to
market the drug.
Phase 4 clinical trials
Companies sometimes continue clinical trials of a drug
after it has been approved for marketing.
Phase 4 trials may be performed to learn more about
side effects and long-term risks and benefits.
Companies also may evaluate different formulations of
a drug (like _________________) or test the drug for a
different indication.
The FDA sometimes requires companies to conduct
Phase 4 trials.
Post-marketing surveillance
The NDA contains extensive data on the investigational
drug and results of the clinical trials.
The company must continue to report information
about new findings and problems after drug approval.
The NDA is many ______________ of pages long. The
FDA hopes that eventually they will be submitted
electronically.
_________________________ can report new findings
to the company or directly to the FDA (consumers can
report information to the FDA as well).
By law, the FDA has ___ days to decide if there is
enough information to continue with the NDA review.
By law, the FDA is required to make a final decision
within 180 days.
In practice this timeframe often is lengthened
(considerably) by mutual agreement.
New Drug Application (NDA) Review
The Center for Drug Evaluation and Research (CDER)
reviews applications for pharmaceuticals.
The Center for Biologics Evaluation and Research (CBER)
reviews applications for biopharmaceuticals, ________,
blood and _____________________.
A typical timetable from test tube to patient
R&D and pre-clinical
3.5 years
Phase 1
1.0 years
Phase 2
2.0 years
Phase 3
3.0 years
NDA evaluation
2.5 years
Total
12.0 years
Producing a Pharmaceutical or
Biopharmaceutical-The Manufacturing
Process
Process development
 Scientists and engineers begin to figure out how
to “_____________” production of a drug even
__________ it receives FDA __________.
 Manufacturing processes might be quite
different than the small-scale lab procedures.
Production
 Production of a pharmaceutical or
biopharmaceutical involves many different,
complex and lengthy steps:
 Synthesis (chemical or cell culture)
 Purification
 Formulation
 Final dosage form preparation
Step 1: Synthesis
 Order the raw materials needed to make the
product.
 Test all raw materials to be sure they meet
quality standards.
 For biomanufacturing, equipment and materials
need to be ____________to avoid bacterial and
other __________________ to the cell cultures.
 The product then is created.
 For pharmaceuticals, there are chemical
processes involved (chemical synthesis).
 For biopharmaceuticals, cell culture or
fermentation is involved.
 The product is referred to as the
“_______________________”
 For the biopharmaceutical, the original cell
culture is started in small bottles (around the
size of large ________________)
 As the cells grow and multiply, they are
introduced into a small __________________.
 Eventually they are grown in large bioreactors,
which can be several ______________ tall!
Step 1: Biosynthesis
A small bioreactor in the foreground, with a
larger one behind it.
Step 2: Purification
 After the active ingredient is synthesized, it
must be purified.
 Purification involves removing the ___________
used in the process.
 For biopharmaceuticals, purification involves
separating the ________ from the cellular
nutrients and ______________ (the “soup”)
they grew in.
 The end result of production is called the bulk
product.
 The bulk product may be sold as is, processed
further at the same plant or shipped to another
plant for further processing.
Step 3: Formulation
 Several other operations are required to get
bulk product into its final form.
 Formulation involves chemical mixing
operations to ________________________
___________________________________,
such as fillers, needed in the final form.
 The final form may be a solid (tablet or capsule),
liquid, gels/creams or aerosols.
 Biopharmaceuticals usually are sold as sterile
___________ or sterile _____________.
Step 4: Final dosage form preparation
 The formulated preparation is made into its
final form.
 The final form is ____________ into containers.
 The containers are ___________ and packaged.
Quality matters
 The standards of quality are high because the
stakes are high.
 Poor quality products can _________ or even
_________ consumers.
 Companies must conform to the stringent
_________________________________ (GMP)
regulations established by the FDA.
Ensuring quality
 Manufacturers have three departments that
ensure quality:
 Quality control (QC)
 Quality assurance (QA)
 Validation
Quality control
QC employees ____________ and ________ the
raw materials and the product during many stages of
the manufacturing process.
