Facility inspections in FDA Complete Response Letters

3. Following a pre-approval inspection a listed in this application, conveyed deficiencies to the representative of the facility.

The facility should provide satisfactory responses to these deficiencies to the FDA office indicated on FDA Form 483 prior to your complete response to your application.

Your complete response should include the date(s) of the facility's response to FDA Form 483. The assessment of application approvability and the resolution of inspection deficiencies would be evaluated upon receipt of the complete response and may include re-inspection of the facility.

The facility should provide satisfactory responses to these deficiencies to the FDA office indicated on the FDA 483 prior to your complete response.

Form 483. The assessment of the application approvability and the resolution of inspection deficiencies would be evaluated upon receipt of the complete response and may include re-inspection of the facility.

The facility should provide satisfactory responses to these deficiencies to the FDA office indicated on the FDA 483 prior to your complete response to your application.

Your complete response should include the date(s) of the facility's response to the FDA Form 483. The assessment of application approvability and the resolution of inspection deficiencies would be evaluated upon receipt of the complete response and may include re-inspection of the facility.

The facility should provide satisfactory responses to these deficiencies to the FDA office indicated on FDA Form 483 prior to your complete response to your application.

Your complete response should include the date(s) of the facility's response to FDA Form 483. The assessment of application approvability and the resolution of inspection deficiencies would be evaluated upon receipt of the complete response and may include re-inspection of the facility.

The facility should provide satisfactory responses to these deficiencies to the FDA office indicated on the FDA Form 483 prior to your complete response to your application.

The facility should provide satisfactory responses to hese deficiencies to the FDA office indicated on the FDA Form 483 prior to your complete response.

In November 2024 we announced the FDA had accepted its NDA and set a Prescription Drug User Fee Act (PDUFA) target action date of June 28, 2025. In June 2025, the FDA issued us a Complete Response Letter (CRL) notifying us that a third-party manufacturing vendor of its main contract development and manufacturing organization (CDMO) was cited for deficiencies following a cGMP inspection.

We resubmitted an NDA in December 2025 and the FDA set a PDUFA target action date of June 29, 2026. If the third party fails inspection again or if the NDA is rejected again, we will need to make another NDA submission and our target PDUFA target action date will be extended by another 6-12 months.

The facility should provide satisfactory responses to these deficiencies to the FDA office indicated on the FDA 483 prior to your complete response.

The facility's satisfactory responses are dependent on FDA's determination that the facility has come into compliance with CGMP and may require reinspection of the facility.

FDA may need to conduct a pre-approval inspection (PAI) of the facility.

Following a CGMP inspection and pre-license inspection 0 conveyed deficiencies to the representative of the facility.

FDA may determine that a CGMP reinspection and/or additional pre-license inspection (PLI) is needed to confirm satisfactory resolution of inspection deficiencies before this application can be approved.

1. During a recent inspection of Tanvex, Inc. manufacturing facility (FEI: 3013021112) for this BLA, our field investigators conveyed deficiencies to the representatives of the facility.

5. Two comparative analytical studies were conducted, one in 2016 and a second study in 2018. During the inspection of the Tanvex Inc. facility (FEI: 3013021112)

Provide evidence that the non-qualified methods and those run without system suitability criteria as indicated in the inspection document "Summary of the History of Changes to the Methods and Reference Standards used for Analytical Similarity Assessment" were suitable for their intended use during the 2016 comparative analytical study.

The facility should provide satisfactory responses to these deficiencies to the FDA office indicated on the FDA 483 prior to your complete response to your application.

(1) Following a CGMP inspection of Loey listed in this application, FDA conveyed deficiencies to the representative of the facility.

The facility should provide satisfactory responses to these deficiencies to the FDA office indicated on FDA Form 483 prior to your Complete Response submission.

1. During a recent inspection of the Tris Pharma, Inc. (FEI: 3004712471) manufacturing facility for this application, our field investigator conveyed deficiencies to the representative of the facility.

The facility's satisfactory responses are dependent on FDA's determination that the facility has come into compliance with CGMP and may require re-inspection of the facility.

Following resolution of the CGMP inspection, FDA may need to conduct a pre-approval inspection (PAI) of the facility.

Satisfactory outcomes of both the PAI and the CGMP inspections will be needed prior to an approval of the application.

The facility should provide satisfactory responses to these deficiencies to the FDA office indicated on the FDA Form 483 prior to your complete response.

The facility should provide satisfactory responses to these deficiencies to the FDA office indicated on the FDA 483 prior to your complete response resubmission.

FDA Form 483. If the FDA determines the deficiencies resolved following a full review of the inspection and 483 responses after this Complete Response Letter, the facility will be informed.

The facility should provide satisfactory responses to these deficiencies to the FDA office indicated on FDA 483 prior to your complete response.

Following resolution of the CGMP inspection, FDA may need to conduct a pre-approval inspection (PAI) of the facility.

