ProRx LLC — FDA Warning Letter Findings

An operator blocked first air by placing gloved hands and/or forearms directly over open tray of stoppers intended to be sterile during critical in-process operations within the ISO 5 production areas.

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).

You did not disinfect materials during transfer from the ISO 7 cleanroom into the ISO 5 laminar airflow workstation (LAFW). Specifically, an operator removed the outer packaging of stoppers in the ISO 7 area and the inner bag was then transferred from the ISO 7 area into the ISO 5 LAFW without surface disinfection. The inner bag of stoppers could be held for up to (b)(4) within the ISO 7 area before being transferred into the ISO 5 LAFW.

You had production areas or equipment that are difficult to clean or contain porous, particle-generating, or visibly dirty (e.g., rusty) equipment or surfaces (e.g., shelving, floors, walls, doors, ceilings). Specifically, the floor of the ISO Class 7 buffer room equipped with an ISO 5 LAFW and Biological Safety Cabinet (BSC) showed significant visible sporadic discoloration, the cause of which remains unknown. The 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 establish an adequate system for cleaning and disinfecting the room and equipment to produce aseptic conditions (21 CFR 211.42(c)(10)(v)). 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…

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

Regarding your March 19, 2025, Dynamic Smoke Study, your response claimed the study demonstrated that first air to the stoppers was maintained and there was no contamination risk from your operator forearms during the stoppering process in your ISO 5 area. However, our review of your dynamic smoke study reveals several critical deficiencies that contradict these claims. The video footage shows operators extending their forearms and gloved hands directly over both the sterile stopper tray and open vial tray during stoppering operations in the ISO 5 hood, contradicting your assertion of no obstruction. Moreover, the stopper tray was empty during the smoke study, operators were simulating stopper pickup with tweezers and transfer over open vials rather than performing a…

Your firm failed to establish and follow appropriate written procedures that are designed to prevent microbiological contamination of drug products purporting to be sterile, and that include validation of all aseptic and sterilization processes (21 CFR 211.113(b)).

Regarding your firm’s deficiency in monitoring environmental conditions, your SOP CSP-080 Viable and Nonviable Air Sampling states viable air sampling “is conducted continuously during the compounding of CSPs in the ISO 5 environment by compounding personnel”. Our review of your SOPs and batch record reveals a fundamental misunderstanding of the distinction between active and passive viable air monitoring methods. Specifically, the viable monitoring documented in your batch…

Regarding your failure to conduct adequate investigations, our comprehensive review of your firm’s multiple deviation reports and SOPs reveals significant deficiencies in documentation and execution procedures for out-of-specification (OOS) events and deviation investigations. The following examples illustrate some of these deficiencies: Your deviation reports (DEV-2025-05 and DEV-2025-06) provide only minimal information, such as the description of the deviation and the…

An operator used non-sterilized scissor within the ISO 5 processing area. This scissor was used to cut open a bag of stoppers inside the ISO 5 LAFW during filling operation of drug product intended to be sterile. This scissor was routinely stored in the ISO 7 area and was only wiped with (b)(4) wipe prior to use.

Your firm’s quality control unit failed to approve or reject all procedures or specifications impacting on the identity, strength, quality, and purity of the drug product (21 CFR 211.22(c)).

You did not perform adequate product evaluation and take appropriate corrective action after microbial contamination was recovered within the ISO 5 production area. Instead, your firm approved and distributed drug products that were produced with colony-forming unit (CFU) recoveries found on ISO 5 operator gloves and settle plates.

Your facility compounded drug products using tirzepatide bulk drug substance. For example, on (b)(4) , your facility compounded (b)(4) vials of Tirzepatide 72MG/4ML injectable drug product and on (b)(4) , your facility compounded (b)(4) vials of Tirzepatide 45MG/2.5ML injectable drug product, using tirzepatide bulk drug substance on both dates. These drug products compounded using tirzepatide bulk drug substance are not eligible for the exemptions provided by section 503B…

Your facility did not submit adverse event reports to FDA in accordance with the content and format requirements established through guidance or regulation under section 310.305 of title 21, Code of Federal Regulations (or any successor regulations). 4 Specifically, your facility’s procedures for reporting adverse events are inadequate. For example, your documented procedures for reporting adverse events do not include an adequate definition of what constitutes a “serious”…