CorMedix · DefenCath · Apr 2021 – Mar 2022
What did CorMedix say it fixed before resubmitting DefenCath in 2022?
An extraction study under an agreed protocol, then a process requalification at the manufacturer, interrupted by issues there unrelated to DefenCath. The resubmission was accepted in March 2022 with an inspection scheduled.
EphemerisX Research · Published · 7 source documents · 2 min read
Short answer
By May 2021 the company reported completing the extraction study and concluding that the filling process needed requalification and validation. In September 2021 it reported delays at the manufacturer from issues unrelated to DefenCath. It resubmitted in February 2022, saying it and the manufacturer had addressed the FDA's concerns; the FDA accepted the resubmission and scheduled an inspection.
What the evidence shows
In April 2021, CorMedix and the manufacturer met the FDA about the letter and the Post-Application Action Letter received by the third-party manufacturer (CMO) from FDA
8-K · Apr 15, 2021. The company said addressing the FDA's concerns regarding the qualification of the filling operation may necessitate adjustments in the process and generation of additional data on operating parameters for manufacture of DefenCath
8-K · Apr 15, 2021, and that the FDA expected all corrections to facility deficiencies to be complete at the time of resubmission
8-K · Apr 15, 2021.
May 2021: CorMedix successfully completed the agreed upon protocol for the manual extraction study identified in the Complete Response Letter
8-K · May 14, 2021, and we have concluded that additional process qualification will be needed with subsequent validation to address the deficiencies identified by FDA
8-K · May 14, 2021. The same release now described the letter as stating the NDA could not be approved until satisfactory resolution of deficiencies at the contract manufacturing facility, including in-process controls for the filling operation
8-K · May 14, 2021.
September 2021: The Company was informed by the CMO that there are issues that are unrelated to DefenCath manufacturing activities
8-K · Sep 7, 2021. November 2021: we have been able to resume manufacturing activities and are continuing to complete the work that is required to address the deficiencies identified at the manufacturing facility
8-K · Nov 9, 2021.
February 2022: the NDA was resubmitted, and the manufacturer submitted responses to the deficiencies identified at the manufacturing facility in the Post-Application Action Letter
8-K · Feb 28, 2022. The company said We believe that we and the manufacturer have adequately addressed the concerns the Agency identified in the CRL and PAAL
8-K · Feb 28, 2022. The FDA's second letter acknowledges the amendment, which constituted a complete response to our February 26, 2021, action letter
FDA · Aug 4, 2022 · p. 2.
March 2022: the FDA treated the resubmission as a complete, Class 2 response with a six month review cycle
8-K · Mar 28, 2022, and the manufacturer had been told that an onsite inspection has been scheduled as part of the review process
8-K · Mar 28, 2022. The second letter reports that inspection's result: our field investigators conveyed deficiencies to the representatives of the facilities
FDA · Aug 4, 2022 · p. 2.
