Come along as we demystify the FDA Form 1572!

Behind the participants, at the heart of clinical research, lies a maze of forms, acronyms, and assumptions, and none fuel more debate or confusion than the FDA Form 1572, the infamous ‘Statement of Investigator.’

What started as a simple question: “Why are we being asked to sign this form outside of the USA?” led us down a rabbit hole of regulations, international comparisons, and practical implications.

Here’s what we discovered in our quest to understand the FDA 1572.

FDA Form 1572

What is the FDA Form 1572?

At its core, Form FDA 1572 is a regulatory agreement between the Principal Investigator (PI) and the U.S. Food and Drug Administration (FDA). It’s required for clinical trials conducted under an Investigational New Drug (IND) application in the United States.

By signing the 1572, the investigator agrees to:

  • Conduct the trial in accordance with the protocol and FDA regulations.
  • Comply with Good Clinical Practice (GCP).
  • Ensure qualified staff and oversight.
  • Allow FDA inspections.

TRA TIP: It’s not just a form. It’s a legal commitment to the FDA under U.S. law (21 CFR Part 312).

What is 21 CFR 312 about?

21 CFR Part 312 is the section of the U.S. Code of Federal Regulations (CFR) that outlines the regulatory requirements for conducting clinical trials with investigational drugs (including biologics) in humans in the United States.

Before conducting clinical trials in the U.S., an Investigator New Drug (IND) submission must be submitted and accepted by the FDA (312.20).

According to this code of federal regulation:

  • The Sponsor is responsible for safety reporting, monitoring, and maintaining records (312.50).
  • The Investigator must obtain Institutional Review Board (IRB) approval, informed consent, and follow the protocol (312.60).
  • Both the sponsor and the investigator must report adverse events and unanticipated problems (312.32) and maintain study records and allow FDA inspections (312.57, 312.62).

What Exactly is an IND? And how is it affiliated with the FDA Form 1572?

Let’s simplify:

TRA Tip: Think of the IND as like the CTF1 form you complete when you submit a study to SAHPRA in South Africa or when you complete the CTIS for a submission in Europe.

Let’s compare:

U.S. (IND Submission to FDA)

  • Required before any human trials with investigational drugs
  • Regulated by 21 CFR Part 312
  • Reviewed by FDA (typically in 30 calendar days)
  • Form 1572 is a core part of the IND documentation
  • No investigator may participate in an IND-regulated trial until they have submitted a completed, signed 1572 to the sponsor (21 CFR 312.53(c)).

South Africa (CTF1 Submission to SAHPRA)

  • Similar purpose: to authorise a clinical trial involving investigational products
  • Submitted to SAHPRA, with ethics approval via a REC
  • Includes CTF1 form, protocol, IB, and regulatory documents. No Form 1572—investigator qualifications and site documentation are submitted differently
  • Review target: 30 – 60 working days

European Union (Clinical Trial Regulation – CTR)

  • The EU uses a centralised system via Clinical Trials Information System (CTIS) under the EU CTR (Regulation 536/2014)
  • One application, submitted via CTIS, undergoes a coordinated review by a Member State Concerned (MSC) and an ethics committee
  • No Form 1572—investigator qualifications and site documentation are submitted differently (via Part II of the dossier)

TRA Tip: All three systems – FDA, SAHPRA, and EU CTR – require robust documentation about the protocol, PI, and site. Only the U.S. requires Form 1572.

Why Do Non-U.S. Investigators Still Get Asked to Sign the FDA 1572?

If it’s a U.S. form, why are investigators in South Africa or Europe asked to sign it?

Here’s what we found – It must be signed:

  • If the study falls under a U.S IND
  • For Sponsor compliance
  • Inspection readiness
  • Strategic Risk Mitigation

Let us explain:

If the trial is part of a global IND submission, the sponsor may need all data – U.S. and international – to meet FDA requirements. Sponsors want to show that all investigators have agreed to comply with U.S. regulations for data that might support FDA approval.

Signing the 1572 indicates that the investigator agrees to FDA inspections and to comply with 21 CFR 312. Even if an IND is not yet filed, sponsors may request the 1572 “just in case” an FDA submission is planned in future phases.

Can an Investigator outside of the US refuse to sign the FDA 1572, because it is not part of local regulations?

Would this result in a regulatory catastrophe?

