Lecture 4 Flashcards
Objectives
-Identify hallmark legislation of the later 20th century and the impact it had on pharmacy practice and pharmaceutical development
-Describe the process of drug development, considering changes implemented over the years
-Review requirements for drug packaging related to patient safety
1961: thalidomide tragedy
- drug was developed in 1952 and available in europe over the counter to help many women with morning sickness
- at the time no testing restrictions related to pregnant patients
Then in 1961 thalidomide was linked to phocomelia which is a rare condition affecting the fetal formation of arms and legs
- more than 10,000 children were born with serious birth defects
1962: Kefauver-Harris Amendment
This was made in response to the thalidomide problems
Required medications to demonstrate not only safety but also efficacy (applies to all drugs marketed between 1938-1962)
Transferred jurisdiction of prescription drug advertising from the FTC to FDA
Established current good manufacturing practice (CGMP) requirments
Added requirements to clinical investigations including informed consent of research subjects and reporting of adverse drug reactions
Current good manufacturing practices (cGMP)
minimum requirments for the manufactures of drug products
Any manufacturer for drugs used in the united states must be registered with the FDA and undergo an inspection at least once every 2 years
IF YOU DO NOT COMPLY WITH cGMP THE PRODUCT IS ADULTERATED
IF YOU DO NOT REGISTER WITH THE FDA THE PRODUCT IS ADULTERATED AND MISBRANDED
making drugs category 1
Pharmacy or Traditional Compounding (503a)
compounding according to prescriptions specific to particular patients on an as needed basis.
Meeting these requirements is important, because compounding within these limits exempts the pharmacy from meeting regulations related to:
cGMP, Misbranding (related to drug labeling), New Drug Requirements
- compound pursuant to a prescription only
- Compounding is for an individual patient
- Compounding is done by a pharmacist, Physician, or any other individual with direct supervision
- Ingredients used in compounding are bulk substances that comply with the USP-NF
- compound cannot be a copy of a commercially available product (unless drug shortage or other specific FDA reasonings)
- Compounding can be done in advanced, but only on a limited basis
Making drugs category 2
Outsourcing Facilities (503b)
manufacturing large batches with or without prescriptions to be sold to facilities for office use only.
- compounding without receiving a prescription for a specific patient
- must register, pay annual fees, and be inspected by the FDA
- Compounding cannot be a copy of a commercially available product
Product labels MUST contain the following:
- 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
Making drugs category 3
Manufacturing:
mass production of drug products that have been approved by the Food and Drug Administration.
Drugs on market before 1962
The are known as grandfathered drugs
These drugs did not have to prove safety and efficacy and were assumed since they were on the market for so long they have to be safe and effective
1968: Drug Efficacy Study Implementation (DESI)
National academy of sciences investigates all medications approved before 1938-1962 and issues recommendations to the FDA
FDA reviews recommendations and makes decisions on those products - products can remain on the market until a decision is made
The Drug Development Process
Discovery and development of novel chemical for drug consideration.
Step 1: Preclinical Research
In Vivo Animal Studies
Step 2: Submission of Investigational New Drug (IND)
Step 3: Clinical Research
Phase I
Phase II
Phase III
Step 4: New Drug Application Process (NDA)
Step 5: Post-Market Safety Monitoring
Phase IV
Step 1: Preclinical Research
Before a drug can be tested on humans it must undergo in vivo animal testing to record data on toxicity and pharmacology of the product
Step 2: Investigational New Drug (IND)
if the drug shows possible safe and effective use the manufacturer may submit an IND
the IND must contain the following:
- Animal pharmacology and toxicology studies
- Manufacturing information
- Clinical protocols and investigator information
Once submitted the sponsor must wait 30 days before initiating any clinical trials to allow the FDA to review the IND
Step 3: Clinical ResearchPhase 1
20-100 healthy human volunteers receive the drug to evaluate the safety and dosage of the compound
- Human pharmacokinetic and pharmacologic properties are also reviews and reported
Step 3: Clinical ResearchPhase 2
Involved several hundred human volunteers who have the disease or condition that is being studied
goal is to expand information about safety and adverse effects of the drug and to determine the effectiveness of the therapy
Step 3: Clinical ResearchPhase 3
given to hundereds or 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.
Step 4: New Drug Application (NDA)
NDA is submitted by the sponsor to the FDA, including everything from the preclinical data to the Phase 3 trial data. Must also include:
-Proposed labeling
-Safety updates
-Drug abuse information
-Patent information
-Any data from studies that may have been conducted -outside the United States
-Institutional review board compliance information
-Directions for use
Step 5: Post-marketing Surveillance Phase 4
FDA reviews MedWatch for trends among adverse events reported by health professionals and patients.
New Drug Application Timeline
Drug discovery: 6 months – 5 years
Preclinical research: 3 months – 1 year
Investigational New Drug Application: 1 month
Phase 1: 6 – 9 months
Phase 2: 6 months – 2 years
Phase 3: 1 – 4 years
NDA: 6 – 10 months
TOTAL TIME: 3 ½ to 13 ½ years…success rate about 3%…seems like a long time with a lot of risk…
1983: Orphan Drug Act
The orphan drug act provided lower statistical burdens for proof of safety and efficacy when focused on orphan disease state
also allowed:
-Tax incentives for orphan drug production
-Enhanced patent protection and marketing
Clinical research subsidies
-Government incentive to engage in drug research
1984: Hatch-Waxman Act
Made to reduce the requirments for approval of generic prescription drugs
after law was placed
-Generic companies can prepare for approval without impinging on patent
-Generic companies only had to prove bioequivalence and proof of acceptable manufacturing practices and controls
Abbreviated New Drug Application
Termed abbreviated because applicant does not need to include animal or human clinical trial data to establish safety and effectiveness.
Bioequivalence: demonstration that the rate of absorption of the generic drug is equivalent to that of the innovator drug. Must deliver the same amount of ingredient in the same amount of time.
This dropped the standard approval time for generic drugs from 3 years to 3 months