The facility should provide satisfactory responses to these deficiencies to the FDA office indicated on the FDA Form 483 prior to your complete response to your application.

Your complete response should include the date(s) of the facility's response to the FDA Form 483. The assessment of application approvability and the resolution of inspection deficiencies would be evaluated upon receipt of the complete response and may include re-inspection of the facility.

In February 2026, the FDA conducted a pre-approval inspection of our CDMO's facility used to manufacture CTx-1301. This facility was issued a Form 483 by the FDA at the conclusion of the inspection with three observations.

In February 2026, the FDA conducted a pre-approval inspection of our CDMO facility used to manufacture CTx-1301. This facility was issued a Form 483 by the FDA at the conclusion of the inspection with three observations.

The facility should provide satisfactory responses to these deficiencies to the FDA office indicated on the FDA 483 prior to your complete response.

The facility's satisfactory responses are dependent on FDA's determination that the facility has come into compliance with CGMP and may require re-inspection of the facility.

Satisfactory outcomes of both the PAI and the CGMP surveillance inspections will be needed prior to an approval of the application.

The facility should provide satisfactory responses to these deficiencies to the FDA office indicated on the FDA Form 483 prior to your complete response.

As previously noted, we received a CRL from the FDA in April 2026 in response to our NDA for GTx-104, which identified certain cGMP deficiencies at our CMO.

The facility should provide satisfactory responses to these deficiencies to the FDA office indicated on FDA Form 483 prior to your complete response to your application.

Your complete response should include the date(s) of the facility's response to FDA Form 483. The assessment of application approvability and the resolution of inspection deficiencies would be evaluated upon receipt of the complete response and may include re-inspection of the facility.

FDA office indicated on the FDA 483 prior to your complete response.

The facility should provide satisfactory responses to these deficiencies to our office indicated on the FDA Form 483 prior to your complete response.

The facility should provide satisfactory responses to these deficiencies to the FDA office indicated on the FDA 483 prior to your complete response to your application.

Your complete response should include the date(s) of the facility's response to the FDA Form 483. The assessment of application approvability and the resolution of inspection deficiencies would be evaluated upon receipt of the complete response and may include re-inspection of the facility.

Following a CGMP inspection and pre-license inspection (PLI) of isted in this application, convey: leficiencies to representative of the facility.

In August 2025, the FDA notified us that it had conducted a cGMP inspection of our third-party manufacturer of reproxalap and conveyed deficiencies to the third-party manufacturer in a Form 483 letter.

The facility should provide satisfactory responses to these deficiencies to the FDA office indicated on the FDA 483 prior to your complete response.

The facility's satisfactory responses are dependent on FDA's determination that the facility has come into compliance with CGMP and may require re-inspection of the facility.

Following resolution of the CGMP inspection, FDA may need to conduct a Preapproval inspection (PAI) of the facility.

Satisfactory outcomes of both the PAI and the CGMP surveillance inspections will be needed prior to approval of the application.

Following a pre-license inspection of ecerceconicreaccirt listed in this application, conveyed deficiencies fo the representative of the facility.

The facility should provide satisfactory responses to these deficiencies to the FDA office indicated on the FDA Form 483 prior to your complete response to your application.

Your complete response should include the date(s) of the facility's response to the FDA Form 483. The assessment of application approvability and the resolution of inspection deficiencies would be evaluated upon receipt of the complete response and may include re-inspection of the facility.

Following inspections of Fresenius Kabi Austria GmbH, Graz, Austria (FEI: 3003708554) and ®® listed in this application, FDA conveyed deficiencies to the representative of the facility.

Due to the deficiencies identified in bioanalytical method validation and bioanalysis for insulin aspart quantitation as indicated on the FDA Form 483 issued on ae.

The facility should provide satisfactory responses to these deficiencies to the FDA office indicated on the FDA Form 483 prior to your complete response to your application.

Your complete response should include the date(s) of the facility's response to the FDA Form 483. The assessment of application approvability and the resolution of inspection deficiencies would be evaluated upon receipt of the complete response and may include re-inspection of the facility.

For example, our facilities in Rancho Cucamonga, CA, Éragny Sur Epte, France, and Nanjing, China have previously been subject to FDA cGMP inspections since 2019 as well as pre-approval, routine and other inspections by the FDA, state, and other regulatory authorities and may be again in the future per applicable law.

The RMIC was designed to support clinical and future commercial production of AAV therapeutics and has been in operation since mid-2022. In 2025, the FDA completed a pre-license inspection (PLI) and bioresearch monitoring (BIMO) inspection as part of the RGX-121 Biologics License Application (BLA) with no observations.

Enrollment in both trials completed in October 2025. To support future commercialization of sura-vec, the cGMP material produced by our NAVXpress platform process has been incorporated in the ongoing pivotal trials, ATMOSPHERE and ASCENT, for the treatment of wet AMD using sura-vec delivered subretinally.

In August 2025, the FDA completed a pre-license inspection and bioresearch monitoring information inspection for the RGX-121 BLA with no observations.

