lev-os IND Application
Drafts a complete IND application under 21 CFR Part 312 for FDA authorization to begin human clinical trials.
Prerequisites
Collect before drafting:
- Drug substance/product info — chemical name, code designation, structural formula, mechanism of action
- Nonclinical reports — pharmacology, toxicology, PK/PD data
- CMC data — manufacturing process, specifications, stability, certificates of analysis
- Clinical protocol(s) — design, objectives, endpoints, statistical analysis plan
- Investigator info — CVs, Form FDA 1572, clinical site details
- Prior human experience (if any) — foreign trials, literature, compassionate use
- IRB documentation — approval letters or submission plans, informed consent forms
Quick Start
- Confirm trial phase (I/II/III) — this drives CMC depth and nonclinical requirements
- Complete Form 1571 cover sheet
- Draft sections in 21 CFR 312.23(a) order (see below)
- Cross-reference all nonclinical citations to specific IND sections
- Run checklists for Form 1571, IB, protocol, and environmental assessment
IND Section Order (21 CFR 312.23(a))
| # | Section | Reference |
|---|---|---|
| 1 | Cover Sheet — FDA Form 1571 | 312.23(a)(1) |
| 2 | Table of Contents — mirror regulatory numbering | 312.23(a)(2) |
| 3 | Introductory Statement — rationale, therapeutic purpose, investigational plan | 312.23(a)(3) |
| 4 | Investigator's Brochure — safety, efficacy, pharmacology, known risks | 312.23(a)(5) |
| 5 | Clinical Protocol(s) — design, dosing, safety monitoring, statistical plan | 312.23(a)(6) |
| 6 | CMC: Drug Substance — synthesis, specs, stability | 312.23(a)(7) |
| 7 | CMC: Drug Product — formulation, controls, container/closure, stability | 312.23(a)(7) |
| 8 | Pharmacology/Toxicology — PK, acute/chronic tox, repro tox, genotox | 312.23(a)(8) |
| 9 | Previous Human Experience — prior clinical data, foreign trials, literature | 312.23(a)(9) |
| 10 | Additional Information — IRB approvals, consent, investigator qualifications | 312.23(a)(10) |
Key Checklists
Form 1571
- Sponsor name, address, contact
- Drug name and code designations
- Trial phase (I, II, III)
- IND number (amendment) or "Initial"
- Serial number
- Indication(s) under investigation
- List of enclosed sections
- Authorized signature with date
Investigator's Brochure
- Physical/chemical/pharmaceutical properties
- Nonclinical pharmacology summary
- Nonclinical PK and metabolism
- Nonclinical toxicology (tabulate: species, route, duration, NOAEL, findings)
- Clinical experience summary (if applicable)
- Known/anticipated adverse effects and precautions
Clinical Protocol
- Title, protocol number, version/date
- Primary and secondary objectives
- Study design and phase
- Inclusion/exclusion criteria
- Dosing regimen with rationale
- Efficacy and safety endpoints
- Stopping rules and dose-limiting toxicity definitions
- Safety monitoring plan (AE reporting, DSMB if applicable)
- Statistical analysis plan with sample size justification
Phase-Appropriate CMC Depth
| Phase | Drug Substance | Drug Product | Stability |
|---|---|---|---|
| I | Synthetic route, preliminary specs, structure confirmation | Formulation description, basic controls | Abbreviated (cover trial duration) |
| II | Refined process, tightened specs, impurity profiles | Validation initiated, expanded controls | 6+ months accelerated + long-term |
| III | Full process validation, complete characterization | Full cGMP, container/closure validation | ICH-compliant program |
Nonclinical Study Table Format
For each study, tabulate: study type, test facility (with GLP status), species/strain, route, dose levels, duration, NOAEL/NOEL, key findings, relevance to clinical dose.
Environmental Assessment
- Most INDs qualify for categorical exclusion under 21 CFR 25.31(e)
- If claiming exclusion: cite the specific 21 CFR 25 provision with basis statement
- If exclusion does not apply: prepare assessment per 21 CFR Part 25 Subpart B
Pitfalls and Checks
- Verify FDA forms — retrieve current Form 1571/1572 from fda.gov; versions update periodically
- Phase-appropriate CMC — do not over-document Phase I or under-document Phase III
- Cross-reference internally — protocol references to nonclinical data must cite specific IND section/page
- GLP compliance — pivotal safety studies require 21 CFR Part 58; flag and justify any non-GLP studies
- No promotional language — avoid unsupported efficacy claims; this is a scientific/regulatory document
- Safety-first framing — every section must demonstrate adequate basis for protecting human subjects
- Confidential info — mark trade secrets per 21 CFR 312.130 if sponsor requests
- eCTD format — for electronic submissions, organize per FDA eCTD Module 1–5 structure
- Pre-IND feedback — if a Type B pre-IND meeting occurred, address each FDA comment explicitly