Will the FDA accept data from a OUS clinical research site in Colombia?

For international inspections of pharmaceutical trials, the FDA requires conducting the trials according to GCP and under the Ethics Committee approval. For medical devices, the FDA requires the conduct of the trial according to the Declaration of Helsinki (a requirement by Colombian law in Resolution 2378) and to the laws and regulations of the country where the trial is taking place.

If a Colombian research site receives conducts a study following ICH/GCP and/or has obtained a Good Clinical Practice Certificate from INVIMA, then it is also compliant with FDA requirements for international inspections for studies involving investigational drugs and biologics as well as for studies involving investigational medical devices.

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The following provides information regarding the Good Clinical Practice Certificate (GCP) that a clinical research site in Colombia receives from Colombia's regulatory agency, INVIMA (Instituto Nacional de Vigilancia de Medicamentos y Alimentos; translated as National Drug and Food Surveillance Institute), and how it relates to conducting an FDA-compliant clinical trial in Colombia.

The International Conference on Harmonization issued the document titled Guidelines for Good Clinical Practice (see Attachment 1 in this folder), which defines a set of guidelines by which clinical studies can be designed, implemented, completed, audited, analyzed, and reported to ensure reliability. Latin American countries are not a part of the International Conference on Harmonization; however, conducting clinical studies in Latin American countries —and the rest of the world— must follow strict ethical and scientific principles as it is described in the Declaration of Helsinki, the Nuremberg Code, the Declaration of Geneva and all the declarations related to the ethical conduction of clinical trials.

In this context, it became necessary to define harmonized GCP criteria in Latin America. In 2005, the Pan-American Health Organization —a regional office of the World Health Organization— held a meeting in the Dominican Republic to develop the Document of the Americas (see Attachment 2 in this folder) to propose the guidelines for Good Clinical Practice throughout the region and to serve, as the foundation for regulatory agencies, investigators, ethics committees, universities and companies engaged in clinical research. The Pan-American Health Organization submitted the document's final version to all Latin American countries to standardize the conduction of clinical trials throughout the continent.

The Ministry of Health and Social Protection of the Republic of Colombia received the Document of the Americas and decided to adopt its proposed Good Clinical Practice guidelines in Colombia by issuing national law through Resolution 2378 (please see Attachment 3 of this folder) by which Good Clinical Practices are adopted by institutions conducting clinical research in human beings. This resolution is a list of requirements clinical research sites in Colombia must follow to receive a Good Clinical Practice Certificate. These requirements apply to the principal investigator, the ethics committee, the clinical laboratory service, and the pharmaceutical service and set standard operating procedures for all the required services and activities, as well as the training that all the personnel involved in clinical research must receive (i.e. research methods, ethics, and Good Clinical Practice).

The Ministry of Health and Social Protection of the Republic of Colombia mandated INVIMA to issue the Good Clinical Practice Certificate to clinical research sites in Colombia that comply with its strict guidelines. Resolution 2378 has a comprehensive checklist that every site must complete. INVIMA then visits every site that applies for the certificate, verifies its compliance with the resolution´s checklist, and grants it (see an example certificate in Attachment 4 of this folder).

Concerning whether the INVIMA Good Clinical Practices Certificate complies with FDA requirements, please refer to the following information, which is taken from the Information Sheet Guidance For IRBs, Clinical Investigators, and Sponsors FDA Inspections of Clinical Investigators (please see Attachment 5 of this folder).

V. INTERNATIONAL INSPECTIONS

Studies Involving Investigational Drugs and Biologics

When FDA considers whether to accept non-U.S., non-IND clinical studies in support of an IND, NDA, or BLA, an FDA inspection may help in determining whether the study was conducted in accordance with 21 CFR 312.120. Specifically, the inspection will evaluate whether the following criteria are met:

  • The study is well-designed and well-conducted.

  • The study is conducted in accordance with Good Clinical Practice (GCP), which is defined as a standard for the design, conduct, performance, monitoring, auditing, recording, analysis, and reporting of clinical trials in a way that provides assurance that the data and reported results are credible and accurate and that the rights, safety, and well-being of trial subjects are protected.

  • The study has been reviewed and approved (or provision of a favorable opinion) by an independent ethics committee (IEC) prior to study initiation, continuing review of an ongoing study by an IEC, and the freely given and documented informed consent of the subject (or the subject’s legally authorized representative if the subject is unable to provide consent) prior to any study-specific procedures.

Studies Involving Investigational Devices

FDA’s inspection of clinical investigators conducting foreign trials includes device trials in support of a premarket approval application (PMA) or a premarket notification (510(k)) submission.

For device studies conducted outside the U.S., FDA will accept research in support of a PMA, but which has not been conducted under an IDE, if certain conditions are met. An FDA inspection may help in determining whether the study was conducted in accordance with 21 CFR 814.15. Specifically, the inspection will evaluate whether the following criteria are met:

  • the data are valid; and

  • the studies are conducted in conformance with the "Declaration of Helsinki," or the laws and regulations of the country in which the research is conducted, whichever affords greater protection to the human subjects.

FDA validates the authenticity and accuracy of data and confirms compliance during an inspection, which is performed under the circumstances listed above in section III. The FDA investigator may request documentation as to whether the study was conducted under the laws and regulations of the non-U.S. country and/or the Declaration of Helsinki, whichever accords greater protection to human subjects.

In February 2018, the FDA issued a final rule on acceptance of data from clinical investigations of medical devices. The FDA updated the requirements in 21 CFR part 814 for acceptance of data from clinical investigations conducted outside the United States (OUS) and amended 21 CFR parts 807 and 812 to identify criteria for acceptance of data from clinical investigations conducted OUS as well as investigations conducted within the United States (US), which are based on the requirements in 21 CFR part 814. The final rule is intended to help ensure the quality and integrity of clinical data and the protection of human subjects. It provides consistency in FDA’s requirements for acceptance of data from device clinical investigations, whatever the application or submission type, and whether conducted inside the US or OUS. Read more.