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49 Cards in this Set
- Front
- Back
Who regulates all drug products manufactured in or imported into the US?
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FDA
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The pharmaceutical company must demonstrate that new drugs are:
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Safe and Effective for it's purpose
& the various processes and controls used in producing the drug substance and in manufacturing, packaging, and labeling are properly controlled and validated to ensure that the product meets established standards of quality |
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cGMP or CGMP
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Current Good Manufacturing Practices
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What are the sources for NCEs?
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Organic Synthesis
Molecular Modification Isolation from plants |
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NCE
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New Chemical Entity
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New Drug Development Process
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NCE --> Preclinical Studies --> IND--> (Clinical Trials & Preclinical Studies) -->NDA --> Postmarketing
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NCE patents
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- last 20 years from filing time
- needs to be for a molecule and it's use |
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Preclinical Studies include:
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- Chemistry
- Physical Properties - Biological = Pharmacology = ADME = Toxicology - Preformulation |
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Preformulation
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making dosage forms
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Pharmacology
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Effects of drug in animals, cells cultues, computer sims, etc.
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IND
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Investigational New Drug Application
= needs to be submitted & reviewed by FDA |
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Phases of Clinical Trials
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- Phase I
- Phase II - Phase III |
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Continued PreClinical Studies include:
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- Long-term animal toxicity
- Product formulation - Manufacturing and Controls - Package and Label Designs |
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NDA
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New Drug Application
= needs to be submitted & reviewed by FDA = needs preapproval FDA plant inspection & FDA action |
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Postmarketing
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Surveillance after release to market
- Phase IV clinical studies = Clinical Pharmacology/ Toxiciology = Additional indications - ADRs - Product Defect Reporting - Product Line Extensions |
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#1 Reason (40%) Drugs don't make it to market
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Biopharmaceutics - the ADME
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API
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Active Pharmaceutical Ingredient
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NME
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New Medical Entity
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Typical Duration & Activities in Preclinical Research & Development
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6 1/2 years
- Initial synthesis and characterization - Short Term Animal Testing |
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Typical Duration & Activities in Clinical Research & Development
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7 years
- Phases 1 to 3 - Longer Term Animal Testing |
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Average Duration & Activities of Postmarketing
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indefinate
- ADR reporting - Surveys/sampling testing - Inspections |
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Average Length of NDA Review
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1 1/2 years
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Average Total Duration between initial synthesis to approval of NDA
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15 years
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ADME stands for
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Absorption
Distribution Metabolism Excretion |
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Preformulation Studies:
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= Just the NCE =
- Solubility (water and lipid) - Partition coefficient (between water and oil) - Dissolution rate - Physical form (crystaline, etc) - Stability |
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Formulation Studies:
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= NCE + excipients =
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Preclinical Studies:
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pharmacology & toxicity in cell, tissue, animal and computer simulations
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When do PreClinical Studies end?
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Until the final Drug Product is made and approved by the FDA
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Phase I Clinical Studies
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- 20-100 person subject size
- 1st in human - usually young, healthy, normal people - mainly tests for safety - very low, usually singular dose of medication - 67% success rate |
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Phase II Clinical Studies
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- 100s of subjects
- studies short term safety - tests for efficacy - usually higher doses - tests normal and people with the target disease state |
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Phase III Clinical Studies
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- 100s - 1,000s subjects
- Lasts 1-4 years - safety, effecacy, dosage, etc. - should be FINAL drug product your're testing |
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NDA must demonstrate Drug is:
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- Safe & Effective for Indicated Use
- Adequate Assurance of it's proper manufacture and control (can you product millions of dosages like this - QC/QA/CGMP) - Final Labeling accurately presents the necessary information for its proper use (what Pt, MD, Rph reads) |
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What drugs are allowed Special Regulations on their NDA?
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- Drugs treating life-threatening illnesses (AIDS & Cancer)
= accelerated or fast-track programs for approval - Orphan Drugs (for diseases that are rare) |
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SNDA
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Supplemental New Drug Application
- for change in labeling or formulation = how, where its manufactured |
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ANDA
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Abbreviated New Drug Application
- for generic drug approval = must prove med is a BIOEQUIVALENT to innovator'r product |
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OTC drug products need to be shown as:
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Safe but not necessarily Effective
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INADA
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Investigational New Animal Drug Application
(for new Vet Drugs) |
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NADA
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New Animal Application
(for Veterinary Products) |
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SNADA
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Supplemental New Animal Application
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Medical Devises
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also regulated by the FDA
- includes Drug Testing Kits, canes, glucometers, etc. |
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Dosage Forms (DF)
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One or more drug substances ( or API) with "usually" one or more excipients formulated together
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Excipients
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inactive pharmaceutical ingredients
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Drug Delivery Systems (DDS)
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- Systems engineered or designed to release drug at specific rate or kinetics.
- Usually takes into account patent factors = ex. transdermal patch (DDS) vs. ointment (DF) |
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10 Needs for DF& DDS
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1. Protection from Air & Water
2. Protection from Gastric Acid following po 3. Mask unpleasant taste or odor 4. Provide liquid form for drugs that are insoluble or unstable in desired vehicle 5. Provide clear liquid dosage forms of ACI 6. Provide DDS to control release & absorption of ACI 7. Provide DF or DDS for topical, transdermal, opth, otic, and intranasal orifice administration 8. Provide DF for insertion of ATI into a body orfice 9. Provide DF/DDS for admin of ATI directly into the bloodstream or other body tissue 10. Provide DF/DDS for inhalational admin of ADI |
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4 Factors to consider when Designing a DF/DDS
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1. Nature of Illness (life threatening; chronic vs. acute)
2. Local or Systemic 3. Demographic ( Age, Gender, Genetic Differences, Cultural Differences) 4. Physiological / Pathophysiology of the patient (if pt is vomiting, etc) |
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4 Chemical Properties to Consider of Solid DF/DDS
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1. Purity
2. Structure (salts vs. esters vs. enanteomeric forms) 3. Form (crystalin vs. amorphous) 4. Reactivity (sensitivity to light, water, air, etc) |
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5 Physical Properties to Consider of Solid DF/DDS
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1. Physical description (crystal structure, viscosity of liquid)
2. Particle Size (smaller particles = larger SA = increase solubility) 3. Crystalline structure (Crystlline vs amorphous (loose arrangement of molecules = faster dissolve rate) 4. Melting Point (Narrow = pure; Broad = impure),also what Temp do you want it to melt at? (suppositories) 5. Solubility (if it doesn't dissolve, it wont be absorbed) |
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Biological Properties of Solid DF/DDS
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Drug's Bioavalability (the rate and extent of absorption into systemic circulation)
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Effect of Particle Size on Solubility
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Small Size = High SA = Increase Solubility
& vice versa |