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WARNING LETTER

August 25, 2020

Dear Ms. Simmers:

From February 27, 2019, to March 8, 2019, U.S. Food and Drug Administration (FDA) investigators inspected your facility, Customceutical Compounding, LLC, located at 4611 East Shea Blvd., Building 3, Suite 180, Phoenix, AZ 85208. During the inspection, the investigators noted serious deficiencies in your practices for producing sterile drug products, which put patients at risk.

FDA issued a Form FDA 483 to your firm on March 8, 2019. FDA acknowledges receipt of your facility’s response, dated March 29, 2019. FDA further acknowledges that your firm ceased sterile compounding as of March 29, 2019. FDA also acknowledges that on April 8, 2019, your firm initiated a voluntary recall of injectables and solutions intended to be sterile within expiry due to a lack of sterility assurance. 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)].¹ Receipt of valid prescriptions for individually-identified patients is one of the conditions for the exemptions under section 503A.

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. The investigators observed poor practices during aseptic processing, including a technician failing to sanitize materials prior to placing them into the ISO 5 classified area. In addition, personnel engaged in aseptic processing exposed facial skin within the ISO 5 classified area.

2. Your firm did not perform adequate product evaluation and take remedial action after microbial contamination was found to be present on a technician’s glove, from post-aseptic processing fingertip testing.

3. Your firm failed to perform adequate smoke studies under dynamic conditions to demonstrate unidirectional airflow within the ISO 5 classified area. Therefore, your products intended to be sterile are produced in an environment that may not provide adequate protection against the risk of contamination.

4. Your firm used non-sterile cleaning wipes inside the ISO 5 aseptic processing area.

5. Personnel failed to adequately sanitize equipment held in your laminar flow hood. In addition, personnel did not allow adequate disinfectant contact time to achieve sporicidal effect.

6. Personnel donned gowning apparel improperly, allowing sleeves and other parts of the coverall to touch the floor in the ISO 8 anteroom prior to entering the ISO 7 classified area room to perform aseptic processing. This practice could cause the gowning apparel to become contaminated, thereby contaminating drug products intended to be sterile.

7. Your firm produced hazardous drug products without providing adequate containment and cleaning of work surfaces and equipment to prevent cross-contamination. Further, personnel produced different drug products prior to adequately removing loose (b)(4) from work surfaces and equipment. Personnel contacted these items repeatedly while they produced different drug products without changing or sanitizing their gloves.

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 response to the Form FDA 483. We acknowledge that your firm ceased sterile compounding on March 29, 2019. We also acknowledge that your firm initiated a recall of injectables and solutions intended to be sterile on April 8, 2019.

Regarding your response related to the insanitary condition of inadequate containment and cleaning to prevent cross-contamination, 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. For example, you state that you have retrained your personnel on proper cleaning procedures and provided your current “SOP Support Process/Training Guide.” You state that this training document will be used to develop a more detailed SOP on cleaning and decontamination, and it will be completed by April 5, 2019. However, this SOP has not been provided for our review. Further, you did not provide documentation of routine observational audits performed by the Pharmacist-In-Charge or documentation of personnel training.

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 if you decide to resume production of sterile drugs, your management first 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 manufacturing 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 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.

If you decide to resume sterile operations, you should take prompt action to correct the violations cited in this letter. Failure to promptly correct these 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 if you have taken any specific steps to correct the violations cited in this letter, or you may inform us that you do not intend to resume production of sterile drugs. If you intend to resume production of sterile drugs in the future, please include an explanation of each step being taken to prevent the recurrence of violations, as well as copies of related documentation. If you do not believe that the products discussed above violated the FDCA, include your reasoning and any supporting information for our consideration. In addition to taking appropriate corrective actions, you should notify this office fifteen (15) working days prior to resuming production of any sterile drugs in the future.

Please send your electronic reply to [email protected] or mail your reply to:

CDR Steven E. Porter, Jr.
Director, Division of Pharmaceutical Quality Operations IV
U.S. Food & Drug Administration
19701 Fairchild Road
Irvine, California 92612-2506

Please identify your response with the unique identifier: CMS 610092.

If you have questions regarding the contents of this letter, please contact Lance De Souza, Compliance Officer at 510-337-6873 or email at [email protected].

Sincerely,
/S/

CAPT Katherine E. Jacobitz
Acting Director, Division of Pharmaceutical Quality Operations IV

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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.