scPharmaceuticals Services, IncFuroscix™ “(Furosemide), 80 mg/10 mL, Drug-device combination product

NDA 209988 COMPLETE RESPONSE

scPharmaceuticals Services, Inc

Attention: Eric Kendig, PhD

Director, Regulatory Strategy

c/o: Camargo Pharmaceuticals Services, LLC 9825 Kenwood Road, Suite 203

Cincinnati, OH 45242

Dear Dr. Kendig:

Please refer to your new drug application (NDA) dated August 23, 2017, received August 23, 2017, and your amendments, submitted pursuant to section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act for Furoscix™ “(Furosemide), 80 mg/10 mL, Drug-device combination product.

We acknowledge receipt of your amendment dated June 30, 2020, which constituted a complete response to our June 11, 2018, action letter.

We have completed our review of this application, as amended, and have determined that we cannot approve this application in its present form. We have described our reasons for this action below and, where possible, our recommendations to address these issues.

Device

1. In SNO040, Section 1.12.4, you state, “scPharmaceuticals and West have subsequently [(i.e. since NDA 209988 resubmission in SN0034)] explored a further modification ™@ anda corresponding software parameter adjustment.” You have made significant changes to the design of your to-be-marketed device during this review cycle without the FDA’s prior knowledge. It is our expectation that you submit your to- be-marketed device and all finalized documentation to support your device functions safely and effectively when responding to a Complete Response or submitting a new application. In addition, changing your device during the review cycle raises additional questions regarding its safety and efficacy and the relevance of all the presented documentation. Therefore, we cannot determine whether the information presented in the original submission supports the safety and effectiveness of the to be marketed design. In responding to this Complete Response (CR) Letter, please make sure all submitted information is representative of your to-be-marketed device. Any testing performed on a previous

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version of your device should be clearly stated and the relevance of said testing should be justified. Please note that due to the device changes, additional deficiencies may be identified once the final device design is submitted.

Ora You reference Master Access File (MAF) oe for significant documentation to support the device constituent of your combination product. There are outstanding deficiencies, which have been separately communicated to the MAF Holder. We recommend: a) you work with MAF Holder to ensure adequate resolution of the identified deficiencies, and b) resubmit your NDA only once the deficiencies are all resolved and adequate documentation is present in the MAF.

Biocompatibility

3.

In report “device-rpt-0352”, you stated that there are differences between the

biocompatibility test article and the final finished product. hey (b) (4)

©. To ensure the final finished device has particulate matters within acceptable range, please provide particulates testing per USP <788> method 1 light obscuration method on the final finished device.

In report “device-rpt-0351” titled Furoscix Drug Compatibility and Particulates with Smart Dose Fluid Path, you provided particulates testing for fluid path, and stated that the testing was conducted per USP <788>. However, it is not clear whether method 1 Light Obscuration Particle Count Test or method 2 Microscopic Particle Count Test from USP <788> was performed. For devices intended to deliver infusion drugs, we recommend particulates testing using USP <788> method 1 light obscuration method. Please clarify which method was used. If method 2 was used, please provide particulates testing per USP <788> method 1 light obscuration method.

In report “3.2.R1P3 — Device Summary”, Table 7 Test Plan and Results Summary, ISO was used to address adhesive patch cytotoxicity endpoint; however, in report “device-rpt-0352,” you provided a summary of Cytotoxicity Study Using the ISO Direct Contact Method for adhesive patch. Please clarify which method is used to evaluate cytotoxicity endpoint for adhesive patch.

a. Please ° (b) (4)

(b) (4)

justification for this method.

Chemical Characterization

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6. You provided the leachable report in the “Leachables Screening of

scPharmaceuticals Inc.'s Furoscix® (Furosemide) Injection in Contact with SmartDose® Gen II 10 mL Fluid Path Assembly” document. In the sample preparation, the drug product was delivered through the fluid path using

™® However, it is unclear if the extraction occurred under clinically relevant conditions. The sample preparation should be performed under clinically relevant conditions to represent the use of the device. Please discuss and clarify if the sample preparation and test extract method is clinically relevant. Alternatively, provide new testing under clinically relevant conditions.