A BLA for RGX-121 seeking accelerated approval was submitted to the FDA in March 2025. The FDA subsequently granted priority review of the BLA and successfully completed mid-cycle meeting, Pre-license inspection (PLI) and Bioresearch monitoring information (BIMO) inspections.

The facility should provide satisfactory responses to these deficiencies to the FDA office indicated on the FDA 483 prior to your complete response to your application.

Your complete response should include the date(s) of the facility's response to the FDA Form 483. The assessment of application approvability and the resolution of inspection deficiencies would be evaluated upon receipt of the complete response and may include re-inspection of the facility.

For example, in October 2023 the U.S. FDA inspected our Biologics facility in Hyderabad, India.

In November 2024, the U.S. FDA issued a complete response letter ("CRL") with additional queries in reference to the ongoing resolution of observations arising from the October 2023 inspection, as well as certain aspects pertaining to our biologics license application ("BLA") for a biosimilar rituximab.

We re-submitted the BLA to the FDA for ONS-5010/LYTENAVA in August 2022 and in August 2023, we received a CRL in which the FDA concluded it could not approve the BLA during this review cycle due to several CMC issues, open observations from pre-approval manufacturing inspections, and a lack of substantial evidence.

We re-submitted the BLA to the FDA for ONS-5010/LYTENAVA on August 30, 2022. On August 29, 2023, we received a CRL in which the FDA concluded it could not approve the BLA during this review cycle due to several CMC issues, open observations from pre-approval manufacturing inspections, and a lack of substantial evidence.

In August 2023, we received a Complete Response Letter, or CRL, in which the FDA concluded it could not approve the BLA during this review cycle due to several chemical, manufacturing and control, or CMC, issues, open observations from pre-approval manufacturing inspections, and a lack of substantial evidence.

The facility should provide satisfactory responses to these deficiencies to the FDA office indicated on the FDA 483 prior to your complete response to your application.

FDA office indicated on the FDA 483 prior to your complete response to your application.

The facility should provide satisfactory responses to these deficiencies to the FDA office indicated on the FDA 483 prior to your complete response to your application.

Your complete response should include the date(s) of the facility's response to the FDA Form 483. The assessment of application approvability and the resolution of inspection deficiencies would be evaluated upon receipt of the complete response and may include re-inspection of the facility.

The facility should provide satisfactory responses to these deficiencies to the FDA office indicated on the FDA Form 483 prior to your complete response to your application.

In October 2025, November 2025 and December 2025, we received CRLs from the FDA regarding, respectively, the BLAs for AVT05, AVT06, and AVT03. The CRLs all stated that the FDA had identified deficiencies related to our Reykjavik manufacturing facility following the FDA's pre‑license inspection in July 2025, which must be satisfactorily resolved before these BLAs may be approved.

The facility should provide satisfactory responses to these deficiencies to the FDA office indicated on the FDA 483 prior to your complete response.

FDA office indicated on the FDA 483 prior to your complete response.

Inspections identified systematic under-reporting of adverse events and incorrect coding of fall events in the original adverse event dataset.

Your complete responses should include the date(s) of the facility's response to the form FDA-483. The assessment of application approvability and the resolution of inspection deficiencies would be evaluated upon receipt of the complete response and may include re-inspection of the facility.

Your complete responses should outline the corrections taken in response to the inspection.

The facility should provide satisfactory responses to these deficiencies to the FDA office indicated on the FDA 483 prior to your complete response.

The facility's satisfactory responses are dependent on FDA's determination that the facility has come into compliance with CGMP and may require re-inspection of the facility.

Satisfactory outcomes of both the PAI and the CGMP surveillance inspections will be needed prior to an approval of the application.

● our ability to obtain regulatory approval for apitegromab is dependent on the timely and satisfactory response to the Complete Response Letter ("CRL") received from the FDA in September 2025 and resolution of the cGMP deficiencies identified in the CRL by our third-party fill-finish facility;

The facility was issued a Form 483 by the FDA in July 2025, and the facility was classified as OAI in October 2025. The observations were site-related and not specific to apitegromab.

The facility was issued a Form 483 by the FDA in July 2025 and the inspection classification of this facility is OAI.

The facility was issued a Form 483 by the FDA in July 2025 and the inspection classification of this facility is official action indicated ("OAI").

The facility should provide satisfactory responses to these deficiencies to the FDA office indicated on the FDA Form 483 prior to your complete response.

The facility's satisfactory responses are dependent on FDA's determination that the facility has come into compliance with CGMP and may require re-inspection of the facility.

Following resolution of the CGMP inspection, FDA may need to conduct a Pre-Approval Inspection (PAI) of the facility.

Satisfactory outcomes of both the PAI and the CGMP surveillance inspections will be needed prior to an approval of the application.

FDA 483 prior to your complete response to your application.

Your complete response should include the date(s) of the facility's response to the FDA Form 483. The assessment of application approvability and the resolution of inspection deficiencies would be evaluated upon receipt of the complete response and may include reinspection of the facility.

