Lecture 4 - Drug Approval and Development Flashcards
Thalidomide Tragedy
-Thalidomide was linked to phocolemia, a rare condition affecting the fetal formation of arms and legs
-More than 10,000 children were born with serious birth defects worldwide, 40% of which died early in childhood
-Frances Oldham Kelsey blocked the drug’s approval in the United States. She received the president’s Award for Distinguished Federal Civilian Service for saving countless American lives
Kefauver-Harris Amendment
-Requires medications to be demonstrated not only safe, but also effective (applies to all drugs marketed between 1938-1962 as well as new drugs)
-Transferred jurisdiction of prescription drug advertising from the Federal Trade Commission (FTC) to the FDA
-Established current Good Manufacturing Practice (cGMP) requirements
-Added requirements to clinical investigations including informed consent of research subjects and reporting of adverse drug reactions
Current Good Manufacturing Practices (cGMP)
-Any manufacturer for drugs used in the United States must be registered with the FDA and undergo an inspection at least once every two years
What happens to a drug if it does not apply to cGMP?
It is adulterated
What happens to a drug if it is not registered with the FDA?
The product is adulterated and misbranded
What are the three categories of making drugs?
-Pharmacy or Traditional Compounding (503a)
-Outsourcing Facilities (503b)
-Manufacturing
What is pharmacy or traditional drug compounding (503a)
-Compounding according to prescriptions specific to particular patients on an as needed basis
-Compound is done by a pharmacist, physician, or another individual under their direct supervision
-Ingredients used are bulk substances that comply with USP-NF
-Compound can not be a copy of a commercially available product
-Compound can be done in advance but on a limited basis
-Meeting these requirements exempts the pharmacy from needing to meet regulations from cGMP, misbranding, New Drug Requirements
What are outsourcing facilities for making drugs(503b)
-Manufacturing large batches with or without prescriptions to be sold to facilities for office use only
-Must register, pay annual fees, and be inspected by the FDA
-Compounding can not be a copy of a commercially available product
What is drug manufacturing?
Mass production of drug products that have been approved by the Food and Drug Administration
What must be included on the product label of drugs made by outsourcing facilities?
-The statement “this is a compounded drug”
-Name, address, and phone number of the outsourcing facility
-Lot number or batch number
-Established name of the drug
-Dosage or strength
-Quantity or volume
-Beyond use date
-Storage and handling instructions
-NDC
-The statement “not for resale”
-A list of active and inactive ingredients
What happened to drugs that came out before 1938 when the Food, Drug, and Cosmetic Act came out?
If a drug came out before 1938, it was assumed to be safe and effective so these drugs were grandfathered in
What happened to drugs between 1938-1962 after the kefauver-harris amendment came out?
-The Drug Efficacy Study Implementation was put into place in 1968
-All drugs between 1938-1962 are reviewed by the National Academy of Sciences and they issue recommendations to the FDA
-FDA makes the decision after reviewing the recommendations on if products may remain on the market
-Products stay on the market until a decision is made
-Some DESI decisions have yet to be made to this day
Steps in the drug development process
-Step 1: preclinical research
-Step 2: submission of investigational new drug
-Step 3: clinical research
-Step 4: New drug application process
-Step 5: Post-market safety monitoring
What happens in step 1 of the drug development process?
In vivo animal testing is utilized to record data on toxicity and pharmacology of the product
What information must be included in an application to proceed from step 1 to step 2 of the drug development process?
-Animal pharmacology and toxicology studies
-Manufacturing information
-Clinical protocols and investigator information
How many phases are there of step 3 of the drug development process?
3 phases
What happens in phase 1 of step 3 of the drug development process?
-20 to 100 healthy human volunteers receive the drug to evaluate the safety and dosage of the compound
-Baseline human pharmacokinetic and pharmacologic properties are also reviewed and reported
What happens in phase 2 of step 3 of the drug development process?
-Several hundred human volunteers who have the disease or condition that is being studied
-Primary goal of this phase is to expand information about safety and adverse effects of the drug, and to determine the effectiveness of therapy
What happens in phase 3 of step 3 of the drug development process?
-Drug is given to thousands of patients in several geographic locations who have the disease or condition that is being treated
-Goal is to demonstrate efficacy at a higher power, and to expand information around adverse effects
What happens in step 4 of the drug development process?
A new drug application is submitted by the sponsor to the FDA, including everything from the preclinical data to the phase 3 trial data
What must be included in a new drug application?
-Proposed labeling
-Safety updates
-Drug abuse information
-Patient information
-Any data from studies that may have been conducted outside of the United States
-Institutional review board compliance information
-Directions for use
What happens in step 5 of the drug development process?
FDA reviews MedWatch for trends among adverse events reported by health professionals and patients
What did the orphan drug act do?
Provided lower statistical burdens for proof of safety and efficacy when appropriate
What did the orphan drug act allow?
-Tax incentives for orphan drug production
-Enhanced patent protection and marketing
-Clinical research subsidies
-Government incentives to engage in drug research