You provided the leachable report in the “Leachables Screening o scPharmaceuticals Inc.' s Furoscix® (Furosemide) Injection in Contact with SmartDose® Gen II 10 mL Fluid Path Assembly” document. In the GC/MS direc! injection results, you reported spike recoveries. However, of

™® ‘it is unclear how you will ensure tha’ the semi-volatile and volatile compounds of the sample are detected. Provide a rationale justifying that the methods are appropriate for detecting semi-volatile and volatile compounds or provide new testing using appropriate methods.

Electrical Safety and Electromagnetic Compatibility

8. Your labeling does not contain adequate electrical safety and electromagnetic

compatibility, as recommended in the IEC 60601-1 series. Please address the following:

a. Label-0063-ifu states, "Do not use the on-body infusor within 12 inches of mobile phones, computers or wireless accessories (for example: TV remote control, Bluetooth computer keyboard or mouse)." However, this warning does not include sufficient EMC information. As is recommended by clause 5.2.1.1.f of IEC 60601-1-2:2014, please revise this warning to “WARNING: Portable RF communications equipment (including peripherals such as antenna cables and external antennas) should be used no closer than 30 cm (12 inches) to any part of the FUROSCIX On-Body Infusor. Otherwise, degradation of the performance of this equipment could result.”

b. Label-0063-ifu does not include essential performance information. As is recommended by clause 5.2.1.1.b of IEC 60601-1-2:2014, please include your device’s essential performance information in your Instructions for Use.

c. Your device includes a battery. However, label-0063-ifu, label-0068, label- 0069, label-0072, and label-0073 do not contain battery information (i.e. battery specifications including the type, RATED voltage, and power), as is recommended per IEC 60601-1. Please provide the battery information (battery specifications including the type, RATED voltage, and power) in your labeling.

Labeling

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9. We acknowledge your response in your SNO036 Section 1.11.1 response to IR #2c, d, e, 3f stating you will update your labeling. You have not; however, updated your labeling as requested. Your labeling needs to warn users against the hazards present in your system. Given the systemic issues in your submission, we recommend you revise your labeling and ensure that your labeling contains the following information, specifically, and follows the guidance in the listed FDA guidance documents:

a. Electrical Safety Labeling/Symbols b. EMC Labeling/Symbols c. Software version d. Factors affecting accuracy e. Residual/hold-up volume f. Warnings/symbols regarding use in CT, ultrasound, and X-ray environments. g. Design Considerations for Devices Intended for Home Use from November 2014 (https://www.fda.gov/media/84830/download) h. Infusion Pumps Total Product Life Cycle from December 2014 (https://www.fda.gov/media/78369/download) Please provide the originally requested labeling updates sent on July 22, 2020 and ensure your labeling matches your proposed use-case.

10.In your SNO036 Section 1.11.1 response to IR #2a, you state, “The Furoscix Infusor is intended to be applied to the patient in a clinic or a home setting and was validated in these environments. | ®® You have provided insufficient evidence {i

™®and your response to the IR #2a,

remains incomplete. Update your device’s Instructions for Use (b) (4)

Human Factors 11.We note that you conducted a validation of adhesive effectiveness and local skin tolerability of the medical adhesive used to attach the on-body infusor to the patient, and that the study protocol lists the following exclusion criteria for the study participants [Clinical Protocol No. scP-00-003 - Appendix 16.1.1 Protocol and Protocol Amendments.pdf Section 4.2, page 24]:

4.2. Exclusion Criteria - A Subject is not eligible for inclusion if any of the following criteria apply:

1. History of chronic skin conditions requiring medical therapy.

2. History of allergy to medical adhesives.

3. Received oral antihistamines (Benadryl, Allegra, Zyrtec, etc.) or systemic steroids (e.g. prednisone, dexamethasone, etc.) in past 7-days.

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4. Used body lotions, oils or ointments on abdomen (adhesion area) within past 24 hours.

