1Aseptic processing and sterility assurance
Regarding your sterilized ointment base, you have not addressed how you will adequately protect it from contamination during transport from the (b)(4) ovens to the ISO 5 classified aseptic processing areas. 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, including the condition on receipt of a prescription for an identified individual patient…
2Aseptic processing and sterility assurance
An operator blocked first air by placing gloved hands directly over open sterile containers and performed aseptic manipulations by holding drug materials in (b)(4) orientation with airflow patterns, thereby preventing first air from protecting aseptic connections inside your ISO 5 classified critical areas.
3Aseptic processing and sterility assurance
Your ISO 5 classified (b)(4) LAFW does not have adequate HEPA filter coverage, in that smoke studies revealed air turbulence, hood recertification studies demonstrated low air velocity, and (b)(4) was leaking from HEPA filters in both your ISO 5 and ISO 7 classified areas.
4Aseptic processing and sterility assurance
An operator did not move in a slow and deliberate manner to prevent disruption of unidirectional airflow in the critical area during aseptic production, instead the operator moved so quickly that drug materials appear to have been inadvertently dropped back onto the workstation.
5Environmental monitoring
Your facility is designed and operated in a way that may permit the influx of lesser quality air into a higher quality air area in that you did not prevent the influx of unclassified air into your ISO 5 classified (b)(4) LAFW from the unclassified space above the ceiling and from the unclassified areas outside your cleanroom.
6Aseptic processing and sterility assurance
You did not perform adequate product evaluation and take appropriate corrective action after microbial contamination was recovered within the ISO 5 aseptic processing area. In June 2020, and between March and October 2022, your firm detected microbial contamination inside your ISO 5 classified critical areas but did not take appropriate steps to correct and prevent reoccurrence.
7Contamination control
An operator allowed trash to accumulate on the front air intake grille of the ISO 5 classified Biological Safety Cabinet which potentially disrupted airflow patterns and thereby introduced contamination risks.
8Aseptic processing and sterility assurance
Your firm has not addressed how you will ensure that your future smoke studies will adequately demonstrate air flow patterns, including but not limited to sufficient smoke production and angle perspectives which allow appropriate evaluation. Regarding your responses related to the insanitary conditions, the following corrective actions appear deficient…
9Aseptic processing and sterility assurance
Materials used to produce drug products intended to be sterile were exposed to lower than ISO 5 classified quality air, in that your firm’s sterilized ophthalmic ointment base was covered with unsecured (b)(4) and was exposed to lesser quality air in the unclassified area where the oven was located. Under section 301(a) of the FDCA [21 U.S.C. § 331(a)], the introduction or delivery for introduction into interstate commerce of any drug that is adulterated is a prohibited act…
10Other quality system
Your firm failed to use a sporicidal agent as part of your disinfection program on the plexiglass shield inside your (b)(4) ISO 5 classified LAFW.
11Aseptic processing and sterility assurance
Regarding your revised media fill procedures, you did not appear to consider fill volume (for example, (b)(4) vs. (b)(4) per unit) when determining the most difficult compounding processes. Further, the new media fill studies that you provided do not demonstrate the most challenging or stressful conditions that your operators perform at your facility. Finally, you have not indicated if operators will be restricted to the types of operations for which they have successfully completed a media fill.
12Aseptic processing and sterility assurance
An operator touched product contact surfaces and aseptic connection points with their gloved hands, including the filling needle, the hub of the syringe, and the downstream end of the (b)(4) .
13Other quality system
Regarding sealing the ceiling tiles, it is unclear if you are ensuring that the light fixtures are sealed in a manner that prevents ingress of lesser quality air from above the ceiling into the newly created ISO 7 area surrounding the new ISO 5 LAFW hoods.
14Other quality system
Your firm has not provided information about the new LAFW hoods that you have purchased to replace the ISO 5 classified (b)(4) LAFW, including but not limited to hood descriptions (such as hood model information and airflow orientation), photographic evidence, certifications, and information about how the new hoods will be cleaned, disinfected, and treated with sporicidal agents.
15Aseptic processing and sterility assurance
Poor aseptic practices (touching product contact surfaces and aseptic connection points, blocking first pass air, quick movements, and trash accumulation inside the ISO 5 classified critical areas) are a repeat observation from the 2017 FDA inspection, and you did not provide sufficient information about the educational materials used to retrain employees to give assurance that these poor aseptic practices will not reoccur. Additionally, you have not provided information about how you will retrain employees on proper aseptic practices in the newly purchased ISO 5 classified LAFW hoods.
16Aseptic processing and sterility assurance
Your firm failed to perform adequate smoke studies under dynamic conditions to demonstrate unidirectional airflow within the ISO 5 area. Therefore, your products intended to be sterile are produced in an environment that may not provide adequate protection against the risk of contamination.
17Aseptic processing and sterility assurance
Your media fills were not performed under the most challenging or stressful conditions. Therefore, there is a lack of assurance that your firm can aseptically produce drug products within your facility.
18Cleaning validation
The ISO 5 and ISO 7 classified areas had difficult to clean, porous, particle-generating, and visibly dirty equipment or surfaces. FDA observed: a. Rust-like discoloration on a HEPA filter, (b)(4) plates, and the return vents; yellow residue on HEPA filters; holes in the wall; and a cracked plexiglass shield inside your ISO 5 classified (b)(4) LAFW. b. Dust and trash underneath work surface/deck in your ISO 5 classified biological safety cabinet. c. Rust-like discoloration on a HEPA filter diffuser in the ISO 7 classified anteroom.
