FDA Warning Letter: ImprimisRx facility features stained HEPA filters

Following a 2022 inspection, ophthalmic medicine production expert ImprimisRx received a 483 form. A year later a warning letter has been sent emphasising major issues with the facility design and operation

At the end of May, ImprimisRx NJ was issued with a warning letter for its sterile medicine production facility.

US-based ImprimisRx is focused on making sight-saving medicines. Owned by the parent company, Harrow Health, ImprimisRx has a patient specific 503A pharmacy and our FDA-Registered Outsourcing Facility.

The facility was first inspected in mid-2022, and the company has since issued a product recall and a response to the FDA's original FDA 483, the predecessor.

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During the inspection, the investigators noted serious deficiencies in practices for producing drug products intended or expected to be sterile, which put patients at risk.

The letter stated: "The FDA investigators noted that drug products intended or expected to be sterile were prepared, packed, or held under insanitary conditions, whereby they may have become contaminated with filth or rendered injurious to health, causing your drug products to be adulterated under section 501(a)(2)(A) of the FDCA."

These were just some of the observations:

1. One of your ISO 5 classified aseptic processing areas contained HEPA filters that were stained.
2. Your facility is designed and operated in a way that may permit the influx of lesser quality air into a higher quality air area.
3. Your cleanroom contained fibre-like particles hanging from the ceiling as well as ceiling tiles with peeling caulking.
4. 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.
5. An operator placed their gloved hands outside the ISO 5 work area to retrieve supplies without sanitizing their gloved hands before re-entry into the ISO 5 hood.
6. Your firm did not disinfect materials during transfer from the ISO 7 cleanroom into the ISO 5 hood.

The letter also revealed some concerns from the Administration about drug strengths that differed from the label. The firm has previously been in hot water with the FDA over promotional materials that made false and misleading claims about one of its eyedrop therapies.

Tackling the problem

Following the recall, ImprimisRx sent a response to the FDA's Form 483.

In a review of this response, the FDA found a mixed bag: "Regarding your responses related to the insanitary conditions, some of your corrective actions appear adequate; however, 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."

A third-party consultant with relevant sterile drug processing expertise should assist you in conducting this comprehensive evaluation

- The FDA Warning Letter to ImprimisRx

These were some of the corrective actions and the FDA's response:

• ImprimisRx stated that it replaced the stained HEPA filter, but did not provide evidence that the ISO Class 6 hood was recertified, or that smoke studies were redone. "Furthermore, you did not provide supporting documentation," the letter stated.
• ImprimisRx stated that it investigated the issue of the gap between the sprinkler heads and the ceiling located in the ISO 7 classified filling room, adding that the fire extinguishing systems was repaired to be flushed with the ceiling. However, the company did not provide evidence for this. "Your response did not include an impact assessment of the lots produced during this timeframe," the letter stated. "Furthermore, you did not provide evidence to substantiate the claims made by the maintenance technician, who repaired the units, that the unclassified air above the ceiling did not flow into the ISO 7 classified filling room. Moreover, you did not provide supporting documentation that the rubber gaskets were in place."
• Smoke studies were redone, but the FDA once again, found insufficient supporting documentation, such as an updated smoke study protocol, an updated detailed report, and/or videos.

In conclusion, the FDA strongly recommended that the company's 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," the letter stated. "A third-party consultant with relevant sterile drug processing expertise should assist you in conducting this comprehensive evaluation."

Companies

• US Food and Drug Administration (FDA)