Below is how the FDA defines a Class 1 resubmission... and why some are suggesting a 2 month review.
Class 1 Resubmission — A resubmission that includes one or more of the following items:
1. Final printed labeling
2. Draft labeling
3. Safety updates submitted in the same format, including tabulations, as the original safety submission with new data and changes highlighted (except
when large amounts of new information, including important new adverse experiences, not previously reported with the product are presented in the resubmission)
4. Stability updates to support provisional or final dating periods
5. Discussions of postmarketing requirements/commitments, including proposals or protocols for such requirements/commitments
6. Assay validation data
7. Final release testing on the last 1 to 2 lots used to support approval
8. A minor re-analysis of data previously submitted to the application (determined by CDER as fitting the Class 1 category)
9. Other minor clarifying information (determined by CDER as fitting the Class 1 category)
In addition, here is a brief side by side comparison FDA draft guidance on the topic of
"Meeting the substantial evidence standard based on one adequate and well controlled clinical investigation plus confirmatory evidence"
|
Column 1 |
Column 2 |
Column 3 |
| 1 |
of confirmatory evidence |
"Demonstrating Substantial Evidence of Effectiveness for Human Drug and Biological Products"Dec19 FDA Draft Guidance |
"Demonstrating Substantial Evidence of Effectiveness With One Adequate and Well-Controlled Clinical Investigation and Confirmatory Evidence"Sep23 FDA Draft Guidance, which complements the Dec19 FDA Draft Guidance |
| 2 |
Adequate and well-controlled clinical investigations in a related disease area |
Yes |
Yes |
| 3 |
Certain types of real world evidence, such as extensive data on outcomes that provide further support for the lack of effect seen in the control group in the randomised trial |
Yes |
Yes |
| 4 |
Compelling mechanistic evidence in the setting of a well-understood disease pathophysiology |
Yes |
Yes |
| 5 |
Well-documented natural history of disease |
Yes |
Yes |
| 6 |
Evidence from a relevant animal model |
Not mentioned |
Yes |
| 7 |
Evidence from other members of the same pharmacological class |
Yes |
Yes |
| 8 |
Evidence from Expanded Access Use |
Not mentioned |
Yes |
| 9 |
|
|
|
Where Mesoblast were trying to present EAP data in the past to demonstrate both the mechanism of action, as well as efficacy, the FDA essentially ignored it due to "confounding factors" and did not treat is as confirmatory clinical evidence.
This is dispite the 240+ patient data submitted back in 2020, and likely many more by now ... all of this was essentially ignored by the FDA.
Fast forward to September 2023, and all the EAP data submitted by MSB suddenly became acceptable confirmatory trial data, provided that the FDA deemed it to be of sufficient quantity and quality... the status of this data may well have been elevated overnight from 'junk status' to 'treasury trove of clinical evidence' .
A subtle update by the FDA, which I believe has allowed the FDA to find the grounds it needed to accept Mesoblast's clinical data set provided to date.
goodluck all
(20min delay)