5. History of major abdominal surgery affecting the site of device placement.

6. Any local abdominal skin condition on the day of treatment i.e. sunburn, rash, eczema, etc.

7. Any surgical or medical condition which in the opinion of the Investigator may interfere with participation in the study or which may affect the outcome of the study.

However, we note that your human factors/usability use-related risk analysis does not assess the risk of a patient applying the infusor if they have the characteristics listed in items 1 through 6 above. We further note that information about these characteristics does not appear in the proposed Instructions for Use (IFU) of your proposed subject device beyond the statement in Step 4: “Do not select a site where the skin is irritated or broken.” This is important because a patient with these characteristics could experience skin injuries from the medical adhesive or that the device could fail to adhere to the skin over the time of treatment. Please submit an updated use-related risk analysis that assesses the risk to the patient of using the device if the patient has these characteristics. If you determine that the related tasks are critical tasks, please update the instructions for use with your proposed tisk mitigations (e.g., contraindication statements, warnings), and submit supplemental human factors validation study data to demonstrate that the device can be used safely and effectively by the intended users for the intended use, or provide a justification for not conducting a supplemental human factors study. In addition, please add the appropriate contraindications to OM the Prescribing Information (Pl) or provide a justification addressing why this information does not need to be provided to the intended prescribers of your proposed subject device.

12.We acknowledge your human factors (HF) study report included with your June 30, 2020, Class 2 resubmission. However, your Device Improvement Report submitted on September 29, 2020 indicates that your proposed device was modified subsequent to the HF study. We expect the HF validation study to be conducted with your to-be-marketed device. Furthermore, it is unclear whether the device modifications affect critical tasks associated with the safe and effective use of the device or require changes to your Instructions for Use (IFU). Thus, additional information is necessary to determine whether the modified device can be used safely and effectively.

We recommend you update your comprehensive use-related risk analysis taking into consideration the device modifications. The comprehensive use-related risk analysis should include a comprehensive and systematic evaluation of all the steps involved in using your product (e.g., based on a task analysis) the errors that users might commit or the tasks they might fail to perform and the potential negative clinical consequences of use errors and task failures.

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Software/Cybersecurity 13.We could not locate information regarding your alarms/errors in your Master File.

Based on the aforementioned information and data, you should determine whether you need to submit the results of another human factors (HF) validation study conducted under simulated use conditions with representative users performing necessary tasks to demonstrate safe and effective use of the product. If you determine that another HF validation study does not need to be submitted for your product, submit your risk analysis, comparative analyses, and justification for not submitting another HF validation study to the Agency for review when you respond ‘0 the application deficiencies. The Agency will notify you if we concur with your determination.

The comparative analyses should include a labeling comparison, a comparative ‘ask analysis, and a physical comparison between the user interface that was validated in your HF validation study and your modified user interface for the purposes of identifying what differences exist between the user interfaces.

If you determine that you do need to submit a HF validation study for your product, he risk analysis can be used to inform the design of a human factors validation study protocol for your product. We recommend you submit your study protocol for eedback from the Agency before commencing your study. Please note we will need 60 days to review and provide comments on the HF validation study protocol. Plan your development program timeline accordingly. Note that submission of a protocol for review is not a requirement. If you decide not to submit a protocol, this approach carries some risk to you because prospective Agency review is not possible, but this is a decision for your company.

The specific requests are communicated to the Master File Holder. As your device is a software medical controlled device, there remain items which you need to identify in your Safety Assurance Case to demonstrate you have adequately defined and verified your software. Please work with the Master file holder and update your Safety Assurance Case to contain the specific information the Master File is instructed to provide to you. This includes:

a. Reliability specifications for your system level alarms/errors.

b. Code coverage requirements for static testing in your reliability section.

Engineering/Performance/Risk Assessment

14. In your SNO036 Section 1.11.1 response to IR #2b, |

©® your justification for not requiring fluid ingress

testing is not adequate for the following reasons: e You provide no evidence that your device design adequately mitigates against fluid ingress. e You refer to a component in your design have changed (See deficiency #1).

