I'm going by the difference is for a Refusal to File (RTF) versus a Complete Response Letter (CRL) response from the FDA guidelines.
There are some additional references that I've read that says the "clock is stopped" at that point in the process.
In their document:
https://www.fda.gov/media/111632/download
It states on the last two pages (emphasis mine):
Nowwwww....if CytoDyn were to file in protest, which I don't think they did, that would resume the clock at the RTF was issued per this FDA document:
https://www.fda.gov/media/108943/download
...
...
Clear as mud, huh ?
There are some additional references that I've read that says the "clock is stopped" at that point in the process.
In their document:
https://www.fda.gov/media/111632/download
It states on the last two pages (emphasis mine):
Quote:SOPP 8404 Appendix A: Refusal to File (RTF) verses Complete Review
In general, an RTF is based on omissions of clearly necessary information (e.g.,
information required under the statute or regulations) or omissions or inadequacies
so severe as to render the application incomplete on its face and where the
omissions or inadequacies are obvious, at least once identified, and not a matter of
interpretation or judgment about the meaning of data submitted.
An RTF:
1. Is not a final determination concerning potential approvability; it can be an
early opportunity for the applicant to develop a complete application, but will
delay, at least for a time, a full review of the application .
2. Is not necessarily a final decision regarding the scientific/medical merits of the
application; instead, it is an early signal to the applicant that the application
has omissions or inadequacies so severe as to render the application
incomplete on its face or to introduce significant impediments to a prompt and
meaningful review (e.g., the need for substantial amounts of additional data
and analyses). This message is transmitted early so that "repairs" can be
promptly initiated by the applicant.
3. Can be made if the applicant submission is based on a study or studies
deemed inadequate during the Investigational New Drug (IND) review
process and which remain uncorrected after the inadequacies were clearly
communicated to the applicant by CBER.
4. May apply if the application contains other uncorrected deficiencies (e.g.,
manufacturing or product specifications) which were clearly communicated to
the applicant before submission of the application sufficient to require
resolution before a meaningful review could occur.
5. Is not an appropriate vehicle for dealing with complex issues and close
judgments on such matters as balancing risks and benefits, magnitude of
clinical effect, acceptability of a plausible surrogate marker, or nuances of
study design (although inadequate designs may lead to RTF, see below).
By contrast, issuance of a Complete Response (CR) Letter (after a complete review)
is generally based on critical omissions of data or analyses as well as on an adverse
judgment about the data, conclusions, rationale, etc., presented in the application.
For example, a Complete Response Letter could be issued based on the conclusion
that:
1. Effectiveness has not been demonstrated,
2. An analysis was incorrectly carried out,
3. Clinical trials were poorly designed or conducted,
4. Safety has not been adequately demonstrated, or
5. Outstanding compliance issues remain.
These judgments would not serve as the basis for RTF unless the deficiencies were
so severe as to render the application incomplete on its face.
Nowwwww....if CytoDyn were to file in protest, which I don't think they did, that would resume the clock at the RTF was issued per this FDA document:
https://www.fda.gov/media/108943/download
...
Quote:E. If an application is filed over protest, the suspended review clock will resume
from the date which CBER received the request to file the application over
protest (providing the user fee accompanies the request as the application will be
Center for Biologics Evaluation and Research SOPP 8404.1
considered a new original application for user fee purposes, and the applicant
must remit the full fee or obtain a waiver).
...
Clear as mud, huh ?
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