Phase 1 IND Guidance Documents
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| IND | Investigational New Drug application |
|---|---|
| CMC | Chemistry, Manufacturing, and Controls |
| CBER | Center for Biologics Evaluation and Research |
| CDER | Center for Drug Evaluation and Research |
| CDRH | Center for Devices and Radiological Health |
| CVM | Center for Veterinary Medicine |
| OCE | Oncology Center of Excellence |
| ORA | Office of Regulatory Affairs |
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| Guidance Title | Status | Date Published | Guidance Topic | Supplemental Topic(s) | Summary | Center |
|---|---|---|---|---|---|---|
| Q8, Q9, and Q10 Questions and Answers (R5) | Final | May 2026 | CMC (Chemistry, Manufacturing, and Controls) | Drugs and biologics; CMC/quality | Clarifies ICH pharmaceutical development, quality risk management, and quality system implementation. | CDER, CBER |
| M11 Clinical Electronic Structured Harmonised Protocol | Final | May 2026 | Clinical Trial Design/Clinical Protocol Development | Clinical trials; drugs and biologics | Establishes harmonized digital clinical trial protocol structure and exchange standards. | CDER, ORP |
| Assessing the Effects of Food on Drugs in INDs and NDAs – Clinical Pharmacology Considerations | Final | May 2026 | Clinical Trial Design/Clinical Protocol Development | Oral small-molecule drugs; INDs/NDAs | Recommends food-effect study design for orally administered drugs in INDs and NDAs. | CDER |
| Development of Non-Opioid Analgesics for Acute Pain | Draft | May 2026 | Clinical Trial Design/Clinical Protocol Development | Acute pain; non-opioid analgesics | Addresses development, labeling claims, and expedited programs for non-opioid acute pain products. | CDER |
| Pulmonary Tuberculosis: Developing Drugs for Treatment | Final | May 2026 | Clinical Trial Design/Clinical Protocol Development | Antibacterials; pulmonary TB | Assists clinical development of new antibacterial drugs for pulmonary tuberculosis treatment. | CDER |
| Oncology Pharmaceuticals: Streamlined Nonclinical Safety Studies for Biologics and Conjugated Products | Draft | May 2026 | Nonclinical Pharmacology/Toxicology Data | Oncology biologics, ADCs, conjugated products | Recommends streamlined nonclinical toxicology approaches to reduce unnecessary animal studies. | OCE |
| M15 General Principles for Model-Informed Drug Development | Final | June 2026 | Clinical Trial Design/Clinical Protocol Development | Drugs and biologics; MIDD | Provides harmonized planning, evaluation, documentation, and regulatory interaction principles for MIDD. | CDER, CBER |
| Clostridioides difficile Infection: Developing Drugs for Treatment, Reduction of Recurrence, and Prevention | Final | May 2026 | Clinical Trial Design/Clinical Protocol Development | Anti-infectives; CDI | Supports clinical development for CDI treatment, recurrence reduction, or prevention indications. | CDER |
| Leveraging Prior Knowledge in the Development of Human Gene Therapy Products Incorporating Genome Editing | FDA | Draft | June 2026 | Pre-IND Planning | Biologics and Gene therapy | Recommends using public and platform knowledge to support CMC, nonclinical, and clinical development. | CBER |
| Considerations for the Design of Early-Phase Clinical Trials of Cellular and Gene Therapy Products | FDA | Final | June 2016 | Clinical Trial Design/Clinical Protocol Development | Cellular therapy and Gene therapy | Provides recommendations for early-phase CGT trials assessing safety, tolerability, and feasibility | CBER |
| Considerations for the Design of Early-Phase Clinical Trials of Cellular and Gene Therapy Products | Final | June 2015 | Clinical Trial Design/Clinical Protocol Development | Cellular therapy, gene therapy, therapeutic vaccines, some biologic combination products | Early-phase trial design recommendations for safety, feasibility, dosing, population, controls, monitoring, and follow-up. | CBER |
| Preclinical Assessment of Investigational Cellular and Gene Therapy Products | Final | November 2013 | Pre-IND planning | Cellular therapy, gene therapy, therapeutic vaccines, xenotransplantation, certain biologic-device combinations | Preclinical study expectations supporting INDs/BLAs for CGT products before clinical testing. | CBER |