Quality assurance
 QA ensures product quality by setting up and
checking the systems of ________________
__________________ (SOPs) and of
documentation.
 SOPs guide every task by defining each
_____________ in detail so it can be performed
____________ the same way every time.
 Companies are required to prepare and follow
SOPs by the FDA.
 Any _______________ from the SOP must be
documented and approved by the QA
department.
 Critical deviations that could affect product
quality are investigated further.
 Documentation __________ that a company
has done what it said.
 A company is required to have a traceable,
written record of all processes and checks.
 “If it isn’t written __________, it doesn’t exist. If
it isn’t written down, it never _____________.”
Validation
 Validation proves that a manufacturing process
will ________________ produce the product to
predefined specifications.
 The operation of every part of the plant that
affects quality must be validated.
 If a manufacturing process is changed or if a
new product is introduced, all processes and
equipment that affect quality must be
validated.
 Validation scientists and engineers have
extensive experience because they must be
very familiar with the regulations.
Five rules for quality
1. Understand _____________ needs
 Companies have internal customers (fellow
employees) as well as external customers.
 For a process technician, your internal customer
is your coworker at the next stage of the
process.
2. Say what you do — write down procedures
 Standard _____________ and ________ are
required for every step.
 Batch records define the steps required to
manufacture the product, the materials used,
etc.
3. Do what you say — ____________________
 Manufacturers are required to consistently and
__________ follow procedures.
 SOPs are _________, and there are SOPs for
every step.
4. Prove it — keep records
 Companies must have _____________, written
records of all processes.
 Again, “If it isn’t written down, it doesn’t exist.
If it isn’t written down, it never happened.”
5. Improve it
 Companies must continually evaluate its
processes and procedures.
 They should take steps to make them
___________.
 Of course, new procedures must be validated!
Standard Operating Procedures
 SOPs define a __________________________
so it can be performed the same way, _______
__________.
 Lengthy regulations related to manufacturing
are found in the Code of Federal Regulations.
 Good Manufacturing Practice (GMP) regulates
methods, equipment, facilities and controls.
 What is included in SOPs?
 Purpose- describes purpose of _____________.
 Scope- states _______ the SOP applies to.
 Responsibility-states ________ should perform
the SOP .
 ______________- lists other SOPs or
documents needed to perform the SOP.
 Materials and equipment- lists what’s needed
to _____________ the SOP.
 Procedures- provides ________________ for
carrying out a task.
 Approval signatures- shows the persons who
have ___________ and ___________ the SOP
 _____________ date- date the SOP takes effect.
Workplace Realities- Getting a Job
and Getting Ahead
What skills are needed to compete for jobs in
biomanufacturing?
•
Companies value one to two years of college
and an associate degree.
Ways to obtain valuable experience
•
1. The appropriate level of education and relevant job
or military experience
Fieldwork or internship in the pharmaceutical
industry
•
Undergraduate research in a laboratory
2. Mastery of basic skills
•
Employment in another type of manufacturing
3. Technical knowledge and skills
2. Mastery of basic skills
4. Employee success skills
Basic skills include:
1. Education and experience
•
Reading
•
Writing
•
At least a high school diploma or GED
•
Calculation
•
Companies rarely hire workers directly out of
high school; they prefer workers who have
______________ outside of the high school
environment.
•
Problem-solving
•
Computer literacy (general office
software)
•
Companies want employees with prior
_____________ or _________________
experience.