Your complete response should include the date of the facility's response to the FDA Form 483. The assessment of application approvability and the resolution of inspection deficiencies would be evaluated upon receipt of the complete response and may include re-inspection of the facility.

The facility should provide satisfactory responses to these deficiencies to the FDA office indicated on the most recent FDA 483 prior to your complete response to your application.

The FDA conducted an expedited, risk-based review of the available information from the inspection and determined that the deficiencies represent significant issues that adversely impact the facility's ability to perform the designated functions described in your application.

The facility should provide satisfactory responses to these deficiencies to the FDA office indicated on the FDA 483 prior to your complete response resubmission.

FDA Form 483. If the FDA determines the deficiencies resolved following a full review of the inspection and 483 responses after this Complete Response Letter, the facility will be informed.

Otherwise, further assessment of application approvability and the resolution of inspection deficiencies would be evaluated upon receipt of the complete response and may include re-inspection of the facility.

The facility should provide satisfactory responses to these deficiencies to the FDA office indicated on the FDA 483 prior to your complete response.

In October 2025, the Company was notified by Catalent that they received an official action indicated ("OAI") letter from the FDA citing unresolved issues related to a July 2025 FDA general site inspection.

The application has been accepted for review, a standard pre-licensing inspection has been scheduled, and an FDA decision on the Company's filing is expected in the second quarter of 2026.

On July 30, 2025, the FDA issued a CRL for the BLA for odronextamab in relapsed/refractory follicular lymphoma after two or more lines of systemic therapy, which was also impacted by the Catalent Indiana LLC site inspection (as described in the "EYLEA HD" section above).

FDA may need to perform an onsite pre-license inspection (PLI) before this application may be approved.

The facility should provide satisfactory responses to these deficiencies to the FDA office indicated on the FDA Form 483 prior to your complete response submission to this application.

Your complete response submission to this application should include the date(s) of the facility's response(s) to the FDA Form 483 observations.

In mid-2025, the FDA completed its Pre-License Inspection ("PLI") of this facility in connection with our Biologics License Application for Deramiocel.

For instance, in July 2025, we received a CRL from the FDA for our BLA for UX111, which cited information and improvements related to the observations from the FDA's inspections at our gene therapy manufacturing facility and that of our third-party manufacturer.

1. During a recent inspection of the Sun Pharmaceutical Industries Ltd manufacturing facility for this application, our field investigator conveyed deficiencies to the representative of the facility.

1. During recent inspections of the Sun Pharmaceutical Industries Limited, FEI:

The facility should provide satisfactory responses to these deficiencies to the FDA office indicated on the FDA 483 prior to your complete response to your application.

FDA may determine that a CGMP reinspection and/or additional pre-approval inspection (PAI) is needed to confirm satisfactory resolution of inspection deficiencies before this application can be approved.

During a recent surveillance inspection of the) a manufacturing facility for this application, our field investigator conveyed iciencies to the representative of the facility.

The facility should provide satisfactory responses to these deficiencies to the FDA office indicated on the FDA 483 prior to submission of your complete response.

PAI and the CGMP surveillance inspections will be needed prior to an approval of the application.

The facility should provide satisfactory responses to these deficiencies to the FDA office indicated on the FDA 483 prior to your complete response.

The facility's satisfactory responses are dependent on FDA's determination that the facility has come into compliance with CGMP and may require re-inspection of the facility.

During a recent inspection of the Celltrion, Inc. (FEI 3005241015) manufacturing facility, our field investigator conveyed deficiencies to the representative of the facility.

1. During a recent inspection of the Celltrion, Inc. (FEI 3005241015) manufacturing facility, the field investigator conveyed deficiencies to the representative of the facility.

The facility should provide satisfactory responses to these deficiencies to the FDA office indicated on the FDA 483 prior to your complete response to your application.

Your complete response should include the date(s) of the facility's response to the FDA Form 483. The assessment of application approvability and the resolution of inspection deficiencies would be evaluated upon receipt of the complete response and may include re-inspection of the facility.

1. Following pre-license inspection of isted in this application, conveyed leficiencies to the representative of the facility.

The facilities should provide satisfactory responses to these deficiencies to the FDA office indicated on the FDA 483 prior to your complete response to your application.

Your complete response should include the date(s) of the facility's response(s) to the FDA Form 483. The assessment of application approvability and the resolution of inspection deficiencies would be evaluated upon receipt of the complete response and may include re-inspection of the facilities.

This determination is based upon information available to the Agency at this time, [i.e., information in your application and the status of current good manufacturing practices (CGMPs) of the facilities used in the manufacture and testing of the drug product].

The facility's satisfactory responses are dependent on FDA's determination hat the facility has come into compliance with CGMP and may require re-inspection of he facility.

The deficiencies identified during the inspection may not be specific to your pending application, therefore, you should coordinate with the facility for timely resolution.

FDA may need to conduct a pre-approval inspection (PAI) of the facility.

