New_Drug_Deveùlllllùmùùùùùùùlopment_101.ppt

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1. Maarika Kimbrell
Deputy Director, Office of New Drug Policy, Office of New Drugs
Center for Drug Evaluation and Research (CDER)
Drug Development 101

2. What is Drug Development?
•A process.
•A long, multifaceted process.
•To develop a product that is intended for use in the
diagnosis, cure, mitigation, treatment, or prevention of
disease; or that is intended to affect the structure or
function of the body.
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3. What is Drug Development?
With the goal being to ultimately bring a new drug to
patients with:
•Proper assurances of identity, quality, purity, and strength
of the drug, and
•established efficacy and safety of the therapy for use in
humans, at a dose range and dosing schedule
that provides an acceptable risk benefit relationship.
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4. What is Drug Development?
What does it look like from a regulatory perspective?
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5. Background
–High levels of risk, uncertainty, and complexity:
•Only 11.3% of drugs that enter clinical testing will be approved in the US
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Source: PhRMA, 2008

6. Drug Development
Back to this pictorial:
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Another Perspective – Three Main Phases:
(1) Drug Discovery, (2) Development, and (3) Post-
Development

7. Drug Development – Broken Down
1) Drug Discovery Phase
Synthesis, Purification, and Characterization
Non-Clinical Development
2) Development Phase
Clinical Development
Formulation development and manufacturing Scale-Up
Regulatory Applications
[Explore Pricing and Reimbursement]
3) Post-Development Phase
Post-Approval Trials
Post- Approval Changes
[Reimbursement]
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8. Drug Discovery: Synthesis & Purification
•Target Identification for a Disease or Condition
–How does the body function, both normally and abnormally, at the most basic
level?
–How might a drug be used to prevent, cure, or treat?
•Lab Synthesis: creating compounds with structures likely to evoke
the desired physiological effect
–Computer Modelling; Chemical Libraries
–Naturally Occurring Compounds
–Chance
•Purification: optimization of the product in to a development
candidate
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9. Drug Discovery: Characterization
•Goal: developing an understanding of the physicochemical
properties of the drug and establishing the molecular identity, its
purity, and other physicochemical properties of the drug
substance.
•Specific properties/attributes to be determined are:
–Molecular structure, solubility, particle sizes, and BCS class, etc., of the drug
substance
–Size of the compound
–Shape of the compound
–Initial Toxicity Profile
–Initial Bioactivity/bioavailability
–Preferred conditions for functioning
–Initial Stability data

10. Drug Discovery: Nonclinical Studies
•To characterize toxic effects
–On organs
–Of Dose
–Of Exposure
•Typically two or more species (one rodent, one non-
rodent)
•Goals to establish:
–Highest tolerable dose
–Proposed dose, route, duration for Phase 1
–Reversibility of Adverse Effects
–Genotoxicity, teratogenicity, reprotoxicity
•“Three Rs” principle:
–Replacement, Reduction, Refinement
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11. Development: Clinical Development
•During clinical trials the investigational product is administered to
humans and is evaluated for safety and effectiveness in treating,
preventing, or diagnosing a specific disease or condition.
•While the goal of clinical trials is to ascertain safety and
effectiveness information on the product, safety of the
participants is of utmost importance.
•Trials in humans can begin only after an IND has been submitted
and reviewed by the FDA, and the trial protocols are reviewed by
an institutional review board(s) (IRB).
•Clinical trials are conducted in a sequence or in phases. Each
specific phase (1, 2, 3) is designed to answer specific research
questions.
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12. Development: Clinical Development
•Phase 1: Clinical Pharmacology Trials
-Usually conducted in healthy volunteers with a small number of subjects
-Primary focus on safety and tolerability, including safe dose range
•Phase 2: Controlled Trials
-Therapy is provided to a larger group of people
-Transition to patients with the disease or condition
-Controlled – placebo and comparators
-Goals to assess effectiveness and further evaluate safety
•Phase 3: Confirmatory Trials
-Large studies, controlled, multi-centered
-Goal to confirm efficacy and safety profile
-Establish information necessary to label the product for safe and effective use in
the target population for the target indication
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13. Development
•Manufacturing
–Test capabilities
–Development knowledge
•Drug substance
•Formulation
•Drug delivery
•Analytical methods
•Packaging
–Scale Up: Preparing for Commercialization/Market Launch,
where drug prepared for drug development clinical trials
often in small batch sizes to allow iterative development and
process improvements
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14. Development: Regulatory Applications
•Marketing Application
–New Drug Application (NDA): a new drug is effective for its intended use
and that the established benefits of the drug outweigh the known risks
–Biologics Licensing Application (BLA): a showing that the product is safe,
pure, and potent
•Includes all in-vitro, animal, and human clinical data
generated from all phases of development, including
integrated summaries of this information
•Quality & Manufacturing information
•FDA staff conduct review and approve when the
application establishes that these standards have been
met.
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15. Post-Development: Post Approval
-Useful to gather additional information on the
drug’s effect in various populations and any side
effects associated with long-term use
-New age groups, patient types, new indications, etc.
-Unknown side effects, safety signals, or risk factors
-May be required or requested by the FDA either
under post-marketing requirements or
commitments agreed upon prior to approval
-Sometimes referred to as “Phase 4” Trials
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16. Questions?
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