© which you

(b) (4)

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Safety Assurance Case: Introduction

(b) (4)

Your device is an on-body infusion pump. There are several user-created routes of fluid and particulate ingress (e.g., washing hands following going to the bathroom). There are credible avenues for fluid and particulate ingress allowed because of your use-case. Furthermore, you have requirements for certain parts of your device to be protected from fluid/particulate ingress in order for the device to function safely and effectively. Provide ingress testing and labeling commensurate with your use-case.

15. Your response in SNO036 Section 1.11.1 to IR #4a is incomplete. You did not

(b) (4) (b) (4)

provide the trigger limits to your alarm function

©) As your response is incomplete, the original request remains. Please provide the trigger limits for all your alarms and ensure these are challenged at your boundary conditions through verification testing to ensure adequate function.

16.In your response in SNO036 Section 1.11.1 to IR #4b, you state, a

(b) (4)

® Please redesign your device to include error notification in a timely fashion so that a user does not unknowingly experience an underdose event for a significant period of time or provide scientifically (i.e., clinically) valid rationale for the selected © error notification time.

In SNO040 you declare a modification has been made to the device (See Deficiency #1). You have not updated your Safety Assurance Case (SAC) based on the modifications discussed. Therefore, your provided SAC contained in SN0034 device- ra0048 is considered irrelevant. A complete SAC is needed to demonstrate the device is safe for its intended use through (1) adequate verification and validation of design requirements, (2) adequate risk mitigations and (3) demonstration of adequate reliability. Therefore, provide a SAC containing all the elements described in the Agency Guidance Document “Infusion Pumps Total Product Life Cycle” (https://www.fda.gov/media/78369/download) for your to-be-marketed device and

address the following high level structural deficiencies as well as those associated with each of the three sections of the safety assurance case:

Safety Assurance Case: Structural Deficiencies

17.All referenced evidence in the safety assurance case should be provided. You did

not include references to all the evidence in your new safety assurance case. For a we); f i S a . example, citing MAF is an inadequate location for evidence. Citing a file

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name is also inadequate, as you have continued to update your device and design; you should include the sequence and/or revision of the file with the file number as it is listed in your submission. Please provide complete reference information for your cited evidence in your SAC. We recommend you work with the MAF holder to gain all applicable reference document pointer information prior to submitting your updated SAC. 18. (b) (4) o@ It remains unclear how you link your performed testing back to the hazards in your system. Your SAC does not trace clearly from your system- level requirements to the performed testing to mitigate hazards, and the specific hazard present. While we note you provide DD-0094 for Design Inputs/Outputs and Hazard and Risk Analyses in RA-0043 and RA-0047, it remains unclear how you trace between your requirements and your hazards to ensure that your testing as mitigated your identified hazards. Please provide a Design Verification and Validation Plan that details your sampling plan, sampling justifications, aging approach, and verification output methods (i.e., specific reports) which traces between the hazards present in your system and your performed testing of your to-be-marketed device.

19. Your SAC does not include justification for the adequacy of your specifications for

your intended use. om (b) (4)

®® Define and justify the adequacy of all your design requirements with scientifically valid rationale. If you determine a consensus recognized standard can be used to demonstrate adequacy of your requirements, please see the recommendations in Adequate Verification and Validation of Design Requirements. Safety Assurance Case: Adequate Verification and Validation of Design Requirements 20.You provide a list of standards in 3.2.R.1.P.3.2 and state that evidence of conformity is contained in individual test reports. However, you did not provide adequate evidence for conformance with FDA recognized standards. Please address the following deficiencies:

(b) (4) a. (b) (4)

wey

When utilizing FDA recognized standards, you should follow the recommendations for documenting such conformance in the Agency Guidance, “Appropriate Use of Voluntary Consensus Standards in Premarket Submission for Medical Devices: Guidance for Industry and Food and Drug Administration Staff’ (https://www.fda.gov/media/71983/download). For FDA _ recognized standards you intend to claim conformity, you will need to provide the

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information in the listed guidance. Alternatively, you can independently demonstrate the acceptability of the methods for evaluating design requirements.

b. In3.2.R.1.P.3.2 you state, Co (b) (4)

© All allowances should be clearly stated, and their adequacy justified. Please see the aforementioned guidance document “Appropriate Use of Voluntary Consensus Standards in Premarket Submission for Medical Devices: Guidance for Industry and Food and Drug Administration Staff,” and clearly state all allowances taken for consensus recognized standards.

