When Is FDA Form 1571 Required? (w/Examples) + FAQs

FDA Form 1571 is required whenever a sponsor submits an Investigational New Drug (IND) application to the FDA, and it must accompany every subsequent submission made to that IND. Under 21 CFR 312.23, no investigational drug can be shipped or given to humans until Form 1571 is filed and the IND goes into effect. This makes Form 1571 the foundational document that creates the legal authorization to test unapproved drugs in clinical trials.

The regulatory burden is significant: the FDA receives approximately 1,400 to 1,500 new IND applications annually, with roughly 8.9% placed on clinical hold during the initial 30-day review period. Most holds result from chemistry, manufacturing, and controls (CMC) deficiencies—problems that proper Form 1571 completion helps identify and address.

In this article, you will learn:

📋 The exact situations that trigger the Form 1571 requirement and exceptions that apply to different IND types

⚠️ How to complete each of the 29 fields on Form 1571 correctly, including critical fields that cause clinical holds

💡 Real-world examples showing how pharmaceutical companies, academic researchers, and physicians use Form 1571 differently

🔍 The most common mistakes that lead to FDA rejection and how to avoid them

✅ The step-by-step process for initial submissions, amendments, and annual reports under your IND

What Is FDA Form 1571?

FDA Form 1571 serves two primary purposes. First, it obtains the sponsor’s agreement to conduct research according to all FDA regulations. Second, it functions as a cover sheet for every submission made under a specific IND number. The form creates a binding legal contract between the sponsor and the FDA.

When a sponsor signs Form 1571, they commit to several obligations. These include not beginning clinical investigations until the IND takes effect, ensuring IRB approval for all studies, reporting safety information promptly, and maintaining accurate records. The FDA relies on these commitments to protect human research subjects.

Form 1571 applies to the Center for Drug Evaluation and Research (CDER) for most drug products and the Center for Biologics Evaluation and Research (CBER) for vaccines, blood products, and gene therapies. The center designation affects where sponsors submit their applications and which specific guidance documents apply.

When Form 1571 Is Required: The Primary Triggers

Initial IND Submissions

The primary trigger for Form 1571 is submitting an original IND application. Under 21 CFR 312.40, sponsors cannot administer investigational drugs to humans or ship them across state lines until the IND goes into effect. The IND becomes effective either 30 days after FDA receives the application or earlier if FDA notifies the sponsor.

The initial submission requires checking only the “Initial Investigational New Drug Application (IND)” box in Field 12A. Sponsors must include comprehensive information about the drug’s chemistry, manufacturing, and controls; preclinical pharmacology and toxicology studies; clinical protocols; and investigator qualifications.

Protocol Amendments

Every time sponsors change their clinical protocols, they must submit Form 1571. The form identifies what type of protocol amendment is being submitted: new protocols, changes to existing protocols, or additions of new investigators. Phase 1 amendments that significantly affect subject safety require submission before implementing changes.

For Phase 2 and Phase 3 studies, sponsors must amend their IND when making changes that significantly affect subject safety, the scope of investigation, or scientific quality. While not always required, submitting all protocol changes represents best practice for regulatory transparency.

Information Amendments

Sponsors use Form 1571 to submit information amendments containing essential data that does not fit within protocol amendments, safety reports, or annual reports. These amendments typically include new toxicology findings, chemistry manufacturing changes, or reports about discontinued investigations. FDA recommends submitting information amendments no more frequently than every 30 days when feasible.

Annual Reports

Within 60 days of the IND’s anniversary date, sponsors must submit an annual report describing the investigation’s progress. Form 1571 accompanies this submission with the “Annual Report” box checked in Field 12A. The annual report summarizes individual study status, adverse events, deaths, manufacturing changes, and plans for the coming year.

IND Safety Reports

When sponsors identify serious and unexpected suspected adverse reactions, they must file IND safety reports within 15 calendar days. Unexpected fatal or life-threatening reactions require reporting within 7 days. Form 1571 accompanies these submissions with either “Initial Written Report” or “Follow-up to a Written Report” checked.

Commercial vs. Research INDs: Critical Differences

The distinction between commercial and research INDs affects submission requirements significantly. Sponsors indicate their IND type in Field 7B of Form 1571.

When research IND sponsors submit Phase 2 or Phase 3 protocols, the IND normally converts to commercial status. However, sponsors can submit justification explaining why the Phase 2/3 study remains solely for research purposes. If FDA agrees, the IND keeps its research designation and avoids electronic Common Technical Document (eCTD) requirements.

