On December 31, 2012, CDRH released three final guidance documents, the drafts of which were issued in the summer and fall of 2012. The quick finalization of these guidance documents is likely due to their fairly uncontroversial nature, since they are more about process than substance. Each guidance is discussed below.
eCopy Program for Medical Device Submissions. The Food and Drug Administration Safety and Innovation Act (“FDASIA”) requires CDRH to issue a guidance document describing the processes for submitting an “eCopy” of medical device submissions. Finalization of the guidance document is intended to meet this FDASIA requirement.
An eCopy is required for nearly all medical device submissions, including 510(k)s, de novo petitions, PMAs, IDEs, HDEs, and pre-submissions. Though an eCopy is not required for a 513(g) submission, FDA “strongly encourages” companies to submit an eCopy for that type of submission.
It is important to note that an eCopy is not considered to be an electronic submission. Rather, it is “an exact duplicate of the paper submission, created and submitted on a compact disc (CD), digital video disc (DVD), or a flash drive. An eCopy is accompanied by a paper copy of the signed cover letter and the complete paper submission.” There may be exceptions to the “exact duplicate” requirement, such as when “a paper copy is not practical or appropriate for analysis purposes (e.g., raw data and statistical analysis programs, data line listings to facilitate bioresearch monitoring review) or is not feasible (e.g., videos, x-rays).” In these limited circumstances, “the eCopy must include all of the required information for FDA review, whereas the paper copy can include a placeholder cross-referencing the location of certain information in the eCopy.” The cover letter should describe any differences in the paper and eCopy versions.
FDA has established a free eSubmitter-eCopies tool, available on its website, which FDA “strongly encourage[s]” submitters to use. That tool meets the standards that FDA lays out in Attachment 1 of this guidance document, so use of the tool should ensure consistency with FDA’s requirements. Review of a submission will not begin until FDA receives a valid eCopy, so compliance with FDA’s requirements is critical.
PDF files are the primary format used for an eCopy, and failure to follow the PDF file requirements described in the guidance will result in the eCopy failing the loading process. The requirements include: (1) Adobe Acrobat PDF Version 10.0 or below. If the submitter uses a more recent version, it must “save the PDF as a reduced size PDF or the eCopy will fail the loading process;” (2) eCopies may not include attachments to PDF files; (3) PDF files may not have security settings; (4) PDFs must conform to an FDA-specified naming convention; and (5) PDF file size must be 50MB or smaller, though there is no limitation on the total size of a submission.
Acceptance and Filing Reviews for Premarket Approval Applications. As discussed in our earlier post on the draft guidance, this guidance separates the criteria for PMA filing into: (1) acceptance criteria; and (2) filing criteria. The guidance document contains a checklist to help clarify the necessary elements and contents of a complete PMA submission.
To be accepted, the submission should include all organization and administrative elements, or a rationale for those determined by the applicant to be not applicable. The acceptance review should be completed within 15 days of receipt of the submission, and FDA should provide a written response to the submitter within that time frame identifying any missing elements, or informing the submitter that the PMA is “Accepted.” If the submitter does not hear from FDA within 15 days, the PMA should be considered accepted. If FDA identifies missing information, the submitter may submit this information under the originally assigned PMA number. FDA will then again conduct the acceptance review to determine the completeness of the submission. The review clock will not begin until FDA has both “accepted” and “filed” an application, and the start date will be determined by the date on which FDA received the submission or amendment that made the PMA complete.
As stated in the draft guidance and repeated in the final version, in determining whether a PMA should be accepted and filed, FDA should not evaluate the submitted information to determine whether it is sufficient to demonstrate reasonable assurance of safety and effectiveness.
Submitters should refer to the “Checklists for Accepting and Filing PMAs” contained in the final guidance document to help ensure their submissions are complete and will be accepted and filed in a timely fashion.
Refuse to Accept Policy for 510(k)s. This guidance document adopts a procedure for 510(k)s similar to that described above for PMAs. The guidance modifies FDA’s prior Refuse to Accept (“RTA”) policy “to include an early review against specific acceptance criteria and to inform the submitter within the first 15 calendar days after receipt of the submission if the submission is administratively complete, or if not, to identify the missing element(s).” The guidance and the checklists in the appendix are intended to “clarify the necessary elements and contents of a complete 510(k) submission.” During acceptance review, FDA should not consider whether the information provided is sufficient to demonstrate substantial equivalence to a legally marketed predicate device, but only administrative completeness.
For FDA to accept the 510(k), all administrative elements identified in the guidance document and checklists should be included, or the submitter should provide a rationale explaining why certain missing elements are not applicable. As with PMAs, the acceptance review will be conducted and completed within 15 calendar days of FDA receipt of the 510(k) notification. FDA will use the appropriate checklist (traditional, special, or abbreviated) depending on the type of 510(k) submitted.
If FDA accepts a submission, it should notify the submitter in writing that the 510(k) has been accepted and substantive review will commence. If FDA does not complete the acceptance review within 15 days, “the submitter should be notified in writing that the acceptance review was not completed and the submission is under substantive review.” FDA can request any information that may have resulted in an RTA during the substantive review, even if FDA provided notice to the submitter that the 510(k) was accepted. The review clock starts on the date of receipt of the submission or of the amendment to the submission that enables FDA to accept the 510(k). If acceptance review was not complete within 15 calendar days, “the submission will be considered to be under substantive review, and the FDA review clock start date will be the . . . receipt date of the most recently received information for the submission. Once the submission is under substantive review the calendar days used to conduct the acceptance review (i.e., up to 15 days) are included within the 60 calendar days to reach the Substantive Interaction goal” described in the commitment letter for MDUFA III.
As with PMAs, submitters should review the checklists provided as appendices to this guidance to help ensure their 510(k)s are complete upon submission.
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