(©) (4)

© "If you are using a standard which is not recognized for your device-type (i.e., an infusion pump), you should justify the adequacy of the standard for your use-case. Please justify the use of standards which are not recognized for your device type. Alternatively, you can independently demonstrate the acceptability of the methods for evaluating design requirements.

d. You discuss your device’s design control process in 3.2.R.1.P.3.1. You do not mention the word ‘regulatory’ in this document. You should complete your device development activities prior to seeking regulatory approval. Specifically, you should receive regulatory approval before completion of

®® and commercialization of your product. We remind you that it is our expectation that you submit your to-be-marketed device for regulatory review and we note you have continued to make changes to your device (Deficiency #1). Therefore, we believe your approach to device design control is inadequate. Revise your approach to design controls to ensure your design is ‘frozen’ before seeking initial regulatory approval. Only submit your device for regulatory review once you have determined the design which you intend to market.

21.You provide device-ddp0038 as your Verification and Validation Plan. However, this document is inadequate for several reasons which are detailed. Without an adequate and complete Verification and Validation Plan, we are uncertain of the relevance of the documentation you present to demonstrate your design requirements have been adequately verified and validated. In order of us to ensure your device is safe and effective, please revise your device design verification and

validation plan and evidence to address the following: a. You point to files within MAF oor significant evidence of your

verification and validation activities. We note the Master File documentation

refers to different risk and sampling documentation than your submission.

We do not know which documentation drives your design, including your U.S. Food and Drug Administration

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requirements, system risks, and sample sizing. Please work with the Master File holder and present unified documentation which contains all the necessary information to understand your design intent and testing design approach.

Your Verification and Validation Plan lacks significant detail expected in this document. Please revise your plan or provide specific pointers to the location of the following documentation locations within your Verification and Validation Plan: i. Sampling Plan ii. Statistical Methods/Approaches iii. Aging Plan iv. Description of the samples used for testing. We note you have changed your device during the review cycle (Deficiency #1). We specifically request that you state for EACH report if the to-be- marketed device is used as test samples. If the samples differ from the to-be-marketed device in ANY manner (form, fit, function, etc.), you should explain this clearly and justify why the modification to the

samples does not impact the results of the testing (b) (4)

We note there are reports in MA which you do not refer to and cont in, the information you need. For example, the information in MAF © does not verify your device © shelf life © "You refer to MAF Les © but there is no Report ‘x.’ Please work with the Master File Holder and refer to the correct documentation evidence in your SAC to support your argument.

We are unable to locate evidence which you refer to in device-ddp0038 (Verification and Validation Plan). For example, we are unable to locate Report-0332: This document is not referred to in your Reviewer Guide. We are unable to review evidence if we cannot locate the referenced information. Please ensure all necessary evidence is contained in your submission.

The evidence you are using to support the safety and efficacy of your device is known to have changed (Deficiency #1). For example, scP-00-004 in SN0040 is not referenced by device-rpt-0360. Provide a revised Verification and Validation Summary and SAC which references the current applicable documentation, including report revision, so we are certain of the evidence you are using to demonstrate your device is safe and effective.

You state several requirements do not require validation. We disagree this this assessment. You need to demonstrate that your device performs as designed (i.e., verification) and the design is adequate for your intended use (i.e., validation). Design Validation is part of 21 CFR 820.30 which is

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required for combination products. Please provide validation evidence or an

explanation of adequacy for the following requirements: oe

g. You do not provide evidence for all the expected Essential Performance Requirements for an Infusion Pump, such as Flow Rate Accuracy. Without defining, verifying, and validating the requirements for your device, we are uncertain how you have determined your device is adequate for your intended use. Please identify all essential performance requirements and provide corresponding evidence to support the verification and validation for each requirement.

h. The data you provide to demonstrate your requirements are met are inadequate. These data are principally contained in the referenced MAF Please work with the Master File Holder to resolve the deficiencies in

the Master File documentation.