| Investigational New Drug Applications Prepared and Submitted by Sponsor-Investigators | Draft | May 2015 | Pre-IND planning | Sponsor-investigators; drugs and biologics | Explains preparation, submission, and regulatory responsibilities for Sponsor-investigators. | CDER; CBER |
| Investigational New Drug Applications (INDs) — Determining Whether Human Research Studies Can Be Conducted Without an IND | Final | September 2013 | Pre-IND planning | Human drug/biologic research; IND exemptions | Clarifies when clinical studies require an IND or qualify for exemption. | CDER; CBER |
| Formal Meetings Between the FDA and Sponsors or Applicants of PDUFA Products | Draft | September 2023 | Pre-IND planning | Small molecules and biologics (PDUFA) | Describes formal FDA meeting types, timelines, packages, and expectations. | CDER; CBER |
| Investigational New Drug Applications for Positron Emission Tomography (PET) Drugs | Final | December 2012 | Pre-IND planning | PET imaging drugs; radiopharmaceuticals | Provides IND recommendations specific to investigational PET drug studies. | CDER |
| Content and Format of Investigational New Drug Applications (INDs) for Phase 1 Studies of Drugs, Including Well-Characterized, Therapeutic, Biotechnology-derived Products | Final | November 1995 | Pre-IND planning | Phase 1 small molecules and biologics | Recommends Phase 1 IND content, format, and supporting nonclinical information. | CDER; CBER |
| Best Practices for Communication Between IND Sponsors and FDA During Drug Development | Final | December 2017 | Pre-IND planning | All IND sponsors; drugs and biologics | Encourages timely, efficient communication between sponsors and FDA. | CDER |
| Content and Format of INDs for Phase 1 Studies of Drugs, Including Well-Characterized, Therapeutic, Biotechnology-Derived Products — Questions and Answers | Final | October 2000 | Pre-IND planning | Phase 1 INDs; drugs and biologics | Clarifies toxicology submission expectations for early-phase INDs. | CDER; CBER |
| IND Submissions for Individualized Antisense Oligonucleotide Drug Products for Severely Debilitating or Life-Threatening Diseases: Clinical Recommendations | Draft | December 2021 | Pre-IND planning | Individualized ASOs; rare genetic diseases | Provides clinical development recommendations for individualized antisense therapies. | CDER |
| IND Submissions for Individualized Antisense Oligonucleotide Drug Products: Administrative and Procedural Recommendations | Draft | January 2021 | Pre-IND planning | Sponsor-investigators; individualized ASOs | Describes administrative processes for individualized ASO IND submissions. | CDER |
| IRB Responsibilities for Reviewing the Qualifications of Investigators, Adequacy of Research Sites, and the Determination of Whether an IND/IDE is Needed | Final | August 2013 | Pre-IND planning | IRBs; drug and device studies | Clarifies IRB oversight of investigators, sites, and IND/IDE determinations. | CDER; CBER; CDRH |
| Bioavailability and Bioequivalence Studies Submitted in NDAs or INDs — General Considerations | Draft | March 2014 | Pre-IND planning | Small molecules; NDAs and INDs | Recommends conduct and analysis of BA/BE studies. | CDER |
| Rare Diseases: Early Drug Development and the Role of Pre-IND Meetings | Draft | October 2018 | Pre-IND planning | Rare disease drugs and biologics | Discusses early development strategies and value of pre-IND meetings. | CDER; CBER |
| Oncology Therapeutic Radiopharmaceuticals: Nonclinical Studies and Labeling Recommendations | Final | August 2019 | Pre-IND planning | Oncology radiopharmaceuticals | Recommends nonclinical testing and labeling approaches for therapeutic radiopharmaceuticals. | CDER |
| S6(R1) Addendum: Preclinical Safety Evaluation of Biotechnology - Derived Pharmaceuticals | Final | May 2012 | Pre-IND planning | Biotechnology-derived biologics | Updates nonclinical safety evaluation principles for biotechnology-derived products. | CDER; CBER |
| Expedited Programs for Regenerative Medicine Therapies for Serious Conditions | Final | February 2019 | Pre-IND planning | Regenerative medicine therapies | Recommendations on expedited development of regenerative therapies | CBER |
| Considerations for the use of the Plausible Mechanism Framework to Develop Individualized Therapies that Target Specific Genetic Conditions with Known Biological Cause; Draft Guidance for Industry | Draft | February 2026 | Pre-IND planning | Individualized therapies targeting specific genetic conditions | Recommendations on generating substantial evidence of effectiveness and safety for individualized therapies based on a plausible mechanism framework | CBER |
