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WARNING LETTER WL # 657453

May 26, 2023

Dear Mr. Saharek:

From July 11 to August 5, 2022, U.S. Food and Drug Administration (FDA) investigators inspected your facility, ImprimisRx NJ, LLC dba Imprimis Rx NJ, located at 1705 Route 46 West, Suite 4, Ledgewood, NJ 07852. During the inspection, the investigators noted serious deficiencies in your practices for producing drug products intended or expected to be sterile, which put patients at risk.

FDA issued a Form FDA 483 to your firm on August 5, 2022. FDA acknowledges receipt of your facility’s responses, dated August 25, 2022, and November 15, 2022. FDA also acknowledges your firm’s recall of subpotent timolol-latanoprost ophthalmic drops with lot numbers 06272022@3 and 08302022@1 initiated on November 9, 2022. Based on this inspection, it appears that you produced drug products that violate the Federal Food, Drug, and Cosmetic Act (FDCA).

A. Compounded Drug Products Under the FDCA

Section 503A of the FDCA describes the conditions under which human drug products compounded by a licensed pharmacist in a State licensed pharmacy or a Federal facility, or a licensed physician, qualify for exemptions from three sections of the FDCA: compliance with current good manufacturing practice (CGMP) (section 501(a)(2)(B)); labeling with adequate directions for use (section 502(f)(1)); and FDA approval prior to marketing (section 505) [21 U.S.C. §§ 351(a)(2)(B), 352(f)(1) and 355(a)].

B. Violations of the FDCA

Adulterated Drug Products

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. For example, the investigators observed that:

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 fiber-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.

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. Further, 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.

In addition, our investigators noted that your firm released and distributed drug products from which the potency differed from the label claim. Specifically, your firm released and distributed the following drug product: Timolol-Latanoprost PF (0.5/0.005%) Ophthalmic Solution. Under section 501(c) of the FDCA [21 U.S.C. § 351(c)], a drug is adulterated if it does not purport to be or is not represented as a drug the name of which is recognized in an official compendium and its strength differs from, or its quality or purity falls below, that which it purports or is represented to possess. The strength of these compounded drug products differed from the strength represented on their labels, causing them to be adulterated under section 501(c) of the FDCA.

Misbranded Drug Products

The strength of compounded drugs, specifically Timolol-Latanoprost PF (0.5/0.005%) Ophthalmic Solution, differed from and fell below their labeled strength. Under section 502(a) of the FDCA [21 U.S.C. § 352(a)], a drug product is misbranded if its labeling is false or misleading in any particular. Because the labeling of this drug product was false, it was misbranded under section 502(a) of the FDCA. The introduction or delivery for introduction into interstate commerce of these products therefore violates section 301(a) of the FDCA [21 U.S.C. § 331(a)]. It is also a prohibited act under section 301(k) [21 U.S.C. § 331(k)] of the FDCA 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 misbranded.

C. Corrective Actions

FDA acknowledges your firm’s recall of subpotent timolol-latanoprost ophthalmic drops with lot numbers 06272022@3 and 08302022@1 initiated on November 9, 2022. During the 2019 inspection, investigators collected samples of Timolol-Latanoprost Ophthalmic Solution. FDA laboratory analysis obtained subpotent results for latanoprost. In your March 25, 2020, correspondence you stated that “the root cause of the Latanoprost failures was determined to be method.” During the 2022 inspection, investigators again collected samples of Timolol-Latanoprost Ophthalmic Solution. FDA laboratory analysis obtained subpotent results for latanoprost. In both 2019 and 2022 you recalled the subpotent lots. However, the subpotency issue for this drug product appears to remain unresolved. You are responsible for the product formulation and assuring product strength through expiry.

We have reviewed your firm’s responses to the Form FDA 483.

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:

1. We acknowledge your response to Observation 1 of the Form FDA 483, where you stated that the HEPA filter was replaced. However, you did not provide evidence that the ISO 5 hood was recertified after the work order was completed nor evidence that the smoke studies were redone after the work order was completed. Furthermore, you did not provide supporting documentation regarding the replacement HEPA filter for the FDA to fully evaluate your response.

2. We acknowledge your response to Observation 5 of the Form FDA 483 which indicated that a work order was initiated to investigate and remediate the issue of the gap between the sprinkler heads and the ceiling located in the ISO 7 classified filling room and your response to Observation 6 on the Form FDA 483, where you stated that the fire extinguishing sprinkler system heads were repaired to stay flush with the ceiling. However, you did not provide evidence of the repair. Your response did not include an impact assessment of the lots produced during this timeframe. 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.

3. We acknowledge your response to Observation 9 of the Form FDA 483 where you stated that the smoke studies were redone. However, we cannot fully evaluate your response as you did not provide sufficient supporting documentation, such as an updated smoke study protocol, an updated detailed report, and/or videos.

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 processing expertise should assist you in conducting this comprehensive evaluation.

D. Conclusion

The violations cited in this letter are not intended to be an all-inclusive statement of violations at your facility. You are responsible for investigating and determining the causes of any violations and for preventing their recurrence or the occurrence of other violations. It is your responsibility to ensure that your firm complies with all requirements of federal law, including FDA regulations.

You should take prompt action to address any violations. Failure to adequately address any violations may result in legal action without further notice, including, without limitation, seizure and injunction.

Within fifteen (15) working days of receipt of this letter, please notify this office in writing of the specific steps that you have taken to address any violations. Please include an explanation of each step being taken to prevent the recurrence of violations, as well as copies of related documentation. This letter notifies you of our concerns and provides you an opportunity to address them. If you believe your products are not in violation of the FDCA, include your reasoning and any supporting information for our consideration. If you cannot completely address this matter within fifteen (15) working days, state the reason for the delay and the time in which you will do so.

Your written notification should refer to the Warning Letter Number above, WL # 657453, and include FEI 3003348498. Send your electronic response to orapharm1_responses@fda.hhs.gov.

If you have questions regarding the contents of this letter, please contact Compliance Officer Barbara Wilimczyk-Macri by email at barbara.wilimczyk@fda.hhs.gov

Sincerely,
/S/

Craig Swanson for Lisa Harlan
Program Division Director
Office of Pharmaceutical Quality Operations
Division I

Cc:
Suja Alum, PharmD
ImprimisRx NJ, LLC, dba ImprimisRx NJ
1705 Route 46 West, Suite 4
Ledgewood, NJ 07852-9720