•
Applying your reading, writing and math skills
•
Reading ___________ reports from
previous shifts
•
Reading SOPs, equipment manuals
•
Writing __________
•
______________ for work regularly and on time
•
Using formulas to make solutions
•
Is willing and able to __________ to shift work
•
Applying your computer literacy skills
•
•
Using computers that control
__________
Manages personal schedule to meet shift
schedules
•
Plans and organizes work and sets priorities
•
Can attend to several tasks at once
•
Completes tasks on time; keeps production on
schedule
•
Writing reports using word processing
software
A. Manage time
3. Technical knowledge and skills
Applying scientific principles and technical
skills
B. Maintain a safe and orderly work environment
•
Complies with health, environmental and safety
regulations
Operating process equipment
•
Follows dress and protective clothing ________
•
Analyzing production samples
•
•
Interpreting lab test results
Assumes _______________ for safety of self
and others
•
Controlling the flow of _________ and
liquids
•
Sets a ________________________ for others
•
Handles and maintains equipment and
materials with care
•
Follows good __________________ practices
•
Growing _________
•
•
Purifying products
•
Identifying microbial _______________
4. Nine employee success skills
A successful applicant demonstrates the ability to:
A. manage ________.
C. Keep learning new skills
•
Shows interest in learning new knowledge, skills
and tasks
•
Is _____________ and can work with
_________ supervision
•
Accepts that ______________ learning is part of
the job
B. maintain a ________ and orderly work environment.
C. keep learning new skills.
D. follow procedures exactly.
E. keep precise records.
D. Follow procedures exactly
(_____________________)
F. communicate effectively.
•
Follows directions exactly as written every time
G. work as a team member.
•
Takes no shortcuts
H. solve problems, troubleshoot and _________ the
process.
I. understand and apply the principles of _________
business.
E. Keep precise records
(___________________)
•
Keeps records that are accurate
•
Keeps records that contain required details
“If it isn’t written down, it doesn’t exist.”
“If it isn’t written down, it never happened.”
H. Solve problems, troubleshoot and improve the
process
•
Is willing to learn the manufacturing process
and how different units in the plant work
together
•
Is sensitive to anything unusual in surroundings
(_________, _________, ________) and
responds with appropriate action and
communication to identify causes and solutions
•
Suggests ways to improve the manufacturing
process, even when production is progressing
without problems
•
Knows and can apply a variety of problemsolving approaches and methods to determine
causes and recommend solutions
F. Communicate effectively
•
Communicates _________ and shares
information with others in a _________ manner
•
Communicates effectively in ________, through
____________ (telephones, radios, e-mails) and
in ___________.
G. Work as a team member
•
Recognizes individual ______________ toward
a goal
•
Accepts _________________ for team’s success
or failure
•
Accepts own mistakes; is ________________ to
corrections and suggestions
•
Understands the need for ____________ in the
manufacturing process
•
Shares concepts, ideas and problems with
others.
•
Can identify factors within the manufacturing
process that determine _________
•
Coordinates own work and the work of others
•
•
Can conduct meetings and help groups make
decisions
Can identify possible ___________ to profit in
the manufacturing process
•
•
Is eager to ________________________ others
Can explain why pleasing internal and external
customers is critical to a company’s __________
I.
Understand and accept the principles of good
business
On the Job- Careers in
Biomanufacturing
 Seizing the Opportunity
 Bioprocess, pharmaceutical and chemical
manufacturing jobs offer unique opportunities
and benefits.
 You will be working in a ____________ industry.
 You will be working in an industry in which
skilled and competent employees are in great
demand.
Advantages of working in this industry
1. Pride in your product
You will have the satisfaction of making
products that ___________ lives and boost the
economy, including products that:
 increase ________ production, making
it possible to feed the world.
 reduce _________ deaths and prevent
childhood diseases.
 relieve painful symptoms, fight disease
and save _________.
2. Higher wages
Employees in bioprocess, pharmaceutical and
chemical manufacturing earn an average wage that is
____________ those in other manufacturing industries.
Example: Entry-level process technicians earn
$25,000 to $35,000 per year.
4. Modern and professional atmosphere
● High-tech, computer-controlled, efficient
environments staffed by well-educated, professional
technicians, engineers and scientists.
● Many companies use a __________ approach and
encourage employees to assume higher levels of
responsibility for problem solving.
