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Federal Register / Vol. 86, No. 190 / Tuesday, October 5, 2021 / Rules and Regulations
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information. With respect to affording requesters an opportunity to review and redact records that may contain trade secret information before they are disclosed, FDA will follow its existing pre-disclosure notification requirements in 20.61.
Since 2010, FDA has posted on its website classification orders and redacted decision summary documents for devices classified through the De Novo classification process. This approach is analogous to our current approach for other marketing authorization pathways: summaries of safety and effectiveness information that formed the basis of FDAs decisions are posted on FDAs website for PMA
approvals, available at https
www.accessdata.fda.gov/scripts/cdrh/
cfdocs/cfPMA/pma.cfm; and for 510k clearances, 510k summaries are available at https www.accessdata.
fda.gov/scripts/cdrh/cfdocs/cfPMN/
pmn.cfm. We believe the comment suggesting that FDA require a De Novo requester to prepare a summary of safety and effectiveness information for public posting to align with PMA and 510k procedures confuses the requirement for a PMA to include a summary that allows the reader to gain a general understanding of the data and information in the application 814.20
21 CFR 814.20b3 with the publicly posted detailed summary of safety and effectiveness data SSED on which an approval or denial decision is based for a PMA. Although some PMA applicants may submit draft SSEDs, the final SSEDs posted online are FDA
documents. The De Novo decision summary is intended to present an objective and balanced summary of the scientific evidence that served as the basis for the decision to grant a De Novo request. Because the Agency already prepares such documents and determines what information supports its decision to grant the De Novo request, FDA is not revising the final rule to require requesters to prepare a similar summary, as this commenter requests. We believe the information that the commenter indicates would be of interest to healthcare providers and patients is already made publicly available through FDAs current approach.
E. Comments and FDA Response on Facility Inspections Comment 14 A comment supported facility inspection prior to granting or declining a De Novo request because the commenter states that it is essential for safety in the case of novel medical devices. Several comments wanted to delete either all of subsection
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860.240c this final rule renumbers proposed 860.256c as 860.240c or paragraph 860.240c2 this final rule renumbers proposed 860.256c2 as 860.240c2 or revise subsection 860.240c because the commenters state these provisions are unduly burdensome or that FDA lacks statutory authority to require facility inspections to assess implementation of the QSR
part 820.
Response 14 Several comments objected to proposed 860.256c this final rule renumbers proposed 860.256c as 860.240c, which relates to the inspection of relevant facilities prior to granting or declining a De Novo request and argued that the FD&C Act does not give FDA this inspection authority. FDA disagrees with the comments, and, as described below, is finalizing the provision with clarifying changes. The inspection would be done only in the two circumstances specified in the regulation. Based on past experience, inspections in these circumstances should arise with a small percentage of De Novo requests.
1. Clinical and Nonclinical Data As explained in the proposed rule preamble, an inspection prior to its De Novo decision is used to help FDA
determine whether clinical or nonclinical data were collected in a manner that ensures the data accurately represents the risks and benefits of the device, in accordance with section 513a1C of the FD&C Act. FDA has been conducting such inspections when data integrity and quality concerns arise during its review of a De Novo request, and information from these inspections has been critically important to the Agencys De Novo determination. For example, based on review of the clinical data provided in the De Novo request, FDA may determine that the results of a clinical investigation are clinically or physiologically improbable. An inspection may be conducted to verify the integrity of the data.
In another example, FDA may receive a whistleblower complaint alleging misconduct at one or more clinical investigational sites, and the results from the clinical investigation are used to support a De Novo request. Our assessment of the subject device is dependent on the veracity of the complaint. FDA inspections of one or more investigational sites to assess the veracity of the complaint would help determine whether evidence submitted in support of the De Novo request e.g., data from a particular site needs to be excluded from FDAs consideration.

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2. Quality System Regulation and Current Good Manufacturing Practices For certain devices with critical and/
or novel manufacturing processes that may impact the safety and effectiveness of the device, FDA also believes that an inspection may be necessary for FDA to determine whether general controls, including the QSR part 820 for devices and current good manufacturing practices 21 CFR part 4, subpart A for combination products, are adequate to provide a reasonable assurance of safety and effectiveness of the device, or whether special controls to mitigate risks must be developed. Such inspections are not for the purpose of reviewing for compliance with the QSR.
Rather, the purpose of such an inspection is to gather information on critical and/or novel manufacturing processes, the methods and procedures used, and such additional information as may be necessary to assess the safety and effectiveness of a drug or biologic constituent part of a combination product. Such information will help classify the device type by providing an understanding of critical and/or novel manufacturing processes to determine if the device type is of low to moderate risk, to determine if general controls and special controls can effectively mitigate the probable risks to health, and to determine if the product specifications can reasonably be met. In some circumstances, this information can only be obtained by an inspectionand not any other means, such as through review of standard operating proceduresbecause it requires a detailed understanding of how manufacturers, in practice, carry out complex and/or safety critical processes, methods, or procedures. In these situations, the information obtained from an inspection would be necessary for FDA to make a De Novo determination.
For example, FDA may receive a De Novo request for a permanent implant with a coating that contains the same active ingredient that is in a new drug application NDA approved drug product. The combination product is intended to reduce the risk of surgical site infections. The safety and effectiveness of the combination product is linked to the ability of the manufacturer to ensure consistent levels of drug coating and drug release batchto-batch. Probable risks associated with inconsistent coating or inconsistent drug release may include local/systemic toxicity, reproductive/genotoxicity, antibiotic resistance, and infection. An inspection would help assess the sampling methodology and laboratory
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