Field-by-Field Guide to Form 1571

Understanding each field prevents clinical holds and rejection. The current Form 1571 (March 2023 version) contains 29 fields organized into sponsor information, drug identification, submission contents, and signature sections.

Fields 1-6: Sponsor and Drug Information

Field 1 (Center Selection): Select CDER for most drug products, including monoclonal antibodies. Select CBER for vaccines, blood products, gene therapies, and cell therapies like CAR-T products.

Fields 2-5 (Sponsor Details): Enter the sponsor’s name, submission date, address, and telephone number. The sponsor is whoever takes legal responsibility for the investigation—not necessarily who funds it. For sponsor-investigator INDs, this is the individual physician or researcher.

Field 6 (Drug Name): List all available names: trade name, generic name, chemical name, and code names. Include the Unique Ingredient Identifier (UNII) term and code for active substances. Use the continuation page for combination products.

Fields 7-9: IND Classification

Field 7A (IND Number): Enter the IND number if previously assigned. For new INDs, leave blank. The FDA assigns numbers using six digits with leading zeros (e.g., IND 012345).

Field 7B (IND Type): This selection has regulatory consequences. Commercial INDs require eCTD electronic format. Research INDs remain exempt from eCTD requirements. Expanded access INDs always use “Research” designation.

Field 8A (Proposed Indication): Describe the disease or condition the drug will treat. Indicate whether the indication involves a rare disease (fewer than 200,000 U.S. patients). If the sponsor holds orphan drug designation, provide the six-digit designation number.

Field 8B (SNOMED CT Code): For original submissions, provide the standardized disease coding from SNOMED CT browser. This standardization helps FDA track development programs across therapeutic areas.

Field 9 (Phase): Check the phases of investigation: Phase 1 (safety, pharmacokinetics), Phase 2 (efficacy, dosing), or Phase 3 (confirmatory). Multiple phases can be checked if the IND covers studies in different phases.

Fields 10-14: Submission Details

Field 10 (Cross Reference): If referencing previously submitted information from another IND or application, provide that application number. Sponsors need a Letter of Authorization (LOA) from the original sponsor unless using a marketed drug without modification.

Field 11 (Serial Number): Number submissions consecutively. The initial IND uses “0000.” The first amendment uses “0001.” Continue sequentially regardless of submission type.

Field 12A (Submission Information): This checklist identifies what the submission contains. For initial INDs, check only “Initial Investigational New Drug Application.” Subsequent submissions may require multiple boxes checked to describe all included information.

Field 12B (Digital Health Technology): Indicate whether the submission includes data from activity trackers, mobile applications, or other remote data acquisition technologies.

Field 13 (Combination Products): For original submissions involving drug-device or drug-biologic combinations, select “Yes” and identify the combination type (1-9). Provide the Request for Designation (RFD) number if one was submitted.

Field 14 (Justification Required): Check boxes only when the cited justification applies, such as expanded access use, emergency research exceptions, or charging for investigational drugs.

Field 15: Contents of Application

This 12-item checklist identifies what sections the submission contains:

For Item 7, sponsors must include either an environmental assessment or claim of categorical exclusion. The standard exclusion statement reads: “I claim categorical exclusion (under 21 CFR 25.31(e)) for the study(ies) under this IND. To my knowledge, no extraordinary circumstances exist.”

Fields 16-29: Responsibility and Signatures

Field 16 (CRO): Indicate whether a Contract Research Organization will conduct the study. If yes, provide the CRO’s name, address, and list of transferred obligations.

Fields 17-18 (Responsible Persons): Name individuals responsible for monitoring clinical investigations and reviewing safety information. For sponsor-investigator INDs, the investigator fulfills both roles.

Fields 19-24 (Sponsor Signature): The sponsor or authorized representative signs, acknowledging commitments to conduct investigations according to regulations, not begin studies until IND takes effect, ensure IRB approval, and report safety findings.

Fields 25-29 (Countersigner): Required only when the signing sponsor does not reside or have business in the United States. The countersigner must be an attorney, agent, or official with a U.S. business address.

Three Critical Scenarios: When Form 1571 Requirements Differ

Scenario 1: Pharmaceutical Company Launching Phase 1 Trial

A pharmaceutical company developing a novel cancer therapy must submit a commercial IND. The company serves as sponsor, assigns internal staff for monitoring and safety review, and plans eventual marketing authorization.

