How did a heparin supplier's warning letter for another product hold up DefenCath?

CorMedix Form 8-K, filed February 28, 2022

API (taurolidine and heparin) sourced from U.S./European manufacturers under contract and are shipped to drug product manufacturer, located in Europe • Multiple heparin suppliers available for sourcing

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.

CorMedix Form 8-K, filed August 9, 2022

Separately, the FDA conducted a recent inspection unrelated to DefenCath at the facility of the company’s heparin supplier, which culminated in the API supplier receiving a warning letter as a result of manufacturing deficiencies for a non-heparin API. CorMedix sought guidance from FDA as to whether these deficiencies would impact the timing of approval of the DefenCath NDA, and by way of the CRL, the FDA has now informed the company that satisfactory resolution of these deficiencies will be required before the DefenCath NDA may be approved. The Company’s heparin supplier has advised CorMedix that it has retained an independent CGMP consultant to expedite the implementation of corrective actions and resolve the warning letter as quickly as possible.

CorMedix Form 8-K, filed March 3, 2023

CorMedix has been informed by its existing supplier of heparin API (“API 1”) that all corrective actions related to its June 2022 FDA Warning Letter for a non-heparin API have been completed and implementation is underway, however it is unclear to the Company based on recent FDA actions if full resolution of the outstanding warning letter would still be required prior to approving the DefenCath NDA with reference to API 1. The supplier has informed CorMedix that it has made updates to the US Heparin Drug Master File (“DMF”) clarifying which activities take place at the site which is identified in the warning letter (early-stage processing) and which activities take place at a different FDA registered facility (final processing and release). The supplier has also informed CorMedix that subsequent to those updates, a supplement to an approved application referring to this DMF was recently approved by FDA. Based on this recent approval and the update to the DMF, it is possible that full resolution of the outstanding warning letter is no longer a barrier to FDA approval of the DefenCath NDA.

CorMedix Form 8-K, filed April 26, 2023

Based on guidance from FDA, CorMedix will resubmit the NDA with manufacturing data generated at CMO 1 and utilizing both the existing source of heparin API (“API 1”) as well as a new supplier of Heparin API (“API 2”). The Company has completed the validation of the manufacturing process using API 2, and believes all batches have met product specifications. Data for submission are currently available and resubmission is targeted for mid-May following receipt of final Type A meeting minutes. As part of validation of manufacturing with this API, the Company will be adding a 3 mL single-dose vial to its 5 mL commercial presentation to meet market preferences and demand. As the submission will contain new manufacturing information, the Company expects it to be classified as a Class 2 resubmission with a 6-month review.

CorMedix Form 8-K, filed June 21, 2023

The Company received a second Complete Response Letter from the FDA last August related to deficiencies at both its primary contract manufacturer and its supplier of heparin API for an unrelated product.

CorMedix Form 8-K, filed June 30, 2023

CorMedix received a second Complete Response Letter from the FDA last August related to deficiencies at both its primary contract manufacturer and its supplier of heparin API.

CorMedix Form 10-K, filed March 5, 2026

In general, the purported bases for these claims are allegedly false and misleading statements and omissions related to the NDA submissions to the FDA for DefenCath, subsequent complete response letters, as well as communications from the FDA related and directed to the Company’s contract manufacturing organization and heparin supplier.

CorMedix Form 10-K, filed March 5, 2026

For DefenCath, we currently have one FDA-approved source (contract manufacturing organization, or “CMO”) for each of our two key active pharmaceutical ingredients (“APIs”), taurolidine and heparin sodium, respectively. With regards to taurolidine, the Company has a drug master file (“DMF”) filed with the FDA. There is a master commercial supply agreement between a third-party manufacturer which has been in place since August 2018. With respect to heparin sodium API, the Company has identified an alternate third-party supplier and may qualify such supplier under the DefenCath NDA in the future.