Clinical trials under US legislation

Use of the FDA 1572 form for clinical trials in Europe

Must investigators sign a 1572 form and is it in accordance with European Union (EU) legislation to conduct a clinical trial in Europe under the United States (US) Investigational New Drug (IND) regulations?

No, an investigator in Denmark cannot comply with the requirements in the 1572 form. A clinical trial conducted at a site in the EU and European Economic Area (EEA) cannot be conducted under any foreign country legislation. The trial must be conducted in accordance with the national legislation that is set forth in the Directives 2001/20/EC, 2001/83/EC, and 2005/28/EC (and the Regulation (EU) No 536/2014 when in force).

Clinical trials submitted to the US Food and Drug Administration (FDA) for marketing approval must comply with the IND regulations found in Title 21 Code of Federal Regulations (CFR) Part 312. Title 21 Code of Federal Regulations (CFR) Part 312. Compliance with 21 CFR 312 can be achieved:

1. by conducting trials either under IND or
2. not under IND (“non-IND foreign clinical studies”) or
3. as a combination of sites within the US as IND-sites and sites outside the US not under the IND application (non-IND sites), whatever is most appropriate.

If the sponsor chooses to submit a single protocol to the IND and conduct the trial for all trial sites under IND, then the sponsor and all investigators must meet all IND requirements.

• However, it is possible to apply for a waiver from FDA for any of the Institutional Review Board requirements for specific research activities or for classes of research activities otherwise covered by the IRB regulations (21 CFR 56.105), when the investigator knows he/ she cannot commit to all of the requirements on the Form FDA 1572. The sponsor should submit the waiver request to the IND under which the trial will be conducted prior to initiating the study. If a waiver is granted, the sponsor should have investigators attach a copy of the letter granting the waiver to the signed Form FDA 1572 in the investigator’s record. If the waiver does not specify what was waived, then a copy of the request for the waiver should be attached.

• If non-US local laws or regulations prohibit the signing of a Form FDA 1572, FDA would expect the sites to operate as non-IND sites and the trial conducted as a non-IND trial.

If the sponsor chooses to conduct a clinical trial without an IND and outside the US, then the trial must be conducted in accordance with 21 CFR 312.120 – Foreign clinical studies not conducted under an IND. The requirements of 21 CFR 312.120 can be met if a clinical trial is conducted in compliance with international ethical and data quality standards set forth by Directives 2001/20/EC, 2001/83/EC, and 2005/28/EC (and the Regulation (EU) No 536/2014 when in force). The Form FDA 1572 does not apply. Read more

If the sponsor chooses to conduct a multinational clinical trial, with some sites outside the US, then the sponsor may choose not to have sites outside the US under the IND application.

• The sponsor can submit one protocol to the FDA that clearly defines and describes IND and non-IND sites. The investigators at these non-IND sites do not have to sign the Form FDA 1572. However, the sponsor must ensure that the non-IND sites complies with 21 CFR 312.120, “Foreign clinical studies not conducted under an IND.”, which requires that the trial be conducted in accordance with good clinical practice (GCP) and that FDA is able to validate the data from the trial through an onsite inspection if the FDA deems it necessary.

• The sponsor can submit one protocol for sites under the IND (U.S. sites and some foreign sites) and a separate protocol for foreign sites not under the IND. The Form FDA 1572 does not apply for non-IND sites. If the intent is to pool the data from U.S. and foreign sites for marketing approval, the protocols would ordinarily be very similar or identical. For sites outside the US that are not included under the IND, the protocol does not need to be submitted to the IND. However, FDA does recommend that the sponsor discuss plans to pool the data from the different sites with the appropriate FDA review division before trial initiation.