10911.1 The following are required for changes the in investigational plan:

1. (a) Except as described in Paragraphs (b) through (d), a sponsor must obtain approval of a supplemental application under § 10910.1, and IRB approval when appropriate (see 21 C.F.R. §§ 56.110 and 56.111), prior to implementing a change to an investigational plan. If a sponsor intends to conduct an investigation that involves an exception to informed consent of this chapter, the sponsor shall submit a separate IDE application in accordance with § 10907.1.
2. (b) The requirements of Subsection (a) regarding the Department approval of a supplement do not apply in the case of a deviation from the investigational plan to protect the life or physical well-being of a subject in an emergency. Such deviation shall be reported to the Department within five (5) working days after the sponsor learns of it (see § 10929.1(d)).
3. (c) A sponsor may make certain changes without prior approval of a supplemental application under Paragraph (a) if the sponsor determines that these changes meet the criteria described in § 10911.2 and 10911.3, on the basis of credible information defined in § 10911.4, and the sponsor provides notice to the Department within five (5) working days of making these changes; and

10911.2 The requirements in § 10911.1(a) regarding the Department approval of a supplement do not apply to developmental changes in the device (including manufacturing changes) that do not constitute a significant change in design or basic principles of operation and that are made in response to information gathered during the course of an investigation.

10911.3 The requirements in § 10911.1(a) regarding the Department approval of a supplement do not apply to changes to clinical protocols that do not affect:

1. (a) The validity of the data or information resulting from the completion of the approved protocol, or the relationship of likely patient risk to benefit relied upon to approve the protocol;
2. (b) The scientific soundness of the investigational plan; or
3. (c) The rights, safety, or welfare of the human subjects involved in the investigation.

10911.4 The definition of credible information shall be as follows:

(a) Credible information to support developmental changes in the device (including manufacturing changes) includes data generated under the design control procedures of § 10705, preclinical or animal testing, peer reviewed published literature, or other reliable information such as clinical information gathered during a trial or marketing; or

(b) Credible information to support changes to clinical protocols is defined as the sponsor's documentation supporting the conclusion that a change does not have a significant impact on the study design or planned statistical analysis, and that the change does not affect the rights, safety, or welfare of the subjects. Documentation shall include information such as peer reviewed published literature, the recommendation of the clinical investigator(s), or the data gathered during the clinical trial or marketing.

10911.5 Changes meeting the criteria in § 10911.2 and 10911.3 that are supported by credible information as defined in Paragraph § 10911.4 may be made without prior Department approval if the sponsor submits a notice of the change to the IDE not later than five (5) working days after making the change. Changes to devices are deemed to occur on the date the device, manufactured incorporating the design or manufacturing change, is distributed to the investigator(s). Changes to a clinical protocol are deemed to occur when a clinical investigator is notified by the sponsor that the change should be implemented in the protocol or, for sponsor-investigator studies, when a sponsor-investigator incorporates the change in the protocol. Such notices shall be identified as a "notice of IDE change."

10911.6 For a developmental or manufacturing change to the device, the notice shall include a summary of the relevant information gathered during the course of the investigation upon which the change was based; a description of the change to the device or manufacturing process (cross-referenced to the appropriate sections of the original device description or manufacturing process); and, if design controls were used to assess the change, a statement that no new risks were identified by appropriate risk analysis and that the verification and validation testing, as appropriate, demonstrated that the design outputs met the design input requirements. If another method of assessment was used, the notice shall include a summary of the information which served as the credible information supporting the change.

10911.7 For a protocol change, the notice shall include a description of the change (cross-referenced to the appropriate sections of the original protocol); an assessment supporting the conclusion that the change does not have a significant impact on the study design or planned statistical analysis; and a summary of the information that served as the credible information supporting the sponsor's determination that

the change does not affect the rights, safety, or welfare of the subjects.

10911.8 The requirements of § 10911.1(a) do not apply to minor changes to the purpose of the study, risk analysis, monitoring procedures, labeling, informed consent materials, and IRB information that do not affect:

(1) The validity of the data or information resulting from the completion of the approved protocol, or the relationship of likely patient risk to benefit relied upon to approve the protocol;

(2) The scientific soundness of the investigational plan; or

(3) The rights, safety, or welfare of the human subjects involved in the investigation. Such changes shall be reported in the annual progress report for the IDE, under § 10929.2(e).

10911.9 A sponsor shall submit to the Department a certification of any IRB approval of an investigation or a part of an investigation not included in the IDE application. If the investigation is otherwise unchanged, the supplemental application shall consist of an updating of the information required by § 10907.2 and §10907.3 and a description of any modifications in the investigational plan required by the IRB as a condition of approval. A certification of IRB approval need not be included in the initial submission of the supplemental application, and such certification is not a re-condition for agency consideration of the application. Nevertheless, a sponsor may not begin a part of an investigation at a facility until the IRB has approved the investigation, the Department has received the certification of IRB approval, and the Department, under § 10910.1, has approved the supplemental application relating to that part of the investigation (see 21 C.F.R. § 56.103(a)).

SOURCE: Final Rulemaking published at 60 DCR 10252 (July 12, 2013).