![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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NEW PRODUC DEVELOPMENT & APPROVAL PROCESS- DR RAI.ppt
- 1. DR.S.K.RAI HOD- R&D AKUMS DRUGS & PHARMACEUTICAL LTD NEW DRUG DEVELOPMENT RESEARCH & DEVELOPMENT
- 2. PROCEDURE OF DRUG DEVELOPMENT? • 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. 2
- 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. 3
- 4. DRUG DEVELOPMENT? What does it look like from a regulatory perspective? 4
- 5. BACKGROUND • High levels of risk, uncertainty, and complexity: • Only 11.3% of drugs that enter clinical testing will be approved in the US 5 Source: PhRMA, 2008
- 6. DRUG DEVELOPMENT Back to this pictorial: 6 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] 7
- 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 8
- 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 10
- 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. 11
- 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 12
- 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 13
- 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. 14
- 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 15
- 16. QUESTIONS? 16
Editor's Notes
- #10: Two or more species are used because drugs may affect one species differently from another. Companies make every effort to use as few animals as possible and to ensure their humane and proper care. Genotoxicity – damaging effects of agents on genetic information Teratogenicity – abnormalities of physical development Reprotoxicity – toxic effects on reproduction capacities or function