Pharmacy Practice and Ethics

Drug Development Process

• The development of new drugs is a complex and costly process, taking an average of 12 years and about $350 million to get a new drug from the laboratory to the pharmacy shelf.
• Only one in 1000 compounds that begin laboratory testing will progress to human testing.
• The patent period for a new compound begins on the date that the patent application is filed with the relevant patent office.

Phases and Stages of Drug Development

• There are five critical steps in the U.S. FDA drug development process, including many phases and stages within each of them.
• The phases of drug development are:
  • Step 1: Discovery and Development
  • Step 2: Preclinical Research
  • Step 3: Clinical Development
  • Step 4: FDA Review
  • Step 5: FDA Post-Market Safety Monitoring

Discovery and Development

• Drug discovery research is how new medications are discovered.
• Investigate chemical libraries, including small molecules, natural products, or plant extracts, and find those with therapeutic effects.
• The drug discovery process gets narrowed when one lead compound is found for a drug candidate, and the process of drug development starts.

Preclinical Studies

• Once a lead compound is found, the preclinical phase of drug development begins with in vivo research to determine the efficacy and safety of the drug.
• Preclinical trials test the new drug on non-human subjects for efficacy, toxicity, and pharmacokinetic (PK) information.
• These trials are conducted by scientists in vitro and in vivo with unrestricted dosages.

Investigational New Drug (IND)

• Investigational New Drug (IND): Application for permission to administer a new drug to humans.
• Outlines the proposal to use the new drug for human testing in clinical trials.
• Studies in humans can only begin after IND is reviewed and approved by the FDA and an institutional review board (IRB).

Clinical Drug Development Process

• Once preclinical research is complete, researchers move on to clinical drug development.
• This includes clinical trials and volunteer studies to fine-tune the drug for human use.

Clinical Studies

• Phase 1: Efficacy studies on healthy volunteers (typically 20-80 healthy volunteers, no women of childbearing potential).
• Phase 2: Clinical studies on a limited scale (typically 100-300 individuals who have the target disease).
• Phase 3: Comparative studies on a large number of patients (typically 1000-3000 patients).
• Phase 4: Continued comparative studies, registration, and market introduction.

New Drug Application (NDA)

• Pre-NDA period: FDA and drug sponsors meet.
• Submission of NDA: Formal step asking the FDA to consider approving a drug for marketing.
• FDA has 60 days to decide whether it will file it for approval consideration.

FDA Review

• The review team evaluates the research on the safety of the drug and its effectiveness.
• The FDA reviews the information to go on the drug label.
• It inspects the facilities where the drug will be manufactured.

Reasons for Drug Failure

• Toxicity: If the toxicity of a new drug is too high in human or animal patients, the drug may be rejected due to safety concerns about its use following manufacture.
• Efficacy: If a new drug's efficacy is not high enough or evidence is inconclusive, the FDA may reject it.
• PK Properties or Bioavailability: PK causes of drug failure include inadequate action duration and unanticipated human drug interactions or poor bioavailability.
• Inadequate Drug Performance: If the new drug performs the desired function, but only at a shallow level, the FDA may reject the application in favor of a formulation that performs better.

Phase 4 - Post-Market Safety Monitoring

• Post-market surveillance of the drug to continually assess the safety of the drug.
• May include incidence and severity of rare adverse reactions, cost-effectiveness analyses, comparative trials, and quality-of-life studies.

Supplemental New Drug Application (SNDA)

• A sponsor of an approved NDA may make changes such as labeling or formulation.
• Depending on the changes proposed, some require FDA approval before implementing; others do not.

Abbreviated New Drug Application (ANDA)

• Application for generic drugs previously approved by NDA.
• A generic drug product is one that is comparable to an innovator drug product in dosage form, strength, route of administration, quality, performance characteristics, and intended use.
• Do not require to include preclinical (animal) and clinical (human) data to establish safety and effectiveness.