• A substance used in the diagnosis, treatment, or A substance used in the diagnosis, treatment, or prevention of a disease or as a component of a prevention of a disease or as a component of a medicationmedication

• A A drugdrug is any chemical or biological substance, is any chemical or biological substance, synthetic or non-synthetic synthetic or non-synthetic

DRUG

• A drug is anything that affects the way an A drug is anything that affects the way an organism works. organism works.

• Drugs can be taken to enhance function, Drugs can be taken to enhance function, such as a student drinking caffeine to such as a student drinking caffeine to enhance alertness. enhance alertness.

• For now we only consider drugs which are For now we only consider drugs which are used to cure a disease. used to cure a disease.

• A disease is often thought of as an A disease is often thought of as an infection, where a bacteria, virus, or other infection, where a bacteria, virus, or other living thing invades the body. living thing invades the body.

• However, a disease is anything which However, a disease is anything which affects the proper functioning of the body. affects the proper functioning of the body.

• It can be an infection, a genetic disorder, It can be an infection, a genetic disorder, or the result of environmental conditions or the result of environmental conditions such as malnourishment, poisoning, or such as malnourishment, poisoning, or stress. stress.

• You may find it easy to think of the body as a You may find it easy to think of the body as a factory. factory.

• Individual organs can be seen as machinery. Individual organs can be seen as machinery. The actual nuts, bolts, screwdrivers, and The actual nuts, bolts, screwdrivers, and wrenches that make up all the machinery are wrenches that make up all the machinery are the equivalent of proteins, little chunks of the equivalent of proteins, little chunks of organic material that move things around in organic material that move things around in the body and attach them together.the body and attach them together.

• Most of the work in our body is done by Most of the work in our body is done by PROTEINSPROTEINS (tiny molecular machines!) (tiny molecular machines!)

Continued

• The body contains thousands of The body contains thousands of different kinds of proteins. different kinds of proteins.

• The construction of each is The construction of each is determined by the DNA in the determined by the DNA in the nucleus of each cell. nucleus of each cell.

• DNA may be thought of as long DNA may be thought of as long strings of instructions which code for strings of instructions which code for how each protein is too be built. how each protein is too be built.

How Pharmaceutical Drugs are MadeHow Pharmaceutical Drugs are Made

1.1. Initial ConceptInitial Concept

2.2. Research & DevelopmentResearch & Development

3.3. Clinical TrialsClinical Trials

4.4. Health Canada/FDA ApprovalHealth Canada/FDA Approval

5.5. Marketing Marketing

Initial ConceptInitial Concept

• The drug company will decide which The drug company will decide which disease to targetdisease to target

• Research will be done to find the Research will be done to find the biological target for the drug’s biological target for the drug’s action (usually a action (usually a PROTEINPROTEIN))

• Once a company decides on a disease and target Once a company decides on a disease and target protein, its next step will be to make a library of chemical protein, its next step will be to make a library of chemical compounds (potential drugs) to test on the protein. compounds (potential drugs) to test on the protein.

• Literally hundreds and sometimes thousands of chemical Literally hundreds and sometimes thousands of chemical compounds must be made and tested in an effort to find compounds must be made and tested in an effort to find one that can achieve a desirable result.one that can achieve a desirable result.

• Computers can be used to simulate a chemical Computers can be used to simulate a chemical compound and design chemical structures that might compound and design chemical structures that might work against it.work against it.

Research & Development -Synthesis and Purification

• In Vitro In Vitro (outside of a living organism) (outside of a living organism) testing is performed on purified proteins testing is performed on purified proteins and well as cultured cell linesand well as cultured cell lines

• In VivoIn Vivo (within a living organism) testing is (within a living organism) testing is performed on living animals. Rodents are performed on living animals. Rodents are typically used for animal testing. typically used for animal testing.

Research &Development -Pre-clinical Drug Development

• Drug companies make every effort to use as few Drug companies make every effort to use as few animals as possible and to ensure their humane and animals as possible and to ensure their humane and proper care.proper care.

• Animal testing is used to measure how much of a Animal testing is used to measure how much of a drug is absorbed into the blood, how it is broken drug is absorbed into the blood, how it is broken down chemically in the body, the toxicity of the drug down chemically in the body, the toxicity of the drug and its breakdown products metabolites, and how and its breakdown products metabolites, and how quickly the drug and its metabolites are excreted quickly the drug and its metabolites are excreted from the bodyfrom the body

• The Three Rs of Animal Use in ResearchThe Three Rs of Animal Use in ResearchRESPECT for the animalRESPECT for the animalREDUCE the number of animals usedREDUCE the number of animals usedREUSE animals for multiple studies if possibleREUSE animals for multiple studies if possible

Research & Development -Animal Testing

Phase 1 Clinical StudiesPhase 1 Clinical Studies• Phase 1 includes the initial introduction of an investigational Phase 1 includes the initial introduction of an investigational

new drug into human.new drug into human.

