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Federal Register / Vol. 86, No. 190 / Tuesday, October 5, 2021 / Rules and Regulations
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the safety and effectiveness of these devices when used as intended.
Requiring these studies for all implantable devices is also inconsistent with FDAs least burdensome approach to medical device regulation, which is intended to eliminate unnecessary burdens that may delay the marketing of beneficial new products, while maintaining the statutory requirements for marketing authorization. As discussed in FDAs guidance, The Least Burdensome Provisions: Concept and Principles Ref. 12, FDA typically follows a stepwise analytical process when requesting additional information to make a decision on a marketing submission to ensure the information requested reflects the least burdensome approach. FDA typically requests clinical data when analytical or nonclinical bench performance testing data, or nonclinical animal 1 and/or biocompatibility studies are insufficient, or available scientific methods are not acceptable, e.g., the scientific methods are deemed unacceptable because they are not clinically validated or are not supported by a valid scientific rationale.
We do not believe any changes are necessary to address the comments request that FDA require information about changes to the research protocol and statistical methodology. In addition to the summary of studies required under 860.220a13 this final rule renumbers proposed 860.234a13 as 860.220a13, the technical sections of the De Novo request must include, among other things, protocols, investigation design, results of statistical analyses, and any other appropriate information, for each clinical investigation used to support the De Novo request 860.220a15, this final rule renumbers proposed 860.234a15 as 860.220a15.
Therefore, the required contents of the technical section would already capture information regarding significant changes made to the protocol or to the statistical methodology that would be important for evaluating the results of the study.
Comment 34 A few comments propose revisions to the human subject study summaries provision at 860.220a13ii this final rule renumbers proposed 860.234a13ii as 860.220a13ii to require that this section of the De Novo request 1 FDA supports the principles of the 3Rs, to reduce, refine, and replace animal use in testing when feasible. We encourage sponsors to consult with us if it they wish to use a non-animal testing method they believe is suitable, adequate, validated, and feasible. We will consider if such an alternative method could be assessed for equivalency to an animal test method.

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include a summary of any clinical data known by or reasonably available to the requester submitted in the De Novo request instead of a summary of each clinical investigation submitted in the De Novo request. The commenters suggest that the language in the proposed rule appeared to assume that the requesters only source of clinical data would be clinical investigations that the requester initiated and note that there may be other sources of clinical data, such as studies described in literature or conducted by others, or in marketing data from other countries. They also recommend limiting the information about such clinical data required in the summary to that known or reasonably available to the requester because it would clarify that when complete data are not available, they are not required.
Response 34 FDA agrees that sources of clinical data other than clinical investigations initiated by the requester may be available to the requester;
however, we do not agree that the proposed requirement for the De Novo request to include a summary of studies limits the types of clinical data that may be submitted in a De Novo request.
Under 860.220a13, this final rule renumbers proposed 860.234a13 as 860.220a13, the De Novo request must include an abstract of any information or report described in the De Novo request under 860.220a16ii this final rule renumbers proposed 860.234a16ii as 860.220a16ii and a summary of the results of technical data submitted under 860.220a15 this final rule renumbers proposed 860.234a15 as 860.220a15. The information required under 860.220a16ii includes information derived from investigations other than those in the request and from commercial marketing experience. Therefore, clinical data derived from other sources, such as marketing experience in other countries, are among the types of data that would be summarized under 860.220a13.
The particular paragraph of 860.220a13 that the commenters suggest revising sets forth additional information that summaries must discuss for those clinical investigations involving human subjects that are submitted in the De Novo request.
FDA also disagrees that it is necessary to limit the information required under 860.220a13ii this final rule renumbers proposed 860.234a13ii as 860.220a13ii to that known or reasonably available to the requester.
The requester should be able to provide the information required under 860.220a13ii for clinical
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investigations submitted in the technical sections in support of the De Novo request. To the extent certain elements required for the summary of such clinical investigations are not included in the De Novo request because they are not reasonably available to the requester, the requester should address why they are not available. Therefore, we are not revising 860.220a13ii in response to these comments.
Comment 35 A comment requests FDA to qualify the requirement for a De Novo request to provide a discussion demonstrating that the data and information in the request constitute valid scientific evidence, with the phrase, if applicable, because a De Novo request for a low-risk device may present de minimis valid scientific evidence.
Response 35 FDA disagrees with this comment. As part of the De Novo classification process, FDA must determine that the device is of low to moderate risk 21 U.S.C.
360cf2Aiv. FDA relies upon valid scientific evidence in determining the safety and effectiveness of a device for purposes of classification, as explained in our response to Comment 23.
Therefore, adding the phrase if applicable as the commenter suggests would not be appropriate.
As discussed in FDAs guidance, Factors to Consider When Making Benefit-Risk Determinations Medical Device Premarket Approval and De Novo Classifications Ref. 3, FDA
assesses the benefits and risks of a device that is the subject of a De Novo request to determine if general or general and special controls are sufficient to provide reasonable assurance of safety and effectiveness see 860.7d1 and e1. While lowrisk devices may not need to show as substantial a benefit to patients to have a favorable benefit-risk profile, FDAs classification determination must still be based on valid scientific evidence.
Comment 36 A comment requests FDA to clarify that, where relevant, requirements for data and information in the technical sections in 860.220a15 this final rule renumbers proposed 860.234a15 as 860.220a15 may be satisfied by cross-referencing data and information submitted in satisfaction of the summary of studies provision 860.220a13, this final rule renumbers proposed 860.234a13 as 860.220a13 to avoid requiring a requester to repeat information provided earlier in the De Novo request. A
comment also requests that FDA remove the list of specific items that must be
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