Given that this site enrolled a relatively large representation of the study population (approximately 9%), as well as the types and frequency of the adverse events observed but were omitted from this site's safety data, these inspection findings raise significant concerns regarding the reliability of the data to inform the benefit-risk assessment of glepaglutide.

The facility should provide satisfactory responses to these deficiencies to the FDA office indicated on the FDA Form 483 prior to resubmitting your application for amivantamab and hyaluronidase injection.

Your complete response addressing these deficiencies must include the date of the facility's response to the FDA Form 483. The assessment of the application approvability and the resolution of inspection deficiencies will be evaluated upon receipt of the complete response addressing the deficiencies and may include reinspection of the facility.

The FDA conducted an expedited, risk-based review of the available information from the inspection and determined that the deficiencies represent significant issues that adversely impact the facility's ability to perform the designated functions described in your application.

The facility should provide satisfactory responses to these deficiencies to the FDA office indicated on the FDA 483 prior to your complete response resubmission.

Otherwise, further assessment of application approvability and the resolution of inspection deficiencies would be evaluated upon receipt of the complete response and may include re-inspection of the facility.

Following the pre-license inspection of a listed in this application, FDA conveyed deficiencies to the facility's representative.

Satisfactory responses to these deficiencies should be provided to the inspection team prior to submitting your complete response.

Your complete response should include the date of the facility's response to the FDA Form 483. The assessment of application approvability and the resolution of inspection deficiencies would be evaluated upon receipt of the complete response and may include re-inspection of the facility.

Your complete response should include the date of the facility's response to the FDA Form 483. The assessment of application approvability and the resolution of inspection deficiencies would be evaluated upon receipt of the complete response and may include re-inspection of the facility.

However, even if these deficiencies are addressed, the application cannot be approved until the required FDA inspection is conducted and any findings are assessed with regard to your application.

The facility should provide satisfactory responses to these deficiencies to the FDA office indicated on the FDA 483 prior to your complete response.

1. Following pre-license inspection of CSL Behring GmbH, Emil-von-BehringStrasse 76, Marburg, Hesse, Germany (FEI 3003098680), listed in this application, the FDA conveyed the deficiencies to the representative of the facility.

The facility should provide satisfactory responses to these deficiencies to the FDA office indicated on the FDA 483 prior to your complete response to your application.

Your complete response should include the date(s) of the facility's response to the FDA Form 483. The assessment of application approvability and the resolution of inspection deficiencies would be evaluated upon receipt of the complete response and may include re-inspection of the facility.

In addition, FDA inspections also identified several unreported adverse events for at least two sites, which increase our concerns about the reliability of the safety data.

During the sponsor inspection, FDA identified that the definition of an adverse event (AE) in the MAPP2 training information and the safety manual were not consistent with the MAPP2 protocol.

(19) Following inspection of a manufacturing facility listed in this application, FDA conveyed deficiencies to the representative of the facility.

The facility should provide satisfactory responses to these deficiencies to the FDA office indicated on the FDA 483 prior to submission of your complete response to your application.

Your complete response should include the date(s) of the facility's response to the FDA Form 483. The assessment of application approvability and the resolution of inspection deficiencies will be evaluated upon receipt of the complete response and may include re-inspection of the facility.

1. Following pre-license inspection of Ch)

The facility should provide satisfactory responses to these deficiencies to the FDA office indicated on the FDA Form 483 prior to your resubmission of the application.

Your resubmission should include the date(s) of the facility's response to the FDA Form 483. The assessment of application approvability and the resolution of inspection deficiencies will be evaluated upon receipt of the resubmission and may include re-inspection of the facility.

The facility should provide satisfactory responses to these deficiencies indicated on the FDA 483 to the FDA office prior to your complete response to your application.

FDA conducted an expedited, risk-based review of the available information from the inspection and determined that the deficiencies represent significant issues that adversely impact the facility's ability to perform the designated functions described in your application.

Otherwise, further assessment of application approvability and the resolution of inspection deficiencies would be evaluated upon receipt of the complete response and may include re-inspection of the facility.

The facility should provide satisfactory responses to these deficiencies to the FDA office indicated on the FDA 483 prior to your complete response to your application.

Your complete response should include the date(s) of the facility's response to the FDA Form 483. The assessment of application approvability and the resolution of inspection deficiencies would be evaluated upon receipt of the complete response and may include re-inspection of the facility.

FDA Form 483. The assessment of application approvability and the resolution of inspection deficiencies would be evaluated upon receipt of the complete response and may include re-inspection of the facility.

BLA resubmission and may include reinspection of the facility.

However, this information has not been reviewed at this time because, based on an assessment of the risk profile of your proposed combination product, FDA has determined that information to demonstrate compliance with the device QS regulation is most appropriately assessed during inspection rather than reviewed as part of the quality assessment of your application.

Currently, the need for a facility inspection, and an assessment of the findings, is the only deficiency with your application.