• Phase 1 studies usually conducted in healthy volunteer.Phase 1 studies usually conducted in healthy volunteer.(Exceptions may include toxic drugs such as chemotherapies) (Exceptions may include toxic drugs such as chemotherapies)

• Researchers test a new drug or treatment in a Researchers test a new drug or treatment in a small groupsmall group of of people for the first time to evaluate its safety, determine a people for the first time to evaluate its safety, determine a safe dosage range, and identify side effects. safe dosage range, and identify side effects.

• The total number of subjects included in Phase I studies The total number of subjects included in Phase I studies varies with the drug, but is generally in the range of 20 to 80varies with the drug, but is generally in the range of 20 to 80

• Phase 1 studies are designed to determine the metabolic and Phase 1 studies are designed to determine the metabolic and pharmacologic actions of the drug in humans, the side effects pharmacologic actions of the drug in humans, the side effects associated with increasing doses, and if possible to gain early associated with increasing doses, and if possible to gain early evidence on effectiveness. evidence on effectiveness.

Phase 2 Clinical StudiesPhase 2 Clinical Studies

• The drug or treatment is given to a The drug or treatment is given to a larger grouplarger group of people of people to see if it is effective and to further evaluate its safety. to see if it is effective and to further evaluate its safety.

• Phase 2 includes the early controlled clinical studies Phase 2 includes the early controlled clinical studies conducted to obtain some preliminary data on the conducted to obtain some preliminary data on the effectiveness of the drug for a particular indication or effectiveness of the drug for a particular indication or indications in patients with the disease or condition.indications in patients with the disease or condition.

• This phase of testing also helps determine the common This phase of testing also helps determine the common short-term side effects and risks associated with the drug.short-term side effects and risks associated with the drug.

• Phase 2 studies are typically well-controlled, closely Phase 2 studies are typically well-controlled, closely monitored, and conducted in a relatively small number of monitored, and conducted in a relatively small number of patients usually involving several hundred people.patients usually involving several hundred people.

• The drug or treatment is given to The drug or treatment is given to large groupslarge groups of people to of people to confirm its effectiveness, monitor side effects, compare it to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will commonly used treatments, and collect information that will allow the drug or treatment to be used safely. allow the drug or treatment to be used safely.

• Phase 3 studies usually include several hundred to several Phase 3 studies usually include several hundred to several thousand people.thousand people.

• They are performed after preliminary evidence suggesting They are performed after preliminary evidence suggesting effectiveness of the drug has been obtained in Phase 2 and effectiveness of the drug has been obtained in Phase 2 and are intended to gather the additional information about are intended to gather the additional information about effectiveness and safety that is needed to evaluate the effectiveness and safety that is needed to evaluate the overall benefit-risk relationship of the drug.overall benefit-risk relationship of the drug.

• Phase 3 studies also provide an adequate basis for Phase 3 studies also provide an adequate basis for extrapolating the results to the general population and extrapolating the results to the general population and transmitting that information in the physician labeling.transmitting that information in the physician labeling.

Phase 3 Clinical StudiesPhase 3 Clinical Studies

Health Canada/FDA Approval… hopefully!Health Canada/FDA Approval… hopefully!

• A NDA (New Drug Application is submitted A NDA (New Drug Application is submitted to the FDA (Food & Drug Administration)to the FDA (Food & Drug Administration)

• Is the drug is safe and effective in its Is the drug is safe and effective in its proposed use(s), and whether the benefits proposed use(s), and whether the benefits of the drug outweigh the risks. of the drug outweigh the risks.

• Is the drug's proposed labeling (package Is the drug's proposed labeling (package insert) is appropriate, and what it should insert) is appropriate, and what it should contain. contain.

• Are the methods used in manufacturing the Are the methods used in manufacturing the drug and the controls used to maintain the drug and the controls used to maintain the drug's quality are adequate to preserve the drug's quality are adequate to preserve the drug's identity, strength, quality, and purity. drug's identity, strength, quality, and purity.

Drug Goes to MarketDrug Goes to Market

• Drug is sold to the general public and Drug is sold to the general public and medical communitymedical community

• Advertisements $$Advertisements $$

• Education of health care workers, Education of health care workers, especially prescribing physicians on the especially prescribing physicians on the usefulness of the new drugusefulness of the new drug

Phase IV Clinical StudiesPhase IV Clinical Studies

Studies are done after the drug or Studies are done after the drug or treatment has been treatment has been marketed marketed to to gather information on the drug's gather information on the drug's effect in various populations and any effect in various populations and any side effects associated with long-side effects associated with long-term use.term use.

If you have ever taken a drug, you If you have ever taken a drug, you have been a study participant in have been a study participant in phase IV clinical trials!phase IV clinical trials!