The company must submit all information electronically through the FDA Electronic Submissions Gateway. eCTD v3.2.2 and v4.0 are currently supported. Testing the gateway connection before submission prevents technical rejections.

Scenario 2: Academic Researcher Conducting Investigator-Initiated Trial

A university physician plans to study an FDA-approved diabetes medication for a new indication in weight management. The investigator becomes the sponsor-investigator.

Because the drug is already marketed, the sponsor-investigator IND requires less extensive information. Manufacturing details can reference the approved product. The investigator need not duplicate animal toxicology studies already in the approved labeling.

Scenario 3: Physician Requesting Emergency Expanded Access

A physician needs to treat a dying patient with an investigational drug not yet approved. The drug sponsor holds an active commercial IND.

Form FDA 3926 provides a streamlined alternative to Form 1571 for individual patient expanded access. The physician must obtain a Letter of Authorization from the drug’s sponsor to reference their IND for chemistry, manufacturing, and toxicology information.

Common Mistakes That Lead to Clinical Holds

The FDA places approximately 8.9% of initial INDs on clinical hold during the first 30 days. Understanding common deficiencies helps sponsors avoid delays.

Chemistry, Manufacturing, and Controls (CMC) Deficiencies

CMC problems represent the most common reason for clinical holds. The FDA must verify that investigators receive product with consistent identity, strength, quality, and purity.

Mistake: Submitting incomplete drug substance specifications without acceptable limits.
Consequence: Clinical hold until specifications demonstrate product consistency.
Prevention: Include identity tests, assays for potency, impurity limits, and stability data supporting the planned study duration.

Mistake: Failing to describe manufacturing facility and controls.
Consequence: FDA cannot assess whether production methods ensure subject safety.
Prevention: Provide facility address, process flow diagrams, and in-process controls. Reference a Drug Master File if applicable.

Clinical Protocol Deficiencies

Phase 2 and 3 studies face clinical holds when protocols are clearly deficient in design to meet stated objectives.

Mistake: Proposing starting doses without adequate justification from preclinical data.
Consequence: Hold until sponsor demonstrates safe dose derivation.
Prevention: Reference ICH M3(R2) guidance for nonclinical study requirements. Justify human starting dose from animal no-observed-adverse-effect levels (NOAELs).

Mistake: Excluding reproductive potential subjects without scientific justification.
Consequence: Hold for failure to plan adequate studies including appropriate populations.
Prevention: Include subjects with reproductive potential or provide concurrent studies or written FDA agreement for exclusion.

Technical Submission Errors

Technical rejection is the most common reason eCTD filings fail before substantive review begins.

Mistake: Incorrect file tags in eCTD submission.
Consequence: Gateway rejects submission; FDA never receives IND.
Prevention: Validate eCTD package using FDA validation tools before submission. Test gateway connection with production account.

Mistake: Submitting commercial IND in paper format.
Consequence: FDA returns submission without review.
Prevention: Commercial INDs require eCTD since May 2018. Only research INDs may use paper.

Do’s and Don’ts for Form 1571 Submissions

Do’s

Do request a pre-IND meeting. Type B pre-IND meetings are scheduled within 60 days of request. FDA provides preliminary responses to questions at least 2 days before meeting. This feedback prevents clinical holds by identifying deficiencies before submission.

Do submit Form 1572 for every investigator. The Statement of Investigator commits each clinical investigator to follow regulations. Sponsors must collect signed 1572s within 30 days of adding investigators. Include CVs showing qualifications for the specific investigation.

Do number submissions consecutively. Serial numbers must follow sequence without gaps. The initial IND is 0000, first amendment is 0001, etc. Skipped numbers create confusion and potential rejection.

Do claim categorical exclusion. Most clinical investigations qualify for environmental categorical exclusion under 21 CFR 25.31(e). Include the required statement in CMC section. Failure to address environmental requirements can delay approval.

Do keep dates consistent. The Form 1571 signature date and cover letter date should match or be very close. Inconsistent dates raise questions about document integrity.

Don’ts

Don’t submit without complete safety review structure. Field 17-18 require naming individuals responsible for monitoring and safety. Leaving these blank or naming unqualified persons triggers review questions.

Don’t begin studies during the 30-day review period. The IND must take effect before administering investigational drug. Study-specific activities including advertising, screening, and consenting cannot begin until the 30-day period passes or FDA authorizes early start.

