Maitland Labs of Central Florida — FDA Warning Letter Findings

In response to Observation 3a of the Form FDA 483, you stated you believe that humidity control is not required for stability studies for products packaged in impermeable containers such as glass per your SOP# QAL-9.020v1, Standardized Stability Study Procedures and the statement from your (b)(4) quality person. However, the justification you provided is not acceptable as impermeable containers are “containers that provide a permanent barrier to the passage of gasses or…

In response to Observation 5 of the Form FDA 483 regarding sterility testing, we have reviewed the documentation provided by your contract testing laboratory. You have not provided the supporting validation documentation for sterility testing to demonstrate that the sterility method is adequate for its intended use. Additionally, we acknowledge your commitment to “look at finding a discreet and stable table or stand for the (b)(4) in the near future as time permits.” However, you have not provided an update on the progress of this corrective action. Regarding the (b)(4) location during the inspection, you stated in your response that, “If there are any types of vibrations, they are minor and we don’t consider this a possible risk, certainly not one that would affect operations or test results.” However, you did not provide evidence to support this statement. Therefore, we remain concerned about this potential impact on endotoxin testing results used to release product to market. In addition, the following corrective actions appear deficient…

Your firm failed to conduct laboratory testing to determine whether each batch of drug product purporting to be sterile and pyrogen-free conforms to such requirements (21 CFR 211.167(a)). 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…

In response to Observation 2a of the Form FDA 483, you stated that, "A form FOR-9.018 will be generated and investigated to see if this will require a CAPA..." However, you have not provided any updates regarding the status of any investigation if applicable per SOP-9.018. Further, during the inspection, it was noted that you have proposed per the SOP #PRO-7.052 entitled, "Inspection Checks for Parenteral Products", Section 6.4.10 that, " (b)(4) ." However, you did not provide a justification on how this limit was established. Drug products intended for parenteral administration should be prepared in a manner designed to exclude particulate matter. Administration of an injectable product with particulates may lead to severe health consequences. In addition, you have not provided the revised SOP #PRO-7.052 for our review.

In response to Observation 3b of the Form FDA 483, we acknowledge your commitment to work with your contract testing laboratory to perform container closure integrity testing (CCIT). However, you have not provided documentation to demonstrate that CCIT has been performed. Before a batch is released, CCIT is expected to be completed on samples aged to or beyond the desired expiration date to ensure that sterility is maintained over that time period. This is of particular concern as during our inspection, it was noted that 21 vials ( (b)(4) vials produced) failed to meet general appearance attributes (crimp caps and stoppers came off during the (b)(4) cycle).

In response to Observation 3c of the Form FDA 483, you have stated that you will work with your contract testing laboratory to determine if the (b)(4) method used for the assay/potency test of Nalbuphine HCL is stability-indicating. You have not provided an update whether the (b)(4) assay/potency method used for testing Nalbuphine HCL is stability indicating and can detect impurities and that no degradants co-elute with active pharmaceutical ingredient or excipients…

Some of your facility’s drug products, for example Nalbuphine 10 mg/mL in 0.2% Saline, did not include the following statements on the label: the established name of the drug and the dosage form as required by section 503B(a)(10)(A)(iii) of the FDCA. Some of your facility’s drug products, for example Nalbuphine 10 mg/mL in 0.2% Saline, did not include the following information on the container: a list of active and inactive ingredients identified by established name, and the quantity or proportion of each ingredient as required by section 503B(a)(10)(B)(i) of the FDCA.

In response to Observation 2b of the Form FDA 483, you stated you acknowledge that per your firm’s existing procedure, a Form FOR-9.018 should have been generated as well as “an impact analysis of this batch to determine risk.” However, you have not provided documentation to demonstrate that you have completed the impact analysis or any further investigation. Furthermore, during the inspection, you indicated that the batch passed the test for sterility and that the (b)(4)…

Your firm failed to thoroughly investigate any unexplained discrepancy or failure of a batch or any of its components to meet any of its specifications, whether or not the batch has already been distributed (21 CFR 211.192).

Your firm failed to establish and follow an adequate written testing program designed to assess the stability characteristics of drug products and to use results of stability testing to determine appropriate storage conditions and expiration dates (21 CFR 211.166(a)).

Your facility’s drug products were not compounded in an outsourcing facility that is in compliance with the requirements of section 503B(b) (see section 503B(a)(1) of the FDCA). Specifically, your facility does not comply with section 503B(b)(5) of the FDCA, which as noted above, requires an outsourcing facility to “submit adverse event reports to …[FDA] in accordance with the content and format requirements established through guidance or regulation under section 310.305 of…