Issued January 1, 2018
Issued
January 1, 2018
Application
Other • 208276
Review center
Other
Stage
Final Decision
Letter type
Approval Letter
The FDA issued a Complete Response letter for New Drug Application (NDA) 208276 for the Implantable System for Remodulin (treprostinil) solution for injection, indicating that the application cannot be approved in its current form. The primary reasons for non-approval include the device component not being approvable, insufficient human factors data for safe and effective use, and insufficient data regarding the risk of microbial contamination in the implantable pump system.
The application cannot be approved in its current form primarily due to outstanding issues with the device component of the combination product, including its overall approvability and insufficient human factors data. Additionally, the agency requires a unified prescribing information, resubmission of the proprietary name, and a comprehensive safety update.
The device component of the combination product received a Not Approvable letter on its PMA. The NDA for the drug-device combination product cannot be approved until the device is determined to be approvable.
Recommended response: Address all outstanding deficiencies for the device component's PMA to achieve approvability, as this is a prerequisite for NDA approval.
Sufficient human factors (HF) data has not been provided to demonstrate that the Implantable System for Remodulin (ISR) user interface supports safe and effective use for intended users, uses, and environments. Original HF deficiencies from March 11, 2016, and February 9, 2017, remain outstanding. The ISR user interface and training plan must be optimized and validated per 21 CFR 820.30. Recommendations include re-evaluating HF validation study results, implementing additional mitigations, finalizing the training program, and supplying additional HF validation data. Submit the HF validation study protocol for agency review.
Recommended response: Re-evaluate HF validation study results, implement additional mitigations, finalize the training program, and provide comprehensive HF validation data. Submit the HF validation study protocol for agency feedback prior to commencing the study.
Cited: 21 CFR 820.30
Final comment on proposed labeling is reserved until the application is otherwise adequate. Propose a unified Prescribing Information incorporating the Implantable System for Remodulin into the existing Remodulin label. Submit updated content of labeling in structured product labeling (SPL) format, including a highlighted/marked-up copy and a clean Microsoft Word version.
Recommended response: Develop a unified Prescribing Information for the combination product, ensuring compliance with PLR requirements and submission in SPL format with both marked-up and clean versions.
Cited: 21 CFR 314.50(l)(1)(i)
The proposed proprietary name, Implantable System for Remodulin, was found acceptable pending approval of the application. It must be resubmitted when responding to the application deficiencies.
Recommended response: Resubmit the previously accepted proprietary name with the complete response to the application deficiencies.
A safety update, as described in 21 CFR 314.50(d)(5)(vi)(b), must be included with the response to deficiencies. This update should detail significant changes in the safety profile, present new safety data from all studies/trials, provide updated exposure information, and summarize worldwide experience.
Recommended response: Prepare a detailed safety update encompassing all new nonclinical and clinical data, updated exposure information, and worldwide experience, adhering to the requirements of 21 CFR 314.50(d)(5)(vi)(b).
Cited: 21 CFR 314.50(d)(5)(vi)(b)
Approval is withheld due to critical deficiencies related to the device component's approvability and human factors validation for this drug-device combination product. Additional requirements include updating labeling, resubmitting the proprietary name, and providing a comprehensive safety update.
Regulatory change impact: Pending sponsor mitigation plan
Approval likelihood after response: 5%
Document viewer
Read the FDA letter and send context to the co-pilot at any time.