New Drug Development and approval process Flashcards
(50 cards)
Food, Drug and Comestic Act (1938)
Mandated testing of all drugs for harmful effects and that drug labels must be accurate and simple
Wheeler-Lea Act (1938)
Defined criteria for non-fraudulent advertising
Durkham-Humphney Amendment (1952)
Distinguish between drugs that can be sold with/without a prescription and those that cannot be refilled
Comprehensive Drug Abuse Prevention and Control Act (1970)
Categorized controlled substances based on their relative potential for abuse
Drug Regulation Reform Act (1978)
Shortened the drug investigation process to release drugs sooner to the public
Drug Names can be categorized into
- Chemical: Precise description of the drug’s chemical composition and molecular structure
- Generic: Name assigned to a new drug by the manufacturer who first develops the drug and is not copyrighted
- Official: Officially assigned to a new drug and listed in official compendium
- Trade/brand: Assigned to a new drug by its manufacturer that sells drug, copyright
What consist of a preclinical study?
- Chemical characterization
- Animal testing and screening
- > application for IND (Investigational New Drug) status
What consist of a clinical study?
Phase 1 - healthy human volunteers
Phase 2 - human patient volunteers
Phase 3 - expansion of human patients
Application for NDA (New Drug Application)
After approval, Phase 4 - post marketing trials
What consist of the Drugs Design Process?
- Find lead compounds from potential drug candidates
- Have some activity against a disease
- May have side effects
- Provide a starting point for structural refinements - Isolate molecular bases for the disease
Know the drug binding on proteins or nucleotides sites to tailor made a drug to bind that specific site
Techniques used:
- Molecular interactions
- Rational drug design techniques (De Nova techniques)
- X-ray crystallography
- Distance geometry ( NMR-NOE) - Drug activity refinements: Examine the molecular structure of the drug to achieve high drug activity and few side effects
Techniques used:
- Synthesis
- Computational
What consist of a Drug Development Process?
- Pharmacology
- Metabolism
- Toxicology
- Preformulation
- Formulation
- Analytical
- Pharmacokinetics
What is pharmacology?
Study of drugs - what they are, how they work, what they do
What is metabolism?
Biotransformation: a series of animal studies of a proposed drug’s ADME to determine:
- extent and rate of drug absorption from various routes of administration
- rate of drug distribution in the body, and the site(s) and duration of drug’s residence
- rate, sites and mechanism of the drug’s metabolism and the chemistry of the metabolites
- proportion of the administered dose eliminated from the body and its rate and route of elimination
What is toxicology?
Study of adverse/undesired effects of drugs
Determine:
- substances potential for toxicity (acute/chronic)
- substances potential for specific organ toxicity
- mode, site and degree of toxicity
- dose-response relationship for low, high and intermediate dose
- gender, reproductive or teratogenic toxicities
- substance’s carcinogenic and genotoxic potential
What is preformulation?
Application of pharmaceutical principles to the physicochemical parameters of a drug for designing an optimum drug delivery system
What consists of preformulation studies?
Drug solubility pKa determination Partition coefficient Chemical stability Crystal properties and polymorphism Particle size, shape and surface area
What is partition coefficient?
Measure of a drug’s lipophilicity and an indication of its ability to cross cell membranes
Factors affecting chemical stability
- Temperature
- pH
- Enzymes
- Excipients
What is polymorphism?
Drugs existing in more than 1 crystalline form with different space lattice arrangements. Polymorphs generally have different physical properties but identical chemical properties
Advantages of polymorphism
- When the absorption of a drug is dissolution rate limited, a more soluble and faster-dissolving polymorph may be used to increase rate and extent of bioavailability
- Chemically more stable polymorph -> less likely to degrade
- Different polymorphs -> different morphology, tensile strength and density of powder bed -> compression characteristics of materials
What is therapeutic index
TI = lethal dose (LD)/ effective dose (ED)
Describe phase I clinical trials
Takes around 2 years, 70% are sent to the next phase. Done on a small no. of healthy subjects (20-100) who take the drug to determine its safety and pharmocokinetics.
Data to be reported to FDA before proceeding
Describe phase II clinical trials
Takes ~2 years, 45% are sent to the next phase.
Done on a small no, of diseased subjects (several 100s) who take the drug in gradually increasing dosages noting effectiveness and side effects
Data to be reported to FDA before proceeding
Describe phase III clinical trials
5-10% pass this phase.
Extended clinical evaluation on a large no. of diseased subjects who take the drug according to protocols to determine clinical effectiveness, drug safety, and establishment of tolerated dosage
Desribe phase IV
- Identify rare adverse reactions not detected during pe-licensure studies
- Monitor increase in known reactions
- Identify risk factors/ pre-existing conditions that may promote reactions
- identify particular lots with unusually high rate/types of events