| M3(R2)Nonclinical Safety Studies for the Conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals: Questions and Answers | Final | March 2013 | Nonclinical Pharmacology/Toxicology Data | Pharmaceuticals; small molecules and biologics; clinical trials/marketing authorization | Clarifies implementation questions for ICH M3(R2) nonclinical safety recommendations. | CDER; CBER |
| M3(R2) Nonclinical Safety Studies for the Conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals | Final | January 2010 | Nonclinical Pharmacology/Toxicology Data | Pharmaceuticals; small molecules and biologics; clinical trials/marketing authorization | Harmonizes nonclinical safety studies supporting clinical trials and marketing applications. | CDER; CBER |
| Monoclonal Antibodies: Streamlined Nonclinical Safety Studies | Draft | December 2025 | Nonclinical Pharmacology/Toxicology Data | Monospecific monoclonal antibodies; biologics; long-term safety, DART, juvenile toxicity | Recommends streamlined mAb safety approaches to reduce unnecessary animal testing. | CDER |
| S9 Nonclinical Evaluation for Anticancer Pharmaceuticals | Final | March 2010 | Nonclinical Pharmacology/Toxicology Data | Anticancer pharmaceuticals; advanced disease and limited therapeutic options | Recommends nonclinical programs for anticancer drug development in advanced disease. | CDER; CBER |
| S9 Nonclinical Evaluation for Anticancer Pharmaceuticals—Questions and Answers | Final | June 2018 | Nonclinical Pharmacology/Toxicology Data | Anticancer pharmaceuticals; ICH S9 implementation | Clarifies ICH S9 implementation and supports 3Rs animal-use principles. | CDER; CBER |
| Oncology Therapeutic Radiopharmaceuticals: Nonclinical Studies and Labeling Recommendations | Final | August 2019 | Nonclinical Pharmacology/Toxicology Data | Systemic oncology therapeutic radiopharmaceuticals; alpha, beta, and/or gamma decay | Guides nonclinical programs and labeling for cancer therapeutic radiopharmaceuticals. | CDER |
| Safety Assessment of Genome Editing in Human Gene Therapy Products Using Next-Generation Sequencing | FDA | Draft | April 2026 | Nonclinical Pharmacology/Toxicology Data | Gene therapy products | Recommendations for next-generation sequencing (NGS)-based methods used in nonclinical studies | CBER |
| Providing Clinical Evidence of Effectiveness for Human Drug and Biological Products | Final | May 1998 | Nonclinical Pharmacology/Toxicology Data | drugs and biologics; NDAs, BLAs, supplemental indications | Explains evidence needed to demonstrate effectiveness for drugs and biologics. | CDER; CBER |
| E9 Statistical Principles for Clinical Trials | Final | September 1998 | Nonclinical Pharmacology/Toxicology Data | Medicinal products; clinical trials supporting marketing applications | Harmonizes statistical principles for trial design, conduct, analysis, and interpretation. | CDER; CBER |
| E10 Choice of Control Group and Related Issues in Clinical Trials | Final | May 2001 | Nonclinical Pharmacology/Toxicology Data | Clinical trials demonstrating treatment efficacy | Guides selection of control groups and explains what different trial designs can demonstrate. | CDER; CBER |
| Enrichment Strategies for Clinical Trials to Support Approval of Human Drugs and Biological Products | Final | March 2019 | Nonclinical Pharmacology/Toxicology Data | drugs and biologics; enrichment designs | Defines enrichment strategies to improve trial ability to demonstrate effectiveness and sometimes safety. | CDER; CBER |
| Non-Inferiority Clinical Trials | Final | November 2016 | Nonclinical Pharmacology/Toxicology Data | drugs and biologics; INDs, NDAs, BLAs, supplements | Advises when NI designs are interpretable, margin selection, and hypothesis testing. | CDER; CBER |
| Adaptive Design Clinical Trials for Drugs and Biologics Guidance for Industry | Final Level 1 | December 2019 | Clinical Trial Design/Clinical Protocol Development | drugs and biologics; adaptive, Bayesian, complex designs | Covers principles for designing, conducting, reporting, and submitting adaptive clinical trials. | CBER; CDER |