5. Safe working environments
●
Because they are highly regulated by the
government and required to follow very detailed good
manufacturing practice (GMP), biotechnology,
pharmaceutical and chemical companies provide a very
_________ place to work.
●
One of the first things you will acquire on the
job is thorough training in __________.
6. Job variety and career advancement
 Employees often have an opportunity for
________ training or moving from one
department to another.
 As employees gain more experience, there also
are opportunities for career advancement.
 Employees can advance in managerial tracks,
with more _______________ responsibility.
 Employees may choose to advance within
scientific or engineering specialty tracks.
 Biotechnology, pharmaceutical and chemical
companies often have programs that ________
employees for their knowledge and skills.
3. Stable employment
 They reward employees for completing inhouse training and formal academic education.
●
A rapidly growing industry increases both the
demand and opportunities for skilled, competent
professionals.
 Many companies provide some ________
support for employees to attend college
courses.
●
Your knowledge is your ___________________
insurance.
●
Your mastery of process manufacturing
technology is portable.
●
If the particular company you work for
downsizes, you are very likely to find a job in a different
company.
On the Job-Educational options
 Many educational options are available:
 Two-year (associate or A.A.S.) degrees
 Four-year (bachelor or B.S./B.A.)
degrees
 Certificate programs
 Even for jobs requiring only a high school
degree, companies _________ hire anyone
straight out of high school.
 Employers look for at least some additional
__________________, prior employment or
military experience that Entry-level positions
are available
 The good news — there are many different
entry-level positions in biomanufacturing.
 Entry-level jobs are ones that require a
particular level of education but no ________
work experience in the pharmaceutical or
biopharmaceutical industries.
Job titles and descriptions
 Production: _____________________
Responsible for a variety of tasks involved in
monitoring and control of manufacturing the product.
 Production: Manufacturing prep process
technician
Responsible for washing, drying and sterilizing
______________.
 Production: Formulation/fill technician
Responsible for preparing the finished product
from the purified active pharmaceutical or
biopharmaceutical ingredients.
 Production: Packaging technician
 The job titles and brief descriptions listed on
these slides illustrate the type of positions that
exist in a generic biomanufacturing facility.
Uses packaging systems to label, ___________
and package the finished product.
 The actual organization of the various divisions,
job titles and job descriptions vary from one
company to another.
These are entry-level positions requiring a fouryear engineering degree — a bachelor of science (B.S.)
in engineering.
The job descriptions are grouped into five areas:
1. Production
2. Quality control (QC), quality assurance
(QA) and validation
3. Manufacturing Support
4. Research and development (R&D)
5. Other divisions
 Production: Process engineers
 Production: Process engineer in manufacturing
●___________, develops and operates the current
manufacturing process.
● Works with technicians to ensure that the product is
manufactured properly.
 Production: Process engineer in process
development
Responsible for the design, ____________ and
validation of new processes, from the laboratory, to
pilot-plant stage, to large-scale manufacturing.
1. Production Positions
Technicians
 Positions include various technicians who work
“___________” in the biomanufacturing facility.
 These entry-level positions require a high school
diploma, a process technician certificate or an
A.A.S. degree, plus some “maturation time”
after high school.
2. Quality control positions
 Quality control (QC) involves checking the ____
______________ and ___________ during
every phase of its manufacture.
 QC jobs include:
 entry-level positions requiring an A.A.S.
 entry-level positions requiring a
B.A./B.S.
 positions requiring B.A./B.S. plus
industry experience.
 QC: Quality control assistant
 Analyzes raw materials, in-process
samples and finished formulations
according to SOPs
 Entry level; requires a two-year degree
(A.A.S.).
 QC: Quality control associate
● Coordinates activities needed to ____________ good
manufacturing practice (GMP) and to update _______’s.
● Reviews data obtained by the QC assistant and
reports abnormalities.
 QC: Quality control engineer
 _________, revises and maintains ___________
for converting raw materials into products.
 Devises SOPs for testing procedures.
 QC: Process quality inspector
Performs a wide variety of inspections, checks,
tests and sampling procedures related to the
manufacturing process.