We also refer to the general advice letter, issued October 14, 2022, notifying you that the extended PDUFA date of October 16, 2022, would be missed due to travel restrictions preventing the inspection of Akeso Biopharma Co., Ltd.

Satisfactory responses to these deficiencies should be provided by the facility to the email address provided on the Form FDA 483 Inspectional Observations, prior to submitting your complete response.

The assessment of application approvability and the resolution of inspection deficiencies would be evaluated upon receipt of the complete response and may require re-inspection of the facility.

Satisfactory inspection is required before this application may be approved.

Satisfactory responses to these deficiencies should be provided by the facility to the email address provided on he Form FDA 483 Inspectional Observations, prior to submitting your complete response.

The assessment of application approvability and the resolution of inspection deficiencies would be evaluated upon receipt of he complete response and may require re-inspection of the facility.

2. Following evaluation of the inspection findings noted above, and the response to hose findings, FDA has identified concerns regarding the reliability of data generated at Samsung Biologics in your BLA submission.

RRA and conducted a pre-license inspection (PLI) to further evaluate the facility.

Your complete response should include the date of the facility's response to the FDA Form 483. The assessment of the application approvability and resolution of inspection deficiencies would be evaluated upon receipt of the complete response and may include a re-inspection of the facility.

In 2023, FDA conducted a pre-license inspection of the manufacturing process of Ryoncil® which did not result in the issuance of a Form 483 and there were no observed concerns.

On January 31, 2023, we resubmitted the BLA and on March 7, 2023, the FDA accepted the BLA and provided a PDUFA goal date of August 2, 2023. The FDA has conducted a pre-license inspection of the manufacturing process of remestemcel-L.

(5) During a recent inspection of the manufacturing facility for this application, our field investigator conveyed deficiencies to the representative of the facility.

Following surveillance inspection of the oe manufacturing facility listed in this application, FDA conveyed deficiencies to the representative of the facility.

However, even if these deficiencies are addressed, the application cannot be approved until the required FDA inspections are completed and any findings are assessed with regard to our application.

1. During a recent inspection of the Hugel, Inc (FEI 3012163998) manufacturing and testing facility of drug substance and drug product for this application, our field investigator conveyed deficiencies to the representative of the facility.

Agency at this time, [i.e., information in your application and the status of current good manufacturing practices (CGMPs) of the facilities used in the manufacture and testing of the drug product].

During a recent inspection of the | manufacturing facility for this application, our field investigator conveyed deficiencies to the representative of the facility.

· CorMedix has been informed by its primary CMO ("CMO 1") that all corrective actions stemming from the FDA's June 2022 inspection have been completed and the CMO has provided to FDA documentation showing effectiveness of the corrective actions.

· CorMedix was informed by its primary contract manufacturing organization ("CMO") that all corrective actions stemming from the FDA's June 2022 inspection have been completed, and the CMO has provided to FDA documentation showing effectiveness of the corrective actions.

Satisfactory inspection is required before this application may be approved.

During a recent inspection of the Braintree Laboratories, Inc., MA (FEI1000513636) manufacturing facility for this application, our field investigator conveyed deficiencies to the representative of the facility.

During a recent inspection of the UCB Pharma SA (FEI: 3003909356) manufacturing facility for this application, our field investigator conveyed deficiencies to the representative of the facility.

However, even if these deficiencies are addressed, the application cannot be approved until the required FDA inspection is conducted and any findings are assessed with regard to your application.

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.

If it is determined that an inspection is needed to approve your application, please note that FDA continues to monitor the public health situation as well as travel restrictions.

Inspections of the Pfizer Ireland Pharmaceuticals, Dublin, Ireland (FEI: 3004145594) and Pfizer Manufacturing Belgium NV (FEI: 1000654629) facilities are required before this application can be approved as the FDA must assess the ability of those facilities to conduct the listed manufacturing operations in compliance with CGMP.

However, even if all other deficiencies are addressed, the application cannot be approved until the required FDA inspections are completed and the findings are assessed with regard to your application.

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.

If it is determined that an inspection is needed to approve your application, please note that FDA continues to monitor the public health situation as well as travel restrictions.

During a recent inspection for this application of the Pharmaceutics International |"

For example, as described elsewhere, we received a CRL from the FDA in August 2020 and November 2021, regarding our NDA for PEDMARK®, stating that it was unable to approve the application in its current form based on deficiencies identified by the FDA after completion of a pre-approval inspection of the manufacturing facility of our third-party drug product manufacturer.

FDA must assess the ability of that facility to conduct the listed manufacturing operations in compliance with CGMP.

However, even if these deficiencies are addressed, the application cannot be approved until the required FDA inspection is conducted and any findings are assessed regarding your application.

Please see the FDA's "Resiliency Roadmap for FDA Inspectional Oversight" for more information on FDA's plan to resume inspections (https:/Awww.fda.gov/media/148197/download).

During a recent inspection of the of the | manufacturing facility for this application, our field investigator conveyed deficiencies to the representative of the facility.