| Co development of Two or More New Investigational Drugs for Use in Combination | Final | June 2013 | Clinical Trial Design/Clinical Protocol Development | CDER-regulated drugs/biologics; new investigational drug combinations | Addresses scientific and regulatory issues for codeveloping multiple new investigational drugs. | CDER |
| M11 Template: Clinical Electronic Structured Harmonised Protocol (CeSHarP) | Final | May 2026 | Clinical Trial Design/Clinical Protocol Development | Clinical trial protocols; electronic structured protocol exchange | Provides standardized protocol template and data fields for electronic exchange and review. | CDER; CBER |
| E6(R3) Good Clinical Practice (GCP) | Final Level 1 | September 2025 | Clinical Trial Design/Clinical Protocol Development | Clinical trials involving human participants; broad trial designs and technologies | Modernizes GCP with risk-based, quality-by-design, technology-enabled trial conduct principles. | CDER; CBER |
| Innovative Designs for Clinical Trials of Cellular and Gene Therapy Products in Small Populations; Draft Guidance for Industry | Draft | September 2025 | Clinical Trial Design/Clinical Protocol Development | Clinical trials of cellular and gene therapies in small populations | Recommendations to sponsors who are planning clinical trials of cell and gene therapies products intended for use in a disease or condition that affects a small population | CBER |
| Frequently Asked Questions — Developing Potential Cellular and Gene Therapy Products; Draft Guidance for Industry | Draft | November 2024 | Clinical Trial Design/Clinical Protocol Development | F&Qs on developing Cellular and gene therapy products | Provides answers to frequently asked questions frequently arising during the development of cellular and gene therapies | CBER |
| Investigational In Vitro Diagnostics in Oncology Trials: Streamlined Submission Process for Study Risk Determination Guidance for Industry | FDA | Final | October 2019 | Clinical Trial Design/Clinical Protocol Development | Oncology trials using investigational IVDs; therapeutic INDs; IDE risk determinations | Optional streamlined process to determine SR, NSR, or IDE-exempt status for oncology-trial IVDs. | CDER; CDRH |
| Considerations for the Development of Chimeric Antigen Receptor (CAR) T Cell Products; Guidance for Industry | Final | January 2024 | Clinical Trial Design/Clinical Protocol Development | Chimeric antigen receptor T cell products | Recommendations regarding chemistry, manufacturing, and control (CMC), pharmacology and toxicology, and clinical study design | CBER |
| Current Good Manufacturing Practice for Phase 1 Investigational Drugs | Final | July 2008 | CMC (Chemistry, Manufacturing, and Controls) | Most Phase 1 IND drugs, including biologics | CGMP/QC expectations for manufacturing Phase 1 investigational drugs to protect subjects. | ORA; CDER; CBER |
| Exploratory IND Studies | Final | January 2006 | CMC (Chemistry, Manufacturing, and Controls) | Early Phase 1 exploratory INDs; drugs and therapeutic biologics; microdose/screening studies | Clarifies preclinical, clinical, and CMC flexibility for limited early human exploratory studies. | CDER |
| Q7A Good Manufacturing Practice Guidance for Active Pharmaceutical Ingredients | Final | August 2001 | CMC (Chemistry, Manufacturing, and Controls) | APIs for human drugs; chemical synthesis, extraction, cell culture/fermentation; excludes vaccines, whole blood, gene therapy APIs | GMP guidance for API manufacturing quality systems, controls, validation, documentation, and clinical-trial APIs. | CDER; CBER |
| INDs for Phase 2 and Phase 3 Studies Chemistry, Manufacturing, and Controls Information | Final | May 2003 | CMC (Chemistry, Manufacturing, and Controls) | Human drugs in Phase 2/3 INDs; excludes botanicals, natural/biotech proteins, other biologics | Recommends CMC submissions for Phase 2/3 INDs, amendments, and annual reports. | CDER |
| Investigational New Drug Application Submissions for Individualized Antisense Oligonucleotide Drug Products… CMC Recommendations | Draft | December 2021 | CMC (Chemistry, Manufacturing, and Controls) | Individualized ASO drug products for SDLT diseases caused by unique variants; typically 1–2 patients | CMC recommendations for sponsor-investigators submitting INDs for individualized ASO drug products. | CDER |
