FDA knocked us back- twice. FDA has since not found fault in our manufacturing process, safety, efficacy and has acknowledged improvements in the potency assay. An answer on acceptance of the BLA is due tomorrow. The relevant standard operating procedures from CBER are below.
G. The resubmission will be considered complete if the applicant responds to each question or issue in the CR letter. The quality of the response will be
evaluated during the review. Some responses by the applicant may be inadequate and will need to be addressed once the review has begun.
H. If the applicant fails to respond to each question or issue, the resubmission will be considered incomplete, and the review will not restart until a complete
response to each question or issue is received. The applicant will be notified of the reasons for the deficiencies. A phone conversation or secure e-mail
will suffice as a means of communication in this regard. If the deficiencies are complex, a letter may also be sent to the applicant. All email
acknowledgements must comply with SOPP 8119: Use of Email for Regulatory Communications. All telecon acknowledgements must comply
with SOPP 8104: Documentation of Telephone Contacts with Regulated Industry
Company announcement
FDA has informed the company that following additional consideration the available clinical data from its Phase 3 study MSB-GVHD001 appears sufficient to support submission of the proposed Biologics License Application (BLA) for remestemcel-L for treatment of pediatric patients
with steroid-refractory acute graft versus host disease (SR-aGVHD).
https://www.fda.gov/media/72140/download?attachment
B. Studies Not To Include in the Clinical Studies Section
The following are the types of studies that should usually not be included in the
CLINICAL STUDIES section, unless they also meet one of the factors in II.A (above).
If an exception is made, the limitations of the study and the reasons for inclusion should
be stated.
1. Clinical studies with results that imply effectiveness for an unapproved
indication, use, or dosing regimen
2. Active control clinical studies that imply comparative effectiveness or safety
claims not supported by substantial evidence
3. Studies that are not adequate and well-controlled within the meaning of
21 CFR 314.126.
Prior to the resubmission, FDA guided Mesoblast to resolve outstanding chemistry, manufacturing and controls (CMC) issues before initiating any additional clinical trial. FDA completed the Pre-License Inspection (PLI) of the manufacturing facility, did not issue any Form 483, and found no objectionable
conditions. In addition, FDA acknowledged in the resubmission review that changes implemented appear to improve assay performance relative to the original version of the assay used in the pediatric Phase 3 trial.
A Form FDA 356h is an application to market a new drug, biologic, or antibiotic drug for use in humans.
The Form FDA 356h contains the following information:
- A summary of information submitted as part of the application. DONE
- Information on the applicant submitting the biologics license application. DONE
- A preclinical data section. DONE
- A clinical data section that includes safety and efficacy data on the product. APPEARS SUFFICIENT
- Draft labeling of the product to be licensed. FINAL STEP
- Information on the manufacturing, chemistry, and controls of the product. Hopefully RESOLVED
- A data summary of validation of important processes and assays involved in the manufacture of the product. DONE
- A description of the facility where the product is manufactured. DONE
- Case report form tabulations on the manufacturer’s clinical experience with the product. DONE
- Case report forms and serious event narratives. DONE
- An index.
Class 1 resubmission is the resubmission of an NDA or efficacy supplement, following receipt of a complete response letter, that contains one or more of the following: Final printed labeling, draft labeling, certain safety updates, stability updates to support provisional or final dating periods, commitments to perform postmarketing studies (including proposals for such studies), assay validation data, final release testing on the last lots used to support approval, minor reanalyses of previously submitted data, and other comparatively minor information.
In my opinion- we are up to Draft and Final Labelling- everything else hopefully resolved-
We should know tomorrow
Reg
PS Check this out- quite often certain non holders state " but you missed the primary endpoint" in other indications-
https://www.fda.gov/media/72140/download?attachment
.• Primary and Secondary Endpoints: The terms primary endpoint and secondary endpoint are used so variably that they are rarely helpful. The appropriate inquiry is whether there is a well-documented, statistically and clinically meaningful effect on a prospectively defined endpoint, not whether the endpoint was identified as primary or secondary.
End Stage Heart accelerated approval a big chance!
(20min delay)