Based on an assessment of the risk profile of your proposed combination product, FDA has determined that information to demonstrate compliance with the device QS regulation is most appropriately assessed during inspection, and this information must be available upon inspection to demonstrate your compliance with 21 CFR part 4.

During the Agency's inspection of Site 104 to determine whether excluding this site was justified, the site personnel were unable to provide documentation on PK blood sample processing and handling.

Based on the findings at Site 104, the Agency conducted an inspection of Site 107 (South Florida Medical Research, Maitland, FL).

During a recent inspection of the Polarean Inc. (FEI:3010132318) manufacturing facility or this application, our field investigator conveyed deficiencies to the representative of he facility.

During a recent inspection of the we manufacturing facility for this application, our field investigator conveyed deficiencies to he representative of the facility.

Pharmaceuticals Co., Ltd. FEI: 3013567704 manufacturing facility at Zhejiang, China, for this application, our field investigator observed objectionable conditions at the facility and conveyed that information to the representative of the facility at the close of the inspection.

1. During a recent inspection of the Kashiv BioSciences, LLC (FEI 3011289655) manufacturing facility for this BLA, our field investigator conveyed deficiencies to the representative of the facility.

3011289655), Chicago, Illinois, is required before this application can be approved as the FDA must assess the ability of that facility to conduct the listed manufacturing operations in compliance with CGMP.

Due to U.S. Government and/or Agency-wide restrictions on travel, we were unable to conduct an inspection of the Kashiv Biosciences LLC facility during the current review cycle, and the application cannot be approved until the required FDA inspection is conducted and the findings are assessed with regard to this application.

(6) During a recent inspection of the om (FEI: 19) manufacturing facility for this application, our field investigators conveyed deficiencies to the representative of the facility.

BLA, which is anticipated in mid-2022. In addition, the FDA's facility inspection schedule which has been affected by COVID-19-related travel restrictions, is required before the FDA can approve the NexoBrid BLA.

An inspection of the Protalix Ltd. (FEl# 3008289067), Carmiel, Israel manufacturing facility is required before this application can be approved.

FDA must assess the ability of that facility to conduct the listed manufacturing operations in compliance with CGMP.

However, even if these deficiencies are addressed, the application cannot be approved until the required FDA inspection is conducted and any findings are assessed with regard to your application.

FDA must assess the ability of these facilities to conduct the listed manufacturing operations in compliance with CGMP.

However, even if these deficiencies are addressed, the application cannot be approved until the required FDA inspections are conducted and any findings are assessed with regard to your application.

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.

If it is determined that an inspection is needed to approve your application, please note that FDA continues to monitor the public health situation as well as travel restrictions.

Comments about Facility Inspection Not Completed Due to Travel Restrictions:

However, even if these deficiencies are addressed, the application cannot be approved until the required FDA inspection is conducted and any findings are assessed.

During a recent inspection of the © facility for this application, our field investigators conveyed deficiencies to the representative of the facility at the close of the inspection.

In March 2019, MDD US Operations, LLC (formerly US WorldMeds, LLC) and its subsidiary, Solstice Neurosciences, LLC (US) (collectively, the MDD Subsidiaries), which are subsidiaries of the Company, entered into a Corporate Integrity Agreement (CIA) with the Office of Inspector General of the U.S. Department of Health and Human Services.

The Company submitted its final report during the second quarter of 2024 and received an official notification of release from the Office of the Inspector General in April 2025 and thus no longer remains subject to its obligations under the CIA.

12.An inspection of the TOYO PHARMACEUTICAL CO. LTD. facility (FEI 3016419927) located in Tsurumi-Ku, Osaka, Japan; is required before this application can be approved.

FDA must assess the ability of that facility to conduct the listed manufacturing operations in compliance with CGMP.

However, even if these deficiencies are addressed, the application cannot be approved until the required FDA inspection is conducted and any findings are assessed with regard to your application.

Contract Manufacturing Site for HTX-011: In February 2020, Heron announced that the contract manufacturing site used to manufacture HTX-011 has been reinspected by the FDA with no Form 483 observations issued and with a recommendation by the FDA inspector for approval of the site.

Satisfactory inspection is required before this application may be approved.

An inspection of the © facility is required before the application can be approved as the FDA must assess the ability of that facility to conduct the listed manufacturing operations in compliance with CGMP.

However, even if all other deficiencies are addressed, the application cannot be approved until the required FDA inspection is conducted and the findings are assessed with regard to your application.

During a recent inspection of the B. Braun Medical, Inc. manufacturing facility (FEI 2021236), our field investigator observed product specific and GMP compliance issues at the facility and conveyed that information to the representative of the facility at the close of the inspection.

During recent inspections of the Po drug substance manufacturing facility) and Intelgenx Corp., (FEI: 3005721224, drug product manufacturing facility) for this NDA, our field investigators conveyed deficiencies to the representatives of the facilities.