Don’t submit excessive unnecessary information. Disorganized, dense submissions slow review and obscure important data. Present information concisely with clear headers. Guide reviewers to relevant sections.

Don’t forget annual reports. Missing the 60-day deadline after IND anniversary can result in FDA placing the IND on inactive status. Calendar the deadline and submit Form 1571 with annual report checkbox.

Don’t assume Form 1571 is only for initial submissions. Every amendment, report, safety report, and correspondence to FDA under the IND requires Form 1571 as a cover sheet. Omitting the form delays processing.

The Investigator’s Brochure Requirement

The Investigator’s Brochure (IB) compiles all clinical and nonclinical data about the investigational product. Form 1571 Field 15 Item 4 requires sponsors to indicate whether an IB is included.

When an Investigator’s Brochure Is Required

Multi-center trials always require IBs so investigators at different sites receive consistent information. Commercial INDs planning Phase 2/3 development need comprehensive IBs. Single-site sponsor-investigator studies of marketed drugs may substitute FDA-approved prescribing information.

What the Investigator’s Brochure Contains

The IB must provide investigators clear understanding of possible risks, adverse reactions, and necessary monitoring procedures. Required elements include:

• Physical, chemical, and pharmaceutical properties
• Nonclinical pharmacology and toxicology summaries
• Effects in humans from prior studies
• Guidance for dosing, administration, and monitoring
• Instructions for recognizing and treating adverse reactions

Sponsors must update the IB annually or whenever new safety information emerges. Updates must reach all investigators promptly. Writing a comprehensive IB typically requires six months with input from clinical, manufacturing, and nonclinical experts.

IND Safety Reporting Through Form 1571

Form 1571 Field 12A includes checkboxes for IND safety reports. 21 CFR 312.32 establishes reporting timelines that sponsors must meet.

15-Day Reports

Sponsors must report within 15 calendar days:

• Serious and unexpected suspected adverse reactions
• Findings from epidemiological studies suggesting significant risk
• Animal or in vitro findings suggesting significant human risk
• Clinically important increases in serious adverse reaction rates

7-Day Reports

Unexpected fatal or life-threatening suspected adverse reactions require initial FDA notification within 7 calendar days. Follow-up information continues the reporting obligation.

Safety Report Submission

Each IND safety report must bear prominent identification (“IND Safety Report”) and transmit to the review division responsible for the IND. Sponsors may use narrative format, FDA Form 3500A, or electronic formats FDA can process. Foreign adverse reactions may use the CIOMS I form.

Sponsors must also notify all participating investigators of safety reports. This includes investigators under the sponsor’s IND and any investigators using the same drug under separate INDs.

Electronic Submission Requirements

Since May 2018, commercial INDs must use eCTD format. FDA will not accept paper submissions for commercial applications without a waiver.

eCTD Format Overview

The electronic Common Technical Document organizes submissions into five modules:

FDA currently supports eCTD v3.2.2 and v4.0. As of September 2024, FDA accepts new applications in v4.0 on a voluntary basis. Sponsors should monitor FDA announcements for mandatory v4.0 transition dates.

Research IND Exemption

Research INDs remain exempt from mandatory eCTD requirements. Academic sponsors may submit paper applications. However, FDA encourages electronic submission even for research INDs because it facilitates faster review.

Expanded access INDs always qualify for research IND status regardless of the commercial IND they reference. Emergency and individual patient access submissions need not use eCTD.

Form 1572: The Investigator’s Commitment

While Form 1571 comes from the sponsor, Form FDA 1572 comes from each clinical investigator. Sponsors must collect signed 1572s before investigators begin participation.

What Form 1572 Accomplishes

The Statement of Investigator provides sponsors with investigator qualifications and site information. It also informs investigators of their regulatory obligations. The investigator’s signature constitutes their commitment to conduct research according to FDA regulations.

When New 1572s Are Required

Investigators sign new 1572s when:

• Participating in a new protocol added to the IND
• A new investigator joins an existing study
• Within 30 days of being added to the investigation

Changes to site information (IRB, laboratory, clinical facility) require updated 1572s. The form must accompany curricula vitae and financial disclosure forms (FDA 3454/3455) to the sponsor.

1572 and Sponsor-Investigator INDs

When an individual serves as both sponsor and investigator, they complete both forms. Form 1571 establishes their sponsor obligations. Form 1572 establishes their investigator obligations. Both forms submit to FDA as part of the initial IND package.

