Nubratori, Inc. dba Nubratori Rx — FDA Warning Letter Findings

Your response to observation #1A included updated SOP 3.83 Placing and Releasing (b)(4) from Quarantine and any current lots of (b)(4) were quarantined and sent out for growth promotion testing. However, you did not provide results of your growth promotion testing. Growth promotion testing should be performed on all lots of prepared media.

Your firm failed to validate and establish the reliability of your component supplier’s test analyses at appropriate intervals. (21 CFR 211.84(d)(2)) Outsourcing facilities must comply with CGMP requirements under section 501(a)(2)(B) of the FDCA. FDA’s regulations regarding CGMP requirements for the preparation of drug products have been established in 21 CFR parts 210 and 211. FDA intends to promulgate more specific CGMP regulations for outsourcing facilities. FDA has…

Your response to observation #5 states you sent out current Active Pharmaceutical Ingredient (API) for microbial and endotoxin testing. You also provided an updated procedure, SOP 3.58 Placing and Releasing API from Quarantine for review. However, you did not provide supporting documentation indicating your new limits for endotoxin and microbial counts in the updated SOP, nor did you provide rational as to how these limits were established. Additionally, you did not provide training information and documentation supporting your employees have been properly trained on your new process of evaluating incoming material. Some of your corrective actions appear deficient…

Your response to observation #3 included training documentation showing operators had been trained on updated SOP 4.11 Cleaning Procedure for Cleanroom Before and After Compounding . However, the updated SOP was not provided for evaluation.

Your firm failed to conduct microbiological testing before use of each lot of a component with potential for objectionable microbiological contamination in light of its intended use. (21 CFR 211.84(d)(6))…

We acknowledge your response to observation #2 and your statement that there was an unplanned deviation from your normal processes. Based on your response, due to this deviation, compounder (b)(4) was unable to return and assist with the batch, as a result, compounder (b)(4) could only take glove fingertip sampling at that moment. However, glove fingertip sampling should take place prior to sanitizing, as it can prevent recovery of microorganisms that were present during aseptic manipulation. While your firm provided training document detailing the information and training session provided to employees, not enough information was provided explaining what future deviations and ISO 5 manipulations would be taken into account before personnel monitoring is performed.

Lack of adequate personnel sampling. Specifically, glove fingertip sampling was conducted after gloves had been sanitized. Therefore, glove fingertip sampling results are not representative of the aseptic process and may not provide accurate results. FDA investigator also noted CGMP violations at your facility, that caused your drug products to be adulterated within the meaning of section 501(a)(2)(B) of the FDCA. The violations include, for example…

Your firm failed to follow written procedures for cleaning and maintenance of equipment. (21 CFR 211.67(b))…

Your firm failed to follow appropriate written procedures that are designed to prevent microbiological contamination of drug products purporting to be sterile. (21 CFR 211.113(b))…

Your firm failed to establish acceptance criteria for the sampling and testing conducted by the quality control unit that are adequate to assure that batches of drug products meet each appropriate specification and appropriate statistical quality control criteria as a condition for their approval and release. (21 CFR 211.165(d))…

In your response to observation #6, you provided updated SOP 3.57 Vendor Setup and Qualification for API and state (b)(4) additional lots have been sent out for full COA testing. Your updated SOP states API re-qualification will be completed (b)(4) . However, your response did not include any additional information on when API re-qualification will occur and what specific testing will be performed. Components that are not approved finished drug products (both APIs and…

In your response to observation #4, you provided updated standard operating procedures (SOP) 3.84 Visual Inspection of Sterile Products and Visual Inspection Personnel Qualification , to describe how you will document the complete results of the Quality Control check, however, you did not provide batch records showing how these forms would be implemented and utilized. In addition, no training documentation was provided to show visual inspectors were trained on updated…

Your firm failed to establish an adequate system for monitoring environmental conditions in aseptic processing areas. (21 CFR 211.42(c)(10)(iv))…