22.In summary, to support the adequate verification of your design requirements, you should provide evidence in the form of test reports which contain clear objectives and quantitative scientific evidence that your design functions to its specification. The test reports you cited lacked all the elements described in the FDA Guidance Document “Recommended Content and Format of Non-Clinical Bench Performance Testing Information in Premarket Submissions” (https://www.fda.gov/media/113230/download) from December 2019. Therefore, please provide test reports which contain clearly defined, objectives, acceptance criteria (including sample sizing based on the associated risks with statistically valid rationale), verifiable objective evidence, analysis, and conclusions so that we can determine whether the evidence supports the device meets the specifications. Please be aware it remains our expectation that you demonstrate your device functions at its labeled boundary conditions. Please provide design verification which evaluates all design requirements at the appropriate boundary conditions of use and demonstrate that your requirements are adequate for your intended use.

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Safety Assurance Case: Adequate Risk Mitigations

23. Your SAC should be driven by the risks in your system, as properly acknowledging

24. You define your severity ratings in SOP-0034.

and addressing the risks associated with your device is essential to understanding your design methodology and verification activities. Your SAC lacks clear tracing between risks and mitigations. Please update your SAC to include proper reference to your risk documentation. Determination of the acceptability of your tisk mitigations is contingent upon successful testing. Please see our comments regarding verification and validation evidence and on your risk documentation.

(b) (4) (b) (4)

© Please provide adequate

mitigations for all severities rated © OR revise your definitions of severity rating based on the need to require medical intervention. If you choose to revise your severity ratings, please ensure your severity assignments are adequate and relate to the risks associated with the stated hazard. Additionally, ensure that your hazard assignments and sampling approaches align to the methods used by the Master File Holder.

25. Your Hazard and Risk Analyses contained in RA-0043 and device-ra0047 and

RCM analysis in device-ra0049 does not clearly illustrate how you mitigate each of your risks. Please update your Hazard Analysis and other referenced risk documentation to specifically illustrate how you mitigate the known risks in your system and ensure that this argument is included in your safety assurance case.

In addition to the overall strategy of the document needing clarification and update,

please address the following specifically: (b) (4) a.

Provide mitigations to all hazards requiring medical intervention. b. Your hazards do not clearly alian to the stated risks. “a

®®Please update your risk documentation to ensure

your hazards and risks align.

c. There are several hazards which do not align to your device design. We believe these are related to a previous version of your device. Please update your hazard analysis to be specific to your device design. This includes the risks associated with charge errors, AC supply errors, battery

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over/under charge, key de-bounce prevention, alarm priority being set incorrectly, incorrect drug library loaded, inadequate device cleaning.

d. We recommend that all hazards, including software only related hazards, are classified by severity For software specifically, it is not possible to predict © software only hazards. You may use a probability of harm if the software hazard occurs.

Safety Assurance Case: Demonstration of Adequate Reliability

26. You have changed your device during this review cycle. Therefore, your provided reliability argument should be revised to be specific to your to-be-marketed device and your proposed use case. The relevance of your documentation is unknown. Please provide updated reliability documentation to support the reliability of the to be marketed device.

27.While we acknowledge your submission of device-memo-0079 Rev 02 containing your reliability analysis, this document does not appear to be governed by a reliability protocol to define your testing. In addition, there are issues with the identified MAF reports in this memo which are communicated to the MAF holder. Your reliability analysis should clearly illustrate, based on prospective testing and analysis, how you achieve the reliability requirements commensurate with your system hazards. Please define a reliability requirement and provide an evidence- based argument for your to-be-marketed device to demonstrate the device's ability to meet this requirement.