Follow the thread
- What changed between the FDA's first and second letters on DefenCath?Extraction study completed, May 2021
- How did CorMedix describe the FDA's second letter?The scheduled inspection, and what it found
This investigation connects to
- What happens after a second FDA Complete Response Letter?Cross-investigation · Divergent outcome · with Aldeyra Therapeutics, Outlook Therapeutics, Replimune, Verrica Pharmaceuticals
- What is a Class 1 or Class 2 resubmission, and how did each play out in these records?Cross-investigation · Regulatory pathway · with Aldeyra Therapeutics, Outlook Therapeutics, Replimune
- What happens when an FDA letter turns on a contract manufacturer, not the drug?Cross-investigation · Shared concern · with Verrica Pharmaceuticals
The documents, by date
The passages quoted
CorMedix Form 8-K, filed April 15, 2021
Addressing FDA’s concerns regarding the qualification of the filling operation may necessitate adjustments in the process and generation of additional data on operating parameters for manufacture of DefenCath. CorMedix and the CMO are currently evaluating available data to determine if additional process qualification will be needed with subsequent validation to address these issues.Open at the source →
CorMedix Form 8-K, filed April 15, 2021
announced today that it has met with the US Food and Drug Administration (FDA) to discuss proposed resolutions for the deficiencies identified in the Complete Response Letter (CRL) to CorMedix and the Post-Application Action Letter received by the third-party manufacturer (CMO) from FDA for the New Drug Application (NDA) for DefenCath™ (taurolidine/heparin catheter lock solution). Representatives from both CorMedix and the CMO participated in the meeting with FDA to ensure that there is alignment on addressing the Agency’s concerns.Open at the source →
CorMedix Form 8-K, filed April 15, 2021
The FDA stated that the review timeline would be determined when the NDA resubmission is received and that it expected all corrections to facility deficiencies to be complete at the time of resubmission so that all corrective actions may be verified during an on-site evaluation in the next review cycle, if the FDA determines it will do an onsite evaluation.Open at the source →
CorMedix Form 8-K, filed May 14, 2021
CorMedix successfully completed the agreed upon protocol for the manual extraction study identified in the Complete Response Letter that FDA is requiring as confirmation of in-process controls to demonstrate that the labeled volume can be consistently withdrawn from the vials. · CorMedix continues to focus our efforts on resolving the deficiencies sent to the third-party manufacturer in the Post-Application Action Letter. Based on our analyses, we have concluded that additional process qualification will be needed with subsequent validation to address the deficiencies identified by FDA.Open at the source →
CorMedix Form 8-K, filed May 14, 2021
The Company received a Complete Response Letter from FDA stating that the NDA could not be approved until satisfactory resolution of deficiencies at the contract manufacturing facility, including in-process controls for the filling operation.Open at the source →
CorMedix Form 8-K, filed September 7, 2021
CorMedix has encountered delays at its third-party contract manufacturer (“CMO”). The Company was informed by the CMO that there are issues that are unrelated to DefenCath manufacturing activities. The timeline for CorMedix and the CMO to address deficiencies at the facility that are required for resubmission of the DefenCath NDA is uncertain at this time.Open at the source →
CorMedix Form 8-K, filed November 9, 2021
As noted previously, there was a delay as a result of issues at the third-party manufacturer, or CMO, unrelated to the manufacture of DefenCath. Together with our CMO, we have been able to resume manufacturing activities and are continuing to complete the work that is required to address the deficiencies identified at the manufacturing facility.Open at the source →
CorMedix Form 8-K, filed February 28, 2022
We believe that we and the manufacturer have adequately addressed the concerns the Agency identified in the CRL and PAAL. As CorMedix has previously announced, FDA has stated that satisfactory resolution of the deficiencies may require a preapproval inspection of the manufacturing facility.”Open at the source →
CorMedix Form 8-K, filed February 28, 2022
today announced that it has resubmitted the New Drug Application (NDA) for DefenCath to address the Complete Response Letter (CRL) issued by the U.S. Food and Drug Administration (FDA) a year ago. In parallel, the Company’s third-party manufacturer submitted responses to the deficiencies identified at the manufacturing facility in the Post-Application Action Letter (“PAAL”) issued by the FDA concurrently with the CRL.Open at the source →
CorMedix Form 8-K, filed March 28, 2022
The Agency considers the resubmission as a complete, Class 2 response with a six month review cycle.Open at the source →
CorMedix Form 8-K, filed March 28, 2022
FDA has begun review of the filing and we have learned from our contract manufacturer that it has been notified by FDA that an onsite inspection has been scheduled as part of the review process. We believe that both CorMedix and our contract manufacturer have adequately addressed the concerns the Agency identified during the review of the original NDA and we are committed to working jointly to ensure a successful inspection.”Open at the source →
FDA Complete Response Letter, August 4, 2022 · page 2
During a recent inspection of the and Rovi Pharma Industrial Services S.A (FEI 3016688535) manufacturing facilities for this application, our field investigators conveyed deficiencies to the representatives of the facilities. Satisfactory resolution of these deficiencies is required before this application may be approved.Open at the source →
FDA Complete Response Letter, August 4, 2022 · page 2
We acknowledge receipt of your amendment dated February 25, 2022, which constituted a complete response to our February 26, 2021, action letter.Open at the source →