Yes, technically, non-US investigators can refuse to sign the FDA 1572 form.

But:

  • The sponsor may decide not to select the site if the PI refuses to sign.
  • Alternatively, sponsors can use other agreements to document investigator commitments (e.g., to ICH GCP).
  • In some EU countries, this is actually the standard to not sign the Form 1572 but then provide equivalent documentation to the sponsor to prove they are qualified and will adhere to GCP and the protocol.

TRA Tip: If there’s documented evidence that the investigator is qualified and agrees to follow GCP, the FDA accepts alternative arrangements – with explanation by Sponsor in the IND. This is why it is easier for Sponsors if all site Investigators just sign the FDA 1572 from the get-go.

Now that we understand what the FDA Form 1572 is and why it must be signed, let’s examine the infamous Section 6 – Who Must Be Listed as “Sub-Investigators”?

What Does Section 6 Require?

A list of all sub-investigators – people “who will be assisting the investigator and making a direct and significant contribution to the data.”

Who Should Be Listed:

  • Study nurses or coordinators who assess or interpret data.
  • Medical staff making clinical decisions or conducting protocol-required assessments
  • Lab or imaging personnel interpreting results relevant to primary endpoints.
  • Pharmacists, if they’re involved in clinical decisions or participant interaction.

Who Does Not Have To Be Listed:

  • Routine sample collectors (e.g., phlebotomists).
  • Tech staff performing but not interpreting procedures.
  • Admin or office staff
  • Pharmacists dispensing only, with no direct role in safety or clinical outcomes

TRA Tip: If someone collects data and interprets or analyses records for the study, they belong in Section 6.

Do You Need to Re-Sign the FDA 1572 for Every Change?

You might have seen this happen:

  • A new sub-investigator joins the study.
  • A new lab starts handling samples.
  • Someone listed in Section 6 resigns.

Suddenly, everyone’s asking for a brand-new 1572 to be completed and signed.

Is this actually required by the FDA? Short answer: No.

Form 1572 itself does not need to be revised and a new 1572 need not be completed and signed by the investigator. Instead, investigators should document the change, inform the sponsor, and ensure the sponsor updates the IND appropriately.

Why Do Sponsors Keep Asking for a New FDA Form 1572?

Most of the time, this is Sponsor policy, not an FDA requirement.

Some sponsors and CROs have adopted internal SOPs that require a new 1572 any time:

  • A new sub-investigator is added or removed (Section 6)
  • A new facility or lab is used (Section 3 or 4)
  • The change of study site address
  • A new protocol version is implemented

This is often for traceability, documentation consistency, or audit readiness, rather than regulatory necessity.

Are there acceptable alternatives to signing a New 1572?

Yes! Indeed, there are:

  • Site note-to-file and training log updates
  • Updated delegation logs
  • Investigator memo or letter to sponsor
  • Sponsor updates via IND Annual Report

TRA Tip: Unless the FDA specifically requests a new 1572 (e.g., after major protocol amendments or site re-initiation), a re-signature isn’t required by regulation.

As a CRA: Always check the sponsor’s policy – but also know what’s FDA-mandated vs. optional. It could save you (and your site) unnecessary back-and-forth.

Take Home Message?

  • Form FDA 1572 is more than a form – it’s a binding commitment under U.S. law.
  • It only applies under a US IND, but many global studies require it due to FDA submission plans.
  • South African and EU investigators may be asked to sign Form 1572 – but this is a sponsor requirement, not a local one.
  • Section 6 requires thought – list only candidates who contribute meaningfully to data.
  • If a site refuses to sign, alternatives must be in place to meet FDA expectations.
  • A change at the site does not necessitate the re-signing of the FDA 1572 form. There are alternatives to consider, although it might be a requirement as per Sponsor SOPs.

Clarity Brings Confidence!

Navigating clinical trial regulations can be overwhelming. But when we break them down with the right questions, they become less daunting. Understanding the FDA Form 1572 – and how it fits into the global research landscape – isn’t just about ticking boxes. It’s about protecting data quality, participant safety, and regulatory integrity.

The FDA 1572 is one of the essential records that are filed in the Investigator and Trial Master file.

To understand the Who, What, Where, Why and How of all essential records, enrol for TASK Research Academy’s course:

Mastering Essential Records in Clinical Trials.

It launches September 2025!