28.We note you do not link your reliability argument to the clinical risks associated

with your device. F

®© Your device is outside the (b) (4)

FDA recognized scope

Please see our recommendations under Adequate Verification and Validation of Design Requirements and ensure that your reliability arguments align to the clinical use-case of your device.

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PRESCRIBING INFORMATION

We reserve comment on the proposed labeling until the application is otherwise adequate. We encourage you to review the labeling review resources on the PLR Requirements for Prescribing Information’ and Pregnancy and Lactation Labeling Final Rule? websites, including regulations and related guidance documents and the Selected Requirements for Prescribing Information (SRPI) - a checklist of important format items from labeling regulations and guidances. Your proposed Prescribing Information (PI) must conform to the content and format regulations found at 21 CFR 201.56(a) and (d) and 201.57. As you develop your proposed PI, we encourage you to review the labeling review resources on the PLR Requirements for Prescribing Information? and Pregnancy and Lactation Labeling Final Rule* websites, which include:

e The Final Rule (Physician Labeling Rule) on the content and format of the PI for human drug and biological products

e The Final Rule (Pregnancy and Lactation Labeling Rule) on the content and format of information in the PI on pregnancy, lactation, and females and males of reproductive potential

e Regulations and related guidance documents e Asample tool illustrating the format for Highlights and Contents, and

e The Selected Requirements for Prescribing Information (SRPI) - a checklist of important format items from labeling regulations and guidances.

e FDA's established pharmacologic class (EPC) text phrases for inclusion in the Highlights Indications and Usage heading.

Prior to resubmitting the labeling, use the SRPI checklist to correct any formatting errors to ensure conformance with the format items in regulations and guidances. Your response must include updated content of labeling [21 CFR 314.50(I)(1)(i)] in structured product labeling (SPL) format as described at FDA.gov.®

’ http:/Awww.fda.gov/Drugs/GuidanceComplianceRequlatoryInformation/LawsActsandRules/ucm08415 2 Tipit Ja. oow/Drugs/DevelopmentApprovalP rocess/Developmentfiesources/Labetingtuom08330 Frit tvww fda. gov/Drups/ Guidance Compllancefiequlatory information awsActsandFules/uom0841 5 + Hin /mww-fda.qov/Drugs/DevelopmentApprovalProcess/DevelopmentResourcesy/Labeling/uem09330 7 itn ww fa.qov/Forlndustry/DataStandards/StructuredProduetlabeling/detault him

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To facilitate review of your submission, provide a highlighted or marked-up copy that shows all changes, as well as a clean Microsoft Word version. The marked-up copy should include annotations that support any proposed changes.

PROPRIETARY NAME

Please refer to correspondence dated, September 9, 2020, which addresses the proposed proprietary name, Furoscix. This name was found acceptable pending approval of the application in the current review cycle. Please resubmit the proposed proprietary name when you respond to the application deficiencies.

FACILITY INSPECTIONS

Facilities Not Found Acceptable we

During a recent inspection of the manufacturing facility for this application

(b) (4) ry ' . our field investigator conveyed

deficiencies to the representative of the facility. Satisfactory resolution of these deficiencies is required before this application may be approved.

Comments about Facility Inspection Not Completed Due to Travel Restrictions: 1. An inspection of the Sharp Corporation (FEI # 3004161147, Allentown, PA) 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. Due to restrictions on travel, we were unable to conduct an inspection during the current review cycle for your application. You may respond to deficiencies in this Complete Response Letter while the travel restrictions remain in effect. However, even if these deficiencies are addressed, the application cannot be approved until the required FDA inspection is conducted and any findings are assessed. We will continue to monitor the public health situation as well as travel restrictions. We are actively working to define an approach for scheduling outstanding inspections, once safe travel may resume and based on public health need and other factors. For more information, please see the FDA guidances related to COVID-19. These guidances can be _ found at: https://www.fda.gov/emergency-preparedness-and-response/coronavirus- disease-2019-covid-19/covid-19-related-quidance-documents-industry-fda-staff- and-other-stakeholders.

