CNPR, NAPSR Exam
Drug Discovery - Answer-• Unlike small molecule drugs (pharmaceuticals), large molecule drugs
(biopharmaceuticals) are mainly protein-based
o These protein-based drugs are similar to natural biological compounds found in human body or
they're fragments that mimic active part of natural compounds
Discovery of Pharmaceuticals - Answer-commences w/ scanning hundreds of compounds, whether w/
actual materials (irrational approach) or virtual simulations (rational approach)
• Pharmaceuticals are new chemical entities (NCE) and are produced (synthesized) in manufacturing
plants using techniques based on chemical reactions of reactants
Discovery of Biopharmaceuticals - Answer-researchers have to examine compounds w/in humans
o Ex. Hormones or other biological response modifiers and how they affect biological processes
o In some cases, study pathogens such as influenza virus or bacteria to derive vaccines
o In other cases, researchers copy these biological response modifiers and use them as replacement
therapy
o Protein-based drugs are manufactured in biological systems, such as living cells, producing desired
protein molecules in large reaction vessels or by extraction from animal serum
o Becoming increasingly important
• More potent and specific—more similar to proteins w/in body therefore more effective in treating our
diseases
,Areas of Biopharmaceuticals - Answer-• Prophylactic→ preventive as in vaccines
• Therapeutic→ antibodies
• Replacement therapy→ hormones, growth factors
Biologics - Answer-FDA definition is:
o Biological product subject to licensure under Public Health Service Act is any virus, therapeutic serum,
toxin, antitoxin, vaccine, blood, a blood component or derivative, allergenic produce, or analogous
product, applicable to prevention, treatment or cure of diseases or injuries to humans. Biological
products include, but are not limited to, bacterial and viral vaccines, human blood and plasma and their
derivatives, and certain products produced by biotechnology, such as interferons and erythropoietins.
Biologics encompass many different protein-based drugs, and include blood products such as clotting
factors extracted from blood.
Vaccines - Answer-• Basis of vaccination is that administering small quantity of a vaccine (antigen that
has been treated) stimulates our immune system and causes antibodies to be secreted to react against
foreign antigen
• Later in life, when we encounter another exposure to same antigen, our immune system will evoke a
memory response and activate defense mechanisms by generating antibodies to combat invading
antigen
• Contains antigenic components that are obtained from or derived from pathogen
o Include mainly viruses, bacteria, parasites and fungi
o Research has shown that part of pathogen that causes disease (virulence) can be decoupled from
protective part (immunity)
• Development focuses on means to reduce virulence factor while retaining immunity stimulation
• Oral or parenteral
Vaccine Preparations - Answer-Attenuated Vaccines
Killed or Inactivated Vaccines
Toxoids
,Attenuated Vaccines - Answer-• Virulence of pathogen that can be reduced in number of ways
• By chemical treatment, by temperature adaptation, or by growing pathogen in specified other than
natural host (passaging)
• Advantages are low cost preparation, elicit desired immunological response, and normally single dose
is sufficient
• Disadvantages are potential to revert to virulence and limited shelf life
Killed or Inactivated Vaccines - Answer-• Chemical and temperature treatment are normally used to kill
or inactivate pathogen
• Formaldehyde treatment most common method
• Other chemicals used are phenol and acetone
• Another method is to irradiate pathogen to render it inactive
• Advantages are non-reversal to virulence and relatively stable shelf life
• Disadvantages are higher cost of production, more control is required for production to ensure reliable
processes for complete inactivation and there is possibility of reduced immunological response due to
treatment processes so multiple booster vaccinations may be required
Toxoids - Answer-• Derived from toxins secreted by pathogen
• Advantages and disadvantages similar to killed or inactivated vaccines(advantages: non-reversal to
virulence and relatively stable shelf life; disadvantages: higher cost of production, more control is
required for production to ensure reliable processes for complete inactivation and there is possiblity of
reduced immunological response due to treatment processes so multiple booster vaccinations may be
required)
New Vaccines - Answer-• Advances in genomics, molecular biology and recombinant technology has
provided new directions for discovery, development and manufacture of vaccines
• Current approach is minimalist strategy to decouple virulence and immunity functions
• Aim is to use only immunity part to confer protection, so vaccine is safe to be administered
, • Approach can be divided into subunit, vector-based, DNA and peptide vaccines
Subunit Vaccines - Answer-• Use only part of bacteria or virus instead of entire pathogen
• Part is derived from outside envelope protein of pathogen
• Requires knowledge of genome sequence of pathogen by identifying open reading frames (ORF) that
potentially encode novel antigenic surface proteins known as epitopes, which bind to antibodies
• When identified, ORFs are cloned to express protein epitopes using self-replicating plasmids
• Binding properties of epitopes can be studied using enzyme linked immunosorbent assay (ELISA) or
fluorescent activated cell sorter (FACS)
• Leading candidates of epitopes are injected into animals to determine whether they elicit any antibody
response
o Those that work are selected and optimized to become vaccine candidates w/ further tests before
human clinical trials
o Also working on multiple epitope subunit vaccines which can provide different antigenic binding sites
Vector-based Vaccines - Answer-• Viruses and bacteria are detoxified and used as vehicles to carry
vaccines
• Subunit vaccines are being delivered by carrier vehicles to elicit immune response
• Multiple types of envelope proteins can be delivered w/ this method
• Clinical trials w/ this type of vector-based vaccines are being investigated
DNA Vaccines - Answer-• Aka nucleic vaccines or genetic immunization
• Host (patient) is directly injected w/ selected viral genes which contain engineered DNA sequences
that code for antigens
• Hosts own cells take up these genes and express antigens which are then presented to immune cells
and activate immune response
Peptide Vaccines - Answer-• Chemically synthesized and normally consist of 8-24 amino acids
