Development Stages
Level 1. Target identification: Therapeutic target identified
Level 2. Target validation: Therapeutic target undergoes validation in appropriate models
Level 3. Therapeutic identification: Small molecule or biologic with potential for therapeutic effect is identified
Level 4. Therapeutic design: Lead molecule is identified
Level 5. Therapeutic optimization: Lead compound is optimized. Clinical development plan is prepared
Level 6. Preclinical I: Pharmacologic/animal model studies demonstrating proof-of-principle are performed
Preclinical drug development stages. Following identification of a drug target and candidate compounds, several early activities, such as pharmacology, in vivo efficacy, and experimental toxicology, can contribute to the selection of a lead candidate for preclinical development. These preclinical activities provide the basis for an Investigational New Drug (IND) application to the FDA for permission to initiate clinical testing in humans. ADME, absorption, distribution, metabolism, and excretion; API, active pharmaceutical ingredient; PK, pharmacokinetics; Prep, preparation; Tox, toxicity.
Preclinical flow diagram. The parallel and inter-related activities contributing to preclinical development are summarized with color coding to denote related components: manufacturing (red), analytical (grey), documentation (orange), safety (blue), clinical (green). API, active pharmaceutical ingredient; CMC, chemistry, manufacturing, and controls; FDA, US Food and Drug Administration; GLP, good laboratory practice; GMP, good manufacturing practice; ICF, informed consent form; IND, Investigational New Drug; PK, pharmacokinetics.
Level 7. Preclinical II: Dose-finding/characterization studies are performed
Level 8. Preclinical III: Toxicology/safety studies are completed
Cash flow 'Valley of Death' diagram. The cash flow 'Valley of Death' as a function of development stage (time) with typical funding sources at various stages (adapted from). RAID, Rapid Access to Interventional Development; SBIR, Small Business Innovative Research; RAPID, Rapid Access to Preventive Intervention Development; STTR, Small Business Technology Transfer.
Level 9. Clinical Phase I: Human testing on a small-scale basis
Level 10. Clinical Phase II: Controlled clinical testing has been conducted in a relatively small number of patients
Level 11. Clinical Phase III: Clinical testing in large patient populations
Level 12. Patient use: Clinical trials completed and technology approved and available for use – post-marketing surveillance (if required) ongoing
Basic Research
Level 1. Target identification
Therapeutic target identified
Level 2. Target validation
Therapeutic target undergoes validation in appropriate models Identification
Level 3. Therapeutic identification
Drug: Small molecule or biologic with potential for therapeutic effect is identified
In vitro/In vivo
Level 4. Therapeutic design
Lead molecule is identified
Level 5. Therapeutic optimization
Lead compound is optimized. Clinical development plan is prepared.
Preclinical POC
Level 6. Preclinical I
Pharmacologic/animal model studies demonstrating proof-of-principle are performed
Preclinical Regulatory
Level 7. Preclinical II
Dose-finding/characterization studies are performed
Level 8. Preclinical III
Drug: Toxicology/safety studies are completed
Clinical
Level 9. Clinical Phase I
Human testing on a small-scale basis
Level 10. Clinical Phase II
Controlled clinical testing has been conducted in a relatively small number of patients
Level 11. Clinical Phase III
Clinical testing in large patient populations
Patient use
Level 12. Patient use
Clinical trials completed and technology approved and available for use – post-marketing surveillance (if required) ongoing