(b) (4)

2. An inspection of 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. Due to restrictions on travel, we were unable to conduct an inspection during the current review cycle for your application. You may respond to deficiencies in this Complete Response Letter while the travel restrictions remain in effect. However, even if these deficiencies are addressed, the application cannot be approved until the required FDA inspection is conducted and any findings are

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NDA 209988 Page 16

assessed. We will continue to monitor the public health situation as well as travel restrictions. We are actively working to define an approach for scheduling outstanding inspections, once safe travel may resume and based on public health need and other factors. For more information, please see the FDA guidances related to COVID-19. These guidances can be found at https://www.fda.gov/emergency-preparedness-and-response/coronavirus- disease-2019-covid-19/covid-19-related-quidance-documents-industry-fda-staff- and-other-stakeholders

ADDITIONAL COMMENTS We have the following comments/recommendations that are not approvability issues: Our evaluation of the proposed labels and labeling identified areas of vulnerability that

may lead to medication errors. We have provided comments below and recommend that you implement them prior to resubmission of this NDA.

Identified Issues and Recommendations

Identified Issue Rationale for Concern Recommendation

General (for all Labels and Labeling)

1.| As proposed, your logo

name, Furoscix, on your

interferes with the proprietary

proposed labels and labeling.

The use of images or logos immediately before or after the proprietary name may lead to misinterpretation of the proprietary name. In this instance, we are concerned the name may be misinterpreted as

(b) (4) the logo appears to be part of the proprietary name.

We recommend that you revise the presentation of the proprietary name and the logo so that the logo does not interfere with the presentation of the proprietary name. For example, consider a larger space between the logo and the proprietary name, or address by other means.

Instructions for Use

©) 4) 2.| Your IFU can be improved to

decrease risk of wrong site of administration medication error,

U.S. Food and Drug Administration Silver Spring, MD 20993 www.fda.gov

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NDA 209988 Page 17

©)

We acknowledge that you have revised © to minimize confusion. However, we have identified additional labeling mitigations to address this error.

3.} Your IFU can be improved to We are concerned that Revise “

better illustrate one infusor is to | users may misinterpret be applied per dose. |" the shapes used |i}

(&) (4)

(b) (4)

PREA

We have completed our review of your revised Pediatric Study Plan (PSP) submitted August 22, 2019 and agree with your proposal. We have no further comments at this time.

OTHER

Within one year after the date of this letter, you are required to resubmit or take other actions available under 21 CFR 314.110. If you do not take one of these actions, we may consider your lack of response a request to withdraw the application under

21 CFR 314.65. You may also request an extension of time in which to resubmit the application.

A resubmission must fully address all the deficiencies listed in this letter and should be clearly marked with "RESUBMISSION" in large font, bolded type at the beginning of the cover letter of the submission. The cover letter should clearly state that you consider this resubmission a complete response to the deficiencies outlined in this letter. A partial response to this letter will not be processed as a resubmission and will not start a new review cycle.

You may request a meeting or teleconference with us to discuss what steps you need to take before the application may be approved. If you wish to have such a meeting,

U.S. Food and Drug Administration Silver Spring, MD 20993 www.fda.gov

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NDA 209988 Page 18

submit your meeting request as described in the draft guidance for industry Formal Meetings Between the FDA and Sponsors or Applicants of PDUFA Products.

The drug product may not be legally marketed until you have been notified in writing that this application is approved.

If you have any questions, please call Brian Proctor, Regulatory Project Manager, at (240) 402-3596.

Sincerely, {See appended electronic signature page}

Norman Stockbridge, MD, PhD

Director

Division of Cardiology and Nephology

Office of Cardiology, Hematology, Endocrinology and Nephrology

Center for Drug Evaluation and Research

U.S. Food and Drug Administration Silver Spring, MD 20993 www.fda.gov

Reference ID: 4711363

Signature Page 1 of 1

This is a representation of an electronic record that was signed electronically. Following this are manifestations of any and all electronic signatures for this electronic record.

NORMAN L STOCKBRIDGE 12/03/2020 02:43:31 PM

Reference ID: 4711363