OSRX, Inc. — FDA Warning Letter Findings

Your facility’s drug products, such as Prednisolone Phosphate 1% Moxifloxacin 0.5% 5ml Sterile Ophthalmic Solution and Atropine Sulfate 0.025% 3.5ml Sterile Ophthalmic Solution, did not include the following on the label: a list of active and inactive ingredients, identified by established name and the quantity or proportion of each ingredient.

Regarding your firm’s failure to thoroughly investigate microbial contamination in the ISO 5 BSC during production, your response failed to ensure a thorough investigation is performed for any microbial recovery in the ISO 5 environment. Your investigations did not include environmental trending reports for each personnel performing work inside the ISO 5 classified area when microorganisms were recovered inside the ISO 5BSC from active viable air sampling plates. Any microbial contamination in the ISO 5 area is considered an insanitary condition and is a serious concern. Upon recovery, your firm should immediately assess the impact on drug products produced. This assessment should include a thorough evaluation of how contamination could have entered this critical area, and over what period of time the contamination could have existed, as well as drug products that remain on the market that could be affected.

Your firm failed to establish and follow adequate control procedures to monitor the output and to validate the performance of those manufacturing processes that may be responsible for causing variability in the characteristics of in-process material and the drug product (21 CFR 211.110(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…

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)).

Your firm failed to perform adequate smoke studies under dynamic conditions to demonstrate unidirectional airflow within the ISO 5 classified critical area. Therefore, your products intended to be sterile are produced in an environment that may not provide adequate protection against the risk of contamination. Specifically, you did not include (b)(4) operators working inside the ISO 5 (b)(4) Biosafety Cabinet (BSC) simultaneously to perform check weighing, filling, and capping activities, as per your production activities.

Regarding your firm’s failure to incubate all integral media fill units, your firm states as part of a corrective action you opened CAPA OEPA-2024-00771.1 and closed it on October 16, 2024, and submitted in your response SOP-CC-0003 titled “Aseptic Process Simulation – Media Fills, Effective Date: Oct 9, 2024”. You stated you would submit a revised SOP-CC-0003, however we received SOP-CC-003 with an effective date of October 9, 2024, which is prior to the FDA inspection. In addition, you failed to provide a revised media fill master batch production record to reflect that all APS media fill units will be incubated and documentations for the reasons why units are rejected.

We acknowledge that you provided SOP-INSP-0003 titled “Visual Inspector Qualification, Effective Date May 20, 2024” but did not address how you intend to qualify your visual inspection sample defect library/kits used for operator visual inspection training of topical ophthalmic solutions nor provide an approved procedure as to how you establish and maintain your sample defect library/kits.

Regarding your firm’s failure to investigate labeling inspection failures that exceeded your specification limits, your investigation document QE-2024-0133 into labeling visual inspection failures, due to wrinkled labels on the bottles, did not include documented training records of all visual inspection personnel for reporting production quality events (deviations/investigations).

Regarding your firm’s failure to simulate the worst-case scenarios of your production process during Aseptic Simulation Process (APS), your firm did not provide your ASP demonstrating simulated worst-case scenarios to include largest number of container units aseptically filled, longest filling duration, performance of identified interventions and aseptic filling operators who are deemed as “Full Qualification”.

Your facility’s drug products, such as such as Prednisolone Phosphate 1% Bromfenac 0.075% 5ml Sterile Ophthalmic Solution and Moxifloxacin 0.5% Bromfenac 0.075% 5ml Sterile Ophthalmic Solution, did not include the following information on the container: (1) information to facilitate adverse event reporting: www.fda.gov/medwatch and 1-800-FDA-1088; and (2) directions for use, including, as appropriate, dosage and administration. Because your compounded drug products have not…

You reference USP <1790> Visual Inspection of Injections and you did not commit to performing 100% visual inspection of all drug products including your sterile topical ophthalmic solutions contained in opaque droptainers and sterile injectable intraocular solution contained in glass vials. USP <771> Ophthalmic Products – Quality Tests considers the 100%-unit inspection as the complete nondestructive inspection of the container-closure system and its contents. The 100%-unit…

Regarding your firm’s failure to establish a dynamic smoke study report/video simulating (b)(4) employees inside the ISO 5 (b)(4) Biosafety Cabinet (BSC) performing check weights, filling and capping activities, your firm committed to repeat the OSRX smoke study video in December 2024. However, you did not provide the revised dynamic smoke study report/video.

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

We acknowledge your commitment to retraining operators to conduct fingertip sampling, however, you did not provide a justification why it would be completed first quarter 2025. Furthermore, your SOP states to use (b)(4) fingers instead of five when applying pressure to the agar plate.

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 perform adequate product evaluation and take appropriate corrective action after microbial contamination was recovered within the ISO 5 aseptic processing area. 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…

Regarding your firm’s failure to perform viable surface sampling in the ISO 5 (b)(4) during filling of a drug product, your response included CAPA QEPA-2024-0121.1, approved on October 22, 2024, which states all compounding and environmental monitoring personnel were trained emphasizing the requirements for surface sampling with each compounded lot. However, you did not provide documentation of retraining of all compounding and environmental monitoring personnel with the requirements set forth under SOP-CC-0026 titled “Routine Environmental Monitoring Cleanroom 100, Effective date Jul 15, 2024”.

Regarding your firm’s failure to establish a gowning qualification program for operators entering the ISO classified areas, your firm provided Document Change Request Number DCR-2024-0114, approved on November 3, 2024, to address a lack of gowning qualification program at your facility for entry to Cleanroom Suite 100, room number (b)(4) (ISO 7) and room number (b)(4) (ISO 7), from the gowning in airlock (room number (b)(4) ) ensuring sterile gowning is donned without contamination. However, changes to procedures FRM-CC-004.1, SOPCC-0023, TRAIN-0005, FRM-CC-0007.2, FRM-CC-0005.2, and FRM-CC-0023.1 remain pending with an estimated completion date of first quarter 2025 as stated in your response.

Regarding your firm’s failure to provide justification for sampling (b)(4) units from two totes to examine for visual inspection as a form of an Acceptable Quality Limit (AQL), your response states your AQL visual inspection samples are selected from a batch (b)(4) from two totes, with (b)(4) samples selected from one tote, and (b)(4) samples from the other, thus representative of the entire batch. You did not provide a scientific rational for selecting the two totes to be sampled; furthermore, you did not provide the revised master batch records for all your drug products. Some of your corrective actions appear deficient…

We acknowledge that you stated in your response that you will revise SOP-CC-0026 titled “Routine Environmental Monitoring Cleanroom 100 to address a change in the action limit for the number of Colony Forming Units (CFUs) to (b)(4) CFUs, however, your estimated completion date is (b)(4) . Furthermore, you failed to implement an interim corrective action to address the reclassification of the action limit to (b)(4) CFU for the ISO5 classified areas.