Drug Discovery - Answer-• Unlike small molecule drugs (pharmaceuticals), large molecule drugs
(biopharmaceuticals) are mainly protein-based
o These protein-based drugs are similar to natural biological compounds found in human body or
they're fragments that mimic active part of natural compounds
Discovery of Pharmaceuticals - Answer-commences w/ scanning hundreds of compounds, whether w/
actual materials (irrational approach) or virtual simulations (rational approach)
• Pharmaceuticals are new chemical entities (NCE) and are produced (synthesized) in manufacturing
plants using techniques based on chemical reactions of reactants
Discovery of Biopharmaceuticals - Answer-researchers have to examine compounds w/in humans
o Ex. Hormones or other biological response modifiers and how they affect biological processes
o In some cases, study pathogens such as influenza virus or bacteria to derive vaccines
o In other cases, researchers copy these biological response modifiers and use them as replacement
therapy
o Protein-based drugs are manufactured in biological systems, such as living cells, producing desired
protein molecules in large reaction vessels or by extraction from animal serum
o Becoming increasingly important
• More potent and specific—more similar to proteins w/in body therefore more effective in treating our
diseases
,Areas of Biopharmaceuticals - Answer-• Prophylactic→ preventive as in vaccines
• Therapeutic→ antibodies
• Replacement therapy→ hormones, growth factors
Biologics - Answer-FDA definition is:
o Biological product subject to licensure under Public Health Service Act is any virus, therapeutic serum,
toxin, antitoxin, vaccine, blood, a blood component or derivative, allergenic produce, or analogous
product, applicable to prevention, treatment or cure of diseases or injuries to humans. Biological
products include, but are not limited to, bacterial and viral vaccines, human blood and plasma and their
derivatives, and certain products produced by biotechnology, such as interferons and erythropoietins.
Biologics encompass many different protein-based drugs, and include blood products such as clotting
factors extracted from blood.
Vaccines - Answer-• Basis of vaccination is that administering small quantity of a vaccine (antigen that
has been treated) stimulates our immune system and causes antibodies to be secreted to react against
foreign antigen
• Later in life, when we encounter another exposure to same antigen, our immune system will evoke a
memory response and activate defense mechanisms by generating antibodies to combat invading
antigen
• Contains antigenic components that are obtained from or derived from pathogen
o Include mainly viruses, bacteria, parasites and fungi
o Research has shown that part of pathogen that causes disease (virulence) can be decoupled from
protective part (immunity)
• Development focuses on means to reduce virulence factor while retaining immunity stimulation
• Oral or parenteral
Vaccine Preparations - Answer-Attenuated Vaccines
Killed or Inactivated Vaccines
Toxoids
,Attenuated Vaccines - Answer-• Virulence of pathogen that can be reduced in number of ways
• By chemical treatment, by temperature adaptation, or by growing pathogen in specified other than
natural host (passaging)
• Advantages are low cost preparation, elicit desired immunological response, and normally single dose
is sufficient
• Disadvantages are potential to revert to virulence and limited shelf life
Killed or Inactivated Vaccines - Answer-• Chemical and temperature treatment are normally used to kill
or inactivate pathogen
• Formaldehyde treatment most common method
• Other chemicals used are phenol and acetone
• Another method is to irradiate pathogen to render it inactive
• Advantages are non-reversal to virulence and relatively stable shelf life
• Disadvantages are higher cost of production, more control is required for production to ensure reliable
processes for complete inactivation and there is possibility of reduced immunological response due to
treatment processes so multiple booster vaccinations may be required
Toxoids - Answer-• Derived from toxins secreted by pathogen
• Advantages and disadvantages similar to killed or inactivated vaccines(advantages: non-reversal to
virulence and relatively stable shelf life; disadvantages: higher cost of production, more control is
required for production to ensure reliable processes for complete inactivation and there is possiblity of
reduced immunological response due to treatment processes so multiple booster vaccinations may be
required)
New Vaccines - Answer-• Advances in genomics, molecular biology and recombinant technology has
provided new directions for discovery, development and manufacture of vaccines
• Current approach is minimalist strategy to decouple virulence and immunity functions
• Aim is to use only immunity part to confer protection, so vaccine is safe to be administered
, • Approach can be divided into subunit, vector-based, DNA and peptide vaccines
Subunit Vaccines - Answer-• Use only part of bacteria or virus instead of entire pathogen
• Part is derived from outside envelope protein of pathogen
• Requires knowledge of genome sequence of pathogen by identifying open reading frames (ORF) that
potentially encode novel antigenic surface proteins known as epitopes, which bind to antibodies
• When identified, ORFs are cloned to express protein epitopes using self-replicating plasmids
• Binding properties of epitopes can be studied using enzyme linked immunosorbent assay (ELISA) or
fluorescent activated cell sorter (FACS)
• Leading candidates of epitopes are injected into animals to determine whether they elicit any antibody
response
o Those that work are selected and optimized to become vaccine candidates w/ further tests before
human clinical trials
o Also working on multiple epitope subunit vaccines which can provide different antigenic binding sites
Vector-based Vaccines - Answer-• Viruses and bacteria are detoxified and used as vehicles to carry
vaccines
• Subunit vaccines are being delivered by carrier vehicles to elicit immune response
• Multiple types of envelope proteins can be delivered w/ this method
• Clinical trials w/ this type of vector-based vaccines are being investigated
DNA Vaccines - Answer-• Aka nucleic vaccines or genetic immunization
• Host (patient) is directly injected w/ selected viral genes which contain engineered DNA sequences
that code for antigens
• Hosts own cells take up these genes and express antigens which are then presented to immune cells
and activate immune response
Peptide Vaccines - Answer-• Chemically synthesized and normally consist of 8-24 amino acids
