Arizona Center for Innovation (AzCI) presents: FDA Drug Development 101 - I discovered a drug which will cure the world disease - now what!
This presentation is part of a series developed for a workshop on "How to Navigate the Biotech Regulatory Process"
The Arizona Center for Innovation is an incubator and innovation center and provides resources in support of startups getting to the next level and become successful enterprises.
3. Innovation Center
The Arizona Center for Innovation (AzCI) assists
technology companies turning their innovative ideas
into successful businesses through:
• Focused programs
• World-class expertise
• High-quality facilities
Access:
• Other technology
entrepreneurs
• Collaborative,
creative
environment
• Advantage of
hands-on support
• Successful
business leaders
Arizona Center for Innovation
4. AzCI
Startup and emerging technology companies
• Community and UA spin-outs
Technology
• Aligned with UA Tech Parks and UA
International
• Softlandings
Who
5. AzCI
Technology Areas:
• Security and Defense
• Mining
• Agriculture and Water
• Biotechnology
• Intelligent Transportation and Vehicles
• Renewable Energy
Informatics/Big Data/Advanced Manufacturing/
Imaging/Optics/Photonics
Focus
6. “How to Navigate to Biotech Regulatory Process”
20 September 2011
Marlene E. Haffner, MD, MPH
Haffner Associates, LLC
7. 1800’s – US Customs Laboratories were
established to administer the Import Drugs Act of
1848
--Mission – US should not be a dumping ground
– purity and potency standards of the USP
8. Opium, morphine, heroin, and cocaine – no restrictions
Cows weren’t tested for TB
Victories over infectious diseases just beginning – Robert
Koch; Louis Pasteur
Agricultural to industrial economy
9. Prohibited Interstate Commerce of misbranded and
adulterated foods and drugs and poisonous patent medicines
Specific labeling – morphine, cannabis, chloral hydrate, …
Did not address
◦ Food or drug standards
Enforced by Division of Chemistry of the Department of
Agriculture
10. 1938 – Food, Drug, and Cosmetic Act
◦ Elixir of sulfanilamide
◦ Safety
◦ Safe tolerances
1962 Kefauver-Harris
◦ Thalidomide
◦ Efficacy and safety before marketing
◦ Adverse events
Further improvements to safety in subsequent years
Each added to the better and more costly products
11. 8000 + dedicated and talented employees across the US
~ 50% in the Washington, DC area
MDs, pharmacists, statisticians, nurses, dentists, policy
analysts, PhDs, and more
No one in the agency bites! They really wish to be
helpful
They are short staffed for the responsibilities they have
Listen carefully to what you are told in meetings
12. Discovery
Screening – including product characterization, formulation,
PK, and drug disposition
Pre-Clinical Toxicology testing
IND Application
Phases 1, 2, 3 – clinical trials
New Drug Application (NDA)/ Biologics Licensing
Agreement (BLA)
Post marketing commitments (REMS – risk evaluation and
mitigation strategy)
13. Often a stumbling block
Acute and short term toxicity in animals – one
rodent and one non- rodent
◦ Genetic
◦ Reproductive
◦ Carcinogenicity
How is the drug absorbed, distributed, metabolized
and excreted in animals
14. Apply to FDA to allow human exposure to the
experimental drug – Go to FDA website
http://www.FDA.gov/cder/guidance/index.htm
Qualification Process for Drug Development tools
(DDT)
IND describes for what the product is being
developed, safety issues as known, studies to be
undertaken – assures safety for first in humans
15. Chances are you are not going to “cure” the disease
How will you show efficacy?
Is your endpoint a clinical endpoint, or a surrogate
endpoint?
Discuss with FDA. If you and FDA do not agree, why?
Further discussion with FDA
16. MEET WITH FDA REVIEW DIVISION – EARLY AND OFTEN
Phases 1, 2, 3
Phase 1 –
◦ usually healthy volunteers
◦ 10 – 80 – determine safety of dosage (12 – 18 mos)
Phase 2 –
◦ 100 – 300 patients volunteers (24 mos)
◦ Dosage, adverse events (AEs), early efficacy
Phase 3 –
◦ 1000 – 3000 patient volunteers
◦ confirm efficacy,
◦ monitor AEs (30 – 40 mos)
17. Begin 30 days following submission of IND providing
no “clinical hold”
20 – 80 volunteers
Duration: 1 year
Determine bioavailability and safety
Determine adverse events associated with increasing
doses
Gain early evidence of efficacy
18. Consult with FDA – often
Assess efficacy in the disease or condition
Monitor safety and AEs
100 – 300 patient volunteers
Duration: 2 years
Less than 33% of INDs survive Phase 2
19. Consult with FDA
1,000 – 3,000 patient volunteers
Multiple testing sites
Duration 3 – 4 years
Confirm safety and efficacy – no drug is ever
confirmed as completelysafe
20. Formal proposal to FDA for approval of a new drug to
be marketed in the US
Must provide sufficient evidence for the FDA to
determine:
◦ Benefits outweigh the risk of the product
◦ Drug is safe and effective for its intended use
◦ Proposed labeling is appropriate
◦ Manufacturing methods and controls maintain drug identity,
strength, quality, purity and stability
21. Must assure continued safe and stable production
Must continue to monitor AEs
FDA may determine need for REMS – especially if
study done on small number of patients
Must report significant Adverse Events to FDA
Adverse events may not be known for many years – e.g.
VIOXX
22. Preclinical 3 – 6 years
Phase 1 1 – 2 years
Phase 2 2 – 3 years
Phase 3 3 – 4 years
________________________________________
9 – 15 years
FDA review 1 year