Phase 1 IND Guidance Documents
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Acronyms and Abbreviations
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
Search for Phase 1 IND Guidance Documents
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Guidance Topic Pre-IND planning Nonclinical Pharmacology/Toxicology Data Clinical Trial Design/Clinical Protocol Development CMC (Chemistry, Manufacturing, and Controls) IND Submission IND Safety Reporting
Center CDER CBER OCE CDRH CVM ORA
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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
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
Final
May 2026
Clinical Trial Design/Clinical Protocol Development
Anti-infectives; CDI
Supports clinical development for CDI treatment, recurrence reduction, or prevention indications.
CDER
Draft
June 2026
Pre-IND Planning
Biologics and Gene therapy
Recommends using public and platform knowledge to support CMC, nonclinical, and clinical development.
CBER
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
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
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
Final
October 2000
Pre-IND planning
Phase 1 INDs; drugs and biologics
Clarifies toxicology submission expectations for early-phase INDs.
CDER; CBER
Draft
December 2021
Pre-IND planning
Individualized ASOs; rare genetic diseases
Provides clinical development recommendations for individualized antisense therapies.
CDER
Draft
January 2021
Pre-IND planning
Sponsor-investigators; individualized ASOs
Describes administrative processes for individualized ASO IND submissions.
CDER
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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Find FDA Guidance Documents related to Phase 1 IND submissions