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.

2. ARIZONA
CENTER

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

23. ?Marlene E. Haffner, MD, MPH
301 984 5729
www.mhaffner.com
mhaffner3@verizon.net

24. https://techparks.arizona.edu/azci