Maintaining Your IND After Approval

The IND takes effect 30 days after FDA receipt unless FDA issues a clinical hold. However, submission of Form 1571 does not end—it continues throughout the investigation.

Protocol Amendments

Submit Form 1571 with protocol amendments when:

• Adding new protocols to the IND
• Making significant safety, scope, or quality changes to existing protocols
• Adding new investigators to previously submitted protocols
• Changing IRB, laboratory, or clinical site information

Phase 1 protocol changes affecting subject safety require submission before implementation. Other changes should be submitted as soon as possible. Combining multiple minor amendments into single submissions improves efficiency.

Information Amendments

Submit Form 1571 with information amendments when providing:

• New chemistry, manufacturing, or controls data
• New toxicology or pharmacology findings
• Reports of discontinued investigations
• Other essential information not fitting other categories

Information amendments should clearly identify their contents (CMC, toxicology, clinical) and summarize the data provided. Sponsors should not submit information amendments more frequently than every 30 days unless necessary.

Annual Reports

Form 1571 accompanies annual reports submitted within 60 days of the IND anniversary. Reports must include:

• Status summaries for each study
• Most frequent and serious adverse experiences by body system
• Summary of IND safety reports submitted during the year
• List of subjects who died with causes
• Preclinical study summaries
• Manufacturing changes
• Investigational plan for the coming year

Development Safety Update Reports (DSURs) may substitute for traditional annual reports. DSURs follow ICH E2F format and provide comprehensive safety assessments.

IND Withdrawal, Inactivation, and Termination

The IND lifecycle may end through withdrawal, inactivation, or termination. Form 1571 accompanies submissions for each status change.

Voluntary Withdrawal

Sponsors may withdraw INDs when abandoning development. The withdrawal letter should include:

• IND number and drug name
• Statement of withdrawal
• Reason for withdrawal
• Status of any ongoing subjects
• Disposition of remaining investigational product
• Confirmation that investigators have been notified

Inactivation

INDs become inactive when no subjects enter trials for 2 years or when clinical holds last 1 year or longer. Sponsors may request inactivation when temporarily pausing development. Inactivation preserves the IND for future reactivation.

FDA Termination

FDA may terminate INDs when human subjects face unreasonable risk or when manufacturing controls are inadequate. Sponsors receive written notice explaining termination grounds and have opportunity to respond. Terminated INDs cannot be used without FDA reinstatement.

FAQs

Can I use Form 3926 instead of Form 1571 for expanded access?
Yes. Form 3926 provides a simplified alternative for individual patient expanded access requests. However, intermediate-size and treatment INDs still require Form 1571.

Does every investigator need their own Form 1571?
No. Form 1571 comes from the sponsor only. Investigators complete Form 1572. Even in sponsor-investigator studies, only one 1571 is submitted.

Can I submit a paper IND for a commercial product?
No. Since May 2018, commercial INDs require eCTD electronic format. FDA grants waivers only under extraordinary circumstances.

Is Form 1571 required for pre-IND meetings?
No. Pre-IND correspondence does not require Form 1571. The form is only required when submitting the actual IND application or subsequent amendments.

What happens if I miss the annual report deadline?
The IND may become inactive. FDA requires annual reports within 60 days of the IND anniversary. Missing this deadline puts the IND at risk of inactive status.

Do I need Form 1571 to report serious adverse events?
Yes. IND safety reports require Form 1571 with the appropriate safety report checkbox selected in Field 12A.

Can academic researchers avoid eCTD requirements?
Yes. Research INDs are exempt from mandatory eCTD submission. Sponsor-investigators at academic institutions may submit paper applications.

Does Form 1571 need to be signed by a physician?
No. The sponsor or sponsor’s authorized representative signs. This person need not be a physician. Corporate officers, regulatory directors, or other authorized individuals may sign.

How long does FDA take to review Form 1571?
30 calendar days for initial INDs. The IND takes effect automatically after 30 days unless FDA issues a clinical hold or provides earlier authorization to proceed.

Is Form 1571 required for bioequivalence studies?
Sometimes. Bioequivalence studies meeting 21 CFR 320.31 exemption criteria do not require INDs. Studies outside exemption criteria need Form 1571.

What serial number should I use for the first amendment?
0001. The initial IND uses serial number 0000. Each subsequent submission increments by one (0001, 0002, etc.) regardless of submission type.

Can I submit Form 1571 by email?
No. Form 1571 must be submitted through the FDA Electronic Submissions Gateway for commercial INDs or by mail for paper submissions of research INDs.