2. Quality assurance positions
 Quality assurance (QA) focuses on the _______
system of manufacturing.
 QA employees set up and check the standard
operating procedures (SOPs) and
documentation.
 Their jobs ensure product quality and
compliance with Good Manufacturing Practice
(GMP) regulations.
 These positions require a B.A./B.S.
 QA: Quality assurance associate
Writes and edits SOPs, laboratory procedures,
manuals and other documents in a ________________.
 QA: Quality assurance auditor
Performs audits of production and quality
control to ensure compliance to in-house specification,
standards and regulatory requirements.
2. Validation positions
 Validation proves that an SOP will ___________
produce the product with certain specifications
when carried out exactly.
 The operation of every part of the plant has to
be validated.
 Generally all validation positions require work
experience in the industry.
 2. Validation positions
● Validation specialist
(minimum A.A.S./B.S. degree)
● Validation engineer
(minimum B.S. in engineering)
● Validation scientist
(minimum B.S. in science)
 Validation specialist, engineer and scientist
 Responsible for ensuring a product is
manufactured in accordance with regulations
and in-house standards.
 Validation engineers and scientists often have
advanced degrees (M.S. or Ph.D.) and generally
need extensive experience in the industry.
 They must be thoroughly familiar with the ____
regulations and how to implement them.
3. Manufacturing support
 Maintenance of the plant and all of its
___________ (electrical systems, water
purification systems and heating, ventilation
and air conditioning)
 Management of _________ products created
during the manufacturing process
 Many of these jobs are entry-level positions.
 Manufacturing support:
_______________/calibration ______________
Responsible for calibrating, testing,
troubleshooting, repairing and maintaining a variety of
circuits, components, analytical equipment and
instrumentation.
 Manufacturing support technicians
Manufacturing support technician
 Maintains manufacturing equipment and solves
production problems caused by machinery.
Environmental technician
 R&D: Research assistant and associate
Research assistant
 Performs lab ___________________ and tests
according to good laboratory practices under
the direction of a research associate.
Research associate
 Seeks out new and more efficient ways to use
and produce existing products.
R&D: Research scientists in drug discovery
 Work in a team in numerous areas
 Identifying new drug ___________
 Performs routine _______________ testing and
carries out waste treatment operations.
 Creating animal models to test new
drugs
 Manufacturing support engineers
 Investigating the causes of and
treatments for ____________.
Maintenance engineer
 Involved with ________________ and repairs of
refrigeration, air conditioning, steam boilers,
etc.
____________________________
 Designs and installs instruments to monitor and
control certain manufacturing processes.
 Disciplines include:
 chemistry
 cell biology
 molecular biology
 biochemistry
Environmental engineer
 Designs waste storage, treatment and recycling
facilities.
4. Research and development (R&D)
 These scientists generally work in labs that are
_____ _________ of the manufacturing facility.
 The educational requirements for these
positions vary considerably.
 Although many companies have entry-level
positions, they greatly value experience in the
industry.
5. Other divisions
● These employees may work in offices within the
facility or at another location.
● The educational requirements vary according to the
job.
● Companies value experience in the industry and often
require it.
 Other divisions: Customer support specialist
 Responsible for ensuring _________ of product
that meets the customers’ requirements.
 May serve as a ___________ for customers with
technical questions.
 Requires a four-year degree and usually some
industry experience.
 May work in offices within the facility or in
another location.
 Other divisions: Clinical trials associate (CRA)
 Assists in the monitoring and management of
clinical trials.
 Position requires knowledge of _________
__________________, clinical research, federal
regulations and good clinical practices.
 Experience in the industry is highly desirable.
 Other divisions: Regulatory affairs specialist

Coordinates and prepares a variety of
documents to submit to the _____.

There is considerable opportunity for
_______________, within the regulatory affairs
department as well as moves into other
departments.

The regulatory affairs associate usually is the
entry-level position (although industry
experience may be required).