Hawaii Health Systems Corporation dba Kona Community Hospital Pharmacy — FDA Warning Letter Findings

Your firm failed to perform adequate smoke studies under dynamic conditions to demonstrate unidirectional airflow within the ISO 5 BSC. Therefore, your products intended to be sterile were produced in an environment that may not provide adequate protection against the risk of contamination.

Your facility design was deficient because: (i) the cleanrooms did not have (b)(4) ; (ii) the cleanrooms were provided with HEPA filtered air (b)(4) . This HEPA filter was not clamped down in the filter housing, had failed leak testing in 2018, and was not tested for leaks during the cleanroom certification performed in June 2019; (iii) the air returns in the cleanrooms were located in the ceilings in proximity to the air supply vents; (iv) (b)(4) between the ISO 7 hazardous buffer room and the unclassified area were (b)(4) and (b)(4) were observed opened at the same time; (v) a differential pressure cascade could not be maintained between rooms of higher air quality and rooms of lower air quality when the doors to the cleanrooms were closed; (vi) the air supply vents in the ISO 7 non-hazardous drug room and anteroom had accumulated what appeared to be dust.

You failed to evaluate whether the recovery of spore-forming organisms indicated a need for more frequent application of a sporicidal agent as part of your routine disinfection program. Please be aware that section 501(a)(2)(A) of the FDCA concerning insanitary conditions applies regardless of whether drug products you compound meet the conditions of section 503A. FDA strongly recommends that your management undertake a comprehensive assessment of operations, including facility design, procedures, personnel, processes, maintenance, materials, and systems. In particular, this review should assess your aseptic processing operations. A third-party consultant with relevant sterile drug manufacturing expertise should assist you in conducting this comprehensive evaluation. D.

Your response stated that cleaning the interior of the ISO 5 areas will be performed using sterile (b)(4) . However, you did not provide supporting evidence to demonstrate that sterile (b)(4) was purchased or whether any modifications or changes have been made to your cleaning practices.

You did not provide additional environmental monitoring data to demonstrate that the ISO 5 BSC, ISO 5 LAF, and the cleanrooms are maintained in a state of control.

You stated that (b)(4) would be purchased for use while the (b)(4) . You have not provided evidence to show that this corrective action has been implemented.

Your response stated that (b)(4) was intended to be completed by (b)(4) . You have not provided details describing the finalized design changes or evidence to demonstrate that the design phase has been completed or that the (b)(4) activities have been planned or performed.

Your firm used a non-sterile disinfectant within the ISO 5 aseptic processing area. It is a prohibited act under section 301(k) of the FDCA [21 U.S.C. § 331(k)] to do any act with respect to a drug, if such act is done while the drug is held for sale after shipment in interstate commerce and results in the drug being adulterated. C. Corrective Actions We have reviewed your firm's response to the Form FDA 483 and subsequent correspondence. We acknowledge that as part of your corrective actions, all drug products intended to be sterile will continue to be assigned a beyond use date (BUD) of 12 hours. However, regarding your responses related to the insanitary conditions, we cannot fully evaluate the adequacy of the following corrective actions described in your response because you did not include sufficient information or supporting documentation…

You failed to remediate the repeated recovery of microbial contamination from the ISO 7 cleanrooms, ISO 5 biological safety cabinet (BSC), and ISO 5 laminar air flow (LAF) hood where drug products intended to be sterile were prepared. Furthermore, you failed to evaluate whether the identified microbial contamination had any impact on aseptically processed drug products that were prepared in your cleanrooms.