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WARNING LETTER

CMS 663403

September 13, 2023

Dear Mr. Taylor:

From August 29, 2022, to September 9, 2022, U.S. Food and Drug Administration (FDA) investigators inspected your facility, Curexa – East, LLC dba Curexa, located at 3007 Ocean Heights Avenue, Egg Harbor Township, NJ 08234. During the inspection, the investigators noted serious deficiencies in your practices for producing drug products, which put patients at risk.

FDA issued a Form FDA 483 to your firm on September 9, 2022. FDA acknowledges receipt of your facility’s response, dated October 7, 2022. Based on this inspection, it appears that you produced drug products that violate the Federal Food, Drug, and Cosmetic Act (FDCA) [21 U.S.C. § 353a].

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)].1

B. Violations of the FDCA

Adulterated Drug Products

The FDA investigators noted that drug products 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:

1. Non-microbial contamination was observed in the production area.

2. Your firm produced hazardous drugs without providing adequate cleaning of utensils, components, or containers to prevent cross-contamination.

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.

C. Corrective Actions

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

Regarding your responses related to the insanitary conditions, 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. Regarding the information provided in response to Observation 1(B), within which tan and grey colored residue clumps were observed within (b)(4) hoods (b)(4), and (b)(4), you reported that hoods (b)(4) and (b)(4) had been cleaned, however, your response only provided photos of hoods (b)(4) and (b)(4). While the remediation of (b)(4) and (b)(4) appears adequate, an evaluation of the other hoods could not be performed due to the lack of supporting documentation, such as photographs of each hood’s remediation. In addition, your response reports that each of the hoods in this Observation are currently within certification, however, having a certified hood does not preclude it from contaminating drug products due to the residue contained within it.

We acknowledge your competency, titled (b)(4) Hood, which requires that the hoods be examined for defects, discoloration, or debris. In addition, it heightens awareness about the necessity to clean hard to reach areas and crevices and includes a (b)(4) necessity to remove and clean paneling within the hoods.

2. Regarding the information provided in response to Observation 1(C) within which reddish-brown discoloration was observed on the HEPA filter of (b)(4) airflow (b)(4) containment hood (b)(4) ((b)(4), model (b)(4)), a full assessment could not be performed as documentation, such as a purchase order for the replacement HEPA filter, was not submitted. In addition, your response did not provide a timetable within which the HEPA filter replacement would be completed, and you did not provide your interim plans regarding utilization of this hood. Therefore, it is unclear whether you will continue to use hood (b)(4) prior to completion of remediation. Furthermore, your proposed remediation includes vacuuming the HEPA filter, however, it is unclear how this process could be performed without damaging the filter.

3. Regarding the information provided in response to Observation 1(E), where materials that are not easily cleanable, such as tape and a tan colored thin paper-like covering were observed being used as coverings of (b)(4) holes on (b)(4) (hoods (b)(4), and (b)(4)), your response stated that the tape and tan colored paper-like material on the (b)(4) have been removed, and (b)(4) were ordered to replace them. Your response, however, did not include additional information such as photographs of the remediation, the cleanability of the grommets, and documentation demonstrating that the (b)(4) fit every hole identified within the Observation.

Regarding your responses related to the insanitary conditions, the following corrective actions appear deficient:

1. Regarding the information provided in response to Observation 1(A)(i), you stated that a professional cleaning service “…found heavy buildup of blue powder internally in the housing & blower motor/wheel…(and) was only able to get the majority of the buildup of those items…”. This implies not only that there was significant buildup of blue reside within the internal components of the air conditioner, but also, that residue remains. Therefore, remediation of the blue residue within the air conditioning unit is inadequate. The air conditioner runs continuously and sits directly above the production area(s), thus presenting a possible risk of product contamination. In addition, FDA strongly recommends that you perform a thorough review of your facility and remediate any blue residue found in areas including, but not limited to, ceiling vents, wall corners, and outlet covers.

2. Regarding the information provided in response to Observation 1(A)(iii), you stated that the V-blender was not in use at the time and would have been appropriately cleaned prior to use by wiping it with (b)(4) as per the (b)(4) Training Document on the V-blender. Your response is inadequate because there is no assurance that wiping with (b)(4), alone, is sufficient to remove product residue on equipment. A review of the V-blender cleaning procedures should have been performed to determine why the residue was not removed. Therefore, we remain concerned that residue may be introduced into subsequent products compounded using the V-blender.

3. Regarding the information provided in response to Observation 2(C), we acknowledge that your procedure is to use (b)(4) and/or (b)(4) the in-process materials and/or equipment, (b)(4) detergent and a sponge. However, your response did not indicate the concentration of (b)(4) used for decontamination. In addition, your firm uses a household detergent, (b)(4) and/or (b)(4) dishwasher detergent to clean in-process materials and/or equipment that are routinely used in the production of your compounded drug products. You have not established that the order of your cleaning process, which utilizes (b)(4) and/or (b)(4) and (b)(4) is adequate to remove detergent residues from your in-process materials and/or equipment.

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.

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 the violations identified above 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 within which you will do so.

Send your electronic reply to orapharm1_responses@fda.hhs.gov. Identify your response with FEI 3011761882 and Warning Letter CMS 663403.

If you have any questions, contact Compliance Officer, Barbara Wilimczyk-Macri, at barbara.wilimczyk@fda.hhs.gov.

Sincerely,
/S/

Lisa Harlan
Program Division Director
Office of Pharmaceutical Quality Operations Div I

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1 We remind you that there are conditions other than those discussed in this letter that must be satisfied to qualify for the exemptions in section 503A of the FDCA.