CorMedix · DefenCath · Feb 2021 → Aug 2022
What changed between the FDA's first and second letters on DefenCath?
Rovi is named in both. A records review became an inspection, a second facility was added, the extraction study dropped out, the name went from conditionally acceptable to unacceptable, and a heparin supplier's facilities appeared in a comment.
EphemerisX Research · Published · 2 source documents · 2 min read
Short answer
Both letters rest on product quality at Rovi Pharma Industrial Services' facility. In 2021 the FDA cited records it had reviewed; in 2022 it cited deficiencies conveyed during a recent inspection of Rovi and a second facility whose name is redacted. The fill-volume item is gone from the 2022 letter, the name Defencath moved from conditionally acceptable to unacceptable, and a new comment concerns facilities in the heparin supplier's drug master file.
What the evidence shows
The 2021 letter: During a review of records requested under Federal Food, Drug, and Cosmetic Act section 704(a)(4), provided by Rovi Pharma Industrial Services S.A. (FEI 3016688535) manufacturing facility, the FDA noted objectionable conditions
FDA · Feb 26, 2021 · p. 8.
The 2022 letter: 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
FDA · Aug 4, 2022 · p. 2. The words between “of the” and “and Rovi” are redacted in the published letter.
Both letters set the same condition: Satisfactory resolution of these objectionable conditions is required
FDA · Feb 26, 2021 · p. 8 (2021) and Satisfactory resolution of these deficiencies is required before this application may be approved
FDA · Aug 4, 2022 · p. 2 (2022).
What changed
Facility: a review of records in 2021; a recent inspection
FDA · Aug 4, 2022 · p. 2 of two facilities in 2022.
Process: the 2021 letter's second item, conduct and provide results of an extraction study
FDA · Feb 26, 2021 · p. 9, has no counterpart among the 2022 letter's four numbered items: the facilities, labeling, carton labeling and the proprietary name. CorMedix had reported the study complete in May 2021: CorMedix successfully completed the agreed upon protocol for the manual extraction study
8-K · May 14, 2021.
Name: from conditionally acceptable pending approval of the application in the current review cycle
FDA · Feb 26, 2021 · p. 10 to This proposed name is unacceptable due to confusion with another product that is also under review
FDA · Aug 4, 2022 · p. 4.
Heparin: a new comment, listed among comments/recommendations that are not approvability issues
FDA · Aug 4, 2022 · p. 5, says there are facilities (e.g., release/stability testing sites) included in DMF
FDA · Aug 4, 2022 · p. 5 for heparin sodium that were not listed in your application
FDA · Aug 4, 2022 · p. 5, and that the FDA cannot provide to you the status of facilities not listed in your application
FDA · Aug 4, 2022 · p. 5. Where heparin went from there: How did a heparin supplier's warning letter for another product hold up DefenCath?
Follow the thread
- What did the FDA's first letter on DefenCath require?Rovi's records, 2021
- What did CorMedix say it fixed before resubmitting DefenCath in 2022?Extraction study completed, May 2021
- How did a heparin supplier's warning letter for another product hold up DefenCath?Heparin DMF facilities not listed
- Why did the FDA call the name Defencath unacceptable in 2022?2022: name “unacceptable”
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 happens when an FDA letter turns on a contract manufacturer, not the drug?Cross-investigation · Shared concern · with Verrica Pharmaceuticals
- What did “no efficacy or safety issues” cover in these FDA letter announcements?Cross-investigation · Shared concern · with Replimune, Verrica Pharmaceuticals
The documents, by date
The passages quoted
FDA Complete Response Letter, February 26, 2021 · page 8
During a review of records requested under Federal Food, Drug, and Cosmetic Act section 704(a)(4), provided by Rovi Pharma Industrial Services S.A. (FEI 3016688535) manufacturing facility, the FDA noted objectionable conditions. These objectionable conditions will be conveyed to the representative of the facility within 10 business days of issuance of this Complete Response letter. Satisfactory resolution of these objectionable conditions is required (e.g., preapproval inspection and/or adequate facility responses addressing these conditions) before this application may be approved.Open at the source →
FDA Complete Response Letter, February 26, 2021 · page 9
You have not demonstrated that the currently proposed in-process control for the ( mL± mL) in the drug product manufacturing process is appropriate. As previously communicated to you, conduct and provide results of an extraction study to demonstrate that the labeled volume of the drug product solution (5 mL) can be consistently withdrawn from vials, including vials that are . Revise the based on the results of the extraction study conducted.Open at the source →
FDA Complete Response Letter, February 26, 2021 · page 10
Please refer to correspondence dated August 28, 2020, which addresses the proposed proprietary name, Defencath. This name was found conditionally acceptable pending approval of the application in the current review cycle. Please resubmit the proposed proprietary name when you respond to the application deficiencies.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 →
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 4
Please refer to correspondence dated July 20, 2022, which addresses the proposed proprietary name, Defencath. This proposed name is unacceptable due to confusion with another product that is also under review. Therefore, the ultimate acceptability of your proposed proprietary name, Defencath, is dependent upon which application is approved first.Open at the source →
FDA Complete Response Letter, August 4, 2022 · page 5
We have the following comments/recommendations that are not approvability issues: Product Quality / Facilities: There are facilities (e.g., release/stability testing sites) included in DMF for HEPARIN SODIUM ( ) that were not listed in your application (i.e., Form FDA 356h and/or in Section 3.2.S.2.1). Please note that the FDA cannot provide to you the status of facilities not listed in your application. Please contact the DMF holder to identify and resolve any discrepancies and clarify which facilities listed in the DMF support your application. We recommend that the DMF related facilities supporting your application be added to your Form FDA 356h and in Section 3.2.S.2.1. If only a subset of the facilities listed in the DMF will be referenced in your application to support commercial manufacturing and/or testing, the letter of authorization (LOA) should specify those facilities. Absent this specificity, the FDA intends to assume that all facilities listed in a referenced DMF support your application.Open at the source →