4) During the recent inspections of IntelGenx Corp. (FEI 3005721224) for oral film products, our field investigator observed objectionable conditions at the drug product manufacturing facility.

Please note that that this information will be reviewed by the Agency during the review of the application and a follow up Pre approval inspection may be needed to verify that the facility has taken necessary corrective actions to ensure oral film product quality.

All submitted facilities must be in compliance with cGMP before this application may be approved.

During a recent inspection of the | manufacturing facility for this application, our field investigator observed objectionable conditions at the facility and conveyed that information to the representative of the facility at the close of the inspection.

Do not submit actual inspectional correspondence to this application.

Note that as a follow-up to the pre-approval inspection, a Post-Action Memorandum with outstanding concerns will be sent to the inspected drug product facility.

Satisfactory resolution of the observations is required before this NDA may be approved or alternative manufacturing facilities which are in compliance with cGMPs must be included in the application.

We note that this is the second Complete Response letter for this NDA that has identified inspectional observations at this manufacturing facility as a deficiency.

We recommend that you work with this manufacturing facility for your insulin glargine product and apply the necessary resources to address these inspectional observations in a timely manner.

This determination is based upon information available to the Agency at this time [i.e., information in your application and the status of current good manufacturing practices (CGMPs) of the facilities used in manufacturing and testing of the drug product].

During a recent inspection of the | manufacturing facility for this application, our field investigator conveyed deficiencies to the representative of the facility.

During a recent inspection of the ow manufacturing facility for this application, our field investigator conveyed deficiencies to the representative of the facility at the close of the inspection.

1. Reference is made to the pre-license inspection at Immunomedics Inc. (Morris Plains, NJ) and subsequent communications between Immunomedics and the Agency:

During a recent inspection of the Immunomedics, Inc., (FEI 1000526871) manufacturing facility for this BLA, our field investigator observed objectionable conditions at the facility and conveyed that information to the representative of the facility at the close of the inspection.

CFR 210 and 211. During a recent inspection of the Bausch & Lomb Inc. (FEI 1000113778) manufacturing facility for this application, our field investigators conveyed observations to the representative of the facility.

Additionally, on May 15, 2018, the Company was informed that the FDA issued to Daewoong Pharmaceutical Co., Ltd. ("Daewoong"), the licensor and manufacturer of DWP-450, an Establishment Inspection Report ("EIR") confirming the completion of the pre-approval inspection of Daewoong's manufacturing facility for DWP-450.

19. In your response to our IR dated February 12, 2018, you explain that visual inspection is performed on all Theragrastim DP vials and syringes manufactured in a lot.

This CRL relates to matters noted in a Warning Letter issued in February 2017 following a routine FDA inspection of Pfizer's manufacturing facility in McPherson, Kansas in 2016. This facility was listed as the potential manufacturing site in the BLA for the proposed epoetin alfa biosimilar.

8. During the facility inspection, it was noted that different equipment was used for the manufacture of clinical trial supplies as compared to that proposed for the commercial product.

Inspection requests may be resubmitted upon receipt of your Complete Response submission.

Satisfactory inspection is required before this application may be approved.

During recent inspection of Sindan-Pharma S.R.L (FEI: 3005566806) manufacturing facility for this application, our field investigators conveyed deficiencies to the representative of the facility.

In each of July 2016 and July 2017, we also received a Complete Response Letter, or CRL, from the FDA regarding our NDA for DEXTENZA pertaining to, among other things, the deficiencies in manufacturing processes, controls, and analytical testing identified during pre-NDA approval inspections of our manufacturing facility documented on Form 483s.

Research, or CDER, including the Office of Process and Facilities, with regard to manufacturing issues and our plans for a resubmission to the NDA. In October 2016, we met with the FDA to discuss our plans for resubmission to the NDA and to attempt to gain clarity on the likelihood of a re-inspection of our manufacturing facility.

Research, or CDER, including the Office of Process and Facilities, with regard to the manufacturing issues and our plan for a resubmission of our NDA. In October 2016, we met with the FDA to discuss plans for resubmission to the NDA and to attempt to gain clarity on the likelihood of a re-inspection of our manufacturing facility.

· Subject to addressing the FDA inspectional observations and demonstrating consistency in future manufacturing runs, the Company plans to resubmit its NDA for DEXTENZA in the first half of 2018.

Satisfactory resolution of these cGMP deficiencies is required before this application may be approved.

Separately, in response to the COVID-19 pandemic, the FDA temporarily postponed routine surveillance inspections of manufacturing facilities in 2020. Additionally, the current administration announced plans to reduce the number of federal employees by establishing voluntary termination programs, by position eliminations or by involuntary terminations.

The Agency expects all facilities involved in the manufacture, processing, packing or holding, which includes packaging and labeling operations, testing and quality control, of the drug product to be ready for inspection at the time of application submission.

During a recent inspection of the Baxter Healthcare manufacturing facility in Cleveland, MS for this application, our investigator conveyed deficiencies to the representative of the facility.