21 C.F.R. § 812.28

2019-09-21
§ 812.28 Acceptance of data from clinical investigations conducted outside the United States

(a) Acceptance of data from clinical investigations conducted outside the United States to support an IDE or a device marketing application or submission (an application under section 515 or 520(m) of the Federal Food, Drug, and Cosmetic Act, a premarket notification submission under section 510(k) of the Federal Food, Drug, and Cosmetic Act, or a request for De Novo classification under section 513(f)(2) of the Federal Food, Drug, and Cosmetic Act). FDA will accept information on a clinical investigation conducted outside the United States to support an IDE or a device marketing application or submission if the investigation is well-designed and well-conducted and the following conditions are met:

(1) A statement is provided that the investigation was conducted in accordance with good clinical practice (GCP). For the purposes of this section, GCP is defined as a standard for the design, conduct, performance, monitoring, auditing, recording, analysis, and reporting of clinical investigations in a way that provides assurance that the data and results are credible and accurate and that the rights, safety, and well-being of subjects are protected. GCP includes review and approval (or provision of a favorable opinion) by an independent ethics committee (IEC) before initiating an investigation, continuing review of an ongoing investigation by an IEC, and obtaining and documenting the freely given informed consent of the subject (or a subject's legally authorized representative, if the subject is unable to provide informed consent) before initiating an investigation. GCP does not require informed consent in life-threatening situations when the IEC reviewing the investigation finds, before initiation of the investigation, that informed consent is not feasible and either that the conditions present are consistent with those described in § 50.23 or § 50.24(a) of this chapter, or that the measures described in the protocol or elsewhere will protect the rights, safety, and well-being of subjects.

(2) In addition to the information required elsewhere in parts 807, 812, and 814 of this chapter, as applicable, the information in paragraph (b) of this section is submitted, as follows:

(i) For an investigation of a significant risk device, as defined in § 812.3(m), the supporting information as described in paragraph (b) of this section is submitted.

(ii) For an investigation of a device, other than a significant risk device, the supporting information as described in paragraphs (b)(1), (4), (5), (7) through (9), and (11) of this section is submitted, and the supporting information as described in paragraph (b)(10) of this section and the rationale for determining the investigation is of a device other than a significant risk device are made available for agency review upon request by FDA.

(iii) For a device investigation that meets the exemption criteria in § 812.2(c), the supporting information as described in paragraphs (b)(1), (4), (5), (7) through (11) of this section and the rationale for determining the investigation meets the exemption criteria in § 812.2(c) are made available for agency review upon request by FDA.

(3) FDA is able to validate the data from the investigation through an onsite inspection, or through other appropriate means, if the agency deems it necessary.

(b) Supporting information. A sponsor or applicant who submits data from a clinical investigation conducted outside the United States to support an IDE or a device marketing application or submission, in addition to information required elsewhere in parts 807, 812, and 814 of this chapter, as applicable, shall provide a description of the actions the sponsor or applicant took to ensure that the research conformed to GCP as described in paragraph (a)(1) of this section. The description is not required to duplicate information already submitted in the application or submission. Instead, the description must provide either the following information, as specified in paragraph (a)(2) of this section, or a cross-reference to another section of the application or submission where the information is located:

(1) The names of the investigators and the names and addresses of the research facilities and sites where records relating to the investigation are maintained;

(2) The investigator's qualifications;

(3) A description of the research facility(ies);

(4) A detailed summary of the protocol and results of the investigation and, should FDA request, case records maintained by the investigator or additional background data such as hospital or other institutional records;

(5) Either a statement that the device used in the investigation conducted outside the United States is identical to the device that is the subject of the submission or application, or a detailed description of the device and each important component (including all materials and specifications), ingredient, property, and principle of operation of the device used in the investigation conducted outside the United States and a comparison to the device that is the subject of the submission or application that indicates how the device used in the investigation is similar to and/or different from the device that is the subject of the submission or application;

(6) If the investigation is intended to support the safety and effectiveness of a device, a discussion demonstrating that the data and information constitute valid scientific evidence within the meaning of § 860.7 of this chapter;

(7) The name and address of the IEC that reviewed the investigation and a statement that the IEC meets the definition in § 812.3(t). The sponsor or applicant must maintain records supporting such statement, including records describing the qualifications of IEC members, and make these records available for agency review upon request;

(8) A summary of the IEC's decision to approve or modify and approve the investigation, or to provide a favorable opinion;

(9) A description of how informed consent was obtained;

(10) A description of what incentives, if any, were provided to subjects to participate in the investigation;

(11) A description of how the sponsor(s) monitored the investigation and ensured that the investigation was carried out consistently with the protocol; and

(12) A description of how investigators were trained to comply with GCP (as described in paragraph (a)(1) of this section) and to conduct the investigation in accordance with the protocol, and a statement on whether written commitments by investigators to comply with GCP and the protocol were obtained. Any signed written commitments by investigators must be maintained by the sponsor or applicant and made available for agency review upon request.

(c) Waivers. (1) A sponsor or applicant may ask FDA to waive any applicable requirements under paragraphs (a)(1) and (b) of this section. A waiver request may be submitted in an IDE or in an amendment or supplement to an IDE, in a device marketing application or submission (an application under section 515 or 520(m) of the Federal Food, Drug, and Cosmetic Act, a premarket notification submission under section 510(k) of the Federal Food, Drug, and Cosmetic Act, or a request for De Novo classification under section 513(f)(2) of the Federal Food, Drug, and Cosmetic Act) or in an amendment or supplement to a device marketing application or submission, or in a pre-submission. A waiver request is required to contain at least one of the following:

(i) An explanation why the sponsor's or applicant's compliance with the requirement is unnecessary or cannot be achieved;

(ii) A description of an alternative submission or course of action that satisfies the purpose of the requirement; or

(iii) Other information justifying a waiver.

(2) FDA may grant a waiver if it finds that doing so would be in the interest of the public health.

(d) Records. A sponsor or applicant must retain the records required by this section for a clinical investigation conducted outside the United States as follows:

(1) If the investigation is submitted in support of an IDE, for 2 years after the termination or completion of the IDE; and

(2) If the investigation is submitted in support of a premarket approval application, a notice of completion of a product development protocol, a humanitarian device exemption application, a premarket notification submission, or a request for De Novo classification, for 2 years after an agency decision on that submission or application.

(e) Clinical investigations conducted outside of the United States that do not meet conditions. For clinical investigations conducted outside the United States that do not meet the conditions under paragraph (a) of this section, FDA may accept the information from such clinical investigations to support an IDE or a device marketing application or submission if FDA believes that the data and results from such clinical investigation are credible and accurate and that the rights, safety, and well-being of subjects have been adequately protected.

[83 FR 7386, Feb. 21, 2018]