| Chemistry, Manufacturing, and Controls Flexibilities for Developing Human Cellular and Gene therapy Products for a Biologics License Application | Final | May 2026 | CMC (Chemistry, Manufacturing, and Controls) | CMC flexibilities for development of human cellular and gene therapies | Describes flexible approach to ensuring applicable CMC requirements are met for CGT products | CBER |
| Providing Regulatory Submissions in Electronic Format — Certain Human Pharmaceutical Product Applications and Related Submissions Using the eCTD Specifications Guidance for Industry | Final | September 2024 | IND Submission | NDAs, ANDAs, BLAs, INDs, DMFs; small molecules and biologics | Defines mandatory eCTD structure and technical requirements for electronic regulatory submissions. | CDER; CBER |
| Providing Regulatory Submissions in Alternate Electronic Format Guidance for Industry | Final | June 2022 | IND Submission | NDAs, ANDAs, BLAs, INDs, DMFs; small molecules and biologics | Describes acceptable alternate formats when eCTD submissions are waived or exempted. | CDER; CBER |
| Providing Regulatory Submissions in Electronic Format — Submissions Under Section 745A(a) of the Federal Food, Drug, and Cosmetic Act | Final | December 2014 | IND Submission | Human drug and biologic submissions | Explains statutory requirements, timelines, and waivers for mandatory electronic submissions. | CDER; CBER |
| Providing Regulatory Submissions in Electronic Format--Receipt Date | Final | February 2014 | IND Submission | Electronic submissions for drugs and biologics | Clarifies how FDA determines receipt dates for electronic submissions. | CDER; CBER |
| Providing Regulatory Submissions in Electronic Format – Drug Establishment Registration and Drug Listing | Final | June 2009 | IND Submission | Drug establishment registration and listing; marketed drugs | Outlines SPL format requirements for drug establishment registration and listing. | CDER; CVM |
| E2A Clinical Safety Data Management: Definitions and Standard for Expedited Reporting | Final | March 1995 | IND Safety Reporting | Clinical trials; drugs and biologics | Defines expedited safety reporting standards and adverse event terminology for clinical trials. | CDER |
| Safety Reporting Requirements for INDs and BA/BE Studies | Final | December 2012 | IND Safety Reporting | INDs; BA/BE studies; small molecules | Clarifies IND safety reporting requirements, thresholds, and expectations for BA/BE studies. | CDER; CBER |
| Investigator Responsibilities – Safety Reporting for Investigational Drugs and Devices | Draft | December 2025 | IND Safety Reporting | Clinical investigators; drugs and devices | Outlines investigator responsibilities for reporting adverse events in drug and device studies. | CDER; CBER; CDRH; OCE |
| M14 General Principles on Planning, Designing, Analyzing, and Reporting of Non-interventional Studies That Utilize Real-World Data for Safety Assessment of Medicines | Final | March 2026 | IND Safety Reporting | Non-interventional studies; real-world data; drugs/biologics | Provides principles for designing and analyzing RWD studies for post-market safety evaluation. | CDER; CBER |
| Sponsor Responsibilities - Safety Reporting Requirements and Safety Assessment for IND and Bioavailability/Bioequivalence Studies | Final | December 2025 | IND Safety Reporting | IND sponsors; BA/BE studies; small molecules | Details sponsor obligations for safety reporting and aggregate safety assessment under IND. | CDER |
| Master Protocols for Drug and Biological Product Development | Draft | June 2026 | Clinical protocol | Recommendations for designing, analyzing, and documenting master-protocol trials to support FDA regulatory review. | Drugs and biologics; clinical trials conducted under master protocols. | CDER; CBER |
| Quantitative Systems Pharmacology (QSP)-Based Dose Selection for Minimum Anticipated Biological Effect Level (MABEL) in First-in-Human (FIH) Trials | Draft | June 2026 | Pharmacology /Toxicology, IND Submission | Recommends using QSP to select MABEL doses for first-in-human phase 1 trials. | Drugs; FIH phase 1dose selection, especially where QSP can inform MABEL. | CDER |
| IND Meetings for Human Drugs and Biologics Chemistry, Manufacturing, and Controls Information Guidance for Industry | Final | May 2001 | IND Submission, CMC | Guidance on CMC information for formal IND meetings with FDA during human drug and biologic development. | Human drugs and biologics under INDs; CMC meeting situations; small molecules and biologics broadly. | CDER; CBER |