Lecture 1 Flashcards
Drug Development Process
Goals for New Drug (8)
- Cheap to manufacture
- Pharmaceutically elegant (accepted, recognizable dosage form)
- Physically and chemically stable
- Specific Desired Effect
- Administered by most desired route (usually oral)
- Optimal onset & duration
- No side effects
- Eliminated from the body efficiently, completely, and without residual effect
New Drug Definition Components (7)
- New chemical entity
- Change in previously approved drug product’s manufacture or formulation
- New combination of drugs if a question of safety is introduced by the change
- New use for an approved drug
- New dosage schedule or regimen
- New route of administration
- New dosage form
* *NOT recognized as being safe & effective under the conditions recommended**
Processes of Drug Discovery (5)
- Random, non-targeted screening
- Testing large numbers of synthetic organic compounds or natural compounds
- Bioassays
- Chemical alterations
- Mechanism-based drug design
2 Types of Bioassays
- High throughput screenings
2. Molecular/Chemical modifications
Chemical Alterations
Changing of an organic compounds to increase its usefulness
Ex: Changing of burimamide (an injection) into Cimetidine (oral tablet with minimal side effects)
Mechanism-based Drug Design
Designing a drug with a known or suspected biochemical pathway or disease process in mind for its mechanism
Drug Nomenclature Characteristics (3)
- Short and distinctive
- Indicate general pharmacologic or therapeutic class
- Embody the syllable(s) characteristic of a related group of compounds
What do Preclinical Studies find?
- Chemical/physical properties
- Pharmacology/Toxcology
- ADME
- Preformulation
How are Preclinical Studies conducted?
- Conducted on animals PRIOR to human administration
- Utilize several animal species
- Certain species are chosen as “best representatives” for particular organ systems or disease states
- At least one rodent and one non-rodent species will be used
Pharmacology
- Finds selectivity and efficacy
- Basic information on drug’s effects that can be used to predict the drug’s safe & effective use in humans
ADME
Aka Pharmacokinetics
- Finds rate & extent of drug absorption from various routes of administration
- Studies how the drug is metabolized and distributes throughout the body, its pathways of metabolism, identification of its metabolites and their possible activity
- Proportion of drug eliminated by various routes and the time it takes to eliminate the drug from the body
- *Helps guide the selection for ideal doses and dosage forms of drug in humans**
Toxicology
Drug Safety Evaluation (DSE)
- Studies its potential toxicity for both short-term (acute) and long-term (chronic) use
- *Human initial dose = 1/10 of the nontoxic dose**
- Potential for specific organ toxicity and its mode, site, and degree of toxicity
- Dose-Response relationships
- Reproductive, gender, teratogenic toxicities and its carcinogenic and genotoxic potentials
Preformulation
Evaluation of a drug’s physical and chemical properties that could effect its formulation
Continues into clinical trials
INDA
Investigational New Drug Application
- Drug sponsor files INDA with FDA before it can be given to humans
- This protects subject’s safety and insures the drug is scientifically sound and has planned protocols to reach its goals
- Once approved, clinical trials are conducted by the sponsor
Clinical Protocol Requirements (8)
- Purpose/objective of study and a study design
- Estimate number of patients
- Basis for subject selection - inclusion/exclusion
- Dosing plan
- Patient Monitoring - tests, measurements, observing
- Contact info & investigators’ credentials
- Locations & descriptions of research facilities
- Approval from authorized Institutional Review Board (IRB)
Clinical Trial Materials (3)
- Initial formulation prepared for trials and human administration
- Capsules containing ONLY active ingredients
- Blinded studies - indistinguishable capsules between the test drug, placebo, and competitor drug
Phase I
- 1st administration of drugs to humans
- Assesses safety and early PK studies
- Conducted in HEALTHY volunteers (~20-100)
Phase II
- 1st administration to PATIENTS (~200-400)
- Evaluate effectiveness and assesses side effects/risks
- Determines effective dose
- Additional PK studies
- Final formulation refined
Phase III
- Usefulness of drug in an expanded patient base (~2000-4000)
- Overall benefit to risk profile
- Several dosage strengths administered
- Information gathered for marketing
Information Gathered for Marketing (5)
- Labeling
- Quality of Life
- Advantages
- Additional Indications
- Post-Marketing Studies
NDA
New Drug Application
- Submitted to FDA by sponsor after trials I-III are complete
- Sponsor must demonstrate sufficient drug safety & therapeutic effectiveness
- If approved, drug is given permission to enter the U.S. market
Additional Drug Aspects Regulated by FDA (6)
- Labeling Requirements
- Package Inserts
- Advertising
- Promotional Material
- Direct-to-Customer advertising of script drugs
- Direct-to-Customer advertising of OTC drugs
Phase IV
- Post-NDA approval and drug on the market
- Post-marketing surveillance done by MedWatch
- Administration of drug to more people may surface information not revealed in controlled studies
Additional Post-Marketing Info to Report (5)
- Drug interactions
- Additional side effects or adverse effects
- New uses
- Better understandings of mechanisms of action
- Need for difference dosage strengths, dosage forms, or routes of administrations
TIND
Treatment Investigation New Drug
-Allows patients with severe or life-threatening diseases to access investigational drugs in clinical trials that may help their condition
SNDA
Supplemental New Drug Application
- Sponsor of approved NDA may request approval for changes to that application
- Changes in formulation, packaging, or labeling for example
ANDA
Abbreviated New Drug Application
- filed after patent expired for a marketed product by companies are making or who made generics
- Generics: omit clinical/non-clinical studies, must show bioequivalence
- Usually uses human PK data
- If class 1, a biowaiver may be available
BLA
Biologics License Application
- Submitted to FDA prior to marketing of vaccines, blood products, toxins, etc.
- *How the flu shot can be released so quickly on a yearly basis**
505(b)
- NDA application that contains full safety and effectiveness reports, but some information (like safety and efficacy information on the active ingredient) to come from studies not completed by applicant
- Includes all 4 clinical trials but trial 1 may be shortened
New Route Applications
- Follows the same general process
- Some pre-formulation and toxicity may be avoided in respect to the active ingredient ONLY
- All studies that involve the new product must be reevaluated
- Can be a significant cost!
