Unresolved cGMP observations at manufacturing facility
Severity: criticalThe methods to be used in, and the facilities and controls used for, the manufacture, processing, packing and holding of the drug substance and the drug product must comply with the current good manufacturing practice (cGMP) regulations in 21 CFR 210 and 211. During the pre-approval inspection of the manufacturing facility for this NDA, 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. 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.
Recommended response: Address all outstanding cGMP observations at the manufacturing facility or propose an alternative, compliant manufacturing site.
Cited: 21 CFR 210, 21 CFR 211
Insufficient clinical use data for SCS Microinjector Delivery System
Severity: majorThere is insufficient information about the drug product to determine whether the product is safe for use under the conditions prescribed, recommended or suggested in the proposed labeling. Clinical use data should be submitted to support the use of the final to-be-marketed SCS Microinjector Delivery System. The final to-be-marketed configuration should be evaluated by at least three physicians and in at least 30 patients.
Recommended response: Conduct and submit clinical use data for the final to-be-marketed SCS Microinjector Delivery System, involving at least three physicians and 30 patients.
Insufficient manufacturing process robustness and stability data for registration batches
Severity: majorPlease provide data generated from three new registration batches using the proposed commercial process to demonstrate process robustness and product meeting quality standards of efficacy, stability, and safety. Please provide at least one registration batch with 3 months stability data at long term storage and 3 months stability data at accelerated condition.
Recommended response: Generate and submit data from three new registration batches using the commercial process, including 3 months of long-term and accelerated stability data for at least one batch.
Non-compliance with patent certification requirements for amendments
Severity: minorOne or more amendments to your pending application does not comply with 21 CFR 314.60(f), which was added by the final rule on Abbreviated New Drug Applications and 505(b)(2) Applications; Final Rule, 81 FR 69580 (October 6, 2016). Section 314.60(f) requires that an amendment to an unapproved 505(b)(2) application contain an appropriate patent certification or statement described in 21 CFR 314.50(i), or a “recertification” for a previously submitted paragraph IV certification, if approval is sought for changes described in any of the following types of amendments: to add a new indication or other condition of use; to add a new strength; to make other than minor changes in product formulation; or to change the physical form or crystalline structure of the active ingredient. If an amendment to the 505(b)(2) application does not contain a patent certification (or recertification) or statement, you must verify that the proposed change described in the amendment is not one of the types of amendments described above. Please provide a list of your amendments submitted to FDA on or after December 5, 2016, clearly referencing each amendment by submission date, and either: i. state that the amendment contains a patent certification (or recertification) or statement required by 21 CFR 314.60(f)(1); or ii. verify that the proposed change described in the amendment is not one of the types of amendments described in 21 CFR 314.60(f)(1), as appropriate. The cover letter for your Complete Response and all future amendments to your unapproved 505(b)(2) application should continue to address the requirements under 21 CFR 314.60(f).
Recommended response: Review all amendments submitted since December 5, 2016, and provide a comprehensive list, ensuring each amendment either includes the required patent certification/statement or verifies that the change does not trigger such a requirement.
Cited: 21 CFR 314.60(f), 21 CFR 314.50(i)
