Lecture 14: Drug Development and Biosimilars Flashcards
What Constitutes a “Drug”?
A drug is a substance that produces change in cellular or physiologic functioning
Drug development influenced by:
High cost of research; complex regulatory environment & legislations;
insurer reimbursements; and patient perspectives
Some of factors that influence drug development include
Development cost (~ $1.3 - $2.8 billion or more) and time (can be as much as or >15 years) Regulatory approval process Changes in laws Patient acceptance Insurance reimbursement
Investing in new drug development is
expensive and risky
FDA Regulates drugs under two legislative acts
- Food, Drug, and Cosmetic Act – for small molecule drugs
- Public Health Service Act – for biologicals
The FDA’s mission is to promote and protect the public health by promoting:
safe and effective products reach the market in a timely safe and effective products reach the market in a timely way
- However: once FDA determines a drug is safe and effective, it has little control over
its use in medical practice, such as for non-approved indications (“off-label” use)
Specific FDA Function/Role in Drug Development
Process and Drugs in the Marketplace
- Approves drugs on the basis of purity, safety, efficacy
- Regulate all labeling of prescription and nonprescription drugs
- Advertising OTCs the responsibility of the Federal Trade Commission (FTC)
- Regulate manufacturing processes of drugs and institution of drug recalls
- Regulate bio-equivalence for generics and bio-similars
- Monitor safety of US blood supply
Conceptualization
performed by independent investigators, small research companies, academic institutions & large pharmaceutical companies
Intramural
NIH investigators perform research
Extramural
independent investigators win research grants to perform research
Drug development has
3 stages prior to approval
STAGE 1
Drug discovery
Discovery ( Laboratory based)
5,000 – 10,000 compounds may be synthesized and tested
- 250 “may” make it to pre-clinical testing
STAGE 2
Pre-clinical Testing
- Tests performed to determine if candidate molecule safe to test in humans
- Candidates for drugs are first tested in animals
- Very few candidate materials for drugs make it through pre-clinical testing
- < 0.1% of potential candidate drugs go from discovery to clinical testing stage
- Varies in number of years it takes
STAGE 3
Clinical testing has 3 DISTINCT PHASES with distinct goals
- Investigational New Drug (IND) application must be submitted to FDA
in order to begin clinical testing in humans
STAGE 4
Post approval and post clinical testing (also called Phase IV)
To begin clinical testing,
Investigational New Drug (IND) Application must be filed
When all clincial testing is complete,
The New Drug Application (NDA) must be filed
PHASE IV
addition research post-marketing by FDA
- Used to identify events not detected during clinical testing
IND
Investigational New Drug
NDA
New Drug Application
3 phases before drug approval : Clinical testing
- Phase 1: Learn how the drug works in (small number) of humans – set dosage
- Phase II: Demonstrate efficacy (proof of concept) and safety (toxicity) in patients
- Phase III: Provide strong evidence of efficacy and safety by studying candidate drug
in a few thousand people with target disease in randomized, controlled trials using
doses and settings more like “real world” practice
Phase I Clinical Testing Goals Include
- Learn how candidate drug works in HEALTHY humans
Studies of <100 healthy individuals
Establish dose range, metabolism, excretion, toxicities
Usually takes one year or less to complete
Phase II Clinical Testing Goals Include
- Study candidate drug in a few hundred people with target disease
- Efficacy (proof of concept) and safety (toxicity) in patients
- Single arm studies (No comparison group)
- Usually takes up to two years to complete
(occurs after Phase I testing is completed)
Phase III Clinical Testing Goals Includ
Study a few thousand people with target disease in randomized, controlled trials
Strong evidence for efficacy and safety
Use doses and settings more like real-world practice
Success is necessary to move to the next stage of approval
Usually takes three to four years to complete
(occurs after Phase I and Phase II testing is completed