New Drugs, Generic Drugs, FDCs

1
New Drugs,Generic Drugs, FDCs

• Mary K. Pendergast
• May 10, 2004

2
FDANew Drug Application (NDA)

• New Molecular Entity (NME)
• New Formulation (Dose, Strength)
• New Combination
• New Manufacturer
• 21 CFR Part 314

3
NDA Supplements

• New Indication for Use
• New Population (pediatrics)

4
NDA Contents

• Must Prove Safe and Effective
• Sections
• CMC - Chemistry, manufacturing controls
• Animal pharmacology toxicology
• Human pharmacokinetics bioavailability
• Microbiology (virology, resistance,
  susceptibility)
• Clinical Studies (dose, safe, effective)
• Risk/Benefit, Post-Marketing Studies

5
Chemist Microbiologist Pharmacologist Biopharmaceu
tist Clinician Statistician
REVIEWERS
Scientific Investigations
Advisory Committee
NDA
Office Drug Safety
Compliance (CMC)
Drug Advertising
6
NDA Process

• Submitted and Filed by FDA
• Discipline Reviews
• Internal Meetings
• Advisory Committee Meeting
• Negotiations with Sponsor (Label, Risk Management
  Plans, Post Approval Commitments)
• Inspections
• Decision
• Publication of FDA Reviews

7
Generic Drugs (ANDA)

• Need a Reference Listed Drug 21 CFR 314.92
• Same Active Ingredients
• Same Route of Administration
• Same Dosage Form
• Same Strength
• Same Indication/Conditions for Use
• Some Changes Allowed Suitability Petition
• (Patents go to marketing, not approvability)

8
Generic Drugs

• Simplified Application 21 CFR 314.94
• Do Not Prove Safe and Effective
• Prove Bioequivalent to the Reference Listed Drug
  21 CFR Part 320
• Bioequivalence based on
• Cmax
• AUC (area under the time-concentration curve)

9
Bioequivalence Example
10
Possible BE Results (90 CI)
11
Fixed Dose Combinations

• Combination Drug Regulation 21 CFR 300.50
• Two or more drugs may be combinedwhen each
  component makes a contribution to the claimed
  effects and the dosage of each component (amount,
  frequency, duration) is safe and effective for a
  significant patient population .

12
Pediatric Drugs

• Children Not Small Adults
• Requires Clinical Assessment are disease,
  disease course, and outcomes the same
• Often New Clinical Trials Needed
• Equivalent Dosing a Challenge
• New Formulations Often Required
• www.fda.gov/cder/pediatric

13
WHO Prequalification

• Authority
• Structural Challenges
• Resource Challenges
• Transparency
• Accountability

14
Thank you Jeff Murray M.D., M.P.H.FDA